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Stochastic models of neuronal dynamics.

Cortical activity is the product of interactions among neuronal populations. Macroscopic electrophysiological phenomena are generated by these interactions. In principle, the mechanisms of these interactions afford constraints on biologically plausible models of electrophysiological responses. In other words, the macroscopic features of cortical activity can be modelled in terms of the microscopic behaviour of neurons. An evoked response potential (ERP) is the mean electrical potential measured from an electrode on the scalp, in response to some event. The purpose of this paper is to outline a population density approach to modelling ERPs. We propose a biologically plausible model of neuronal activity that enables the estimation of physiologically meaningful parameters from electrophysiological data. The model encompasses four basic characteristics of neuronal activity and organization: (i) neurons are dynamic units, (ii) driven by stochastic forces, (iii) organized into populations with similar biophysical properties and response characteristics and (iv) multiple populations interact to form functional networks. This leads to a formulation of population dynamics in terms of the Fokker-Planck equation. The solution of this equation is the temporal evolution of a probability density over state-space, representing the distribution of an ensemble of trajectories. Each trajectory corresponds to the changing state of a neuron. Measurements can be modelled by taking expectations over this density, e.g. mean membrane potential, firing rate or energy consumption per neuron. The key motivation behind our approach is that ERPs represent an average response over many neurons. This means it is sufficient to model the probability density over neurons, because this implicitly models their average state. Although the dynamics of each neuron can be highly stochastic, the dynamics of the density is not. This means we can use Bayesian inference and estimation tools that have already been established for deterministic systems. The potential importance of modelling density dynamics (as opposed to more conventional neural mass models) is that they include interactions among the moments of neuronal states (e.g. the mean depolarization may depend on the variance of synaptic currents through nonlinear mechanisms).Here, we formulate a population model, based on biologically informed model-neurons with spike-rate adaptation and synaptic dynamics. Neuronal sub-populations are coupled to form an observation model, with the aim of estimating and making inferences about coupling among sub-populations using real data. We approximate the time-dependent solution of the system using a bi-orthogonal set and first-order perturbation expansion. For didactic purposes, the model is developed first in the context of deterministic input, and then extended to include stochastic effects. The approach is demonstrated using synthetic data, where model parameters are identified using a Bayesian estimation scheme we have described previously.

Bayes Theorem↗

Development and validation of a spatially explicit individual-based mixed crop growth model.

Spatial disposition of plants in intercrops, and differences in sowing time between species, can strongly affect their ecological interactions and, in consequence, the system's viability and performance. Empirical exploration of a wide range of spatial and temporal plant arrangements is costly and time-consuming. Modelling the growth of mixed crops is a tool which, combined with empirical tests, can greatly reduce the time and investment required for this task. Spatially explicit, individual-based dynamic models seem well suited for this purpose; their exploration and experimental validation for the case of simple, two-species, artificial plant communities, can also provide further insight as to how the spatial and temporal scales of a plant's multispecific neighbourhood affect its growth and performance. The aim of this investigation was to further develop a published spatially explicit individual-based mixed crop growth model [Vandermeer, J. H. (1989). The Ecology of Intercropping, Cambridge, U.K.: Cambridge University Press, p. 237], and to validate it experimentally. With this purpose in mind: (1) computer programs to simulate individual plant growth and to perform statistical analysis of both deterministic and stochastic versions of the model were developed; (2) the model was parametrized using a complex experimental diculture with several cohorts and spatial arrangements; (3) the predictive capacity of the model was tested using independent spatio-temporal experimental arrangements; (4) a modified version of the model was written, which abandons the assumption of linearity of the neighbourhood index at the cost of increasing the number of parameters; (5) The performance of stochastic versions of both Vandermeer's and our modified model were compared, employing a non-parametric measure of goodness of fit. We conclude that this approach to modelling plant growth subject to intra and interspecific competition is a remarkably efficient, general, conceptually elegant, heuristic tool whose predictive power can be further improved when nonlinear terms are introduced into the neighbourhood competition index, as done in our modified version of Vandermeer's model.

Agriculture↗

An experimental test for synergistic epistasis and its application in Chlamydomonas.

