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An energy-conserving one-way coupled mode propagation model.

The equations of motion for pressure and displacement fields in a waveguide have been used to derive an energy-conserving, one-way coupled mode propagation model. This model has three important properties: First, since it is based on the equations of motion, rather than the wave equation, instead of two coupling matrices, it only contains one coupling matrix. Second, the resulting coupling matrix is anti-symmetric, which implies that the energy among modes is conserved. Third, the coupling matrix can be computed using the local modes and their depth derivatives. The model has been applied to two range-dependent cases: Propagation in a wedge, where range dependence is due to variations in water depth and propagation through internal waves, where range dependence is due to variations in water sound speed. In both cases the solutions are compared with those obtained from the parabolic equation (PE) method.

Acoustics↗

Wave instability induced by nonlocal spatial coupling in a model of the light-sensitive Belousov-Zhabotinsky reaction.

We study spatiotemporal patterns resulting from instabilities induced by nonlocal spatial coupling in the Oregonator model of the light-sensitive Belousov-Zhabotinsky reaction. In this system, nonlocal coupling can be externally imposed by means of an optical feedback loop which links the intensity of locally applied illumination with the activity in a certain vicinity of a particular point weighted by a given coupling function. This effect is included in the three-variable Oregonator model by an additional integral term in the photochemically induced bromide flow. A linear stability analysis of this modified Oregonator model predicts that wave and Turing instabilities of the homogeneous steady state can be induced for experimentally realistic parameter values. In particular, we find that a long-range inhibition in the optical feedback leads to a Turing instability, while a long-range activation induces wave patterns. Using a weakly nonlinear analysis, we derive amplitude equations for the wave instability which are valid close to the instability threshold. Therein, we find that the wave instability occurs supercritically or subcritically and that traveling waves are preferred over standing waves. The results of the theoretical analysis are in good agreement with numerical simulations of the model near the wave instability threshold. For larger distances from threshold, a secondary breathing instability is found for traveling waves.

Journal Article↗

[Evaluation of the effect of cardiotropic agents using a mathematical model of electromechanical coupling].

An assessment of the ionic action mechanism of cardiotropic substances with the aid of a mathematical model for excitation-contraction coupling in myocardium is proved to be possible. The technique developed consists in the model parameter identification from the experimental data on electrical and mechanical activity of myocardial strip. The validity of the technique is tested using the known mechanism drugs. An example is given of analysis by the technique suggested of the action mechanism of diltiazem on the rat papillary muscle.

Animals↗

Alternating oscillations and chaos in a model of two coupled biochemical oscillators driving successive phases of the cell cycle.

The animal cell cycle is controlled by the periodic variation of two cyclin-dependent protein kinases, cdk1 and cdk2, which govern the entry into the M (mitosis) and S (DNA replication) phases, respectively. The ordered progression between these phases is achieved thanks to the existence of checkpoint mechanisms based on mutual inhibition of these processes. Here we study a simple theoretical model for oscillations in cdk1 and cdk2 activity, involving mutual inhibition of the two oscillators. Each minimal oscillator is described by a three-variable cascade involving a cdk, together with the associated cyclin and cyclin-degrading enzyme. The dynamics of this skeleton model of coupled oscillators is determined as a function of the strength of their mutual inhibition. The most common mode of dynamic behavior, obtained under conditions of strong mutual inhibition, is that of alternating oscillations in cdk1 and cdk2, which correspond to the physiological situation of the ordered recurrence of the M and S phases. In addition, for weaker inhibition we obtain evidence for a variety of dynamic phenomena such as complex periodic oscillations, chaos, and the coexistence between multiple periodic or chaotic attractors. We discuss the conditions of occurrence of these various modes of oscillatory behavior, as well as their possible physiological significance.

Cell Cycle↗

A model for the coupling between cerebral blood flow and oxygen metabolism during neural stimulation.

A general mathematical model for the delivery of O2 to the brain is presented, based on the assumptions that all of the brain capillaries are perfused at rest and that all of the oxygen extracted from the capillaries is metabolized. The model predicts that disproportionately large changes in blood flow are required in order to support small changes in the O2 metabolic rate. Interpreted in terms of this model, previous positron emission tomography (PET) studies of the human brain during neural stimulation demonstrating that cerebral blood flow (CBF) increases much more than the oxygen metabolic rate are consistent with tight coupling of flow and oxidative metabolism. The model provides a basis for the quantitative interpretation of functional magnetic resonance imaging (fMRI) studies in terms of changes in local CBF.

