Black Hole Lightning from the Peculiar Gamma-Ray Loud Active Galactic Nucleus IC 310

The nearby active galaxy IC 310, located in the outskirts of the Perseus cluster of galaxies is a bright and variable multi-wavelength emitter from the radio regime up to very high gamma-ray energies above 100 GeV. Originally, the nucleus of IC 310 has been classified as a radio galaxy. However, studies of the multi-wavelength emission showed several properties similarly to those found from blazars as well as radio galaxies. In late 2012, we have organized the first contemporaneous multi-wavelength campaign including radio, optical, X-ray and gamma-ray instruments. During this campaign an exceptionally bright flare of IC 310 was detected with the MAGIC telescopes in November 2012 reaching an averaged flux level in the night of up to one Crab above 1 TeV with a hard spectrum over two decades in energy. The intra-night light curve showed a series of strong outbursts with flux-doubling time scales as fast as a few minutes. The fast variability constrains the size of the gamma-ray emission regime to be smaller than 20% of the gravitational radius of its central black hole. This challenges the shock acceleration models, commonly used to explain gamma-ray radiation from active galaxies. Here, we will present more details on the MAGIC data and discuss several possible alternative emission models.Comment: 8 pages, 5 figures, Proceedings of the 34th International Cosmic Ray Conference, 30 July - 6 August, 2015, The Hague, The Netherland

The EVN view of the highly variable TeV active galaxy IC 310

Very-high-energy $\gamma$-ray observations of the active galaxy IC 310 with the MAGIC telescopes have revealed fast variability with doubling time scales of less than 4.8min. This implies that the emission region in IC 310 is smaller than 20% of the gravitational radius of the central supermassive black hole with a mass of $3\times 10^8 M_\odot$, which poses serious questions on the emission mechanism and classification of this enigmatic object. We report on the first quasi-simultaneous multi-frequency VLBI observations of IC 310 conducted with the EVN. We find a blazar-like one-sided core-jet structure on parsec scales, constraining the inclination angle to be less than $\sim 20^\circ$ but very small angles are excluded to limit the de-projected length of the large-scale radio jet.Comment: 4 pages, proceedings of the 12th European VLBI Network Symposium and Users Meeting - EVN 2014, 7-10 October 2014, Cagliari, Italy. Published online in PoS, ID.10

Insights into the particle acceleration of a peculiar gamma -ray radio galaxy IC 310

IC 310 has recently been identified as a gamma-ray emitter based on observations at GeV energies with Fermi-LAT and at very high energies (VHE, E > 100 GeV) with the MAGIC telescopes. Despite IC 310 having been classified as a radio galaxy with the jet observed at an angle > 10 degrees, it exhibits a mixture of multiwavelength properties of a radio galaxy and a blazar, possibly making it a transitional object. On the night of 12/13th of November 2012 the MAGIC telescopes observed a series of violent outbursts from the direction of IC 310 with flux-doubling time scales faster than 5 min and a peculiar spectrum spreading over 2 orders of magnitude. Such fast variability constrains the size of the emission region to be smaller than 20% of the gravitational radius of its central black hole, challenging the shock acceleration models, commonly used in explanation of gamma-ray radiation from active galaxies. Here we will show that this emission can be associated with pulsar-like particle acceleration by the electric field across a magnetospheric gap at the base of the jet.Comment: 2014 Fermi Symposium proceedings - eConf C14102.

The blazar-like radio structure of the TeV source IC310

Context. The radio galaxy IC310 in the Perseus cluster has recently been detected in the gamma-ray regime at GeV and TeV energies. The TeV emission shows time variability and an extraordinarily hard spectrum, even harder than the spectrum of the similar nearby gamma-ray emitting radio galaxy M87. Aims. High-resolution studies of the radio morphology help to constrain the geometry of the jet on sub-pc scales and to find out where the high-energy emission might come from. Methods. We analyzed May 2011 VLBA data of IC310 at a wavelength of 3.6 cm, revealing the parsec-scale radio structure of this source. We compared our findings with more information available from contemporary single-dish flux density measurements with the 100-m Effelsberg radio telescope. Results. We have detected a one-sided core-jet structure with blazar-like, beamed radio emission oriented along the same position angle as the kiloparsec scale radio structure observed in the past by connected interferometers. Doppler-boosting favoritism is consistent with an angle of theta < 38 degrees between the jet axis and the line-of-sight, i.e., very likely within the boundary dividing low-luminosity radio galaxies and BL Lac objects in unified schemes. Conclusions. The stability of the jet orientation from parsec to kiloparsec scales in IC310 argues against its classification as a headtail radio galaxy; i.e., there is no indication of an interaction with the intracluster medium that would determine the direction of the tail. IC310 seems to represent a low-luminosity FRI radio galaxy at a borderline angle to reveal its BL Lac-type central engine.Comment: 5 pages, 3 figures (1 color); A&A, accepte

