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Petia Radeva, Amir Amini, Jintao Huang, & Enric Marti. (1996). "Deformable B-Solids: application for localization and tracking of MRI-SPAMM data ". CVC (UAB).
Abstract: To date, MRI-SPAMM data from different image slices have been analyzed independently. In this paper, we propose an approach for 3D tag localization and tracking of SPAMM data by a novel deformable B-solid. The solid is defined in terms of a 3D tensor product B-spline. The isoparametric curves of the B-spline solid have special importance. These are termed implicit snakes as they deform under image forces from tag lines in different image slices. The localization and tracking of tag lines is performed under constraints of continuity and smoothness of the B-solid. The framework unifies the problems of localization, and displacement fitting and interpolation into the same procedure utilizing B-spline bases for interpolation. To track motion from boundaries and restrict image forces to the myocardium, a volumetric model is employed as a pair of coupled endocardial and epicardial B-spline surfaces. To recover deformations in the LV an energy-minimization problem is posed where both tag and ...
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David Roche, Debora Gil, & Jesus Giraldo. (2014). "Mathematical modeling of G protein-coupled receptor function: What can we learn from empirical and mechanistic models? " In G Protein-Coupled Receptors – Modeling and Simulation Advances in Experimental Medicine and Biology (Vol. 796, pp. 159–181). Springer Netherlands.
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.
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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David Roche, Debora Gil, & Jesus Giraldo. (2013). "Mechanistic analysis of the function of agonists and allosteric modulators: Reconciling two-state and operational models " . British Journal of Pharmacology, 169(6), 1189–202.
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.
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David Roche, Debora Gil, & Jesus Giraldo. (2013). "Multiple active receptor conformation, agonist efficacy and maximum effect of the system: the conformation-based operational model of agonism, " . Drug Discovery Today, 18(7-8), 365–371.
Abstract: The operational model of agonism assumes that the maximum effect a particular receptor system can achieve (the Em parameter) is fixed. Em estimates are above but close to the asymptotic maximum effects of endogenous agonists. The concept of Em is contradicted by superagonists and those positive allosteric modulators that significantly increase the maximum effect of endogenous agonists. An extension of the operational model is proposed that assumes that the Em parameter does not necessarily have a single value for a receptor system but has multiple values associated to multiple active receptor conformations. The model provides a mechanistic link between active receptor conformation and agonist efficacy, which can be useful for the analysis of agonist response under different receptor scenarios.
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David Roche, Debora Gil, & Jesus Giraldo. (2012). "Assessing agonist efficacy in an uncertain Em world " In A. Christopoulus and M. Bouvier (Ed.), 40th Keystone Symposia on mollecular and celular biology (79). Keystone Symposia.
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.
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David Roche, Debora Gil, & Jesus Giraldo. (2011). "Using statistical inference for designing termination conditions ensuring convergence of Evolutionary Algorithms " In 11th European Conference on Artificial Life.
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.
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David Roche, Debora Gil, & Jesus Giraldo. (2011). "An inference model for analyzing termination conditions of Evolutionary Algorithms " In 14th Congrès Català en Intel·ligencia Artificial (pp. 216–225).
Abstract: In real-world problems, it is mandatory to design a termination condition for Evolutionary Algorithms (EAs) ensuring stabilization close to the unknown optimum. Distribution-based quantities are good candidates as far as suitable parameters are used. A main limitation for application to real-world problems is that such parameters strongly depend on the topology of the objective function, as well as, the EA paradigm used.
We claim that the termination problem would be fully solved if we had a model measuring to what extent a distribution-based quantity asymptotically behaves like the solution accuracy. We present a regression-prediction model that relates any two given quantities and reports if they can be statistically swapped as termination conditions. Our framework is applied to two issues. First, exploring if the parameters involved in the computation of distribution-based quantities influence their asymptotic behavior. Second, to what extent existing distribution-based quantities can be asymptotically exchanged for the accuracy of the EA solution.
Keywords: Evolutionary Computation Convergence, Termination Conditions, Statistical Inference
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Oriol Rodriguez-Leon, Debora Gil, Eduard Fernandez-Nofrerias, H.Tizon, S.Montserrat, Vicente del Valle, et al. (2007)." Caracterització de la Perfusió Miocàrdica mitjançant anàlisi estadístic de l espectre en l angiografia de contrast" In XIX Congrés de la Societat Catalana de Cardiologia de Barcelona (130). Barcelona (Spain).
Abstract: La valoració de la integritat de la microcirculació coronària aporta informació pronòstica en pacients amb infart agut de miocardi en els que es realitza angioplastia primària. Aquesta valoració és subjectiva i presenta una important variabilitat si no es duta a terme per personal experimentat. Presentem una eina d’anàlisi d’imatge que permet fer una valoració de la microcirculació coronària a partir de seqüències d’angiografia. Hem analitzat les variacions locals en el nivell de gris de la imatge durant la seqüència angiogràfica. Hem identificat els principals fenòmens observats (respiració, batec cardíac, tinció arterial, tinció miocàrdica i soroll radiològic) mitjançant un anàlisi estadístic de l’espectre de Fourier de l’evolució al llarg del temps de la mitja local. Aquest mateix anàlisis permet determinat la influència de cadascun d’ells en la extracció del patró de tinció i selecciona la respiració com el fenomen que més distorsiona el patró de tinció original. Els descriptors proposats s’obtenen fora del rang espectral respiratori. Hem testat la seva capacitat per a detectar els tres fenòmens principals (tinció miocàrdica (MS), tinció arterial (AS) i soroll (NS)) independentment de la respiració. La capacitat de discriminació dels descriptors ha estat valorada mitjançant un mètode de crossvalidation en 30 seqüències d’angiografia. Els descriptors emprats permeten caracteritzar la tinció miocàrdica amb una alta eficiència i fiabilitat. A més no hi ha diferències significatives en l’anàlisi de les seqüències obtingudes amb el pacient respirant amb normalitat o en apnea
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Oriol Rodriguez-Leon, Debora Gil, & Eduard Fernandez-Nofrerias. (2006)." Analisis en los cambios en el nivel de gris en las secuencias angiograficas mediante descriptores estadisticos para determinar la perfusion miocardica" . Revista Española de Cardiología, 59 Supl 2-166(2), 128.
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Oriol Rodriguez-Leon, Eduard Fernandez-Nofrerias, Josefina Mauri, Vicente del Valle, Debora Gil, A.Barrios, et al. (2006)." Perfusion ratio: A new tool to objectively assess microcirculation perfusion after primary Percutaneous Coronary Intervention" In World Congress of Cardiology (859). Barcelona (Spain).
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