Brain↗

Hybrid molecular-continuum fluid models: implementation within a general coupling framework.

Over the past three years we have been developing a new approach for the modelling and simulation of complex fluids. This approach is based on a multiscale hybrid scheme, in which two or more contiguous subdomains are dynamically coupled together. One subdomain is described by molecular dynamics while the other is described by continuum fluid dynamics; such coupled models are of considerable importance for the study of fluid dynamics problems in which only a restricted aspect requires a fully molecular representation. Our model is representative of the generic set of coupled models whose algorithmic structure presents interesting opportunities for deployment on a range of architectures including computational grids. Here we describe the implementation of our HybridMD code within a coupling framework that facilitates flexible deployment on such architectures.

Computer Simulation↗

Internal forward models in the cerebellum: fMRI study on grip force and load force coupling.

Internal models are neural mechanisms that can mimic the input-output or output-input properties of the motor apparatus and external objects. Forward internal models predict sensory consequences from efference copies of motor commands. There is growing acceptance of the idea that forward models are important in sensorimotor integration as well as in higher cognitive function, but their anatomical loci and neural mechanisms are still largely unknown. Some of the most convincing evidence that the central nervous system (CNS) makes use of forward models in sensory motor control comes from studies on grip force-load force coupling. We first present a brief review of recent computational and behavioral studies that provide decisive evidence for the utilization of forward models in grip force-load force coupling tasks. Then, we used functional magnetic resonance imaging (fMRI) to measure the brain activity related to this coupling and demonstrate that the cerebellum is the most likely site for forward models to be stored.

Adult↗

Acute leukemia and chemotherapy: a modeling viewpoint.

A couple of models of acute myeloblastic leukemia (AML) are proposed. Normal and leukemic cells are assumed to exist side-by-side with the two cell populations obeying Gompertzian dynamics but with the leukemic cells exercising inhibition over the normal cells. The kinetic equations and steady-state properties of one of the models is analytically obtained. Possible situations of detection or nondetection of malignancy are then discussed. Based on the models of AML, a treatment model is proposed and numerically simulated. Consequently, the option of aggressive treatment of the disease with heavy doses of drugs is shown to be a plausible and worthwhile chemotherapeutic strategy.

Antineoplastic Agents↗

[Modeling of mechanoelectric coupling in cardiomyocytes in norm and pathology].

We developed mathematical models of the electromechanical function of cardiomyocytes and the simplest mechanically heterogeneous myocardial systems, muscle duplexes. By means of these models we studied the contribution of mechanoelectric feedbacks to the contractile activity of the myocardium in norm and pathology. In particular, we simulated and clarified the effects of mechanical conditions on both the form and the duration of the action potential during contractions. From this standpoint different kinds of myocardium mechanical heterogeneity were analyzed. As we have established, the latter can play both a positive and a negative role, depending on the distribution of mechanical nonuniformity and the sequence of activation of heterogeneous myocardium system elements. By means of the same models, we studied the contribution of mechanical factors to the arrhythmogenicity in the case of the cardiomyocyte calcium overload caused by the attenuation of the sodium-potassium pump and outlined the ways for correcting the contractile function in these disturbances.

Action Potentials↗

Suppression of chaos and other dynamical transitions induced by intercellular coupling in a model for cyclic AMP signaling in Dictyostelium cells.

The effect of intercellular coupling on the switching between periodic behavior and chaos is investigated in a model for cAMP oscillations in Dictyostelium cells. We first analyze the dynamic behavior of a homogeneous cell population which is governed by a three-variable differential system for which bifurcation diagrams are obtained as a function of two control parameters. We then consider the mixing of two populations behaving in a chaotic and periodic manner, respectively. Cells are coupled through the sharing of a common chemical intermediate, extracellular cAMP, which controls its production and release by the cells into the extracellular medium; the dynamics of the mixed suspension is governed by a five-variable differential system. When the two cell populations differ by the value of a single parameter which measures the activity of the enzyme that degrades extracellular cAMP, the bifurcation diagram established for the three-variable homogeneous population can be used to predict the dynamic behavior of the mixed suspension. The analysis shows that a small proportion of periodic cells can suppress chaos in the mixed suspension. Such a fragility of chaos originates from the relative smallness of the domain of aperiodic oscillations in parameter space. The bifurcation diagram is used to obtain the minimum fraction of periodic cells suppressing chaos. These results are related to the suppression of chaos by the small-amplitude periodic forcing of a strange attractor. Numerical simulations further show how the coupling of periodic cells with chaotic cells can produce chaos, bursting, simple periodic oscillations, or a stable steady state; the coupling between two populations at steady state can produce similar modes of dynamic behavior.

