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PubMed1992

Neural modeling with dynamically adjustable threshold and refractory period.

A variant of the FitzHugh-Nagumo model is proposed in order to fully make use of the computational properties of intraneuronal dynamics. The mechanisms of threshold and refractory periods resulting from the double dynamical processes are qualitatively studied through computer simulation. The results show that the variant neuron model has the property that its threshold, refractory period and response amplitude are dynamically adjustable. This paper has also discussed some problems relating to collective property, learning and implementation of the neural network based on the neuron model proposed. It is noted that the implicit way to describe threshold and refractory period is advantageous to adaptive learning in neural networks and that molecular electronics probably provides an effective approach to implementing the above neuron model.

Animals↗

PubMed2001

Error threshold for spatially resolved evolution in the quasispecies model.

The error threshold for quasispecies in 1, 2, 3, and infinity dimensions is investigated by stochastic simulation and analytically. The results show a monotonic decrease in the maximal sustainable error probability with decreasing diffusion coefficient, independently of the spatial dimension. It is thereby established that physical interactions between sequences are necessary in order for spatial effects to enhance the stabilization of biological information. The analytically tractable behavior in an infinity-dimensional (simplex) space provides a good guide to the spatial dependence of the error threshold in lower dimensional Euclidean space.

Evolution, Molecular↗

PubMed1998

A four-state kinetic model of the temporary threshold shift after loud sound based on inactivation of hair cell transduction channels.

A model of the temporary threshold shift (TTS) following loud sound is presented based on inactivation of the mechano-electrical transduction (MET) channels at the apex of the outer hair cells (OHCs). This inactivation is assumed to reduce temporarily the OHC receptor current with a consequent drop in the mechanical sensitivity of the organ of Corti. With acoustic over-stimulation some of the hair cells' MET channels are assumed to adopt one of three closed and non-transducing conformations or 'TTS states'. The sound-induced inactivation is assumed to occur because the sound makes the TTS states more energetically favourable when compared with the transducing states, and the distribution between these states is assumed to depend on the relative energies of the states and the time allowed for migration between them. By lumping the fast transducing states (one open and two closed) into a single transducing 'pseudo-state', the kinetics of the inactivation and re-activation processes (corresponding to the onset and recovery of TTS) can be described by a four-state kinetic model. The model allows an elegant description of the onset and recovery of TTS time-course in a human subject under a variety of continuous exposure conditions, and some features of intermittent exposure as well. The model also suggests that recovery of TTS may be accelerated by an intermittent tone during the recovery period which may explain some variability TTS in the literature. Other implications of the model are also discussed.

Acoustic Stimulation↗

PubMedDate not supplied

[A simulated mathematical model of the blood coagulation system intrinsic pathway].

A mathematical model of the blood coagulation system intrinsic pathway is developed based on a reaction cascade scheme with two positive feedbacks. The model describes quantitatively well-known experimental data on blood plasma coagulation kinetics for various levels of activation and varying calcium concentrations. In the limit of experimental variety of the values of the rate for individual stages of coagulation cascade, obtained in [5-12], a good agreement with experimental data was shown for two discrete sets of the constants. The model relates unambiguously the threshold properties in coagulation activation by calcium with existence of the activation threshold. The model allows numerical estimates of the threshold activation values for various calcium concentrations. At calcium concentration of 0.2 mM, corresponding to normal calcium content in blood, the activation threshold is equal to 0.00016 nM and 0.0019 nM of Factor XIa for the first and the second sets of the system parameters, respectively.

Blood Coagulation↗

PubMed2004

Fatigue models as practical tools: diagnostic accuracy and decision thresholds.

