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PubMed2004

Spatial and temporal regulation of cancellous bone structure: characterization of a rate equation of trabecular surface remodeling.

A computer simulation of trabecular surface remodeling was carried out to investigate the spatial and temporal regulation of the cancellous bone structure caused by bone cellular activities responding to a local mechanical environment. In the remodeling simulation, the rate of trabecular surface movement was directly related to stress at the trabecular level. Two model parameters, the threshold value of the lazy zone and the sensing distance of the mechanical environment, were introduced into the remodeling rate equation to express the sensitivity of bone cells to mechanical stimuli. A rectangular cancellous bone model under simple and nonuniform compressive loads was constructed using pixel finite elements. A simulation result revealed that the trabecular structure underwent a temporal and spatial change depending on the loading condition. It was found that the threshold value of the lazy zone regulates the rate of structural changes in time, and that sensing distance regulates the spatial distribution of the trabecular structure. The results demonstrate the possibility that the spatial and temporal regulation of the trabecular structure is determined by the sensitivities of bone cells to mechanical stimuli.

Animals↗

PubMed2006

Threshold-dependent BMP-mediated repression: a model for a conserved mechanism that patterns the neuroectoderm.

Subdivision of the neuroectoderm into three rows of cells along the dorsal-ventral axis by neural identity genes is a highly conserved developmental process. While neural identity genes are expressed in remarkably similar patterns in vertebrates and invertebrates, previous work suggests that these patterns may be regulated by distinct upstream genetic pathways. Here we ask whether a potential conserved source of positional information provided by the BMP signaling contributes to patterning the neuroectoderm. We have addressed this question in two ways: First, we asked whether BMPs can act as bona fide morphogens to pattern the Drosophila neuroectoderm in a dose-dependent fashion, and second, we examined whether BMPs might act in a similar fashion in patterning the vertebrate neuroectoderm. In this study, we show that graded BMP signaling participates in organizing the neural axis in Drosophila by repressing expression of neural identity genes in a threshold-dependent fashion. We also provide evidence for a similar organizing activity of BMP signaling in chick neural plate explants, which may operate by the same double negative mechanism that acts earlier during neural induction. We propose that BMPs played an ancestral role in patterning the metazoan neuroectoderm by threshold-dependent repression of neural identity genes.

Animals↗

PubMed1999

The characteristics of epidemics and invasions with thresholds.

In this paper we report the development of a highly efficient numerical method for determining the principal characteristics (velocity, leading edge width, and peak height) of spatial invasions or epidemics described by deterministic one-dimensiohal reaction-diffusion models whose dynamics include a threshold or Allee effect. We prove that this methodology produces the correct results for single-component models which are generalizations of the Fisher model, and then demonstrate by numerical experimentation that analogous methods work for a wide class of epidemic and invasion models including the S-I and S-E-I epidemic models and the Rosenzweig-McArthur predator-prey model. As examplary application of this approach we consider the atto-fox effect in the classic reaction-diffusion model of rabies in the European fox population and show that the appropriate threshold for this model is within an order of magnitude of the peak disease incidence and thus has potentially significant effects on epidemic properties. We then make a careful re-parameterisation of the model and show that the velocities calculated with realistic thresholds differ surprisingly little from those calculated from threshold-free models. We conclude that an appropriately thresholded reaction-diffusion model provides a robust representation of the initial epidemic wave and thus provides a sound basis on which to begin a properly mechanistic modelling enterprise aimed at understanding the long-term persistence of the disease.

Animals↗

PubMed1981

A model for discharge patterns of primary auditory-nerve fibers.

A model for the synapse between an inner hair cell and afferent fiber is presented. The hair cell is assumed to release 25-100 quantized neurotransmitter packets per sec. Each packet causes an exponentially shaped unitary excitatory postsynaptic potential (EPSP). Any particular afferent fiber is assumed to have a discharge threshold either above or below that of the unitary EPSP. Using any reasonable distribution of threshold values, the model produces a bimodal distribution of spontaneous discharge patterns. The group producing high spontaneous rates (greater than 20/sec) all have discharge thresholds below the unitary EPSP level, while the low-spontaneous group (rates less than 20/sec) all have discharge thresholds above that level. Other physiologically realistic results are obtained from the two groups.

