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PubMed1990

An empirical model for analysing and interpreting ventricular measures.

Given the abundant and, at times, contradictory studies of ventricular enlargement in neurological and psychiatric disorders, the current study was carried out to provide an empirical basis for analysing and interpreting these measures. A sample of CT scans on 100 control subject was drawn from the files of the University of British Columbia Department of Radiology and 19 measures of ventricular and head diameter or area were made. The interrelationships of these measures were then examined using factor analytic procedures. Three ventricular dimensions were found. To validate these three dimensions, the relationship of each with age was examined and then the age-corrected scores of seven clinical groups were compared on each of these dimensions. The magnitude of the relationship between these dimensions and age was impressive and each dimension contributed unique information regarding these age-related changes. Moreover, the analysis of the clinical groups suggested that differential patterns of ventricular change were present dependent upon the disease. These results are discussed with a view to integrating the findings of previous studies and planning future studies.

Adult↗
PubMed2002

Poincaré plot interpretation using a physiological model of HRV based on a network of oscillators.

In this paper, we develop a physiological oscillator model of which the output mimics the shape of the R-R interval Poincaré plot. To validate the model, simulations of various nervous conditions are compared with heart rate variability (HRV) data obtained from subjects under each prescribed condition. For a variety of sympathovagal balances, our model generates Poincaré plots that undergo alterations strongly resembling those of actual R-R intervals. By exploiting the oscillator basis of our model, we detail the way that low- and high-frequency modulation of the sinus node translates into R-R interval Poincaré plot shape by way of simulations and analytic results. With the use of our model, we establish that the length and width of a Poincaré plot are a weighted combination of low- and high-frequency power. This provides a theoretical link between frequency-domain spectral analysis techniques and time-domain Poincaré plot analysis. We ascertain the degree to which these principles apply to real R-R intervals by testing the mathematical relationships on a set of data and establish that the principles are clearly evident in actual HRV records.

Biological Clocks↗
PubMed1979

Metabolism of totally ischemic excised dog heart. II. Interpretation of a computer model.

Analysis of the ischemic dog heart preparation described in the preceding paper indicates that it is an analogue in slow motion of the tissue in the center of a cardiac infarct. It is respiring very slowly and not capable of performing mechanical work. Glycolysis starts up with both glucose and glycogen as inputs. Later hexokinase and to some extent phosphofructokinase become limiting owing to inhibitor accumulation or acidosis. Metabolism then results primarily from cAMP-driven glycogenolysis, largely limited by the glycogen debranching enzymes at later times, with accumultion not only of lactate and alpha-glycerophosphate but of glucose as well. Amino acid levels oscillate with time while fatty acids accumulate at late times. The elevation of cAMP at later times may involve disturbances in its metabolism as well as mechanisms such as adenosine accumulation that are more important in cardiac ischemia than in normal heart. The clinical implications of this behavior are discussed.

Amino Acids↗
PubMed1991

Effects of gene mutations in lipoprotein and hepatic lipases as interpreted by a molecular model of the pancreatic triglyceride lipase.

A molecular model of human pancreatic lipase (Winkler, F. K., D'Arcy, A., and Hunziker, W. (1990) Nature 343, 771-774) is used to explain the possible structural effects of the amino acid mutations identified to date in the human lipoprotein and hepatic lipase genes. A sequence homology profile was used to evaluate the alignment of the amino acid sequences of all three lipolytic enzymes (Kirchgessner, T. G., Chuat, J.-C., Heinzmann, C., Etienne, J., Guilhot, S., Svenson, K., Ameis, D., Pilon, C., D'Auriol, L., Andalibi, A., Schotz, M. C., Galibert, F., and Lusis, A. J. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 9647-9651) with respect to the secondary structure elements identified in the pancreatic lipase. As expected, maximum homology is observed in internal regions namely the hydrophobic strands of the central beta-pleated sheet. This observation strongly supports the hypothesis that all three molecules exhibit a very similar three-dimensional structure, particularly in the N-terminal catalytic domain. There is considerable variation in some of the surface loops connecting the individual strands, whereas others are conserved. It is hypothesized that the most conserved loops located around the active site are responsible for the catalytic function (similar for all three enzymes), whereas those that markedly differ are involved in the regulation at the molecular level, namely the binding of colipase (pancreatic enzyme) and apolipoprotein CII (lipoprotein lipase). The currently available library of hepatic and lipoprotein gene mutations seems to indicate that the majority of mutants disrupt the folding of the polypeptide chain, rather than affect specific constellations in and around the catalytic site or regulatory loops.

