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PubMed1997

Spectral mechanisms of spatially induced blackness: data and quantitative model.

Spectral efficiency functions and tests of additivity were obtained with three observers to identify possible chromatic contributions to spatially induced blackness. Stimuli consisted of a series of monochromatic (400-700 nm; 10-nm steps), 52-arcmin circular test lights surrounded by broadband (x = 0.31, y = 0.37), 63-138-arcmin annuli of fixed retinal illuminance. The stimuli were imaged on the fovea in Maxwellian view as 500-ms flashes with 10-s interstimulus intervals. Observers decreased the intensity of the test center until it was first perceived as completely black. Action spectra determined for two surround levels [2.5 and 3.5 log trolands] had three sensitivity peaks (at approximately 440, 540, and 600 nm), However, when monochromatic surrounds were adjusted to induce blackness in a broadband center, action spectra were unimodal and identical to functions obtained by heterochromatic flicker photometry. Tests of additivity revealed that when blackness is induced by broadband surround into a bichromatic center, there is an additivity failure of the cancellation type. This additivity failure indicates that blackness induction is influenced, in part, by signals from opponent-chromatic pathways. A quantitative model is presented to account for these data. This model assumes that blackness induction is determined by the ratio of responses to the stimulus center and the annulus, and while signals form the annulus are based only on achromatic information, responses from the center are based on both chromatic and achromatic properties of the stimulus.

Color Perception↗
PubMed1985

Adherence of coagulase-negative staphylococci to plastic tissue culture plates: a quantitative model for the adherence of staphylococci to medical devices.

The adherence of coagulase-negative staphylococci to smooth surfaces was assayed by measuring the optical densities of stained bacterial films adherent to the floors of plastic tissue culture plates. The optical densities correlated with the weight of the adherent bacterial film (r = 0.906; P less than 0.01). The measurements also agreed with visual assessments of bacterial adherence to culture tubes, microtiter plates, and tissue culture plates. Selected clinical strains were passed through a mouse model for foreign body infections and a rat model for catheter-induced endocarditis. The adherence measurements of animal passed strains remained the same as those of the laboratory-maintained parent strain. Spectrophotometric classification of coagulase-negative staphylococci into nonadherent and adherent categories according to these measurements had a sensitivity, specificity, and accuracy of 90.6, 80.8, and 88.4%, respectively. We examined a previously described collection of 127 strains of coagulase-negative staphylococci isolated from an outbreak of intravascular catheter-associated sepsis; strains associated with sepsis were more adherent than blood culture contaminants and cutaneous strains (P less than 0.001). We also examined a collection of 84 strains isolated from pediatric patients with cerebrospinal fluid (CSF) shunts; once again, pathogenic strains were more adherent than were CSF contaminants (P less than 0.01). Finally, we measured the adherence of seven endocarditis strains. As opposed to strains associated with intravascular catheters and CSF shunts, endocarditis strains were less adherent than were saprophytic strains of coagulase-negative staphylococci. The optical densities of bacterial films adherent to plastic tissue culture plates serve as a quantitative model for the study of the adherence of coagulase-negative staphylococci to medical devices, a process which may be important in the pathogenesis of foreign body infections.

Animals↗
PubMed1988

In vitro quantitative model of catheter infection during simulated parenteral nutrition.

We developed a quantitative in vitro model of catheter infection. Colonization was initiated by inoculating the catheter lumen with a small number of bacteria (approximately 5 x 10(3) viable organisms). Then the inoculated catheters were used for simulated total parenteral nutrition therapy consisting of infusions for 9 h a day, and bacteria were counted in the effluent fluid against time, enabling us to monitor catheter colonization quantitatively. Bacterial colonization of prosthetic devices is a progressive process, as evidenced by the slow day-to-day increase of bacterial release seen here. On the other hand, bacterial strains of various representative species exhibited significant differences in their ability to infect catheters. These results suggest that the in vitro model presented here is a reliable tool for monitoring the degree of catheter colonization under standardized conditions and could be used for further studying the main factors of catheter-related sepsis or the treatment of this information.

Bacteria↗
PubMed1988

Platelet deposition in a capillary perfusion model: quantitative and morphological aspects.

