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PubMed1987

An account of responses of spectrally opponent neurons in macaque lateral geniculate nucleus to successive contrast.

Coloured surfaces in the normal environment may be brighter or dimmer than the mean adaptation level. Changes in the firing rate of cells of the parvocellular layers of macaque lateral geniculate nucleus were studied with such stimuli; chromatic mixtures briefly replaced a white adaptation field. This paradigm is therefore one of successive contrast. Families of intensity-response curves for different wavelengths were measured. When taking sections at different luminance ratios through these families of curves, strongly opponent cells displayed spectrally selective responses at low luminance ratios, while weakly opponent cells had higher chromatic thresholds and responded well to stimuli at higher luminance ratios, brighter than the adaptation field. Strength of cone opponency, defined as the weight of the inhibitory cone mechanism relative to the excitatory one, was thus related to the range of intensity in which cells appeared to operate most effectively. S-cone inputs, as tested with lights lying along tritanopic confusion lines, could either be excitatory or inhibitory. Families of curves for different wavelengths can be simulated mathematically for a given cell by a simple model by using known cone absorption spectra. Hyperbolic response functions relate cone absorption to the output signals of the three cone mechanisms, which are assumed to interact linearly. Parameters from the simulation provided estimates of strength of cone opponency and cone sensitivity which were shown to be continuously distributed. Cell activity can be related to cone excitation in a trichromatic colour space with the help of the model, to give an indication of suprathreshold coding of colour and lightness.

Action Potentials↗
PubMedDate not supplied

Flow, diffusion, and thermal convection in percolation clusters: NMR experiments and numerical FEM/FVM simulations.

Percolation objects were fabricated based on computer-generated, two- or three-dimensional templates. Random-site, semi-continuous swiss cheese, and semi-continuous inverse swiss-cheese percolation models above the percolation threshold were considered. The water-filled pore space was investigated by NMR imaging and, in the presence of a pressure gradient, NMR velocity mapping. The fractal dimension, the correlation length, and the percolation probability were evaluated both from the computer-generated templates and the corresponding NMR spin density maps. Based on velocity maps, the percolation backbones were determined. The fractal dimension of the backbones turned out to be smaller than that of the complete cluster. As a further relation of interest, the volume-averaged velocity was calculated as a function of the probe volume radius. In a certain scaling window, the resulting dependence can be represented by a power law the exponent of which was not yet considered in the theoretical literature. The experimental results favorably compare to computer simulations based on the finite-element method (FEM) or the finite-volume method (FVM). Percolation theory suggests a relationship between the anomalous diffusion exponent and the fractal dimension of the cluster, i.e., between a dynamic and a structural parameter. We examined interdiffusion between two compartments initially filled with H2O and D2O, respectively, by proton imaging. The results confirm the theoretical expectation. As a third transport mechanism, thermal convection in percolation clusters of different porosities was studied with the aid of NMR velocity mapping. The velocity distribution is related to the convection roll size distribution. Corresponding histograms consist of a power law part representing localized rolls, and a high-velocity cut-off for cluster-spanning rolls. The maximum velocity as a function of the porosity clearly visualizes the percolation transition.

Computer Simulation↗
PubMed1996

A tidal breathing model of the forced inspired inert gas sinewave technique.

We have shown previously that it is possible to assess the cardio-respiratory function using sinusoidally oscillating inert gas forcing signals of nitrous oxide and argon (Hahn et al., 1993). This method uses an extension of a mathematical model of respiratory gas exchange introduced by Zwart et al. (1976), which assumed continuous ventilation. We investigate the effects of this assumption by developing a mathematical model using a single alveolar compartment and incorporating tidal ventilation, which must be solved using numerical methods. We compare simulated results from the tidal model with those from the continuous model, as the governing ventilatory and cardiac parameters are varied. The mathematical model is designed to be the basis of an on-line, non-invasive, cardio-respiratory measurement method, and will only be useful if the associated parameter recovery techniques are both reliable and robust. We demonstrate, in the presence of simulated measurement errors, that: (a) accurate recovery of the ventilatory parameters end-tidal volume, VA, and airways series dead-space, VD, are possible using the tidal breathing model; and (b) that a robust technique for recovery of pulmonary blood flow, QP, can be obtained using the more familiar continuous ventilation model.

