Transcriptional Profile Associated with Clinical Outcomes in Metastatic Hormone-Sensitive Prostate Cancer Treated with Androgen Deprivation and Docetaxel

(1) Background: Androgen deprivation therapy (ADT) and docetaxel (DX) combination is a standard therapy for metastatic hormone-sensitive prostate cancer (mHSPC) patients. (2) Methods: We investigate if tumor transcriptomic analysis predicts mHSPC evolution in a multicenter retrospective biomarker study. A customized panel of 184 genes was tested in mRNA from tumor samples by the nCounter platform in 125 mHSPC patients treated with ADT+DX. Gene expression was correlated with castration-resistant prostate cancer-free survival (CRPC-FS) and overall survival (OS). (3) Results: High expression of androgen receptor (AR) signature was independently associated with longer CRPC-FS (hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.3-0.9; p = 0.015), high expression of estrogen receptor (ESR) signature with longer CRPC-FS (HR 0.6, 95% CI 0.4-0.9; p = 0.019) and OS (HR 0.5, 95% CI 0.2-0.9, p = 0.024), and lower expression of tumor suppressor genes (TSG) (RB1, PTEN and TP53) with shorter OS (HR 2, 95% CI 1-3.8; p = 0.044). ARV7 expression was independently associated with shorter CRPC-FS (HR 1.5, 95% CI 1.1-2.1, p = 0.008) and OS (HR 1.8, 95% CI 1.2-2.6, p = 0.004), high ESR2 was associated with longer OS (HR 0.5, 95% CI 0.2-1, p = 0.048) and low expression of RB1 was independently associated with shorter OS (HR 1.9, 95% CI 1.1-3.2, p = 0.014). (4) Conclusions: AR, ESR, and TSG expression signatures, as well as ARV7, RB1, and ESR2 expression, have a prognostic value in mHSPC patients treated with ADT+DX

The role of mergers in driving morphological transformation over cosmic time

Accepted for publication in MNRASUnderstanding the processes that trigger morphological transformation is central to understanding how and why the Universe transitions from being disc-dominated at early epochs to having the morphological mix that is observed today. We use Horizon-AGN, a cosmological hydrodynamical simulation, to perform a comprehensive study of the processes that drive morphological change in massive (M*/M ⊙ > 10 10) galaxies over cosmic time. We show that (1) essentially all the morphological evolution in galaxies that are spheroids at z = 0 is driven by mergers with mass ratios greater than 1: 10; (2) major mergers alone cannot produce today's spheroid population - minor mergers are responsible for a third of all morphological transformation over cosmic time and are its dominant driver after z ~ 1; (3) prograde mergers trigger milder morphological transformation than retrograde mergers - while both types of event produce similar morphological changes at z > 2, the average change due to retrograde mergers is around twice that due to their prograde counterparts at z ~ 0; (4) remnant morphology depends strongly on the gas fraction of a merger, with gas-rich mergers routinely re-growing discs; and (5) at a given stellar mass, discs do not exhibit drastically different merger histories from spheroids - disc survival in mergers is driven by acquisition of cold gas (via cosmological accretion and gas-rich interactions) and a preponderance of prograde mergers in their merger histories.Peer reviewedFinal Accepted Versio

Limits to dark matter annihilation cross-section from a combined analysis of MAGIC and Fermi-LAT observations of dwarf satellite galaxies

We present the first joint analysis of gamma-ray data from the MAGIC Cherenkov telescopes and the Fermi Large Area Telescope (LAT) to search for gamma-ray signals from dark matter annihilation in dwarf satellite galaxies. We combine 158 hours of Segue 1 observations with MAGIC with 6-year observations of 15 dwarf satellite galaxies by the Fermi-LAT. We obtain limits on the annihilation cross-section for dark matter particle masses between 10 GeV and 100 TeV - the widest mass range ever explored by a single gamma-ray analysis. These limits improve on previously published Fermi-LAT and MAGIC results by up to a factor of two at certain masses. Our new inclusive analysis approach is completely generic and can be used to perform a global, sensitivity-optimized dark matter search by combining data from present and future gamma-ray and neutrino detectors.Comment: 19 pages, 3 figures. V2: Few typos corrected and references added. Matches published version JCAP 02 (2016) 03

Long-term multi-wavelength variability and correlation study of Markarian 421 from 2007 to 2009

