KDM2B/FBXL10 targets c-Fos for ubiquitylation and degradation in response to mitogenic stimulation.

KDM2B (also known as FBXL10) controls stem cell self-renewal, somatic cell reprogramming and senescence, and tumorigenesis. KDM2B contains multiple functional domains, including a JmjC domain that catalyzes H3K36 demethylation and a CxxC zinc-finger that recognizes CpG islands and recruits the polycomb repressive complex 1. Here, we report that KDM2B, via its F-box domain, functions as a subunit of the CUL1-RING ubiquitin ligase (CRL1/SCF(KDM2B)) complex. KDM2B targets c-Fos for polyubiquitylation and regulates c-Fos protein levels. Unlike the phosphorylation of other SCF (SKP1-CUL1-F-box)/CRL1 substrates that promotes substrates binding to F-box, epidermal growth factor (EGF)-induced c-Fos S374 phosphorylation dissociates c-Fos from KDM2B and stabilizes c-Fos protein. Non-phosphorylatable and phosphomimetic mutations at S374 result in c-Fos protein which cannot be induced by EGF or accumulates constitutively and lead to decreased or increased cell proliferation, respectively. Multiple tumor-derived KDM2B mutations impaired the function of KDM2B to target c-Fos degradation and to suppress cell proliferation. These results reveal a novel function of KDM2B in the negative regulation of cell proliferation by assembling an E3 ligase to targeting c-Fos protein degradation that is antagonized by mitogenic stimulations

4.5 years multi-wavelength observations of Mrk 421 during the ARGO-YBJ and Fermi common operation time

We report on the extensive multi-wavelength observations of the blazar Markarian 421 (Mrk 421) covering radio to gamma-rays, during the 4.5 year period of ARGO-YBJ and Fermi common operation time, from August 2008 to February 2013. In particular, thanks to the ARGO-YBJ and Fermi data, the whole energy range from 100 MeV to 10 TeV is covered without any gap. In the observation period, Mrk 421 showed both low and high activity states at all wavebands. The correlations among flux variations in different wavebands were analyzed. Seven large flares, including five X-ray flares and two GeV gamma-ray flares with variable durations (3-58 days), and one X-ray outburst phase were identified and used to investigate the variation of the spectral energy distribution with respect to a relative quiescent phase. During the outburst phase and the seven flaring episodes, the peak energy in X-rays is observed to increase from sub-keV to few keV. The TeV gamma-ray flux increases up to 0.9-7.2 times the flux of the Crab Nebula. The behavior of GeV gamma-rays is found to vary depending on the flare, a feature that leads us to classify flares into three groups according to the GeV flux variation. Finally, the one-zone synchrotron self-Compton model was adopted to describe the emission spectra. Two out of three groups can be satisfactorily described using injected electrons with a power-law spectral index around 2.2, as expected from relativistic diffuse shock acceleration, whereas the remaining group requires a harder injected spectrum. The underlying physical mechanisms responsible for different groups may be related to the acceleration process or to the environment properties.Comment: 17 pages, 9 figures, 5 tables, Accepted for publication in ApJ

The cosmic ray proton plus helium energy spectrum measured by the ARGO-YBJ experiment in the energy range 3-300 TeV

The ARGO-YBJ experiment is a full-coverage air shower detector located at the Yangbajing Cosmic Ray Observatory (Tibet, People's Republic of China, 4300 m a.s.l.). The high altitude, combined with the full-coverage technique, allows the detection of extensive air showers in a wide energy range and offer the possibility of measuring the cosmic ray proton plus helium spectrum down to the TeV region, where direct balloon/space-borne measurements are available. The detector has been in stable data taking in its full configuration from November 2007 to February 2013. In this paper the measurement of the cosmic ray proton plus helium energy spectrum is presented in the region 3-300 TeV by analyzing the full collected data sample. The resulting spectral index is $\gamma = -2.64 \pm 0.01$. These results demonstrate the possibility of performing an accurate measurement of the spectrum of light elements with a ground based air shower detector.Comment: 18 pages, 8 figures, preprint submitted to Phys. Rev.

EAS age determination from the study of the lateral distribution of charged particles near the shower axis with the ARGO-YBJ experiment

The ARGO-YBJ experiment, a full coverage extensive air shower (EAS) detector located at high altitude (4300 m a.s.l.) in Tibet, China, has smoothly taken data, with very high stability, since November 2007 to the beginning of 2013. The array consisted of a carpet of about 7000 m$^2$ Resistive Plate Chambers (RPCs) operated in streamer mode and equipped with both digital and analog readout, providing the measurement of particle densities up to few particles per cm$^2$. The unique detector features (full coverage, readout granularity, wide dynamic range, etc) and location (very high altitude) allowed a detailed study of the lateral density profile of charged particles at ground very close to the shower axis and its description by a proper lateral distribution function (LDF). In particular, the information collected in the first 10 m from the shower axis have been shown to provide a very effective tool for the determination of the shower development stage ("age") in the energy range 50 TeV - 10 PeV. The sensitivity of the age parameter to the mass composition of primary Cosmic Rays is also discussed

