Disease-associated mutations in KCNE potassium channel subunits (MiRPs) reveal promiscuous disruption of multiple currents and conservation of mechanism.

KCNE genes encode single transmembrane-domain subunits, the MinK-related peptides (MiRPs), which assemble with pore-forming alpha subunits to establish the attributes of potassium channels in vivo. To investigate whether MinK, MiRP1, and MiRP2 operate similarly with their known native alpha subunit partners (KCNQ1, HERG, and Kv3.4, respectively) two conserved residues associated with human disease and influential in channel function were evaluated. As MiRPs assemble with a variety of alpha subunits in experimental cells and may do so in vivo, each peptide was also assessed with the other two alpha subunits. Inherited mutation of aspartate to asparagine (D --> N) to yield D76N-MinK is linked to cardiac arrhythmia and deafness; the analogs D82N-MiRP1 and D90N-MiRP2 were studied. Mutation of arginine to histidine (R --> H) to yield R83H-MiRP2 is associated with periodic paralysis; the analogs K69H-MinK and K75H-MiRP1 were also studied. Macroscopic and single-channel currents showed that D --> N mutations suppressed a subset of functions whereas R/K --> H changes altered the activity of MinK, MiRP1, and MiRP2 with all three alpha subunits. The findings indicate that the KCNE peptides interact similarly with different alpha subunits and suggest a hypothesis: that clinical manifestations of inherited KCNE point mutations result from disruption of multiple native currents via promiscuous interactions

Isospin Diffusion in Heavy-Ion Collisions and the Neutron Skin Thickness of Lead

The correlation between the thickness of the neutron skin in Pb-208, and the degree of isospin diffusion in heavy-ion collisions is examined. The same equation of state is used to compute the degree of isospin diffusion in an isospin-depedent transport model and the neutron skin thickness in the Hartree-Fock approximation. We find that skin thicknesses less than 0.15 fm are excluded by the isospin diffusion data.Comment: 5 pages, 4 figures; few minor corrections and updates; version to appear in PR

A meshless, integration-free, and boundary-only RBF technique

Based on the radial basis function (RBF), non-singular general solution and dual reciprocity method (DRM), this paper presents an inherently meshless, integration-free, boundary-only RBF collocation techniques for numerical solution of various partial differential equation systems. The basic ideas behind this methodology are very mathematically simple. In this study, the RBFs are employed to approximate the inhomogeneous terms via the DRM, while non-singular general solution leads to a boundary-only RBF formulation for homogenous solution. The present scheme is named as the boundary knot method (BKM) to differentiate it from the other numerical techniques. In particular, due to the use of nonsingular general solutions rather than singular fundamental solutions, the BKM is different from the method of fundamental solution in that the former does no require the artificial boundary and results in the symmetric system equations under certain conditions. The efficiency and utility of this new technique are validated through a number of typical numerical examples. Completeness concern of the BKM due to the only use of non-singular part of complete fundamental solution is also discussed