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

Minimally-intrusive Navigation in Dense Crowds with Integrated Macro and Micro-level Dynamics

In mobile robot navigation, despite advancements, the generation of optimal paths often disrupts pedestrian areas. To tackle this, we propose three key contributions to improve human-robot coexistence in shared spaces. Firstly, we have established a comprehensive framework to understand disturbances at individual and flow levels. Our framework provides specialized computational strategies for in-depth studies of human-robot interactions from both micro and macro perspectives. By employing novel penalty terms, namely Flow Disturbance Penalty (FDP) and Individual Disturbance Penalty (IDP), our framework facilitates a more nuanced assessment and analysis of the robot navigation's impact on pedestrians. Secondly, we introduce an innovative sampling-based navigation system that adeptly integrates a suite of safety measures with the predictability of robotic movements. This system not only accounts for traditional factors such as trajectory length and travel time but also actively incorporates pedestrian awareness. Our navigation system aims to minimize disturbances and promote harmonious coexistence by considering safety protocols, trajectory clarity, and pedestrian engagement. Lastly, we validate our algorithm's effectiveness and real-time performance through simulations and real-world tests, demonstrating its ability to navigate with minimal pedestrian disturbance in various environments.Comment: 23 pages, 13 figure

The Interaction between the First Transmembrane Domain and the Thumb of ASIC1a Is Critical for Its N-Glycosylation and Trafficking

Acid-sensing ion channel-1a (ASIC1a), the primary proton receptor in the brain, contributes to multiple diseases including stroke, epilepsy and multiple sclerosis. Thus, a better understanding of its biogenesis will provide important insights into the regulation of ASIC1a in diseases. Interestingly, ASIC1a contains a large, yet well organized ectodomain, which suggests the hypothesis that correct formation of domain-domain interactions at the extracellular side is a key regulatory step for ASIC1a maturation and trafficking. We tested this hypothesis here by focusing on the interaction between the first transmembrane domain (TM1) and the thumb of ASIC1a, an interaction known to be critical in channel gating. We mutated Tyr71 and Trp287, two key residues involved in the TM1-thumb interaction in mouse ASIC1a, and found that both Y71G and W287G decreased synaptic targeting and surface expression of ASIC1a. These defects were likely due to altered folding; both mutants showed increased resistance to tryptic cleavage, suggesting a change in conformation. Moreover, both mutants lacked the maturation of N-linked glycans through mid to late Golgi. These data suggest that disrupting the interaction between TM1 and thumb alters ASIC1a folding, impedes its glycosylation and reduces its trafficking. Moreover, reducing the culture temperature, an approach commonly used to facilitate protein folding, increased ASIC1a glycosylation, surface expression, current density and slowed the rate of desensitization. These results suggest that correct folding of extracellular ectodomain plays a critical role in ASIC1a biogenesis and function

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

The Dynamical Cluster Approximation: Non-Local Dynamics of Correlated Electron Systems

We recently introduced the dynamical cluster approximation(DCA), a new technique that includes short-ranged dynamical correlations in addition to the local dynamics of the dynamical mean field approximation while preserving causality. The technique is based on an iterative self-consistency scheme on a finite size periodic cluster. The dynamical mean field approximation (exact result) is obtained by taking the cluster to a single site (the thermodynamic limit). Here, we provide details of our method, explicitly show that it is causal, systematic, $\Phi$-derivable, and that it becomes conserving as the cluster size increases. We demonstrate the DCA by applying it to a Quantum Monte Carlo and Exact Enumeration study of the two-dimensional Falicov-Kimball model. The resulting spectral functions preserve causality, and the spectra and the CDW transition temperature converge quickly and systematically to the thermodynamic limit as the cluster size increases.Comment: 19 pages, 13 postscript figures, revte

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

Securitization in Chinese climate and energy politics

This article provides an overview of securitization in Chinese climate and energy debates. Scholars have debated the merits as well as the potentially problematic implications of securitization, or framing issues as ‘security,’ since the early 1990s. Early concern focused on the potential problems with linking environmental issues with ‘security,’ and the debate has since also turned specifically to the climate and energy. However, it is only recently that this debate has begun to pay attention to China. Energy and climate concerns are of increasing importance to China: the sheer scale of its energy consumption and air pollution struggles dwarf the challenges seen by other states, and its policy choices play a key role in shaping global climate and energy dynamics. Thus, while securitization in the Chinese context is rarely studied, how China frames its energy and climate policy matters. Both energy and climate are taken increasingly seriously, and security plays an increasing role in debates. This review surveys the increasing popularity of linking security with climate and energy issues both in the academic debate on China and in official discourse, and some of the potential implications

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