Multistable Pulse-like Solutions in a Parametrically Driven Ginzburg-Landau Equation

It is well known that pulse-like solutions of the cubic complex Ginzburg-Landau equation are unstable but can be stabilised by the addition of quintic terms. In this paper we explore an alternative mechanism where the role of the stabilising agent is played by the parametric driver. Our analysis is based on the numerical continuation of solutions in one of the parameters of the Ginzburg-Landau equation (the diffusion coefficient $c$), starting from the nonlinear Schr\"odinger limit (for which $c=0$). The continuation generates, recursively, a sequence of coexisting stable solutions with increasing number of humps. The sequence "converges" to a long pulse which can be interpreted as a bound state of two fronts with opposite polarities.Comment: 13 pages, 6 figures; to appear in PR

A Role for Rebinding in Rapid and Reliable T Cell Responses to Antigen

Experimental work has shown that T cells of the immune system rapidly and specifically respond to antigenic molecules presented on the surface of antigen-presenting-cells and are able to discriminate between potential stimuli based on the kinetic parameters of the T cell receptor-antigen bond. These antigenic molecules are presented among thousands of chemically similar endogenous peptides, raising the question of how T cells can reliably make a decision to respond to certain antigens but not others within minutes of encountering an antigen presenting cell. In this theoretical study, we investigate the role of localized rebinding between a T cell receptor and an antigen. We show that by allowing the signaling state of individual receptors to persist during brief unbinding events, T cells are able to discriminate antigens based on both their unbinding and rebinding rates. We demonstrate that T cell receptor coreceptors, but not receptor clustering, are important in promoting localized rebinding, and show that requiring rebinding for productive signaling reduces signals from a high concentration of endogenous pMHC. In developing our main results, we use a relatively simple model based on kinetic proofreading. However, we additionally show that all our results are recapitulated when we use a detailed T cell receptor signaling model. We discuss our results in the context of existing models and recent experimental work and propose new experiments to test our findings

Barcoding T Cell Calcium Response Diversity with Methods for Automated and Accurate Analysis of Cell Signals (MAAACS)

International audienceWe introduce a series of experimental procedures enabling sensitive calcium monitoring in T cell populations by confocal video-microscopy. Tracking and post-acquisition analysis was performed using Methods for Automated and Accurate Analysis of Cell Signals (MAAACS), a fully customized program that associates a high throughput tracking algorithm, an intuitive reconnection routine and a statistical platform to provide, at a glance, the calcium barcode of a population of individual T-cells. Combined with a sensitive calcium probe, this method allowed us to unravel the heterogeneity in shape and intensity of the calcium response in T cell populations and especially in naive T cells, which display intracellular calcium oscillations upon stimulation by antigen presenting cells

Resonant spatio-temporal forcing of oscillatory media

An extension of the complex Ginzburg-Landau equation describing resonant spatio-temporal forcing of oscillatory media is investigated. Periodic forcing in space and time leads to spatial structures with two different symmetries: harmonic patterns with the same and subharmonic patterns with twice the wavelength of the external forcing. A linear stability analysis of the homogeneous state carried out analytically leads to subharmonic patterns for intermediate forcing strength, while harmonic modes prevail for very weak and strong forcing amplitudes. Numerical simulations confirm the analytical predictions for weak forcing and show coexistence between the two types of patterns beyond threshold. In addition, traveling localized patterns such as phase flips in subharmonic patterns and traveling patches of subharmonic patterns in a harmonic background have been discovered. In the parameter range of Benjamin-Feir turbulence, stable subharmonic patterns occur upon forcing, which undergo a transition scenario back to irregular dynamics for increasing values of the control parameter

Resonant spatio-temporal forcing of oscillatory media

An extension of the complex Ginzburg-Landau equation describing resonant spatio-temporal forcing of oscillatory media is investigated. Periodic forcing in space and time leads to spatial structures with two different symmetries: harmonic patterns with the same and subharmonic patterns with twice the wavelength of the external forcing. A linear stability analysis of the homogeneous state carried out analytically leads to subharmonic patterns for intermediate forcing strength, while harmonic modes prevail for very weak and strong forcing amplitudes. Numerical simulations confirm the analytical predictions for weak forcing and show coexistence between the two types of patterns beyond threshold. In addition, traveling localized patterns such as phase flips in subharmonic patterns and traveling patches of subharmonic patterns in a harmonic background have been discovered. In the parameter range of Benjamin-Feir turbulence, stable subharmonic patterns occur upon forcing, which undergo a transition scenario back to irregular dynamics for increasing values of the control parameter

Lytic versus stimulatory synapse in cytotoxic T lymphocyte/target cell interaction: manifestation of a dual activation threshold.

Activation of biological functions in T lymphocytes is determined by the molecular dynamics occurring at the T cell/opposing cell interface. In the present study, a central question of cytotoxic T lymphocyte (CTL) biology was studied at the single-cell level: can two distinct activation thresholds for cytotoxicity and cytokine production be explained by intercellular molecular dynamics between CTLs and targets? In this study, we combine morphological approaches with numerical analysis, which allows us to associate specific patterns of calcium mobilization with different biological responses. We show that CTLs selectively activated to cytotoxicity lack a mature immunological synapse while exhibiting a low threshold polarized secretion of lytic granules and spike-like patterns of calcium mobilization. This finding is contrasted by fully activated CTLs, which exhibit a mature immunological synapse and smooth and sustained calcium mobilization. Our results indicate that intercellular molecular dynamics and signaling characteristics allow the definition of two activation thresholds in individual CTLs: one for polarized granule secretion (lytic synapse formation) and the other for cytokine production (stimulatory synapse formation)

Lytic versus stimulatory synapse in cytotoxic T lymphocyte/target cell interaction: manifestation of a dual activation threshold.

Activation of biological functions in T lymphocytes is determined by the molecular dynamics occurring at the T cell/opposing cell interface. In the present study, a central question of cytotoxic T lymphocyte (CTL) biology was studied at the single-cell level: can two distinct activation thresholds for cytotoxicity and cytokine production be explained by intercellular molecular dynamics between CTLs and targets? In this study, we combine morphological approaches with numerical analysis, which allows us to associate specific patterns of calcium mobilization with different biological responses. We show that CTLs selectively activated to cytotoxicity lack a mature immunological synapse while exhibiting a low threshold polarized secretion of lytic granules and spike-like patterns of calcium mobilization. This finding is contrasted by fully activated CTLs, which exhibit a mature immunological synapse and smooth and sustained calcium mobilization. Our results indicate that intercellular molecular dynamics and signaling characteristics allow the definition of two activation thresholds in individual CTLs: one for polarized granule secretion (lytic synapse formation) and the other for cytokine production (stimulatory synapse formation)