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PubMed2002

Modeling extracellular matrix degradation balance with proteinase/transglutaminase cycle.

Extracellular matrix mass balance is implied in many physiological and pathological events, such as metastasis dissemination. Widely studied, its destructive part is mainly catalysed by extracellular proteinases. Conversely, the properties of the constructive part are less obvious, cellular neo-synthesis being usually considered as its only element. In this paper, we introduce the action of transglutaminase in a mathematical model for extracellular matrix remodeling. This extracellular enzyme, catalysing intermolecular protein cross-linking, is considered here as a reverse proteinase as far as the extracellular matrix physical state is concerned. The model is based on a proteinase/transglutaminase cycle interconverting insoluble matrix and soluble proteolysis fragments, with regulation of cellular proteinase expression by the fragments. Under "closed" (batch) conditions, i.e. neglecting matrix influx and fragment efflux from the system, the model is bistable, with reversible hysteresis. Extracellular matrix proteins concentration abruptly switches from low to high levels when transglutaminase activity exceeds a threshold value. Proteinase concentration usually follows the reverse complementary kinetics, but can become apparently uncoupled from extracellular matrix concentration for some parameter values. When matrix production by the cells and fragment degradation are taken into account, the dynamics change to sustained oscillations because of the emergence of a stable limit cycle. Transitions out of and into oscillation areas are controlled by the model parameters. Biological interpretation indicates that these oscillations could represent the normal homeostatic situation, whereas the other exhibited dynamics can be related to pathologies such as tumor invasion or fibrosis. These results allow to discuss the insights that the model could contribute to the comprehension of these complex biological events.

Animals↗

PubMed2006

An imaging-based computational approach to model ventilation distribution and soft-tissue deformation in the ovine lung.

RATIONALE AND OBJECTIVES: A computational modeling framework of soft-tissue mechanics and air flow has been developed toward the aim of linking computed tomography measures of ventilation distribution to subject-specific predictions in imaging-based geometric models of the lung. The aim of this approach is to enable predictions of the effect of perturbations in geometry or functional parameters on imaged function of the lung. MATERIALS AND METHODS: Computational techniques that can deal with anatomic detail and spatially distributed nonlinear material properties are used to model parenchymal soft-tissue mechanics in a physically realistic model of the ovine lung. The lung is modeled as a homogeneous, compressible, nonlinearly elastic body. Using equations for large deformation mechanics, change in geometry of the lung is simulated at static inflation pressures from 25 cm H2O to 0 cm H2O. Multidetector row computed tomography imaging defines the model geometry, the movement of the model lung surface during inflation, and displacement of airway bifurcations for comparison with predicted internal displacements of the model. RESULTS: A novel modeling framework has been formulated that links equations for large deformation of the lung tissue to equations for airway flow and pressure. This preliminary model predicts airway displacements that are in good agreement with imaged displacements (total root mean square [RMS] error < 4 mm from 25 to 0 cm H2O). CONCLUSIONS: State-of-the-art computed tomography imaging is interpreted using a modeling framework to predict ventilation distribution and changes in the geometry of the lung during increments in inflation pressure. Further development will provide a predictive link between subject-specific anatomy and function.

Algorithms↗

PubMed2005

Performance assessment of a zeolite treatment wall for removing Sr-90 from groundwater.

Laboratory and modeling studies were conducted to assess the potential performance of a permeable reactive barrier constructed of a natural zeolite material at the West Valley Demonstration Project in western New York State. The results of laboratory column tests indicated that the barrier material would be effective at removing strontium from groundwater under natural gradient conditions. Two one-dimensional contaminant transport models were developed to interpret the data. A single-solute retardation factor model provided good agreement with the column test data, but time-consuming extraction and analysis of the zeolite material was required to parameterize the model. A preliminary six-solute model was also developed based on the assumption of competitive cation exchange as the primary removal mechanism. Both models yielded similar predictions of the long-term performance of the barrier, but the cation exchange model predicted higher effluent concentrations during the first 1000 pore volumes of operation. The cation exchange framework has several advantages, including the ability to calibrate the model using only data from column effluent samples, and the ability to account for site-specific differences in the groundwater cation composition. However, additional laboratory work is needed to develop a suitably robust model.

Ion Exchange↗

PubMed2005

A semi-analytical model for predicting multiple propagating axially symmetric modes in cylindrical waveguides.