The capillary perfusion model according to Cazenave and co-workers was characterized by investigating the effects of protein precoating, perfusion time and shear rate on platelet deposition using 111Indium labelling of human platelets and scanning electron microscopy (SEM). Compared with uncoated polyethylene, platelet deposition was increased after precoating with purified human von Willebrand factor, fibrinogen or fibronectin, and decreased by preadsorbed immunoglobulin G, albumin or whole plasma. Platelet aggregates were observed on immunoglobulin G-coated polyethylene, whereas all other surfaces showed single adherent platelets. Complete platelet spreading was only observed after precoating with fibronectin. The quantitative data concerning platelet deposition were evaluated by using the convective-diffusion theory. Our results indicate the applicability of this perfusion model for the in vitro testing of biomaterials.

Adsorption↗
PubMed1994

Nerve growth dynamics. Quantitative models for nerve development and regeneration.

The quantitative analysis of nerve growth dynamics is critical to our understanding of nerve development and regeneration, but only recently has a quantitative framework begun to emerge to help define key objectives and to direct experimental measurements towards achieving this goal. Conceptually, the framework centers on the dynamic processes commonly observed for individual growth cones of growing neurites at the phase microscopy level, namely lamellipodial and filopodial extension and retraction. Because these activities essentially define the position of the axon tip, understanding how they are regulated offers to yield direct insight into factors governing the growth trajectory of the axon. In addition, much biological interest and effort is focused on the lamellipodial and filopodial behavior of the growth cone, which should facilitate experimental quantitation. Characterization of lamellipodial and filopodial activity has not been straightforward, however, because their inherent randomness leads to a requirement for considerable data and for less common mathematical techniques, such as time-series analysis. The work reviewed above has identified key analytical tools and experimental parameters needed to develop an integrated model of growth cone dynamics. Detailed measurement and analysis will be required to carry this development process to the next step. The cellular model of growth cone motility resulting from the characterization of lamellipodial and filopodial dynamics represents an intermediate description that can be extended to encompass both molecular mechanisms of growth cone behavior and axonal growth in multicellular tissue environments. For example, on the molecular level, filopodia contain a central core of actin filaments whose polymerization and depolymerization is thought to correspond to filopodial extension and retraction, with significant regulation possible through receptor-mediated effects on actin dynamics. By rewriting the parameters of filopodia dynamics in the current model in terms of these molecular events, one can begin to investigate their effects on growth cone behavior and to examine hypotheses of molecular mechanisms. Processes underlying lamellipodial behavior can be examined in a similar manner. At the tissue level, the effects of environmental factors on model parameters can be incorporated to yield predictions of the neurite outgrowth response to a particular environment. Such predictions offer a basis for designing microenvironments with optimal characteristics for enhancing nerve regeneration or manipulating the nerve growth response. Although the quantitative framework described here has focused on growth by peripheral nerve cells, it represents concepts known to apply to neurons of the central nervous system, as well.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Quantitative modeling of responses of anuran retina: stimulus shape and size dependency.

Teeters and Arbib presented a model of the anuran retina which qualitatively accounts for the characteristic response properties used to distinguish ganglion cell type in anurans. In this paper we test the model's ability to reproduce quantitatively tabulated data on the dependency on stimulus shape and size, with a new implementation of the model in the neural simulation language NSL. Data of Ewert and Hock relating toad R2, R3, and R4 ganglion cell responses to moving worm, antiworm, and square-shaped stimuli of various edge lengths are used to test stimulus shape and size dependency. A close match to the data can be achieved by tuning some of the model parameters while still retaining the characteristic responses to the typical stimulus types. We stress here the importance of a populational approach to the models. We place more emphasis on the variation of response properties in a population of neurons of the same class, rather than questing for the neuron of a given type. As an example of the populational approach we offer a model for the respiratory R3 response following researchers who argue that a subclass of R3 neurons are activated by stationary boundaries owing to the anuran's self induced respiratory eye movement.

Algorithms↗
PubMed1999

Satiety threshold: a quantitative model of maintained cocaine self-administration.

