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Modelling of the life cycle of Chironomus species using an energy-based model.

Little is known about the differences between the species of the genus Chironomus relatively to their life cycle strategies. This knowledge is however crucial to fully understand the response of the Chironomus community to field perturbations. Here, we proposed to study four Chironomus species by using an energy-based model to describe growth, emergence and reproduction. We used data from the literature for two species (Chironomus plumosus and Chironomus tentans) and data from our experiments for two other species (Chironomus prasinus and Chironomus riparius). We showed that our model is able to accurately describe the life-history attributes for all the species tested, which suggests that Chironomus species have the same fundamental characteristics (low maintenance energetic costs, isomorphism), which makes possible the building of a common modelling framework to assess effects of toxicants at individual and population level. The species showed a few differences relatively to the parameters of the models with possible consequences when assessing effects of chemicals on Chironomus community. For instance, due to differences in growth parameters, C. riparius population dynamics should be more sensitive to effects on individual growth than C. prasinus or C. plumosus ones.

Animals↗

Explanatory limitations of the HKB model: incentives for a two-tiered model of rhythmic interlimb coordination.

The HKB model for rhythmic interlimb coordination has highlighted the importance of coordinative stability and loss of stability, and introduced, with this focus, a new set of explanatory constructs. However, the phenomenological character of both parts of this model (i.e., the potential and the associated system of coupled oscillators) precludes an understanding of how the observed stability characteristics are related to more specific (e.g., biomechanical and neurophysiological) aspects of the movement system. A two-tiered model (involving a distinction between 'neural' and 'effector' dynamics) is discussed that offers handles for addressing such underpinnings of the identified coordination dynamics. The promise of the model in this regard is illustrated by two recent studies showing how explicit accounts of the effector dynamics may help disclose why (and how) particular properties of the peripheral system affect the overall coordination dynamics.

Attention↗

Mathematical and numerical models for transfer of low-density lipoproteins through the arterial walls: a new methodology for the model set up with applications to the study of disturbed lumenal flow.

In this work we introduce and discuss several mathematical models, based on partial differential equations, devised to study the coupled transport of macromolecules as low-density lipoproteins in the blood stream and in the arterial walls. These models are accurate provided that a suitable set of physical parameters characterizing the physical properties of the molecules and of the wall layers are available. Here we turn our attention on this aspect, and propose a new methodology to compute the physical parameters needed for the model set up, starting from available in vivo measurements. Then, we focus on the study of the accumulation of low-density lipoproteins in vascular districts featuring a highly disturbed flow. Our results demonstrate that mathematical models whose set up procedure benefits from an experimental feedback provide reliable information not only qualitatively, but also quantitatively. Their application to geometrically perturbed vascular districts (as for example a severe stenosis) shows that geometrical parameters such as curvature and variations of the lumenal section strongly influence the accumulation of low-density lipoproteins within the wall. For instance, in a stenotic segment with 75% area constriction, the LDL concentration at the lumenal side of the wall is about 10% higher than for the undisturbed segment.

Arterial Occlusive Diseases↗

Modeling development of sleep-wake behaviors: I. Using the mixed general linear model.

The purpose of this paper is to demonstrate the use of the mixed general linear model (MixMod) for modeling development of sleep-wake behaviors in preterm infants. The mixed general linear model allows the concurrent identification of both group and individual developmental patterns in longitudinal data sets with inconsistently timed data, irregularly timed data, and randomly missing values. This statistical technique is well suited to data from preterm infants because these infants enter and leave longitudinal studies at varying times depending on their health status. One sleep organizational variable--the regularity of respiration in quiet sleep--obtained from a study of 37 preterm infants was used as an example. Seven infant characteristics were used as covariates. The various steps involved in conducting a mixed model analysis of this variable are illustrated. The strengths and limitations of this technique are discussed.

Aging↗

Homology modeling of wild type and pyrimethamine/cycloguanil-cross resistant mutant type Plasmodium falciparum dihydrofolate reductase. A model for antimalarial chemotherapy resistance.

