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PubMed1992

Bioeconomic evaluation of embryo transfer in beef production systems: I. Description of a biological model for steer production.

Concepts used to derive a deterministic model for evaluating embryo transfer for commercial steer production taking into consideration genetic merit for growth and mature size, herd feed supply, and recipient maternal environment are discussed. Genetic potential of an embryo is used to derive optimal growth rates that can be sustained by available herd feed per animal per day. Equations are provided for various measures of performance as functions of the feed, genotype of the embryo, and recipient maternal contribution. To assess the value of a particular line of embryos, interactions between genotype and nutrient environment are quantified, so that the benefits of embryos of high genetic merit are evaluated objectively. Product quality and weight are predicted from the model to provide a framework that will allow commercial beef producers to determine marketing strategies likely to result in optimal return.

Animal Feed↗
PubMed2005

Modelling biological complexity: a physical scientist's perspective.

We discuss the modern approaches of complexity and self-organization to understanding dynamical systems and how these concepts can inform current interest in systems biology. From the perspective of a physical scientist, it is especially interesting to examine how the differing weights given to philosophies of science in the physical and biological sciences impact the application of the study of complexity. We briefly describe how the dynamics of the heart and circadian rhythms, canonical examples of systems biology, are modelled by sets of nonlinear coupled differential equations, which have to be solved numerically. A major difficulty with this approach is that all the parameters within these equations are not usually known. Coupled models that include biomolecular detail could help solve this problem. Coupling models across large ranges of length- and time-scales is central to describing complex systems and therefore to biology. Such coupling may be performed in at least two different ways, which we refer to as hierarchical and hybrid multiscale modelling. While limited progress has been made in the former case, the latter is only beginning to be addressed systematically. These modelling methods are expected to bring numerous benefits to biology, for example, the properties of a system could be studied over a wider range of length- and time-scales, a key aim of systems biology. Multiscale models couple behaviour at the molecular biological level to that at the cellular level, thereby providing a route for calculating many unknown parameters as well as investigating the effects at, for example, the cellular level, of small changes at the biomolecular level, such as a genetic mutation or the presence of a drug. The modelling and simulation of biomolecular systems is itself very computationally intensive; we describe a recently developed hybrid continuum-molecular model, HybridMD, and its associated molecular insertion algorithm, which point the way towards the integration of molecular and more coarse-grained representations of matter. The scope of such integrative approaches to complex systems research is circumscribed by the computational resources available. Computational grids should provide a step jump in the scale of these resources; we describe the tools that RealityGrid, a major UK e-Science project, has developed together with our experience of deploying complex models on nascent grids. We also discuss the prospects for mathematical approaches to reducing the dimensionality of complex networks in the search for universal systems-level properties, illustrating our approach with a description of the origin of life according to the RNA world view.

Animals↗
PubMedDate not supplied

Predicting carcinogenicity with short-term tests: biological models and operational approaches.

This paper illustrates the basic biological models that have had an influence on the development and deployment of short-term assays for carcinogens. A tentative description of such a conceptual framework is provided with the use of methods for the quantitative analysis of information. This picture is contrasted with the results of a series of statistical mathematical analyses carried out on real genotoxicity data bases. The resulting evidence indicates that the biological models derived from basic laboratory research are not adequate or sufficient to interpret the operational performances of short-term assays. Obviously these models are of great importance, but, this observed discrepancy suggests the need for articulated approaches, with particular emphasis on analytical tools able to interpret the complexity of these systems. In particular, the multivariate data analysis methods are indicated as suitable for the description of large and complex bodies of data, and the identification of typologies and regularities. A number of applications of such methods are also presented. The conclusion is that biological models and operational approaches have to interact on the same level. The operational approach should indicate whether the conceptual framework of the experimenter is adequate to describe the experimental situation and possibly point to new relationships and trends, as well as to practical solutions.

Animals↗
PubMed2002

Integrative biological modelling in silico.

In silico models of biological systems provide a powerful tool for integrative analysis of physiological function. Using the computational models of the heart as examples, we discuss three types of integration: structural integration implies integration across physical scales of biological organization from protein molecule to whole organ; functional integration of interacting physiological processes such as signalling, metabolism, excitation and contraction; and the synthesis of experimental observation with physicochemical and mathematical principles.

