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Modelling oculomotor data with decision tree induction.

We studied relationships between oculomotor test results and the site of lesion in the data set containing patient cases with operated cerebello-pontine angle tumour, operated hemangioblastoma, infarction of cerebello-brainstem or Meniere's disease and control subjects. Several classification models were generated by decision tree induction to find parameter combinations which are efficient in classification. The studied data were characterised by missing values and scarcity of example cases. This study suggested that decision tree induction can be a useful method even in problematic real world classification tasks. Models generated by decision tree induction and evaluated by an expert physician may give information that is beneficial for research.

Brain Stem Infarctions↗

A model for collicular efferent mechanisms underlying the generation of saccades.

A quantitative model for the generation of saccades is presented which is based on the accepted notion that saccade metrics are coded in the deeper layers of the superior colliculus by the population of recruited movement-related cells. The model has important features derived from electrophysiological data in the monkey: a nonhomogeneous and anisotropic afferent-mapping function relating the outside visual world to collicular coordinates and a dome-shaped activity profile in the deeper layers describing the spatial extent of the recruited movement-related cell population. It is proposed that each cell generates a small movement contribution which is determined both by the neuron's location in the collicular map and its firing rate. The individual cell contributions are then added vectorially to yield the total saccade. The model can generate saccades to single visual stimuli in all directions and simulate electrical stimulation experiments. To account for some nonlinear properties of the saccadic system in the computation of saccade metrics, a nonlinear version of the linear summation model is discussed.

Efferent Pathways↗

Modeling the role of the interstitial nucleus of Cajal in otolithic control of static eye position.

Previous models of ocular counterroll assumed that static eye position was controlled by direct brainstem pathways from the vestibular nuclei via the ocular motor nuclei to the extraocular eye muscles. However, recent experimental evidence has shown that the interstitial nucleus of Cajal (INC), known as the vertical-torsional velocity-to-position integrator, plays a crucial role in torsional otolith-dependent eye position, i.e. for the modification of Listing's plane by static head tilts. To evaluate possible mechanisms by which otolithic input may influence eye position via the INC, we constructed a 3D mathematical model of saccade and nystagmus generation. The model includes the burst generators located in the rostral interstitial nucleus of the medial longitudinal fasciculus (MLF) and paramedian pontine reticular formation and the velocity-to-position integrators located in the INC and prepositus hypoglossi. The model simulations suggest that otolith pathways to the neural integrator that adjust Listing's plane may involve the cerebellum.

Humans↗

Computational model of the motor program generator for pursuit.

A parallel processing neural network model of a motor program generator (MPG) for pursuit eye movements (PEM) was developed. The MPG model consists of two neural networks (velocity maps), which represent velocity values theta R and theta L respectively, as eccentric locations on the map with zero in the center. Neurons are arranged in a circular layer and connected only to their immediate neighbors. The potential field P of all neurons is analogous to a flat circular membrane whose center can be pushed up or down. During PEM one of the two maps, which are connected in a push-pull fashion, always features an activity peak (AP) which travels with constant velocity vT from one neuron to the next. The shape of P defines whether AP travels in a circle (theta = constant), towards the periphery (theta increase) or towards the center (theta decrease). Such a model provides a novel approach for understanding neural generators of non-periodical motor programs.

Animals↗

Internal standard signal suppression by co-eluting analyte in isotope dilution LC-ESI-MS.

The suppression of the internal standard by increasing concentrations of the co-eluting analyte in calibration series and plasma samples analysed by LC-ESI-MS was studied using the isotope dilution technique. A series of three analyte/deuterated analyte pairs including fexofenadine/d6-fexofenadine, dapsone/d4-dapsone and peudoephedrine/d3-ephedrine were investigated. Suppression of the internal standard signal was noticed in extracted plasma samples containing fexofenadine and d6-fexofenadine as internal standard, as well as in solvent based calibration solutions of the three pair of compounds noted above during LC-ESI-MS analysis at flow rates greater than 100 microL min(-1). This signal suppression effect was described by invoking Enke's model of electrospray ion generation. This model suggests that signal suppression can be ascribed to the competition between ionic species for charged surface sites present on the generated droplets during the electrospray process. The slopes of the calibration curves of the three analytes were close to unity (fexofenadien/d6-fexofenadine 0.964 +/- 0.008, pseudoephedrine/d3-ephedrine 1.02 +/- 0.080 and dapsone/d4-dapsone 0.905 +/- 0.048) as predicted by the model, indicating that quantitation should not be affected by the variation in the peak area of the internal standard.

Calibration↗

A stochastic model of temporally regulated generation of oligodendrocytes in cell culture.

