Platelet G i protein Gα i2 is an essential mediator of thrombo-inflammatory organ damage in mice

Platelets are crucial for hemostasis and thrombosis and exacerbate tissue injury following ischemia and reperfusion. Important regulators of platelet function are G proteins controlled by seven transmembrane receptors. The Gi protein Gα(i2) mediates platelet activation in vitro, but its in vivo role in hemostasis, arterial thrombosis, and postischemic infarct progression remains to be determined. Here we show that mice lacking Gα(i2) exhibit prolonged tail-bleeding times and markedly impaired thrombus formation and stability in different models of arterial thrombosis. We thus generated mice selectively lacking Gα(i2) in megakaryocytes and platelets (Gna(i2)(fl/fl)/PF4-Cre mice) and found bleeding defects comparable to those in global Gα(i2)-deficient mice. To examine the impact of platelet Gα(i2) in postischemic thrombo-inflammatory infarct progression, Gna(i2)(fl/fl)/PF4-Cre mice were subjected to experimental models of cerebral and myocardial ischemia/reperfusion injury. In the model of transient middle cerebral artery occlusion stroke Gna(i2)(fl/fl)/PF4-Cre mice developed significantly smaller brain infarcts and fewer neurological deficits than littermate controls. Following myocardial ischemia, Gna(i2)(fl/fl)/PF4-Cre mice showed dramatically reduced reperfusion injury which correlated with diminished formation of the ADP-dependent platelet neutrophil complex. In conclusion, our data provide definitive evidence that platelet Gα(i2) not only controls hemostatic and thrombotic responses but also is critical for the development of ischemia/reperfusion injury in vivo.Fil: Devanathan, Vasudharani. University of Tübingen; AlemaniaFil: Hagedorn, Ina. University Hospital; AlemaniaFil: Köhler, David. University of Tübingen; AlemaniaFil: Pexa, Katja. Universitat Dusseldorf; AlemaniaFil: Cherpokova, Deya. University Hospital; AlemaniaFil: Kraft, Peter. Universität Würzburg; AlemaniaFil: Singh, Madhurendra. Universitat Dusseldorf; AlemaniaFil: Rosenberger, Peter. University of Tübingen; AlemaniaFil: Stoll, Guido. Universität Würzburg; AlemaniaFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Research Triangle Park; AlemaniaFil: Piekorz, Roland P.. Universitat Dusseldorf; AlemaniaFil: Beer-Hammer, Sandra. University of Tübingen; AlemaniaFil: Nieswandt, Bernhard. University Hospital; AlemaniaFil: Nürnberg, Bernd. University of Tübingen; Alemani

Characterization of the radiation tolerance of cryogenic diodes for the High Luminosity LHC inner triplet circuit

Cryogenic bypass diodes are part of the baseline powering layout for the circuits of the new Nb3Sn based final focus magnets of the high luminosity Large Hadron Collider. They will protect the magnets against excessive transient voltages during a nonuniform quenching process. The diodes are located inside an extension to the magnet cryostat, operated in superfluid helium and exposed to ionizing radiation. Therefore, the radiation tolerance of different types of diodes has been tested at cryogenic temperatures in CERN’s CHARM irradiation test facility during its 2018 run. The forward bias characteristics, the turn-on voltage and the reverse blocking voltage of each diode were measured weekly at 4.2 K and 77 K, as a function of the accumulated radiation dose. The diodes were submitted to a total dose close to 12 kGy and a 1 MeV neutron equivalent fluence of 2.2×1014  cm−2. After the end of the irradiation program the annealing behavior of the diodes was tested by increasing the temperature slowly to 293 K. This paper describes the experimental setup, the measurement procedure and the analysis of the measurements performed during the irradiation program as well as the results of the annealing study

Experimental Setup to Characterize the Radiation Hardness of Cryogenic Bypass Diodes for the HL-LHC Inner Triplet Circuits