Human fatigue models are increasingly being used in a variety of industrial settings, both civilian and military. Current uses include education, awareness, and analysis of individual or group work schedules. Perhaps the ultimate and potentially most beneficial use of human fatigue models is to diagnose if an individual is sufficiently rested to perform a period of duty safely or effectively. When used in this way, two important questions should be asked: 1) What is the accuracy of the diagnosis for duty-specific performance in this application; and 2) What decision threshold is appropriate for this application (i.e., how "fatigued" does an individual have to be to be considered "not safe"). In the simplest situation, a diagnostic fatigue test must distinguish between two states: "fatigued" and "not fatigued," and the diagnostic decisions are "safe" (or "effective") and "not safe" (or "not effective"). The resulting four decision outcomes include diagnostic errors because diagnostic tests are not perfectly accurate. Moreover, since all outcomes have costs and benefits associated with them that differ between applications, the choice of a decision criterion is extremely important. Signal Detection Theory (SDT) has demonstrated usefulness in measuring the accuracy of diagnostic tests and optimizing diagnostic decisions. This paper describes how SDT can be applied to foster the development of fatigue models as practical diagnostic and decision-making tools. By clarifying the difference between accuracy (or sensitivity) and decision criterion (or bias) in the use of fatigue models as diagnostic and decision-making tools, the SDT framework focuses on such critical issues as duty-specific performance, variability (model and performance), and model sensitivity, efficacy, and utility. As fatigue models become increasingly used in a variety of different applications, it is important that end-users understand the interplay of these factors for their particular application.

Decision Support Techniques↗

PubMed2005

Threshold dissociation and molecular modeling of transition metal complexes of flavonoids.

The relative threshold dissociation energies of a series of flavonoid/transition metal/auxiliary ligand complexes of the type [MII (flavonoid - H) auxiliary ligand]+ formed by electrospray ionization (ESI) were measured by energy-variable collisionally activated dissociation (CAD) in a quadrupole ion trap (QIT). For each of the isomeric flavonoid diglycoside pairs, the rutinoside (with a 1-6 inter-saccharide linkage) requires a greater CAD energy and thus has a higher dissociation threshold than its neohesperidoside (with a 1-2 inter-saccharide linkage) isomer. Likewise, the threshold energies of complexes containing flavones are higher than those containing flavanones. The monoglycoside isomers also have characteristic threshold energies. The flavonoids that are glycosylated at the 3-O- position tend to have lower threshold energies than those glycosylated at the 7-O- or 4'-O- position, and those that are C- bonded have lower threshold energies than the O- bonded isomers. The structural features that substantially influence the threshold energies include the aglycon type (flavanone versus flavone), the type of disaccharide (rutinose versus neohesperidose), and the linkage type (O- bonded versus C- bonded). Various computational means were applied to probe the structures and conformations of the complexes and to rationalize the differences in threshold energies of isomeric flavonoids. The most favorable coordination geometry of the complexes has a plane-angle of about 62 degrees , which means that the deprotonated flavonoid and 2,2'-bipyridine within a complex do not reside on the same plane. Stable conformations of five cobalt complexes and five deprotonated flavonoids were identified. The conformations were combined with the point charges and helium accessible surface areas to explain qualitatively the differences in threshold energies for isomeric flavonoids.

Electrochemistry↗

PubMedDate not supplied

An exponential model used for optimal threshold selection on ROC curves.

A two-parameter exponential equation for modeling a receiver operating characteristic (ROC) curve is presented, where the area under the curve is a simple function of one of the parameters. The model makes no distributional assumptions about the underlying normal and abnormal patient populations or about the shape of the resulting ROC curves. In a computer simulation of 75 ROC curves, the model provides a fit equivalent to the maximum likelihood estimate method commonly used for ROC curve fitting. Similar results are obtained using the model to fit ROC curve data from the literature. The model's equation calculates the true-positive ratio as a function of the false-positive ratio, and has a first derivative that is useful for finding the optimal decision threshold for a diagnostic testing procedure. In particular, the model is useful in a computer program for finding jointly optimal thresholds for multiple sequential tests.

Computer Simulation↗

PubMed1996

Signal-detection, threshold, and dual-process models of recognition memory: ROCs and conscious recollection.

Threshold- and signal-detection-based models have dominated theorizing about recognition memory. Building upon these theoretical frameworks, we have argued for a dual-process model in which conscious recollection (a threshold process) and familiarity (a signal-detection process) contribute to memory performance. In the current paper we assessed several memory models by examining the effects of levels of processing and the number of presentations on recognition memory receiver operating characteristics (ROCs). In general, when the ROCs were plotted in probability space they exhibited an inverted U shape; however, when they were plotted in z space they exhibited a U shape. An examination of the ROCs showed that the dual-process model could account for the observed ROCs, but that models based solely on either threshold or signal-detection processes failed to provide a sufficient account of the data. Furthermore, an examination of subjects' introspective reports using the remember/know procedure showed that subjects were aware of recollection and familiarity and were able to consistently report on their occurrence. The remember/know data were used to accurately predict the shapes of the ROCs, and estimates of recollection and familiarity derived from the ROC data mirrored the subjective reports of these processes.

