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PubMed1999

Molecular and evolutionary computation: the tug of war between context freedom and context sensitivity.

Proteins and nucleic acids constitute a vast potential reservoir of pattern recognizers that operate on the basis of shape complementarity. It is possible to construct models of computing in which these shape-based interactions contribute directly to recognition of signal patterns at the device (or cell) level. The input-output transform is molded by variation-selection evolution. Such models provide clues as to the organizational features that enable biomolecular matter to acquire nonevolutionary modes of problem solving through the evolutionary process. The requisite organizations are characterized by a high dimensionality that allows them to simultaneously exhibit aspects of context-sensitivity and context-independence.

Animals↗
PubMed2005

Prediction of cis-regulatory elements using binding site matrices--the successes, the failures and the reasons for both.

Protein-DNA interactions control many aspects of animal development and cellular responses to the environment. Although profiling of individual transcription factor binding sites is not a reliable guide for predicting the position of cis-regulatory elements in large genomes, modelling the evolution and the organization of regulatory elements has provided enough information to make some successful predictions. For vertebrate genomes, the field is limited by the lack of sufficient experimental data upon which to build reliable models. Nonetheless, a combination of experimental, computational and comparative data is likely to reveal aspects of complex regulatory networks in vertebrates, just as it has already done for simple eukaryotic genomes.

Animals↗
PubMed1996

A model of wound-healing angiogenesis in soft tissue.

Angiogenesis, or blood vessel growth, is a critical step in the wound-healing process, involving the chemotactic response of blood vessel endothelial cells to macrophage-derived factors produced in the wound space. In this article, we formulate a system of partial differential equations that model the evolution of the capillary-tip endothelial cells, macrophage-derived chemoattractants, and the new blood vessels during the tissue repair process. Chemotaxis is incorporated as a dominant feature of the model, driving the wave-like ingrowth of the wound-healing unit. The resulting model admits traveling wave solutions that exhibit many of the features characteristic of wound healing in soft tissue. The steady propagation of the healing unit through the wound space, the development of a dense band of fine, tipped capillaries near the leading edge of the wound-healing unit (the brush-border effect), and an elevated vessel density associated with newly healed wounds, prior to vascular remodeling, are all discernible from numerical simulations of the full model. Numerical simulations mimic not only the normal progression of wound healing but also the potential for some wounds to fail to heal. Through the development and analysis of a simplified model, insight is gained into how the balance between chemotaxis, tip proliferation, and tip death affects the structure and speed of propagation of the healing unit. Further, expressions defining the healed vessel density and the wavespeed in terms of known parameters lead naturally to the identification of a maximum wavespeed for the wound-healing process and to bounds on the healed vessel density. The implications of these results for wound-healing management are also discussed.

Animals↗
PubMed2005

Age-specific changes in epistatic effects on mortality rate in Drosophila melanogaster.

Models for the evolution of senescence assume that genes with age-specific effects act independently of one another. Although recent empirical data show that longevity is influenced in part by interactions between genes, there are currently few data on whether epistasis influences age-specific components of mortality. To gauge if and how interactions affect age-specific traits, we incorporated the Drosophila visible marker mutations ebony, forked, and purple into seven wild-caught strains of D. melanogaster to examine gene x genetic background interactions. We found significant natural genetic variation for longevity and baseline mortality rates. Gene x genetic background interactions were prevalent not only for longevity but also for baseline mortality rates and age-specific mortality rates. We conclude that gene x genetic background epistasis is prevalent for aging-related traits and could play a significant role in the evolution of aging. These results suggest that future genetic models for the evolution of aging should incorporate the effects of epistasis.

Age Factors↗
PubMed2002

Production of antibodies against glycolipids from the Mycobacterium tuberculosis cell wall in aerosol murine models of tuberculosis.