Theoretically, one of the most general benefits of sex is given by its function in facilitating selection against deleterious mutations. This advantage of sex may be deterministic if deleterious mutations affect the fitness of an individual in a synergistic way, i.e., if mutations increase each others' negative fitness effect. We present a new test for synergistic epistasis that considers the skewness of the log fitness distribution of offspring from a cross. We applied this test to data of the unicellular alga Chlamydomonas moewussii. For this purpose, two crosses were made: one between two strains that are presumed to have accumulated slightly deleterious mutations, the other between two strains without a history of mutation accumulation. Fitness was measured by estimating the two parameters of logistic growth in batch culture, the maximum growth rate (r) and the carrying capacity (K). The finding of a negatively skewed distribution for K in the accumulation cross suggests synergism between mutations affecting the carrying capacity, while the absence of skewness for tau in both crosses is consistent with independent effects of mutations affecting this parameter. The results suggest a possible alternative explanation for the general observation that sex is related to constant environments, where selection on K predominates, while asexual reproduction is found in more variable environments, where selection on r is more important.

Animals↗

Nearly deterministic linear optical controlled-NOT gate.

We show how to construct a near deterministic CNOT gate using several single photons sources, linear optics, photon number resolving quantum nondemolition detectors, and feed forward. This gate does not require the use of massively entangled states common to other implementations and is very efficient on resources with only one ancilla photon required. The key element of this gate is nondemolition detectors that use a weak cross-Kerr nonlinearity effect to conditionally generate a phase shift on a coherent probe if a photon is present in the signal mode. These potential phase shifts can then be measured using highly efficient homodyne detection.

Journal Article↗

Pyrotechnic shock response predictions combining statistical energy analysis and local random phase reconstruction.

Numerous pyrotechnic devices are used on satellites to separate structural subsystems, deploy appendages, and activate on-board operating subsystems. The firing of these pyrotechnic mechanisms leads to severe impulsive loads which could sometimes lead to failures in electronic systems. The objective of the present investigation is to assess the relevance of a method combining deterministic calculations and statistical energy analysis to predict the time overall shock environment of electronic equipment components. The methods are applied to the low- and high-frequency ranges, respectively, which may be defined using a modal parameter based on the effective transmissibility. Initially, in order to address the problem of the low-frequency content of the mechanical shock pulse, the linear dynamic response of the equipment was calculated using direct time integration of a finite element model of the structure. The inputs in the form of the accelerations measured in all three directions at each of the four bolted interfaces were injected into the model. The high-frequency content of the shock response is taken into account by considering the intrinsic dynamic filtering of the equipment. This frequency filter magnitude is extrapolated from the transfer function given by statistical energy analysis between the different imposed accelerations and the response accelerations. Their associated phases are synthesized by considering pseudo-modal phase variations around the group velocity of the structural flexural waves. Combining the effects of the high-frequency filter outputs and the low-frequency finite element calculations yields good predictions of the equipment shock time response over the whole frequency range of interest.

Journal Article↗

Chaos and physiology: deterministic chaos in excitable cell assemblies.

In this review we examined the emerging science of deterministic chaos (nonlinear systems theory) and its application to selected physiological systems. Although many of the popular images of fractals represent fascination and beauty that by analogy corresponds to nature as we see it, the question remains as to its ultimate meaning for physiological processes. It was our intent to help clarify this somewhat popular, somewhat obscure area of nonlinear dynamics in the context of an ever-changing procedural base. We examined not only the basic concepts of chaos, but also its applications ranging from observations in single cells to the complexity of the EEG. We have not suggested that nonlinear dynamics will answer all of our questions; however, we did attempt to illustrate ways in which this approach may help us to answer new questions and to rearticulate old ones. Chaos is revolutionary in that the overall approach requires us to adopt a different frame of reference which, at times, may move us away from previous concerns and methods of data analysis. In sections I-IV, we summarized the nonlinear dynamics approach and described its application to physiology and neural systems. First, we presented a general overview of the application of nonlinear dynamical techniques to neural systems. We discussed the manner in which even apparently simple deterministic systems can behave in an unpredictable manner. Second, we described the principles of nonlinear dynamical systems including the derived analytical techniques. We now see a variety of procedures for delineating whether frenetic chaotic behavior results from a nonlinear dynamical system with a few degrees of freedom, or whether it is caused by an infinite number of variables, i.e., noise. Third, we approached the applications of nonlinear procedures to the cardiovascular systems and to the neurosciences. In terms of time series, we described initial studies which applied the now "traditional" measures of dimensionality (e.g., based on the algorithm by Grassberger and Procaccia) and information change (e.g., Lyapunov exponents). Examples include our own work and that of Pritchard et al., demonstrating that the dynamics of neural mass activity reflect psychopathological states. Today, however, the trend has expanded to include the use of surrogate data and statistical null hypotheses testing to examine whether a given time series can be considered different from that of white or colored noise (cf. Ref. 262). One of the most important potential applications is that of quantifying changes in nonlinear dynamics to predict future states of the system.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Benefits and limitations of modeling for optimization of Porphyridium cruentum cultures in an annular photobioreactor.

