Target-specific glioma therapy in an immunocompetent mouse model : meeting abstract

Objective: Establishment of an immunocompetent mouse model representing the typical progressive stages observed in malignant human gliomas for the in vivo evaluation of novel target-specific regimens. Methods: Isolated clones from tumours that arose spontaneously in GFAP-v-src transgenic mice were used to develop a transplantable brain tumour model in syngeneic B6C3F1 mice. STAT3 protein was knocked down by infection of tumour cells with replication-defective lentivirus encoding STAT3-siRNA. Apoptosis is designed to be induced by soluble recombinant TRAIL + chemical Bcl-2/Bcl-xL inhibitors. Results: Striatal implantation of 105 mouse tumour cells resulted in the robust development of microscopically (2 – 3 mm) infiltrating malignant gliomas. Immunohistochemically, the gliomas displayed the astroglial marker GFAP and the oncogenic form of STAT3 (Tyr-705-phosphorylated) which is found in many malignancies including gliomas. Phosphorylated STAT3 was particularly prominent in the nucleus but was also found at the plasma membrane of peripherally infiltrating glioma cells. To evaluate the role of STAT3 in tumour progression, we stably expressed siRNA against STAT3 in several murine glioma cell lines. The effect of STAT3 depletion on proliferation, invasion and survival will be first assessed in vitro and subsequently after transplantation in vivo. Upstream and downstream components of the STAT3 signalling pathway as well as possible non-specific side effects of STAT3-siRNA expression after lentiviral infection will be examined, too. Conclusions: Its high rate of engraftment, its similarity to the malignant glioma of origin, and its rapid locally invasive growth should make this murine model useful in testing novel therapies for malignant gliomas

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

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ 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 $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ 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

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

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

Network-Integrated Multimedia Middleware, Services, and Applications

Today, there is a strong trend towards networked multimedia devices. However, common multimedia software architectures are restricted to perform all processing on a single system. Available software infrastructures for distributed computing — commonly referred to as middleware — only partly provide the facilities needed for supporting multimedia in distributed and dynamic environments. Approaches from the research community only focus on specific aspects and do not achieve the coverage needed for a full-featured multimedia middleware solution. The Network-Integrated Multimedia Middleware (NMM) presented in this thesis considers the network as an integral part. Despite the inherent heterogeneity of present networking and device technologies, the architecture allows to extend control and cooperation to the network and enables the development of distributed multimedia applications that transparently use local and remote components in combination. The base architecture of this middleware is augmented by several middleware services that especially aim at providing additional support for developing complex applications that involve mobile users and devices. To this end, previously not available services and corresponding abstractions are proposed, realized, and evaluated. The performance and applicability of the developed middleware and its additional services are demonstrated by describing different realized application scenarios.Eine wachsende Anzahl von Multimedia-Geraeten verfuegt heute bereits ueber Netzwerkschnittstellen. Verfueugbare Multimedia Software-Architekturen beschraeanken jedoch die gesamte Datenverarbeitung auf ein einzelnes System. Verbreitete Software-Infrastrukturen fuer Verteilte Systeme — ueblicherweise Middleware genannt — bieten nur teilweise die Eigenschaften, die fuer die Multimedia-Datenverarbeitung in vernetzten und dynamischen Umgebungen benoetigt werden. Ansaetze aus der Forschung behandeln nur spezielle Teilaspekte und erreichen deshalb nicht den Funktionsumfang einer vollwertigen Middleware fuer Multimedia. Die in dieser Arbeit beschriebene Netzwerk-Integrierte Multimedia Middleware (NMM) betrachtet das Netzwerk als integralen Bestandteil. Die Architektur erlaubt trotz der inhaerenten Heterogenitaet der vorhandenen Netzwerk- und Geraetetechnologie die Kontrolle und das Zusammenspiel von Systemen auf das Netzwerk auszuweiten. Dies ermoeglicht die Entwicklung verteilter Multimedia-Anwendungen, die transparent lokale und entfernte Komponenten zusammen einsetzen. Die Kernarchitektur dieser Middleware wird durch verschiedene Dienste erweitert, die speziell die Realisierung komplexer Anwendungsszenarien mitmobilen Geraeten und Benutzern unterstuetzt. Insbesondere werden neue, bisher nicht vorhandene Middleware-Dienste und zugehoerige Abstraktionen vorgeschlagen, realisiert und evaluiert. Anhand verschiedener Anwendungsszenarien wird die Leistungfaehigkeit, die Effizienz und die praktische Relevanz der entwickelten Middleware und der ergaenzenden Dienste demonstriert

A Resource-Adaptive Mobile Navigation System

The design of mobile navigation systems adapting to limited resources will be an important future challenge. Since typically several different means of transportation have to be combined in order to reach a destination, the user interface of such a system has to adapt to the user's changing situation. This applies especially to the alternating use of different technologies to detect the user's position, which should be as seamless as possible. This article presents a hybrid navigation system that relies on different technologies to determine the user's location and that adapts the presentation of route directions to the limited technical resources of the output device and the limited cognitive resources of the user