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PubMed1998

On new opportunities for absorptiometry.

Mechanical loads cause bone strains; and muscle forces, not body weight, cause the largest strains. The strains help to control the effects of bone modeling and remodeling on bone strength and "mass." When strains exceed a threshold range, modeling increases bone strength and "mass." When strains stay below a smaller threshold range, remodeling begins removing bone next to marrow. As a result, increasing muscle strength increases bone strength and "mass," and decreasing muscle strength decreases bone strength and "mass." Estrogen apparently lowers the remodeling threshold, which reduces bone losses. Loss of estrogen raises that threshold to cause losses of bone next to marrow. Such facts help to explain: 1. Bone loss in aging adults. 2. An increase in bone "mass" in girls at menarche. 3. The loss of bone during menopause. 4. The greater bone "mass" in obese than in slender subjects, and in weightlifters than in marathon runners. 5. And the pathogenesis of physiologic osteopenias and true osteoporoses. Thus new standards are needed for the relationships between bone and muscle strengths, and as functions of sex, age, race, disease, endocrine status, nutrition, vitamin and mineral intakes, medications, puberty, and menopause. Obtaining those standards and studying such relationships provide many new opportunities for studies that involve dual energy X-ray absorptiometry (DXA) and peripheral quantitative computer tomography (pQCT) and, perhaps some day, ultrasound and magnetic resonance imaging (MRI) techniques.

Journal Article↗
PubMed1996

Rotation and radical motion thresholds support a two-stage model of differential-motion analysis.

Lower motion thresholds for rotational and radial flow have been measured for stimuli consisting of four closely packed circular apertures, each containing patches of drifting grating or plaid. Detection and direction thresholds were measured for gratings and plaids as a function of the relative orientation of the pattern components. There was a similarity between both types of threshold, supporting the existence of specialised rotation and radial-flow detectors. Further, thresholds increased with the relative component orientation for both gratings and plaids. This suggests that component information from a first stage, tuned spatiotemporally and to orientation, is being used directly to compute the optic flow in a two-stage process. A model based on this architecture is described by means of simple template receptive-field arrays with separable temporal and spatial tuning at the first stage.

Humans↗
PubMed1995

The "Expected Visual Outcome" (EVO) model: methodology and clinical validation.

PROBLEM: If changes are made to the optics of the eye (e.g., intraocular lens implants, contact lenses, etc.) how will they affect performance on clinical tests of vision? METHOD: A phenomenological method is presented based on in vitro optical transfer function (OTF) and a simple model of human threshold detection. RESULTS: The model is used to predict and the results are compared with clinical data (acuity, contrast sensitivity) obtained from pseudophakic patients implanted with a multifocal intraocular lens (IOL). A good qualitative agreement is found with the clinical data. SIGNIFICANCE: This model predicts the relative change in clinical performance for a given change in the optical components of the human eye. This simple phenomenological model permits numerical prediction of clinical tests and is easily calculable.

Cataract Extraction↗
PubMed1992

Genetic and environmental relationships among somatic cell count, bacterial infection, and clinical mastitis.

Incidence of bacterial infection in 9784 lactations of 7763 cows in 31 herds, SCC in 32,448 lactations of 19,764 cows from 54 herds, and incidence of first parity mastitis recorded in the first lactations of 148,143 cows in 828 herds were analyzed. Bacterial infection was analyzed dichotomously by both threshold and linear models. The effects of parity, season, stage of lactation, and parity by stage of lactation interaction on SCC were estimated. Heritability of mean lactation log SCC--corrected for the effects of parity, season, and stage of lactation--varied from .13 to .27 for all parities in different data sets. Heritability of bacterial infection was .04 for the threshold model and .02 for the linear models. Heritability of field-recorded mastitis was .01. The genetic correlation between bacterial infection and SCC was near unity, but the genetic correlation between SCC and mastitis was .3. Selection for lowered SCC should reduce incidence of bacterial infection by 2% per unit of selection intensity.

Animals↗
PubMed2002

Analysis of solvent central nervous system toxicity and ethanol interactions using a human population physiologically based kinetic and dynamic model.