A deterministic Markov process was developed to estimate the efficiency of a fully controlled photobioreactor by calculating the growth of the Rhodophyte Porphyridium cruentum. It was assumed that microalgal growth, in strictly controlled and non-nutrient-limited conditions, is a function of the amount of light energy received. The light sources delivered a continuous 206 microE m(-2) s(-1) average photon flux density to cultures reaching concentrations of 3 g l(-1) in batch and 0.7 g l(-1) in chemostat. The concentration time-courses calculated compared satisfactorily with measured results for both batch and continuous cultures. The quality of simulation in these two cases validated the hypotheses made, especially for the linearity of light bioconversion, and allowed the model to be used for further exploration of the photobioreactor-operating domain. Distribution of the specific growth rate as a function of time and radial position was compared for the two simulated cases. The use of an initial batch of several days prior to the dilution of a continuous culture proved theoretically beneficial for overall production. The influence of the dilution rate and of light-path length on surface productivity and concentration at steady state were demonstrated.

Bioreactors↗

Connectance in Sorghum development: beyond the genotype-phenotype duality.

Connectance, the level of linkage between organs, was measured in different lines of Sorghum bicolor during their reproductive development. It was compared with expression of characters, their level of variability and their heritability. A negative relationship is observed between connectance and heritability. Further results indicate that connectance does not simply introduce a noise factor in expression of a pre-existing information, but that it is directly involved in phenotypic expression and plasticity. Connectance appears as partly determined by the nature and dynamics of the network of relationships. It is concluded that the phenotype is not restricted to the deterministic expression of a pre-existing program, the genotype. Morphogenesis also involves another dimension, self-organized, which confers reliability, stability and adaptability to the developmental processes. The complex interactions between these two dimensions and their evolutionary consequences are discussed.

Edible Grain↗

Subsurface damage in some single crystalline optical materials.

We present a nondestructive method for estimating the depth of subsurface damage (SSD) in some single crystalline optical materials (silicon, lithium niobate, calcium fluoride, magnesium fluoride, and sapphire); the method is established by correlating surface microroughness measurements, specifically, the peak-to-valley (p-v) microroughness, to the depth of SSD found by a novel destructive method. Previous methods for directly determining the depth of SSD may be insufficient when applied to single crystals that are very soft or very hard. Our novel destructive technique uses magnetorheological finishing to polish spots onto a ground surface. We find that p-v surface microroughness, appropriately scaled, gives an upper bound to SSD. Our data suggest that SSD in the single crystalline optical materials included in our study (deterministically microground, lapped, and sawed) is always less than 1.4 times the p-v surface microroughness found by white-light interferometry. We also discuss another way of estimating SSD based on the abrasive size used.

Journal Article↗

Single atoms in an optical dipole trap: towards a deterministic source of cold atoms

We describe a simple experimental technique which allows us to store a small and deterministic number of neutral atoms in an optical dipole trap. The desired atom number is prepared in a magneto-optical trap overlapped with a single focused Nd:YAG laser beam. Dipole trap loading efficiency of 100% and storage times of about one minute have been achieved. We have also prepared atoms in a certain hyperfine state and demonstrated the feasibility of a state-selective detection via resonance fluorescence at the level of a few neutral atoms. A spin relaxation time of the polarized sample of 4.2+/-0.7 s has been measured. Possible applications are briefly discussed.