Animals↗

PubMed2000

Differential effect of brain-derived neurotrophic factor on high-threshold mechanosensitivity in a rat neuropathic pain model.

We investigated the effect of the systemic infusion of brain derived neurotrophic factor (BDNF) on the behavioral response in a rat neuropathic pain model. One microgram per hour infusion of BDNF significantly attenuated mechanical hyperalgesia tested by the pin-prick test, however, 20 microg/h-BDNF infusion, on the contrary, enhanced the response. Neither 0.5 nor 10 microg/h-BDNF infusion influenced the mechanical hyperalgesia. Mechanical allodynia and thermal hyperalgesia, tested using a von Frey filament (23.0 mN) and the plantar test, were not influenced by BDNF treatment. These data suggest that systemic BDNF treatment can specifically alter high-threshold mechanosensitivity.

Animals↗

PubMed2002

The timing of sequences of saccades in visual search.

According to the LATER model (linear approach to thresholds with ergodic rate), the latency of a single saccade in response to target appearance can be understood as a decision process, which is subject to (i) variations in the rate of (visual) information processing; and (ii) the threshold for the decision. We tested whether the LATER model can also be applied to the sequences of saccades in a multiple fixation search, during which latencies of second and subsequent saccades are typically shorter than that of the initial saccade. We found that the distributions of the reciprocal latencies for later saccades, unlike those of the first saccade, are highly asymmetrical, much like a gamma distribution. This suggests that the normal distribution of the rate r, which the LATER model assumes, is not appropriate to describe the rate distributions of subsequent saccades in a scanning sequence. By contrast, the gamma distribution is also appropriate to describe the distribution of reciprocal latencies for the first saccade. The change of the gamma distribution parameters as a function of the ordinal number of the saccade suggests a lowering of the threshold for second and later saccades, as well as a reduction in the number of target elements analysed.

Humans↗

PubMed1997

Visibility of wavelet quantization noise.

The discrete wavelet transform (DWT) decomposes an image into bands that vary in spatial frequency and orientation. It is widely used for image compression. Measures of the visibility of DWT quantization errors are required to achieve optimal compression. Uniform quantization of a single band of coefficients results in an artifact that we call DWT uniform quantization noise; it is the sum of a lattice of random amplitude basis functions of the corresponding DWT synthesis filter. We measured visual detection thresholds for samples of DWT uniform quantization noise in Y, Cb, and Cr color channels. The spatial frequency of a wavelet is r 2-lambda, where r is display visual resolution in pixels/degree, and lambda is the wavelet level. Thresholds increase rapidly with wavelet spatial frequency. Thresholds also increase from Y to Cr to Cb, and with orientation from lowpass to horizontal/vertical to diagonal. We construct a mathematical model for DWT noise detection thresholds that is a function of level, orientation, and display visual resolution. This allows calculation of a "perceptually lossless" quantization matrix for which all errors are in theory below the visual threshold. The model may also be used as the basis for adaptive quantization schemes.

Adult↗

PubMed1995

Threshold parameters for epidemics in different community settings.

Threshold parameters of epidemic models play a central role in the assessment of proposed control strategies for infectious diseases. They have been determined for numerous standard epidemic models. This paper points out, with several examples, that threshold parameters depend on the social setting of the community and the variations in the behavior of the members of the community. Specifically, communities are considered in which individuals have fixed patterns of behavior or random patterns of behavior as well as communities of households with fixed or random patterns of behavior. A threshold parameter is computed for each of the different settings. Some comparisons are made to provide insights into the effects that social settings and behavior changes have on the threshold parameters.

Communicable Diseases↗

PubMedDate not supplied

The level of small nerve fiber dysfunction does not predict pain in diabetic Neuropathy: a study using quantitative sensory testing.