Evolution of antibodies against glycolipids from the Mycobacterium tuberculosis cell wall has been studied for the first time in experimental murine models of tuberculosis induced by aerosol, in which infection, reinfection, reactivation, prophylaxis and treatment with antibiotics have been assayed. Results show a significant humoral response against these antigens, where diacyltrehaloses (DAT) and sulpholipid I (SL-I) elicited higher antibody levels than protein antigens like antigen 85 protein complex (Ag85), culture filtrate proteins (CFP) and purified protein derivative (PPD). Only immunoglobulin M (IgM) antibodies have been detected against DAT and SL-I. Their evolution has a positive correlation with bacillary concentration in tissues.

Acyltransferases↗
PubMed2002

Dwarfism in insular sloths: biogeography, selection, and evolutionary rate.

The islands of Bocas del Toro, Panama, were sequentially separated from the adjacent mainland by rising sea levels during the past 10,000 years. Three-toed sloths (Bradypus) from five islands are smaller than their mainland counterparts, and the insular populations themselves vary in mean body size. We first examine relationships between body size and physical characteristics of the islands, testing hypotheses regarding optimal body size, evolutionary equilibria, and the presence of dispersal in this system. To do so, we conduct linear regressions of body size onto island area, distance from the mainland, and island age. Second, we retroactively calculate two measures of the evolutionary rate of change in body size (haldanes and darwins) and the standardized linear selection differential, or selection intensity (i). We also test the observed morphological changes against models of evolution by genetic drift. The results indicate that mean body size decreases linearly with island age, explaining up to 97% of the variation among population means. Neither island area nor distance from the mainland is significant in multiple regressions that include island age. Thus, we find no evidence for differential optimal body size among islands, or for dispersal in the system. In contrast, the dependence of body size on island age suggests uniform directional selection for small body size in the insular populations. Although genetic drift cannot be discounted as the cause for this evolution in body size, the probability is small given the consistent direction of evolution (repeated dwarfism). The insular sloths show a sustained rate of evolution similar to those measured in haldanes over tens of generations, appearing to unite micro- and macroevolutionary time scales. Furthermore, the magnitude and rate of this example of rapid differentiation fall within predictions of theoretical models from population genetics. However, the linearity of the relationship between body size and island age is not predicted, suggesting that either more factors are involved than those considered here, or that theoretical advances are necessary to explain constant evolutionary rates over long time spans in new selective environments.

Animals↗
PubMed2006

Evolution in group-structured populations can resolve the tragedy of the commons.

Public goods are the key features of all human societies and are also important in many animal societies. Collaborative hunting and collective defence are but two examples of public goods that have played a crucial role in the development of human societies and still play an important role in many animal societies. Public goods allow societies composed largely of cooperators to outperform societies composed mainly of non-cooperators. However, public goods also provide an incentive for individuals to be selfish by benefiting from the public good without contributing to it. This is the essential paradox of cooperation-known variously as the Tragedy of the Commons, Multi-person Prisoner's Dilemma or Social Dilemma. Here, we show that a new model for evolution in group-structured populations provides a simple and effective mechanism for the emergence and maintenance of cooperation in such a social dilemma. This model does not depend on kin selection, direct or indirect reciprocity, punishment, optional participation or trait-group selection. Since this mechanism depends only on population dynamics and requires no cognitive abilities on the part of the agents concerned, it potentially applies to organisms at all levels of complexity.

Animals↗
PubMed1996

A Hidden Markov Model approach to variation among sites in rate of evolution.

The method of Hidden Markov Models is used to allow for unequal and unknown evolutionary rates at different sites in molecular sequences. Rates of evolution at different sites are assumed to be drawn from a set of possible rates, with a finite number of possibilities. The overall likelihood of phylogeny is calculated as a sum of terms, each term being the probability of the data given a particular assignment of rates to sites, times the prior probability of that particular combination of rates. The probabilities of different rate combinations are specified by a stationary Markov chain that assigns rate categories to sites. While there will be a very large number of possible ways of assigning rates to sites, a simple recursive algorithm allows the contributions to the likelihood from all possible combinations of rates to be summed, in a time proportional to the number of different rates at a single site. Thus with three rates, the effort involved is no greater than three times that for a single rate. This "Hidden Markov Model" method allows for rates to differ between sites and for correlations between the rates of neighboring sites. By summing over all possibilities it does not require us to know the rates at individual sites. However, it does not allow for correlation of rates at nonadjacent sites, nor does it allow for a continuous distribution of rates over sites. It is shown how to use the Newton-Raphson method to estimate branch lengths of a phylogeny and to infer from a phylogeny what assignment of rates to sites has the largest posterior probability. An example is given using beta-hemoglobin DNA sequences in eight mammal species; the regions of high and low evolutionary rates are inferred and also the average length of patches of similar rates.

