1H nuclear magnetic resonance spectroscopy characterisation of metabolic phenotypes in the medulloblastoma of the SMO transgenic mice

BACKGROUND: Human medulloblastomas exhibit diverse molecular pathology. Aberrant hedgehog signalling is found in 20-30% of human medulloblastomas with largely unknown metabolic consequences. METHODS: Transgenic mice over-expressing smoothened (SMO) receptor in granule cell precursors with high incidence of exophytic medulloblastomas were sequentially followed up by magnetic resonance imaging (MRI) and characterised for metabolite phenotypes by ¹H MR spectroscopy (MRS) in vivo and ex vivo using high-resolution magic angle spinning (HR-MAS) ¹H MRS. RESULTS: Medulloblastomas in the SMO mice presented as T₂ hyperintense tumours in MRI. These tumours showed low concentrations of N-acetyl aspartate and high concentrations of choline-containing metabolites (CCMs), glycine, and taurine relative to the cerebellar parenchyma in the wild-type (WT) C57BL/6 mice. In contrast, ¹H MRS metabolite concentrations in normal appearing cerebellum of the SMO mice were not different from those in the WT mice. Macromolecule and lipid ¹H MRS signals in SMO medulloblastomas were not different from those detected in the cerebellum of WT mice. The HR-MAS analysis of SMO medulloblastomas confirmed the in vivo ¹H MRS metabolite profiles, and additionally revealed that phosphocholine was strongly elevated in medulloblastomas accounting for the high in vivo CCM. CONCLUSIONS: These metabolite profiles closely mirror those reported from human medulloblastomas confirming that SMO mice provide a realistic model for investigating metabolic aspects of this disease. Taurine, glycine, and CCM are potential metabolite biomarkers for the SMO medulloblastomas. The MRS data from the medulloblastomas with defined molecular pathology is discussed in the light of metabolite profiles reported from human tumours

ICAR: endoscopic skull‐base surgery

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Investigation of the correlation patterns and the Compton dominance variability of Mrk 421 in 2017

Aims. We present a detailed characterisation and theoretical interpretation of the broadband emission of the paradigmatic TeV blazar Mrk 421, with a special focus on the multi-band flux correlations.Methods. The dataset has been collected through an extensive multi-wavelength campaign organised between 2016 December and 2017 June. The instruments involved are MAGIC, FACT, Fermi-LAT, Swift, GASP-WEBT, OVRO, Medicina, and Metsahovi. Additionally, four deep exposures (several hours long) with simultaneous MAGIC and NuSTAR observations allowed a precise measurement of the falling segments of the two spectral components.Results. The very-high-energy (VHE; E > 100 GeV) gamma rays and X-rays are positively correlated at zero time lag, but the strength and characteristics of the correlation change substantially across the various energy bands probed. The VHE versus X-ray fluxes follow different patterns, partly due to substantial changes in the Compton dominance for a few days without a simultaneous increase in the X-ray flux (i.e., orphan gamma-ray activity). Studying the broadband spectral energy distribution (SED) during the days including NuSTAR observations, we show that these changes can be explained within a one-zone leptonic model with a blob that increases its size over time. The peak frequency of the synchrotron bump varies by two orders of magnitude throughout the campaign. Our multi-band correlation study also hints at an anti-correlation between UV-optical and X-ray at a significance higher than 3 sigma. A VHE flare observed on MJD 57788 (2017 February 4) shows gamma-ray variability on multi-hour timescales, with a factor ten increase in the TeV flux but only a moderate increase in the keV flux. The related broadband SED is better described by a two-zone leptonic scenario rather than by a one-zone scenario. We find that the flare can be produced by the appearance of a compact second blob populated by high energetic electrons spanning a narrow range of Lorentz factors, from gamma(min)' = 2 x 10(4) to gamma(max)' = 6 x 10(5).</p

Broadband characterisation of the very intense TeV flares of the blazar 1ES 1959+650 in 2016

1ES 1959+650 is a bright TeV high-frequency-peaked BL Lac object exhibiting interesting features like "orphan" TeV flares and broad emission in the high-energy regime that are difficult to interpret using conventional one-zone Synchrotron Self-Compton (SSC) scenarios. We report the results from the Major Atmospheric Gamma Imaging Cherenkov (MAGIC) observations in 2016 along with the multi-wavelength data from the Fermi Large Area Telescope (LAT) and Swift instruments. MAGIC observed 1ES 1959+650 with different emission levels in the very-high-energy (VHE, E> 100 GeV) gamma -ray band during 2016. In the long-term data, the X-ray spectrum becomes harder with increasing flux and a hint of a similar trend is also visible in the VHE band. An exceptionally high VHE flux reaching similar to 3 times the Crab Nebula flux was measured by MAGIC on the 13 and 14 of June, and 1 July 2016 (the highest flux observed since 2002). During these flares, the high-energy peak of the spectral energy distribution (SED) lies in the VHE domain and extends up to several TeV. The spectrum in the gamma -ray (both Fermi-LAT and VHE bands) and the X-ray bands are quite hard. On 13 June and 1 July 2016, the source showed rapid variations in the VHE flux within timescales of less than an hour. A simple one-zone SSC model can describe the data during the flares requiring moderate to large values of the Doppler factors (delta >= 30-60). Alternatively, the high-energy peak of the SED can be explained by a purely hadronic model attributed to proton-synchrotron radiation with jet power L-jet similar to 10(46) erg s(-1) and under high values of the magnetic field strength (similar to 100 G) and maximum proton energy (similar to few EeV). Mixed lepto-hadronic models require super-Eddington values of the jet power. We conclude that it is difficult to get detectable neutrino emission from the source during the extreme VHE flaring period of 2016

Measurement of the extragalactic background light using MAGIC and Fermi-LAT gamma-ray observations of blazars up to z=1

We present a measurement of the extragalactic background light (EBL) based on a joint likelihood analysis of 32 gamma-ray spectra for 12 blazars in the redshift range z = 0.03-0.944, obtained by the MAGIC telescopes and Fermi-LAT. The EBL is the part of the diffuse extragalactic radiation spanning the ultraviolet, visible, and infrared bands. Major contributors to the EBL are the light emitted by stars through the history of the Universe, and the fraction of it that was absorbed by dust in galaxies and re-emitted at longer wavelengths. The EBL can be studied indirectly through its effect on very high energy photons that are emitted by cosmic sources and absorbed via gamma gamma interactions during their propagation across cosmological distances. We obtain estimates of the EBL density in good agreement with state-of-the-art models of the EBL production and evolution. The 1 sigma upper bounds, including systematic uncertainties, are between 13 per cent and 23 per cent above the nominal EBL density in the models. No anomaly in the expected transparency of the Universe to gamma-rays is observed in any range of optical depth. We also perform a wavelength-resolved EBL determination, which results in a hint of an excess of EBL in the 0.18-0.62 mu m range relative to the studied models, yet compatible with them within systematics