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

High sensitivity and multifunctional micro-Hall sensors fabricated using InAlSb/InAsSb/InAlSb heterostructures

Further diversification of Hall sensor technology requires development of materials with high electron mobility and an ultrathin conducting layer very close to the material's surface. Here, we describe the magnetoresistive properties of micro-Hall devices fabricated using InAlSb/InAsSb/InAlSb heterostructures where electrical conduction was confined to a 30 nm-InAsSb two-dimensional electron gas layer. The 300 K electron mobility and sheet carrier concentration were 36 500 cm(2) V-1 s(-1) and 2.5 x 10(11) cm(-2), respectively. The maximum current-related sensitivity was 2 750 V A(-1) T-1, which was about an order of magnitude greater than AlGaAs/InGaAs pseudomorphic heterostructures devices. Photolithography was used to fabricate 1 mu m x 1 mu m Hall probes, which were installed into a scanning Hall probe microscope and used to image the surface of a hard disk

A Comparative Study of the Parker Instability under Three Models of the Galactic Gravity

To examine how non-uniform nature of the Galactic gravity might affect length and time scales of the Parker instability, we took three models of gravity, uniform, linear and realistic ones. To make comparisons of the three gravity models on a common basis, we first fixed the ratio of magnetic pressure to gas pressure at $\alpha$ = 0.25, that of cosmic-ray pressure at $\beta$ = 0.4, and the rms velocity of interstellar clouds at $a_s$ = 6.4 km s$^{-1}$, and then adjusted parameters of the gravity models in such a way that the resulting density scale heights for the three models may all have the same value of 160 pc. Performing linear stability analyses onto equilibrium states under the three models with the typical ISM conditions, we calculate the maximum growth rate and corresponding length scale for each of the gravity models. Under the uniform gravity the Parker instability has the growth time of 1.2$\times10^{8}$ years and the length scale of 1.6 kpc for symmetric mode. Under the realistic gravity it grows in 1.8$\times10^{7}$ years for both symmetric and antisymmetric modes, and develops density condensations at intervals of 400 pc for the symmetric mode and 200 pc for the antisymmetric one. A simple change of the gravity model has thus reduced the growth time by almost an order of magnitude and its length scale by factors of four to eight. These results suggest that an onset of the Parker instability in the ISM may not necessarily be confined to the regions of high $\alpha$ and $\beta$.Comment: Accepted for publication in ApJ, using aaspp4.sty, 18 text pages with 9 figure

Low density molecular gas in the galaxy

The distributions and physical conditions in molecular gas in the interstellar medium have been investigated in both the Galaxy and towards external galaxies. For example, Galactic plane surveys in the CO J =1-0 line with the Columbia 1.2-m telescope and with the Five College Radio Astronomy Observatory (FCRAO) 14-m telescopes have been able to trace spiral arms more clearly than HI surveys have been able to reveal, and indicate that most of molecular mass is contained in Giant Molecular Clouds (GMCs). Extensive maps of the whole Milky Way showed two prominent features, the 4-kpc molecular ring and the Galactic center. The physical conditions in the Galaxy have been studied by comparing the intensity of CO J =1-0 line with those of other lines, e.g., 13CO J =1-0, higher J transitions of CO, and dense gas tracers such as HCO+, CS, and HCN. Previous studies were however strongly biased towards regions where CO emission was known to be intense. The radial distribution of molecular hydrogen shows that most of the H2 gas which is indirectly traced by observations of its associated CO emission, originates from the inner Galaxy (Dame 1993). Extending outwards from a galacto-centric distance of ~7 kpc, the H2 mass surface density decreases dramatically, and HI dominates over H2 in the outer Galaxy. What are physical conditions of molecular gas where the CO emission is relatively weak, and can we really trace all of the molecular gas through obervations of CO? These kinds of problems have not been solved yet, but are addressed in our study

Radio and gamma-ray constraints on dark matter annihilation in the Galactic center

We determine upper limits on the dark matter (DM) self-annihilation cross section for scenarios in which annihilation leads to the production of electron--positron pairs. In the Galactic centre (GC), relativistic electrons and positrons produce a radio flux via synchroton emission, and a gamma ray flux via bremsstrahlung and inverse Compton scattering. On the basis of archival, interferometric and single-dish radio data, we have determined the radio spectrum of an elliptical region around the Galactic centre of extent 3 degrees semi-major axis (along the Galactic plane) and 1 degree semi-minor axis and a second, rectangular region, also centered on the GC, of extent 1.6 degrees x 0.6 degrees. The radio spectra of both regions are non-thermal over the range of frequencies for which we have data: 74 MHz -- 10 GHz. We also consider gamma-ray data covering the same region from the EGRET instrument (about GeV) and from HESS (around TeV). We show how the combination of these data can be used to place robust constraints on DM annihilation scenarios, in a way which is relatively insensitive to assumptions about the magnetic field amplitude in this region. Our results are approximately an order of magnitude more constraining than existing Galactic centre radio and gamma ray limits. For a DM mass of m_\chi =10 GeV, and an NFW profile, we find that the velocity-averaged cross-section must be less than a few times 10^-25 cm^3 s^-1.Comment: 14 pages, 9 figures. Version accepted for publication in PRD. Reference section updated/extended