We propose a low-resolution model for both the wild type and the pyrimethamine (Pyr)/cycloguanil (Cyc) cross-resistant mutant type Plasmodium falciparum DHFR (PfDHFR), based on homology modeling using chicken liver DHFR as a template. The built models contain five alpha-helices, eight beta-sheets, eight tight turns and several loops. The Ramachandran plot for the models shows 95.3 and 100% of the amino acid residues in the favorable regions for the whole enzymes and for the active sites, respectively. Furthermore, we made a preliminary analysis of the complexes Pyr/Cyc-wild DHFR and Pyr/Cyc-mutant DHFR in order to explain the probable mechanism of resistance. Our results show that the steric factor may be the main structural cause of P. falciparum resistance toward antifolate drugs.

Amino Acid Sequence↗

Animal models in gastrointestinal alcohol research-a short appraisal of the different models and their results.

Alcohol-related diseases of the gastrointestinal tract play an important role in clinical gastroenterology. However, the mechanisms and pathophysiology underlying the effects of ethanol on the organs of the digestive tract are not yet completely understood. Animal models represent an essential tool for investigating alcohol-related diseases because they give researchers the opportunity to use methods that cannot be used in humans, such as knockout technology. However, there is still a need for new animal models resembling the human condition, since for some alcohol-related diseases such as chronic alcoholic pancreatitis, the ideal animal model does not yet exist. In this chapter, we provide an overview of the most commonly used animal models in gastrointestinal alcohol research. We will also briefly discuss the current concepts of the pathophysiological mechanisms involved in acute and chronic alcoholic damage of the oesophagus, stomach, small and large intestine, pancreas and liver.

Alcohol Drinking↗

The E-Z reader model of eye-movement control in reading: comparisons to other models.

The E-Z Reader model (Reichle et al. 1998; 1999) provides a theoretical framework for understanding how word identification, visual processing, attention, and oculomotor control jointly determine when and where the eyes move during reading. In this article, we first review what is known about eye movements during reading. Then we provide an updated version of the model (E-Z Reader 7) and describe how it accounts for basic findings about eye movement control in reading. We then review several alternative models of eye movement control in reading, discussing both their core assumptions and their theoretical scope. On the basis of this discussion, we conclude that E-Z Reader provides the most comprehensive account of eye movement control during reading. Finally, we provide a brief overview of what is known about the neural systems that support the various components of reading, and suggest how the cognitive constructs of our model might map onto this neural architecture.

Eye Movements↗

Model of a quinary structure between Krebs TCA cycle enzymes: a model for the metabolon.

The enzymes which are responsible for catalyzing sequential reactions in several metabolic pathways have been proposed to be highly organized in supramolecular complexes termed metabolons. However, the in situ existence of these weak complexes is difficult to demonstrate because many of them are dissociated during isolation due to dilution effects. Consequently, the metabolon concept is subject to controversy. A model system consisting of genetically prepared bienzymatic fusion proteins has been used to immobilize sequential metabolic enzymes in close proximity and to demonstrate possible kinetic advantages of metabolons. These experiments use the sequential Krebs TCA cycle enzymes from yeast mitochondrial malate dehydrogenase (MDH), citrate synthase (CS), and aconitase (ACO). Using the porcine high-definition structures of these three enzymes, we have performed computer-modeling studies in order to understand how the molecules may interact. Among the thousands of docking orientations we have tried, one was found to respond to the structural and experimental constraints from the results obtained with the yeast fusion proteins. Interestingly, this quinary structure model shows substantial interacting surface areas with spatial and electrostatic complementarities which make the complex thermodynamically stable. This structure also contains an unbroken electrostatically favorable channel connecting the active sites of ACO and CS, as well as the one previously reported between CS and MDH active sites. Charged amino acids which could be involved in interactions stabilizing the complex have been identified. This model will be used as the basis for further experimental work on the structure of the Krebs TCA cycle metabolon.

