Facilitation of I Kr current by some hERG channel blockers suppresses early afterdepolarizations.

Drug-induced block of the cardiac rapid delayed rectifying potassium current (I Kr), carried by the human ether-a-go-go-related gene (hERG) channel, is the most common cause of acquired long QT syndrome. Indeed, some, but not all, drugs that block hERG channels cause fatal cardiac arrhythmias. However, there is no clear method to distinguish between drugs that cause deadly arrhythmias and those that are clinically safe. Here we propose a mechanism that could explain why certain clinically used hERG blockers are less proarrhythmic than others. We demonstrate that several drugs that block hERG channels, but have favorable cardiac safety profiles, also evoke another effect; they facilitate the hERG current amplitude in response to low-voltage depolarization. To investigate how hERG facilitation impacts cardiac safety, we develop computational models of I Kr block with and without this facilitation. We constrain the models using data from voltage clamp recordings of hERG block and facilitation by nifekalant, a safe class III antiarrhythmic agent. Human ventricular action potential simulations demonstrate the ability of nifekalant to suppress ectopic excitations, with or without facilitation. Without facilitation, excessive I Kr block evokes early afterdepolarizations, which cause lethal arrhythmias. When facilitation is introduced, early afterdepolarizations are prevented at the same degree of block. Facilitation appears to prevent early afterdepolarizations by increasing I Kr during the repolarization phase of action potentials. We empirically test this prediction in isolated rabbit ventricular myocytes and find that action potential prolongation with nifekalant is less likely to induce early afterdepolarization than action potential prolongation with dofetilide, a hERG channel blocker that does not induce facilitation. Our data suggest that hERG channel blockers that induce facilitation increase the repolarization reserve of cardiac myocytes, rendering them less likely to trigger lethal ventricular arrhythmias

DWBA analysis of the 13C(6Li,d)17O reaction at 10 MeV/nucleon and its astrophysical implications

The value of the alpha spectroscopic factor (S_alpha) of the 6.356 MeV 1/2+ state of 17O is believed to have significant astrophysical implications due to the importance of the 13C(alpha,n)16O reaction as a possible source of neutron production for the s process. To further study this effect, an accurate measurement of the 13C(6Li,d)17O reaction at E_lab = 60 MeV has been performed recently by Kubono et al., who found a new value for the spectroscopic factor of the 6.356 MeV 1/2+ state of 17O based on a distorted wave Born approximation (DWBA) analysis of these data. This new value, S_alpha approximately = 0.011, is surprisingly much smaller than those used previously in astrophysical calculations (S_alpha approximately = 0.3-0.7) and thus poses a serious question as to the role of the 13C(alpha,n)16O reaction as a source of neutron production. In this work we perform a detailed analysis of the same 13C(6Li,d)17O data within the DWBA as well as the coupled reaction channel (CRC) formalism. Our analysis yields an S_alpha value of over an order of magnitude larger than that of Kubono et al. for the 6.356 MeV 1/2+ state of 17O.Comment: 17 pages, 4 figures, minor changes, accepted by Nuclear Physics

Important role of the spin-orbit interaction in forming the 1/2^+ orbital structure in Be isotopes

The structure of the second 0^+ state of ^{10}Be is investigated using a microscopic $\alpha+\alpha+n+n$ model based on the molecular-orbit (MO) model. The second 0^+ state, which has dominantly the (1/2^+)^2 configuration, is shown to have a particularly enlarged $\alpha-\alpha$ structure. The kinetic energy of the two valence neutrons occupying along the $\alpha-\alpha$ axis is reduced remarkably due to the strong $\alpha$ clustering and, simultaneously, the spin-orbit interaction unexpectedly plays important role to make the energy of this state much lower. The mixing of states with different spin structure is shown to be important in negative-parity states. The experimentally observed small-level spacing between 1^- and 2^- (~ 300 keV) is found to be an evidence of this spin-mixing effect. ^{12}{Be} is also investigated using $\alpha+\alpha+4n$ model, in which four valence neutrons are considered to occupy the (3/2^-)^2(1/2^+)^2 configuration. The energy surface of ^{12}Be is shown to exhibit similar characteristics, that the remarkable $\alpha$ clustering and the contribution of the spin-orbit interaction make the binding of the state with (3/2^-)^2(1/2^+)^2 configuration properly stronger in comparison with the closed p-shell (3/2^-)^2(1/2^-)^2 configuration.Comment: 14 pages, 4 figure

Design and Test of a Forward Neutron Calorimeter for the ZEUS Experiment

A lead scintillator sandwich sampling calorimeter has been installed in the HERA tunnel 105.6 m from the central ZEUS detector in the proton beam direction. It is designed to measure the energy and scattering angle of neutrons produced in charge exchange ep collisions. Before installation the calorimeter was tested and calibrated in the H6 beam at CERN where 120 GeV electrons, muons, pions and protons were made incident on the calorimeter. In addition, the spectrum of fast neutrons from charge exchange proton-lucite collisions was measured. The design and construction of the calorimeter is described, and the results of the CERN test reported. Special attention is paid to the measurement of shower position, shower width, and the separation of electromagnetic showers from hadronic showers. The overall energy scale as determined from the energy spectrum of charge exchange neutrons is compared to that obtained from direct beam hadrons.Comment: 45 pages, 22 Encapsulated Postscript figures, submitted to Nuclear Instruments and Method