Amino Acid Sequence↗
PubMedDate not supplied

[Interpretation of a vitality model from the clinico-experimental viewpoint].

The vitality model conceived by Beier from a theoretical point of view is corroborated by clinical and experimental investigations of the authors. From a randomized study on the biological age of a statistically representative population group it can be concluded that the speed of ageing of this group is not linear in its course and hardly displays any differences between the sexes. Besides, distinct selection effects in advanced age suggest that the human population might consist of two sub-populations (the potentially long-lived and the potentially short-lived) who differ from one another with regard to the speed of ageing, morbidity and to the duration of life. Furthermore, similarities of the sex-specific change in vitality as occurs in the course of life, and the significance of this change for a possible reduction of male over-mortality are pointed out.

Adaptation, Physiological↗
PubMed1985

Functional case analysis: an interpretation of the Skeffington model.

The four components of the model of vision developed by Skeffington are described. The influence of stress induced by reading on the interrelation between accommodation (identification) and convergence (centering) is discussed. The use of a convex lens to reduce the need for adaptive responses is presented.

Accommodation, Ocular↗
PubMed2004

A new interpretation of the Keller-Segel model based on multiphase modelling.

In this paper an alternative derivation and interpretation are presented of the classical Keller-Segel model of cell migration due to random motion and chemotaxis. A multiphase modelling approach is used to describe how a population of cells moves through a fluid containing a diffusible chemical to which the cells are attracted. The cells and fluid are viewed as distinct components of a two-phase mixture. The principles of mass and momentum balance are applied to each phase, and appropriate constitutive laws imposed to close the resulting equations. A key assumption here is that the stress in the cell phase is influenced by the concentration of the diffusible chemical. By restricting attention to one-dimensional cartesian geometry we show how the model reduces to a pair of nonlinear coupled partial differential equations for the cell density and the chemical concentration. These equations may be written in the form of the Patlak-Keller-Segel model, naturally including density-dependent nonlinearities in the cell motility coefficients. There is a direct relationship between the random motility and chemotaxis coefficients, both depending in an inter-related manner on the chemical concentration. We suggest that this may explain why many chemicals appear to stimulate both chemotactic and chemokinetic responses in cell populations. After specialising our model to describe slime mold we then show how the functional form of the chemical potential that drives cell locomotion influences the ability of the system to generate spatial patterns. The paper concludes with a summary of the key results and a discussion of avenues for future research.

Body Patterning↗
PubMedDate not supplied

[Understanding of environmental impact with inpatients based on structural modeling].

This study examined how inpatients perceive environmental impacts using the ISM(Interpretive Structural Modeling)method. 18 new items among inpatients perceiving the environmental impacts were selected through a discussion with three researchers, two nurses, and six patients. This was applied to two inpatients who were not in the same ambulatory state in order to establish the validity of the structural models. As a result, the structuring models showed the difference depending on each patient. Therefore the structuring model is effective to assess the environmental impacts on individuals.

Humans↗
PubMed2006

Synthesis of voltage-sensitive optical signals: application to panoramic optical mapping.

Fluorescent photon scattering is known to distort optical recordings of cardiac transmembrane potentials; however, this process is not well quantified, hampering interpretation of experimental data. This study presents a novel model, which accurately synthesizes fluorescent recordings over the irregular geometry of the rabbit ventricles. Using the model, the study aims to provide quantification of fluorescent signal distortion for different optical characteristics of the preparation and of the surrounding medium. A bi-domain representation of electrical activity is combined with finite element solutions to the photon diffusion equation simulating both the excitation and emission processes, along with physically realistic boundary conditions at the epicardium, which allow simulation of different experimental setups. We demonstrate that distortion in the optical signal as a result of fluorescent photon scattering is truly a three-dimensional phenomenon and depends critically upon the geometry of the preparation, the scattering properties of the tissue, the direction of wavefront propagation, and the specifics of the experimental setup. Importantly, we show that in an anatomically accurate model of ventricular geometry and fiber orientation, the morphology of the optical signal does not provide reliable information regarding the intramural direction of wavefront propagation. These findings underscore the potential of the new model in interpreting experimental data.

Animals↗
PubMed2004

Characterizing fluorescence recovery curves for nuclear proteins undergoing binding events.

