Self-organization of conducting pathways explains electrical wave propagation in cardiac tissues with high fraction of nonconducting cells

Cardiac fibrosis occurs in many forms of heart disease and is considered to be one of the main arrhythmogenic factors. Regions with a high density of fibroblasts are likely to cause blocks of wave propagation that give rise to dangerous cardiac arrhythmias. Therefore, studies of the wave propagation through these regions are very important, yet the precise mechanisms leading to arrhythmia formation in fibrotic cardiac tissue remain poorly understood. Particularly, it is not clear how wave propagation is organized at the cellular level, as experiments show that the regions with a high percentage of fibroblasts (65-75%) are still conducting electrical signals, whereas geometric analysis of randomly distributed conducting and non-conducting cells predicts connectivity loss at 40% at the most (percolation threshold). To address this question, we used a joint in vitro-in silico approach, which combined experiments in neonatal rat cardiac monolayers with morphological and electrophysiological computer simulations. We have shown that the main reason for sustainable wave propagation in highly fibrotic samples is the formation of a branching network of cardiomyocytes. We have successfully reproduced the morphology of conductive pathways in computer modelling, assuming that cardiomyocytes align their cytoskeletons to fuse into cardiac syncytium. The electrophysiological properties of the monolayers, such as conduction velocity, conduction blocks and wave fractionation, were reproduced as well. In a virtual cardiac tissue, we have also examined the wave propagation at the subcellular level, detected wavebreaks formation and its relation to the structure of fibrosis and, thus, analysed the processes leading to the onset of arrhythmias. © 2019 Kudryashova et al

Control of scroll wave turbulence using resonant perturbations

Turbulence of scroll waves is a sort of spatio-temporal chaos that exists in three-dimensional excitable media. Cardiac tissue and the Belousov-Zhabotinsky reaction are examples of such media. In cardiac tissue, chaotic behaviour is believed to underlie fibrillation which, without intervention, precedes cardiac death. In this study we investigate suppression of the turbulence using stimulation of two different types, "modulation of excitability" and "extra transmembrane current". With cardiac defibrillation in mind, we used a single pulse as well as repetitive extra current with both constant and feedback controlled frequency. We show that turbulence can be terminated using either a resonant modulation of excitability or a resonant extra current. The turbulence is terminated with much higher probability using a resonant frequency perturbation than a non-resonant one. Suppression of the turbulence using a resonant frequency is up to fifty times faster than using a non-resonant frequency, in both the modulation of excitability and the extra current modes. We also demonstrate that resonant perturbation requires strength one order of magnitude lower than that of a single pulse, which is currently used in clinical practice to terminate cardiac fibrillation. Our results provide a robust method of controlling complex chaotic spatio-temporal processes. Resonant drift of spiral waves has been studied extensively in two dimensions, however, these results show for the first time that it also works in three dimensions, despite the complex nature of the scroll wave turbulence.Comment: 13 pages, 12 figures, submitted to Phys Rev E 2008/06/13. Last version: 2008/09/18, after revie

Intrinsic Localized Modes Observed in the High Temperature Vibrational Spectrum of NaI

Inelastic neutron measurements of the high-temperature lattice excitations in NaI show that in thermal equilibrium at 555 K an intrinsic mode, localized in three dimensions, occurs at a single frequency near the center of the spectral phonon gap, polarized along [111]. At higher temperatures the intrinsic localized mode gains intensity. Higher energy inelastic neutron and x-ray scattering measurements on a room-temperature NaI crystal indicate that the creation energy of the ground state of the intrinsic localized mode is 299 meV.Comment: 17 pages, 5 figures Revised version; final versio