Humans↗
PubMed1992

Estimating the probability of toxicity at the recommended dose following a phase I clinical trial in cancer.

The problem of point and interval estimation following a Phase I trial, carried out according to the scheme outlined by O'Quigley, Pepe, and Fisher (1990, Biometrics 46, 33-48), is investigated. A reparametrization of the model suggested in this earlier work can be seen to be advantageous in some circumstances. Maximum likelihood estimators, Bayesian estimators, and one-step estimators are considered. The continual reassessment method imposes restrictions on the sample space such that it is not possible for confidence intervals to achieve exact coverage properties, however large a sample is taken. Nonetheless, our simulations, based on a small finite sample of 20, not atypical in studies of this type, indicate that the calculated intervals are useful in most practical cases and achieve coverage very close to nominal levels in a very wide range of situations. The relative merits of the different estimators and their associated confidence intervals, viewed from a frequentist perspective, are discussed.

Antineoplastic Agents↗
PubMed2005

An incremental approach to genetic-algorithms-based classification.

Incremental learning has been widely addressed in the machine learning literature to cope with learning tasks where the learning environment is ever changing or training samples become available over time. However, most research work explores incremental learning with statistical algorithms or neural networks, rather than evolutionary algorithms. The work in this paper employs genetic algorithms (GAs) as basic learning algorithms for incremental learning within one or more classifier agents in a multiagent environment. Four new approaches with different initialization schemes are proposed. They keep the old solutions and use an "integration" operation to integrate them with new elements to accommodate new attributes, while biased mutation and crossover operations are adopted to further evolve a reinforced solution. The simulation results on benchmark classification data sets show that the proposed approaches can deal with the arrival of new input attributes and integrate them with the original input space. It is also shown that the proposed approaches can be successfully used for incremental learning and improve classification rates as compared to the retraining GA. Possible applications for continuous incremental training and feature selection are also discussed.

Algorithms↗
PubMed2003

Analytical methods for predicting the behaviour of population models with general spatial interactions.

Many biologists use population models that are spatial, stochastic and individual based. Analytical methods that describe the behaviour of these models approximately are attracting increasing interest as an alternative to expensive computer simulation. The methods can be employed for both prediction and fitting models to data. Recent work has extended existing (mean field) methods with the aim of accounting for the development of spatial correlations. A common feature is the use of closure approximations for truncating the set of evolution equations for summary statistics. We investigate an analytical approach for spatial and stochastic models where individuals interact according to a generic function of their distance; this extends previous methods for lattice models with interactions between close neighbours, such as the pair approximation. Our study also complements work by Bolker and Pacala (BP) [Theor. Pop. Biol. 52 (1997) 179; Am. Naturalist 153 (1999) 575]: it treats individuals as being spatially discrete (defined on a lattice) rather than as a continuous mass distribution; it tests the accuracy of different closure approximations over parameter space, including the additive moment closure (MC) used by BP and the Kirkwood approximation. The study is done in the context of an susceptible-infected-susceptible epidemic model with primary infection and with secondary infection represented by power-law interactions. MC is numerically unstable or inaccurate in parameter regions with low primary infection (or density-independent birth rates). A modified Kirkwood approximation gives stable and generally accurate transient and long-term solutions; we argue it can be applied to lattice and to continuous-space models as a substitute for MC. We derive a generalisation of the basic reproduction ratio, R(0), for spatial models.

Computer Simulation↗
PubMed2004

A laryngeal dissection station: educational paradigms in phonosurgery.

