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PubMed1981

The random transition model of the cell cycle. A critical review.

The random transition model of the cell cycle has received much attention in recent years in attempts to describe and explain variations in cell cycle times. In this review we suggest statistical procedures for fitting the model to experimental data in place of the invalid techniques currently used. However, we also argue that there have been misconceptions about criteria for quality of fit of the model, and consequent biological interpretations. Other models fit just as well, and the analyses we describe do not provide evidence for any particular biological mechanism.

Animals↗

PubMed1993

A diffusion model of early visual search: theoretical analysis and experimental results.

Meinecke (1989, Exp. 1, cond. HO) showed that the detectability of a visual target embedded in a linear noise array decreases with increasing retinal eccentricity, while the reaction time (RT) of the hits increases. One of the most interesting features of her results was that the RT of the correct rejections is consistently larger than the RT for signals presented near the fovea. This finding suggests that initially visual attention is concentrated near the fixation point and then diffuses across the stimulus array to perform a serial, exhaustive search. We present a diffusion model of early visual-search processes that quantitatively describes this evolution of attention in time and space; in contrast to most previous conceptions, it is based on a genuine relation between the spatial and temporal dimensions of the search processes performed. The model predicts quantitatively both detection performance and RT. We conducted an experiment similar to that of Meinecke (1989), but with an additional variation of the presentation time. All the main features of the 189 predictions could be explained by the model. The interpretation of the four model's parameters is discussed in some detail and compared with previous estimates of the microscopic search speed derived from alternative models. Finally, we consider some possible modifications related to results of Kehrer (1987, 1989), and some generalizations to multi target detection and two-dimensional stimulus arrays.

Adult↗

PubMed2004

Refining the measurement of rate constants in the BIAcore.

When estimating rate constants using the BIAcore surface plasmon resonance (SPR) biosensor, one must have an accurate mathematical model to interpret sensogram data. Several models of differing complexity are discussed, including the effective rate constant (ERC) approach. This model can be shown formally to be good within O(Da) in the limit of small Damköhler number Da, which is the ratio of the reaction rate to the rate of transport to the surface. Numerical results are presented that show that except for very slow reactions, parameter estimates from the ERC model are very close to those estimated using a more complicated model. The BIAcore measures the behavior of an evanescent wave whose signal strength decays as it penetrates into the device. It is shown that this decay does not appreciably affect the sensogram readout at low Da, but at moderate Da can lead to situations where two vastly different rate constants can produce the same short-time sensogram data.

Algorithms↗

PubMed2003

Prediction of the effect of mobile-phase salt type on protein retention and selectivity in anion exchange systems.

This study examines the effect of different salt types on protein retention and selectivity in anion exchange systems. Particularly, linear retention data for various proteins were obtained on two structurally different anion exchange stationary-phase materials in the presence of three salts with different counterions. The data indicated that the effects are, for the most part, nonspecific, although various specific effects could also be observed. Quantitative structure retention relationship (QSRR) models based on support vector machine feature selection and regression models were developed using the experimental chromatographic data in conjunction with various molecular descriptors computed from protein crystal structure geometries. Star plots for each descriptor used in the final model were generated to aid in interpretation. The resulting QSRR models were predictive, with cross-validated r2 values of 0.9445, 0.9676, and 0.8897 for Source 15Q and 0.9561, 0.9876, and 0.9760 for Q Sepharose resins in the presence of three different salts. The predictive power of these models was validated using a set of test proteins that were not used in the generation of these models. Interpretation of the models revealed that particular trends for proteins and salts could be captured using QSRR techniques.

Algorithms↗

PubMed1998

Modelling variability in lymphatic filariasis: macrofilarial dynamics in the Brugia pahangi--cat model.