Aconitate Hydratase↗

Linking animal models of psychosis to computational models of dopamine function.

Psychosis is linked to dysregulation of the neuromodulator dopamine and antipsychotic drugs (APDs) work by blocking dopamine receptors. Dopamine-modulated disruption of latent inhibition (LI) and conditioned avoidance response (CAR) have served as standard animal models of psychosis and antipsychotic action, respectively. Meanwhile, the 'temporal difference' algorithm (TD) has emerged as the leading computational model of dopamine neuron firing. In this report TD is extended to include action at the level of dopamine receptors in order to explain a number of behavioral phenomena including the dose-dependent disruption of CAR by APDs, the temporal dissociation of the effects of APDs on receptors vs behavior, the facilitation of LI by APDs, and the disruption of LI by amphetamine. The model also predicts an APD-induced change to the latency profile of CAR--a novel prediction that is verified experimentally. The model's primary contribution is to link dopamine neuron firing, receptor manipulation, and behavior within a common formal framework that may offer insights into clinical observations.

Action Potentials↗

Methods for combining ancillary data in stochastic compartment models of cancer mortality: generalization of heterogeneity models.

"We present a mortality model where nationally representative survey data on risk factor distributions are combined with data on cohort mortality rates to increase information, i.e., a fixed marginal risk factor distribution is combined with a cohort model representing unobserved individual risk heterogeneity. The model is applied to lung cancer mortality in nine U.S. white male cohorts aged 30 to 70 in 1950 and followed 38 years. Estimates of the cohort specific proportions of smokers were made from the National Health Interview Survey. Comparisons are made for models with different patterns of changes with age of individual heterogeneity." (SUMMARY IN FRE)

Americas↗

Improving measurement in health education and health behavior research using item response modeling: introducing item response modeling.

This paper is the first of several papers designed to demonstrate how the application of item response models in the behavioral sciences can be used to enhance the conceptual and technical toolkit of researchers and developers and to understand better the psychometric properties of psychosocial measures. The papers all use baseline data from the Behavior Change Consortium data archive. This paper begins with an introduction to item response models, including both dichotomous and polytomous versions. The concepts of respondent and item location, model interpretation, standard errors and testing model fit are introduced and described. A sample analysis based on data from the self-efficacy scale is used to illustrate the concepts and techniques.

Data Interpretation, Statistical↗

A transformational model for the practice of professional nursing. Part 1, The model.

Our healthcare system is undergoing major transformation. Most nurse executives know that change is necessary and inevitable, but are less certain how to position their departments for these changes. The Transformational Model for the Practice of Professional Nursing was developed as a "road map" for that purpose. Part 1 of the model discusses the paradigm shifts that need to occur in professional practice for future success. The various components of the model are presented, and applications are identified. Part 2 will appear in the May 1994 issue of JONA, and will discuss the implementation of this model into a practice setting.

Humans↗

Competition model for aperiodic stochastic resonance in a Fitzhugh-Nagumo model of cardiac sensory neurons.

Regional cardiac control depends upon feedback of the status of the heart from afferent neurons responding to chemical and mechanical stimuli as transduced by an array of sensory neurites. Emerging experimental evidence shows that neural control in the heart may be partially exerted using subthreshold inputs that are amplified by noisy mechanical fluctuations. This amplification is known as aperiodic stochastic resonance (ASR). Neural control in the noisy, subthreshold regime is difficult to see since there is a near absence of any correlation between input and the output, the latter being the average firing (spiking) rate of the neuron. This lack of correlation is unresolved by traditional energy models of ASR since these models are unsuitable for identifying "cause and effect" between such inputs and outputs. In this paper, the "competition between averages" model is used to determine what portion of a noisy, subthreshold input is responsible, on average, for the output of sensory neurons as represented by the Fitzhugh-Nagumo equations. A physiologically relevant conclusion of this analysis is that a nearly constant amount of input is responsible for a spike, on average, and this amount is approximately independent of the firing rate. Hence, correlation measures are generally reduced as the firing rate is lowered even though neural control under this model is actually unaffected.