A semi-analytical model for multiple mode axially symmetric wave propagation in finite solid cylindrical waveguides is presented. The model is designed as a tool for predicting and interpreting experimental signals. The model is based on a common experimental configuration and considers the excitation, propagation and reception of the ultrasonic signal in the waveguide. The Pochhammer-Chree solution for an infinite cylinder is the basis for the model. Extensions are made to enable comparison to experimental results. Comparisons with experiment are performed in the time, frequency and joint-time frequency domain for both narrow band and broad band excitation of the piezo-electric transducer.

Journal Article↗

PubMed2002

ERP 'old/new' effects: memory strength and decisional factor(s).

Event-related potentials (ERPs) were recorded while subjects made old/new recognition judgments on new unstudied words and old words which had been presented at study either once ('weak') or three times ('strong'). The probability of an 'old' response was significantly higher for strong than weak words and significantly higher for weak than new words. Comparisons were made initially between ERPs to new, weak and strong words, and subsequently between ERPs associated with six strength-by-response conditions. The N400 component was found to be modulated by memory trace strength in a graded manner. Its amplitude was most negative in new word ERPs and most positive in strong word ERPs. This 'N400 strength effect' was largest at the left parietal electrode (in ear-referenced ERPs). The amplitude of the late positive complex (LPC) effect was sensitive to decision accuracy (and perhaps confidence). Its amplitude was larger in ERPs evoked by words attracting correct versus incorrect recognition decisions. The LPC effect had a left>right, centro-parietal scalp topography (in ear-referenced ERPs). Hence, whereas, the majority of previous ERP studies of episodic recognition have interpreted results from the perspective of dual-process models, we provide alternative interpretations of N400 and LPC old/new effects in terms of memory strength and decisional factor(s).

Adult↗

PubMed2000

Tissue structure study through ultrasonic forward scattering.

A procedure is demonstrated for characterization of biological tissues at small scattering angles. The power spectra of ultrasonic pulses transmitted through excised tissue samples were measured and compared to the spectra of signals transmitted through a water path. The specimens were examined in two spatial-frequency bands by acquiring data at scattering angles of 10 degrees and 20 degrees using 2.25 MHz transducers. Peaks in the measured power spectra are interpreted using two signal models. The medium is modelled either as a periodic structure producing a single spectral peak, or by two discrete targets producing a periodic modulation of the spectrum. The periodic structure model appears to be the more promising method for interpretation of forward-scattered signals. Data acquired from hyperplastic spleen and atheromatous aorta specimens both exhibited increases in pulse-tissue interaction at low spatial frequencies compared to normal specimens of those tissues. This observation is tentatively linked to increases in the size or separation of distributed scattering structures resulting from those pathologies.

Animals↗

PubMed2000

The importance of phase data and model dimensionality to cochlear mechanics.

The vulnerability of the mammalian cochlear amplifier to surgical trauma hinders observations of its behaviour in vivo. This produces a greater need for realistic models to aid the interpretation of the experimental observations. The emphasis in most modelling studies has been to simulate the gain of the response of the basilar membrane. This paper argues that matching the phase behaviour of the response should be given at least equal importance. When it is, many of the models used to justify hypotheses regarding the operation of the cochlear amplifier cannot simulate the response even of the dead cochlea. This discrepancy is due to oversimplification of the mechanics of the cochlear fluids. It is argued that three-dimensional fluid behaviour should be regarded as a bare minimum in any quantitative description of cochlear mechanics. Furthermore, it is shown that a three-dimensional model is consistent with experimental data from a healthy cochlea only when the main effect of the cochlear amplifier is to inject mechanical energy into the basilar membrane. The injection of mechanical energy is fundamentally different to modifying the stiffness of the basilar membrane. This means that existing models which possess cochlear amplifiers that effect large changes on the stiffness of the basilar membrane may not be accurate representations of the real organ.

Animals↗

PubMed2005

Small-angle neutron scattering and theoretical investigation of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) stabilized oil-in-water microemulsions.

The aim of this study is to determine the effects of oil solutes and alcohol cosolvents on the structure of oil-in-water microemulsions stabilized by poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymers. The systems investigated involved the solubilization of 1,3,5-trimethylbenzene or 1,2-dichlorobenzene by P123 (EO(20)-PO(70)-EO(20)) pluronic surfactant micelles in water and water + ethanol solvents. The structures of these swollen micelles were determined by small-angle neutron scattering (SANS). A thermodynamic model was employed to interpret the characterization data. The results of the thermodynamic model for micellization agreed well with the SANS data from samples of micelles swollen by both oils. The model predicted the size of the micelles within 5% accuracy using only one fitting parameter, the micelle polydispersity. Ethanol had significantly different effects on the polymer micelles that contained solubilized oil compared to pure polymer micelles. For pure polymer micelles, the addition of ethanol increased the solubility of the polymer and, therefore, decreased the total volume fraction of micelles, while for polymer-oil aggregates, ethanol tended to have a positive effect on the volume fraction of micelles. SANS results showed that the greatest divergence from pure aqueous solvent results occurred at oil concentrations above the microemulsion stability limit.