OBJECTIVES: To introduce a new tool for phonosurgical training and education. A multitude of innovations in complex laryngeal surgery has catalyzed new educational initiatives. Establishing dexterity in phonomicrosurgery is often difficult to achieve while working on patients because of the narrow margin for success. Furthermore, laryngoplastic phonosurgery and open partial laryngectomy require sophisticated knowledge of precise anatomic relationships, which can be difficult to express in images. Finally, many teaching programs do not have a high volume of these procedures, and there is a significant need to transmit this information in continuing education courses. STUDY DESIGN: Prototype design. METHODS: A laryngeal dissection station (LDS) was designed to facilitate the acquisition of high-level procedural skill sets for both transoral and transcervical techniques. RESULTS: This LDS can be used in existing temporal-bone laboratories by using cadaveric larynges. A rectangular frame supports two adjustable holders, one for the larynx and one for the examining speculum of a laryngoscope. Procedures are performed with the larynx fixed in space by a novel fixator. Variation in position and orientation of the components affords simulation of both microlaryngoscopy and open surgery. The dissection station can accommodate virtually any laryngoscope, regardless of size or shape. CONCLUSIONS: This training apparatus should facilitate laryngeal surgical instruction in residency training and continuing medical education. This device and others like it can help establish clinical competency in laryngology, should this become necessary in future educational models of residency training and recertification.

General Surgery↗
PubMed2005

Dynamic physiological modeling for functional diffuse optical tomography.

Diffuse optical tomography (DOT) is a noninvasive imaging technology that is sensitive to local concentration changes in oxy- and deoxyhemoglobin. When applied to functional neuroimaging, DOT measures hemodynamics in the scalp and brain that reflect competing metabolic demands and cardiovascular dynamics. The diffuse nature of near-infrared photon migration in tissue and the multitude of physiological systems that affect hemodynamics motivate the use of anatomical and physiological models to improve estimates of the functional hemodynamic response. In this paper, we present a linear state-space model for DOT analysis that models the physiological fluctuations present in the data with either static or dynamic estimation. We demonstrate the approach by using auxiliary measurements of blood pressure variability and heart rate variability as inputs to model the background physiology in DOT data. We evaluate the improvements accorded by modeling this physiology on ten human subjects with simulated functional hemodynamic responses added to the baseline physiology. Adding physiological modeling with a static estimator significantly improved estimates of the simulated functional response, and further significant improvements were achieved with a dynamic Kalman filter estimator (paired t tests, n=10, P<0.05). These results suggest that physiological modeling can improve DOT analysis. The further improvement with the Kalman filter encourages continued research into dynamic linear modeling of the physiology present in DOT. Cardiovascular dynamics also affect the blood-oxygen-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI). This state-space approach to DOT analysis could be extended to BOLD fMRI analysis, multimodal studies and real-time analysis.

Blood Pressure↗
PubMed2000

Biologically weighted measurement of UV radiation in space and on Earth with the biofilm technique.

Biological dosimetry has provided experimental proof of the high sensitivity of the biologically effective UVB doses to changes in atmospheric ozone and has thereby confirmed the predictions from model calculations. The biological UV dosimeter 'biofilm' whose sensitivity is based on dried spores of B. subtilis as UV target weights the incident UV radiation according to its DNA damaging potential. Biofilm dosimetry was applicated in space experiments as well as in use in remote areas on Earth. Examples are long-term UV measurements in Antarctica, measurements of diurnal UV profiles parallel in time at different locations in Europe, continuous UV measurements in the frame of the German UV measurement network and personal UV dosimetry. In space biofilms were used to determine the biological efficiency of the extraterrestrial solar UV, to simulate the effects of decreasing ozone concentrations and to determine the interaction of UVB and vitamin D production of cosmonauts in the MIR station.

Bacillus subtilis↗
PubMed2004

Simulating evolution by gene duplication of protein features that require multiple amino acid residues.

