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The kinesin walk: a dynamic model with elastically coupled heads.

Recently individual two-headed kinesin molecules have been studied in in vitro motility assays revealing a number of their peculiar transport properties. In this paper we propose a simple and robust model for the kinesin stepping process with elastically coupled Brownian heads that show all of these properties. The analytic and numerical treatment of our model results in a very good fit to the experimental data and practically has no free parameters. Changing the values of the parameters in the restricted range allowed by the related experimental estimates has almost no effect on the shape of the curves and results mainly in a variation of the zero load velocity that can be directly fitted to the measured data. In addition, the model is consistent with the measured pathway of the kinesin ATPase.

Adenosine Triphosphate↗

A model of the coupling between grip aperture and hand transport during human prehension.

It has been repeatedly demonstrated that the opening between the index finger and thumb (grasp component) during an object-directed reach-to-grasp movement achieves maximum aperture approximately two-thirds of the way through the duration of the reaching movement (transport component). Here we offer a quantitative model of the temporal coupling between grip aperture and wrist velocity which shows experimentally that the correlation between grip aperture and object size is a sigmoidal function of movement duration. When wrist velocity reaches its peak value, the correlation between the grip aperture and the size of the goal object has reached half of the correlation that is achieved by the end of the movement.

Hand↗

Computational model of electrically coupled, intrinsically distinct pacemaker neurons.

Electrical coupling between neurons with similar properties is often studied. Nonetheless, the role of electrical coupling between neurons with widely different intrinsic properties also occurs, but is less well understood. Inspired by the pacemaker group of the crustacean pyloric network, we developed a multicompartment, conductance-based model of a small network of intrinsically distinct, electrically coupled neurons. In the pyloric network, a small intrinsically bursting neuron, through gap junctions, drives 2 larger, tonically spiking neurons to reliably burst in-phase with it. Each model neuron has 2 compartments, one responsible for spike generation and the other for producing a slow, large-amplitude oscillation. We illustrate how these compartments interact and determine the dynamics of the model neurons. Our model captures the dynamic oscillation range measured from the isolated and coupled biological neurons. At the network level, we explore the range of coupling strengths for which synchronous bursting oscillations are possible. The spatial segregation of ionic currents significantly enhances the ability of the 2 neurons to burst synchronously, and the oscillation range of the model pacemaker network depends not only on the strength of the electrical synapse but also on the identity of the neuron receiving inputs. We also compare the activity of the electrically coupled, distinct neurons with that of a network of coupled identical bursting neurons. For small to moderate coupling strengths, the network of identical elements, when receiving asymmetrical inputs, can have a smaller dynamic range of oscillation than that of its constituent neurons in isolation.

Animals↗

A neural mass model for MEG/EEG: coupling and neuronal dynamics.

Although MEG/EEG signals are highly variable, systematic changes in distinct frequency bands are commonly encountered. These frequency-specific changes represent robust neural correlates of cognitive or perceptual processes (for example, alpha rhythms emerge on closing the eyes). However, their functional significance remains a matter of debate. Some of the mechanisms that generate these signals are known at the cellular level and rest on a balance of excitatory and inhibitory interactions within and between populations of neurons. The kinetics of the ensuing population dynamics determine the frequency of oscillations. In this work we extended the classical nonlinear lumped-parameter model of alpha rhythms, initially developed by Lopes da Silva and colleagues [Kybernetik 15 (1974) 27], to generate more complex dynamics. We show that the whole spectrum of MEG/EEG signals can be reproduced within the oscillatory regime of this model by simply changing the population kinetics. We used the model to examine the influence of coupling strength and propagation delay on the rhythms generated by coupled cortical areas. The main findings were that (1) coupling induces phase-locked activity, with a phase shift of 0 or pi when the coupling is bidirectional, and (2) both coupling and propagation delay are critical determinants of the MEG/EEG spectrum. In forthcoming articles, we will use this model to (1) estimate how neuronal interactions are expressed in MEG/EEG oscillations and establish the construct validity of various indices of nonlinear coupling, and (2) generate event-related transients to derive physiologically informed basis functions for statistical modelling of average evoked responses.

Algorithms↗

A fully coupled binary biochemical reactive-diffusion model with analytic solution.

