Biological Modeling

Cognition in living entities -- and their social groupings or institutional artifacts -- is necessarily as complicated as their embedding environments, which, for humans, includes a particularly rich cultural milieu. The asymptotic limit theorems of information and control theories permit construction of a new class of empirical 'regression-like' statistical models for cognitive developmental processes, their dynamics, and modes of dysfunction. Such models may, as have their simpler analogs, prove useful in the study and remediation of cognitive failure at and across (...) the scales and levels of organization that constitute and drive the phenomena of life. These new models particularly focus on the roles of sociocultural environment and stress, in a large sense, as both trigger for the failure of the regulation of biocognition and as 'riverbanks' determining the channels of pathology, with implications across life-course developmental trajectories. We examine the effects of an embedding cultural milieu and its socioeconomic implementations using the 'lenses' of metabolic optimization, control system theory, and an extension of symmetry-breaking appropriate to information systems. A central implication is that most, if not all, human developmental disorders are fundamentally culture-bound syndromes. This has deep implications for both individual treatment and public health policy. (shrink)

There is considerable correspondence between theories and models used in biology and the social sciences. One type of model that is in use in both biology and the social sciences is the fitness landscape model. The properties of the fitness landscape model have been applied rather freely in the social domain. This is partly due to the versatility of the model, but it is also due to the difficulties of transferring a model to another domain. We will demonstrate that in (...) order to transfer the biological fitness landscape model to the social science it needs to be substantially modified. We argue that the syntactic structure of the model can remain unaltered, whilst the semantic dimension requires considerable modification in order to fit the specific phenomena in the social sciences. We will first discuss the origin as well as the basic properties of the model. Subsequently, we will demonstrate the considerations and modifications pertaining to such a transfer by showing how and why we altered the model to analyse collective decision-making processes. We will demonstrate that the properties of the target domain allow for a transfer of the syntactic structure but don’t tolerate the semantic transfer. (shrink)

This computational study generates a hypothesis for the coagulation protein whose initial concentration greatly influences the course of coagulation. Many clinical malignancies of blood coagulation arise due to abnormal initial concentrations of coagulation factors. Sensitivity analysis of mechanistic models of blood coagulation is a convenient method to assess the effect of such abnormalities. Accordingly, the study presents sensitivity analysis, with respect to initial concentrations, of a recently developed mechanistic model of blood coagulation. Both the model and parameters to which model (...) sensitivity is being analyzed provide newer insights into blood coagulation: the model incorporates distinct equations for plasma-phase and platelet membrane-bound species, and sensitivity to initial concentrations is a new dimension in sensitivity analysis. The results show that model predictions are most uncertain with respect to changes in initial concentration of factor VIII, and this hypothesis is supported by results from other models developed independently. (shrink)

In a broad brush, biological models are often constructed in two general types: as a concrete model; as an abstract model. A concrete model is a material model such as model organisms, while an abstract model is a mathematical or computational model consists of equations or algorithms. Though there are types of biological models that cannot be strictly categorized as either concrete or abstract, they are falling somewhere in between this spectrum. In view of the fact that biological phenomena are (...) sui generis and distinct from physical phenomena in many respects, using the concepts in standard modeling fails to account for the differences between biological sciences and physical sciences. Drawing from the resources of a credible-world account of models in economic modeling, I propose to reinterpret abstract models and concrete models in the light of the credible world account of models. (shrink)

The state-of-art research in the field of life’s organization confronts the need to investigate a number of interacting components, their properties and conditions of sustainable behaviour within a natural system. In biology, ecology and life sciences, the performance of such stable system is usually related to homeostasis, a property of the system to actively regulate its state within a certain allowable limits. In our previous work, we proposed a deterministic model for systems’ homeostasis. The model was based on dynamical system’s (...) theory and pairwise relationships of competition, amensalism and antagonism taken from theoretical biology and ecology. However, the present paper proposes a different dimension to our previous results based on the same model. In this paper, we introduce the influence of inter-component relationships in a system, wherein the impact is characterized by direction (neutral, positive, or negative) as well as its (absolute) value, or strength. This makes the model stochastic which, in our opinion, is more consistent with real-world elements affected by various random factors. The case study includes two examples from areas of hydrobiology and medicine. The models acquired for these cases enabled us to propose a convincing explanation for corresponding phenomena identified by different types of natural systems. (shrink)