Gene duplication is thought to be a major source of evolutionary innovation because it allows one copy of a gene to mutate and explore genetic space while the other copy continues to fulfill the original function. Models of the process often implicitly assume that a single mutation to the duplicated gene can confer a new selectable property. Yet some protein features, such as disulfide bonds or ligand binding sites, require the participation of two or more amino acid residues, which could require several mutations. Here we model the evolution of such protein features by what we consider to be the conceptually simplest route-point mutation in duplicated genes. We show that for very large population sizes N, where at steady state in the absence of selection the population would be expected to contain one or more duplicated alleles coding for the feature, the time to fixation in the population hovers near the inverse of the point mutation rate, and varies sluggishly with the lambda(th) root of 1/N, where lambda is the number of nucleotide positions that must be mutated to produce the feature. At smaller population sizes, the time to fixation varies linearly with 1/N and exceeds the inverse of the point mutation rate. We conclude that, in general, to be fixed in 10(8) generations, the production of novel protein features that require the participation of two or more amino acid residues simply by multiple point mutations in duplicated genes would entail population sizes of no less than 10(9).

Amino Acids↗
PubMedDate not supplied

A novel mechanism for irregular firing of a neuron in response to periodic stimulation: irregularity in the absence of noise.

Irregular firing of action potentials (AP's) is a characteristic feature of neurons in the brain. The variability has been attributed to noise from various sources. This study illustrates an alternative mechanism, namely, deterministic irregularity within a model of ionic conductances. Specifically, a model based on modern measurements of the Na+ and K+ current components from the squid giant axon fires irregularly in response to a continuous train of near-threshold current pulses. The interspike interval histogram from these simulations is multi-modal, a result which in other systems has been attributed to stochastic resonance. Moreover, the simulations exhibited short burst of spikes followed by relatively long quiescent periods, a result suggestive of patterned input to the model even though the input consisted of a train of regularly spaced current pulses. The variability of firing is attributable to variations in AP parameters, in particular AP amplitude. The action potential for squid giant axons is not all-or-none. Rather, it is fundamentally a continuous function of stimulus amplitude. That is, the membrane lacks a threshold. Variation in AP amplitude, and to a lesser extent, AP duration, can produce variations in the time to a subsequent AP, which represents a paradigm shift for understanding irregular neuronal firing. The emphasis is not as much on events prior to an AP as it is on the AP's themselves.

Acoustic Stimulation↗
PubMed1992

Electrical impedance tomography. The provision of an electric field of controllable penetration into a cylinder.

If a cylinder carries on its surface an electric charge of a density which is constant in the axial direction, but which varies sinusoidally with an integral number of wavelengths around the circumference, then inside the cylinder the electric field has its maximum value at points adjacent to the surface, and reduces continuously as the axis is approached. The rate of reduction increases with the number of wavelengths. A rotating cylinder of such charge may be simulated by a number (divisable by three) of equally spaced conducting bars mounted longitudinally on the surface of a stationary cylinder, the bars being connected in sequence to the lines of a three-phase voltage supply. The number of wavelengths of charge around the circumference can be varied by the connection together of a chosen number of adjacent bars effectively to form a single bar, and so fields of varying penetration depths can be produced from a fixed frequency supply. The variation of the resulting currents would be related to the corresponding variation in the complex conductivity of the cylinder material.

Electric Conductivity↗
PubMed2000

Unsupervised learning of binary vectors: a Gaussian scenario.

We study a model of unsupervised learning where the real-valued data vectors are isotropically distributed, except for a single symmetry-breaking binary direction Bin¿-1,+1¿(N), onto which the projections have a Gaussian distribution. We show that a candidate vector J undergoing Gibbs learning in this discrete space, approaches the perfect match J=B exponentially. In addition to the second-order "retarded learning" phase transition for unbiased distributions, we show that first-order transitions can also occur. Extending the known result that the center of mass of the Gibbs ensemble has Bayes-optimal performance, we show that taking the sign of the components of this vector (clipping) leads to the vector with optimal performance in the binary space. These upper bounds are shown generally not to be saturated with the technique of transforming the components of a special continuous vector, except in asymptotic limits and in a special linear case. Simulations are presented which are in excellent agreement with the theoretical results.

