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PubMed2000

Dynamic model of ex vivo granulocytic kinetics to examine the effects of oxygen tension, pH, and interleukin-3.

OBJECTIVE: Evaluating kinetics in hematopoietic cultures is complicated by the distribution of cells over various stages of differentiation and by the presence of cells from different lineages. Thus, an observed response is an integral response from distributed cell populations. Growth factors and other parameters can greatly affect the lineage and maturation stage of the culture outcome. To resolve the kinetics and more clearly define the differential effects of O(2) tension (pO(2)), pH, and interleukin-3 (IL-3) on granulopoiesis, a mathematical model-based approach was undertaken. MATERIALS AND METHODS: Granulocytic differentiation is described within a continuous, deterministic framework in which cells develop from primitive granulocytic progenitors to mature neutrophils. The model predicts two distributed populations-quiescent and cycling cells-by incorporating rates of growth, death, differentiation, and transition between quiescence and active cycling. The response of these four model processes to changes in the culture environment was examined. RESULTS: Model simulations of experimental data revealed the following: 1) pO(2) effects are exerted only on the growth rate but not maturation times. 2) pH effects between pH 7.25 and 7.4 on growth and differentiation are coupled; however, with increasing pH values, especially at pH 7. 6, the death rate for cells in the early stages of differentiation becomes increasingly significant. 3) The absence of IL-3 increases the death rate for primitive cells only minimally but markedly enhances the rate of differentiation through the myeloblast window in the differentiation pathway. The combined effects of these environmental factors can be predicted based on changes in the model parameters derived from the individual effects. CONCLUSIONS: Experimental data combined with mathematical modeling can elucidate the mechanisms underlying the regulation of granulopoiesis by pO(2), pH, and IL-3. The model also can be readily adapted to evaluate the effects of other culture conditions. The increased understanding of experimental results gained with this approach can be used to modify culture conditions to optimize ex vivo production of neutrophil precursors.

Antigens, CD34↗

PubMed1991

Oligomeric protein associations: transition from stochastic to deterministic equilibrium.

Transfer of electronic excitation energy (sensitized fluorescence) between donor and acceptor fluorophores separately attached to dimer or tetramer proteins is used to demonstrate the exchange of subunits among the undissociated particles. In dimers subjected to a pressure that produces half-dissociation, the exchange occurs at a rate that approaches the rate of dissociation. In the tetramers of glyceraldehydephosphate dehydrogenase and lactate dehydrogenase at 0 degrees C, the times for subunit exchange are nearly 2 orders of magnitude, and at room temperature 5-10 times longer than the time required to reach the dissociation equilibrium. By application of a novel method, pressure is shown to preferentially increase the rate of dissociation in dimers and decrease the rate of association in tetramers. From these observations, we conclude that the tetramers constitute a heterogeneous population, the members of which are dissociated by pressure according to individual molecular properties that can be retained over periods of time much longer than the time for equilibration of the dissociation. The dissociation of dimers exhibits the characteristics of the classical stochastic chemical equilibria, while those of the tetramers, like the more complex protein aggregates, must already be considered similar to the deterministic mechanical equilibria of macroscopic bodies.

Animals↗

PubMed2001

On the mod resc model and the evolution of Wolbachia compatibility types.

Cytoplasmic incompatibility (CI) is induced by the endocellular bacterium Wolbachia. It results in an embryonic mortality occurring when infected males mate with uninfected females. The mechanism involved is currently unknown, but the mod resc model allows interpretation of all observations made so far. It postulates the existence of two bacterial functions: modification (mod) and rescue (resc). The mod function acts in the males' germline, before Wolbachia are shed from maturing sperm. If sperm is affected by mod, zygote development will fail unless resc is expressed in the egg. Interestingly, CI is also observed in crosses between infected males and infected females when the two partners bear different Wolbachia strains, demonstrating that mod and resc interact in a specific manner: Two Wolbachia strains are compatible with each other only if they harbor the same compatibility type. Here we focus on the evolutionary process involved in the emergence of new compatibility types from ancestral ones. We argue that new compatibility types are likely to evolve under a wider range of conditions than previously thought, through a two-step process. First, new mod variants can arise by mutation and spread by drift. This is possible because mod is expressed in males and Wolbachia is transmitted by females. Second, once such a mod variant achieves a certain frequency, it can create the conditions for the deterministic invasion of a new resc variant, allowing the invasion of a new mod resc pair. Furthermore, we show that a stable polymorphism might be maintained in natural populations, allowing the long-term existence of "suicidal" Wolbachia strains.

