204 research outputs found

    Structure of smAKAP and its regulation by PKA-mediated phosphorylation

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    The A-kinase anchoring protein (AKAP) smAKAP has three extraordinary features; it is very small, it is anchored directly to membranes by acyl motifs, and it interacts almost exclusively with the type I regulatory subunits (RI) of cAMP-dependent kinase (PKA). Here, we determined the crystal structure of smAKAP's A-kinase binding domain (smAKAP-AKB) in complex with the dimerization/docking (D/D) domain of RIα which reveals an extended hydrophobic interface with unique interaction pockets that drive smAKAP's high specificity for RI-subunits. We also identify a conserved PKA phosphorylation site at Ser66 in the AKB domain which we predict would cause steric clashes and disrupt binding. This correlates with in vivo co-localization and fluorescence polarization studies where Ser66 AKB phosphorylation ablates RI-binding. Hydrogen/deuterium exchange studies confirm that the AKB helix is accessible and dynamic. Furthermore, full-length smAKAP as well as the unbound AKB is predicted to contain a break at the phosphorylation site, and circular dichroism measurements confirm that the AKB domain loses its helicity following phosphorylation. Since the active site of PKA's catalytic subunit does not accommodate α-helices, we predict that the inherent flexibility of the AKB domain enables its phosphorylation by PKA. This represents a novel mechanism, whereby activation of anchored PKA can terminate its binding to smAKAP affecting the regulation of localized cAMP-signaling events. This article is protected by copyright. All rights reserved

    National Athletic Trainers' Association Position Statement: Preventing Sudden Death in Sports

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    To present recommendations for the prevention and screening, recognition, and treatment of the most common conditions resulting in sudden death in organized sports

    Außerschulische Lernorte von Kindern : Reflexionen - Konzeptionen - Perspektiven

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    Weitere Hrsg.: Martin Gröger, Daria Johanna Schneider, Jutta Wiesemann. Publikation anlässlich der Tagung „Orte und Räume der Generationenvermittlung – Außerschulisches Lernen von Kindern“, Universität Siegen, 5.-6. Oktober 2017Die Wertschätzung des außerschulischen Lernens hat in der Schulpädagogik eine lange Tradition und ist besonders in der Grundschule und im Sachunterricht etabliert. Mit einem Blick auf Möglichkeiten der Vernetzung schulischer und außerschulischer Lernwelten rückt das Bildungspotenzial und die Bildungswirksamkeit außerschulischer Lernorte zunehmend in den Aufmerksamkeitsfokus bildungspolitischer, schulpädagogischer sowie didaktischer Reflexion. Eine Gelegenheit zu einer vertieften Auseinandersetzung mit diversen außerschulischen Lernarrangements bot die Tagung zum Thema „Orte und Räume der Generationenvermittlung – außerschulisches Lernen von Kindern“, die im Oktober 2017 an der Universität Siegen stattfand. Die vielfältigen Impulse und wertvollen Überlegungen der Tagungsteilnehmerinnen und -teilnehmer werden in der vorliegenden Publikation „Außerschulische Lernorte von Kindern – Reflexionen – Konzeptionen – Perspektiven“ aufgegriffen. Die Beiträge des Bandes gliedern sich in drei Themenblöcke: zum einen werden konzeptionelle Überlegungen zum außerschulischen Lernort vorgestellt, zum anderen eröffnet der Band Einblicke in die Entwicklung und Ausgestaltung sowie in den Einsatz von Materialien am außerschulischen Lernort. Der dritte Themenblock gibt abschließend einige Beispiele für die mannigfaltigen Möglichkeiten, schulische und außerschulische Lernorte effektiv zu vernetzen

    Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

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    A measurement of the cosmic-ray spectrum for energies exceeding 4×10184{\times}10^{18} eV is presented, which is based on the analysis of showers with zenith angles greater than 6060^{\circ} detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above 5.3×10185.3{\times}10^{18} eV, the "ankle", the flux can be described by a power law EγE^{-\gamma} with index γ=2.70±0.02(stat)±0.1(sys)\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)} followed by a smooth suppression region. For the energy (EsE_\text{s}) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find Es=(5.12±0.25(stat)1.2+1.0(sys))×1019E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19} eV.Comment: Replaced with published version. Added journal reference and DO

    Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

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    The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

    Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

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    We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file
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