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

Comparison of spin dynamics in YBa2Cu3O7-δ and La2-xSrxCuO4: Effects of Fermi-surface geometry

Neutron experiments have indicated that the structure factor S(q,ω) for the two cuprates YBa2Cu3O7-δ and La2-xSrxCuO4 has a different q dependence. Commensurate peaks at (π/a,π/a) are observed in the former case, whereas clearly incommensurate peaks are seen in the latter, for metallic hole concentrations. We attribute this contrasting q dependence to differences in the Fermi-surface geometry, obtained in band-structure approaches, and (for the YBaCuO system) also corroborated by photoemission experiments. Using a large Coulomb-U, Fermi-liquid-based scheme, we present results for the q,ω and temperature dependence of the neutron cross section as well as for the temperature dependence of the NMR relaxation, in both cuprate families at various hole concentrations. When antiferromagnetic quasiparticle interactions of moderate strength are included, these calculations compare favorably with experiment. It should be stressed that the Fermi-surface shape must be accurately represented in both systems in order to produce this good agreement with the neutron data. We conclude that the close correspondence found, thus far, between band-structure-derived spin dynamics and the detailed fermiology of both cuprates provides support for Fermi-liquid-based schemes. Furthermore, this correspondence suggests important constraints which should be included in theoretical schemes ranging from the marginal and nearly antiferromagnetic Fermi liquid to more exotic scenarios for the normal state. Within this context, it is extremely important to determine the characteristic energy scales of the Fermi liquid. Comparison of our calculations with the measured energy scales of the spin dynamics indicates that these are sufficiently low so that one can reconcile deviations from canonical behavior above Tc with a Fermi-liquid ground state. Explicit effects of these low-energy scales are discussed in the context of the quasiparticle lifetime as a function of frequency and temperature. Our detailed studies also yield predictions for future experiments which will help to test futher the validity of this approach

Superconducting Order Parameter in Bi-Layer Cuprates: Occurrence of π\pi Phase Shifts in Corner Junctions

We study the order parameter symmetry in bi-layer cuprates such as YBaCuO, where interesting $\pi$ phase shifts have been observed in Josephson junctions. Taking models which represent the measured spin fluctuation spectra of this cuprate, as well as more general models of Coulomb correlation effects, we classify the allowed symmetries and determine their associated physical properties. $\pi$ phase shifts are shown to be a general consequence of repulsive interactions, independent of whether a magnetic mechanism is operative. While it is known to occur in d-states, this behavior can also be associated with (orthorhombic) s-symmetry when the two sub-band gaps have opposite phase. Implications for the magnitude of $T_c$ are discussed.Comment: 5 pages, RevTeX 3.0, 9 figures (available upon request

Theory of Neutron Scattering in the Normal and Superconducting State of YBCO

We analyze neutron experiments on \ybco at various stoichiometries in the superconducting state, within the context of a bi-layer theory which yields good agreement with the normal state Cu-NMR and neutron data as a function of \omega, q and T. A d-wave superconducting state exhibits peaks at q = ( \pi , \pi , \pi ) and sharp maxima as a function of \omega, at twice the gap frequency. This behavior may have been observed experimentally. The counterpart behavior for other choices of order parameter symmetry is discussed.Comment: uuencoded postscript file for the entire paper enclose

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

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

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