This book analyses the impact computerization has had on contemporary science and explains the origins, technical nature and epistemological consequences of the current decisive interplay between technology and science: an intertwining of formalism, computation, data acquisition, data and visualization and how these factors have led to the spread of simulation models since the 1950s. -/- Using historical, comparative and interpretative case studies from a range of disciplines, with a particular emphasis on the case of plant studies, the author shows how (...) and why computers, data treatment devices and programming languages have occasioned a gradual but irresistible and massive shift from mathematical models to computer simulations. -/- . (shrink)

Simple regression (regression analysis with a single explanatory variable), and multiple regression (regression models with multiple explanatory variables), typically correspond to very different biological questions. The former use regression lines to describe univariate associations. The latter describe the partial, or direct, effects of multiple variables, conditioned on one another. We suspect that the superficial similarity of simple and multiple regression leads to confusion in their interpretation. A clear understanding of these methods is essential, as they underlie a large range of (...) procedures in common use in biology. Beyond simple and multiple regression in their most basic forms, understanding the key principles of these procedures is critical to understanding, and properly applying, many methods, such as mixed models, generalised models, and causal inference using graphs (including path analysis and its extensions). A simple, but careful, look at the distinction between these two analyses is valuable in its own right, and can also be used to clarify widely-held misconceptions about collinearity (correlations among explanatory variables). There is no general sense in which collinearity is a problem. We suspect that the perception of collinearity as a hindrance to analysis stems from misconceptions about interpretation of multiple regression models, and so we pursue discussions about these misconceptions in this light. In particular, collinearity causes multiple regression coefficients to be less precisely estimated than corresponding simple regression coefficients. This should not be interpreted as a problem, as it is perfectly natural that direct effects should be harder to characterise than univariate associations. Purported solutions to the perceived problems of collinearity are detrimental to most biological analyses. (shrink)

This paper deals with designing a harvesting control strategy for a predator–prey dynamical system, with parametric uncertainties and exogenous disturbances. A feedback control law for the harvesting rate of the predator is formulated such that the population dynamics is asymptotically stabilized at a positive operating point, while maintaining a positive, steady state harvesting rate. The hierarchical block strict feedback structure of the dynamics is exploited in designing a backstepping control law, based on Lyapunov theory. In order to account for unknown (...) parameters, an adaptive control strategy has been proposed in which the control law depends on an adaptive variable which tracks the unknown parameter. Further, a switching component has been incorporated to robustify the control performance against bounded disturbances. Proofs have been provided to show that the proposed adaptive control strategy ensures asymptotic stability of the dynamics at a desired operating point, as well as exact parameter learning in the disturbance-free case and learning with bounded error in the disturbance prone case. The dynamics, with uncertainty in the death rate of the predator, subjected to a bounded disturbance has been simulated with the proposed control strategy. (shrink)

Busseola fusca is a maize and sorghum pest that can cause significant damage to both crops. Given that maize is one of the main cereals grown in the worldwide, this pest is a major challenge for maize production and therefore for the economies of several countries . In this paper , based on the life cycle of B. fusca, we propose a mathematical model to study the population dynamics of this insect pest . A sensitivity analysis using the eFast method (...) was performed to show the most important parameters of the model. We present the theoretical analysis of the model. More precisely, we derive a threshold parameter 0 , called basic offspring number and show that the trivial equilibrium is globally asymptotically stable whenever 0≤1 , while if 0>1 , the non trivial equilibrium is globally asymptotically stable. The theoretical results are supported by numerical simulations. (shrink)

Thanks to genetic and biochemical advances on the molecular mechanism of circadian rhythms in Drosophila, theoretical models closely related to experimental observations can be considered for the regulatory mechanism of the circadian clock in this organism. Modeling is based on the autoregulatory negative feedback exerted by a complex between PER and TIM proteins on the expression of per and tim genes. The model predicts the occurrence of sustained circadian oscillations in continuous darkness. When incorporating light‐induced TIM degradation, the model accounts (...) for damping of oscillations in constant light, entrainment of the rhythm by light‐dark cycles of varying period or photoperiod, and phase shifting by light pulses. The model further provides a molecular dynamical explanation for the permanent or transient suppression of circadian rhythmicity triggered in a variety of organisms by a critical pulse of light. Finally, the model shows that to produce a robust rhythm the various clock genes must be expressed at the appropriate levels since sustained oscillations only occur in a precise range of parameter values. BioEssays 22:84–93, 2000. ©2000 John Wiley & Sons, Inc. (shrink)

