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Voltage distribution in sub-cellular micro-domains such as neuronal synapses, small protrusions or dendritic spines regulates the opening and closing of ionic channels, energy production and thus cellular homeostasis and excitability. Yet how voltage changes at such a small scale in vivo remains challenging due to the experimental diffraction limit, large signal fluctuations and the still limited resolution of fast voltage indicators. Here, we study the voltage distribution in nano-compartments using a computational approach based on the Poisson-Nernst-Planck equations for the electro-diffusion motion of ions, where inward and outward fluxes are generated between channels. We report a current-voltage (I-V) logarithmic relationship generalizing Nernst law that reveals how the local membrane curvature modulates the voltage. We further find that an influx current penetrating a cellular electrolyte can lead to perturbations from tens to hundreds of nanometers deep depending on the local channels organization. Finally, we show that the neck resistance of dendritic spines can be completely shunted by the transporters located on the head boundary, facilitating ionic flow. To conclude, we propose that voltage is regulated at a subcellular level by channels organization, membrane curvature and narrow passages., Comment: 9 pages, 5 figures, 1 table

The flow of ions through permeable channels causes voltage drop in physiological nanodomains such as synapses, dendrites and dendritic spines, and other protrusions. How the voltage changes around channels in these nanodomains has remained poorly studied. We focus this book chapter on summarizing recent efforts in computing the steady-state current, voltage and ionic concentration distributions based on the Poisson-Nernst-Planck equations as a model of electro-diffusion. We first consider the spatial distribution of an uncharged particle density and derive asymptotic formulas for the concentration difference by solving the Laplace's equation with mixed boundary conditions. We study a constant particles injection rate modeled by a Neumann flux condition at a channel represented by a small boundary target, while the injected particles can exit at one or several narrow patches. We then discuss the case of two species (positive and negative charges) and take into account motions due to both concentration and electrochemical gradients. The voltage resulting from charge interactions is calculated by solving the Poisson's equation. We show how deep an influx diffusion propagates inside a nanodomain, for populations of both uncharged and charged particles. We estimate the concentration and voltage changes in relations with geometrical parameters and quantify the impact of membrane curvature., Comment: 17 pages, 8 figures, 1 table

End-to-end image and video compression using auto-encoders (AE) offers new appealing perspectives in terms of rate-distortion gains and applications. While most complex models are on par with the latest compression standard like VVC/H.266 on objective metrics, practical implementation and complexity remain strong issues for real-world applications. In this paper, we propose a practical implementation suitable for realistic applications, leading to a low-complexity model. We demonstrate that some gains can be achieved on top of a state-of-the-art low-complexity AE, even when using simpler implementation. Improvements include off-training entropy coding improvement and encoder side Rate Distortion Optimized Quantization. Results show a 19% improvement in BDrate on basic implementation of fully-factorized model, and 15.3% improvement compared to the original implementation. The proposed implementation also allows a direct integration of such approaches on a variety of platforms.

Cellular networks are often composed of thin tubules connecting much larger node compartments. These structures serve for active or diffusion transport of proteins. Examples are glial networks in the brain, the endoplasmic reticulum in cells or dendritic spines located on dendrites. In this latter case, a large ball forming the head is connected by a narrow passage. In all cases, how the transport of molecules, ions or proteins is regulated determines the time scale of chemical reactions or signal transduction. In the present study, based on modeling diffusion in three dimensions, we compute the mean time for a Brownian particle to reach a narrow target inside such a composite network made of tubules connected to spherical nodes. We derive asymptotic formulas by solving a mixed Neumann-Dirichlet boundary value problem with small Dirichlet part. We first consider the case of a network domain organized in a 2-D lattice structure that consists of spherical ball compartments connected via narrow cylindrical passages. When there is a single target we derive a matrix equation for each Mean First Passage Time (MFPT) averaged over each spherical compartment. We then consider a composite domain consisting of a spherical head-like domain connected to a large cylinder via a narrow cylindrical neck. For Brownian particles starting within the narrow neck, we derive formulas for the MFPT to reach a target on the spherical head. When diffusing particles can be absorbed upon hitting additional absorbing boundaries of the large cylinder, we compute the probability and conditional MFPT to reach a target. We compare these formulas with numerical solutions of the mixed boundary value problem and with Brownian simulations. To conclude, the present analysis reveals that the mean arrival time, driven by diffusion in heterogeneous networks, is controlled by the target and narrow passage sizes., Comment: 33 pages and 13 figures

When a flux of Brownian particles is injected in a narrow window located on the surface of a bounded domain, these particles diffuse and can eventually escape through a cluster of narrow windows. At steady-state, we compute asymptotically the distribution of concentration between the different windows. The solution is obtained by solving Laplace's equation using Green's function techniques and second order asymptotic analysis, and depends on the influx amplitude, the diffusion properties as well as the geometrical organization of all the windows, such as their distances and the mean curvature. We explore the range of validity of the present asymptotic expansions using numerical simulations of the mixed boundary value problem. Finally, we introduce a length scale to estimate how deep inside a domain a local diffusion current can spread. We discuss some applications in biophysics., Comment: 28 pages and 11 figures

