Mutations of the ret protooncogene in German multiple endocrine neoplasia families: Relation between genotype and phenotype.

It has been suggested that not only the position but also the nature of the mutations of the ret protooncogene strongly correlate with the clinical manifestation of the multiple endocrine neoplasm type 2 (MEN 2) syndrome. In particular, individuals with a Cys634-Arg substitution should have a greater risk of developing parathyroid disease. We, therefore, analyzed 94 unrelated families from Germany with inherited medullary thyroid carcinoma (MTC) for mutation of the ret protooncogene. In all but 1 of 59 families with MEN 2A, germline mutations in the extracellular domain of the ret protein were found. Some 81% of the MEN 2A mutations affected codon 634. Phenotype-genotype correlations suggested that the prevalence of pheochromocytoma and hyperparathyroidism is significantly higher in families with codon 634 mutations, but there was no correlation with the nature of the mutation. In all but 1 of 27 familial MTC (FMTC) families, mutations were detected in 1 of 4 cysteines in the extracellular domain of the ret protooncogene. Half of the FMTC mutations affected codon 634. Mutations outside of codon 634 occurred more often in FMTC families than in MEN 2A families. In all but 1 of 8 MEN 2B patients, de novo mutations in codon 918 were found. These data confirm the preferential localization of MEN 2-associated mutations and the correlation between disease phenotype and the position of the ret mutation, but there was no correlation between the occurrence of hyperparathyroidism or pheochromocytoma and the nature of the mutation

The 2010 M 87 VHE flare and its origin: the multi-wavelength picture

The giant radio galaxy M 87, with its proximity (16 Mpc) and its very massive black hole ((3 - 6) \times 10^9 M_solar), provides a unique laboratory to investigate very high energy (E>100 GeV; VHE) gamma-ray emission from active galactic nuclei and, thereby, probe particle acceleration to relativistic energies near supermassive black holes (SMBH) and in relativistic jets. M 87 has been established as a VHE gamma-ray emitter since 2005. The VHE gamma-ray emission displays strong variability on timescales as short as a day. In 2008, a rise in the 43 GHz Very Long Baseline Array (VLBA) radio emission of the innermost region (core; extension of < 100 Rs ; Schwarzschild radii) was found to coincide with a flaring activity at VHE. This had been interpreted as a strong indication that the VHE emission is produced in the direct vicinity of the SMBH. In 2010 a flare at VHE was again detected triggering further multi-wavelength (MWL) observations with the VLBA, Chandra, and other instruments. At the same time, M 87 was also observed with the Fermi-LAT telescope at MeV/GeV energies, the European VLBI Network (EVN), and the Liverpool Telescope (LT). Here, preliminary results from the 2010 campaign will be reported.Comment: 6 pages, 2 figures; Procceedings of the workshop "High Energy Phenomena in Relativistic Outflows III" (HEPRO III), Barcelona, June 27 - July 1, 201

Bewertung der Grenzlast von elastisch-plastischen Tragwerken mit Hilfe stochastischer Methoden

Für die Analyse von Tragwerken sowohl des Stahlbaus als auch des Massivbaus eröffnet die nationale und internationale Normengebung in zunehmendem Maße die Anwendung physikalisch nichtlinearer Berechnungsmodelle. Es ist zu erwarten, daß neben dem traditionellen elastischen Berechnungsmodell das linearelastisch-idealplastische Materialmodell in die Tragwerksanalyse Eingang finden wird. Während bei den traditionellen Berechnungsverfahren auf der Grundlage der Elastizitätstheorie hinreichende Erfahrungen durch die Planungspraxis bestehen und umfangreiche Untersuchungen zur dabei erreichten Sicherheit vorliegen, stellen die nichtlinearen Berechnungsmethoden sowohl in mechanischer als auch in sicherheitstheoretischer Hinsicht ein neues Erfahrungsfeld dar. Im vorliegenden Beitrag werden aus der Vielzahl der anstehenden Probleme folgende Teilprobleme behandelt: Bestimmung der Versagenswahrscheinlichkeit elasto-plastischer Tragsysteme nach dem Kriterium der plastischen Grenzlast Ermittlung stochastischer Eigenschaften des plastischen Grenzlastparameters elasto-plastischer Tragsysteme. Die Lösung des mechanischen Problems geschieht über eine lineare Optimierungsaufgabe, die nach dem statischen Theorem der plastischen Grenzlast formuliert ist. Als stochastische Methode wird die Simulation angewandt, die zum einen auf einer zufälligen Erzeugung der Realisierungen (stochastische Simulation) und zum anderen auf einer planmäßigen Erzeugung der Realisierungen (konstruktive Simulation) beruhen kann. Für jedes der Teilprobleme wird ein Beispiel vorgestellt

"Chiamo uomo chi \ue8 padrone delle sue lingue". modelli di plurilinguismo da Lampedusa in su.