The effect of acute ethanol-mediated inhibition of m-xylene metabolism on central nervous system (CNS) depression in the human worker population was investigated using physiologically based pharmacokinetic (PBPK) models and probabilistic random (Monte Carlo) sampling. PBPK models of inhaled m-xylene and orally ingested ethanol were developed and combined by a competitive enzyme (CYP2E1) inhibition model. Human interindividual variability was modeled by combining estimated statistical distributions of model parameters with the deterministic PBPK models and multiple random or Monte Carlo simulations. A simple threshold pharmacodynamic model was obtained by simulating m-xylene kinetics in human studies where CNS effects were observed and assigning the peak venous blood m-xylene concentration (C(V,max)) as the dose surrogate of toxicity. Probabilistic estimates of an individual experiencing CNS disturbances given exposure to the current UK occupational exposure standard (100 ppm time-weighted average over 8 h), with and without ethanol ingestion, were obtained. The probability of experiencing CNS effects given this scenario increases markedly and nonlinearly with ethanol dose. As CYP2E1-mediated metabolism of other occupationally relevant organic compounds may be inhibited by ethanol, simulation studies of this type should have an increasingly significant role in the chemical toxicity risk assessment.

Administration, Oral↗
PubMed1976

A genetic model of narcolepsy.

An analysis of recently published family history data on rapid eye movement (REM) narcolepsy was undertaken to determine the goodness-of-fit of a multifactorial (MF) model of inheritance. The analysis revealed that a two-threshold MF model can successfully account for the prevalence of REM narcolepsy and other disorders of excessive sleep (DES) observed in the first-degree relatives of the REM narcoleptic probands studied.

Humans↗
PubMed2004

Electric field induced order reconstruction in a nematic cell.

We have experimentally observed the biaxial switching between two topologically distinct textures of a nematic liquid crystal cell submitted to a strong electric field. The effect is deduced from optical and electrical measurements across the cell. Above a static threshold, a bulk order reconstruction is observed, where the final nematic orientation in the centre becomes perpendicular to its initial one, inducing a total pi change of orientation across the cell. Using short electric field pulses, a higher dynamical threshold is observed. These experiments are explained by a Landau-de Gennes-Khalatnikov model. The threshold implies the local exchange of two eigenvalues of the nematic order tensor through intermediate biaxial states. The onset of the effect in a thin splay-bend wall decreases the static threshold by almost an order of magnitude. The model explains reasonably well the static and dynamic measurements within the present description of nematic biaxiality.

Electricity↗
PubMed2000

Increased synchrony with increase of a low-threshold calcium conductance in a model thalamic network: a phase-shift mechanism.

A computer model of a thalamic network was used in order to examine the effects of an isolated augmentation in a low-threshold calcium current. Such an isolated augmentation has been observed in the reticular thalamic (RE) nucleus of the genetic absence epilepsy rat from the Strasbourg (GAERS) model of absence epilepsy. An augmentation of the low-threshold calcium conductance in the RE neurons (gTs) of the model thalamic network was found to lead to an increase in the synchronized firing of the network. This supports the hypothesis that the isolated increase in gTs may be responsible for epileptic activity in the GAERS rat. The increase of gTs in the RE neurons led to a slight increase in the period of the isolated RE neuron firing. In contrast, the low-threshold spike of the RE neuron remained relatively unchanged by the increase of gTs. This suggests that the enhanced synchrony in the network was primarily due to a phase shift in the firing of the RE neurons with respect to the thalamocortical neurons. The ability of this phase-shift mechanism to lead to changes in synchrony was further examined using the model thalamic network. A similar increase in the period of RE neuron oscillations was obtained through an increase in the conductance of the calcium-mediated potassium channel. This change was once again found to increase synchronous firing in the network.

Action Potentials↗
PubMed1984

The frequency response function and sinusoidal threshold properties of the Hodgkin-Huxley model of action potential encoding.

The behavior of the space-clamped Hodgkin-Huxley model has been studied using band-limited white noise (0-50 Hz) as the input membrane current and taking the output as a point process in time given by the peaks of the action potentials. The frequency response and coherence functions were measured by use of the Fourier transform and digital filtering of the spike train. The results obtained are in good agreement with those already published for the simple integrator and leaky integrator models of neuronal encoding, as well as the earlier studies on the response of the Hodgkin-Huxley model to steady currents. In addition, the threshold of the model to sinusoidal membrane currents has been measured as a function of frequency over the range of 0.1-100 Hz. This shows a relatively constant level up to 2 Hz and then a clear minimum at 60 Hz, in agreement with measured thresholds of squid axons. These results are discussed in terms of the possible contributions of action potential encoding mechanisms to the frequency responses and sinusoidal thresholds which have been measured for rapidly adapting receptors.

Action Potentials↗
PubMed1999

Muscle and bone-aging and space.