OBJECTIVES: To determine whether small nerve fiber dysfunction predicts pain in diabetic neuropathy using quantitative sensory testing of thermal thresholds. METHODS: Diabetic patients with or without painful neuropathy (n=191) were studied. Small nerve fiber function was assessed by quantitative sensory testing of cold detection and heat pain thresholds. Subjects were also categorized as being hyperalgesic (<10th percentile) or hyposensitive (>90th percentile) by comparing with normative data. Vibration perception threshold, a large nerve fiber function, was measured using a biothesiometer (Bio-medical Instrument, Newbury, OH). RESULTS: In the patients with pain, cold stimulus was detected after a greater reduction in temperature from baseline (-3.7 degrees C vs. -0.6 in the no-pain group, P<0.0001). There were no differences between the pain and painless groups in the heat pain tests, with hyperalgesia noted in about 60% of subjects. Vibration perception threshold and loss of ankle reflexes were significant determinants of pain, but together they accounted for only 6.8% of the variance. If these were removed from the model, cold detection threshold became a significant determinant of pain but accounted for only 3.0% of the variance. CONCLUSIONS: Quantitative sensory testing of small nerve fiber function is a useful test to detect the presence of neuropathy, and overall diabetic patients with neuropathic pain have more sensory loss. However, small nerve fiber abnormalities detected by quantitative sensory testing do not predict the presence of pain in diabetic neuropathy.

Afferent Pathways↗

PubMed1996

On the existence of a lactate threshold during incremental exercise: a systems analysis.

The relationship between blood lactate concentration ([La]) and O2 uptake (VO2) during incremental exercise remains controversial: does [La] increase smoothly as a function of VO2 (continuous model), or does it begin to increase abruptly above a particular metabolic rate (threshold model)? The dynamic characteristics of the underlying physiological system are investigated using system identification analysis techniques. A multivariate deterministic time series model of the [La] and VO2 response to incremental changes in work rate was fitted to simulated and experimental data. Time-varying system response parameters were determined through the application of a weighted recursive least squares algorithm. The model, using the identified time-varying parameters, provided a good fit to the data. The variation of these parameters over time was then examined. Two major transitions in the parameters were found to occur at intensity levels equivalent to 53 +/- 8% and 77 +/- 9% maximal VO2 (experimental data). These changes in the model parameters indicate that the best linear dynamic model that fits the observed system behavior has changed. This implies that the system has changed its operation in some way, by altering its structure or by moving to a different operating region. The identified parameter changes over time suggest that the exercise intensity range (from rest to maximal VO2) is divided into three main intensity domains, each with distinct dynamics. Further study of this three-phase system may help in the understanding of the underlying physiological mechanisms that affect the dynamics of [La] and VO2 during exercise.

Exercise↗

PubMed1984

A multiple-channel model for grating detection.

The multiple-channel model that was proposed in 1974 by MacLeod and Rosenfeld to describe the sensitivity of the visual system to complex gratings has been applied to a variety of complex gratings. The model predicts correctly the contrast sensitivity at both high and low spatial frequencies to square-wave gratings, square-wave with missing fundamental, sawtooth-wave, and trapezoid-wave gratings of different ramp widths. It provides a physiologically reasonable explanation of the detection of luminance gradients without requiring special gradient detectors. The model resembles the threshold behavior of the visual system in that it is sensitive to the relative phase of frequency components at low frequencies, but not at high frequencies.

Form Perception↗

PubMedDate not supplied

[A model for evoked activity of hippocampal neuronal population].

A system of equations governing the activity of hippocampal neuron populations is proposed. This continual firing-rate model is aimed to simulate evoked potentials and synchronous wave activity of the neural tissue. The populations of excitatory and inhibitory neurons and the types of synaptic receptors are distinguished. The model is based on the idea of control and averaging of Hodgkin-Huxley equations, a simple model of a threshold elicitation of population action potential bursts, approximations of synaptic currents by the second-order differential equations, and hyperbolic partial derivative equation of axonal excitation propagation. The model was fitted to intracellular cordings of postsynaptic potentials and postsynaptic currents in CA1 of rat hippocampal slices.

Algorithms↗

PubMed1997

An approach for modeling noncancer dose responses with an emphasis on uncertainty.