For the high luminosity upgrade of the Large Hadron Collider (LHC), it is planned to replace the existing triplet quadrupole magnets with Nb₃Sn quadrupole magnets, which provide a comparable integrated field gradient with a significantly increased aperture. These magnets will be powered through a novel superconducting link based on MgB₂ cables. One option for the powering layout of this triplet circuit is the use of cryogenic bypass diodes, where the diodes are located inside an extension to the magnet cryostat and operated in superfluid helium. Hence, they are exposed to radiation. For this reason the radiation hardness of existing LHC type bypass diodes and more radiation tolerant prototype diodes needs to be tested up to the radiation doses expected at their planned position during their lifetime. A first irradiation test is planned in CERN's CHARM facility starting in spring 2018. Therefore, a cryo-cooler based cryostat to irradiate and test LHC type diodes in-situ has been designed and constructed. This paper will describe the properties of the sample diodes, the experimental roadmap and the setup installed in CHARM. Finally, the first measurement results will be discussed

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Zur Lage des wissenschaftlichen Nachwuchses in Deutschland

ZusammenfassungDer vorliegende Bericht gibt Auskunft über die Stellenstruktur, die Zusammensetzung der Professorien und des akademischen Mittelbaus sowie die Entwicklung der Qualifikationsarbeiten und anstehende Emeritierungen an den Fakultäten und nichtfakultären Einrichtungen für Katholische Theologie in Deutschland. Im Zehnjahresvergleich sank die Zahl der Professuren lediglich um 9 %. Demgegenüber reduzierte sich die Zahl der Habilitationen pro Jahr gegenüber dem Zeitraum 2000 – 2006 um 37 % auf durchschnittlich 14,4 Habilitationen pro Jahr. Der Frauenanteil an den ProfessorInnen liegt bei 17 %; beim Mittelbau sind es 44 %. Überdurchschnittlich viele Frauen schließen ihre Promotionsprojekte gar nicht oder erst nach langer Zeit ab. Bei den haushaltsfinanzierten Stellen für Wissenschaftliche MitarbeiterInnen gab es in den letzten fünf Jahren einen deutlichen Zuwachs, so dass der akademische Mittelbau heute wieder größer ist als 2006. Durch den Einbezug der Katholisch-Theologischen Fakultäten in Österreich, Südtirol und der Schweiz lässt sich schließlich abschätzen, dass im deutschsprachigen Raum bis 2020 etwa mit 76 Ausschreibungen von Professuren zu rechnen ist, auf die etwa 186 habilitierte BewerberInnen kommen könnten (Nachwuchsquote 2,4). Eine besonders geringe Zahl an BewerberInnen ist u. a. für praktisch-theologische Fächer zu erwarten.AbstractThis report provides information about the structure of academic positions, the composition of professorships and academic junior faculty, as well as the development of scientific qualification works and upcoming retirements (“Emeritierungen”) within departments and other institutions of Catholic Theology in Germany. The results show that the number of professorships dropped 9 percent in the last ten years. Moreover, compared to the previous study period between 2000 and 2006, the number of postdoctoral lecture qualifications (“Habilitationen”) decreased by 37 percent to an average of 14.4 per year. The share of women holding professorships is 17 percent; the share of women in academic junior faculty is 44 percent. According to the data, an above average number of women require a longer period of time to finish their dissertation or don’t finish it at all. Internally financed jobs for research assistants strongly increased during the last five years. The academic junior faculty is now bigger than in 2006. Until 2020, we estimate that 186 qualified scientists will apply for 76 professorship vacancies (professional qualification rate 2.4) in German speaking countries including Austria, Switzerland and South Tyrol. We expect an especially low number of applicants for the practical theological disciplines

Meller: Resonances in a box

Abstract We investigate a numerical method for studying resonances in quantum mechanics. We prove rigorously that this method yields accurate approximations to resonance energies and widths for shape resonances in the semiclassical limit. I Introduction In this paper we rigorously analyze the validity of a numerical technique for studying resonances in quantum mechanics. The technique is called, "A spherical box approach to resonances," by its inventors, Maier et al The technique is an "L 2 method," in contrast to time-independent scattering theory methods, such as the calculation of phase shifts near energies where a resonance is expected. These L 2 methods are surveyed, e.g. , in The basic physical idea underlying all L 2 methods is that a resonance wavefunction is a state that is concentrated mainly in the interaction region. In contrast, states associated with the rest of the continuous spectrum are not concentrated in any bounded interval. As a consequence, when the system is confined to a box that is large compared to the interaction region and the size of the box is varied, the resonance wavefunction is much less influenced than the states from the rest of the continuous spectrum. This should be visible in the spectrum, and is the basis of the technique we study. To make this precise, we consider the Schrödinger operato