Triaxial deformation in 10Be

The triaxial deformation in $^{10}$Be is investigated using a microscopic $\alpha+\alpha+n+n$ model. The states of two valence neutrons are classified based on the molecular-orbit (MO) model, and the $\pi$-orbit is introduced about the axis connecting the two $\alpha$-clusters for the description of the rotational bands. There appear two rotational bands comprised mainly of $K^\pi = 0^+$ and $K^\pi = 2^+$, respectively, at low excitation energy, where the two valence neutrons occupy $K^\pi = 3/2^-$ or $K^\pi = 1/2^-$ orbits. The triaxiality and the $K$-mixing are discussed in connection to the molecular structure, particularly, to the spin-orbit splitting. The extent of the triaxial deformation is evaluated in terms of the electro-magnetic transition matrix elements (Davydov-Filippov model, Q-invariant model), and density distribution in the intrinsic frame. The obtained values turned out to be $\gamma = 15^o \sim 20^o$.Comment: 15 pages, latex, 3 figure

Grassmannian flows and applications to nonlinear partial differential equations

We show how solutions to a large class of partial differential equations with nonlocal Riccati-type nonlinearities can be generated from the corresponding linearized equations, from arbitrary initial data. It is well known that evolutionary matrix Riccati equations can be generated by projecting linear evolutionary flows on a Stiefel manifold onto a coordinate chart of the underlying Grassmann manifold. Our method relies on extending this idea to the infinite dimensional case. The key is an integral equation analogous to the Marchenko equation in integrable systems, that represents the coodinate chart map. We show explicitly how to generate such solutions to scalar partial differential equations of arbitrary order with nonlocal quadratic nonlinearities using our approach. We provide numerical simulations that demonstrate the generation of solutions to Fisher--Kolmogorov--Petrovskii--Piskunov equations with nonlocal nonlinearities. We also indicate how the method might extend to more general classes of nonlinear partial differential systems.Comment: 26 pages, 2 figure

Structure of the mirror nuclei 9^9Be and 9^9B in a microscopic cluster model

The structure of the mirror nuclei $^9$Be and $^9$B is studied in a microscopic $\alpha+ \alpha+ n$ and $\alpha+ \alpha+ p$ three-cluster model using a fully antisymmetrized 9-nucleon wave function. The two-nucleon interaction includes central and spin-orbit components and the Coulomb potential. The ground state of $^9$Be is obtained accurately with the stochastic variational method, while several particle-unbound states of both $^9$Be and $^9$B are investigated with the complex scaling method.The calculation for $^9$Be supports the recent identification for the existence of two broad states around 6.5 MeV, and predicts the $\frac{3}{2}^{-}_2$ and $\frac{5}{2}^{-}_2$ states at about 4.5 MeV and 8 MeV, respectively. The similarity of the calculated spectra of $^9$Be and $^9$B enables one to identify unknown spins and parities of the $^9$B states. Available data on electromagnetic moments and elastic electron scatterings are reproduced very well. The enhancement of the $E$1 transition of the first excited state in $^9$Be is well accounted for. The calculated density of $^9$Be is found to reproduce the reaction cross section on a Carbon target. The analysis of the beta decay of $^9$Li to $^9$Be clearly shows that the wave function of $^9$Be must contain a small component that cannot be described by the simple $\alpha+ \alpha+ n$ model. This small component can be well accounted for by extending a configuration space to include the distortion of the $\alpha$-particle to $t+p$ and $h+n$ partitions.Comment: 24 page

Western Pacific atmospheric nutrient deposition fluxes, their impact on surface ocean productivity

The atmospheric deposition of both macronutrients and micronutrients plays an important role in driving primary productivity, particularly in the low-latitude ocean. We report aerosol major ion measurements for five ship-based sampling campaigns in the western Pacific from similar to 25 degrees N to 20 degrees S and compare the results with those from Atlantic meridional transects (similar to 50 degrees N to 50 degrees S) with aerosols collected and analyzed in the same laboratory, allowing full incomparability. We discuss sources of the main nutrient species (nitrogen (N), phosphorus (P), and iron (Fe)) in the aerosols and their stoichiometry. Striking north-south gradients are evident over both basins with the Northern Hemisphere more impacted by terrestrial dust sources and anthropogenic emissions and the North Atlantic apparently more impacted than the North Pacific. We estimate the atmospheric supply rates of these nutrients and the potential impact of the atmospheric deposition on the tropical western Pacific. Our results suggest that the atmospheric deposition is P deficient relative to the needs of the resident phytoplankton. These findings suggest that atmospheric supply of N, Fe, and P increases primary productivity utilizing some of the residual excess phosphorus (P*) in the surface waters to compensate for aerosol P deficiency. Regional primary productivity is further enhanced via the stimulation of nitrogen fixation fuelled by the residual atmospheric iron and P*. Our stoichiometric calculations reveal that a P* of 0.1 mu mol L-1 can offset the P deficiency in atmospheric supply for many months. This study suggests that atmospheric deposition may sustain similar to 10% of primary production in both the western tropical Pacific