The ventricular pressure profile is characteristic of the cardiac contraction progress and is useful to evaluate the cardiac performance. In this contribution, a tissue-level electromechanical model of the left ventricle is proposed, to assist the interpretation of left ventricular pressure waveforms. The left ventricle has been modeled as an ellipsoid composed of twelve mechano-hydraulic sub-systems. The asynchronous contraction of these twelve myocardial segments has been represented in order to reproduce a realistic pressure profiles. To take into account the different energy (...) domains involved, the tissue-level scale and to facilitate the building of a modular model, multiple formalisms have been used: Bond Graph formalism for the mechano-hydraulic aspects and cellular automata for the electrical activation. An experimental protocol has been defined to acquire ventricular pressure signals from three pigs, with different afterload conditions. Evolutionary Algorithms have been used to identify the model parameters in order to minimize the error between experimental and simulated ventricular pressure signals. Simulation results show that the model is able to reproduce experimental ventricular pressure. In addition, electro-mechanical activation times have been determined in the identification process. For example, the maximum electrical activation time is reached, respectively, 96.5, 139.3 and 131.5 ms for the first, second, and third pigs. These preliminary results are encouraging for the application of the model on non-invasive data like ECG, arterial pressure or myocardial strain. (shrink)

A geometrical model of the emergence of a primordium at the shoot apex in dicotyledons is proposed. It is based on recent fundamental results on plant morphogenesis, i.e.: the emergence is preceded by the reorganization of the microtubules of the cortical cytoskeleton, leading to a new orientation of the synthesis of the cell wall microfibrils; the resulting global stress is related to the general orientation of the cell growth.So the model sums up the continuous interactions linking the microtubules, the microfibrils (...) and the cell growth axis.This paper tries to answer three questions which are essential from a botanical point of view: Why does the principal stem shift its growth direction after each lateral emergence? Why do the three axes involved in any ramification exhibit a plane configuration whereas this is an essentially three dimensional phenomenon? Does phyllotaxis exclusively depend upon the local emergence of a primordium?A come and go between the botanical knowledge and the mathematical model leads to an integrated view of the compatibility mechanisms linking the different microtubules and microfibrils networks, without forgetting the apical dome restoration.A geometrical formalism allows a modern redefinition of both the “generating centre” and the “organizing centre” and their field effects.Un modèle géométrique de l'émergence d'un primordium à l'apex des Dicotylédones est proposé. Il s'appuie sur les résultats les plus recents de rétude de la morphogenèse végétale, à savoir: l'émergence est précédée par la réorganisation des microtubules du cytosquelette cortical, determinant ainsi une nouvelle direction de synthese des microfibrilles de la paroi squelettique. la résultante générale des contraintes osmotiques correspond à l'orientation générale de l'allongement cellulaire.Ainsi, le modèle résume les interactions continuelles existant entre les microtubules, les microfibrilles et l'axe de l'allongement cellulaire.Cet article tente de répondre à trois question essentielles d'un point de vue botanique: pourquoi l'axe principal infléchit-il sa direction de croissance après emergence laterale? pourquoi les trois directions ainsi mises en évidence, à savoir les ancienne et nouvelle tiges principales et l'émergence latérale, présentent-elles une configuration plane, alors que le phénomène est essentiellement tridimensionnel? la phyllotaxie dépend-elle exclusivement du phénomène local de l'emergence laterale?L'aller-retour entre les acquis de la Botanique et le modèle mathématique permet de construire une vision intégrée des mécanismes de compatibilité entre les divers réseaux de microtubules et microfibrilles, incluant la restauration du dôme apical. Le formalisme géometrique mène à une reformulation moderne des anciens concepts de “centre générateur” et de “centre organisateur”, fonctionnant par effet de champ. (shrink)

The selection strategies of individuals and 2-person cooperative groups were investigated in 5 concept-attainment problems. 2 types of stimulus displays were used: (a) form displays, consisting of geometric forms varying in 6 attributes with 2 levels of each, (b) sequence displays, consisting of 6 plus and/or minus signs in a row. The arrangement of cards in the stimulus displays was ordered or random. The principal results were: (a) 2-person groups used the focusing strategy more, required fewer card choices to solution, (...) and required more time than individuals; (b) form displays resulted in more use of the focusing strategy than sequence displays, with no difference in number of card choices; (c) no difference between ordered and random arrays in use of the focusing strategy or number of card choices. (PsycINFO Database Record (c) 2016 APA, all rights reserved). (shrink)