Fluorescence recovery after photobleaching (FRAP) is an experimental technique used to measure the mobility of proteins within the cell nucleus. After proteins of interest are fluorescently tagged for their visualization and monitoring, a small region of the nucleus is photobleached. The experimental FRAP data are obtained by recording the recovery of the fluorescence in this region over time. In this paper, we characterize the fluorescence recovery curves for diffusing nuclear proteins undergoing binding events with an approximate spatially homogeneous structure. We analyze two mathematical models for interpreting the experimental FRAP data, namely a reaction-diffusion model and a compartmental model. Perturbation analysis leads to a clear explanation of two important limiting dynamical types of behavior exhibited by experimental recovery curves, namely, (1) a reduced diffusive recovery, and (2) a biphasic recovery characterized by a fast phase and a slow phase. We show how the two models, describing the same type of dynamics using different approaches, relate and share common ground. The results can be used to interpret experimental FRAP data in terms of protein dynamics and to simplify the task of parameter estimation. Application of the results is demonstrated for nuclear actin and type H1 histone.

Genome↗
PubMed2003

Polymyositis--a further investigation.

In essence, this paper describes the model-based interpretation of measurements in order to gain insight into physiological processes. The paper extends the mathematical model developed previously to control and monitor a polymyositis patient. The extension considers two further yet different types of muscle attack. The model is applied to simulate, first, the total serum creatine kinase levels, which then are matched to the observed values. The outcomes of this approach yield considerable information about the reactions taking place including various concentration levels over time such as prednisolone. The changes in the muscle attack are estimated. Examples illustrate how the model may be used to assess, for a single patient, the maximum reduction of the muscle attack whilst keeping the prednisolone concentration as low as possible. The model has been successfully used to interpret variations in daily heart rate measurements of a polymyositis patient. Consequently, it is shown how daily heart rate measurements may now be used to complement the control and monitoring of the polymyositis patient. The model is used to explore multi-patient statistics. It shows the dangers of using such an approach. The model illustrates the need for longitudinal studies.

Antibodies↗
PubMed1993

Hybrid lethal systems in the Drosophila melanogaster species complex.

Lethal phases of the hybrids between Drosophila melanogaster and its sibling species, D. simulans are classified into three types: (1) embryonic lethality in hybrids carrying D. simulans cytoplasm and D. melanogaster X chromosome, (2) larval lethality in hybrids not carrying D. simulans X, and (3) temperature-sensitive pupal lethality in hybrids carrying D. simulans X. The same lethal phases are also observed when either of the two other sibling species, D. mauritiana or D. sechellia, is employed for hybridization with D. melanogaster. Here, we describe genetic analyses of each hybrid lethality, and demonstrate that these three types of lethality are independent phenomena. We then propose two models to interpret the mechanisms of each hybrid lethality. The first model is a modification of the conventional X/autosome imbalance hypothesis assuming a lethal gene and a suppressor gene are involved in the larval lethality, while the second model is for embryonic lethality assuming an interaction between a maternal-effect lethal gene and a suppressor gene.

Alleles↗
PubMed2001

Estimation of radiance reflectance and the concentrations of optically active substances in Lake Mälaren, Sweden, based on direct and inverse solutions of a simple model.

A semi-analytical model which predicts radiance reflectance just below the water surface (Lu/Ed 0-) has been developed and used to predict the spectral variability of radiance reflectance in Lake Mälaren, Sweden. Radiance reflectance is predicted as a function of the optically active substances in the water, which include the concentrations of chlorophyll-a + phaeophytin-a, suspended particular inorganic material (SPIM), suspended particulate organic material (SPOM), and dissolved yellow substances. These substances are linked to the absorption and backscattering coefficients through a series of empirical relationships, and ultimately radiance reflectance is estimated as a function of the ratio of backscattering to absorption. Parameterization of the model, i.e. the development of the empirical relationships linking the optically active substances to the inherent optical properties (IOPs), is based on both in situ measurements and laboratory analyses. We have collected data that allowed us to examine the potential variability in radiance reflectance, as predicted by our model, due to both variations in the optically active substances, and in the model parameterization. Simulations based on a data set collected during the fall of 1997 from 12 sites, which span a large range in water quality (secchi depth 0.8-5.0 m), suggest that, with the proper parameterization, the model can accurately predict the spectra of radiance reflectance as a function of the concentration of optically active substances. Variations in the concentrations of optically active substances accounted for a large portion of the total simulated variability in radiance reflectance (i.e. that resulting from variations in parameterization and in the concentrations of optically active substances). However, the measured variability in parameterization could account for up to 50% of the total variability in simulated radiance reflectance. This suggests that variability in the model parameterization, arising from both real variability and experimental error, will limit the use of this model for interpreting remote sensing data. Nevertheless, inverse solutions of the model are able to estimate the concentrations of chlorophyll, suspended inorganic material (SPIM) and the absorption of yellow substances from measured radiance reflectance spectra The average error for the 12 sites was a -0.07 for chlorophyll, -0.15 for dissolved yellow substances (measured as the absorption at 400 nm) and 0.07 for SPIM, even though individual errors could be as great as 50%.