Bayes Theorem↗
PubMed2006

Emergence of hexatic and threefold hidden order in two-dimensional smectic liquid crystals: A Monte Carlo study.

Using a high resolution Monte Carlo simulation technique based on a multihistogram method and cluster algorithm, we have investigated the critical properties of a coupled XY model, consisting of a sixfold symmetric hexatic and a hidden order parameter of threefold symmetry in two dimensions. The simulation results demonstrate a series of continuous transitions in which both kinds of orderings are established simultaneously. It is found that the specific-heat anomaly exponents for some regions in coupling constants space are in excellent agreement with the experimentally measured exponents extracted from heat-capacity data near the smectic- A -hexatic- B transition of two-layer free standing films.

Journal Article↗
PubMed2001

Renal function of rats in response to 37 days of head-down tilt.

Spaceflight induces changes in human renal function, suggesting similar changes may occur in rats. Since rats continue to be the prime mammalian model for study in space, the effects of chronic microgravity on rat renal function should be clarified. Acute studies in rats using the ground-based microgravity simulation model, head-down tilt (HDT), have shown increases in glomerular filtration rate (GFR), electrolyte excretion, and a diuresis. However, long term effects of HDT have not been studied extensively. This study was performed to elucidate rat renal function following long-term simulated microgravity. Chronic exposure to HDT will cause an increase in GFR and electrolyte excretion in rats, similar to acute exposures, and lead to a decrease in the fractional excretion of filtered electrolytes. Experimental animals (HDT, n=10) were tail-suspended for 37 days and renal function compared to ambulatory controls (AMB, n=10). On day 37 of HDT, GFR, osmolal clearance, and electrolyte excretion were decreased, while plasma osmolality and free water clearance were increased. Urine output remained similar between groups. The fractional excretion of the filtered electrolytes was unchanged except for a decrease in the percentage of filtered calcium excreted. Chronic exposure to HDT results in decreased GFR and electrolyte excretion, but the fractional excretion of filtered electrolytes remained primarily unaffected.

Animals↗
PubMed2005

Spatiotemporal complexity of patchy invasion in a predator-prey system with the Allee effect.

Invasion of an exotic species initiated by its local introduction is considered subject to predator-prey interactions and the Allee effect when the prey growth becomes negative for small values of the prey density. Mathematically, the system dynamics is described by two nonlinear diffusion-reaction equations in two spatial dimensions. Regimes of invasion are studied by means of extensive numerical simulations. We show that, in this system, along with well-known scenarios of species spread via propagation of continuous population fronts, there exists an essentially different invasion regime which we call a patchy invasion. In this regime, the species spreads over space via irregular motion and interaction of separate population patches without formation of any continuous front, the population density between the patches being nearly zero. We show that this type of the system dynamics corresponds to spatiotemporal chaos and calculate the dominant Lyapunov exponent. We then show that, surprisingly, in the regime of patchy invasion the spatially average prey density appears to be below the survival threshold. We also show that a variation of parameters can destroy this regime and either restore the usual invasion scenario via propagation of continuous fronts or brings the species to extinction; thus, the patchy spread can be qualified as the invasion at the edge of extinction. Finally, we discuss the implications of this phenomenon for invasive species management and control.

Animals↗
PubMed2002

[Sensitivity of MRI in detecting alveolar Infiltrates: Experimental studies].

