Structural optimization and biological evaluation of 2-substituted 5-hydroxyindole-3-carboxylates as potent inhibitors of human 5-lipoxygenase.

Pharmacological suppression of leukotriene biosynthesis by inhibitors of 5-lipoxygenase (5-LO) is a strategy to intervene with inflammatory and allergic disorders. We recently presented 2-amino-5-hydroxy-1H-indoles as efficient 5-LO inhibitors in cell-based and cell-free assays. Structural optimization led to novel benzo[g]indole-3-carboxylates exemplified by ethyl 2-(3-chlorobenzyl)-5- hydroxy-1H-benzo[g]indole-3-carboxylate (compound 11a), which inhibits 5-LO activity in human neutrophils and recombinant human 5-LO with IC50 values of 0.23 and 0.086 μM, respectively. Notably, 11a efficiently blocks 5-LO product formation in human whole blood assays (IC50 = 0.83-1.6 μM) and significantly prevented leukotriene B4 production in pleural exudates of carrageenan-treated rats, associated with reduced severity of pleurisy. Together, on the basis of their high potency against 5-LO and the marked efficacy in biological systems, these novel and straightforward benzo[g]indole-3-carboxylates may have potential as anti-inflammatory therapeutics

Ueber das Carcinom

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Measurements and Simulation Studies of Piezoceramics for Acoustic Particle Detection

Calibration sources are an indispensable tool for all detectors. In acoustic particle detection the goal of a calibration source is to mimic neutrino signatures as expected from hadronic cascades. A simple and promising method for the emulation of neutrino signals are piezo ceramics. We will present results of measruements and simulations on these piezo ceramics.Comment: 5 pages, 5 figure

Spectroscopy of electronic defect states in Cu(In, Ga)(S, Se)2_2-based heterojunctions and Schottky diodes under damp-heat exposure

The changes of defect characteristics induced by accelerated lifetime tests on the heterostructure n-ZnO/i-ZnO/CdS/Cu(In, Ga)(S, Se)$_2$/Mo relevant for photovoltaic energy conversion are investigated. We subject heterojunction and Schottky devices to extended damp heat exposure at 85$^{\circ}$C ambient temperature and 85% relative humidity for various time periods. In order to understand the origin of the pronounced changes of the devices, we apply current--voltage and capacitance--voltage measurements, admittance spectroscopy, and deep-level transient spectroscopy. The fill factor and open-circuit voltage of test devices are reduced after prolonged damp heat treatment, leading to a reduced energy conversion efficiency. We observe the presence of defect states in the vicinity of the CdS/chalcopyrite interface. Their activation energy increases due to damp heat exposure, indicating a reduced band bending at the Cu(In, Ga)(S, Se)$_2$ surface. The Fermi-level pinning at the buffer/chalcopyrite interface, maintaining a high band bending in as-grown cells, is lifted due to the damp-heat exposure. We also observe changes in the bulk defect spectra due to the damp-heat treatment.Comment: 4 pages, 5 figure

Two-phonon 1- state in 112Sn observed in resonant photon scattering

Results of a photon scattering experiment on 112Sn using bremsstrahlung with an endpoint energy of E_0 = 3.8 MeV are reported. A J = 1 state at E_x = 3434(1) keV has been excited. Its decay width into the ground state amounts to Gamma_0 = 151(17) meV, making it a candidate for a [2+ x 3-]1- two-phonon state. The results for 112Sn are compared with quasiparticle-phonon model calculations as well as the systematics of the lowest-lying 1- states established in other even-mass tin isotopes. Contrary to findings in the heavier stable even-mass Sn isotopes, no 2+ states between 2 and 3.5 MeV excitation energy have been detected in the present experiment.Comment: 10 pages, including 2 figures, Phys. Rev. C, in pres