The accurate annotation of an unknown protein sequence depends on extant data of template sequences. This could be empirical or sets of reference sequences, and provides an exhaustive pool of probable functions. Individual methods of predicting dominant function possess shortcomings such as varying degrees of inter-sequence redundancy, arbitrary domain inclusion thresholds, heterogeneous parameterization protocols, and ill-conditioned input channels. Here, I present a rigorous theoretical derivation of various steps of a generic algorithm that integrates and utilizes several statistical methods to predict (...) the dominant function in unknown protein sequences. The accompanying mathematical proofs, interval definitions, analysis, and numerical computations presented are meant to offer insights not only into the specificity and accuracy of predictions, but also provide details of the operatic mechanisms involved in the integration and its ensuing rigor. The algorithm uses numerically modified raw hidden markov model scores of well defined sets of training sequences and clusters them on the basis of known function. The results are then fed into an artificial neural network, the predictions of which can be refined using the available data. This pipeline is trained recursively and can be used to discern the dominant principal function, and thereby, annotate an unknown protein sequence. Whilst, the approach is complex, the specificity of the final predictions can benefit laboratory workers design their experiments with greater confidence. -/- . (shrink)

Models of biological and cultural evolution that developed from the 19th century onward are characterized by two main features:They were mostly centered on the unilinear transmission of cultural and biological replicators, and They were centered on phylogenetic images of descent, that means, specifically, the tree of life and the tree of languages metaphors. The purpose of this paper is to show that theories of unilinear descent in biology, linguistics and anthropology represent just one among several approaches in explain evolutionary development (...) in all three realms. ‘Antidotes’ to the pedigree and tree of life metaphors have been presented as early as phylogenetic models, but have been often neglected, surpressed or simply been ignored. We try to draw attention to these alternative models of lateral and vertical transfer of words, genes, and culture traits which form an indispensable part of an all-encompassing evolutionary epistemiology. (shrink)

A mathematical model for Vibrio Cholerae (V. Cholerae) in a closed environment is considered, with the aim of investigating the impact of climatic factors which exerts a direct influence on the bacterial metabolism and on the bacterial reservoir capacity. We first propose a V. Cholerae mathematical model in a closed environment. A sensitivity analysis using the eFast method was performed to show the most important parameters of the model. After, we extend this V. cholerae model by taking account climatic factors (...) that influence the bacterial reservoir capacity. We present the theoretical analysis of the model. More precisely, we compute equilibria and study their stabilities. The stability of equilibria was investigated using the theory of periodic cooperative systems with a concave nonlinearity. Theoretical results are supported by numerical simulations which further suggest the necessity to implement sanitation campaigns of aquatic environments by using suitable products against the bacteria during the periods of growth of aquatic reservoirs. (shrink)

The growth characteristics of the recently derived Trans-Gompertz function are compared to those of the Generalized Logistic function. Both functions are defined by one shaping parameter and one rate parameter. The functions are matched at a specified point on the growth curve by equating both the first and second derivatives. Analysis shows that the matched Trans-Gompertz function will have grown at a faster rate with a larger inflection point ratio.

The present paper deals with a free boundary problem modeling the growth process of necrotic multi-layer tumors. We prove the existence of flat stationary solutions and determine the linearization of our model at such an equilibrium. Finally, we compute the solutions of the stationary linearized problem and comment on bifurcation.

Many predator species feed on prey that fluctuates in abundance from year to year. Birds of prey can face large fluctuations in food abundance i.e. small mammals, especially voles. These annual changes in prey abundance strongly affect the reproductive success and mortality of the individual predators and thus can be expected to influence their population dynamics and persistence. The barn owl, for example, shows large fluctuations in breeding success that correlate with the dynamics in voles, their main prey species. Analysis (...) of the impact of fluctuations in vole abundance (their amplitude, peaks and lows, cycle length and regularity) with a simple predator prey model parameterized with literature data indicates population persistence is especially affected by years with low vole abundance. In these years the population can decline to low owl numbers such that the ensuing peak vole years cannot be exploited. This result is independent of the length and regularity of vole fluctuations. The relevance of this result for conservation of the barn owl and other birds of prey that show a numerical response to fluctuating prey species is discussed. (shrink)

The House Sparrow (Passer domesticus), formerly a common bird species, has shown a rapid decline in Western Europe over recent decades. In The Netherlands, its decline is apparent from 1990 onwards. Many causes for this decline have been suggested that all decrease the vital rates, i.e. survival and reproduction, but their actual impact remains unknown. Although the House Sparrow has been dominant in The Netherlands, data on life history characteristics for this bird species are scarce: data on reproduction are non-existent, (...) and here we first present survival estimates based on live encounters and dead recoveries of marked individuals over the period 1976–2003, 14 years before and 14 years during the decline, reported to the Dutch Ringing Centre. We show that there is an indication that both juvenile and adult survival are lower during the period of decline. -/- Secondly, to be able to analyse the relative impact of changes in the vital rates, we formulated a general matrix model based on a range of survival values between zero and one with a step size of 0.01 (both juvenile and adult yearly survival) and a range of realistic reproduction values (one, three or five fledglings per pair per year). With the matrix model, we calculated the finite rate of population change (λ) and applied elasticity analysis. To diagnose the cause of the decline in the Dutch House Sparrow, we parameterised the model with estimates of survival values before and during the decline and present the resulting λ. With the survival estimates from the declining period, λ < 1 only if reproduction is relatively low. We discuss this result within the light of available literature data on survival in the House Sparrow. Finally, we evaluate which of the suggested causes of population decline should be reversed to mitigate the decline and how this can be achieved. (shrink)