Adult↗

PubMed2006

Modelling SARS data using threshold geometric process.

During the outbreak of an epidemic disease, for example, the severe acute respiratory syndrome (SARS), the number of daily infected cases often exhibit multiple trends: monotone increasing during the growing stage, stationary during the stabilized stage and then decreasing during the declining stage. Lam first proposed modelling a monotone trend by a geometric process (GP) [X(i), i=1,2,...] directly such that [a(i-1)X(i), i=1,2,...] forms a renewal process for some ratio a>0 which measures the direction and strength of the trend. Parameters can be conveniently estimated using the LSE methods. Previous GP models limit to data with only a single trend. For data with multiple trends, we propose a moving window technique to locate the turning point(s). The threshold GP model is fitted to the SARS data from four regions in 2003.

Data Interpretation, Statistical↗

PubMed1998

Modeling otoacoustic emission and hearing threshold fine structures.

A class of cochlear models which account for much of the characteristic variation with frequency of human otoacoustic emissions and hearing threshold microstructure is presented. The models are based upon wave reflections via distributed spatial cochlear inhomogeneities and tall and broad cochlear activity patterns, as suggested by Zweig and Shera [J. Acoust. Soc. Am. 98, 2018-2047 (1995)]. They successfully describe in particular the following features: (1) the characteristic quasiperiodic frequency variations (fine structures) of the hearing threshold, synchronous and click-evoked emissions, distortion-product emissions, and spontaneous emissions; (2) the relationships between these fine structures; and (3) the distortion product emission filter shape. All of the characteristic frequency spacings are approximately the same (0.4 bark) and are mainly determined by the phase behavior of the apical reflection function. The frequency spacings for spontaneous emissions and threshold microstructure are predicted to be the same, but some deviations from these values are predicted for synchronous and click-evoked and distortion-product emissions. The analysis of models is aided considerably by the use of the solutions of apical, and basal, moving solutions (basis functions) of the cochlear wave equation in the absence of inhomogeneities.

Acoustic Stimulation↗

PubMed1985

Isolation of newt lung ciliated cell models: characterization of motility and coordination thresholds.

Demembranated ciliated cell models are useful for studying mechanisms responsible for the regulation of ciliary coordination and waveform. This paper describes procedures for isolating ciliated cells from the newt, Taricha granulosa, by trypsin dissociation, their subsequent demembranation by Triton X-100, and their reactivation with MgATP to produce highly motile, coordinated, ciliated cell models. Reactivation of cell models with a high degree of mechanochemical coupling depended on avoiding mechanical damage and maintaining optimal conditions during all stages of isolation and reactivation. Highly motile models were prepared from cells incubated in trypsin, treated briefly with EDTA, separated by gentle agitation, and concentrated by centrifugation at low gravitational forces. Optimal demembranation and reactivation conditions were similar to those described previously for isolated newt lung axonemes. Under these conditions, nearly 100% of the models were reactivated when provided with MgATP and 90-95% beat with coordinated waves. The ciliary tufts beat at frequencies within the range measured in living cells and their reactivated motility was stable for at least 30 min at constant MgATP. These highly coupled models were used to show (1) that development of coordination in the ciliary tuft occurs at a higher substrate concentration range (10-25 microM) than that required to initiate motility per se (2-10 microM; (2) that outer dynein arms may not contribute to beat frequency at substrate concentrations below 35 microM; and (3) that vanadate has effects both on beat frequency and coordination of the tufts.

Animals↗

PubMedDate not supplied

Stochastic resonance in the LIF models with input or threshold noise.

In this paper, two stochastic versions of the LIF neural model are considered: one with the noise signal applied to the firing threshold, the other having it added to the input current. Then, adopting a discontinuous stepwise noise whose innovations are uncorrelated and gaussian distributed, the behaviours of the two models pertaining to the stochastic resonance (SR) are analysed and compared. Furthermore, it is shown that introducing a suitable time correlation into the noise signal brings us from the first model to the second one.

Models, Biological↗

PubMed2005

The effects of amplitude-spectrum statistics on foveal and peripheral discrimination of changes in natural images, and a multi-resolution model.