Animals↗

Three-dimensional mixed-wet random pore-scale network modeling of two- and three-phase flow in porous media. I. Model description.

We present a three-dimensional network model to simulate two- and three-phase capillary dominated processes at the pore level. The displacement mechanisms incorporated in the model are based on the physics of multiphase flow observed in micromodel experiments. All the important features of immiscible fluid flow at the pore scale, such as wetting layers, spreading layers of the intermediate-wet phase, hysteresis, and wettability alteration are implemented in the model. Wettability alteration allows any values for the advancing and receding oil-water, gas-water, and gas-oil contact angles to be assigned. Multiple phases can be present in each pore or throat (element), in wetting and spreading layers, as well as occupying the center of the pore space. In all, some 30 different generic fluid configurations for two- and three-phase flow are analyzed. Double displacement and layer formation are implemented as well as direct two-phase displacement and layer collapse events. Every element has a circular, square, or triangular cross section. A random network that represents the pore space in Berea sandstone is used in this study. The model computes relative permeabilities, saturation paths, and capillary pressures for any displacement sequence. A methodology to track a given three-phase saturation path is presented that enables us to compare predicted and measured relative permeabilities on a point-by-point basis. A robust displacement-based clustering algorithm is also presented.

Absorption↗

Using computational auditory models to predict simultaneous masking data: model comparison.

In order to develop improved remediation techniques for hearing impairment, auditory researchers must gain a greater understanding of the relation between the psychophysics of hearing and the underlying physiology. One approach to studying the auditory system has been to design computational auditory models that predict neurophysiological data such as neural firing rates [15], [1]. To link these physiologically-based models to psychophysics, theoretical bounds on detection performance have been derived using signal detection theory to analyze the simulated data for various psychophysical tasks [20]. Previous efforts, including our own recent work using the Auditory Image Model, have demonstrated the validity of this type of analysis; however, theoretical predictions often continue to exceed experimentally-measured performance [9], [21]. In this paper, we compare predictions of detection performance across several computational auditory models. We also reconcile some of the previously observed discrepancies by incorporating appropriate signal uncertainty into the optimal detector.

Computer Simulation↗

Using graphical models and genomic expression data to statistically validate models of genetic regulatory networks.

We propose a model-driven approach for analyzing genomic expression data that permits genetic regulatory networks to be represented in a biologically interpretable computational form. Our models permit latent variables capturing unobserved factors, describe arbitrarily complex (more than pair-wise) relationships at varying levels of refinement, and can be scored rigorously against observational data. The models that we use are based on Bayesian networks and their extensions. As a demonstration of this approach, we utilize 52 genomes worth of Affymetrix GeneChip expression data to correctly differentiate between alternative hypotheses of the galactose regulatory network in S. cerevisiae. When we extend the graph semantics to permit annotated edges, we are able to score models describing relationships at a finer degree of specification.

Bayes Theorem↗

Modeling and simulation of molecular biology systems using petri nets: modeling goals of various approaches.

Petri nets are a discrete event simulation approach developed for system representation, in particular for their concurrency and synchronization properties. Various extensions to the original theory of Petri nets have been used for modeling molecular biology systems and metabolic networks. These extensions are stochastic, colored, hybrid and functional. This paper carries out an initial review of the various modeling approaches based on Petri net found in the literature, and of the biological systems that have been successfully modeled with these approaches. Moreover, the modeling goals and possibilities of qualitative analysis and system simulation of each approach are discussed.

Cells, Cultured↗

Commentary: model building, quantitative testing, and model comparison.

The final goal is to create mathematical models that are based on our current knowledge of the underlying physiology and that explain all of the experimental data available. To do this, we suggest a consideration of several potential mathematical structures in the formulation of models and the formal comparison of these various structures with other models in the literature. However, when making these comparisons, one must pay careful attention to the systems being modeled and the data sets chosen to represent those systems.

Data Interpretation, Statistical↗