Functional modulation of the transient outward current Ito by KCNE beta-subunits and regional distribution in human non-failing and failing hearts

Objectives: The function of Kv4.3 (KCND3) channels, which underlie the transient outward current I,, in human heart, can be modulated by several accessory subunits such as KChIP2 and KCNE1-KCNE5. Here we aimed to determine the regional expression of Kv4.3, KChIP2, and KCNE mRNAs in non-failing and failing human hearts and to investigate the functional consequences of subunit coexpression in heterologous expression systems. Methods: We quantified mRNA levels for two Kv4.3 isoforms, Kv4.3-S and Kv4.3-L, and for KChIP2 as well as KCNE1-KCNE5 with real-time RT-PCR. We also studied the effects of KCNEs on Kv4.3 + KChIP2 current characteristics in CHO cells with the whole-cell voltage-clamp method. Results: In non-failing hearts, low expression was found for KCNE1, KCNE3, and KCNE5, three times higher expression for KCNE2, and 60 times higher for KCNE4. Transmural gradients were detected only for KChIP2 in left and right ventricles. Compared to non-failing tissue, failing hearts showed higher expression of Kv4.3-L and KCNE1 and lower of Kv4.3-S, KChIP2, KCNE4, and KCNE5. In CHO cells, Kv4.3 + KChIP2 currents were differentially modified by co-expressed KCNEs: time constants of inactivation were shorter with KCNE1 and KCNE3-5 while time-to-peak was decreased, and V-0.5 of steady-state inactivation was shifted to more negative potentials by all KCNE subunits. Importantly, KCNE2 induced a unique and prominent 'overshoot' of peak current during recovery from inactivation similar to that described for human I-to while other KCNE subunits induced little (KCNE4,5) or no overshoot. Conclusions: All KCNEs are expressed in the human heart at the transcript level. Compared to It. in native human myocytes, none of the combination of KChIP2 and KCNE produced an ideal congruency in current characteristics, suggesting that additional factors contribute to the regulation of the native I-to channel

Analytic models of ducted turbomachinery tone noise sources. Volume 2: Subprogram documentation

Analytical models were developed for computing the periodic sound pressures of subsonic fans in an infinite hardwall annular duct with uniform flow. The computer programs are described which are used for numerical computations of sound pressure mode amplitudes. The data are applied to the acoustic properties of turbomachinery

Analytic models of ducted turbomachinery tone noise sources. Volume 1: Analysis

The analytic models developed for computing the periodic sound pressure of subsonic fans and compressors in an infinite, hardwall annular duct with uniform flow are described. The basic sound-generating mechanism is the scattering into sound waves of velocity disturbances appearing to the rotor or stator blades as a series of harmonic gusts. The models include component interactions and rotor alone

Analytic models of ducted turbomachinery tone noise sources. Volume 3: Program test case results

Computer programs for analyzing the acoustic properties of turbomachinery with ducted flow were developed. The models include component interactions and rotor alone. Test case results determined from the computer programs are presented

Simulation and Analysis Chain for Acoustic Ultra-high Energy Neutrino Detectors in Water

Acousticneutrinodetectionisapromisingapproachforlarge-scaleultra-highenergyneutrinodetectorsinwater.In this article, a Monte Carlo simulation chain for acoustic neutrino detection devices in water will be presented. The simulation chain covers the generation of the acoustic pulse produced by a neutrino interaction and its propagation to the sensors within the detector. Currently, ambient and transient noise models for the Mediterranean Sea and simulations of the data acquisition hardware, equivalent to the one used in ANTARES/AMADEUS, are implemented. A pre-selection scheme for neutrino-like signals based on matched filtering is employed, as it is used for on-line filtering. To simulate the whole processing chain for experimental data, signal classification and acoustic source reconstruction algorithms are integrated in an analysis chain. An overview of design and capabilities of the simulation and analysis chain will be presented and preliminary studies will be discussed.Comment: 6 pages, 5 figures, ARENA 2012. arXiv admin note: substantial text overlap with arXiv:1304.057

GREAT: the SOFIA high-frequency heterodyne instrument

We describe the design and construction of GREAT, the German REceiver for Astronomy at Terahertz frequencies operated on the Stratospheric Observatory for Infrared Astronomy (SOFIA). GREAT is a modular dual-color heterodyne instrument for highresolution far-infrared (FIR) spectroscopy. Selected for SOFIA's Early Science demonstration, the instrument has successfully performed three Short and more than a dozen Basic Science flights since first light was recorded on its April 1, 2011 commissioning flight. We report on the in-flight performance and operation of the receiver that - in various flight configurations, with three different detector channels - observed in several science-defined frequency windows between 1.25 and 2.5 THz. The receiver optics was verified to be diffraction-limited as designed, with nominal efficiencies; receiver sensitivities are state-of-the-art, with excellent system stability. The modular design allows for the continuous integration of latest technologies; we briefly discuss additional channels under development and ongoing improvements for Cycle 1 observations. GREAT is a principal investigator instrument, developed by a consortium of four German research institutes, available to the SOFIA users on a collaborative basis