The intervals between self-injections of cocaine by rats are defined by an equation that contains only three parameters: the dose of cocaine administered, the elimination half-life of cocaine, and an amount of cocaine in the body, which we have termed the cocaine satiety threshold. This latter parameter is defined as the maximal level of cocaine at which the probability of self-administration approximates one and above which the probability of self-administration is low. The mathematical model generated mean values for the satiety threshold and the functional elimination half-life of cocaine of approximately 1.7 mg/kg (i.v.) and 8.2 min, respectively. Therefore, the simple equations presented here permit the measurement of the pharmacokinetics and pharmacodynamics of cocaine using self-administration behavior as a bioassay. Our satiety model predicts that when cocaine levels are maintained above the satiety threshold, rats would not self-administer cocaine. The elimination rate of cocaine at the satiety threshold was calculated to be approximately 2 microg kg(-1) s(-1). Therefore, an infusion of cocaine at this rate should maintain cocaine levels fractionally above the satiety threshold. A continuous infusion of cocaine at this rate prevented cocaine self-administration for the duration of the infusion, thereby confirming the validity of the satiety model. These equations provide a quantitative description of cocaine self-administration and contain no subjective terms, implying that concepts such as "craving", drug "wanting" and "liking" and "reinforcement", used in psychologically oriented models, are not necessary for descriptions of this behavior in rats.

Animals↗
PubMed1983

The discontinuous nature of electrical propagation in cardiac muscle. Consideration of a quantitative model incorporating the membrane ionic properties and structural complexities. The ALZA distinguished lecture.

The propagation of excitation in cardiac muscle has generally been treated as though it occurred in a continuous structure. However, new evidence indicates that propagation in cardiac muscle often displays a discontinuous nature. In this paper, we consider the hypothesis that this previously unrecognized type of propagation is caused by recurrent discontinuities of effective axial resistivity which affect the membrane currents. The major implication is that the combination of discontinuities of axial resistivity at several size scales can produce most currently known cardiac conduction disturbances previously though to require spatial nonuniformities of the membrane properties. At present there is no appropriate model or simulation for propagation in anisotropic cardiac muscle. However, the recent quantitative description of the fast sodium current in voltage-clamped cardiac muscle membrane makes it possible, for the first time, to apply experimentally based quantitative membrane models to propagation in cardiac muscle. The major task now is to account for the functional role of the structural complexities of cardiac muscle. The importance of such a model is that it would establish how the membrane ionic currents and the complexities of cell and tissue structure interact to determine propagation in both normal and abnormal cardiac muscle.

Biomedical Engineering↗
PubMed2002

A quantitative model of optimal data selection in Wason's selection task.

The optimal data selection model proposed by Oaksford and Chater (1994) successfully formalized Wason's selection task (Wason, 1966). The model, however, involved some questionable assumptions and was also not sufficient as a model of the task because it could not provide quantitative predictions of the card selection frequencies. In this paper, the model was revised to provide quantitative fits to the data. The model can predict the selection frequencies of cards based on a selection tendency function (STF), or conversely, it enables the estimation of subjective probabilities from data. Past experimental data were first re-analysed based on the model. In Experiment 1, the superiority of the revised model was shown. However, when the relationship between antecedent and consequent was forced to deviate from the biconditional form, the model was not supported. In Experiment 2, it was shown that sufficient emphasis on probabilistic information can affect participants' performance. A detailed experimental method to sort participants by probabilistic strategies was introduced. Here, the model was supported by a subgroup of participants who used the probabilistic strategy. Finally, the results were discussed from the viewpoint of adaptive rationality.

Adult↗
PubMed1982

Quantitative model for gene regulation by lambda phage repressor.

A statistical thermodynamic model has been developed to account for the cooperative interactions of the bacteriophage lambda repressor with the lambda right operator. The model incorporates a general theory for quantitatively interpreting cooperative site-specific equilibrium binding data. Values for all interaction parameters of the model have been evaluated at 37 degrees C, 0.2 M KCl, from results of DNase protection experiments in vitro [A. D. Johnson, B. J. Meyer, & M. Ptashne, Proc. Natl. Acad. Sci. USA (1979) 76, 5061-5065]. With these values, the model predicts repression curves at the divergent promoters PR and PRM that control transcription of genes coding for the regulatory proteins cro and repressor, respectively. At physiological repressor concentrations, repression at PR is predicted to be nearly complete whereas PRM is predicted to remain highly active. The results demonstrate the importance of cooperative interactions between repressor dimers bound to the adjacent operator sites OR1 and OR2 in maintaining a stable lysogenic state and in allowing efficient switchover to the lytic state during induction.

