Pathogenic Cav3.2 channel mutation in a child with primary generalized epilepsy.

Two paternally-inherited missense variants in CACNA1H were identified and characterized in a 6-year-old child with generalized epilepsy. Febrile and unprovoked seizures were present in this child. Both variants were expressed in cis or isolation using human recombinant Cav3.2 calcium channels in tsA-201 cells. Whole-cell patch-clamp recordings indicated that one variant (c.3844C > T; p.R1282W) caused a significant increase in current density consistent with a pathogenic gain-of-function phenotype; while the other cis-related variant (c.5294C > T; p.A1765V) had a benign profile

Chaotic Hypothesis, Fluctuation Theorem and singularities

The chaotic hypothesis has several implications which have generated interest in the literature because of their generality and because a few exact predictions are among them. However its application to Physics problems requires attention and can lead to apparent inconsistencies. In particular there are several cases that have been considered in the literature in which singularities are built in the models: for instance when among the forces there are Lennard-Jones potentials (which are infinite in the origin) and the constraints imposed on the system do not forbid arbitrarily close approach to the singularity even though the average kinetic energy is bounded. The situation is well understood in certain special cases in which the system is subject to Gaussian noise; here the treatment of rather general singular systems is considered and the predictions of the chaotic hypothesis for such situations are derived. The main conclusion is that the chaotic hypothesis is perfectly adequate to describe the singular physical systems we consider, i.e. deterministic systems with thermostat forces acting according to Gauss' principle for the constraint of constant total kinetic energy (``isokinetic Gaussian thermostats''), close and far from equilibrium. Near equilibrium it even predicts a fluctuation relation which, in deterministic cases with more general thermostat forces (i.e. not necessarily of Gaussian isokinetic nature), extends recent relations obtained in situations in which the thermostatting forces satisfy Gauss' principle. This relation agrees, where expected, with the fluctuation theorem for perfectly chaotic systems. The results are compared with some recent works in the literature.Comment: 7 pages, 1 figure; updated to take into account comments received on the first versio

Glassy behavior of light

We study the nonlinear dynamics of a multi-mode random laser using the methods of statistical physics of disordered systems. A replica-symmetry breaking phase transition is predicted as a function of the pump intensity. We thus show that light propagating in a random non-linear medium displays glassy behavior, i.e. the photon gas has a multitude of metastable states and a non vanishing complexity, corresponding to mode-locking processes in random lasers. The present work reveals the existence of new physical phenomena, and demonstrates how nonlinear optics and random lasers can be a benchmark for the modern theory of complex systems and glasses.Comment: 5 pages, 1 figur

Is it possible to experimentally verify the fluctuation relation? A review of theoretical motivations and numerical evidence

The theoretical motivations to perform experimental tests of the stationary state fluctuation relation are reviewed. The difficulties involved in such tests, evidenced by numerical simulations, are also discussed.Comment: 36 pages, 4 figures. Extended version of a presentation to the discussion "Is it possible to experimentally verify the fluctuation theorem?", IHP, Paris, December 1, 2006. Comments are very welcom

Mean field theory of hard sphere glasses and jamming

Hard spheres are ubiquitous in condensed matter: they have been used as models for liquids, crystals, colloidal systems, granular systems, and powders. Packings of hard spheres are of even wider interest, as they are related to important problems in information theory, such as digitalization of signals, error correcting codes, and optimization problems. In three dimensions the densest packing of identical hard spheres has been proven to be the FCC lattice, and it is conjectured that the closest packing is ordered (a regular lattice, e.g, a crystal) in low enough dimension. Still, amorphous packings have attracted a lot of interest, because for polydisperse colloids and granular materials the crystalline state is not obtained in experiments for kinetic reasons. We review here a theory of amorphous packings, and more generally glassy states, of hard spheres that is based on the replica method: this theory gives predictions on the structure and thermodynamics of these states. In dimensions between two and six these predictions can be successfully compared with numerical simulations. We will also discuss the limit of large dimension where an exact solution is possible. Some of the results we present here have been already published, but others are original: in particular we improved the discussion of the large dimension limit and we obtained new results on the correlation function and the contact force distribution in three dimensions. We also try here to clarify the main assumptions that are beyond our theory and in particular the relation between our static computation and the dynamical procedures used to construct amorphous packings.Comment: 59 pages, 25 figures. Final version published on Rev.Mod.Phy