Individual Profiling of Circulating Tumor Cell Composition and Therapeutic Outcome in Patients with Hepatocellular Carcinoma

AbstractBACKGROUND AND AIMS: Circulating tumor cells (CTCs) have been proposed as a monitoring tool in patients with solid tumors. So far, automated approaches are challenged by the cellular heterogeneity of CTC, especially the epithelial-mesenchymal transition. Recently, Yu and colleagues showed that shifts in these cell populations correlated with response and progression, respectively, to chemotherapy in patients with breast cancer. In this study, we assessed which non-hematopoietic cell types were identifiable in the peripheral blood of hepatocellular carcinoma (HCC) patients and whether their distribution during treatment courses is associated with clinical characteristics. METHODS: Subsequent to few enrichment steps, cell suspensions were spun onto glass slides and further characterized using multi-immunofluorescence staining. All non-hematopoietic cells were counted and individual cell profiles were analyzed per patient and treatment. RESULTS:We detected a remarkable variation of cells with epithelial, mesenchymal, liver-specific, and mixed characteristics and different size ranges. The distribution of these subgroups varied significantly between different patient groups and was associated with therapeutic outcome. Kaplan-Meier logrank test showed that a change in the ratio of epithelial to mesenchymal cells was associated with longer median time to progression (1 vs 15 months; P = .03; hazard ratio = 0.18; 95%confidence interval = 0.01-2.75). CONCLUSIONS: Our data suggest that different CTC populations are identifiable in peripheral blood of HCC patients and, for the first time in HCC, that these individual cell type profiles may have distinct clinical implications. The further characterization and analysis of patients in this ongoing study seems to be warranted

Evaluation of the biomarker candidate MFAP4 for non-invasive assessment of hepatic fibrosis in hepatitis C patients

$\textbf {Background:}$ The human microfibrillar-associated protein 4 (MFAP4) is located to extracellular matrix fibers and plays a role in disease-related tissue remodeling. Previously, we identified MFAP4 as a serum biomarker candidate for hepatic fibrosis and cirrhosis in hepatitis C patients. The aim of the present study was to elucidate the potential of MFAP4 as biomarker for hepatic fibrosis with a focus on the differentiation of no to moderate (F0–F2) and severe fibrosis stages and cirrhosis (F3 and F4, Desmet-Scheuer scoring system). $\textbf {Methods:}$ MFAP4 levels were measured using an AlphaLISA immunoassay in a retrospective study including $\it n$ = 542 hepatitis C patients. We applied a univariate logistic regression model based on MFAP4 serum levels and furthermore derived a multivariate model including also age and gender. Youden-optimal cutoffs for binary classification were determined for both models without restrictions and considering a lower limit of 80% sensitivity (correct classification of F3 and F4), respectively. To assess the generalization error, leave-one-out cross validation (LOOCV ) was performed. $\textbf {Results:}$ MFAP4 levels were shown to differ between no to moderate fibrosis stages F0–F2 and severe stages (F3 and F4) with high statistical significance ($\it t$ test on log scale, $\it p$ value $<2.2·10^{-16}$). In the LOOCV, the univariate classification resulted in 85.8% sensitivity and 54.9% specificity while the multivariate model yielded 81.3% sensitivity and 61.5% specificity (restricted approaches). $\textbf {Conclusions:}$ We confirmed the applicability of MFAP4 as a novel serum biomarker for assessment of hepatic fibrosis and identification of high-risk patients with severe fibrosis stages in hepatitis C. The combination of MFAP4 with existing tests might lead to a more accurate non-invasive diagnosis of hepatic fibrosis and allow a cost-effective disease management in the era of new direct acting antivirals

