Computer analysis of biological systems, using approaches such as metabolic control analysis is common. A typical example is a language like Herbert Sauro's SCAMP (Sauro & Fell, 1991), which allows simulations of enzyme systems, and calculation of control coefficients and elasticities. However such systems are motivated by the underlying biochemical theory and often have limitations as programming languages which mean that they can only be applied to particular classes of problems.ABPL (a biochemical programming language) extends these ideas by adding all (...) the facilities of a fully-fledged programming language, together with some of the capabilities of a modern computer algebra system. Syntactically it derives from the programming language LISP, while the underlying functionality is that of iMAP, the successor to SCAMP. (shrink)

The aim of this work is to present aggregation methods of hierarchically organized systems allowing one to replace the initial micro-system by a macro-system described by a few global variables. We also study the relations between the fast micro-dynamics and the slow macro-dynamics which can produce global properties. Emergence corresponds to a bottom-up coupling that is the result effected by a micro-level at a macro-level. As an example, we present prey-predator models with different time scales in an heterogeneous environment. A (...) fast time scale is associated to the migration process on spatial patches and a slow time scale is associated to growth and interactions between the populations. Preys must go on spatial patches where resources are located and where predators can attack them. The efficiency of the predators to catch preys is patch dependent. Perturbation methods allow us to aggregate the initial system of differential equations for the patch sub-populations into a macro-system of two differential equations governing the total population densities. We study the case of density independent and density dependent migrations. In the latter case, we show that different functional responses can emerge in the macro prey-predator model as a result of the coupling between the slow and fast systems. (shrink)

Several key areas in modeling the cardiovascular and respiratory control systems are reviewed and examples are given which reflect the research state of the art in these areas. Attention is given to the interrelated issues of data collection, experimental design, and model application including model development and analysis. Examples are given of current clinical problems which can be examined via modeling, and important issues related to model adaptation to the clinical setting.

Abstract This paper provides an account of the experimental conditions required for establishing whether correlating or causally relevant factors are constitutive components of a mechanism connecting input (start) and output (finish) conditions. I argue that two-variable experiments, where both the initial conditions and a component postulated by the mechanism are simultaneously manipulated on an independent basis, are usually required in order to differentiate between correlating or causally relevant factors and constitutively relevant ones. Based on a typical research project molecular biology, (...) a flowchart model detailing typical stages in the formulation and testing of hypotheses about mechanistic components is also developed. Content Type Journal Article Category Original paper in Philosophy of Biology Pages 1-17 DOI 10.1007/s13194-011-0045-3 Authors Tudor M. Baetu, Department of Philosophy, University of Maryland, College Park, MD, USA Journal European Journal for Philosophy of Science Online ISSN 1879-4920 Print ISSN 1879-4912. (shrink)

We show how a simple nonlinear dynamical system (the discrete quadratic iteration on the unit segment) can be the basis for modelling the embryogenesis process. Such an approach, even though being crude, can nevertheless prove to be useful when looking with the two main involved processes:i) on one hand the cell proliferation under successive divisions ii) on the other hand, the differentiation between cell lineages. We illustrate this new approach in the case of Caenorhabditis elegans by looking at the early (...) stages of embryogenesis, up to several hundreds of cells (lima bean larval stage). We show how the many results that have been obtained by several groups can be interpreted in terms of values for the parameters controlling the dynamical system. Furthermore, we can extend the model to the cases of genetic mutations. More precisely the teratogenetic and lethal effects are associated with abnormal variation of the control parameters with time. (shrink)

We used computer simulations to study the possible role of the dispersion of cellular coupling, refractoriness or both, in the mechanisms underlying cardiac arrhythmias. Local ischemia was first assumed to induce cell to cell dispersion of the coupling resistance (Case 1), refractory period (Case 2), or both of them (Case 3). Our numerical experiments based on the van Capelle and Durrer model showed that vortices could not be induced by cell to cell variations. With cellular properties dispersed in a patchy (...) way within the ischemic zone, a single activation wave could give rise to abnormal activities. This demonstrates the stability of the wave front under small inhomogeneities. Probabilities of reentry, estimated for the three cases cited above showed that a severe alteration of the coupling resistance may be an important factor in the genesis of reentry. Moreover, use of isochronal maps revealed that vortices were both stable and sustained with an alteration of the coupling alone or combined with a reduction of the action potential duration. Conversely, simulations with reduction of the refractoriness alone, inducing only transient patterns, could exhibit functionally determined reentries. (shrink)

The present work is aimed at investigating the effects of myocardial infarction and ischemia on induction of ventricular fibrillation. Electrophysiologic effects of global and local ischemia (variation of the dispersion of refractory periods as well as conduction velocity) on initiation of reentry mechanisms was studied by means of computer simulations based on a cellular automata model of propagation of activation wave through a ventricular surface element. A local area of ischemia where effects of the dispersion of refractory periods are investigated (...) is then simulated. This is made using a Gaussian distribution characterized by its mean and standard deviation. These simulations show that ischemia is capable of initiating reentry phenomena which propagate through the whole ventricle; they are responsible for ventricular fibrillation which causes sudden cardiac death, even when ischemia only involves limited parts of the myocardium. Statistical study of the probability of reentries as a function of both of the size of ischemic zones and the rate of dispersion of refractory periods shows that the latter parameter is of primary importance in triggering cardiac reentries. (shrink)