Animals↗
PubMed1985

[Implications of biological models on psychiatric clinical practice.].

The explanatory models of a biological nature are growing in popularity in psychiatry. The reason for this ideological tendency is studied and contradictory evidences are underlined. It seems that an exclusively biological conception of psychiatric disorders is more prescriptive than descriptive of the facts. Biological models, seemingly more "scientific" are particularly of interest to the professionals with a bio-medical training, and, in this sense, bear important implications for the practice of psychiatry. Their influences on clinical practice, professional training and research are reviewed and discussed.

English Abstract↗
PubMed2005

Toward efficient riparian restoration: integrating economic, physical, and biological models.

This paper integrates economic, biological, and physical models to explore the efficient combination and spatial allocation of conservation efforts to protect water quality and increase salmonid populations in the Grande Ronde basin, Oregon. We focus on the effects of shade on water temperatures and the subsequent impacts on endangered juvenile salmonid populations. The integrated modeling system consists of a physical model that links riparian conditions and hydrological characteristics to water temperature; a biological model that links water temperature and riparian conditions to salmonid abundance, and an economic model that incorporates both physical and biological models to estimate minimum cost allocations of conservation efforts. Our findings indicate that conservation alternatives such as passive and active riparian restoration, the width of riparian restoration zones, and the types of vegetation used in restoration activities should be selected based on the spatial distribution of riparian characteristics in the basin. The relative effectiveness of passive and active restoration plays an important role in determining the efficient allocations of conservation efforts. The time frame considered in the restoration efforts and the magnitude of desired temperature reductions also affect the efficient combinations of restoration activities. If the objective of conservation efforts is to maximize fish populations, then fishery benefits should be directly targeted. Targeting other criterion such as water temperatures would result in different allocations of conservation efforts, and therefore are not generally efficient.

Animals↗
PubMed1973

Ionic partition between surface and bulk water in a silica gel. A biological model.

Distribution of the biologically important ions between two aqueous phases of different structure has been used as a model for ionic distribution in living tissue. When other sources of specificity had been eliminated or corrected for, surface-oriented water in a silica gel was found to have increased solvent power for water-structure-breaking ions and decreased solvent power for water-structure-making ions; and the relative solubility of an ion in the phase of enhanced structure increased regularly with the water-structure-breaking powers of the ion. The ionic selectivity was decreased in the presence of urea. The selectivity of the gel water for potassium relative to sodium increased to a maximum when the gel surface was partially ionized so that distribution of cations was not linked to distribution of anions, and then decreased as the surface changed from a hydrogen bonding to an ionic surface. It is pointed out that the distribution of ions across most living cell membranes is qualitatively the same as that found in this silica gel, and it is suggested that the membrane separates two aqueous phases of different structure, and that the enhanced structure of cell water contributes to the observed ionic distributions.

Cell Membrane Permeability↗
PubMed2006

Simplification and its consequences in biological modelling: conclusions from a study of calcium oscillations in hepatocytes.

Systems Biology requires that biological modelling is scaled up from small components to system level. This can produce exceedingly complex models, which obscure understanding rather than facilitate it. The successful use of highly simplified models would resolve many of the current problems faced in Systems Biology. This paper questions whether the conclusions of simple mathematical models of biological systems are trustworthy. The simplification of a specific model of calcium oscillations in hepatocytes is examined in detail, and the conclusions drawn from this scrutiny generalized. We formalize our choice of simplification approach through the use of functional 'building blocks'. A collection of models is constructed, each a progressively more simplified version of a well-understood model. The limiting model is a piecewise linear model that can be solved analytically. We find that, as expected, in many cases the simpler models produce incorrect results. However, when we make a sensitivity analysis, examining which aspects of the behaviour of the system are controlled by which parameters, the conclusions of the simple model often agree with those of the richer model. The hypothesis that the simplified model retains no information about the real sensitivities of the unsimplified model can be very strongly ruled out by treating the simplification process as a pseudo-random perturbation on the true sensitivity data. We conclude that sensitivity analysis is, therefore, of great importance to the analysis of simple mathematical models in biology. Our comparisons reveal which results of the sensitivity analysis regarding calcium oscillations in hepatocytes are robust to the simplifications necessarily involved in mathematical modelling. For example, we find that if a treatment is observed to strongly decrease the period of the oscillations while increasing the proportion of the cycle during which cellular calcium concentrations are rising, without affecting the inter-spike or maximum calcium concentrations, then it is likely that the treatment is acting on the plasma membrane calcium pump.