Toward a successful clinical neuroproteomics : the 11th HUPO Brain Proteome Project Workshop 3 March, 2009, Kolymbari, Greece

The HUPO Brain Proteome Project (HUPO BPP) held its 11th workshop in Kolymbari on March 3, 2009. The principal aim of this project is to obtain a better understanding of neurodiseases and ageing, with the ultimate objective of discovering prognostic and diagnostic biomarkers, in addition to the development of novel diagnostic techniques and new medications. The attendees came together to discuss sub-project progress in the clinical neuroproteomics of human or mouse models of Alzheimer's and Parkinson's disease, and to define the needs and guidelines required for more advanced proteomics approaches. With the election of new steering committees, the members of the HUPO BPP elaborated an actual plan promoting activities, outcomes, and future directions of the HUPO BPP to acquire new funding and new participants

Calibration and performance of the photon sensor response of FACT -- The First G-APD Cherenkov telescope

The First G-APD Cherenkov Telescope (FACT) is the first in-operation test of the performance of silicon photo detectors in Cherenkov Astronomy. For more than two years it is operated on La Palma, Canary Islands (Spain), for the purpose of long-term monitoring of astrophysical sources. For this, the performance of the photo detectors is crucial and therefore has been studied in great detail. Special care has been taken for their temperature and voltage dependence implementing a correction method to keep their properties stable. Several measurements have been carried out to monitor the performance. The measurements and their results are shown, demonstrating the stability of the gain below the percent level. The resulting stability of the whole system is discussed, nicely demonstrating that silicon photo detectors are perfectly suited for the usage in Cherenkov telescopes, especially for long-term monitoring purpose

FACT -- Operation of the First G-APD Cherenkov Telescope

Since more than two years, the First G-APD Cherenkov Telescope (FACT) is operating successfully at the Canary Island of La Palma. Apart from its purpose to serve as a monitoring facility for the brightest TeV blazars, it was built as a major step to establish solid state photon counters as detectors in Cherenkov astronomy. The camera of the First G-APD Cherenkov Telesope comprises 1440 Geiger-mode avalanche photo diodes (G-APD aka. MPPC or SiPM) for photon detection. Since properties as the gain of G-APDs depend on temperature and the applied voltage, a real-time feedback system has been developed and implemented. To correct for the change introduced by temperature, several sensors have been placed close to the photon detectors. Their read out is used to calculate a corresponding voltage offset. In addition to temperature changes, changing current introduces a voltage drop in the supporting resistor network. To correct changes in the voltage drop introduced by varying photon flux from the night-sky background, the current is measured and the voltage drop calculated. To check the stability of the G-APD properties, dark count spectra with high statistics have been taken under different environmental conditions and been evaluated. The maximum data rate delivered by the camera is about 240 MB/s. The recorded data, which can exceed 1 TB in a moonless night, is compressed in real-time with a proprietary loss-less algorithm. The performance is better than gzip by almost a factor of two in compression ratio and speed. In total, two to three CPU cores are needed for data taking. In parallel, a quick-look analysis of the recently recorded data is executed on a second machine. Its result is publicly available within a few minutes after the data were taken. [...]Comment: 19th IEEE Real-Time Conference, Nara, Japan (2014

FACT -- The G-APD revolution in Cherenkov astronomy

Since two years, the FACT telescope is operating on the Canary Island of La Palma. Apart from its purpose to serve as a monitoring facility for the brightest TeV blazars, it was built as a major step to establish solid state photon counters as detectors in Cherenkov astronomy. The camera of the First G-APD Cherenkov Telesope comprises 1440 Geiger-mode avalanche photo diodes (G-APD), equipped with solid light guides to increase the effective light collection area of each sensor. Since no sense-line is available, a special challenge is to keep the applied voltage stable although the current drawn by the G-APD depends on the flux of night-sky background photons significantly varying with ambient light conditions. Methods have been developed to keep the temperature and voltage dependent response of the G-APDs stable during operation. As a cross-check, dark count spectra with high statistics have been taken under different environmental conditions. In this presentation, the project, the developed methods and the experience from two years of operation of the first G-APD based camera in Cherenkov astronomy under changing environmental conditions will be presented.Comment: Proceedings of the Nuclear Science Symposium and Medical Imaging Conference (IEEE-NSS/MIC), 201