Kosmische Strahlung

Das vorliegende Unterrichtsmaterial bietet Ihnen und Ihren Schülern Einblicke in das faszinierende Forschungsfeld der Astroteilchenphysik. Dabei steht die experimentelle Untersuchung von kosmischen Teilchen am Beispiel der Myonen im Vordergrund. In den KAPITELN 1 und 2 werden zunächst einige Hintergrundinformationen für Lehrkräfte, wie beispielsweise Anknüpfungspunkte an den Lehrplan, benötigte Vorkenntnisse der Schüler, Lernziele sowie fachliche und methodische Hinweise gegeben. KAPITEL 3 beschäftigt sich dann mit der kosmischen Strahlung an sich. Mit Hilfe der Betrachtung von Teilchen in einer Nebelkammer gelingt der Einstieg in das Thema der Astroteilchenphysik. Neben den Spuren bereits bekannter Teilchen wie z. B. Elektronen und Alpha-Teilchen begegnen den Schülern hier erstmalig auch Myonen. Mittels anderer Experimente werden diese dann genauer untersucht. Die Experimente und Fachtexte werden durch entsprechende Aufgaben ergänzt. Abschließend wird dann die Entstehung der Myonen thematisiert. In KAPITEL 4 finden sich die vollständigen Lösungen zu allen Aufgaben. KAPITEL 5 bietet einen Überblick über weiterführende Materialien zum Thema kosmische Strahlung

Integration of Acoustic Detection Equipment into ANTARES

The ANTARES group at the University of Erlangen is working towards the integration of a set of acoustic sensors into the ANTARES Neutrino Telescope. With this setup, tests of acoustic particle detection methods and background studies shall be performed. The ANTARES Neutrino Telescope, which is currently being constructed in the Mediterranean Sea, will be equipped with the infrastructure to accommodate a 3-dimensional array of photomultipliers for the detection of Cherenkov light. Within this infrastructure, the required resources for acoustic sensors are available: Bandwidth for the transmission of the acoustic data to the shore, electrical power for the off-shore electronics and physical space to install the acoustic sensors and to route the connecting cables (transmitting signals and power) into the electronics containers. It will be explained how the integration will be performed with minimal modifications of the existing ANTARES design and which setup is foreseen for the acquisition of the acoustic data.Comment: 5 pages, 1 figure, to appear in the proceedings of the 1st International ARENA Workshop, May 17-19th, 2005, DESY Zeuthen (Germany

Testing Thermo-acoustic Sound Generation in Water with Proton and Laser Beams

Experiments were performed at a proton accelerator and an infrared laser acility to investigate the sound generation caused by the energy deposition of pulsed particle and laser beams in water. The beams with an energy range of 1 PeV to 400 PeV per proton beam spill and up to 10 EeV for the laser pulse were dumped into a water volume and the resulting acoustic signals were recorded with pressure sensitive sensors. Measurements were performed at varying pulse energies, sensor positions, beam diameters and temperatures. The data is well described by simulations based on the thermo-acoustic model. This implies that the primary mechanism for sound generation by the energy deposition of particles propagating in water is the local heating of the media giving rise to an expansion or contraction of the medium resulting in a pressure pulse with bipolar shape. A possible application of this effect would be the acoustical detection of neutrinos with energies greater than 1 EeV.Comment: 5 pages, 2 figures, to appear in the proceedings of the 1st International ARENA Workshop, May 17-19th, 2005, DESY Zeuthe

How to predict relapse in leukemia using time series data: A comparative in silico study

Risk stratification and treatment decisions for leukemia patients are regularly based on clinical markers determined at diagnosis, while measurements on system dynamics are often neglected. However, there is increasing evidence that linking quantitative time-course information to disease outcomes can improve the predictions for patient-specific treatment responses. We designed a synthetic experiment simulating response kinetics of 5,000 patients to compare different computational methods with respect to their ability to accurately predict relapse for chronic and acute myeloid leukemia treatment. Technically, we used clinical reference data to first fit a model and then generate de novo model simulations of individual patients’ time courses for which we can systematically tune data quality (i.e. measurement error) and quantity (i.e. number of measurements). Based hereon, we compared the prediction accuracy of three different computational methods, namely mechanistic models, generalized linear models, and deep neural networks that have been fitted to the reference data. Reaching prediction accuracies between 60 and close to 100%, our results indicate that data quality has a higher impact on prediction accuracy than the specific choice of the particular method. We further show that adapted treatment and measurement schemes can considerably improve the prediction accuracy by 10 to 20%. Our proof-of-principle study highlights how computational methods and optimized data acquisition strategies can improve risk assessment and treatment of leukemia patients