Algorithms↗

PubMed1995

A method for computing the decision level for samples containing radioactivity in the presence of background.

It is often necessary to make a decision whether or not a sample contains radioactivity in excess of background. The most common procedure is a deterministic approach that compares the result from each sample against a critical level, Lc. Originally Lc was derived from the case where each sample is paired with a blank or control that is known not to contain excess radioactivity. However, most analytic laboratories do not process a blank with each and every sample. Another approach computes Lc using a collection of measurements to form a "well defined" background. This paper presents a method for determining a decision level, L delta, that includes the uncertainties in both the mean and variance of background and how these combine to form uncertainties in estimating the tails of the background distribution. The values of L delta are greater than Lc for a given Type I error. It can be applied whenever the true distribution of background is either normal or log normal. The process is not restricted to counting statistics and is valid for identifying excess contamination of any type providing that unknown samples are processed identically to background samples.

Biological Assay↗

PubMed1999

Parameter dependence of stochastic resonance in the stochastic Hodgkin-Huxley neuron.

Recently, the phenomena of stochastic resonance (SR) have attracted much attention in the studies of the excitable systems under inherent noise, in particular, nervous systems. We study SR in a stochastic Hodgkin-Huxley neuron under Ornstein-Uhlenbeck noise and periodic stimulus, focusing on the dependence of properties of SR on stimulus parameters. We find that the dependence of the critical forcing amplitude on the frequency of the periodic stimulus shows a bell-shaped structure with a minimum at the stimulus frequency, which is quite different from the monotonous dependence observed in the bistable system at a small frequency range. The frequency dependence of the critical forcing amplitude is explained in connection with the firing onset bifurcation curve of the Hodgkin-Huxley neuron in the deterministic situation. The optimal noise intensity for maximal amplification is also found to show a similar structure.

Animals↗

PubMed2002

Topologically inequivalent orbits induced by noise.

In this Letter we extend the concept of stochastic resonance. We show that in forced excitable systems noise can be responsible for the appearance of recurrences presenting a robust topological organization inequivalent to the periodic orbits of the deterministic system. As in stochastic resonance, these new structures are most pronounced at an optimal noise intensity.

Models, Theoretical↗

PubMed1986

The statistics of quantifiable homeostasis. I. Simple linear homeostasis.

The statistical properties are explored of the least-squares estimators of the parameters of a deterministic linear model for homeostasis with random, normally distributed technical errors. The parameters are: the amplitude of perturbation (A), the homing value (H), the restoration constant (B), and the lag time (L). The former two, although important in their own right, tell us nothing about the processes of biologic restitution and are thus considered "nuisance" parameters; the latter two are the "business" parameters, which tell us about the processes of biologic adjustment. The properties studied include bias and precision and their relationships to the number of data points and to the size of the technical error. Efforts have been concentrated on data points equally spaced over six lag times (which corresponds roughly to the period of observation used in loading studies, such as glucose tolerance tests). The distributions of these four estimators are studied in sets of 100 Monte Carlo simulations, each with 15, 30, and 100 data points, respectively. The estimators are virtually unbiased and all satisfactorily close to Gaussian. The residual mean-square errors (the divisor being four less than the number of data points, since four parameters are estimated) seem to be unbiased estimators of the variances of the errors. Moreover, when suitably scaled, the residual sums of squares have distributions close to the chi-square distribution for the appropriate degrees of freedom and with the corresponding means and variances. The correlations among the estimators are modest and, except where A is involved, small.

Homeostasis↗

PubMed1988

Earthquakes, influenza and cycles of Indian kala-azar.

It is suggested that previous data indicate 3 major epidemics of kala-azar in Assam between 1875 and 1950, with inter-epidemic periods of 30-45 and 20 years. This deviates from the popular view of regular cycles with a 10-20 year period. A deterministic mathematical model of kala-azar is used to find the simplest explanation for the timing of the 3 epidemics, paying particular attention to the role of extrinsic (drugs, natural disasters, other infectious diseases) versus intrinsic (host and vector dynamics, birth and death rates, immunity) processes in provoking the second. We conclude that, whilst widespread influenza in 1918-1919 may have magnified the second epidemic, intrinsic population processes provide the simplest explanation for its timing and synchrony throughout Assam. The model also shows that the second inter-epidemic period is expected to be shorter than the first, even in the absence of extrinsic agents, and highlights the importance of a small fraction of patients becoming chronically infectious (with post kala-azar dermal leishmaniasis) after treatment during an epidemic.