Bacteriophage lambda↗
PubMed2001

A quantitative model of the domain structure of the photosynthetic membrane.

A model is presented that gives a quantitative picture of the distribution of the photosynthetic components in the photosynthetic membrane of higher plants. A salient feature of the model is that most of the pigments are located in the grana where photosystem I and II carry out linear electron transport, whereas the stroma lamellae, which harbour <20% of the pigments, carry out photosystem-I-mediated cyclic electron transport. This arrangement derives from the observation that more pigments are associated with photosystem I, which therefore captures more quanta than photosystem II. The excess pigments associated with photosystem I are thought to be located in the stroma lamellae.

Chloroplasts↗
PubMed2002

A quantitative model of human DNA base excision repair. I. Mechanistic insights.

Base excision repair (BER) is a multistep process involving the sequential activity of several proteins that cope with spontaneous and environmentally induced mutagenic and cytotoxic DNA damage. Quantitative kinetic data on single proteins of BER have been used here to develop a mathematical model of the BER pathway. This model was then employed to evaluate mechanistic issues and to determine the sensitivity of pathway throughput to altered enzyme kinetics. Notably, the model predicts considerably less pathway throughput than observed in experimental in vitro assays. This finding, in combination with the effects of pathway cooperativity on model throughput, supports the hypothesis of cooperation during abasic site repair and between the apurinic/apyrimidinic (AP) endonuclease, Ape1, and the 8-oxoguanine DNA glycosylase, Ogg1. The quantitative model also predicts that for 8-oxoguanine and hydrolytic AP site damage, short-patch Polbeta-mediated BER dominates, with minimal switching to the long-patch subpathway. Sensitivity analysis of the model indicates that the Polbeta-catalyzed reactions have the most control over pathway throughput, although other BER reactions contribute to pathway efficiency as well. The studies within represent a first step in a developing effort to create a predictive model for BER cellular capacity.

DNA Repair↗
PubMed2001

Quantitative modeling of category learning in amnesic patients.

Category rule learning was examined in two amnesic patients using the perceptual categorization task (e.g., Ashby & Gott, 1988; Filoteo & Maddox, 1999). Traditional accuracy-based analyses as well as quantitative model-based analyses were performed. Unlike accuracy-based analyses, the model-based approach allowed us to examine both categorization rule learning and variability in the trial-by-trial application of the participant's categorization rule. The results indicated that the amnesic patients were as accurate as the controls in learning a complex, nonlinear rule over a large number of trials. The model-based analysis indicated that, in general, the amnesic patients learned the categorization rule as well as controls and applied their rule as consistently as controls. Categorization performance on a second day of testing revealed that amnesic patients can retain the categorization rule over a 24-h period. These results suggest that the brain regions damaged in amnesia are not involved in category learning or memory for the category structures.

Adult↗
PubMed1998

Quantitative modeling of stochastic systems in molecular biology by using stochastic Petri nets.

An integrated understanding of molecular and developmental biology must consider the large number of molecular species involved and the low concentrations of many species in vivo. Quantitative stochastic models of molecular interaction networks can be expressed as stochastic Petri nets (SPNs), a mathematical formalism developed in computer science. Existing software can be used to define molecular interaction networks as SPNs and solve such models for the probability distributions of molecular species. This approach allows biologists to focus on the content of models and their interpretation, rather than their implementation. The standardized format of SPNs also facilitates the replication, extension, and transfer of models between researchers. A simple chemical system is presented to demonstrate the link between stochastic models of molecular interactions and SPNs. The approach is illustrated with examples of models of genetic and biochemical phenomena where the ULTRASAN package is used to present results from numerical analysis and the outcome of simulations.

Animals↗
PubMed1999

A quantitative model for designing keyboard layout.