A striking feature of lymphatic filariasis is the considerable heterogeneity in infection burden observed between hosts, which greatly complicates the analysis of the population dynamics of the disease. Here, we describe the first application of the moment closure equation approach to model the sources and the impact of this heterogeneity for macrofilarial population dynamics. The analysis is based on the closest laboratory equivalent of the life cycle and immunology of infection in humans--cats chronically infected with the filarial nematode Brugia pahangi. Two sets of long-term experiments are analysed: hosts given either single primary infections or given repeat infections. We begin by quantifying changes in the mean and aggregation of adult parasites (inversely measured by the negative binomial parameter, kappa in cohorts of hosts using generalized linear models. We then apply simple stochastic models to interpret observed patterns. The models and empirical data indicate that parasite aggregation tracks the decline in the mean burden with host age in primary infections. Conversely, in repeat infections, aggregation increases as the worm burden declines with experience of infection. The results show that the primary infection variability is consistent with heterogeneities in parasite survival between hosts. By contrast, the models indicate that the reduction in parasite variability with time in repeat infections is most likely due to the 'filtering' effect of a strong, acquired immune response, which gradually acts to remove the initial variability generated by heterogeneities in larval mortality. We discuss this result in terms of the homogenizing effect of host immunity-driven density-dependence on macrofilarial burden in older hosts.

Animals↗

PubMed2001

Comparative two- and three-dimensional finite element modelling techniques for tibial fractures.

Often the choice of a two-dimensional modelling approach over a three-dimensional approach is made on the basis of available resources, and not on task appropriateness. In the case of simulating the mechanical behaviour of irregular anatomical structures in biomedical engineering, the authenticity of two-dimensional model behaviour and the interpretation of model solutions is of particular concern since little comparable two-dimensional and three-dimensional data have been published. As part of a research programme, a comparison was made between two-dimensional and three-dimensional finite element models (FEMs) that examine the stress-strain environment of a clinical bone fracture and callus. In comparison with the three-dimensional model, the two-dimensional model substantially underestimated peak compressive principal stresses in the callus tissue and peak equivalent strains. This was a consequence of geometrical and structural asymmetry in a plane perpendicular to the two-dimensional model. However, the two-dimensional model predicted similar patterns of stress and strain distribution to the corresponding mid-longitudinal plane of the three-dimensional model, and underestimates of peak stress and strain were much reduced. This confirmed that despite the irregular geometry and structure of the subject, the two-dimensional model provided a valid mechanical simulation in the plane of the fracture that it represented.

Biomechanical Phenomena↗

PubMed2002

A haemodynamic model for the physiological interpretation of in vivo measurements of the concentration and oxygen saturation of haemoglobin.

We present a model that describes the effect of physiological parameters such as the speed of blood flow, local oxygen consumption, capillary recruitment, and vascular dilation/constriction on the concentration and oxygen saturation of haemoglobin in tissue. This model can be used to guide the physiological interpretation of haemodynamic and oximetric data collected in vivo with techniques such as optical imaging, near-infrared spectroscopy and functional magnetic resonance imaging. In addition to providing a formal description of well-established results (exercise-induced hyperemia, reperfusion hyperoxia, decrease in the concentration of deoxyhaemoglobin induced by brain activity, measurement of arterial saturation by pulse oximetry, etc.), this model suggests that the superposition of asynchronous contributions from the arterial, capillary and venous haemoglobin compartments may be at the origin of observed out-of-phase oscillations of the oxyhaemoglobin and deoxyhaemoglobin concentrations in tissue.

Hemodynamics↗

PubMed2003

Model selection for the interpretation of protein side chain methyl dynamics.

A number of different dynamics models are considered for fitting (13)C and (2)H side chain methyl relaxation rates. It is shown that in cases where nanosecond time scale dynamics are present the extended Lipari-Szabo model which is explicitly parameterized to include the effects of slow motions can produce wide distributions of fitting parameters even in cases where the errors are relatively small and large numbers of relaxation rates are considered. In contrast, fits of (15)N backbone dynamics using this model are far more robust. The origin of this difference is analyzed and can be explained by the different functional forms of the spectral density in these two cases. The utility of a number of models for the analysis of methyl side chain dynamics is presented.

Amino Acids↗

PubMed1989

A model for multisystem evaluation, interpretation, and treatment of individuals with neurologic dysfunction.