Journal Article↗

PubMed1996

Job stress and cardiovascular disease: a theoretic critical review.

During the last 15 years, the research on job stress and cardiovascular diseases has been dominated by the job strain model developed by R. Karasek (1979) and colleagues (R. Karasek & T. Theorell, 1990). In this article the results of this research are briefly summarized, and the theoretical and methodological basis is discussed and criticized. A sociological interpretation of the model emphasizing theories of technological change, qualifications of the workers, and the organization of work is proposed. Furthermore, improvements with regard to measuring the job strain dimensions and to sampling the study base are suggested. Substantial improvements of the job strain research could be achieved if the principle of triangulation were used in the measurements of stressors, stress, and sickness and if occupation-based samples were used instead of large representative samples.

Cardiovascular Diseases↗

PubMedDate not supplied

Studying the determinants of exposure: a review of methods.

To better understand where, when, and how to control occupational exposures, it is vital that hygienists understand the factors that contribute to elevated or reduced exposure levels. Over the last two decades a burgeoning literature examining the determinants of exposure has developed, yet to date the methods used in this regard have rarely been summarized in texts or elsewhere. The purpose of this article is to provide an overview of the techniques used to study the predictors of workplace exposures. Both experimental and observational studies are examined, and the advantages and limitations of each are discussed. Fundamental study design features are reviewed. These include the selection and measurement of factors potentially related to exposure, as well as the measurement of exposure itself. Decisions reached by investigators in selecting the number of sites and workers, the number of repeated observations per worker, and the duration of sampling are discussed. Also examined are issues that commonly arise in the course of data analysis of exposure determinants. These include transformation of exposure variables, correlation of predictor variables, empirical model building, and interpretation of results. Finally, methods employed to evaluate the validity of findings are summarized.

Environmental Monitoring↗

PubMed2000

Conformational dynamics of a metallomesogen studied by 2H-NMR spectroscopy

In this work we present a quantitative analysis of both quadrupolar splittings and deuterium Zeeman and quadrupolar spin-lattice relaxation times reported in the literature for two isotopomers of Azpac, an acetylacetonate derivative of the cyclopalladated 4, 4'-bis(hexyloxy) azoxybenzene. Azpac-d(4) is deuterated at the aromatic rings and Azpac-d(26) is deuterated on the alkoxy chains. The additive potential method is used to model the splittings, while the derived spectral densities are interpreted using the decoupled model in conjunction with the Nordio model. The two side chains are assumed to be noninteracting and identical in their conformations in order to limit the size of the transition rate matrix needed to describe correlated internal bond rotations in the chains. Rotational diffusion constants and internal jump rate constants are derived for this metallomesogen.

Journal Article↗

PubMed1991

Freeze substitution reveals a new model for sporangial cleavage in Phytophthora, a result with implications for cytokinesis in other eukaryotes.

Rapid freezing and freeze substitution (RF-FS) have been used to re-examine the process by which the multinucleate sporangium of the Oomycetes, Phytophthora cinnamomi and P. palmivora, is subdivided into uninucleate zoospores. The results indicate a new model for sporangial cleavage in Phytophthora and suggest that the currently accepted model is based on interpretation of artefacts caused by chemical fixation. The previous model describes cleavage as a two-stage process in which specialized cleavage vesicles first become positioned at the boundaries of each future subdivision and later fuse to compartmentalize the sporangium. RF-FS, however, indicates that cleavage results from the progressive extension of paired sheets of membrane along the future subdivision boundaries. These sheets finally interconnect and subdivide the sporangium. Cleavage vesicles are only evident in preliminary stages of this process and are never aligned along the future boundaries, contrary to the observations of studies based on chemical fixation. Chemical fixation apparently causes the membranous sheets to vesiculate, even at relatively advanced stages of cleavage, thus giving the misleading impression that the resulting network of lined-up vesicles is an intermediate stage in the cleavage process. This finding has wide-ranging implications for the understanding of eukaryotic cytokinesis, because all previous studies that describe vesicle alignment and fusion have relied upon chemical fixation. Other novel features revealed by RF-FS include an extensive extracellular matrix within the sporangium that could be involved in zoospore release, and a trans-Golgi network.