Disasters↗

PubMed2000

Pathological tremors: Deterministic chaos or nonlinear stochastic oscillators?

Pathological tremors exhibit a nonlinear oscillation that is not strictly periodic. We investigate whether the deviation from periodicity is due to nonlinear deterministic chaotic dynamics or due to nonlinear stochastic dynamics. To do so, we apply various methods from linear and nonlinear time series analysis to tremor time series. The results of the different methods suggest that the considered types of pathological tremors represent nonlinear stochastic second order processes. Finally, we evaluate whether two earlier proposed features capturing nonlinear effects in the time series allow for a discrimination between two pathological forms of tremor for a much larger sample of time series than previously investigated. (c) 2000 American Institute of Physics.

Journal Article↗

PubMed2006

Hybrid quantum processors: molecular ensembles as quantum memory for solid state circuits.

We investigate a hybrid quantum circuit where ensembles of cold polar molecules serve as long-lived quantum memories and optical interfaces for solid state quantum processors. The quantum memory realized by collective spin states (ensemble qubit) is coupled to a high-Q stripline cavity via microwave Raman processes. We show that, for convenient trap-surface distances of a few microm, strong coupling between the cavity and ensemble qubit can be achieved. We discuss basic quantum information protocols, including a swap from the cavity photon bus to the molecular quantum memory, and a deterministic two qubit gate. Finally, we investigate coherence properties of molecular ensemble quantum bits.

Journal Article↗

PubMed2005

Time reversal of ocean noise.

It has recently been shown [Roux et al., "Extracting coherent wave fronts from acoustic ambient noise in the ocean," J. Acoust. Soc. Am. 116, 1995-2003 (2004)] that the time-averaged correlation of ocean noise between two points yields a deterministic waveguide arrival structure embedded in the time-domain Green's function. By performing a set of these correlations between a vertical receive array and a single receiver, transfer functions necessary for time reversal can be extracted from ocean noise. Theory and simulation demonstrate this process and data of opportunity from the North Pacific Acoustic Laboratory experiment confirm the expected performance of a noise-based time reversal mirror.

Acoustics↗

PubMed2002

The duality of the brain and the multiplicity of minds: can you have it both ways?

Multiple Personality Disorder (MPD), now known as Dissociative Identity Disorder (DID), has been of great interest to the public for over a century. Case histories of MPD can be found in the literature as far back as the eighteenth century; nevertheless, publications from the latter part of the nineteenth century best describe this disorder as we know it today. This paper traces the case history literature of DID (MPD) from the earliest period to the present. This is done in such a way as to illuminate the basic theoretical and epistemological issues that are necessary to understand the process of dissociation (both normal, and abnormal aspects) and the role of hypnosis and its relationship to organic and 'hysterical epilepsy.' The theories of Fanet, Prince and Sidis are the major authorities discussed. The paper concludes with a discussion of the danger inherent in fostering a deterministic or reductionistic theory of consciousness.

Brain Diseases↗

PubMed2004

Automatic generation of lymphocyte heterogeneity: Division-dependent changes in the expression of CD27, CCR7 and CD45 by activated human naive CD4+ T cells are independently regulated.

Lymphocyte differentiation is a complex process regulated by the integration of signals received through a variety of cell surface receptors that results in populations of differentiated cells that have acquired novel characteristics and effector functions. Differentiation of T and B lymphocytes into effector cells, such as cytokine-secreting CD4+ T cells, cytotoxic CD8+ T cells and Ig-secreting B cells, as well as alterations in cell surface phenotype, have been reported to be associated with cell division. Nevertheless, the genesis of heterogeneity in effector cell type is unknown. A strictly deterministic view holds that heterogeneity arises from distinct signalling histories for each functionally or phenotypically different cell type. In contrast, a probabilistic interpretation proposes that internal stochastic regulation of gene expression gives rise to lymphocytes of mixed phenotypes. To help distinguish between these explanations, we examined the expression of CD27, CCR7, CD45RA and CD45RO by human naive CD4+ T cells in the context of the division history of the lymphocyte. Our results show that each marker independently changes with progressive divisions, strongly supporting the proposal that phenotypic heterogeneity in lymphocytes can arise as the result of independent stochastic processes controlling the expression of individual molecules.

Antibodies, Monoclonal↗

PubMed2005

Reverse engineering chemical structures from molecular descriptors: how many solutions?