Journal Article↗

Selection and evolution in macromolecular systems.

The notion of a quasi-species represents the ensemble of macromolecular sequences derived by the mechanism of mutation and replication from a single wild type. In Eigen (1971) and Eigen & Schuster (1979), the deterministic evolution of this ensemble under constant environmental conditions is given in terms of continuous models which describe the dynamics of the distribution of polynucleotides. This paper starts from a discrete model of macromolecular evolution and introduces the notion of a genealogy in order to study the dynamics of the quasi-species in constant and variable environments. We introduce, in terms of these genealogies, the notions of entropy and adaptive value of a quasi-species and the notion of capacity of the environment. We discuss the significance of these indices as measures of selective value and we analyse the conditions under which these measures coincide with the growth rate of the quasi-species.

Base Sequence↗

State vector description of the proliferation of mammalian cells in tissue culture. I. Exponential growth.

Proliferation of mammalian cells, even under conditions of unlimited growth, presents a complex problem because of the interaction of deterministic and stochastic processes. Division of the cell cycle into a finite number of parts establishes a multidimensional vector space. In this space an arbitrary culture can be represented by a vector called the state vector. The culture's subsequent growth is represented mathematically as a series of transformations of the state vector. The operators effecting these transformations are presented in matrix form and their relationship to the distribution of cell generation times is described. As an application of the model, the growth of an initially synchronized culture is considered and an unambiguous measure of the degree of synchrony is proposed. Results of a computer simulation of such a culture show the behavior with time of the degree of synchrony, the total cell number, and the mitotic index. In particular the importance of the magnitude of the coefficient of variation of the generation time distribution is illustrated.

Animals↗

Robustness properties of apoptosis models with respect to parameter variations and intrinsic noise.

Analyses of different robustness aspects for models of the direct signal transduction pathway of receptor-induced apoptosis is presented. Apoptosis is a form of programmed cell death, removing unwanted cells within multicellular organisms to maintain a proper balance between cell reproduction and death. Its signalling pathway includes an activation feedback loop that generates bistable behaviour, where the two steady states can be seen as 'life' and 'death'. Inherent robustness, widely recognised in biological systems, is of major importance in apoptosis signalling, as it guarantees the same cell fate for similar conditions. First, the influence of the stochastic nature of reactions indicating a role for inhibition reactions as noise filters and justifying a deterministic approach in the further analyses is evaluated. Second, the robustness of the bistable threshold with respect to parameter changes is evaluated by statistical methods, showing the need to balance both the forward and the back part of the activation loop. These analyses can also discriminate between the models favouring the model consistent with novel biological findings. The parameter robustness analyses are also applicable to other signal transduction networks, as several have been shown to display bistable behaviour. These methods therefore have a range of possible applications in systems biology not only to measure robustness, but also for model discrimination.

Animals↗

Community inertia of Quaternary small mammal assemblages in North America.

One of the longest running debates in ecology is whether chance or determinism structures biotic communities, and this question is often studied by looking for the presence or absence of community inertia (lack of change) over time or space. Results have been equivocal. We adopted three tactics for a fresh approach: (i) allowing the answer to vary with the geographic, temporal, and taxonomic scale of study, (ii) using appropriate reference points for the amount of inertia in random biological systems, and (iii) using a robust approach for measurement of inertia. We examined fossil assemblages of mammalian communities across almost 1,000,000 years and at sites spanning approximately 3,500 km. We showed that in general there is good evidence for inertia but that the results change in a quantifiable fashion with taxonomic, spatial, and temporal scales. By using neutral theory we place a reference point on the degree of inertia and demonstrate that empirical mammalian communities show greater inertia than neutral communities over time scales >3,000 year. Although our results do not specifically reveal mechanism, they emphasize that deterministic forces are at work in structuring communities over millennia.

Animals↗

User subjectivity in Monte Carlo modeling of pesticide exposure.