Nuclear spin driven quantum relaxation in LiY_0.998Ho_0.002F_4

Staircase hysteresis loops of the magnetization of a LiY_0.998Ho_0.002F_4 single crystal are observed at subkelvin temperatures and low field sweep rates. This behavior results from quantum dynamics at avoided level crossings of the energy spectrum of single Ho^{3+} ions in the presence of hyperfine interactions. Enhanced quantum relaxation in constant transverse fields allows the study of the relative magnitude of tunnel splittings. At faster sweep rates, non-equilibrated spin-phonon and spin-spin transitions, mediated by weak dipolar interactions, lead to magnetization oscillations and additional steps.Comment: 5 pages, 5 eps figures, using RevTe

Theory of spiral wave dynamics in weakly excitable media: asymptotic reduction to a kinematic model and applications

In a weakly excitable medium, characterized by a large threshold stimulus, the free end of an isolated broken plane wave (wave tip) can either rotate (steadily or unsteadily) around a large excitable core, thereby producing a spiral pattern, or retract causing the wave to vanish at boundaries. An asymptotic analysis of spiral motion and retraction is carried out in this weakly excitable large core regime starting from the free-boundary limit of the reaction-diffusion models, valid when the excited region is delimited by a thin interface. The wave description is shown to naturally split between the tip region and a far region that are smoothly matched on an intermediate scale. This separation allows us to rigorously derive an equation of motion for the wave tip, with the large scale motion of the spiral wavefront slaved to the tip. This kinematic description provides both a physical picture and exact predictions for a wide range of wave behavior, including: (i) steady rotation (frequency and core radius), (ii) exact treatment of the meandering instability in the free-boundary limit with the prediction that the frequency of unstable motion is half the primary steady frequency (iii) drift under external actions (external field with application to axisymmetric scroll ring motion in three-dimensions, and spatial or/and time-dependent variation of excitability), and (iv) the dynamics of multi-armed spiral waves with the new prediction that steadily rotating waves with two or more arms are linearly unstable. Numerical simulations of FitzHug-Nagumo kinetics are used to test several aspects of our results. In addition, we discuss the semi-quantitative extension of this theory to finite cores and pinpoint mathematical subtleties related to the thin interface limit of singly diffusive reaction-diffusion models

Inverse temperature dependence of the dust submillimeter spectral index

We present a compilation of PRONAOS-based results concerning the temperature dependence of the dust submillimeter spectral index, including data from Galactic cirrus, star-forming regions, dust associated to a young stellar object, and a spiral galaxy. We observe large variations of the spectral index (from 0.8 to 2.4) in a wide range of temperatures (11 to 80 K). These spectral index variations follow a hyperbolic-shaped function of the temperature, high spectral indices (1.6-2.4) being observed in cold regions (11-20 K) while low indices (0.8-1.6) are observed in warm regions (35-80 K). Three distinct effects may play a role in this temperature dependence: one is that the grain sizes change in dense environments, another is that the chemical composition of the grains is not the same in different environments, a third one is that there is an intrinsic dependence of the dust spectral index on the temperature due to quantum processes. This last effect is backed up by laboratory measurements and could be the dominant one.Comment: 5 pages, 3 figures, Letter accepted April 2003 in A&

Genetic Dissection of an Exogenously Induced Biofilm in Laboratory and Clinical Isolates of E. coli

Microbial biofilms are a dominant feature of many human infections. However, developing effective strategies for controlling biofilms requires an understanding of the underlying biology well beyond what currently exists. Using a novel strategy, we have induced formation of a robust biofilm in Escherichia coli by utilizing an exogenous source of poly-N-acetylglucosamine (PNAG) polymer, a major virulence factor of many pathogens. Through microarray profiling of competitive selections, carried out in both transposon insertion and over-expression libraries, we have revealed the genetic basis of PNAG-based biofilm formation. Our observations reveal the dominance of electrostatic interactions between PNAG and surface structures such as lipopolysaccharides. We show that regulatory modulation of these surface structures has significant impact on biofilm formation behavior of the cell. Furthermore, the majority of clinical isolates which produced PNAG also showed the capacity to respond to the exogenously produced version of the polymer