Physical, chemical and biological properties are the ultimate information of interest for chemical compounds. Molecular descriptors that map structural information to activities and properties are obvious candidates for information sharing. In this paper, we consider the feasibility of using molecular descriptors to safely exchange chemical information in such a way that the original chemical structures cannot be reverse engineered. To investigate the safety of sharing such descriptors, we compute the degeneracy (the number of structure matching a descriptor value) of several 2D descriptors, and use various methods to search for and reverse engineer structures. We examine degeneracy in the entire chemical space taking descriptors values from the alkane isomer series and the PubChem database. We further use a stochastic search to retrieve structures matching specific topological index values. Finally, we investigate the safety of exchanging of fragmental descriptors using deterministic enumeration.

Chemical Engineering↗

PubMed2000

Comparison of deterministic and stochastic SIS and SIR models in discrete time.

The dynamics of deterministic and stochastic discrete-time epidemic models are analyzed and compared. The discrete-time stochastic models are Markov chains, approximations to the continuous-time models. Models of SIS and SIR type with constant population size and general force of infection are analyzed, then a more general SIS model with variable population size is analyzed. In the deterministic models, the value of the basic reproductive number R0 determines persistence or extinction of the disease. If R0 < 1, the disease is eliminated, whereas if R0 > 1, the disease persists in the population. Since all stochastic models considered in this paper have finite state spaces with at least one absorbing state, ultimate disease extinction is certain regardless of the value of R0. However, in some cases, the time until disease extinction may be very long. In these cases, if the probability distribution is conditioned on non-extinction, then when R0 > 1, there exists a quasi-stationary probability distribution whose mean agrees with deterministic endemic equilibrium. The expected duration of the epidemic is investigated numerically.

Disease Outbreaks↗

PubMed2001

Stochastic-convective transport with nonlinear reaction and mixing: application to intermediate-scale experiments in aerobic biodegradation in saturated porous media.

Aerobic biodegradation of benzoate by Pseudomonas cepacia sp. in a saturated heterogeneous porous medium was simulated using the stochastic-convective reaction (SCR) approach. A laboratory flow cell was randomly packed with low permeability silt-size inclusions in a high permeability sand matrix. In the SCR upscaling approach, the characteristics of the flow field are determined by the breakthrough of a conservative tracer. Spatial information on the actual location of the heterogeneities is not used. The mass balance equations governing the nonlinear and multicomponent reactive transport are recast in terms of reactive transports in each of a finite number of discrete streamtubes. The streamtube ensemble members represent transport via a steady constant average velocity per streamtube and a conventional Fickian dispersion term, and their contributions to the observed breakthroughs are determined by flux-averaging the streamtube solute concentrations. The resulting simulations were compared to those from a high-resolution deterministic simulation of the reactive transport, and to alternative ensemble representations involving (i) effective Fickian travel time distribution function, (ii) purely convective streamtube transport, and (iii) streamtube ensemble subset simulations. The results of the SCR simulation compare favorably to that of a sophisticated high-resolution deterministic approach.

Aerobiosis↗

PubMed2003

Explaining and predicting patterns in stochastic population systems.

Lattice effects in ecological time-series are patterns that arise because of the inherent discreteness of animal numbers. In this paper, we suggest a systematic approach for predicting lattice effects. We also show that an explanation of all the patterns in a population time-series may require more than one deterministic model, especially when the dynamics are complex.

Animals↗

PubMed2006

Stimulus-invariant processing and spectrotemporal reverse correlation in primary auditory cortex.

The spectrotemporal receptive field (STRF) provides a versatile and integrated, spectral and temporal, functional characterization of single cells in primary auditory cortex (AI). In this paper, we explore the origin of, and relationship between, different ways of measuring and analyzing an STRF. We demonstrate that STRFs measured using a spectrotemporally diverse array of broadband stimuli-such as dynamic ripples, spectrotemporally white noise, and temporally orthogonal ripple combinations (TORCs)-are very similar, confirming earlier findings that the STRF is a robust linear descriptor of the cell. We also present a new deterministic analysis framework that employs the Fourier series to describe the spectrotemporal modulations contained in the stimuli and responses. Additional insights into the STRF measurements, including the nature and interpretation of measurement errors, is presented using the Fourier transform, coupled to singular-value decomposition (SVD), and variability analyses including bootstrap. The results promote the utility of the STRF as a core functional descriptor of neurons in AI.

Acoustic Stimulation↗