The results of our previous analyses suggest that O-2A progenitor cells become competent for differentiation in vitro after they complete a certain number of critical mitotic cycles. The number of critical cycles varies from clone to clone and should be thought of as a random variable. We propose an approach to the analysis of oligodendrocyte generation in vitro based on a stochastic model allowing for an arbitrary distribution of this random variable with a finite support. When applied to experimental data on clonal growth and differentiation of purified O-2A progenitor cells obtained from optic nerves of 1 and 7 day-old rats, the model provides a good quantitative description not only of the first two moments (mean and variance) of the number of O-2A progenitor cells and oligodendrocytes at different times after the start of experiment, but of the corresponding distributions as well. As our estimates show, there are scarcely any O-2A progenitor cells that divide in vitro more than twice before they acquire the competence for differentiation. Those O-2A cells that have undergone the critical divisions differentiate into an oligodendrocyte in each of the subsequent mitotic cycles with a certain probability. We give estimates of this probability for O-2A cells under different growth conditions. Our analysis suggests that the effect of thyroid hormone is twofold: it reduces the mean duration of the mitotic cycle for progenitor cells, and it increases the probability of their transformation into oligodendrocytes.

Animals↗

Domain-based homology modeling and mapping of the conformational epitopes of envelope glycoprotein of west nile virus.

Knowledge-based modeling has proved significantly accurate for generating the quality models for proteins whose sequence identity with the structurally known targets is greater than or equal to 40%. On the other hand, models obtained for low sequence identities are not reliable. Hence, a reliable and alternative strategy that uses knowledge of domains in the protein can be used to improve the quality of the model generated by the homology method. Here, we report a method for developing a 3D-model for the envelope glycoprotein (Egp) of west nile virus (WNV), using knowledge of structurally conserved functional domains amongst the target sequence (Egp of WNV) and its homologous templates belonging to the same protein family, flaviviridae. This strategy is found to be highly effective in reducing the root mean square deviation (RMSD) value at the Calpha positions of the target and its experimental homologues. The 3D structure of a protein is a prerequisite for structure-based drug design as well as for identifying the conformational epitopes that are essential for the designing vaccines. The conformational epitopes are mapped from the 3D structure of Egp of WNV modeled using the concept of an antigenic domain. A total of five such epitope regions/sites have been identified. They have been found distributed in the loop regions (surface) of the whole protein model composed of dimerization, central and immunological domains. These sites are proposed as the binding sites for HLA proteins/B-cell receptors. Binding is required to activate the immune response against WNV.

Amino Acid Sequence↗

Effect of sodium perturbations on rat chemoreceptor spike generation: implications for a Poisson model.

1. The sensitivity of arterial chemoreceptor spike generation to reductions in excitability was examined using rat chemoreceptors in vitro. Axonal excitability was reduced by reducing extracellular sodium concentration ([Na+]o) by 10-40% or by applying low doses of tetrodotoxin (TTX). 2. In normoxia and in hypoxia, an isosmotic reduction in [Na+]o caused a proportional decrease in single-fibre, spiking nerve activity. For a 20% reduction in [Na+]o, nerve activity decreased to 54 +/- 7% of control in normoxia and 41 +/- 5% in hypoxia. 3. Low doses of TTX (25-50 nM) caused a similar decrease in spiking frequency, but this response was variable amongst fibres, with some fibres unaffected by TTX. 4. A reduction in [Na+]o by 20% caused a slowing of conduction velocity, measured using an electrical stimulus delivered to an electrode placed in the carotid body. Threshold current for spike generation was increased by about 2.7 +/- 1.4%. Threshold current increased by 6.5 +/- 3.7% following a 40% reduction in [Na+]o. 5. The spike generation process was modelled as a Poisson process in which depolarizing events summate and give rise to an action potential. The experimental data were best fitted to a high order process characterized by a large number of events and high event threshold. 6. This result is not consistent with depolarization events caused by episodic transmitter release, but suggests that afferent spike generation is an endogenous process in the afferent nerve fibres, perhaps linked to random channel activity or to thermal noise fluctuations.

Animals↗

A modified Zeeman model for producing HRV signals and its application to ECG signal generation.

Developing a mathematical model for the artificial generation of electrocardiogram (ECG) signals is a subject that has been widely investigated. One of the challenges is to generate ECG signals with a wide range of waveforms, power spectra and variations in heart rate variability (HRV)--all of which are important indexes of human heart functions. In this paper we present a comprehensive model for generating such artificial ECG signals. We incorporate into our model the effects of respiratory sinus arrhythmia, Mayer waves and the important very low-frequency component in the power spectrum of HRV. We use a new modified Zeeman model for generating the time series for HRV, and a single cycle of ECG is produced by using a simple neural network. The importance of the work is the model's ability to produce artificial ECG signals that resemble experimental recordings under various physiological conditions. As such the model provides a useful tool to simulate and analyse the main characteristics of ECG, such as its power spectrum and HRV under different conditions. Potential applications of this model include using the generated ECG as a flexible signal source to assess the effectiveness of a diagnostic ECG signal-processing device.

