A Heterozygous Deletion Mutation in the Cardiac Sodium Channel Gene SCN5A with Loss- and Gain-of-Function Characteristics Manifests as Isolated Conduction Disease, without Signs of Brugada or Long QT Syndrome.

BACKGROUND: The SCN5A gene encodes for the α-subunit of the cardiac sodium channel NaV1.5, which is responsible for the rapid upstroke of the cardiac action potential. Mutations in this gene may lead to multiple life-threatening disorders of cardiac rhythm or are linked to structural cardiac defects. Here, we characterized a large family with a mutation in SCN5A presenting with an atrioventricular conduction disease and absence of Brugada syndrome. METHOD AND RESULTS: In a large family with a high incidence of sudden cardiac deaths, a heterozygous SCN5A mutation (p.1493delK) with an autosomal dominant inheritance has been identified. Mutation carriers were devoid of any cardiac structural changes. Typical ECG findings were an increased P-wave duration, an AV-block I° and a prolonged QRS duration with an intraventricular conduction delay and no signs for Brugada syndrome. HEK293 cells transfected with 1493delK showed strongly (5-fold) reduced Na(+) currents with altered inactivation kinetics compared to wild-type channels. Immunocytochemical staining demonstrated strongly decreased expression of SCN5A 1493delK in the sarcolemma consistent with an intracellular trafficking defect and thereby a loss-of-function. In addition, SCN5A 1493delK channels that reached cell membrane showed gain-of-function aspects (slowing of the fast inactivation, reduction in the relative fraction of channels that fast inactivate, hastening of the recovery from inactivation). CONCLUSION: In a large family, congregation of a heterozygous SCN5A gene mutation (p.1493delK) predisposes for conduction slowing without evidence for Brugada syndrome due to a predominantly trafficking defect that reduces Na(+) current and depolarization force.

Nonlinear Saffman-Taylor instability

We show, both theoretically and experimentally, that the interface between two viscous fluids in a Hele-Shaw cell can be nonlinearly unstable before the Saffman-Taylor linear instability point is reached. We identify the family of exact elastica solutions [Nye et al., Eur. J. Phys. 5, 73 (1984)] as the unstable branch of the corresponding subcritical bifurcation which ends up at a topological singularity defined by interface pinchoff. We devise an experimental procedure to prepare arbitrary initial conditions in a Hele-Shaw cell. This is used to test the proposed bifurcation scenario and quantitatively asses its practical relevance.

Anomalous specific-heat jump in a two-component ultracold Fermi gas

The thermodynamic functions of a Fermi gas with spin population imbalance are studied in the temperature-asymmetry plane in the BCS limit. The low-temperature domain is characterized by an anomalous enhancement of the entropy and the specific heat above their values in the unpaired state, decrease of the gap and eventual unpairing phase transition as the temperature is lowered. The unpairing phase transition induces a second jump in the specific heat, which can be measured in calorimetric experiments. While the superfluid is unstable against a supercurrent carrying state, it may sustain a metastable state if cooled adiabatically down from the stable high-temperature domain. In the latter domain the temperature dependence of the gap and related functions is analogous to the predictions of the BCS theory.

Systematic weakly nonlinear analysis of interfacial instabilities in Hele-Shaw flows

We develop a systematic method to derive all orders of mode couplings in a weakly nonlinear approach to the dynamics of the interface between two immiscible viscous fluids in a Hele-Shaw cell. The method is completely general: it applies to arbitrary geometry and driving. Here we apply it to the channel geometry driven by gravity and pressure. The finite radius of convergence of the mode-coupling expansion is found. Calculation up to third-order couplings is done, which is necessary to account for the time-dependent Saffman-Taylor finger solution and the case of zero viscosity contrast. The explicit results provide relevant analytical information about the role that the viscosity contrast and the surface tension play in the dynamics of the system. We finally check the quantitative validity of different orders of approximation and a resummation scheme against a physically relevant, exact time-dependent solution. The agreement between the low-order approximations and the exact solution is excellent within the radius of convergence, and is even reasonably good beyond this radius.