Artifacts↗

PubMed2005

Framework for multivariate selectivity analysis, part I: theoretical and practical merits.

A number of definitions of multivariate selectivity have been proposed in the literature. Arguably, the one that enjoys the greatest chemometric attention has been the net analyte signal (NAS) based definitions of Lorber and Zinn. Recent works have suggested that similar inference can be made for inverse least-squares calibration methods (e.g., principal components regression). However, the properties of inverse calibration methods are markedly different than classical methods, so in many practical cases involving inverse models classically derived figures of merit cannot be transparently interpreted. In Part I of this work, we discuss a selectivity framework that is theoretically consistent regardless of the calibration method. Importantly, it is also experimentally measurable, either through controlled selectivity experiments, or through analysis on opportunistically acquired sample measurements. It is statistically advantageous to use the former if such control is achievable. Selectivity is defined to be a function of the change in predicted analyte concentration that will result from a change in the concentration of an interferant, an approach consistent with traditional definitions of analytical selectivity and National Committee for Clinical Laboratory Standards recommendations for interference testing. Unlike the NAS-based definition of selectivity, the definition discussed herein is relevant to only a particular analyte-interferant pair. The theoretical and experimental aspects of this approach are illustrated with simulated data herein and in Part II of this paper, which investigates several experimental near-infrared data sets.

Algorithms↗

PubMed2000

Kinetic study of the inactivation of ascorbate peroxidase by hydrogen peroxide.

The activity of ascorbate peroxidase (APX) has been studied with H(2)O(2) and various reducing substrates. The activity decreased in the order pyrogallol>ascorbate>guaiacol>2, 2'-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS). The inactivation of APX with H(2)O(2) as the sole substrate was studied. The number of H(2)O(2) molecules required for maximal inactivation of the enzyme was determined as approx. 2.5. Enzymic activity of approx. 20% of the original remained at the end of the inactivation process (i.e. approx. 20% resistance) when ascorbate or ABTS was used as the substrate in activity assays. With pyrogallol or guaiacol no resistance was seen. Inactivation by H(2)O(2) followed over time with ascorbate or pyrogallol assays exhibited single-exponential decreases in enzymic activity. Hyperbolic saturation kinetics were observed in both assay systems; a similar dissociation constant (0.8 microM) for H(2)O(2) was obtained in each case. However, the maximum rate constant (lambda(max)) obtained from the plots differed depending on the assay substrate. The presence of reducing substrate in addition to H(2)O(2) partly or completely protected the enzyme from inactivation, depending on how many molar equivalents of reducing substrate were added. An oxygen electrode system has been used to confirm that APX does not exhibit a catalase-like oxygen-releasing reaction. A kinetic model was developed to interpret the experimental results; both the results and the model are compared and contrasted with previously obtained results for horseradish peroxidase C. The kinetic model has led us to the conclusion that the inactivation of APX by H(2)O(2) represents an unusual situation in which no enzyme turnover occurs but there is a partition of the enzyme between two forms, one inactive and the other with activity towards reducing substrates such as ascorbate and ABTS only. The partition ratio is less than 1.

Ascorbate Peroxidases↗

PubMed1999

Brain-spinal cord interactions stabilize the locomotor rhythm to an external perturbation.

Motor networks within the spinal cord of vertebrates are capable of generating rhythmic locomotor output even in the absence of phasic sensory input. In an intact animal these spinal pattern generators are affected by descending inputs from the brain and by sensory inputs. The role of the feedforward-feedback (FF-FB) loops between the brain and the spinal cord in the control of locomotion are not well understood. We hypothesized that the dynamic interaction between the brain and the spinal cord would affect the response of the neural system to external perturbation. We investigated this hypothesis in an in-vitro brain-spinal cord fictive locomotion preparation of a primitive vertebrate, lamprey. In tandem, we analyzed the behavior of a neural network model representing the brain and multiple segments of the spinal cord. Our experimental results indicate that with intact FF-FB loops, phase locked entrainment of the spinal motor activity can be obtained on direct stimulation of the spinal cord. However, the effect is localized with minimal influence on distal spinal segments. The intersegmental coupling strength is strong as indicated by a fast recovery of the perturbed rhythm to the natural frequency on termination of the perturbation. With the FF-FB loop interrupted, the perturbation was capable of altering the motor activity from multiple sites in the spinal cord. Also, upon termination of the perturbation there was a prolonged period before recovery of the original natural frequency. Model analyses support our interpretation of the experimental results. In the neural network model with the brain-spinal cord loops closed there was a localized effect on the oscillatory rhythm and strong intersegmental coupling. Also, the analysis indicated the presence of a smaller entrainment range and many more periodic orbits than with the loops open. The results suggest that the increased variability in the locomotor rhythm and decreased sensitivity to perturbation observed in the presence of intact brain spinal cord connections may be a reflection of a higher dimensional system with many periodic orbits. The higher dimension could allow the system to collectively remain within the attractor space of one of these periodic orbits and thus remain resilient to perturbation.