Arrhythmia, Sinus↗

A comparison of reflectance and transmittance near-infrared spectroscopic techniques in determining drug content in intact tablets.

Drug contents of intact tablets were determined using non-destructive near infrared (NIR) reflectance and transmittance spectroscopic techniques. Tablets were compressed from blends of Avicel PH-101 and 0.5% w/w magnesium stearate with varying concentrations of anhydrous theophylline (0, 1, 2, 5, 10, 20 and 40% w/w). Ten tablets from each drug content batch were randomly selected for spectral analysis. Both reflectance and transmittance NIR spectra were obtained from these intact tablets. Actual drug contents of the tablets were then ascertained using a UV-spectrophotometer at 268 nm. Multiple linear regression (MLR) models at 1116 nm and partial least squares (PLS) calibration models were generated from the second derivative spectral data of the tablets in order to predict drug contents of intact tablets. Both the reflectance and the transmittance techniques were able to predict the drug contents in intact tablets over a wide range. However, a comparison of the results of the study indicated that the lowest percent errors of prediction were provided by the PLS calibration models generated from spectral data obtained using the transmittance technique.

Bronchodilator Agents↗

The identification of Class III malocclusions by discriminant analysis.

Lateral cephalometric radiographs of 210 control and 285 Class III subjects were traced, digitized, and 43 calculated variables submitted to a stepwise discriminant analysis. A 10-factor model was generated, giving 95.2 per cent correct classification of the control children and 95.1 per cent accurate identification of the Class III group. Ten control and 14 Class III children were categorized incorrectly. To test the validity of the analysis, radiographs of these 24 individuals were examined in detail. In all cases, a satisfactory reason for the misgrouping was identified. This investigation underlined the importance of rigorous standards of case selection when compiling the groups. The robustness of the 10-factor model was also examined. Subjects were arbitrarily split into two groups, the odd- and the even-numbered cases, and the discriminant analysis repeated on each. Both new models contained the same 10 variables, but with slightly different values for their accompanying coefficients. The cases erroneously identified by the whole group analysis were again misclassified, together with a few additional cases. Each new model performed equally well on the data from the opposing group as on that from which it had been derived. Thus, the model generated in this study was both valid and acceptably robust. It would therefore appear that discriminant analysis may be a viable tool in the identification and classification of groups of individuals.

Adolescent↗

Tool-assisted mesh generation based on a tissue-growth model.

An heuristic mesh generation technique is proposed that is based on the model of forced particle motion, an edgewise cell-splitting algorithm and a moving tool concept. The method differs from conventional mesh generators in that it uses outward growth of the mesh, in contrast to the inward growth used in traditional meshing techniques. The method does not require prior meshing and patching of two-dimensional (2D) boundary surfaces. Instead, it uses a pre-defined skeleton of one-dimensional segments, or an arbitrary tool motion in three-dimensional (3D) space. In this respect, the technique can be considered as a 3D extension of a 2D drawing tool and can find applications in virtual reality systems. The method also guarantees the smoothness of the outer boundary of the mesh at each step of mesh generation, which is not the case with traditional propagating-front methods. The approach is based on the model of tissue growth and is suitable for meshing complex networks of bifurcating branches commonly found in biological structures: blood vessels, lungs, neural networks, plants etc. The generated meshes were used in solving unsteady flow and particle transport problems in lungs.

Biological Products↗

A comparison of conscious and automatic memory processes for picture and word stimuli: a process dissociation analysis.

Four experiments were conducted to evaluate explanations of picture superiority effects previously found for several tasks. In a process dissociation procedure (Jacoby, 1991) with word stem completion, picture fragment completion, and category production tasks, conscious and automatic memory processes were compared for studied pictures and words with an independent retrieval model and a generate-source model. The predictions of a transfer appropriate processing account of picture superiority were tested and validated in "process pure" latent measures of conscious and unconscious, or automatic and source, memory processes. Results from both model fits verified that pictures had a conceptual (conscious/source) processing advantage over words for all tasks. The effects of perceptual (automatic/word generation) compatibility depended on task type, with pictorial tasks favoring pictures and linguistic tasks favoring words. Results show support for an explanation of the picture superiority effect that involves an interaction of encoding and retrieval processes.

Adult↗

The distributions of cell size and generation time in a model of the cell cycle incorporating size control and random transitions.

