We report on studies of the viability and sensitivity of the Askaryan Radio Array (ARA), a new initiative to develop a Teraton-scale ultra-high energy neutrino detector in deep, radio-transparent ice ...near Amundsen-Scott station at the South Pole. An initial prototype ARA detector system was installed in January 2011, and has been operating continuously since then. We describe measurements of the background radio noise levels, the radio clarity of the ice, and the estimated sensitivity of the planned ARA array given these results, based on the first five months of operation. Anthropogenic radio interference in the vicinity of the South Pole currently leads to a few-percent loss of data, but no overall effect on the background noise levels, which are dominated by the thermal noise floor of the cold polar ice, and galactic noise at lower frequencies. We have also successfully detected signals originating from a 2.5km deep impulse generator at a distance of over 3 km from our prototype detector, confirming prior estimates of kilometer-scale attenuation lengths for cold polar ice. These are also the first such measurements for propagation over such large slant distances in ice. Based on these data, ARA-37, the ∼200km2 array now in its initial construction phase, will achieve the highest sensitivity of any planned or existing neutrino detector in the 1016–1019eV energy range.
Cardiac inwardly rectifying Kir current (IK1) mediates terminal repolarisation and is critical for the stabilization of the diastolic membrane potential. Its predominant molecular basis in mammalian ...ventricle is heterotetrameric assembly of Kir2.1 and Kir2.2 channel subunits. It has been shown that PKC inhibition of IK1 promotes focal ventricular ectopy. However, the underlying molecular mechanism has not been fully elucidated to date.
In the Xenopus oocyte expression system, we observed a pronounced PKC-induced inhibition of Kir2.2 but not Kir2.1 currents. The PKC regulation of Kir2.2 could be reproduced by an activator of conventional PKC isoforms and antagonized by pharmacological inhibition of PKCβ. In isolated ventricular cardiomyocytes (rat, mouse), pharmacological activation of conventional PKC isoforms induced a pronounced inhibition of IK1. The PKC effect in rat ventricular cardiomyocytes was markedly attenuated following co-application of a small molecule inhibitor of PKCβ. Underlining the critical role of PKCβ, the PKC-induced inhibition of IK1 was absent in homozygous PKCβ knockout-mice. After heterologous expression of Kir2.1-Kir2.2 concatemers in Xenopus oocytes, heteromeric Kir2.1/Kir2.2 currents were also inhibited following activation of PKC.
We conclude that inhibition of cardiac IK1 by PKC critically depends on the PKCβ isoform and Kir2.2 subunits. This regulation represents a potential novel target for the antiarrhythmic therapy of focal ventricular arrhythmias.
BACKGROUND AND PURPOSE TASK1 (K2P3.1) two‐pore‐domain K+ channels contribute substantially to the resting membrane potential in human pulmonary artery smooth muscle cells (hPASMC), modulating ...vascular tone and diameter. The endothelin‐1 (ET‐1) pathway mediates vasoconstriction and is an established target of pulmonary arterial hypertension (PAH) therapy. ET‐1‐mediated inhibition of TASK1 currents in hPASMC is implicated in the pathophysiology of PAH. This study was designed to elucidate molecular mechanisms underlying inhibition of TASK1 channels by ET‐1.
EXPERIMENTAL APPROACH Two‐electrode voltage clamp and whole‐cell patch clamp electrophysiology was used to record TASK1 currents from hPASMC and Xenopus oocytes.
KEY RESULTS ET‐1 inhibited TASK1‐mediated IKN currents in hPASMC, an effect attenuated by Rho kinase inhibition with Y‐27632. In Xenopus oocytes, TASK1 current reduction by ET‐1 was mediated by endothelin receptors ETA (IC50= 0.08 nM) and ETB (IC50= 0.23 nM) via Rho kinase signalling. TASK1 channels contain two putative Rho kinase phosphorylation sites, Ser336 and Ser393. Mutation of Ser393 rendered TASK1 channels insensitive to ETA‐ or ETB‐mediated current inhibition. In contrast, removal of Ser336 selectively attenuated ETA‐dependent TASK1 regulation without affecting the ETB pathway.