Most mathematical models used to examine the role of different stages of human immunodeficiency virus infection unrealistically assume that HIV is transmitted through one-off contacts or that transmission rates are the same between males and females. We sought to examine whether inferences from previous models are robust to the relaxation of those unrealistic assumptions. We developed a model of HIV transmissions through sexual partnerships assuming that sexual partnerships have variable duration, sexual partnerships are concurrent, and the male-to-female transmission rate is (...) higher than the female-to-male transmission rate, with a focus on the third assumption. Assuming a higher rate for male-to-female than female-to-male transmissions decreases the overall transmission of HIV but increases the equilibrium fraction of transmissions during primary HIV infection in long-term partnerships, compared to the case where transmission rates are assumed to be symmetric between males an females. Previous modeling studies that assume symmetric transmission rates between males and females may have overestimated the overall spread of HIV, but underestimated the relative contribution of PHI. To make robust inferences on the role of different stages of HIV infection in the sexual spread of HIV, models should take into account that transmission rates may be asymmetric by sex. (shrink)

We describe reversible adaptive trees, a class of stochastic algorithms modified from the formerly described adaptive trees. They evolve in time a finite subset of an ambient Euclidean space of any dimension, starting from a seed point and, accreting points to the evolving set, they grow branches towards a target set which can depend on time. In contrast with plain adaptive trees, which were formerly proven to have strong convergence properties to a static target, the points of reversible adaptive trees (...) are removed from the tree when they have not been used recently enough in a path from the root to an accreted point. This, together with a straightening process performed on the branches, permits the tree to follow some moving targets and still remain adapted to it. We then discuss in what way one can see such reversible trees as a model for a qualitative property of resilience, which leads us to discuss qualitative modeling. (shrink)

Heart rate variability is an indicator of the regulation of the heart, see Task Force :1043–1065, 1996). This study compares the regulation of the heart in two cases of healthy subjects within real life situations: Marathon runners and shift workers. After an update on the state of the art on HRV processing, we specify our probabilistic model: We choose modeling heartbeat series by locally stationary Gaussian process . HRV is then processed by the combination of two statistical methods: Continuous wavelet (...) transform for calculating the spectral density energy in the high frequency and low frequency bands and Change point analysis to detect changes of heart regulation. Next, we plot the variations of the HF and LF energy in extreme conditions for both populations. This puts in light, that physical activities can be ordered in a logical continuum. This allows to define a new index based on HF and LF energy that is log HF + log LF which appears relevant to measure HR regulation. The results obtained are pertinent but have to be completed by further studies. (shrink)

Of all global problems world population growth is the most significant. The growth of the number of people expresses the sum outcome of all economic, social and cultural activities that comprise human history. Demographic data in a concise and quantitative way describe this process in the past and present. By applying the concepts of nonlinear dynamics and synergetics, it is possible to work out a mathematical model for a phenomenological description of the global demographic process and project its trends into (...) the future. Assuming self-similarity as the dynamic principle of development, growth can be described over practically the whole of human history, with a growth rate proportional to the square of the number of people. This is due to a collective interaction, responsible for the growth of human numbers, as the result of the informational nature of development. The large parameter of the theory and the effective size of a coherent population group is of the order of 105. As the microscopic parameter of the phenomenology, the human life span is introduced into the theory. Estimates of the beginning of human development 4-5 million years ago and of the total number of people who have ever lived since then ≈ 100 billion are made. In the framework of the model, large scale cycles defined by history and anthropology are shown to follow an exponential pattern of growth, culminating in the demographic transition, a veritable revolution when population growth is to stabilize at 10 to 12 billion. (shrink)

This paper describes a traditional SIR type epidemic model with saturated infection rate and treatment function. The dynamics of the model is studied from the point of view of stability and bifurcation. Basic reproduction number is obtained and it is shown that the model system may possess a backward bifurcation. The global asymptotic stability of the endemic equilibrium is studied with the help of a geometric approach. Optimal control problem is formulated and solved. Some numerical simulation works are carried out (...) to validate our analytical results. (shrink)

