Basic statistics and variational concepts behind the reverse Monte Carlo technique

We revise the statistical foundations of the reverse Monte Carlo (RMC) technique by constructing the associated functional of a variational principle which incorporates, without any ad hoc assumptions, the inherent errors accompanying the simulation and the experimental data. We propose a Bayesian criteria for acceptance/rejection of configurations, in terms of the variations of the functional. The loss function and variational functional minimization approaches are compared.     

Basic concepts and principles of stoichiometric modeling of metabolic networks

Metabolic networks supply the energy and building blocks for cell growth and maintenance. Cells continuously rewire their metabolic networks in response to changes in environmental conditions to sustain fitness. Studies of the systemic properties of metabolic networks give insight into metabolic plasticity and robustness, and the ability of organisms to cope with different environments. Constraint-based stoichiometric modeling of metabolic networks has become an indispensable tool for such studies. Herein, we review the basic theoretical underpinnings of constraint-based stoichiometric modeling of metabolic networks. Basic concepts, such as stoichiometry, chemical moiety conservation, flux modes, flux balance analysis, and flux solution spaces, are explained with simple, illustrative examples. We emphasize the mathematical definitions and their network topological interpretations.     

Regulation of feeding behavior,gastrointestinal function and fluid homeostasis by apelin

Apelin was first identified and characterized from bovine stomach extracts as an endogenous ligand for the APJ receptor. Apelin/APJ system is abundantly present in peripheral tissues and central nervous system. Apelin plays a broad role in regulating physiological and pathological functions. Recently, many reports have showed the effects of apelin on feeding behavior, however the results are inconsistent, due to different administration routes, animal species, forms of apelin, etc. Apelin has been involved in stimulating gastric cell proliferation, cholecystokinin (CCK) secretion, histamine release, gastric acid and bicarbonate secretion, and regulation of gastrointestinal motility. In addition, apelin produced regulatory effects on drinking behavior, diuresis, arginine vasopressin (AVP) release and glucocorticoids secretion. This article reviews the role of apelin on feeding behavior, gastrointestinal function and fluid homeostasis.     

Comparative analysis of male androgen responsiveness to social environment in birds: the effects of mating system and paternal incubation

Male androgen responses to social challenges have been predicted to vary with mating system, male-male aggressiveness, and the degree of paternal investment in birds ("challenge hypothesis," Am. Nat. 136 (1990), 829). This study focused on the interspecific predictions of the challenge hypothesis. Comparative methods were used to control for effects of the phylogenetic relatedness among the sampled species. Male androgen data of 84 bird species were collected from literature records on seasonal androgen patterns. From these, the androgen responsiveness (AR) was calculated as described in the original challenge hypothesis (i.e., maximum physiological level/breeding baseline). Scatterplots of AR versus mating strategy, male-male aggressiveness, and the degree of paternal care confirmed the expected interspecific patterns. When phylogenetic analyses were performed among all of the sampled species, the effects of paternal investment disappeared while the AR remained covarying to a high degree with mating system and male-male aggressiveness. Although these mechanisms may be different at the intraspecific level, this suggests that interspecific differences of AR in male birds may have evolved in response to changes of mating strategies, rather than in response to altered paternal duties. However, control for phylogeny among the subsample of 32 passerine species revealed that if any paternal investment contributed to the observed variance in AR, then the change from "no male incubation" to "male shares incubation duties" represented the most effective, whereas the male's contribution to feeding offspring did not explain the observed variation of AR.     

Integration of detailed modules in a core model of body fluid homeostasis and blood pressure regulation

This paper presents a contribution to the definition of the interfaces required to perform heterogeneous model integration in the context of integrative physiology. A formalization of the model integration problem is proposed and a coupling method is presented. The extension of the classic Guyton model, a multi-organ, integrated systems model of blood pressure regulation, is used as an example of the application of the proposed method. To this end, the Guyton model has been restructured, extensive sensitivity analyses have been performed, and appropriate transformations have been applied to replace a subset of its constituting modules by integrating a pulsatile heart and an updated representation of the renin-angiotensin system. Simulation results of the extended integrated model are presented and the impacts of their integration within the original model are evaluated.     

Indicators of landscape organization and functionality in semi-arid former agricultural lands under a passive restoration management over two periods of abandonment

Abandoned lands previously used for agricultural purposes may constitute an opportunity for understanding the variables involved in the restoration of native ecosystems over time. In this study, we assessed the functional status of an abandoned farmland currently used for conservation, using a methodology based on indicators of landscape organization and soil surface. We analyzed changes in plant cover, patch and interpatches structure and several soil surface properties during two periods of land abandonment (less and more than 40 years). Using this methodology, we characterize the potential of the ecosystem to capture and transfer resources, and the state of functional properties such as infiltration capacity, soil stability and nutrient cycling.We detected a significant development of the shrub layer and an increase of the number, type and area occupied by vegetated patches in old fields. The contribution of vegetated patches to the recovery of stability, infiltration and nutrient functions was significant at the local scale. Nonetheless, when analyzing the landscape as a whole only the nutrient cycling index was significantly higher in old fields. The lack of improvement of the stability and infiltration in old fields can lead to further degradation and indicates that even though vegetation cover may have improved over time in old fields, the current cover might not be enough to prevent further degradation by erosion. Our results reinforce the importance of using functionality indexes in future studies focused on adequate restoration measures to protect the function of desert ecosystems, especially when aimed for biodiversity conservation. Hence, the use of monitoring systems based on organization and function indicators is a useful tool to represent the current state and potential recovery of previously disturbed ecosystems, provided that the time scale is taken into account.     

Group sequential and adaptive designs - a review of basic concepts and points of discussion

In recent times, group sequential and adaptive designs for clinical trials have attracted great attention from industry, academia and regulatory authorities. These designs allow analyses on accumulating data - as opposed to classical, "fixed-sample" statistics. The rapid development of a great variety of statistical procedures is accompanied by a lively debate on their potential merits and shortcomings. The purpose of this review article is to ease orientation in both respects. First, we provide a concise overview of the essential technical concepts, with special emphasis on their interrelationships. Second, we give a structured review of the current controversial discussion on practical issues, opportunities and challenges of these new designs.     

Importance of material parameters and strain energy function on the wall stresses in the left ventricle

Patient-specific estimates of the stress distribution in the left ventricles (LV) may have important applications for therapy planning, but computing the stress generally requires knowledge of the material behaviour. The passive stress-strain relation of myocardial tissue has been characterized by a number of models, but material parameters (MPs) remain difficult to estimate. The aim of this study is to implement a zero-pressure algorithm to reconstruct numerically the stress distribution in the LV without precise knowledge of MPs. We investigate the sensitivity of the stress distribution to variations in the different sets of constitutive parameters. We show that the sensitivity of the LV stresses to MPs can be marginal for an isotropic constitutive model. However, when using a transversely isotropic exponential strain energy function, the LV stresses become sensitive to MPs, especially to the linear elastic coefficient before the exponential function. This indicates that in-vivo identification efforts should focus mostly on this MP for the development of patient-specific finite-element analysis.