Limitations of antiarrhythmic drugs on cardiac sudden death prevention appeared since the early 80's. The "Cardiac Arrhythmia Suppression Trial"(CAST) showed more recently that mortality was significantly higher inpatients treated with some particular antiarrhythmic drugs than in non-treated patients. In this field, our group recently demonstrated that a bolus of a Class 1B antiarrhythmic drug was able to trigger a ventricular fibrillation due to transient blocks induction. The aim of the present work was to systematically study, by use of the van (...) Capelle and Durrer (VCD) model which allows to simulate ventricular activation wave propagation, the link between arrhythmogenic effects and the ability of transient blocks to possibly degenerate in severe arrhythmias. A fragment of the ventricular wall is represented by an array of 16384elements electrically coupled. Effects of induction of one or several transient blocks, as the effects of their size and duration on possible induction of reentries have been studied. Results obtained show that various combinations between these different parameters may trigger reentries, ventricular tachycardia and/or more complex patterns assimilable to ventricular fibrillation. These results clearly evidence the fact that possible induction of transient blocks may directly be related to risk factor associated to arrhythmogenic effects of antiarrhythmic drugs. (shrink)

Systems biology is a vigorous and expanding discipline, in many ways a successor to genomics and perhaps unprecendented in its combination of biology with a ...

Historically embryogenesis has been among the most philosophically intriguing phenomena. In this paper I focus on one aspect of biological development that was particularly perplexing to the ancients: self-organisation. For many ancients, the fact that an organism determines the important features of its own development required a special model for understanding how this was possible. This was especially true for Aristotle, Alexander, and Simplicius who all looked to contemporary technology to supply that model. However, they did not all agree on (...) what kind of device should be used. In this paper I explore the way these ancients made use of technology as a model for the developing embryo. However, my purpose here is more than just the historical interest of knowing which devices were used by whom and how each of them worked; I shall largely ignore the details of how the various devices actually worked. Instead I shall look at the use of technology from a philosophical perspective. As we shall see, the different choices of device reveal fundamental differences in the way each thinker understood the nature of biological development itself. Thus, the central aim of this paper is to examine, not who used what devices and how they worked, but why they used those particular devices and what they thought their functioning could tell us about the nature of embryological phenomena. (shrink)

The concepts of adaptive/fitness landscapes and adaptive peaks are a central part of much of contemporary evolutionary biology; the concepts are introduced in introductory texts, developed in more detail in graduate-level treatments, and are used extensively in papers published in the major journals in the field. The appeal of visualizing the process of evolution in terms of the movement of populations on such landscapes is very strong; as one becomes familiar with the metaphor, one often develops the feeling that it (...) is possible to gain deep insights into evolution by thinking about the movement of populations on landscapes consisting of adaptive valleys and peaks. But, since Wright first introduced the metaphor in 1932, the metaphor has been the subject of persistent confusion, from equivocation over just what the features of the landscape are meant to represent to how we ought to expect the landscapes to look. Recent advances—conceptual, empirical, and computational—have pointed towards the inadequacy and indeed incoherence of the landscapes as usually pictured. I argue that attempts to reform the metaphor are misguided; it is time to give up the pictorial metaphor of the landscape entirely and rely instead on the results of formal modeling, however difficult such results are to understand in ‘intuitive’ terms. (shrink)

A formal theory of the ecological niche is indispensable not only for semantic precision in philosophy to understand and compare it with other meanings of niche, but also when computer scientists and ecologists desire to create interoperable software where one can retrieve the niche of a species and compare their parameters. The proposed model is a more fine-grained description of the ecological niche, including the distinction between its complex concept, the abstract niche (‘fundamental niche’) with its hypervolume in multidimensional space, (...) and its realisations (‘realised niches’). The presented ecological niche may initiate new avenues for research in ecology, particularly concerning the conditions/categories of a hypervolume, as well as further philosophical inquiry and comparison with other niches. (shrink)

This paper aims to identify the key characteristics of model organisms that make them a specific type of model within the contemporary life sciences: in particular, we argue that the term “model organism” does not apply to all organisms used for the purposes of experimental research. We explore the differences between experimental and model organisms in terms of their material and epistemic features, and argue that it is essential to distinguish between their representational scope and representational target. We also examine (...) the characteristics of the communities who use these two types of models, including their research goals, disciplinary affiliations, and preferred practices to show how these have contributed to the conceptualization of a model organism. We conclude that model organisms are a specific subgroup of organisms that have been standardized to fit an integrative and comparative mode of research, and that it must be clearly distinguished from the broader class of experimental organisms. In addition, we argue that model organisms are the key components of a unique and distinctively biological way of doing research using models. (shrink)

Despite their best efforts, scientists may be unable to construct models that simultaneously exemplify every theoretical virtue. One explanation for this is the existence of tradeoffs: relationships of attenuation that constrain the extent to which models can have such desirable qualities. In this paper, we characterize three types of tradeoffs theorists may confront. These characterizations are then used to examine the relationships between parameter precision and two types of generality. We show that several of these relationships exhibit tradeoffs and discuss (...) what consequences those tradeoffs have for theoretical practice. (shrink)

Coordination of immune responses in the gut is a complex task. In order to fight pathogens and maintain a defined population of commensal microbes, the mucosal immune system has to coordinate information from the external (luminal) and internal (abluminal) environment and respond accordingly. Dendritic cells (DCs) are crucial cell types involved in this process as they integrate these signals and direct immunogenic or tolerogenic responses. Here, we review how various functions of DCs depend on microbial stimuli and how these stimuli (...) influence the course of immune activation. (shrink)