Chlorophyll↗
PubMedDate not supplied

Noise exposure among construction electricians.

Data-logging noise dosimetry was used to assess the exposure levels of electricians working for a major electrical subcontractor in Washington State at five sites using four types of construction methods. Subjects documented activities and work environment information throughout their work shift, resulting in an activity/exposure record for each of the 174 full-shift samples collected over the 4-month duration of the study. Over 24% of the TWA samples exceeded 85 dBA; 5.2% exceeded the federal Occupational Safety and Health Administration permissible exposure limit of 90 dBA. The National Institute for Occupational Safety and Health exposure metric, which specifies a 3-dB ER, was also utilized; using this metric, 67.8% of the samples exceeded 85 dBA and 27% exceeded 90 dBA. Subjects were directly observed for a subset of 4469 min during which more detailed activity and environmental information was recorded. Linear and logistic regression models using this subset were used to identify the determinants of average exposure, and exposure exceedences, respectively. These models demonstrated the importance of multiple variable modeling in interpreting exposure assessments, and the feasibility and utility of modeling exposure exceedences using logistic regression. The results further showed that presumably quiet trades such as electrician are at risk of exposure to potentially harmful noise exposures, and that other workers' activities and the general environment contribute substantially to that risk. These results indicate that noise control strategies will have to address the construction work environment as an integrated system.

Adult↗
PubMed2005

Effects of Bcl-2 levels on Fas signaling-induced caspase-3 activation: molecular genetic tests of computational model predictions.

Fas-induced apoptosis is a critical process for normal immune system development and function. Although many molecular components in the Fas signaling pathway have been identified, a systematic understanding of how they work together to determine network dynamics and apoptosis itself has remained elusive. To address this, we generated a computational model for interpreting and predicting effects of pathway component properties. The model integrates current information concerning the signaling network downstream of Fas activation, through both type I and type II pathways, until activation of caspase-3. Unknown parameter values in the model were estimated using experimental data obtained from human Jurkat T cells. To elucidate critical signaling network properties, we examined the effects of altering the level of Bcl-2 on the kinetics of caspase-3 activation, using both overexpression and knockdown in the model and experimentally. Overexpression was used to distinguish among alternative hypotheses for inhibitory binding interactions of Bcl-2 with various components in the mitochondrial pathway. In comparing model simulations with experimental results, we find the best agreement when Bcl-2 blocks the release of cytochrome c by binding to both Bax and truncated Bid instead of Bax, truncated Bid, or Bid alone. Moreover, although Bcl-2 overexpression strongly reduces caspase-3 activation, Bcl-2 knockdown has a negligible effect, demonstrating a general model finding that varying the expression levels of signal molecules frequently has asymmetric effects on the outcome. Finally, we demonstrate that the relative dominance of type I vs type II pathways can be switched by varying particular signaling component levels without changing network structure.

Apoptosis↗
PubMed1995

[Hematopoietic dynamics in mammals under combined radiation exposures (mathematical modelling)].

The mathematical models describing the dynamics of hemopoiesis in the mammals exposed to a combination of chronic irradiation are devised and studied. The models reproduce the increased radiosensitivity of the systems of thrombocytopoiesis, erythropoiesis and lymphopoiesis in the animals resulting from prolonged radiation exposure. Succeeding acute radiation exposure causes a more severe damage of the above-mentioned systems than it occurs for the species not being previously exposed to radiation. The model of granulocytopoiesis simulates both the decrease and the increase in radiosensitivity of this system due to the effect of chronic exposure using low and somewhat higher radiation doses, respectively. The postchronic acute radiation exposure has respectively the decreased or increased damaging effect. Within the limits of the models an interpretation of these effects is suggested. The results of modelling have an important theoretical significance in studies of the mechanisms of an effect of small doses of radiation on the mammalian organism as well as point to the perspectives of simulation experiments when evaluating the real radiation risks during long-term space missions.

Acute Disease↗