Nine selection‐survival strategies were implemented in a genetic algorithm experiment, and differences in terms of evolution were assessed. The moments of evolution (expressed as generation numbers) were recorded in a contingency of three strategies (i.e., proportional, tournament, and deterministic) for two moments (i.e., selection for crossover and mutation and survival for replacement). The experiment was conducted for the first 20,000 generations in 46 independent runs. The relative moments of evolution (where evolution was defined as a significant increase in the determination (...) coefficient relative to the previous generation) when any selection‐survival strategy was used fit a Log‐Pearson type III distribution. Moreover, when distributions were compared to one another, functional relationships were identified between the population parameters, revealing a degeneration of the Log‐Pearson type III distribution in a one‐parametrical distribution that can be assigned to the chosen variable—evolution strategy. The obtained theoretical population distribution allowed comparison of the selection‐survival strategies that were used. © 2012 Wiley Periodicals, Inc. Complexity, 2012. (shrink)

Basic quantitative genetic models of human behavioral variation have made clear that individual differences in behavior cannot be understood without acknowledging the importance of genetic influences. Yet these basic models estimate average, population-level genetic and environmental influences, obscuring differences that might exist within the population and masking systematic transactions between specific genetic and environmental influences. This article discusses a newer, more sophisticated and powerful quantitative genetic model that articulates these transactions. Results from this model highlight the ways in which the (...) gene- environment interaction and correlation are intertwined. They can be used to integrate findings from quantitative and molecular genetic studies and to understand the roles of genetic influences and social forces in manifested behaviors, even when DNA sequence variation is not relevant. (PsycINFO Database Record (c) 2016 APA, all rights reserved). (shrink)

The guard-guardee model for plant immunity describes how resistance proteins in host cells monitor host target proteins that are manipulated by pathogen effector proteins. A recently suggested extension of this model includes decoys, which are duplicated copies of guardee proteins, and have the sole function to attract the effector and, when modified by the effector, trigger the plant immune response. Here we present a proof-of-principle model for the functioning of decoys in plant immunity, quantitatively developing this experimentally derived concept. Our (...) model links the basic cellular chemistry to the outcomes of pathogen infection and resulting fitness costs for the host. In particular, the model allows identification of conditions under which it is optimal for decoys to act as triggers for the plant immune response, and of conditions under which it is optimal for decoys to act as sinks that bind the pathogen effectors but do not trigger an immune response. (shrink)

Philosophers of science have recently focused on the scientific activity of modeling phenomena, and explicated several of its properties, as well as the activities embedded into it. A first approach to modeling has been elaborated in terms of representing a target system: yet other epistemic functions, such as producing data or detecting phenomena, are at least as relevant. Additional useful distinctions have emerged, such as the one between phenomenological and mechanistic models. In biological sciences, besides mathematical models, models now come (...) in three forms: in vivo, in vitro and in silico. Each has been investigated separately, and many specific problems they raised have been laid out. Another relevant distinction is disciplinary: do models differ in significant ways according to the discipline involved—medicine or biology, evolutionary biology or earth science? Focusing on either this threefold distinction or the disciplinary boundaries reveals that they might not be sufficient from a philosophical perspective. On the contrary, focusing on the interaction between these various kinds of models, some interesting forms of explanation come to the fore, as is exemplified by the papers included in this issue. On the other hand, a focus on the use of models, rather than on their content, shows that the distinction between biological and medical models is theoretically sound. (shrink)

The pervasive use of computer simulations in the sciences brings novel epistemological issues discussed in the philosophy of science literature since about a decade. Evolutionary biology strongly relies on such simulations, and in relation to it there exists a research program (Artificial Life) that mainly studies simulations themselves. This paper addresses the specificity of computer simulations in evolutionary biology, in the context (described in Sect. 1) of a set of questions about their scope as explanations, the nature of validation processes (...) and the relation between simulations and true experiments or mathematical models. After making distinctions, especially between a weak use where simulations test hypotheses about the world, and a strong use where they allow one to explore sets of evolutionary dynamics not necessarily extant in our world, I argue in Sect. 2 that (weak) simulations are likely to represent in virtue of the fact that they instantiate specific features of causal processes that may be isomorphic to features of some causal processes in the world, though the latter are always intertwined with a myriad of different processes and hence unlikely to be directly manipulated and studied. I therefore argue that these simulations are merely able to provide candidate explanations for real patterns. Section 3 ends up by placing strong and weak simulations in Levins’ triangle, that conceives of simulations as devices trying to fulfil one or two among three incompatible epistemic values (precision, realism, genericity). (shrink)