Systematic weakly nonlinear analysis of radial viscous fingering

We present a weakly nonlinear analysis of the interface dynamics in a radial Hele-Shaw cell driven by both injection and rotation. We extend the systematic expansion introduced in [E. Alvarez-Lacalle et al., Phys. Rev. E 64, 016302 (2001)] to the radial geometry, and compute explicitly the first nonlinear contributions. We also find the necessary and sufficient condition for the uniform convergence of the nonlinear expansion. Within this region of convergence, the analytical predictions at low orders are compared satisfactorily to exact solutions and numerical integration of the problem. This is particularly remarkable in configurations (with no counterpart in the channel geometry) for which the interplay between injection and rotation allows that condition to be satisfied at all times. In the case of the purely centrifugal forcing we demonstrate that nonlinear couplings make the interface more unstable for lower viscosity contrast between the fluids.

The nonlinear relaxation time and quasideterministic-theory approaches to characterize the decay of unestable states

We present the relationship between nonlinear-relaxation-time (NLRT) and quasideterministic approaches to characterize the decay of an unstable state. The universal character of the NLRT is established. The theoretical results are applied to study the dynamical relaxation of the Landau model in one and n variables and also a laser model.

Confinement of discrete breathers in inhomogeneously profiled nonlinear chains

We investigate numerically the scattering of a moving discrete breather on a pair of junctions in a Fermi-Pasta-Ulam chain. These junctions delimit an extended region with different masses of the particles. We consider (i) a rectangular trap, (ii) a wedge shaped trap, and (iii) a smoothly varying convex or concave mass profile. All three cases lead to DB confinement, with the ease of trapping depending on the profile of the trap. We also study the collision and trapping of two DBs within the profile as a function of trap width, shape, and approach time at the two junctions. The latter controls whether one or both DBs are trapped.

Heat fluctuations in Brownian transducers

The heat fluctuation probability distribution function in Brownian transducers operating between two heat reservoirs is studied. We find, both analytically and numerically, that the recently proposed fluctuation theorem for heat exchange [C. Jarzynski and D. K. Wojcik, Phys. Rev. Lett. 92, 230602 (2004)] has to be applied carefully when the coupling mechanism between both baths is considered. We also conjecture how to extend such a relation when an external work is present.

Magnetization versus heat treatment in rapidly solidified NdFeB alloys

NdFeB melt-spun amorphous or partially amorphous alloys of four compositions were prepared. Their crystallization kinetics induced by thermal treatment was studied by differential scanning calorimetry and scanning and transmission electron microscopy. Scanning electron microscopy demonstrated that heterogeneous nucleation occurs preferentially at the ribbon surface which was in contact with the wheel. The explicit form of the kinetic equation that best describes the first stage of crystallization under high undercooling conditions was obtained for each alloy. From the crystallization results, the lower part of the experimental time-temperature-transformation curves was deduced for each alloy and extrapolated up to the high-temperature limit of their validity. Microstructural observations showed a typical size of the microcrystals obtained by heat treatment of ~100 nm. From the magnetic properties measured with a vibrating sample magnetometer, the same magnetic behavior of partially crystallized alloys is observed regardless of the temperature of annealing provided the same crystallization fraction, x, is achieved, at least for small values of x (typically ~10%).

A classical particle in heat bath under the influence of external noise

A very simple model of a classical particle in a heat bath under the influence of external noise is studied. By means of a suitable hypothesis, the heat bath is reduced to an internal colored noise (OrnsteinUhlenbeck noise). In a second step, an external noise is coupled to the bath. The steady state probability distributions are obtained.

Heat capacity measurements on the equiatomic compounds in Ni-X (X = Al, In, Si, Ge and Bi) and M-Sb (with M = Ni, Co and Fe) systems

Molar heat capacities of the binary compounds NiAl, NiIn, NiSi, NiGe, NiBi, NiSb, CoSb and FeSb were determined every 10 K by differential scanning calorimetry in the temperature range 310-1080 K. The experimental results have been fitted versus temperature according to C-p = a + b . T + c . T-2 + d . T-2. Results are given, discussed and compared to estimations found in the literature. Two compounds, NiBi and FeSb, are subject to transformations between 460 and 500 K. (C) 1999 Elsevier Science Ltd. All rights reserved.

From lattice-gas models to nonlinear diffusion models: A derivation of macroscopic equations and fluctuations

We derive nonlinear diffusion equations and equations containing corrections due to fluctuations for a coarse-grained concentration field. To deal with diffusion coefficients with an explicit dependence on the concentration values, we generalize the Van Kampen method of expansion of the master equation to field variables. We apply these results to the derivation of equations of phase-separation dynamics and interfacial growth instabilities.