This paper presents an approach for characterizing the probability of adverse effects occurring in a population exposed to dose rates in excess of the Reference Dose (RfD). The approach uses a linear threshold (hockey stick) model of response and is based on the current system of uncertainty factors used in setting RfDs. The approach requires generally available toxicological estimates such as No-Observed-Adverse-Effect Levels (NOAELs) or Benchmark Doses and doses at which adverse effects are observed in 50% of the test animals (ED50s). In this approach, Monte Carlo analysis is used to characterize the uncertainty in the dose response slope based on the range and magnitude of the key sources of uncertainty in setting protective doses. The method does not require information on the shape of the dose response curve for specific chemicals, but is amenable to the inclusion of such data. The approach is applied to four compounds to produce estimates of response rates for dose rates greater than the RfD.

Acetamides↗

PubMed2004

[Neuropathic pain intensity depends on the degree of peripheral nerve injury in the rat].

Partial peripheral nerve injury produces a persistent neuropathic pain which is difficult to relieve. In order to determine whether different degrees of peripheral nerve injury are related with the severity of neuropathic pain, we examined pain-related behaviors, histological changes and NGF in the skin in rats treated with different types of spinal nerve injury: tight ligation of the left L5 spinal nerve, incomplete ligation of the left L4 and L5 spinal nerves and incomplete crush of the left L4 and L5 spinal nerves. In all model rats, the thresholds of paw withdrawal in response to mechanical and heat stimuli began to decrease on the injured side 1 day after the operation, and the decreases in the thresholds persisted for more than 1 month. Incomplete ligation and incomplete crush of the left L4 and L5 spinal nerves caused more severe allodynia and hyperalgesia than tight ligation of the left L5 spinal nerve on the injured side. In rats treated with incomplete crush, the threshold of withdrawal response to mechanical or heat stimuli was improved on day 32 after the operation as compared with that on day 15. Histological analysis revealed that about 80% of the fibers in the sciatic nerve were injured after incomplete ligation and incomplete crush of the left L4 and L5 spinal nerves on day 15, while about 50% of the fibers were damaged by tight ligation of the left L5 spinal nerve. In accordance with pain-relieving, the sciatic nerve fibers regenerated to about 50% of the number of the intact sciatic nerve fibers on day 32 in the crush model. Nerve growth factor (NGF) in the skin of the hindpaw on the injured side was accumulated after incomplete ligation and incomplete crush of the left L4 and L5 spinal nerves, but not tight ligation of the left L5 spinal nerve, on day 15 after the operation, possibly due to impairment of transport via unmyelinated primary afferents. Regeneration of the sciatic nerve alleviated the accumulation of NGF in the injured side hindpaw skin on day 32. The present results suggested that the severity of neuropathic pain was related with the degrees of both degeneration and/or regeneration of myelinated fibers and of functional damage of unmyelinated fibers.

Animals↗

PubMed2006

Image segmentation of trabecular spongiosa by visual inspection of the gradient magnitude.

Recent advances in physical models of skeletal dosimetry utilize high-resolution 3-dimensional microscopic computed tomography images of trabecular spongiosa. These images are coupled to radiation transport codes to assess energy deposition within active bone marrow and trabecular endosteum. These transport codes rely primarily on the segmentation of the spongiosa images into bone and marrow voxels. Image thresholding has been the segmentation of choice for bone sample images because of its extreme simplicity. However, the ability of the segmentation to reproduce the physical boundary between bone and marrow depends on the selection of the threshold value. Statistical models, as well as visual inspection of the image, have been employed extensively to determine the correct threshold. Both techniques are affected by partial volume effect and can provide unexpected results if performed without care. In this study, we propose a new technique to threshold trabecular spongiosa images based on visual inspection of the image gradient magnitude. We first show that the gradient magnitude of the image reaches a maximum along a surface that remains almost independent of partial volume effect and that is a good representation of the physical boundary between bone and marrow. A computer program was then developed to allow a user to compare the position of the iso-surface produced by a threshold with the gradient magnitude. The threshold that produces the iso-surface that best coincides with the maximum gradient is chosen. The technique was finally tested with a set of images of a true bone sample with different resolutions, as well as with three images of a cube of Duocell aluminium foam of known mass and density. Both tests demonstrate the ability of the gradient magnitude technique to retrieve sample volumes or media volume fractions with 1% accuracy at 30 microm voxel size.