We study the multi-band variability and correlations of the TeV blazar Mrk 421 on year time scales, which can bring additional insight on the processes responsible for its broadband emission. We observed Mrk 421 in the very high energy (VHE) gamma-ray range with the Cherenkov telescope MAGIC-I from March 2007 to June 2009 for a total of 96 hours of effective time after quality cuts. The VHE flux variability is quantified with several methods, including the Bayesian Block algorithm, which is applied to data from Cherenkov telescopes for the first time. The 2.3 year long MAGIC light curve is complemented with data from the Swift/BAT and RXTE/ASM satellites and the KVA, GASP-WEBT, OVRO, and Mets\"ahovi telescopes from February 2007 to July 2009, allowing for an excellent characterisation of the multi-band variability and correlations over year time scales. Mrk 421 was found in different gamma-ray emission states during the 2.3 year long observation period. Flares and different levels of variability in the gamma-ray light curve could be identified with the Bayesian Block algorithm. The same behaviour of a quiet and active emission was found in the X-ray light curves measured by Swift/BAT and the RXTE/ASM, with a direct correlation in time. The behaviour of the optical light curve of GASP-WEBT and the radio light curves by OVRO and Mets\"ahovi are different as they show no coincident features with the higher energetic light curves and a less variable emission. The fractional variability is overall increasing with energy. The comparable variability in the X-ray and VHE bands and their direct correlation during both high- and low-activity periods spanning many months show that the electron populations radiating the X-ray and gamma-ray photons are either the same, as expected in the Synchrotron-Self-Compton mechanism, or at least strongly correlated, as expected in electromagnetic cascades.Comment: Corresponding authors: Ann-Kristin Overkemping ([email protected]), Marina Manganaro ([email protected]), Diego Tescaro ([email protected]), To be published in Astronomy&Astrophysics (A&A), 12 pages, 9 figure

Multi-Wavelength Observations of the Blazar 1ES 1011+496 in Spring 2008

The BL Lac object 1ES 1011+496 was discovered at Very High Energy gamma-rays by MAGIC in spring 2007. Before that the source was little studied in different wavelengths. Therefore a multi-wavelength (MWL) campaign was organized in spring 2008. Along MAGIC, the MWL campaign included the Metsahovi radio observatory, Bell and KVA optical telescopes and the Swift and AGILE satellites. MAGIC observations span from March to May, 2008 for a total of 27.9 hours, of which 19.4 hours remained after quality cuts. The light curve showed no significant variability. The differential VHE spectrum could be described with a power-law function. Both results were similar to those obtained during the discovery. Swift XRT observations revealed an X-ray flare, characterized by a harder when brighter trend, as is typical for high synchrotron peak BL Lac objects (HBL). Strong optical variability was found during the campaign, but no conclusion on the connection between the optical and VHE gamma-ray bands could be drawn. The contemporaneous SED shows a synchrotron dominated source, unlike concluded in previous work based on nonsimultaneous data, and is well described by a standard one zone synchrotron self Compton model. We also performed a study on the source classification. While the optical and X-ray data taken during our campaign show typical characteristics of an HBL, we suggest, based on archival data, that 1ES 1011+496 is actually a borderline case between intermediate and high synchrotron peak frequency BL Lac objects.Comment: 13 pages, accepted for publication in MNRA

Measurement of the Crab Nebula spectrum over three decades in energy with the MAGIC telescopes

The MAGIC stereoscopic system collected 69 hours of Crab Nebula data between October 2009 and April 2011. Analysis of this data sample using the latest improvements in the MAGIC stereoscopic software provided an unprecedented precision of spectral and night-by-night light curve determination at gamma rays. We derived a differential spectrum with a single instrument from 50 GeV up to almost 30 TeV with 5 bins per energy decade. At low energies, MAGIC results, combined with Fermi-LAT data, show a flat and broad Inverse Compton peak. The overall fit to the data between 1 GeV and 30 TeV is not well described by a log-parabola function. We find that a modified log-parabola function with an exponent of 2.5 instead of 2 provides a good description of the data ($\chi^2=35/26$). Using systematic uncertainties of red the MAGIC and Fermi-LAT measurements we determine the position of the Inverse Compton peak to be at (53 $\pm$ 3stat + 31syst -13syst) GeV, which is the most precise estimation up to date and is dominated by the systematic effects. There is no hint of the integral flux variability on daily scales at energies above 300 GeV when systematic uncertainties are included in the flux measurement. We consider three state- of-the-art theoretical models to describe the overall spectral energy distribution of the Crab Nebula. The constant B-field model cannot satisfactorily reproduce the VHE spectral measurements presented in this work, having particular difficulty reproducing the broadness of the observed IC peak. Most probably this implies that the assumption of the homogeneity of the magnetic field inside the nebula is incorrect. On the other hand, the time-dependent 1D spectral model provides a good fit of the new VHE results when considering a 80 {\mu}G magnetic field. However, it fails to match the data when including the morphology of the nebula at lower wavelengths.Comment: accepted by JHEAp, 9 pages, 6 figure

Detection of bridge emission above 50 GeV from the Crab pulsar with the MAGIC telescopes

The Crab pulsar is the only astronomical pulsed source detected at very high energy (VHE, E>100GeV) gamma-rays. The emission mechanism of VHE pulsation is not yet fully understood, although several theoretical models have been proposed. In order to test the new models, we measured the light curve and the spectra of the Crab pulsar with high precision by means of deep observations. We analyzed 135 hours of selected MAGIC data taken between 2009 and 2013 in stereoscopic mode. In order to discuss the spectral shape in connection with lower energies, 4.6 years of {\it Fermi}-LAT data were also analyzed. The known two pulses per period were detected with a significance of $8.0 \sigma$ and $12.6 \sigma$. In addition, significant emission was found between the two pulses with $6.2 \sigma$. We discovered the bridge emission above 50 GeV between the two main pulses. This emission can not be explained with the existing theories. These data can be used for testing new theoretical models.Comment: 5 pages, 4 figure