CONCLUSIONS AND IMPLICATIONS ET‐1 regulated vascular TASK1 currents through ETA and ETB receptors mediated by downstream activation of Rho kinase and direct channel phosphorylation. The Rho kinase pathway in PASMC may provide a more specific therapeutic target in pulmonary arterial hypertension treatment.
Since summer 2021, the Radio Neutrino Observatory in Greenland (RNO-G) is searching for astrophysical neutrinos at energies Formula omitted PeV by detecting the radio emission from particle showers ...in the ice around Summit Station, Greenland. We present an extensive simulation study that shows how RNO-G will be able to measure the energy of such particle cascades, which will in turn be used to estimate the energy of the incoming neutrino that caused them. The location of the neutrino interaction is determined using the differences in arrival times between channels and the electric field of the radio signal is reconstructed using a novel approach based on Information Field Theory. Based on these properties, the shower energy can be estimated. We show that this method can achieve an uncertainty of 13% on the logarithm of the shower energy after modest quality cuts and estimate how this can constrain the energy of the neutrino. The method presented in this paper is applicable to all similar radio neutrino detectors, such as the proposed radio array of IceCube-Gen2.
Over the last 25 years, radiowave detection of neutrino-generated signals, using cold polar ice as the neutrino target, has emerged as perhaps the most promising technique for detection of ...extragalactic ultra-high energy neutrinos (corresponding to neutrino energies in excess of 0.01 Joules, or 1017 electron volts). During the summer of 2021 and in tandem with the initial deployment of the Radio Neutrino Observatory in Greenland (RNO-G), we conducted radioglaciological measurements at Summit Station, Greenland to refine our understanding of the ice target. We report the result of one such measurement, the radio-frequency electric field attenuation length $L_\alpha$. We find an approximately linear dependence of $L_\alpha$ on frequency with the best fit of the average field attenuation for the upper 1500 m of ice: $\langle L_\alpha \rangle = ( ( 1154 \pm 121) - ( 0.81 \pm 0.14) \, ( \nu /{\rm MHz}) ) \,{\rm m}$ for frequencies ν ∈ 145 − 350 MHz.
► We describe a dark matter experiment using NaI crystals deployed in South Pole ice. ► We explore the sensitivity of a 250kg NaI dark matter experiment. ► A 250kg NaI experiment will investigate the ...annual modulation reported by DAMA/LIBRA.
Astrophysical observations and cosmological data have led to the conclusion that nearly one quarter of the Universe consists of dark matter. Should dark matter interact with nucleons, it has been postulated that an observable signature of dark matter is an annual modulation in the rate of dark matter-nucleon interactions taking place in an Earth-bound experiment. To search for this effect, we introduce the concept for a new dark matter experiment using NaI scintillation detectors deployed deep in the South Pole ice. This experiment complements dark matter search efforts in the Northern Hemisphere and will investigate the observed annual modulation in the DAMA/LIBRA and DAMA/NaI experiments. The unique location will permit the study of background effects correlated with seasonal variations and the surrounding environment. This paper describes the experimental concept and explores the sensitivity of a 250kg NaI experiment at the South Pole.
We report the measurement of muons and muon-induced phosphorescence in DM-Ice17, a NaI(Tl) direct detection dark matter experiment at the South Pole. Muon interactions in the crystal are identified ...by their observed pulse shape and large energy depositions. The measured muon rate in DM-Ice17 is 2.93+ or -0.04 mu /crystal/day with a modulation amplitude of 12.3+ or -1.7%, consistent with expectation. Following muon interactions, we observe long-lived phosphorescence in the NaI(Tl) crystals with a decay time of 5.5+ or -0.5s. The prompt energy deposited by a muon is correlated to the amount of delayed phosphorescence, the brightest of which consist of tens of millions of photons. These photons are distributed over tens of seconds with a rate and arrival timing that do not mimic a scintillation signal above 2keV sub(ee). While the properties of phosphorescence vary among individual crystals, the annually modulating signal observed by DAMA cannot be accounted for by phosphorescence with the characteristics observed in DM-Ice17.
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