Animals↗

PubMed2001

Extensiometric determination of the rheological properties of the epidermis of growing tomato fruit.

This paper examines the rheological properties of the fruit epidermis of tomato (Lycopersicon esculentum L.). This research was conducted because previous work had demonstrated that the rate of tomato fruit growth is determined by the interaction of tissue pressure and epidermal properties. A constant-load (or 'creep') extensiometer was employed in these experiments and the results interpreted using a model which describes creep retardation using a limited number of rheological elements, one of which appears analogous to plant growth and is of similar magnitude to fruit growth rate in vivo. The effects of pH, applied force and boiling upon the individual components of the model have been examined and indicate that several elements are strongly pH-dependent and that this dependency is eliminated by boiling. These results suggest that enzyme activity (plausibly that of one or more expansins) reduces the viscosity of the cell wall over a wide range of time scales. Further consideration of the creep of tomato epidermis in terms of models developed to describe the behaviour of artificial polymers suggests that the types of molecular event described by each rheological element can tentatively be identified and that pH-dependent enzyme activity facilitates both conformer rotation and macromolecular movement within the plant cell wall. These interpretations ascribe considerable importance to the time scale over which creep occurs.

Biomechanical Phenomena↗

PubMed2002

[Hypochondriasis and cognitive therapy].

BACKGROUND: Hypochondriasis is an annoying disorder. Diagnostic criteria for primary and secondary hypochondriasis as well as comorbidity are explained. MATERIAL AND METHODS: Some studies of prevalence, aetiology and treatment are reviewed. Special emphasis is given to the cognitive model. RESULTS AND INTERPRETATION: The prevalence of primary hypochondriasis in population studies is around 1%, while the prevalence in medical outpatient clinics is 3-4.5%. Several controlled, clinical studies have found positive effect of cognitive-behavioural therapy. Excessive health anxiety that is secondary to depression disappears when the primary disorder is treated. Controlled clinical trials of medication is lacking. Traditionally, hypochondriasis has been considered a difficult diagnosis to present to the patient and hard to treat. Research has increased our knowledge and understanding of the disease, and structured treatment protocols have led to a well founded optimism concerning prognosis. Central themes in the consultations are the question of life and death, interpretation of subjective somatic symptoms and the ability to make decisions when still in doubt.

Cognitive Behavioral Therapy↗

PubMed1986

Linear-lumped-parameter modeling of pulmonary impedance in monkeys.

Pulmonary impedance, ZL, measured from 2 to 32 Hz in anesthetized, intubated and paralyzed bonnet monkeys (Macaca radiata) was fitted to a variety of linear-lumped parameter mechanical networks. Parameter values for each network were obtained by minimizing the average of the percent distance, Dr, between the computed network impedance and measured ZL at all frequencies. Measured resistance, RL, decreased from 2 to 8 Hz and increased from 8 to 32 Hz indicating that a single series resistance-inertance-compliance (RIC) network was not optimal (Dr approximately 19%). Networks consisting of two series RIC pathways in parallel resulted in a lower Dr (approximately 14%), but parameter values were difficult to interpret. Despite not modeling the decrease in RL with frequency below 8 Hz, an airway wall compliance, Caw, network in which the airways were separated into central and peripheral components resulted in an even lower Dr (approximately 11%). In addition, parameter values were easy to interpret, consistent among our "normal" monkeys and changed consistently and explainably with change in lung mechanics induced by decrease in lung volume. We conclude that networks containing both parallel pathways and Caw are necessary to model ZL over the entire frequency range (2-32 Hz), the effect of Caw is an important determinant of ZL above 8 Hz, and a six-parameter Caw network with the ratio of Caw to parenchymal compliance, Cp, fixed may prove useful in interpreting changes in ZL induced by alterations in lung mechanics in monkeys.

Airway Resistance↗