Psychophysical thresholds were measured for discriminating small changes in spatial features of naturalistic scenes (morph sequences), for foveal and peripheral vision, and under M-scaling. Sensitivity was greatest for scenes with near natural Fourier amplitude slope, perhaps implying that human vision is optimised for natural scene statistics. A low-level model calculated differences in local contrast between pairs of images within a few spatial frequency channels with bandwidth like neurons in V1. The model was "customised" to each observer's contrast sensitivity function for sinusoidal gratings, and it could replicate the "U-shaped" relationships between discrimination threshold and spectral slope, and many differences between picture sets and observers. A single-channel model and an ideal-observer analysis both failed to capture the U-shape.

Contrast Sensitivity↗

PubMed1996

Mechanisms underlying the detection of increments in parafoveal retina.

It is well established that the spectral sensitivity under photopic conditions varies across the human retina. We investigate the mechanisms underlying these spectral changes. Through the use of color appearance, flicker sensitivity, additivity, discrimination at threshold and modeling, we show that the changes in spectral sensitivity on a photopic white background across parafoveal retina are consistent with shifts in cone weightings to (L-M) and (M-L) chromatic channels. This two channel model, developed to account for foveal spectral sensitivity curves (Sperling & Harwerth, 1971 Science, 172, 180-184), provides a better description of parafoveal data than both a single color channel upper envelope model (comprised of a single red-green opponent channel and an achromatic mechanism) and a vector model (combining a red-green opponent channel with an achromatic component). Thus while the two channel model ([L-M] and [M-L]) of foveal color vision is generalizable to the parafovea, simple models with a unitary red/green process are not. Although the two channel model can accurately fit parafoveal spectral sensitivity curves without it, a small contribution from a luminance mechanism might improve the ability of the two channel model to account for threshold discrimination and additivity data.

Color Perception↗

PubMed2005

Genetic analysis of age at first service, return rate, litter size, and weaning-to-first service interval of gilts and sows.

The aim of this study was to estimate genetic parameters of seven traits related to sow reproductive performance. Data on all Norwegian Landrace pigs (NL) born in nucleus herds and raised in nucleus or multiplying herds from 1990 to 2000 were extracted from the Norwegian national recording scheme. Reproductive traits investigated were age at first service (AFS), return rate in gilts (RRg), age at first farrowing (AFF), live-born piglets in the first litter (NBA1), interval from weaning to first service after first litter (WTS1), return rate after first litter (RR1), live-born piglets in the second litter (NBA2), and interval from weaning to first service after second litter (WTS2). After editing, the data set comprised 12,583 to 56,042 records, depending on the trait. A mixed linear and a joint linear threshold animal model were used to estimate (co)variance components. A full Bayesian approach via Gibbs sampling was adopted. The statistical model used for analysis included contemporary groups of herd-year (-season), purebred or crossbred litter, single or double insemination, mating type, parity in which the animal was born, a regression on lactation length, and an additive genetic effect. Neither the estimated heritabilities nor the genetic correlations differed much between the two approaches, but there was a tendency for higher genetic correlations using the joint linear threshold model approach. Average heritabilities were as follows: AFS = 0.31; RRg = 0.03; RR1 = 0.02; NBA1 = 0.12; NBA2 = 0.14; WTS1 = 0.08; and WTS2 = 0.03. The highest genetic correlations were estimated between NBA1 and NBA2 (r(g) = 0.95), RR1 and WTS1 (r(g) = 0.93), and between WTS1 and WTS2 (r(g) = 0.78). The estimated genetic correlation between NBA and WTS were close to zero. Selection for increased NBA will slightly increase AFS and reduce the probability of a return. Selection for decreased AFS will have a favorable effect on WTS intervals; however, selection for decreased AFS seems to have an unfavorable effect on return rate both on gilts and sows. Conversely, selection for decreased WTS intervals will reduce the probability of a return. Potential selection candidates to include in a multivariate fertility index are AFS, NBA, and WTS1. Due to the low heritability and low, but favorable, genetic correlations to NBA and WTS, RR is not recommended as a selection candidate.

Age Factors↗

PubMed1992

Modelling spatial vision at the threshold level.