Philosophers of science have recently focused on the scientific activity of modeling phenomena, and explicated several of its properties, as well as the activities embedded into it. A first approach to modeling has been elaborated in terms of representing a target system: yet other epistemic functions, such as producing data or detecting phenomena, are at least as relevant. Additional useful distinctions have emerged, such as the one between phenomenological and mechanistic models. In biological sciences, besides mathematical models, models now come (...) in three forms: in vivo, in vitro and in silico. Each has been investigated separately, and many specific problems they raised have been laid out. Another relevant distinction is disciplinary: do models differ in significant ways according to the discipline involved—medicine or biology, evolutionary biology or earth science? Focusing on either this threefold distinction or the disciplinary boundaries reveals that they might not be sufficient from a philosophical perspective. On the contrary, focusing on the interaction between these various kinds of models, some interesting forms of explanation come to the fore, as is exemplified by the papers included in this issue. On the other hand, a focus on the use of models, rather than on their content, shows that the distinction between biological and medical models is theoretically sound. (shrink)

Philosophers of science increasingly believe that much of science is concerned with understanding the mechanisms responsible for the production of natural phenomena. An adequate understanding of scientific research requires an account of how scientists develop and test models of mechanisms. This paper offers a general account of the nature of mechanical models, discussing the representational relationship that holds between mechanisms and their models as well as the techniques that can be used to test and refine such models. The analysis is (...) supported by study of two competing models of a mechanism of speech perception. (shrink)

In a recent article in this Journal, Fumagalli argues that economists are provisionally justified in resisting prominent calls to integrate neural variables into economic models of choice. In other articles, various authors engage with Fumagalli’s argument and try to substantiate three often-made claims concerning neuroeconomic modelling. First, the benefits derivable from neurally informing some economic models of choice do not involve significant tractability costs. Second, neuroeconomic modelling is best understood within Marr’s three-level of analysis framework for information-processing systems. And third, (...) neural findings enable choice modellers to confirm the causal relevance of variables posited by competing economic models, identify causally relevant variables overlooked by existing models, and explain observed behavioural variability better than standard economic models. In this paper, I critically examine these three claims and respond to the related criticisms of Fumagalli’s argument. Moreover, I qualify and extend Fumagalli’s account of how trade-offs between distinct modelling desiderata hamper neuroeconomists’ attempts to improve economic models of choice. I then draw on influential neuroeconomic studies to argue that even the putatively best available neural findings fail to substantiate current calls for a neural enrichment of economic models. (shrink)

The classic model of blood pressure regulation by Guyton et al. (Annu Rev Physiol 34:13–46, 1972a; Ann Biomed Eng 1:254–281, 1972b) set a new standard for quantitative exploration of physiological function and led to important new insights, some of which still remain the focus of debate, such as whether the kidney plays the primary role in the genesis of hypertension (Montani et al. in Exp Physiol 24:41–54, 2009a; Exp Physiol 94:382–388, 2009b; Osborn et al. in Exp Physiol 94:389–396, 2009a; Exp (...) Physiol 94:388–389, 2009b). Key to the success of this model was the fact that the authors made the computer code (in FORTRAN) freely available and eventually provided a convivial user interface for exploration of model behavior on early microcomputers (Montani et al. in Int J Bio-med Comput 24:41–54, 1989). Ikeda et al. (Ann Biomed Eng 7:135–166, 1979) developed an offshoot of the Guyton model targeting especially the regulation of body fluids and acid–base balance; their model provides extended renal and respiratory functions and would be a good basis for further extensions. In the interest of providing a simple, useable version of Ikeda et al.’s model and to facilitate further such extensions, we present a practical implementation of the model of Ikeda et al. (Ann Biomed Eng 7:135–166, 1979), using the ODE solver Berkeley Madonna. (shrink)

Traditionally, a scientific model is thought to provide a good scientific explanation to the extent that it satisfies certain scientific goals that are thought to be constitutive of explanation. Problems arise when we realize that individual scientific models cannot simultaneously satisfy all the scientific goals typically associated with explanation. A given model’s ability to satisfy some goals must always come at the expense of satisfying others. This has resulted in philosophical disputes regarding which of these goals are in fact necessary (...) for explanation, and as such which types of models can and cannot provide explanations. Explanatory monists argue that one goal will be explanatory in all contexts, while explanatory pluralists argue that the goal will vary based on pragmatic considerations. In this paper, I argue that such debates are misguided, and that both monists and pluralists are incorrect. Instead of any goal being given explanatory priority over others in a given context, the different goals are all deeply dependent on one another for their explanatory power. Any model that sacrifices some explanatory goals to attain others will always necessarily undermine its own explanatory power in the process. And so when forced to choose between individual scientific models, there can be no explanatory victors. Given that no model can satisfy all the goals typically associated with explanation, no one model in isolation can provide a good scientific explanation. Instead we must appeal to collections of models. Collections of models provide an explanation when they satisfy the web of interconnected goals that justify the explanatory power of one another. (shrink)