One of the major concerns of aging, but also during and after spaceflight, is loss of muscle and bone mass. In aging, this is associated with an increasing risk of fractures. Recently, the possibility of aged and aging astronauts has been arisen. Thus considering the perspectives of aging and space we want to discuss, in how far the adaptations during spaceflight and during aging interfere. In other words: does spaceflight push the astronauts along the irreversible axis of aging? And which of the spaceflight effects will be reversible? Bones adapt to their mechanical function. For convenience, a simple model has been proposed: Bone, as a 'mechanostat', keeps the strains within certain thresholds, namely one threshold for modeling, i.e. formation of new bone, and one for remodeling, i.e. repair and removal. These thresholds are usually expressed as strains. A crucial role in physiological strain detection is obviously played by the osteocytes. The largest forces in the musculo-skeletal systems arise from muscle contractions. The reason for this are the poor levers, against which the muscles pull. For example: during a one-leg vertical jump, a young subject (body weight 70 kg) exerts a vertical ground reaction force of 2500 N. Due to the lever ratio of os calcis and forefoot around the tibio-talar joint, the calf muscles must exert a force 3 times greater, so that together with the body weight the bones of the lower leg are loaded with 10000 N, i.e. 14 times the body weight. Accordingly, good correlations can be observed between muscle strength and bone strength, or muscle mass and bone mass. It is therefore reasonable to discuss the accumulated knowledge about loss of muscle and bone in a combined approach. In this respect, two points must be considered: (i) for structural adaptation of bone, the muscular variable of interest arc force and rate of force development, but not power, and (ii) women before menopause have a greater bone to muscle ratio than men.

Adaptation, Physiological↗
PubMed2004

Activation-threshold tuning in an affinity model for the T-cell repertoire.

Naive T cells respond to peptides from foreign proteins and remain tolerant to self peptides from endogenous proteins. It has been suggested that self tolerance comes about by a 'tuning' mechanism, i.e. by increasing the T-cell activation threshold upon interaction with self peptides. Here, we explore how such an adaptive mechanism of T-cell tolerance would influence the reactivity of the T-cell repertoire to foreign peptides. We develop a computer simulation model in which T cells are tolerized by increasing their activation-threshold dependent on the affinity with which they see self peptides presented in the thymus. Thus, different T cells acquire different activation thresholds (i.e. different cross-reactivities). In previous mathematical models, T-cell tolerance was deletional and based on a fixed cross-reactivity parameter, which was assumed to have evolved to an optimal value. Comparing these two different tolerance-induction mechanisms, we found that the tuning model performs somewhat better than an optimized deletion model in terms of the reactivity to foreign antigens. Thus, evolutionary optimization of clonal cross-reactivity is not required. A straightforward extension of the tuning model is to delete T-cell clones that obtain a too high activation threshold, and to replace these by new clones. The reactivity of the immune repertoires of such a replacement model is enchanced compared with the basic tuning model. These results demonstrate that activation-threshold tuning is a functional mechanism for self tolerance induction.

Computer Simulation↗
PubMed1982

Interactions between rod and cone channels above threshold: a test of various models.

Brightness-matching and magnitude estimation data were obtained to test alternative explanations of the rod-cone interaction above threshold. Steady adapting fields were selected such that 500 and 640 nm test flashes presented in the parafovea stimulated largely the rod and cone systems, respectively. In the brightness-matching experiment stimuli of combined 500 and 640 nm light were matched to a white foveal standard flash set at various levels above threshold. Similarly, in the magnitude estimation experiment, brightness estimates were obtained for single 500 and 640 nm flashes as well as for super-imposed combination flashes. Combination stimuli appeared brighter than their individual components. Overall, the results suggest that rod and cone signals elicited by a single flash combine in an excitatory fashion; there is no evidence for rod-cone inhibition in this study. Further, the results for the suprathreshold and threshold conditions are qualitatively similar. The signals from the rod and cone systems combine less well than signals within a system but to a greater degree than predicted by probability summations or vector addition models.

Adaptation, Ocular↗
PubMed1999

Contact analysis of biphasic transversely isotropic cartilage layers and correlations with tissue failure.