PURPOSE: An experimental study using porcine lung explants and a dedicated chest phantom to evaluate the signal intensity of artificial alveolar infiltrates with T 1 - and T 2 -weighted MRI sequences. MATERIAL AND METHODS: 10 porcine lung explants were intubated, transferred into the cavity of a MRI-compatible chest phantom and inflated by continuous evacuation of the artificial pleural space. All lungs were examined with MRI at 1.5 T before and after intra-tracheal instillation of either 100 or 200 ml gelatine-stabilised liquid to simulate alveolar infiltrates. MR-examination comprised gradient echo (2D- and 3D-GRE) and fast spin echo sequences (T 2 -TSE and T 2 -HASTE). The signal intensity of lung parenchyma was evaluated at representative cross sections using a standardised scheme. Control studies were acquired with helical CT. RESULTS: The instilled liquid caused patchy confluent alveolar infiltrates resembling the findings in patients with pneumonia or ARDS. CT revealed typical ground-glass opacities. Before the application of the liquid, only T 2 -HASTE and T 2 -TSE displayed lung parenchyma signals with a signal/noise ratio of 3.62 and 1.39, respectively. After application of the liquid, both T 2 -weighted sequences showed clearly visible infiltrates with an increase in signal intensity of approx. 30 % at 100 ml (p < 0.01) and 60 % at 200 ml (p < 0.01). With 2D- and 3D-GRE the infiltrates were not visible, although the lung parenchyma signal increase was statistically significant. On 2D-GRE the increase in signal intensity reached 0.74 % (p = 0.32) after 100 ml and 5.6 % (p < 0.01) after 200 ml (for 3D-GRE: 2.2 % [p = 0.02] at 100 ml and 4.4 % at 200 ml [p < 0.01]). The CT controls revealed a significant increase of lung density of 17 H.E. at 100 ml (p = 0.02) and 75 H.E. at 200 ml (p < 0.01). CONCLUSIONS: MRI with T 2 -weighted sequences detects artificial alveolar infiltrates with high signal intensity and may be a highly sensitive tool to detect pneumonia in patients.

Animals↗
PubMed1991

Solution conformations of the gamma-carboxyglutamic acid domain of bovine prothrombin fragment 1, residues 1-65.

Molecular dynamics simulations have been performed (AMBER version 3.1) on solvated residues 1-65 of bovine prothrombin fragment 1 (BF1) by using the 2.8-A resolution crystallographic coordinates as the starting conformation for understanding calcium ion-induced conformational changes that precede experimentally observable phospholipid binding. Simulations were performed on the non-metal-bound crystal structure, the form resulting from addition of eight calcium ions to the 1-65 region of the crystal structure, the form resulting from removal of calcium ions after 107 ps and continuing the simulation, and an isolated hexapeptide loop (residues 18-23). In all cases, the 100-ps time scale seemed adequate to sample an ensemble of solution conformers within a particular region of conformation space. The non-metal-containing BF1 did not unfold appreciably during a 106-ps simulation starting from the crystallographic geometry. The calcium ion-containing structure (Ca-BF1) underwent an interesting conformational reorganization during its evolution from the crystal structure: during the time course of a 107-ps simulation, Ca-BF1 experienced a trans----cis isomerization of the gamma-carboxyglutamic acid-21 (Gla-21)-Pro-22 peptide bond. Removal of the calcium ions from this structure followed by 114 ps of additional molecular dynamics showed significant unfolding relative to the final 20-ps average structure of the 107-ps simulation; however, the Gla-21-Pro-22 peptide bond remained cis. A 265-ps simulation on the termini-protected hexapeptide loop (Cys-18 to Cys-23) containing two calcium ions also did not undergo a trans----cis isomerization. It is believed that the necessary activation energy for the transitional event observed in the Ca-BF1 simulation was largely supplied by global conformational events with a possible assist from relief of intermolecular crystal packing forces. The presence of a Gla preceding Pro-22, the inclusion of Pro-22 in a highly strained loop structure, and the formation of two long-lived salt bridges prior to isomerization may all contribute to this finding.

1-Carboxyglutamic Acid↗