Journal Article↗

Nonlinear local electrovascular coupling. I: A theoretical model.

Here we present a detailed biophysical model of how brain electrical and vascular dynamics are generated within a basic cortical unit. The model was obtained from coupling a canonical neuronal mass and an expandable vasculature. In this proposal, we address several aspects related to electroencephalographic and functional magnetic resonance imaging data fusion: (1) the impact of the cerebral architecture (at different physical levels) on the observations; (2) the physiology involved in electrovascular coupling; and (3) energetic considerations to gain a better understanding of how the glucose budget is used during neuronal activity. The model has three components. The first is the canonical neural mass model of three subpopulations of neurons that respond to incoming excitatory synaptic inputs. The generation of the membrane potentials in the somas of these neurons and the electric currents flowing in the neuropil are modeled by this component. The second and third components model the electrovascular coupling and the dynamics of vascular states in an extended balloon approach, respectively. In the first part we describe, in some detail, the biophysical model and establish its face validity using simulations of visually evoked responses under different flickering frequencies and luminous contrasts. In a second part, a recursive optimization algorithm is developed and used to make statistical inferences about this forward/generative model from actual data.

Brain↗

Carbon and nitrogen fluxes across the Hebridean shelf break, estimated by a 2D coupled physical-microbiological model.

A two-dimensional coupled physical-biological model is described and used to compute the annual cycle of primary production across the Hebridean shelf and slope based on information collected during the Land Ocean Interaction Study (LOIS), with the focus on data for 1995. Calculations of modelled carbon and nitrate fluxes indicate an annual on-shelf near-surface flux of nitrate of 65 kmol N m(-1) year(-1) at the top of the slope (140 m deep) and an off-shelf near-bottom carbon flux of 23 kmol C m(-1) year(-1). Further down the slope (at 300 m deep) the on-shelf nitrate flux increased to 126 kmol N m(-1) year(-1) and the off-shelf carbon flux increased to 41 kmol C m(-1) year(-1). Carbon deposition to the sea floor was less than 0.4 mol C m(-2) year(-1) on the upper slope and 1.1 mol C m(-2) year(-1) lower down the slope, values which are four-fold lower than those inferred from benthic oxygen demand measurements made during the Shelf Edge Study but of similar magnitude to observations made during OMEX I.

Atlantic Ocean↗

An elementary kinetic model of energy coupling in biological membranes.

The purpose of this work is to contribute to the understanding of the fundamental kinetic properties of the processes of energy coupling in biological membranes. For this, we consider a model of a microorganism that, in its plasma membrane, expresses two electrogenic enzymes (E(1) and E(2)) transporting the same monovalent cation C and electrodiffusive paths for C and for a monovalent anion A. E(1) (E(2)) couples transport C to the reaction S(1)<-->P(1) (S(2)<-->P(2)). We developed a mathematical model that describes the rate of change of the electrical potential difference across the membrane, of the internal concentrations of C and A, and of the concentrations of S(2) and P(2). The enzymes are incorporated via two-state kinetic models; the passive ionic fluxes are represented by classical formulations of electrodiffusion. The microorganism volume is maintained constant by accessory regulatory devices. The model is utilized for stationary and dynamic studies for the case of bacteria employing the electrochemical gradient of Na(+) as energetic intermediate. Among other conclusions, the results show that the membrane potential represents the relevant kinetic intermediate for the overall coupling between the energy donor reaction S(1)<-->P(1) and the synthesis of S(2).

Bacteria↗

Frequency-dependent hyperpolarizabilities of the Ne, Ar, and Kr atoms using the approximate coupled cluster triples model CC3.