Animals↗
PubMed1962

Some formal approaches to the analysis of kinetic data in terms of linear compartmental systems.

A formal approach to the routine analysis of kinetic data in terms of linear compartmental systems is presented. The methods of analysis are general in that they include much of the theory in common use, such as direct solution of differential equations, integral equations, transfer functions, fitting of data to sums of exponentials, matrix solutions, etc. The key to the formalism presented lies in the fact that a basic operational unit-called "compartment"-has been defined, in terms of which physical and mathematical models as well as input and output functions can be expressed. Additional features for calculating linear combinations of functions and for setting linear dependence relations between parameters add to the versatility of this method. The actual computations for the values of model parameters to yield a least squares fit of the data are performed on a digital computer. A general computer program was developed that permits the routine fitting of data and the evolution of models.

Biophysical Phenomena↗
PubMed2003

MCMC genome rearrangement.

MOTIVATION: As more and more genomes have been sequenced, genomic data is rapidly accumulating. Genome-wide mutations are believed more neutral than local mutations such as substitutions, insertions and deletions, therefore phylogenetic investigations based on inversions, transpositions and inverted transpositions are less biased by the hypothesis on neutral evolution. Although efficient algorithms exist for obtaining the inversion distance of two signed permutations, there is no reliable algorithm when both inversions and transpositions are considered. Moreover, different type of mutations happen with different rates, and it is not clear how to weight them in a distance based approach. RESULTS: We introduce a Markov Chain Monte Carlo method to genome rearrangement based on a stochastic model of evolution, which can estimate the number of different evolutionary events needed to sort a signed permutation. The performance of the method was tested on simulated data, and the estimated numbers of different types of mutations were reliable. Human and Drosophila mitochondrial data were also analysed with the new method. The mixing time of the Markov Chain is short both in terms of CPU times and number of proposals. AVAILABILITY: The source code in C is available on request from the author.

Algorithms↗
PubMed1995

Teaching, training or educating patients? Influence of contexts and models of education and care on practice in patient education.

This paper presents the rationale, theoretical developments and operationalization of the role of contexts of care and education in practice, choice of methods and effects of patient education in chronic diseases. Starting from a review on the evolution of models of care, education and health education, and on the influence of characteristics of organization of care, it proposes an analysis model of contexts of care and education. A study carried out in 1993 in 10 Belgian and northern France hospitals, with 400 patients, is presented. Simultaneously, pre-post test evaluations of the effects of current patient education work on 40 compliance factors, and in-depth analyses of contexts of care and education were undertaken. The possible relationship between variety and number of effects of education and type of care and education is examined and discussed.

Chronic Disease↗
PubMed1990

Some evolutionary properties of parental investment per offspring in a heterogeneous environment.

The possibility of protected polymorphisms and of monomorphic evolutionarily stable strategies for parental investment per offspring in a heterogeneous environment is theoretically analysed. A high density two-niche model of the classical soft selection kind is used, although it incorporates the possibility of rare strategies invading an empty niche the contribution of which is not constant. Protected polymorphisms can be found whether or not both strategies included produce surviving offspring in both niches. However, a monomorphic evolutionarily stable strategy exists unless offspring of the optimal size in one of the niches cannot survive in the other. The robustness of the model is graphically illustrated under a variety of circumstances, and some evolutionary consequences are briefly discussed.

Animals↗
PubMed2006

Shock-wave mach-reflection slip-stream instability: a secondary small-scale turbulent mixing phenomenon.