Aluminum Compounds↗

PubMed2002

Chemical characterization of the aroma of Grenache rosé wines: aroma extract dilution analysis, quantitative determination, and sensory reconstitution studies.

The aroma of a Grenache rosé wine from Calatayud (Zaragoza, Spain) has been elucidated following a strategy consisting of an aroma extract dilution analysis (AEDA), followed by the quantitative analysis of the main odorants and the determination of odor activities values (OAVs) and, finally, by a series of reconstitution and omission tests with synthetic aroma models. Thirty-eight aroma compounds were found in the AEDA study, 35 of which were identified. Twenty-one compounds were at concentrations higher than their corresponding odor thresholds. An aroma model prepared by mixing the 24 compounds with OAV > 0.5 in a synthetic wine showed a high qualitative similarity with the aroma of the rosé wine. The addition of compounds with OAV < 0.5 did not improve the model, whereas the aroma of a model containing only odorants with OAV > 10 was very different from that of the wine. Omission tests revealed that the most important odorant of this Grenache rosé wine was 3-mercapto-1-hexanol, with a deep impact on the wine fruity and citric notes. The synergic action of Furaneol and homofuraneol also had an important impact on wine aroma, particularly in its fruity and caramel notes. The omission of beta-damascenone, which had the second highest OAV, caused only a slight decrease on the intensity of the aroma model. Still weaker was the sensory effect caused by the omission of 10 other compounds, such as fatty acids and their ethyl esters, isoamyl acetate, and higher alcohols.

Chromatography, Gas↗

PubMed1998

Glycine receptor reduction within segmental gray matter in a rat model in neuropathic pain.

Glycine is an amino acid neurotransmitter found in the spinal cord and is closely associated with interneurons that modulate afferent activity. We have previously shown that low segmental glycine concentrations or blockade of normal glycinergic activity lowers the threshold for pain thresholds. In addition, intrathecal glycine infusion increases the pain threshold in animal models of neuropathic pain. However, the role of the glycine receptor in neuropathic pain is not clear and is the basis for the current study. Using a unilateral sciatic nerve constriction injury model of neuropathic pain, the strychnine sensitive glycine receptor population was studied using immunohistochemical techniques. Glycine receptors are reduced in number in the dorsal horn bilaterally in injured animals. Glycine and related compounds are potentially valuable agents for treating chronic pain conditions in humans. A better understanding of glycine-receptor interactions should prove valuable as these compounds are studied in greater depth.

Animals↗

PubMed2006

Anodal vs cathodal stimulation of motor cortex: a modeling study.

OBJECTIVE: To explore the effects of electrical stimulation performed by an anode, a cathode or a bipole positioned over the motor cortex for chronic pain management. METHODS: A realistic 3D volume conductor model of the human precentral gyrus (motor cortex) was used to calculate the stimulus-induced electrical field. The subsequent response of neural elements in the precentral gyrus and in the anterior wall and lip of the central sulcus was simulated using compartmental neuron models including the axon, soma and dendritic trunk. RESULTS: While neural elements perpendicular to the electrode surface are preferentially excited by anodal stimulation, cathodal stimulation excites those with a direction component parallel to its surface. When stimulating bipolarly, the excitation of neural elements parallel to the bipole axis is additionally facilitated. The polarity of the contact over the precentral gyrus determines the predominant response. Inclusion of the soma-dendritic model generally reduces the excitation threshold as compared to simple axon model. CONCLUSIONS: Electrode polarity and electrode position over the precentral gyrus and central sulcus have a large and distinct influence on the response of cortical neural elements to stimuli. SIGNIFICANCE: Modeling studies like this can help to identify the effects of electrical stimulation on cortical neural tissue, elucidate mechanisms of action and ultimately to optimize the therapy.

Axons↗