Some available single- and multiple-channel models are reviewed. Multichannel models are generalized and tested against threshold data on various stimulus sets. Without using the explicit assumption of spatial probability summation, simple multichannel models are shown to provide good simultaneous predictions of threshold curves of sinewave gratings and other gratings. They fail in predicting threshold curves of disk-shaped stimuli. If global or local spatial probability summation within channels is incorporated into the models, correctly shaped threshold curves of disks can be predicted. However, the predicted curves appear still too low if compared to measured curves. The same holds for noise gratings. Possible extensions of the models, based on local summation between channel responses and/or models consisting of initial isotropic channels (retina) followed by anisotropic channels (cortex), are discussed.

Humans↗

PubMed2000

Rod-mediated increment threshold functions in infants.

PURPOSE: To obtain and analyze scotopic increment threshold functions to test the hypothesis that rod photoreceptor immaturity accounts for the elevation of infants' over controls' dark-adapted thresholds and elevation of parafoveal over peripheral thresholds in infants. METHODS: Using a preferential looking method, thresholds for detection of 2(o), 50 msec, blue stimuli presented 10(o) (parafoveal) or 30(o) (peripheral) eccentric were measured in the dark and in the presence of steady red backgrounds. Ten 10-week-old infants and four control subjects (8-35 years) were tested. To evaluate pre- and postadaptation site determinants of threshold, a model of the increment threshold function was fit to the data, and the dark-adapted threshold (T(D)) and eigengrau (A(O)) were calculated. The values of T(D) and A(O) were compared between infants and controls and between parafoveal and peripheral eccentricities. RESULTS: At both parafoveal and peripheral eccentricities, infants' values of T(D) and A(O) were significantly higher than those of controls. The locus of the coordinates (A(O), T(D)) differed significantly between parafoveal and peripheral eccentricities. In every infant, the parafoveal value of T(D) was higher (by 0.3-0.6 log unit) and A(O) lower (by 0.2-0.5 log unit) than the peripheral value, whereas controls had no difference in T(D) and A(O) at the two eccentricities. CONCLUSIONS: The results indicate that both receptoral and postreceptoral immaturities have a role in the elevation of infants' over controls' thresholds. In infants, rod photoreceptor immaturity before the site of adaptation accounts for elevation of parafoveal over peripheral thresholds.

Adolescent↗

PubMed1996

Physiologically based pharmacodynamic modeling of an interaction threshold between trichloroethylene and 1,1-dichloroethylene in Fischer 344 rats.

Physiologically based pharmacokinetic modeling (PBPK) and gas uptake experiments have been used by researchers to demonstrate the competitive inhibition mechanism between trichloroethylene (TCE) and 1,1-dichloroethylene (DCE). Expanding on their work, we showed that this pharmacokinetic interaction was absent at levels of 100 ppm or less of either chemical in gas uptake systems. In this study, we further illustrate the presence of such an interaction threshold at the pharmacodynamic level by examining the interaction effect of either chemical on the other's ability to bind and deplete hepatic glutathione (GSH) in Fischer 344 rats. However, at this end point, the pharmacodynamic interaction is complicated by the ability of the liver to resynthesize GSH in response to its depletion. To quantitatively resolve the interaction effects on GSH content from the resynthesis effects, physiologically based pharmacodynamic (PBPD) modeling is applied. Initially, the PBPD model description of hepatic GSH kinetics was calibrated against previously published data and by gas uptake experiments conducted in our laboratory. Then, the model was used to determine the duration of the gas uptake exposure experiments by identifying the critical time point at which hepatic GSH is at a minimum in response to both chemicals. Subsequently, gas uptake experiments were designed following the PBPK/PD model predictions. In these model-directed experiments, DCE was the only chemical capable of significantly depleting hepatic GSH. The application of TCE to the rats at concentrations higher than 100 ppm obstructed the ability of DCE to deplete hepatic GSH. Since the metabolites of DCE bind to hepatic GSH, this obstruction signaled the presence of metabolic inhibition by TCE. However, TCE, at concentrations less than 100 ppm, was not effective in inhibiting DCE from significantly depleting hepatic GSH. The same observations were made when the ability of DCE to cause hepatic injury, as measured by aspartate aminotransferase serum activity, was assessed. Both conclusions validated the previous findings of the presence of the interaction threshold at the pharmacokinetic level.

Animals↗