Coupled multicomponent biochemical reactive diffusion underlies a variety of biological signalling processes and pharmacokinetic applications, such as paracrine signalling involving "cocktails" comprised of growth promoter/inhibitor factors and proteases associated with tumor angiogenesis, invasion and metastasis, extravascular drug delivery, and polymeric controlled-release drug codelivery design. Here, we present a model and develop a new analytic solution to illustrate the spatiotemporal behavior associated with fully coupled binary biochemical reactive diffusion. The complete coupling renders the solution appreciably more complex in structure and behavior than solutions for unicomponent or partially coupled models. Concentration behavior is illustrated by the computational simulation of binary-species tumor angiogenesis factor reactive-diffusion in the extravascular tissue matrix. The computational results indicate that (a) steady-state concentration profiles are achieved within 1 h of a change in factor production; (b) in the steady state, the spatial profiles of the two components tend to be similar; (c) exceedingly steep concentration gradients, involving several orders-of-magnitude differences in concentration over a few tenths of a millimeter, can occur in the vicinity of boundary sources due to inter-species reaction; (d) the concentration profiles of the two species differ from unicomponent predictions due to the simultaneous mass interchange between the two species. The analytic solution predictions are also used to provide a first-ever validation of a time-dependent, binary-component Crank-Nicholson numerical solution. The ability to quantitatively model interacting and often strongly varying concentration levels as a function of time and position can serve as a powerful complementary tool to experimental analyses for assessing disease state and interventional pharmacological efficacy, especially when the spatial scales on which in vivo behavior occurs taxes the limits of imaging capabilities.

Angiogenesis Inducing Agents↗

Electron-phonon coupling and a polaron in the t-J model: from the weak to the strong coupling regime.

We present numeric results for ground state and angle resolved photoemission spectra (ARPES) for a single hole in the t-J model coupled to optical phonons. The systematic-error-free diagrammatic Monte Carlo method is employed where the Feynman graphs for the Matsubara Green function in imaginary time are summed up completely with respect to phonon variables, while magnetic variables are subjected to the noncrossing approximation. We obtain that at electron-phonon coupling constants relevant for high T(c) cuprates the polaron undergoes a self-trapping crossover to the strong-coupling limit and theoretical ARPES demonstrate features observed in experiment: A broad peak in the bottom of the spectra has momentum dependence which coincides with that of a hole in the pure t-J model.

Journal Article↗

Experimental model for an ectopic focus coupled to ventricular cells.

BACKGROUND: We used a mathematical model of a sinoatrial nodal cell (SAN model) electrically coupled to real ventricular cells (VCs) to investigate action potential conduction from an automatic focus. METHODS AND RESULTS: Since input resistance of a VC is less than that of an SAN cell, coupling of the SAN model, with a size factor of 1, to a VC produced either (1) spontaneous pacing at the slower rate of the SAN model but without driving (activation) of the VC for lower values of coupling conductance (Gj) or (2) inhibition of pacing of the SAN model by electrical coupling to the VC for higher values of Gj. When the SAN model was adjusted in size to be 3 to 5 times larger than a sinoatrial nodal cell, thus making effective SAN model capacitance 3 to 5 times larger and input resistance 3 to 5 times smaller, the SAN model propagated activity to the coupled VC for Gj above a critical value. When the VC was paced at 1 Hz, the coupled cell pair demonstrated a stable rhythm of alternating cycle lengths and alternating conduction directions. By increasing pacing frequency to 2 Hz, we converted this rhythm to a regular 2-Hz frequency in which each action potential originated in the VC. More complex periodic interactions were observed at intermediate cycle lengths and lower or higher values of Gj. CONCLUSIONS: The phenomena we observed demonstrate the critical role of the size of an automatic focus as well as the coupling in the propagation of activity from the focus into surrounding myocardium.

Action Potentials↗

Calculations of one-, two- and three-bond nuclear spin-spin couplings in a model peptide and correlations with experimental data.

We present ab initio calculations of the Fermi contact term and experimental correlations of six coupling constants, 3JHNH alpha, 1JC alpha H alpha, 2JC'H alpha, 1JC alpha N, 2JC alpha N and 1JC'N, in a peptide as functions of the backbone dihedral angles, phi and psi. Given estimates of experimental uncertainties, we find semiquantitative experimental correlations for 3JHNH alpha, 1JC alpha N and 2JC alpha N, qualitative correlations for 1JC alpha H alpha and 2JC'H alpha, but no experimental correlations of practical utility for 1JC'N, owing to its complex dependence on at least four dihedral angles. Errors in the estimation of dihedral angles from X-ray crystallographic data for proteins, which result from uncertainties in atom-to-atom distances, place substantial limitations on the quantitative reliability of coupling constant calculations fitted to such data. In the accompanying paper [Edison, A.S. et al., J. Biomol. NMR, 4, 543-551] we apply the results of the coupling constant calculations presented here to the estimation of phi and psi angles in staphylococcal nuclease from experimental coupling constants.

Alanine↗

In-phase and antiphase self-oscillations in a model of two electrically coupled pacemakers.

The dynamic behavior of a model of two electrically coupled oscillatory neurons was studied while the external polarizing current was varied. It was found that the system with weak coupling can demonstrate one of five stable oscillatory modes: (1) in-phase oscillations with zero phase shift; (2) antiphase oscillations with half-period phase shift; (3) oscillations with any fixed phase shift depending on the value of the external polarizing current; (4) both in-phase and antiphase oscillations for the same current value, where the oscillation type depends on the initial conditions; (5) both in-phase and quasiperiodic oscillations for the same current value. All of these modes were robust, and they persisted despite small variations of the oscillator parameters. We assume that similar regimes, for example antiphase oscillations, can be detected in neurophysiological experiments. Possible applications to central pattern generator models are discussed.