Theoretical and experimental research, on the previously unresolved instability occurring along the slip stream of a shock-wave Mach reflection, is presented. Growth rates of the large-scale Kelvin-Helmholtz shear flow instability are used to model the evolution of the slip-stream instability in ideal gas, thus indicating secondary small-scale growth of the Kelvin-Helmholtz instability as the cause for the slip-stream thickening. The model is validated through experiments measuring the instability growth rates for a range of Mach numbers and reflection wedge angles. Good agreement is found for Reynolds numbers of Re 2 x 10(4). This work demonstrates, for the first time, the use of large-scale models of the Kelvin-Helmholtz instability in modeling secondary turbulent mixing in hydrodynamic flows, a methodology which could be further implemented in many important secondary mixing processes.

Journal Article↗
PubMed2003

Modularity and the cost of complexity.

In this work we consider the geometrical model of R. A. Fisher, in which individuals are characterized by a number of phenotypic characters under optimizing selection. Recent work on this model by H. A. Orr has demonstrated that as the number of characters increases, there is a significant reduction in the rate of adaptation. Orr has dubbed this a "cost of complexity." Although there is little evidence as to whether such a cost applies in the natural world, we suggest that the prediction is surprising, at least naively. With this in mind, we examine the robustness of Orr's prediction by modifiying the model in various ways that might reduce or remove the cost. In particular, we explore the suggestion that modular pleiotropy, in which mutations affect only a subset of the traits, could play an important role. We conclude that although modifications of the model can mitigate the cost to a limited extent, Orr's finding is robust.

Adaptation, Biological↗
PubMed1984

[Longitudinal study of the evolution of the frequency of dental caries in a school milieu: a statistical model].

Following a 3-year epidemiological study of the appearance of dental caries in a population of children aged 6 to 9 years (and examined every 12 months), a model of the evolution of the frequency of caries based on a Poisson "with zeros" distribution is proposed. The multivariate distribution of the above phenomena appears as a mixture of multiple negative binomial distribution (MNB) of the following form: sigma mjMNB(a;k0jb,k1jb,k2jb) with sigma mj = 1. The experimental data from the sample of 501 children validate the model in its successive stages. Simulations using the bootstrap method show that the estimates of the model parameters remain stable in the neighbourhood of the distribution observed; at the same time they permit establishing the margins of confidence. Finally, it is shown why the total number of dental faces affected during the experimental period remained strongly asymmetrical.

Child↗
PubMed2002

Mechanisms of scale formation and carbon dioxide partial pressure influence. Part II. Application in the study of mineral waters of reference.

In the first part, we have designed a new model of evolution for the calco-carbonic system which includes the hydrated forms of CaCO3: CaCO3 amorphous, CaCO3 x 6H2O (ikaite) and CaCO3 x H2O (monohydrate) (J. Eur. Hydr. 30 (1999) 47). According to this model, it is the precipitation of one or other of these hydrated forms which could be responsible for the breakdown of the metastable state. After this first step, the precipitates evolve to dehydrated solid forms. Through the elaboration of computer programs in which the CaCO3(0) (aq) ion pair formation was considered, this model was compared to experimental data obtained by the critical pH method applied to synthetic solutions. In the present article, the same method was applied for four French mineral waters, at 25 degrees C under study. Three samples formed a precipitation during the sodium hydroxide addition. For these three cases, this precipitation began for the CaCO3 H2O saturation. The added volume of sodium hydroxide was more than what was required for neutralizing free CO2 initially in solution. These results indicate that during a spontaneous scaling phenomenon, the pH rises at the same time by loss of the initial free CO2 and of the one produced by the hydrogen carbonate ions decomposition. Then we calculated, at various temperatures for the three studied scaling waters: CO2 partial pressures and loss of total carbon corresponding to the solubility products of CaCO3 hydrated forms. The results show that the partial pressure monitoring of the carbon dioxide is important in managing the behavior of scaling waters.

Carbon Dioxide↗