SCORPIO-II: Spectral indices of weak Galactic radio sources

In the next few years the classification of radio sources observed by the large surveys will be a challenging problem, and spectral index is a powerful tool for addressing it. Here we present an algorithm to estimate the spectral index of sources from multiwavelength radio images. We have applied our algorithm to SCORPIO (Umana et al. 2015), a Galactic Plane survey centred around 2.1 GHz carried out with ATCA, and found we can measure reliable spectral indices only for sources stronger than 40 times the rms noise. Above a threshold of 1 mJy, the source density in SCORPIO is 20 percent greater than in a typical extra-galactic field, like ATLAS (Norris et al. 2006), because of the presence of Galactic sources. Among this excess population, 16 sources per square degree have a spectral index of about zero, suggesting optically thin thermal emission such as Hii regions and planetary nebulae, while 12 per square degree present a rising spectrum, suggesting optically thick thermal emission such as stars and UCHii regions.Comment: 12 pages, 11 figures, accepted by MNRA

The MEV project: design and testing of a new high-resolution telescope for Muography of Etna Volcano

The MEV project aims at developing a muon telescope expressly designed for the muography of Etna Volcano. In particular, one of the active craters in the summit area of the volcano would be a suitable target for this experiment. A muon tracking telescope with high imaging resolution was built and tested during 2017. The telescope is a tracker based on extruded scintillating bars with WLS fibres and featuring an innovative read-out architecture. It is composed of three XY planes with a sensitive area of \SI{1}{m^2}; the angular resolution does not exceeds \SI{0.4}{\milli\steradian} and the total angular aperture is about $\pm$\SI{45}{\degree}. A special effort concerned the design of mechanics and electronics in order to meet the requirements of a detector capable to work in a hostile environment such as the top of a tall volcano, at a far distance from any facility. The test phase started in January 2017 and ended successfully at the end of July 2017. An extinct volcanic crater (the Monti Rossi, in the village of Nicolosi, about 15km from Catania) is the target of the measurement. The detector acquired data for about 120 days and the preliminary results are reported in this work

A warm molecular ring in AG Car: composing the mass-loss puzzle

We present APEX observations of CO J=3-2 and ALMA observations of CO J=2-1, 13CO J=2-1 and continuum toward the galactic luminous blue variable AG Car. These new observations reveal the presence of a ring-like molecular structure surrounding the star. Morphology and kinematics of the gas are consistent with a slowly expanding torus located near the equatorial plane of AG Car. Using non-LTE line modelling, we derived the physical parameters of the gas, which is warm (50 K) and moderately dense (10$^3$ cm$^{-3}$. The total mass of molecular gas in the ring is 2.7$\pm$0.9 solar masses. We analysed the radio continuum map, which depicts a point-like source surrounded by a shallow nebula. From the flux of the point-like source, we derived a current mass-loss date of $1.55\pm0.21\times10^{-5}$ solar masses / yr. Finally, to better understand the complex circumstellar environment of AG Car, we put the newly detected ring in relation to the main nebula of dust and ionised gas. We discuss possible formation scenarios for the ring, namely, the accumulation of interstellar material due to the action of the stellar wind, the remnant of a close binary interaction or merger, and an equatorially enhanced mass-loss episode. If molecular gas formed in situ as a result of a mass eruption, it would account for at least a 30$\%$ of the total mass ejected by AG Car. This detection adds a new piece to the puzzle of the complex mass-loss history of AG Car, providing new clues about the interplay between LBV stars and their surroundings.Comment: 16 pages, 13 figures. Accepted for publication in MNRA

Acidic tumor microenvironment abrogates the efficacy of mTORC1 inhibitors.

Blocking the mechanistic target of rapamycin complex-1 (mTORC1) with chemical inhibitors such as rapamycin has shown limited clinical efficacy in cancer. The tumor microenvironment is characterized by an acidic pH which interferes with cancer therapies. The consequences of acidity on the anti-cancer efficacy of mTORC1 inhibitors have not been characterized and are thus the focus of our study. Cancer cell lines were treated with rapamycin in acidic or physiological conditions and cell proliferation was investigated. The effect of acidity on mTORC1 activity was determined by Western blot. The anticancer efficacy of rapamycin in combination with sodium bicarbonate to increase the intratumoral pH was tested in two different mouse models and compared to rapamycin treatment alone. Histological analysis was performed on tumor samples to evaluate proliferation, apoptosis and necrosis. Exposing cancer cells to acidic pH in vitro significantly reduced the anti-proliferative effect of rapamycin. At the molecular level, acidity significantly decreased mTORC1 activity, suggesting that cancer cell proliferation is independent of mTORC1 in acidic conditions. In contrast, the activation of mitogen-activated protein kinase (MAPK) or AKT were not affected by acidity, and blocking MAPK or AKT with a chemical inhibitor maintained an anti-proliferative effect at low pH. In tumor mouse models, the use of sodium bicarbonate increased mTORC1 activity in cancer cells and potentiated the anti-cancer efficacy of rapamycin. Combining sodium bicarbonate with rapamycin resulted in increased tumor necrosis, increased cancer cell apoptosis and decreased cancer cell proliferation as compared to single treatment. Taken together, these results emphasize the inefficacy of mTORC1 inhibitors in acidic conditions. They further highlight the potential of combining sodium bicarbonate with mTORC1 inhibitors to improve their anti-tumoral efficacy

Targeting carbonic anhydrase IX improves the anti-cancer efficacy of mTOR inhibitors.

The inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) by chemical inhibitors, such as rapamycin, has demonstrated anti-cancer activity in preclinical and clinical trials. Their efficacy is, however, limited and tumors eventually relapse through resistance formation. In this study, using two different cancer mouse models, we identify tumor hypoxia as a novel mechanism of resistance of cancer cells against mTORC1 inhibitors. Indeed, we show that the activity of mTORC1 is mainly restricted to the non-hypoxic tumor compartment, as evidenced by a mutually exclusive staining pattern of the mTORC1 activity marker pS6 and the hypoxia marker pimonidazole. Consequently, whereas rapamycin reduces cancer cell proliferation in non-hypoxic regions, it has no effect in hypoxic areas, suggesting that cancer cells proliferate independently of mTORC1 under hypoxia. Targeting the hypoxic tumor compartment by knockdown of carbonic anhydrase IX (CAIX) using short hairpin RNA or by chemical inhibition of CAIX with acetazolamide potentiates the anti-cancer activity of rapamycin. Taken together, these data emphasize that hypoxia impairs the anti-cancer efficacy of rapalogs. Therapeutic strategies targeting the hypoxic tumor compartment, such as the inhibition of CAIX, potentiate the efficacy of rapamycin and warrant further clinical evaluation

Modeling Initiation of Ewing Sarcoma in Human Neural Crest Cells

Ewing sarcoma family tumors (ESFT) are aggressive bone and soft tissue tumors that express EWS-ETS fusion genes as driver mutations. Although the histogenesis of ESFT is controversial, mesenchymal (MSC) and/or neural crest (NCSC) stem cells have been implicated as cells of origin. For the current study we evaluated the consequences of EWS-FLI1 expression in human embryonic stem cell-derived NCSC (hNCSC). Ectopic expression of EWS-FLI1 in undifferentiated hNCSC and their neuro-mesenchymal stem cell (hNC-MSC) progeny was readily tolerated and led to altered expression of both well established as well as novel EWS-FLI1 target genes. Importantly, whole genome expression profiling studies revealed that the molecular signature of established ESFT is more similar to hNCSC than any other normal tissue, including MSC, indicating that maintenance or reactivation of the NCSC program is a feature of ESFT pathogenesis. Consistent with this hypothesis, EWS-FLI1 induced hNCSC genes as well as the polycomb proteins BMI-1 and EZH2 in hNC-MSC. In addition, up-regulation of BMI-1 was associated with avoidance of cellular senescence and reversible silencing of p16. Together these studies confirm that, unlike terminally differentiated cells but consistent with bone marrow-derived MSC, NCSC tolerate expression of EWS-FLI1 and ectopic expression of the oncogene initiates transition to an ESFT-like state. In addition, to our knowledge this is the first demonstration that EWS-FLI1-mediated induction of BMI-1 and epigenetic silencing of p16 might be critical early initiating events in ESFT tumorigenesis

Genome-wide functional perturbation of human microsatellite repeats using engineered zinc finger transcription factors.

Repeat elements can be dysregulated at a genome-wide scale in human diseases. For example, in Ewing sarcoma, hundreds of inert GGAA repeats can be converted into active enhancers when bound by EWS-FLI1. Here we show that fusions between EWS and GGAA-repeat-targeted engineered zinc finger arrays (ZFAs) can function at least as efficiently as EWS-FLI1 for converting hundreds of GGAA repeats into active enhancers in a Ewing sarcoma precursor cell model. Furthermore, a fusion of a KRAB domain to a ZFA can silence GGAA microsatellite enhancers genome wide in Ewing sarcoma cells, thereby reducing expression of EWS-FLI1-activated genes. Remarkably, this KRAB-ZFA fusion showed selective toxicity against Ewing sarcoma cells compared with non-Ewing cancer cells, consistent with its Ewing sarcoma-specific impact on the transcriptome. These findings demonstrate the value of ZFAs for functional annotation of repeats and illustrate how aberrant microsatellite activities might be regulated for potential therapeutic applications

Performance of prototypes for the ALICE electromagnetic calorimeter

The performance of prototypes for the ALICE electromagnetic sampling calorimeter has been studied in test beam measurements at FNAL and CERN. A $4\times4$ array of final design modules showed an energy resolution of about 11% /$\sqrt{E(\mathrm{GeV})}$ $\oplus$ 1.7 % with a uniformity of the response to electrons of 1% and a good linearity in the energy range from 10 to 100 GeV. The electromagnetic shower position resolution was found to be described by 1.5 mm $\oplus$ 5.3 mm /$\sqrt{E \mathrm{(GeV)}}$. For an electron identification efficiency of 90% a hadron rejection factor of $>600$ was obtained.Comment: 10 pages, 10 figure

Performance of ALICE pixel prototypes in high energy beams

The two innermost layers of the ALICE inner tracking system are instrumented with silicon pixel detectors. Single chip assembly prototypes of the ALICE pixels have been tested in high energy particle beams at the CERN SPS. Detection efficiency and spatial precision have been studied as a function of the threshold and the track incidence angle. The experimental method, data analysis and main results are presented.Comment: 10 pages, 9 figures, contribution to PIX2005 Workshop, Bonn (Germany), 5-8 September 200