Animals↗
PubMed2002

BioMOL: a computer-assisted biological modeling tool for complex chemical mixtures and biological processes at the molecular level.

A chemical engineering approach for the rigorous construction, solution, and optimization of detailed kinetic models for biological processes is described. This modeling capability addresses the required technical components of detailed kinetic modeling, namely, the modeling of reactant structure and composition, the building of the reaction network, the organization of model parameters, the solution of the kinetic model, and the optimization of the model. Even though this modeling approach has enjoyed successful application in the petroleum industry, its application to biomedical research has just begun. We propose to expand the horizons on classic pharmacokinetics and physiologically based pharmacokinetics (PBPK), where human or animal bodies were often described by a few compartments, by integrating PBPK with reaction network modeling described in this article. If one draws a parallel between an oil refinery, where the application of this modeling approach has been very successful, and a human body, the individual processing units in the oil refinery may be considered equivalent to the vital organs of the human body. Even though the cell or organ may be much more complicated, the complex biochemical reaction networks in each organ may be similarly modeled and linked in much the same way as the modeling of the entire oil refinery through linkage of the individual processing units. The integrated chemical engineering software package described in this article, BioMOL, denotes the biological application of molecular-oriented lumping. BioMOL can build a detailed model in 1-1,000 CPU sec using standard desktop hardware. The models solve and optimize using standard and widely available hardware and software and can be presented in the context of a user-friendly interface. We believe this is an engineering tool with great promise in its application to complex biological reaction networks.

Animals↗
PubMed1999

The importance of specifying the underlying biologic model in estimating the probability of causation.

There are a number of contexts in which interested parties wish to estimate the probability that an individual's injury was caused by radiation or a toxic chemical. It has been shown, however, that such calculations cannot be made based on epidemiologic data alone, without assumption of a biologic model for the disease process and without a specific definition of causation. To illustrate the relevant theorems, we present a number of examples in which different biologic models produce different values for the probability of causation for individuals from the same population-based epidemiologic data and dose-response curves. As a result of these ambiguities, it is important that anyone attempting to calculate probability of causation for individuals explicitly state the biologic model that has been assumed, as well as state the definition of causation being used. The analyst should test the robustness of the calculations by repeating them for a broad range of underlying biologic models.

Female↗
PubMed1982

Extraction of morphological features from biological models and cells by Fourier analysis of static light scatter measurements.

Models of biological cells of varying geometric complexity were used to generate data to test a method of extracting geometric features from light scatter distributions. Measurements of the dynamic range and angular distribution of intensity and light scatter from these models was compared to the distributions predicted by a complete theory of light scatter (Mie) and by diffraction theory (Fraunhofer). An approximation to the Fraunhofer theory provides a means of obtaining size and shape features from the data by a spectrum analysis. Experimental verification using nucleated erythrocytes as the biological material show the potential application of this method for the extraction of important size and shape parameters from light scatter data.

Animals↗
PubMed1999

Biologic model of bone transport distraction osteogenesis and vascular response.

We developed an experimental model in the rabbit of distraction osteogenesis through bone transport that closely corresponds to the clinical use of bone transport in humans. We also applied injection angiography to study the arterial response of a limb undergoing bone transport. This model includes a proximal osteotomy and bone transport to fill in a segmental tibial diaphyseal defect. Regenerate bone formed well in the gap that was created that trailed the transport segment, and slow healing at the docking site was observed, as seen in humans. The angiographic techniques clearly revealed, by radiography and anatomic dissection, the arterial response to bone transport. The results showed that the transport segment had an arterial supply after osteotomy and after transport. They also demonstrated an extensive increase in vessels in limbs that had undergone distraction osteogenesis, an observation made clinically in humans but not well demonstrated experimentally. Furthermore, angiography showed proximal stretching and distal kinking of the major artery of the leg. This model closely resembles distraction osteogenesis through bone transport in humans and definitively demonstrates that the transport segment can maintain blood supply and remain viable during the transport process. The results of this study provide a basis for further work on factors that enhance and interfere with successful bone transport in humans.

Angiography↗