Failure of articular cartilage has been investigated experimentally and theoretically, but there is only partial agreement between observed failure and predicted regions of peak stresses. Since trauma and repetitive stress are implicated in the etiopathogenesis of osteoarthritis, it is important to develop cartilage models which correctly predict sites of high stresses. Cartilage is anisotropic and inhomogeneous, though it has been difficult to incorporate these complexities into engineering analyses. The objectives of this study are to demonstrate that a transversely isotropic, biphasic model of cartilage can provide agreement between predicted regions of high stresses and observed regions of cartilage failure and that with transverse isotropy cartilage stresses are more sensitive to convexity and concavity of the surfaces than with isotropy. These objectives are achieved by solving problems of diarthrodial joint contact by the finite-element method. Results demonstrate that transversely isotropic models predict peak stresses at the cartilage surface and the cartilage-bone interface, in agreement with sites of fissures following impact loading; isotropic models predict peak stresses only at the cartilage-bone interface. Also, when convex cartilage layers contacted concave layers in this study, the highest tensile stresses occur in the convex layer for transversely isotropic models; no such differences are found with isotropic models. The significance of this study is that it establishes a threshold of modeling complexity for articular cartilage that provides good agreement with experimental observations under impact loading and that surface curvatures significantly affect stress and strain within cartilage when using a biphasic transversely isotropic model.

Animals↗
PubMed1976

Theory of spatial-frequency filtering by the human visual system. I. Performance limited by quantum noise.

A theory and model of the visual system are presented to explain the detection of static sinusoidal gratings near the threshold. The model incorporates a set of independent decision centers and associated photoreceptive fields (PRFs). The decision criterion value at each decision center is proportional to the standard deviation of the excitation current transmitted from a PRF to its associated decision center caused by quantum fluctuations in the absorption of light. It is well known that the spatial-frequency-response (SFR) function and the spatial-impulse-response (SIR) function of a photodetector are a Fourier transform pair. A systematic examination of the SIR and SFR functions of PRF configurations consisting of rectangular regions of alternately excitatory and inhibitory response reveals that modulation sensitivity of the visual system is explained at scotopic and photopic illuminance by a set of PRFs composed of a single excitatory region and a central excitatory region bordered by inhibitory regions, respectively. The complete model is shown to yield a high degree of conformity between theoretical and experimental threshold modulation curves.

Decision Making↗
PubMed1997

A new generation of algorithms for computerized threshold perimetry, SITA.

PURPOSE: The purpose of this work was to develop a new family of test algorithms for computerized static threshold perimetry which significantly reduces test time without any reduction of data quality. METHODS: A comprehensive visual field model constructed from available knowledge of normal and glaucomatous visual fields is continuously updated during testing. The model produces threshold estimates and also estimates of the certainty to which the threshold is known at each point. Testing is interrupted at each test location at predetermined levels of threshold certainty. New time-saving methods are employed for estimation of false answers, and test pacing is optimized. After completion of the test, all threshold estimates are re-computed, taking into account the complete body of patient responses. Computer simulations were used to optimize the different parameters of the new algorithms, to evaluate the relative importance of those parameters, and to evaluate the performance of the algorithm as a whole in comparison with a standard algorithm. RESULTS: Simulated test results obtained with this algorithm were slightly more accurate than those of the Humphrey Full Threshold test algorithm. The number of simulated stimuli presented was reduced by an average of 29% in normal fields and 26% in glaucomatous fields. Actual clinical test time should be further reduced, since the influence of the improved timing algorithm was not included in the simulations. CONCLUSIONS: We applied new methods which take available knowledge of visual field physiology and pathophysiology into account, and employ modern computer-intensive mathematical methods for real time estimates of threshold values and threshold error estimates. In this way it was possible to design a family of testing algorithms which significantly reduced perimetric test time without any loss of quality in results.

Algorithms↗
PubMed2006

Afterdischarge threshold reduction in the kindling model of epilepsy.

Female Wistar rats were implanted with electrodes in the right amygdala, and initial--pre-kindling--afterdischarge thresholds (ADT's) were determined 1, 2, 4, and 8 weeks after electrode implantation. Pre-kindling ADT's were highest 1 week after implantation, lower at 2 weeks, and lowest at 4 weeks. This drop in non-stimulated thresholds had largely disappeared by 8 weeks post-implantation. Half of each group was then kindled, while the other half was "sham" kindled. ADTs were re-measured 1 week after the 10th Stage 5 seizure. When kindling was begun 1 or 2 weeks after implantation (when non-stimulated thresholds were dropping), no effect of kindling on ADT's could be seen. When kindling was begun 4 or 8 weeks after implantation (when non-stimulated thresholds were rising), however, kindling clearly lowered thresholds.

Amygdala↗