This study analyzed the quantitative relationship between keytapping times and ergonomic principles in typewriting skills. Keytapping times and key-operating characteristics of a female subject typing on the Qwerty and Dvorak keyboards for six weeks each were collected and analyzed. The results showed that characteristics of the typed material and the movements of hands and fingers were significantly related to keytapping times. The most significant factors affecting keytapping times were association frequency between letters, consecutive use of the same hand or finger, and the finger used. A regression equation for relating keytapping times to ergonomic principles was fitted to the data. Finally, a protocol for design of computerized keyboard layout based on the regression equation was proposed.

Adult↗
PubMed1995

Use of quantitative modelling in methylene chloride risk assessment.

The benefits of basing quantitative risk assessment on measures of 'internal dose', i.e. target organ exposures as estimated, for instance, by pharmacokinetic models, have been extensively discussed. Recasting risk assessment methods at the level of internal dose raises novel issues, however, some of which are explored by examining the 1987 revision by the US Environmental Protection Agency (EPA) of its cancer risk assessment for inhaled methylene chloride, which was based on the 1987 pharmacokinetic model results of Andersen and coworkers. The internal dose measure was the daily amount of methylene chloride metabolized by a glutathione-S-transferase pathway per 1 of target organ (liver and lung). Owing to high-dose saturation of a competing detoxification reaction, this metabolic activation is less-than-proportionally active at low exposure levels. For a given inhalation exposure, humans have relatively less metabolic activation than do mice, but this is shown to be a foreseeable consequence of their relatively lower breathing rate, a cross-species difference already accounted for in standard EPA methodology. Indeed, many species differences in the rates and tempos of physiological processes evince regular 'scaling' relationships across differently sized mammals. EPA's practice of scaling carcinogen doses by body surface area for cross-species extrapolation, often viewed as a correction for metabolic activation, is shown to be more reasonably regarded as an accommodation for the more general species variation in the pace of physiological processes underlying both pharmacokinetics and the carcinogenic response to internal doses. Under this view, the issue of cross-species dose scaling is not obviated by the use of pharmacokinetics.

Administration, Inhalation↗
PubMed2001

A quantitative model of work-related fatigue: empirical evaluations.

Systematic and quantitative management of work-related fatigue within workplaces has been a challenging task due to a lack of useful tools. A previous paper provided background and development of a work-related fatigue modelling approach. The current paper outlines model evaluations using sleep deprivation experiments and recommendations of work scheduling. Previous studies have reported cumulative effects of sleep restriction (4-5 h per night) on a number of measures. Model predictions were correlated against psychomotor vigilance task lapses (r = 0.92) and reaction time responses (slowest 10%, r = 0.91) as well as sleep latency (r = -0.97). Further correlations were performed on four measures from a 64 h continuous sleep deprivation study; that is objective vigilance (r = -0.75) as well as subjective performance (r = -0.75), sleepiness (r = 0.82) and tiredness (r = 0.79). Evaluation against current scheduling recommendations illustrated consistency with the literature with the exception that forward rotation did not provide benefits over backward rotation. The results indicate that model predictions correlate well across a range of objective and subjective measures. This relationship also appears to hold for cumulative and continuous sleep deprivation protocols. Future studies will also focus on field-based evaluation.

Ergonomics↗
PubMed2001

Striatal contributions to category learning: quantitative modeling of simple linear and complex nonlinear rule learning in patients with Parkinson's disease.

The contribution of the striatum to category learning was examined by having patients with Parkinson's disease (PD) and matched controls solve categorization problems in which the optimal rule was linear or nonlinear using the perceptual categorization task. Traditional accuracy-based analyses, as well as quantitative model-based analyses were performed. Unlike accuracy-based analyses, the model-based analyses allow one to quantify and separate the effects of categorization rule learning from variability in the trial-by-trial application of the participant's rule. When the categorization rule was linear, PD patients showed no accuracy, categorization rule learning, or rule application variability deficits. Categorization accuracy for the PD patients was associated with their performance on a test believed to be sensitive to frontal lobe functioning. In contrast, when the categorization rule was nonlinear, the PD patients showed accuracy, categorization rule learning, and rule application variability deficits. Furthermore, categorization accuracy was not associated with performance on the test of frontal lobe functioning. Implications for neuropsychological theories of categorization learning are discussed.

Aged↗