We have presented a model that can be used to organize current concepts of neuroanatomy, neurophysiology, and motor control theory into a clinically relevant context. This model can be used to postulate the causal relationship among pathology, impairments, and disabilities. Knowledge of the insult often provides predictive information regarding stability of the disability, progression of the disease, and possibly recovery. Knowledge of neuropathology should guide the clinician regarding the types of impairments that are expected. Thus, by knowing the type and location of the lesion, the clinician already has a perspective regarding which evaluative tests should be emphasized and what treatment strategies will be most effective. In the absence of known pathology, knowledge of motor control theory, neuroanatomy, and neuropathology can still help the clinician make educated judgments regarding the interrelationship of the patient's impairments. In this model, we separate impairments that result directly from neuropathology and those that arise indirectly to help the clinician keep the total patient in perspective and to focus intervention. This separation emphasizes the applicability and limitations of motor control theories in the treatment of neurologically impaired individuals. Motor control theory helps to identify the relationship between direct impairments and their likely consequences; motor control theory does not address the very real issue of impairments that arise indirectly in systems such as the musculoskeletal and cardiopulmonary systems. Impairments that occur as a composite effect of multiple causes are identified as a separate category. Some of the causes of these impairments can often be addressed by physical therapy intervention, and some cannot.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebrovascular Disorders↗

PubMedDate not supplied

[Socio-economic inequalities and mental health. I. Concepts, theories, and interpretations].

AIMS: Reconstructing the models used for approaching the inequalities issues in health, identifying the most relevant theoretical and conceptual contributions. METHOD: Literature electronic-search on Medline, Psyclit, Econlit, Social Science Index and SocioSearch using the key-words inequalities, deprivation, poverty, socio-economic status, social class, occupational class, mental health for the period 1965-2002; integrated with manual search. The material was classified according to the conceptual and theoretical interpretative models or to the analyses of the association 'inequalities-health' where health was expressed as mortality, morbidity or services utilisation. RESULTS: Four different interpretative models about the genesis of inequalities were identified. Further theoretical developments overcome the distinction among conceptuals contrapositions selection versus causation, statistic artefactual versus real differences, individual behaviours versus material context. Since the 80's the concept of material deprivation has been enlarged to include social deprivation to explain health inequalities. The social exclusion is related to material deprivation and to social fragility enlarging the traditional aspects of poverty. The theories that better adapt to the psychiatric field are the social selection and social causation. CONCLUSIONS: The social exclusion and the new methodologies for measuring the inequalities seems to be an effective way for understanding of the inexplored aspects of the mental health inequalities.

Health Services Accessibility↗

PubMed2002

From heart attacks to melanoma: do common sense models of somatization influence symptom interpretation for female victims?

Common sense models regarding gender and stress influenced how laypeople responded to information about symptoms in 3 experiments. In Study 1, medical intervention was perceived to be less important for female targets reporting chest pain and stressful events than for male targets experiencing identical symptoms and stressors. In addition, chest pain was less likely to be attributed to cardiac causes for female targets. This gender-based stress-discounting effect was replicated for symptoms of gallstones and melanoma in Study 2, where participants again were less likely to recommend medical care for female than for male targets. Recognition memory for information about a somatizing target was tested in Study 3; results suggested that laypeople hold stereotypes associating somatization with female gender. The authors' findings provide insight into the naive theories that shape symptom interpretation and self-referral behavior.

Adolescent↗

PubMed1991

Improved methods for building protein models in electron density maps and the location of errors in these models.

Map interpretation remains a critical step in solving the structure of a macromolecule. Errors introduced at this early stage may persist throughout crystallographic refinement and result in an incorrect structure. The normally quoted crystallographic residual is often a poor description for the quality of the model. Strategies and tools are described that help to alleviate this problem. These simplify the model-building process, quantify the goodness of fit of the model on a per-residue basis and locate possible errors in peptide and side-chain conformations.

Chemical Phenomena↗

PubMed1985

The use of a logistic model for the quantitative interpretation of indirect sandwich enzyme labelled immunosorbent assays (ELISA) for antibodies and antigens in foot and mouth disease.

A three parameter logistic model is described for the analysis of profiles of optical density vs log dose for indirect sandwich ELISA tests in foot and mouth disease. The model describes the observed phenomenon of saturability with increasing dose, and its parameters can be interpreted in terms of molecular binding events. A computer program to fit the model is described. An approximate statistical test is developed which can be used to test for departures from equivalence for replicate profiles. It is found that correlation of the optical density values to a standard reference reaction considerably improves reproducibility.

Animals↗

PubMed2003

Topology of gene expression networks as revealed by data mining and modeling.