The frequency-dependent electric field-induced second harmonic generation (ESHG) second hyperpolarizabilities gamma of neon, argon, and krypton are calculated using the approximate coupled cluster triples model CC3. Systematic basis set investigations are carried out to establish basis set limits, and scalar relativistic effects are accounted for by direct perturbation theory. To estimate higher-order correlation effects, full configuration-interaction results are used to benchmark the accuracy of CC3. The best theoretical estimates obtained thereby for the static second hyperpolarizabilities gamma(0) are 107.4, 1159, and 2589 a.u. for neon, argon, and krypton, respectively. These values as well as the results for the dispersion curve of the parallel component gamma( parallel) agree well with the latest experimental values from electric field-induced second harmonic generation. In addition, the dispersion of the perpendicular component gamma( perpendicular) and the hyperpolarizability ratios gamma( parallel)gamma( perpendicular) has been studied for the first time on a consistently correlated ab initio level. The analysis of the results indicates that, in particular for neon and krypton, the presently available experimental values are flawed.

Journal Article↗

Modeling a longitudinally coupled dual-mode leaky-SAW resonator filter with enhanced upper-sideband suppression.

Recently, it has been experimentally reported that enhanced upper-sideband suppression of a longitudinally coupled (first/third) dual-mode leaky SAW (LSAW) resonator filter may be obtained by incorporation of a selectively valued capacitor between input and output terminals. In this paper, coupling-of-modes (COM) and bandstop-filter modeling is applied to realize this enhanced suppression. Tradeoffs are examined between upper and lower side-band suppression levels caused by the ensuing capacitive coupling between input and output terminals. Good agreement is obtained between this theory and reported experimental results for an 800-MHz band cellular filter.

Journal Article↗

Paired moving charges in mitochondrial energy coupling.

A model of mitochondrial energy coupling has been proposed based on the principles of paired charge separation and vectorial paired charge flow. The unique role of the electron transfer chain and ionophores in mediating charge separation is emphasized.

Biological Transport, Active↗

A model of the coupling between brain electrical activity, metabolism, and hemodynamics: application to the interpretation of functional neuroimaging.

In order to improve the interpretation of functional neuroimaging data, we implemented a mathematical model of the coupling between membrane ionic currents, energy metabolism (i.e., ATP regeneration via phosphocreatine buffer effect, glycolysis, and mitochondrial respiration), blood-brain barrier exchanges, and hemodynamics. Various hypotheses were tested for the variation of the cerebral metabolic rate of oxygen (CMRO(2)): (H1) the CMRO(2) remains at its baseline level; (H2) the CMRO(2) is enhanced as soon as the cerebral blood flow (CBF) increases; (H3) the CMRO(2) increase depends on intracellular oxygen and pyruvate concentrations, and intracellular ATP/ADP ratio; (H4) in addition to hypothesis H3, the CMRO(2) progressively increases, due to the action of a second messenger. A good agreement with experimental data from magnetic resonance imaging and spectroscopy (MRI and MRS) was obtained when we simulated sustained and repetitive activation protocols using hypotheses (H3) or (H4), rather than hypotheses (H1) or (H2). Furthermore, by studying the effect of the variation of some physiologically important parameters on the time course of the modeled blood-oxygenation-level-dependent (BOLD) signal, we were able to formulate hypotheses about the physiological or biochemical significance of functional magnetic resonance data, especially the poststimulus undershoot and the baseline drift.

Adenosine Triphosphate↗

Repetitive BOP coupling (REBOP) in solid phase peptide synthesis. Luliberin synthesis as model.

The coupling reagent (benzotriazol-1-yloxy)tris-(dimethylamino)phosphonium (BOP) hexafluorophosphate was tested in the synthesis of luliberin (LH-RH) with inexpensive classically protected Boc-amino acids, in slight excess, and benzhydryl amino resin, without any other additive. The good solubility of this reagent and its by-products is of particular interest for automated peptide synthesis. [D-His2]LH-RH was also synthesized and compared with LH-RH by proton nuclear magnetic resonance spectroscopy. As shown by the biological tests and the high performance liquid chromatography study, unprotected pyroGlu and Boc-His can be used without any significant racemization but Boc-His(Boc) was found to be preferable since it gave no detectable racemization and no by-products. The difficult isolation of the minority D-derivative from the crude preparation of LH-RH was resolved by a recycling procedure in reversed phase HPLC.

Amino Acid Sequence↗