A deterministic/probabilistic model of the cell division cycle is analysed mathematically and compared to experimental data and to other models of the cell cycle. The model posits a random-exiting phase of the cell cycle and a minimum-size requirement for entry into the random-exiting phase. By design, the model predicts exponential "beta-curves", which are characteristic of sister cell generation times. We show that the model predicts "alpha-curves" with exponential tails and hyperbolic-sine-like shoulders, and that these curves fit observed generation-time data excellently. We also calculate correlation coefficients for sister cells and for mother-daughter pairs. These correlation coefficients are more negative than is generally observed, which is characteristic of all size-control models and is generally attributed to some unknown positive correlation in growth rates of related cells. Next we compare theoretical size distributions with observed distributions, and we calculate the dependence of average cell mass on specific growth rate and show that this dependence agrees with a well-known relation in bacteria. In the discussion we argue that unequal division is probably not the source of stochastic fluctuations in deterministic size-control models, transition-probability models with no feedback from cell size cannot account for the rapidity with which the new, stable size distribution is established after perturbation, and Kubitschek's rate-normal model is not consistent with exponential beta-curves.

Bacteria↗

Predicting structural models for silicon clusters.

This article introduces an efficient method to generate structural models for medium-sized silicon clusters. Geometrical information obtained from previous investigations of small clusters is initially sorted and then introduced into our predictor algorithm in order to generate structural models for large clusters. The method predicts geometries whose binding energies are close (95%) to the corresponding value for the ground-state with very low computational cost. These predictions can be used as a very good initial guess for any global optimization algorithm. As a test case, information from clusters up to 14 atoms was used to predict good models for silicon clusters up to 20 atoms. We believe that the new algorithm may enhance the performance of most optimization methods whenever some previous information is available.

Journal Article↗

Minimal model of arterial chaos generated by coupled intracellular and membrane Ca2+ oscillators.

We have developed a mathematical model of arterial vasomotion in which irregular rhythmic activity is generated by the nonlinear interaction of intracellular and membrane oscillators that depend on cyclic release of Ca2+ from internal stores and cyclic influx of extracellular Ca2+, respectively. Four key control variables were selected on the basis of the pharmacological characteristics of histamine-induced vasomotion in rabbit ear arteries: Ca2+ concentration in the cytosol, Ca2+ concentration in ryanodine-sensitive stores, cell membrane potential, and the open state probability of Ca2+-activated K+ channels. Although not represented by independent dynamic variables, the model also incorporates Na+/Ca2+ exchange, the Na+-K+-ATPase, Cl- fluxes, and Ca2+ efflux via the extrusion ATPase. Simulations reproduce a wide spectrum of experimental observations, including 1) the effects of interventions that modulate the functionality of Ca2+ stores and membrane ion channels, 2) paradoxes such as the apparently unpredictable dual action of Ca2+ antagonists and low extracellular Na+ concentration, which can abolish vasomotion or promote the appearance of large-amplitude oscillations, and 3) period-doubling, quasiperiodic, and intermittent routes to chaos. Nonlinearity is essential to explain these diverse patterns of experimental vascular response.

Animals↗

A stochastic version of corticosteriod pharmacogenomic model.

The purpose of this study was to develop a stochastic version of corticosteriod fifth generation pharmacogenomic model. The Gillespie algorithm was used to generate the independent time courses of the receptor messenger RNA (mRNA). Initial parameters for the stochastic simulation were adapted from the study by Jin et al. The result obtained from the proposed stochastic model showed an overall agreement with the deterministic fifth generation model. This study suggested that because the stochastic model takes into account the "noise" nature of gene regulation, it would have potential application in pharmacogenomic modeling.

Adrenal Cortex Hormones↗

Cutting edge: elimination of an endogenous adjuvant reduces the activation of CD8 T lymphocytes to transplanted cells and in an autoimmune diabetes model.

The generation of adaptive immune responses is thought to require the presence of adjuvants. Although microbial adjuvants are well characterized, little is known about what provides the adjuvant effect in responses to transplanted cells or in autoimmune diseases. It had been postulated that, in these situations, injured cells instead released "endogenous adjuvants." We previously identified uric acid as an endogenous adjuvant for coinjected Ags. We now report that elimination of uric acid reduced the generation of CTL to an Ag in transplanted syngeneic cells and the proliferation of autoreactive T cells in a transgenic diabetes model. In contrast, uric acid depletion did not reduce the stimulation of T cells to mature APCs or when endogenous APCs were activated with anti-CD40 Ab. These findings support the concept that danger signals contribute to the T cell responses to cell-associated Ags by activating APCs and identify uric acid as one of these signals.

Adjuvants, Immunologic↗