Precursor gradients in a reaction-diffusion system are spatially varying coefficients in the reaction-kinetics. Such gradients have been used in various applications, such as the head formation in the Hydra, to model the effect of pre-patterns and to localize patterns in various spatial regions. For the 1-D Gierer-Meinhardt (GM) model we show that a simple precursor gradient in the decay rate of the activator can lead to the existence of stable, asymmetric, two-spike patterns, corresponding to localized peaks in the activator of different heights. This is a qualitatively new phenomena for the GM model, in that asymmetric spike patterns are all unstable in the absence of the precursor field. Through a determination of the global bifurcation diagram of two-spike steady-state patterns, we show that asymmetric patterns emerge from a supercritical symmetry-breaking bifurcation along the symmetric two-spike branch as a parameter in the precursor field is varied. Through a combined analytical-numerical approach we analyze the spectrum of the linearization of the GM model around the two-spike steady-state to establish that portions of the asymmetric solution branches are linearly stable. In this linear stability analysis a new class of vector-valued nonlocal eigenvalue problem (NLEP) is derived and analyzed., Comment: 22 pages, 14 figures

We study the dynamics of systems consisting of two spatially segregated ODE compartments coupled through a one-dimensional bulk diffusion field. For this coupled PDE-ODE system, we first employ a multi-scale asymptotic expansion to derive amplitude equations near codimension-one Hopf bifurcation points for both in-phase and anti-phase synchronization modes. The resulting normal form equations pertain to any vector nonlinearity restricted to the ODE compartments. In our first example, we apply our weakly nonlinear theory to a coupled PDE-ODE system with Sel'kov membrane kinetics, and show that the symmetric steady state undergoes supercritical Hopf bifurcations as the coupling strength and the diffusivity vary. We then consider the PDE diffusive coupling of two Lorenz oscillators. It is shown that this coupling mechanism can have a stabilizing effect, characterized by a significant increase in the Rayleigh number required for a Hopf bifurcation. Within the chaotic regime, we can distinguish between synchronous chaos, where both the left and right oscillators are in-phase, and chaotic states characterized by the absence of synchrony. Finally, we compute the largest Lyapunov exponent associated with a linearization around the synchronous manifold that only considers odd perturbations. This allows us to predict the transition to synchronous chaos as the coupling strength and the diffusivity increase., Comment: 20 pages, 12 figures

Reaction-diffusion systems have been widely used to study spatio-temporal phenomena in cell biology, such as cell polarization. Coupled bulk-surface models naturally include compartmentalization of cytosolic and membrane-bound polarity molecules. Here we study the distribution of the polarity protein Cdc42 in a mass-conserved membrane-bulk model, and explore the effects of diffusion and spatial dimensionality on spatio-temporal pattern formation. We first analyze a 1-D model for Cdc42 oscillations in fission yeast, consisting of two diffusion equations in the bulk domain coupled to nonlinear ODEs for binding kinetics at each end of the cell. In 1-D, our analysis reveals the existence of symmetric and asymmetric steady states, as well as anti-phase relaxation oscillations typical of slow-fast systems. We then extend our analysis to a 2-D model with circular bulk geometry, for which species can either diffuse inside the cell or become bound to the membrane and undergo a nonlinear reaction-diffusion process. We also consider a nonlocal system of PDEs approximating the dynamics of the 2-D membrane-bulk model in the limit of fast bulk diffusion. In all three model variants we find that mass conservation selects perturbations of spatial modes that simply redistribute mass. In 1-D, only anti-phase oscillations between the two ends of the cell can occur, and in-phase oscillations are excluded. In higher dimensions, no radially symmetric oscillations are observed. Instead, the only instabilities are symmetry-breaking, either corresponding to stationary Turing instabilities, leading to the formation of stationary patterns, or to oscillatory Turing instabilities, leading to traveling and standing waves. Codimension-two Bogdanov--Takens bifurcations occur when the two distinct instabilities coincide, causing traveling waves to slow down and to eventually become stationary patterns., Comment: 31 pages, 20 figures

On a two-dimensional circular domain, we analyze the formation of spatio-temporal patterns for a class of coupled bulk-surface reaction-diffusion models for which a passive diffusion process occurring in the interior bulk domain is linearly coupled to a nonlinear reaction-diffusion process on the domain boundary. For this coupled PDE system we construct a radially symmetric steady state solution and from a linearized stability analysis formulate criteria for which this base state can undergo either a Hopf bifurcation, a symmetry-breaking pitchfork (or Turing) bifurcation, or a codimension-two pitchfork-Hopf bifurcation. For each of these three types of bifurcations, a multiple time-scale asymptotic analysis is used to derive normal form amplitude equations characterizing the local branching behavior of spatio-temporal patterns in the weakly nonlinear regime. Among the novel aspects of this weakly nonlinear analysis are the two-dimensionality of the bulk domain, the systematic treatment of arbitrary reaction kinetics restricted to the boundary, the bifurcation parameters which arise in the boundary conditions, and the underlying spectral problem where both the differential operator and the boundary conditions involve the eigenvalue parameter. The normal form theory is illustrated for both Schnakenberg and Brusselator reaction kinetics, and the weakly nonlinear results are favorably compared with numerical bifurcation results and results from time-dependent PDE simulations of the coupled bulk-surface system. Overall, the results show the existence of either subcritical or supercritical Hopf and symmetry-breaking bifurcations, and mixed-mode oscillations characteristic of codimension-two bifurcations. Finally, the formation of global structures such as large amplitude rotating waves is briefly explored through PDE numerical simulations., Comment: 40 pages and 39 figures

This paper reports main results of the phase noise comparison that has been performed between october 2005 and december 2006, using two oscillators at 5 and 100 MHz and un DRO at 3.5 GHz. The problem is not to compare the performances of several oscillators, but to compare and to make an evaluation of the uncertainties, and of course the resolution and the reproducibility of the measurements. This comparison allow us to determine the ability to get various systems traceable together in order to increase the trust that one can have in phase noise measurements.