MOTIVATION: Interpretation of high-throughput gene expression profiling requires a knowledge of the design principles underlying the networks that sustain cellular machinery. Recently a novel approach based on the study of network topologies has been proposed. This methodology has proven to be useful for the analysis of a variety of biological systems, including metabolic networks, networks of protein-protein interactions, and gene networks that can be derived from gene expression data. In the present paper, we focus on several important issues related to the topology of gene expression networks that have not yet been fully studied. RESULTS: The networks derived from gene expression profiles for both time series experiments in yeast and perturbation experiments in cell lines are studied. We demonstrate that independent from the experimental organism (yeast versus cell lines) and the type of experiment (time courses versus perturbations) the extracted networks have similar topological characteristics suggesting together with the results of other common principles of the structural organization of biological networks. A novel computational model of network growth that reproduces the basic design principles of the observed networks is presented. Advantage of the model is that it provides a general mechanism to generate networks with different types of topology by a variation of a few parameters. We investigate the robustness of the network structure to random damages and to deliberate removal of the most important parts of the system and show a surprising tolerance of gene expression networks to both kinds of disturbance.

Algorithms↗

PubMed1995

A linear modelling approach to automatic interpretation of quality control measurements in mammography.

An approach to the automated interpretation of quality control data is described in which the relationship between small changes in system performance and the resulting small changes in the measured quality control test results are approximated as a set of linear equations in matrix form. The inverse of this forward matrix is then used to identify causal changes from the set of measured changes. This approach has been investigated for the case of mammographic screening quality assurance and shown to provide a potentially useful tool to assist in the interpretation task.

Autoanalysis↗

PubMed1997

Fourier models and the loci of adaptation.

First measures of sensitivity and the need for a model to interpret them are addressed. Then modeling in the Fourier domain is promoted by a demonstration of how much an approach explains spatial sensitization and its dependence on luminance. Then the retinal illuminance and receptor absorptions produced by various stimuli are derived to foster interpretation of the neural mechanisms underlying various psychophysical phenomena. Finally, the sequence and the anatomical loci of the processes controlling visual sensitivity are addressed. It is concluded that multiplicative adaptation often has effects identical to response compression followed by subtractive adaptation and that, perhaps as a consequence, there is no evidence of retinal gain changes in human cone vision until light levels are well above those available in natural scenes and in most contemporary psychophysical experiments; that contrast gain control fine tunes sensitivity to patterns at all luminances; and that response compression, modulated by subtractive adaptation, predominates in the control of sensitivity in human cone vision.

Adaptation, Physiological↗

PubMed1999

Electrostatic Contribution to the Enthalpy of Charging at Hematite/Electrolyte Interface.

A calorimetry study of hematite surface reactions is reported, with special emphasis on the estimation of the electrostatic contribution to the enthalpy of charging. The calorimetry titrations were performed outside the point of zero charge region where the electrostatic contribution is significant. The results were interpreted by the surface complexation model. The interpretation enabled the evaluation of standard protonation and deprotonation enthalpies as well as the electrostatic contribution to these quantities. Copyright 1999 Academic Press.

Journal Article↗

PubMed1994

The GALEN project.

The GALEN project is developing language independent concept representation systems as the foundations for the next generation of multilingual coding systems. It aims to support the flexibility required to cope with the diversity amongst medical applications, while ensuring the coherence necessary for integration and re-use of terminologies. GALEN is developing a fully compositional and generative formal system for modelling concepts: the GALEN Representation and Integration Language (GRAIL) Kernel. Its goal is to overcome many of the problems with traditional coding and classification systems, in particular the combinatorial explosion of terms in enumerative systems and the generation of nonsensical terms in partially compositional systems. It will also provide a clean separation between the concept model and linguistic mechanisms which interpret that model (i.e., the words in a specific language, syntax, alternative phrasings, etc.) in order to allow the development of multilingual systems. GRAIL aims to be formally sound and produce models that are verifiable and contain no contradictions or ambiguities, with realistic human effort. A Coding Reference (CORE) Model of medical terminology covering is being developed which aims to represent the core concepts in for example pathology, anatomy and therapeutics, that have widespread applicability in medical applications. It should also provide the basis for specialist extensions according to the formal principles of GRAIL. The main results of GALEN will be delivered as a Terminology Server (TeS) which encapsulates and coordinates the functionality of the concept module, multilingual module, and code conversion module, and also provides a uniform applications programming interface and network services for use by external applications.

Databases, Bibliographic↗