Monte Carlo techniques are increasingly used in pesticide exposure modeling to evaluate the uncertainty in predictions arising from uncertainty in input parameters and to estimate the confidence that should be assigned to the modeling results. The approach typically involves running a deterministic model repeatedly for a large number of input values sampled from statistical distributions. In the present study, six modelers made choices regarding the type and parameterization of distributions assigned to degradation and sorption data for an example pesticide, the correlation between the parameters, the tool and method used for sampling, and the number of samples generated. A leaching assessment was carried out using a single model and scenario and all data for sorption and degradation generated by the six modelers. The distributions of sampled parameters differed between the modelers, and the agreement with the measured data was variable. Large differences were found between the upper percentiles of simulated concentrations in leachate. The probability of exceeding 0.1 microg/L ranged from 0 to 35.7%. The present study demonstrated that subjective choices made in Monte Carlo modeling introduce variability into probabilistic modeling and that the results need to be interpreted with care.

Monte Carlo Method↗

Mutation-selection balance: ancestry, load, and maximum principle.

We analyze the equilibrium behavior of deterministic haploid mutation-selection models. To this end, both the forward and the time-reversed evolution processes are considered. The stationary state of the latter is called the ancestral distribution, which turns out as a key for the study of mutation-selection balance. We find that the ancestral genotype frequencies determine the sensitivity of the equilibrium mean fitness to changes in the corresponding fitness values and discuss implications for the evolution of mutational robustness. We further show that the difference between the ancestral and the population mean fitness, termed mutational loss, provides a measure for the sensitivity of the equilibrium mean fitness to changes in the mutation rate. The interrelation of the loss and the mutation load is discussed. For a class of models in which the number of mutations in an individual is taken as the trait value, and fitness is a function of the trait, we use the ancestor formulation to derive a simple maximum principle, from which the mean and variance of fitness and the trait may be derived; the results are exact for a number of limiting cases, and otherwise yield approximations which are accurate for a wide range of parameters. These results are applied to threshold phenomena caused by the interplay of selection and mutation (known as error thresholds). They lead to a clarification of concepts, as well as criteria for the existence of error thresholds.

Animals↗

Optical imaging in medicine: II. Modelling and reconstruction.

The desire for a diagnostic optical imaging modality has motivated the development of image reconstruction procedures involving solution of the inverse problem. This approach is based on the assumption that, given a set of measurements of transmitted light between pairs of points on the surface of an object, there exists a unique three-dimensional distribution of internal scatterers and absorbers which would yield that set. Thus imaging becomes a task of solving an inverse problem using an appropriate model of photon transport. In this paper we examine the models that have been developed for this task, and review current approaches to image reconstruction. Specifically, we consider models based on radiative transfer theory and its derivatives, which are either stochastic in nature (random walk, Monte Carlo, and Markov processes) or deterministic (partial differential equation models and their solutions). Image reconstruction algorithms are discussed which are based on either direct backprojection, perturbation methods, nonlinear optimization, or Jacobian calculation. Finally we discuss some of the fundamental problems that must be addressed before optical tomography can be considered to be an understood problem, and before its full potential can be realized.

Diagnostic Imaging↗

Nonlinear EEG analysis and its potential role in epileptology.

Deterministic chaos offers a striking explanation for apparently irregular behavior of the brain that is evidenced in the EEG. Recent developments in the physical-mathematical framework of the theory of nonlinear dynamics (colloquially often termed chaos theory) provide new concepts and powerful algorithms to analyze such time series. Because of its high versatility, nonlinear time series analysis has already gone beyond the physical sciences and, at present, is being successfully applied in a variety of disciplines, including cardiology, neurology, psychiatry, and epileptology. However, it is well known that different influencing factors limit the use of nonlinear measures to characterize EEG dynamics in a strict sense. Nevertheless, when interpreted with care, relative estimates of, e.g., the correlation dimension or the Lyapunov exponents, can reliably characterize different states of normal and pathologic brain function. In epileptology, extraction of nonlinear measures from the intracranially recorded EEG promises to be important for clinical practice. In addition to an immense reduction of information content of long-lasting EEG recordings, previous studies have shown that these measures enable (a) localization of the primary epileptogenic area in different cerebral regions during the interictal state, (b) investigations of antiepileptic drug effects, (c) analyses of spatio-temporal interactions between the epileptogenic zone and other brain areas, and (d) detection of features predictive of imminent seizure activity. Nonlinear time series analysis provides new and supplementary information about the epileptogenic process and thus contributes to an improvement in presurgical evaluation.

Brain Mapping↗