Development of Combined Opto-Acoustical Sensor Modules

The faint fluxes of cosmic neutrinos expected at very high energies require large instrumented detector volumes. The necessary volumes in combination with a sufficient shielding against background constitute forbidding and complex environments (e.g. the deep sea) as sites for neutrino telescopes. To withstand these environments and to assure the data quality, the sensors have to be reliable and their operation has to be as simple as possible. A compact sensor module design including all necessary components for data acquisition and module calibration would simplify the detector mechanics and ensures the long term operability of the detector. The compact design discussed here combines optical and acoustical sensors inside one module, therefore reducing electronics and additional external instruments for calibration purposes. In this design the acoustical sensor is primary used for acoustic positioning of the module. The module may also be used for acoustic particle detection and marine science if an appropriate acoustical sensor is chosen. First tests of this design are promising concerning the task of calibration. To expand the field of application also towards acoustic particle detection further improvements concerning electromagnetic shielding and adaptation of the single components are necessary.Comment: 4 pages, 2 figures, ARENA2010 proceeding

Thermo-acoustic Sound Generation in the Interaction of Pulsed Proton and Laser Beams with a Water Target

The generation of hydrodynamic radiation in interactions of pulsed proton and laser beams with matter is explored. The beams were directed into a water target and the resulting acoustic signals were recorded with pressure sensitive sensors. Measurements were performed with varying pulse energies, sensor positions, beam diameters and temperatures. The obtained data are matched by simulation results based on the thermo-acoustic model with uncertainties at a level of 10%. The results imply that the primary mechanism for sound generation by the energy deposition of particles propagating in water is the local heating of the medium. The heating results in a fast expansion or contraction and a pressure pulse of bipolar shape is emitted into the surrounding medium. An interesting, widely discussed application of this effect could be the detection of ultra-high energetic cosmic neutrinos in future large-scale acoustic neutrino detectors. For this application a validation of the sound generation mechanism to high accuracy, as achieved with the experiments discussed in this article, is of high importance.Comment: 12 pages, 15 figure

Sulphur-bearing molecules in diffuse molecular clouds: new results from SOFIA/GREAT and the IRAM 30 m telescope

We have observed five sulphur-bearing molecules in foreground diffuse molecular clouds lying along the sight-lines to five bright continuum sources. We have used the GREAT instrument on SOFIA to observe the 1383 GHz $^2\Pi_{3/2} J=5/2-3/2$ transitions of SH towards the star-forming regions W31C, G29.96-0.02, G34.3+0.1, W49N and W51, detecting foreground absorption towards all five sources; and the EMIR receivers on the IRAM 30m telescope at Pico Veleta to detect the H$_2$S 1(10)-1(01), CS J=2-1 and SO 3(2)-2(1) transitions. In nine foreground absorption components detected towards these sources, the inferred column densities of the four detected molecules showed relatively constant ratios, with N(SH)/N(H$_2$S) in the range 1.1 - 3.0, N(CS)/N(H$_2$S) in the range 0.32 - 0.61, and N(SO)/N(H$_2$S) in the range 0.08 - 0.30. The observed SH/H$_2$ ratios - in the range (0.5-2.6) $\times 10^{-8}$ - indicate that SH (and other sulphur-bearing molecules) account for << 1% of the gas-phase sulphur nuclei. The observed abundances of sulphur-bearing molecules, however, greatly exceed those predicted by standard models of cold diffuse molecular clouds, providing further evidence for the enhancement of endothermic reaction rates by elevated temperatures or ion-neutral drift. We have considered the observed abundance ratios in the context of shock and turbulent dissipation region (TDR) models. Using the TDR model, we find that the turbulent energy available at large scale in the diffuse ISM is sufficient to explain the observed column densities of SH and CS. Standard shock and TDR models, however, fail to reproduce the column densities of H$_2$S and SO by a factor of about 10; more elaborate shock models - in which account is taken of the velocity drift, relative to H$_2$, of SH molecules produced by the dissociative recombination of H$_3$S$^+$ - reduce this discrepancy to a factor ~ 3.Comment: 30 pages, accepted for publication in A&

[12CII] and [13CII] 158 mum emission from NGC 2024: Large column densities of ionized carbon

Context: We analyze the NGC 2024 HII region and molecular cloud interface using [12CII] and [13CII] observations. Aims: We attempt to gain insight into the physical structure of the interface layer between the molecular cloud and the HII region. Methods. Observations of [12CII] and [13CII] emission at 158 {\mu}m with high spatial and spectral resolution allow us to study the detailed structure of the ionization front and estimate the column densities and temperatures of the ionized carbon layer in the PDR. Results: The [12CII] emission closely follows the distribution of the 8 mum continuum. Across most of the source, the spectral lines have two velocity peaks similar to lines of rare CO isotopes. The [13CII] emission is detected near the edge-on ionization front. It has only a single velocity component, which implies that the [12CII] line shape is caused by self-absorption. An anomalous hyperfine line-intensity ratio observed in [13CII] cannot yet be explained. Conclusions: Our analysis of the two isotopes results in a total column density of N(H)~1.6\times10^23 cm^-2 in the gas emitting the [CII] line. A large fraction of this gas has to be at a temperature of several hundred K. The self-absorption is caused by a cooler (T<=100 K) foreground component containing a column density of N(H)~10^22 cm^-2