Pluripotency can be considered a functional characteristic of pluripotent stem cells (PSCs) populations and their niches, rather than a property of individual cells. In this view, individual cells within the population independently adopt a variety of different expression states, maintained by different signaling, transcriptional, and epigenetics regulatory networks. In this review, we propose that generation of integrative network models from single cell data will be essential for getting a better understanding of the regulation of self‐renewal and differentiation. In particular, we (...) suggest that the identification of network stability determinants in these integrative models will provide important insights into the mechanisms mediating the transduction of signals from the niche, and how these signals can trigger differentiation. In this regard, the differential use of these stability determinants in subpopulation‐specific regulatory networks would mediate differentiation into different cell fates. We suggest that this approach could offer a promising avenue for the development of novel strategies for increasing the efficiency and fidelity of differentiation, which could have a strong impact on regenerative medicine. (shrink)

Increasingly, biologists are using computers to model and to create biological representations. However, the exponential growth in available biological dataposes a challenge for experimental and theoretical researchers in both Biology and in Computer Science. In short, when even the simple retrieval of relevant biological information for a researcher becomes a complex task — its analysis and synthesis with other biological information will become even more daunting and unlikely. In this context, specially organized ‘structures of representation’ are needed for the efficient (...) interpretation of experimentally generated data. The “semantic Web” is a recent trend in networking techniques that we will examine here as a possible strategy for the computation of biological data — one that may allow us to take into account both the semiotic dimensions of biological processes, as well as their dynamic organization into stable and systemic levels. Thereupon, we propose that a semantic network for biology could benefit from principles rooted in such previous representation efforts as computer-generated ‘landscapes’ and ‘physical attractors’ — and that such principles could, in turn, then be better integrated into biological research through the development of a more semiotically informed user / computer interface design. (shrink)

New class of therapies, including bipolar therapies and “paradoxical” unipolar therapies were firstly proposed in relation to a clinical insight and to some results of biological investigations, then they gave rise to mathematical modeling which brought a justification of these therapies, at least from a theoretical point of view. After recalling the mathematical model for the regulation of agonistic antagonistic couples, and reporting the fundamental types of control simulation by means of it, we point out the validity of therapeutical applications (...) inferred from this model. These therapy modalities, including BPT and PUT, now concern the following diseases: astrocytomas, epilepsia and trials on multiple sclerosis. Even if such attempts are in their early stage, noticeably for the last case where biological changes have mainly been studied, it seems that a large span of treatments is open to BPT and PUT. Improvement of these techniques in the future depends, in our opinion, on a parallel working on the dynamics of the mathematical model and the dynamics, perceived by clinical insight and confirmed by biological investigations, of the body reactions to such strategies. Justification of BPT and PUT was given, by resorting to the notion of “pathological homeostasis” which, too often, intervenes in order to nullify the effects of unilateral therapies. This research has elicited some therapies which use two agents with antagonistic effects or only an agent with effects similar to the agent already in excess in the body - in both cases at nearly physiological doses. (shrink)

A formal neuron has been studied mathematically. The spiking behaviour of a single neuron has been considered and the influence of the other neurons has been replaced by an average activity level. Four different kinds of spiking behaviour are predicted by the model: B, C, P and S neurons and several real neurons can be classified within these four categories. Some properties of the spiking neuron are calculated: 1) the time between spikes, 2) the spike train length and 3) the (...) silent time. Because these magnitudes can be measured in the laboratory, an experimental validation of the model is proposed. (shrink)

This paper considers how the relationship between mathematical models and theories in biology may change over time, on the basis of a historical analysis of the development of a mathematical model of metabolism, metabolic control analysis, and its relationship to theories of metabolic control. I argue that one can distinguish two ways of characterising the relationship between models and theories, depending on the stage of model and/or theory development that one is considering: partial independence and autonomy. Partial independence describes a (...) model's relationship with existing theory, thus referring to relationships that have already been established between model and theory during model construction. By contrast, autonomy is a feature of relationships which may become established between model and theory in the future, and is expressed by a model's open ended role in constructing emerging theory. These characteristics have often been conflated by existing philosophical accounts, partly because they can only be identified and analysed when adopting a historical perspective on scientific research. Adopting a clear distinction between partial independence and autonomy improves philosophical insight into the changing relationship between models and theories. (shrink)