Parker Instability in a Self-Gravitating Magnetized Gas Disk: I. Linear Stability Analysis

To be a formation mechanism of such large-scale structures as giant molecular clouds (GMCs) and HI superclouds, the classical Parker instability driven by external gravity has to overcome three major obstacles: The convective motion accompanying the instability generates thin sheets than large condensations. The degree of density enhancement achieved by the instability is too low to make dense interstellar clouds. The time and the length scales of the instability are significantly longer and larger than the estimated formation time and the observed mean separation of the GMCs, respectively. This paper examines whether a replacement of the driving agent from the external to the self gravity might remove these obstacles by activating the gravitational instability in the Galactic ISM disk. The self gravity can suppress the convective motions, and a cooperative action of the Jeans and the Parker instabilities can remove all the obstacles confronting the classical version of the Parker instability. The mass and mean separation of the structures resulting from the odd-parity undular mode solution are shown to agree better with the HI superclouds than with the GMCs. We briefly discuss how inclusions of the external gravity and cosmic rays would modify behaviors of the odd-parity undular mode solution.Comment: 53 pages, 21 figure

Multimodal Neuroimages of Adrenoleukodystrophy in Early Stage

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Three-dimensional simulations of the Parker instability in a uniformly rotating disk

We investigate the effects of rotation on the evolution of the Parker instability by carrying out three-dimensional numerical simulations with an isothermal magnetohydrodynamic code. These simulations extend our previous work on the nonlinear evolution of the Parker instability by J. Kim and coworkers. The initial equilibrium system is composed of exponentially stratified gas and a field (along the azimuthal direction) in a uniform gravity (along the downward vertical direction). The computational box, placed at the solar neighborhood, is set to rotate uniformly around the Galactic center with a constant angular speed. The instability has been initialized by random velocity perturbations. In the linear stage, the evolution is not much different from that without rotation, and the mixed (undular + interchange) mode regulates the system. The interchange mode induces alternating dense and rarefied regions with small radial wavelengths, while the undular mode bends the magnetic field lines in the plane of the azimuthal and vertical directions. In the nonlinear stage, flow motion overall becomes chaotic, as in the case without rotation. However, as the gas in higher positions slides down along field lines forming supersonic flows, the Coriolis force becomes important. As oppositely directed flows fall into valleys along both sides of the magnetic field lines, they experience the Coriolis force toward opposite directions, which twists the magnetic field lines there. Hence, we suggest that the Coriolis force plays a role in randomizing the magnetic field. The three-dimensional density structure formed by the instability is still sheetlike with the short dimension along the radial direction, as in the case without rotation. However, the long dimension is now slightly tilted with respect to the mean field direction. The shape of high-density regions is a bit rounder. The maximum enhancement factor of the vertical column density relative to its initial value is about 1.5, which is smaller than that in the case without rotation. We conclude that uniform rotation does not change our point of view that the Parker instability alone is not a viable mechanism for the formation of giant molecular cloudsopen252

Search for the Electric Dipole Moment of the tau Lepton

We have searched for a CP violation signature arising from an electric dipole moment (d_tau) of the tau lepton in the e+e- -> tau+tau- reaction. Using an optimal observable method and 29.5 fb^{-1} of data collected with the Belle detector at the KEKB collider at sqrt{s} = 10.58 GeV, we find Re(d_tau) = (1.15 +- 1.70) x 10^{-17} ecm and Im(d_tau) = (-0.83 +- 0.86) x 10^{-17} ecm and set the 95% confidence level limits -2.2 < Re(d_tau) < 4.5 (10^{-17}ecm) and -2.5 < Im(d_tau) < 0.8 (10^{-17}ecm).Comment: 15 pages, LaTeX, 21 figures, submitted to Phys. Lett.

Radio Frequency Spectra of 388 Bright 74 MHz Sources

As a service to the community, we have compiled radio frequency spectra from the literature for all sources within the VLA Low Frequency Sky Survey (VLSS) that are brighter than 15 Jy at 74 MHz. Over 160 references were used to maximize the amount of spectral data used in the compilation of the spectra, while also taking care to determine the corrections needed to put the flux densities from all reference on the same absolute flux density scale. With the new VLSS data, we are able to vastly improve upon previous efforts to compile spectra of bright radio sources to frequencies below 100 MHz because (1) the VLSS flux densities are more reliable than those from some previous low frequency surveys and (2) the VLSS covers a much larger area of the sky (declination >-30 deg.) than many other low frequency surveys (e.g., the 8C survey). In this paper, we discuss how the spectra were constructed and how parameters quantifying the shapes of the spectra were derived. Both the spectra and the shape parameters are made available here to assist in the calibration of observations made with current and future low frequency radio facilities.Comment: Accepted to ApJ