Animals↗

The cultural context model: therapy for couples with domestic violence.

This article offers a brief analysis of heterosexual dominance within various cultures toward a larger understanding of domestic violence. It then describes the Cultural Context Model, developed over 15 years of experience treating domestic violence in its broader context, utilizing separate "culture circles" for men and women before and during couple therapy. It then identifies guidelines for assessment and intervention with a discussion of the special issues raised when substance abuse is involved.

Culture↗

Muscle-joint models incorporating activation dynamics, moment-angle, and moment-velocity properties.

Muscle input/output models incorporating activation dynamics, moment-angle, and moment-velocity factors are commonly used to predict the moment produced by muscle during nonisometric contractions; the three factors are generally assumed to be independent. We examined the ability of models with independent factors, as well as models with coupled factors, to fit input/output data measured during simultaneous modulation of the fraction of muscle stimulated (recruitment) and joint angle inputs. The models were evaluated in stimulated cat soleus muscles producing ankle extension moment, with regard to their potential applications in neuroprostheses with either fixed parameters or parameter adaptation. Both uncoupled and coupled models predicted the output moment well for random angle perturbation sizes ranging from 10 degrees to 30 degrees. For the uncoupled model, the best parameter values depended on the range of perturbations and the mean angle. Introducing coupling between activation and velocity in the model reduced this parameter sensitivity; one set of model parameter values fit the data for all perturbation sizes and also fit the data under isometric or constant stimulation conditions. Thus, the coupled model would be the most appropriate for applications requiring fixed parameter values. In contrast, with continuous parameter adaptation, errors due to changing test conditions decreased more quickly for the uncoupled model, suggesting that it would perform well in adaptive control of neuroprostheses.

Animals↗

Lower limits on R-parity-violating couplings in supersymmetric models with light squarks.

We interpret the results of searches for strongly interacting massive particles to place absolute lower limits on R-parity-violating couplings for squarks with mass (m(q) below 100 GeV. Recent searches for anomalous isotopes require that there be a baryon-number-violating or lepton-number-violating coupling larger than 10(-22)-10(-21) if m(q)>18 GeV. Using data from searches for stable particles at the CERN Large Electron Positron Collider (LEP) we demonstrate that this lower limit increases by 14 orders of magnitude, to an R-parity-violating coupling larger than 10(-8)-10(-7) for any squarks of mass less than 90 GeV. In the presence of an R-parity-violating coupling of this magnitude, neutralinos cannot explain the dark matter density in the Universe.

Journal Article↗

Structural determinations by circular dichroism spectra analysis using coupled oscillator methods: an update of the applications of the DeVoe polarizability model.

The exciton (coupled oscillator) model for optical activity is a very useful and powerful method which allows to analyze a circular dichroism (CD) spectrum in a nonempirical way, arriving at a safe assignment of the absolute configuration of organic and inorganic compounds. Usually in this model only the exciton coupling of two electrically allowed transitions (oscillators) is taken into account. This approach has the important advantage of an easy application but, sometimes, it may lead to wrong results. Thus, in this review article a more general treatment, which allows considering the simultaneous coupling of several oscillators, i.e., the DeVoe model, is presented and critically analyzed, discussing in detail the latest applications reported in the literature. In the authors opinion, since the DeVoe model joins generality and reliability requiring an almost negligible computational effort, it represents the method of choice for stereochemical assignments, even by nonspecialists.

Journal Article↗

Neurovascular coupling in terms of a control system: validation of a second-order linear system model.

Neurovascular coupling (NC) adapts cerebral blood flow to cortical activity. Functional transcranial Doppler (f-TCD) investigations revealed a typical time course of evoked blood flow responses with an initial overshoot and a stabilization at a lower, but stable, level. This blood flow reaction can be described in terms of a control-system model. We tested reliability and validity of this new approach using different stimulation paradigms. The P2 segment of the posterior cerebral artery was insonated in 14 healthy volunteers and, subsequently, NC was stimulated using two tests, a checkerboard stimulus of 1 s with different repetition rates and a reading test. Data were analyzed according to algorithms of control-system theory. The reading test was used to measure test reliability and side differences. A second-order linear system can describe blood flow regulation of NC. Different stimulation protocols of the checkerboard test and the related evoked blood flow curves could be described by the same control-system model. Further, there were no differences between the checkerboard and reading test nor between right and left side or test and retest of the reading test. NC can be described in a much more detailed manner using control-system analysis. We were able to show that blood flow response due to different visual stimuli follow one common control-system model. Unlike quantification of NC using overshoot, parameters of the control system have smaller SDs, increasing the statistical power and, thereby, usefulness of f-TCD as a diagnostic instrument.

Adult↗