Il plurilinguismo dei nuovi migranti viene analizzato insieme al ruolo della lingua nella costruzione di modelli di societ\ue0 inclusiva e plural

Electronic Structure of Transition Metals Fe, Ni and Cu in the GW Approximation

The quasiparticle band structures of 3d transition metals, ferromagnetic Fe, Ni and paramagnetic Cu, are calculated by the GW approximation. The width of occupied 3d valence band, which is overestimated in the LSDA, is in good agreement with experimental observation. However the exchange splitting and satellite in spectra are not reproduced and it is required to go beyond the GW approximation. The effects of static screening and dynamical correlation are discussed in detail in comparison with the results of the static COHSEX approximation. The dynamical screening effects are important for band width narrowing.Comment: 4 pages, 3 figure

Efficacy of Bravecto® Plus spot-on solution for cats (280 mg/ml fluralaner and 14 mg/ml moxidectin) for the prevention of aelurostrongylosis in experimentally infected cats

Background: The feline lungworm Aelurostrongylus abstrusus affects the lower respiratory tract in cats worldwide. As infections may lead to chronic respiratory changes or even death, preventive treatment in cats with outdoor access is warranted. Methods: The preventive efficacy of a spot-on solution (Bravecto® Plus spot-on solution for cats, MSD) against cat aelurostrongylosis was evaluated using three different preventive treatment regimes in a negative controlled, randomized and partially blinded laboratory efficacy study with 31 purposed-bred cats. The minimum recommended dose of 2.0 mg moxidectin + 40 mg fluralaner/kg bodyweight was applied once 12 (Group [G]1), 8 (G2) or 4 (G3) weeks before experimental infection with 300 third-stage larvae (L3) of A.&nbsp;abstrusus. Another group served as untreated control (G4). Individual faecal samples were analysed as of day 30 post infection (pi) to monitor larvae excretion. Necropsy was performed at days 47–50 pi. The lungs were examined macroscopically for pathological findings and (pre-)adult worms were counted to assess preventive efficacy. Results: Beginning at day 32–40 pi, all cats of the control group were constantly shedding larvae of A.&nbsp;abstrusus, whereas only one animal of G1 excreted larvae at several consecutive days. In addition, two cats of G1 and G3 and three of G2 were positive on a single occasion. The geometric mean (GM) of the maximum number of excreted larvae was 7574.29 in the control group compared to 1.10 (G1), 1.19 (G2) and 0.53 (G3), resulting in a GM reduction of &gt; 99.9% in all treatment groups. All lungs of the control animals showed severe or very severe alterations at necropsy, while in 94.44% of the treated cats lung pathology was rated as absent or mild. The GM number of (pre-)adult A.&nbsp;abstrusus retrieved from the lungs was 26.57 in the control group, 0.09 in G1 and 0.00 in G2 and G3. Thus, GM worm count reduction was 99.66% in G1 and 100% in G2 and G3. Conclusions: A single application of Bravecto® Plus spot-on solution at a dose of 2.0 mg moxidectin + 40 mg fluralaner/kg bodyweight reliably prevents cat aelurostrongylosis for at least 12 weeks.[Figure not available: see fulltext.

Probing the origin of VHE emission from M 87 with MWL observations in 2010

The large majority of extragalactic very high energy (VHE; E>100 GeV) sources belongs to the class of active galactic nuclei (AGN), in particular the BL Lac sub-class. AGNs are characterized by an extremely bright and compact emission region, powered by a super-massive black hole (SMBH) and an accretion disk, and relativistic outflows (jets) detected all across the electro-magnetic spectrum. In BL Lac sources the jet axis is oriented close to the line of sight, giving rise to a relativistic boosting of the emission. In radio galaxies, on the other hand, the jet makes a larger angle to the line of sight allowing to resolve the central core and the jet in great details. The giant radio galaxy M 87 with its proximity (1 6Mpc) and its very massive black hole ((3-6) x 10^9 M_solar) provides a unique laboratory to investigate VHE emission in such objects and thereby probe particle acceleration to relativistic energies near SMBH and in jets. M 87 has been established as a VHE emitter since 2005. The VHE emission displays strong variability on time-scales as short as a day. It has been subject of a large joint VHE and multi-wavelength (MWL) monitoring campaign in 2008, where a rise in the 43 GHz VLBA radio emission of the innermost region (core) was found to coincide with a flaring activity at VHE. This had been interpreted as a strong indication that the VHE emission is produced in the direct vicinity of the SMBH black hole. In 2010 again a flare at VHE was detected triggering further MWL observations with the VLBA, Chandra, and other instruments. At the same time M 87 was also observed with the Fermi-LAT telescope at GeV energies and the European VLBI Network (EVN). In this contribution preliminary results from the campaign will be presented.Comment: 5 pages, 2 figures, in the proceedings of the "International Workshop on Beamed and Unbeamed Gamma-Rays from Galaxies" 11-15 April 2011, Lapland Hotel Olos, Muonio, Finland, Journal of Physics: Conference Series Volume 355, 201