Replica analysis of the generalized p-spin interaction glass model

We investigate stability of replica symmetry breaking solutions in generalized $p$-spin models. It is shown that the kind of the transition to the one-step replica symmetry breaking state depends not only on the presence or absence of the reflection symmetry of the generalized "spin"-operators $\hat{U}$ but on the number of interacting operators and their individual characteristics.Comment: 14 pages, 1 figur

Scanning mutagenesis of omega-atracotoxin-Hv1a reveals a spatially restricted epitope that confers selective activity against insect calcium channels

We constructed a complete panel of alanine mutants of the insect-specific calcium channel blocker omega-atracotoxin-Hv1a. Lethality assays using these mutant toxins identified three spatially contiguous residues, Pro(10), Asn(27), and Arg(35), that are critical for insecticidal activity against flies (Musca domestica) and crickets (Acheta domestica). Competitive binding assays using radiolabeled omega-atracotoxin-Hv1a and neuronal membranes prepared from the heads of American cockroaches (Periplaneta americana) confirmed the importance of these three residues for binding of the toxin to target calcium channels presumably expressed in the insect membranes. At concentrations up to 10 muM, omega-atracotoxin-Hv1a had no effect on heterologously expressed rat Ca(v)2.1, Ca(v)2.2, and Ca(v)1.2 calcium channels, consistent with the previously reported insect selectivity of the toxin. 30 muM omega-atracotoxin-Hv1a inhibited rat Ca-v currents by 10-34%, depending on the channel subtype, and this low level of inhibition was essentially unchanged when Asn(27) and Arg(35), which appears to be critical for interaction of the toxin with insect Ca-v channels, were both mutated to alanine. We propose that the spatially contiguous epitope formed by Pro(10), Asn(27), and Arg(35) confers specific binding to insect Ca-v channels and is largely responsible for the remarkable phyletic selectivity of omega-atracotoxin-Hv1a. This epitope provides a structural template for rational design of chemical insecticides that selectively target insect Ca-v channels

Glassy behavior of light in random lasers

A theoretical analysis [Angelani et al., Phys. Rev. Lett. 96, 065702 (2006)] predicts glassy behaviour of light in a nonlinear random medium. This implies slow dynamics related to the presence of many metastable states. We consider very general equations (that also apply to other systems, like Bose-Condensed gases) describing light in a disordered non-linear medium and through some approximations we relate them to a mean-field spin-glass-like model. The model is solved by the replica method, and replica-symmetry breaking phase transition is predicted. The transition describes a mode-locking process in which the phases of the modes are locked to random (history and sample-dependent) values. The results are based on very general theory, and embrace a variety of physical phenomena.Comment: 21 pages, 3 figures. Revised and enlarged version. To be published in Physical Review

Crossover between Equilibrium and Shear-controlled Dynamics in Sheared Liquids

We present a numerical simulation study of a simple monatomic Lennard-Jones liquid under shear flow, as a function of both temperature and shear rate. By investigating different observables we find that i) It exists a line in the (temperature-shear) plane that sharply marks the boarder between an ``equilibrium'' and a ``shear-controlled'' region for both the dynamic and the thermodynamic quantities; and ii) Along this line the structural relaxation time, is proportional to the inverse shear rate, i.e. to the typical time-scale introduced by the shear flow. Above the line the liquid dynamics is unaffected by the shear flow, while below it both temperature and shear rate control the particle motion.Comment: 14 pages, 5 figure