Mean Interplanetary Magnetic Field Measurement Using the ARGO-YBJ Experiment

The sun blocks cosmic ray particles from outside the solar system, forming a detectable shadow in the sky map of cosmic rays detected by the ARGO-YBJ experiment in Tibet. Because the cosmic ray particles are positive charged, the magnetic field between the sun and the earth deflects them from straight trajectories and results in a shift of the shadow from the true location of the sun. Here we show that the shift measures the intensity of the field which is transported by the solar wind from the sun to the earth.Comment: 6 papges,3 figure

Observation of TeV gamma rays from the Cygnus region with the ARGO-YBJ experiment

We report the observation of TeV gamma-rays from the Cygnus region using the ARGO-YBJ data collected from 2007 November to 2011 August. Several TeV sources are located in this region including the two bright extended MGRO J2019+37 and MGRO J2031+41. According to the Milagro data set, at 20 TeV MGRO J2019+37 is the most significant source apart from the Crab Nebula. No signal from MGRO J2019+37 is detected by the ARGO-YBJ experiment, and the derived flux upper limits at 90% confidence level for all the events above 600 GeV with medium energy of 3 TeV are lower than the Milagro flux, implying that the source might be variable and hard to be identified as a pulsar wind nebula. The only statistically significant (6.4 standard deviations) gamma-ray signal is found from MGRO J2031+41, with a flux consistent with the measurement by Milagro.Comment: 14 pages, 4 figure

Observation of TeV gamma-rays from the unidentified source HESS J1841-055 with the ARGO-YBJ experiment

We report the observation of a very high energy \gamma-ray source, whose position is coincident with HESS J1841-055. This source has been observed for 4.5 years by the ARGO-YBJ experiment from November 2007 to July 2012. Its emission is detected with a statistical significance of 5.3 standard deviations. Parameterizing the source shape with a two-dimensional Gaussian function we estimate an extension \sigma=(0.40(+0.32,-0.22}) degree, consistent with the HESS measurement. The observed energy spectrum is dN/dE =(9.0-+1.6) x 10^{-13}(E/5 TeV)^{-2.32-+0.23} photons cm^{-2} s^{-1} TeV^{-1}, in the energy range 0.9-50 TeV. The integral \gamma-ray flux above 1 TeV is 1.3-+0.4 Crab units, which is 3.2-+1.0 times the flux derived by HESS. The differences in the flux determination between HESS and ARGO-YBJ, and possible counterparts at other wavelengths are discussed.Comment: 17 pages, 4 figures, have been accepted for publication in Ap

Long-term monitoring of the TeV emission from Mrk 421 with the ARGO-YBJ experiment

ARGO-YBJ is an air shower detector array with a fully covered layer of resistive plate chambers. It is operated with a high duty cycle and a large field of view. It continuously monitors the northern sky at energies above 0.3 TeV. In this paper, we report a long-term monitoring of Mrk 421 over the period from 2007 November to 2010 February. This source was observed by the satellite-borne experiments Rossi X-ray Timing Explorer and Swift in the X-ray band. Mrk 421 was especially active in the first half of 2008. Many flares are observed in both X-ray and gamma-ray bands simultaneously. The gamma-ray flux observed by ARGO-YBJ has a clear correlation with the X-ray flux. No lag between the X-ray and gamma-ray photons longer than 1 day is found. The evolution of the spectral energy distribution is investigated by measuring spectral indices at four different flux levels. Hardening of the spectra is observed in both X-ray and gamma-ray bands. The gamma-ray flux increases quadratically with the simultaneously measured X-ray flux. All these observational results strongly favor the synchrotron self-Compton process as the underlying radiative mechanism.Comment: 30 pages, 8 figure

Study of the diffuse gamma-ray emission from the Galactic plane with ARGO-YBJ

The events recorded by ARGO-YBJ in more than five years of data collection have been analyzed to determine the diffuse gamma-ray emission in the Galactic plane at Galactic longitudes 25{\deg} < l < 100{\deg} and Galactic latitudes . The energy range covered by this analysis, from ~350 GeV to ~2 TeV, allows the connection of the region explored by Fermi with the multi-TeV measurements carried out by Milagro. Our analysis has been focused on two selected regions of the Galactic plane, i.e., 40{\deg} < l < 100{\deg} and 65{\deg} < l < 85{\deg} (the Cygnus region), where Milagro observed an excess with respect to the predictions of current models. Great care has been taken in order to mask the most intense gamma-ray sources, including the TeV counterpart of the Cygnus cocoon recently identified by ARGO-YBJ, and to remove residual contributions. The ARGO-YBJ results do not show any excess at sub-TeV energies corresponding to the excess found by Milagro, and are consistent with the predictions of the Fermi model for the diffuse Galactic emission. From the measured energy distribution we derive spectral indices and the differential flux at 1 TeV of the diffuse gamma-ray emission in the sky regions investigated.Comment: 11 pages, 6 figures, published in AP