Stem cell marker (Nanog) and Stat-3 signaling promote MicroRNA-21 expression and chemoresistance in hyaluronan/CD44-activated head and neck squamous cell carcinoma cells.

MicroRNAs are often associated with the pathogenesis of many cancers, including head and neck squamous cell carcinoma (HNSCC). In particular, microRNA-21 (miR-21) appears to have a critical role in tumor cell survival, chemoresistance and HNSCC progression. In this study, we investigated matrix hyaluronan (HA)-induced CD44 (a primary HA receptor) interaction with the stem cell markers, Nanog and Stat-3, in HNSCC cells (HSC-3 cells). Our results indicate that HA binding to CD44 promotes Nanog-Stat-3 (also tyrosine phosphorylated Stat-3) complex formation, nuclear translocation and transcriptional activation. Further analyses reveal that miR-21 is controlled by an upstream promoter containing Stat-3 binding site(s), while chromatin immunoprecipitation assays demonstrate that stimulation of miR-21 expression by HA/CD44 signaling is Nanog/Stat-3-dependent in HNSCC cells. This process results in a decrease of a tumor suppressor protein (PDCD4), and an upregulation of i nhibitors of the apoptosis family of proteins (IAPs) as well as chemoresistance in HSC-3 cells. Treatment of HSC-3 cells with Nanog- and/or Stat-3-specific small interfering RNAs effectively blocks HA-mediated Nanog-Stat-3 signaling events, abrogates miR-21 production and increases PDCD4 expression. Subsequently, this Nanog-Stat-3 signaling inhibition causes downregulation of survival protein (IAP) expression and enhancement of chemosensitivity. To further evaluate the role of miR-21 in tumor cell-specific functions, HSC-3 cells were also transfected with a specific anti-miR-21 inhibitor in order to silence miR-21 expression and block its target functions. Our results demonstrate that anti-miR-21 inhibitor not only upregulates PDCD4 expression but also decreases IAP expression and enhances chemosensitivity in HA-treated HNSCC cells. Together, these findings indicate that the HA-induced CD44 interaction with Nanog and Stat-3 has a pivotal role in miR-21 production leading to PDCD4 reduction, IAP upregulation and chemoresistance in HNSCC cells. This novel Nanog/Stat-3 signaling pathway-specific mechanism involved in miR-21 production is significant for the formation of future intervention strategies in the treatment of HA/CD44-activated HNSCC

The mystery of the 'Kite' radio source in Abell 2626: insights from new Chandra observations

We present the results of a new Chandra study of the galaxy cluster A2626. The radio emission of the cluster shows a complex system of four symmetric arcs without known correlations with the X-ray emission. The mirror symmetry of the radio arcs toward the center and the presence of two optical cores in the central galaxy suggested that they may be created by pairs of precessing radio jets powered by dual AGNs inside the cD galaxy. However, previous observations failed to observe the second jetted AGN and the spectral trend due to radiative age along the radio arcs, thus challenging this interpretation. The new Chandra observation had several scientific objectives, including the search for the second AGN that would support the jet precession model. We focus here on the detailed study of the local properties of the thermal and non-thermal emission in the proximity of the radio arcs, in order to get more insights into their origin. We performed a standard data reduction of the Chandra dataset deriving the radial profiles of temperature, density, pressure and cooling time of the intra-cluster medium. We further analyzed the 2D distribution of the gas temperature, discovering that the south-western junction of the radio arcs surrounds the cool core of the cluster. We studied the X-ray SB and spectral profiles across the junction, finding a cold front spatially coincident with the radio arcs. This may suggest a connection between the sloshing of the thermal gas and the nature of the radio filaments, raising new scenarios for their origin. A possibility is that the radio arcs trace the projection of a complex surface connecting the sites where electrons are most efficiently reaccelerated by the turbulence that is generated by the gas sloshing. In this case, diffuse emission embedded by the arcs and with extremely steep spectrum should be most visible at very low radio frequencies.Comment: 7 pages, 7 figures. Accepted for publication on A&

Multi-Agent Reinforcement Learning-Based Buffer-Aided Relay Selection in IRS-Assisted Secure Cooperative Networks

This paper proposes a multi-agent deep reinforcement learning-based buffer-aided relay selection scheme for an intelligent reflecting surface (IRS)-assisted secure cooperative network in the presence of an eavesdropper. We consider a practical phase model where both phase shift and reflection amplitude are discrete variables to vary the reflection coefficients of the IRS. Furthermore, we introduce the buffer-aided relay to enhance the secrecy performance, but the use of the buffer leads to the cost of delay. Thus, we aim to maximize either the average secrecy rate with a delay constraint or the throughput with both delay and secrecy constraints, by jointly optimizing the buffer-aided relay selection and the IRS reflection coefficients. To obtain the solution of these two optimization problems, we divide each of the problems into two sub-tasks and then develop a distributed multi-agent reinforcement learning scheme for the two cooperative sub-tasks, each relay node represents an agent in the distributed learning. We apply the distributed reinforcement learning scheme to optimize the IRS reflection coefficients, and then utilize an agent on the source to learn the optimal relay selection based on the optimal IRS reflection coefficients in each iteration. Simulation results show that the proposed learning-based scheme uses an iterative approach to learn from the environment for approximating an optimal solution via the exploration of multiple agents, which outperforms the benchmark schemes

Highly Improved Staggered Quarks on the Lattice, with Applications to Charm Physics

We use perturbative Symanzik improvement to create a new staggered-quark action (HISQ) that has greatly reduced one-loop taste-exchange errors, no tree-level order a^2 errors, and no tree-level order (am)^4 errors to leading order in the quark's velocity v/c. We demonstrate with simulations that the resulting action has taste-exchange interactions that are at least 3--4 times smaller than the widely used ASQTAD action. We show how to estimate errors due to taste exchange by comparing ASQTAD and HISQ simulations, and demonstrate with simulations that such errors are no more than 1% when HISQ is used for light quarks at lattice spacings of 1/10 fm or less. The suppression of (am)^4 errors also makes HISQ the most accurate discretization currently available for simulating c quarks. We demonstrate this in a new analysis of the psi-eta_c mass splitting using the HISQ action on lattices where a m_c=0.43 and 0.66, with full-QCD gluon configurations (from MILC). We obtain a result of~111(5) MeV which compares well with experiment. We discuss applications of this formalism to D physics and present our first high-precision results for D_s mesons.Comment: 21 pages, 8 figures, 5 table

Precise charm to strange mass ratio and light quark masses from full lattice QCD

By using a single formalism to handle charm, strange and light valence quarks in full lattice QCD for the first time, we are able to determine ratios of quark masses to 1%. For $m_c/m_s$ we obtain 11.85(16), an order of magnitude more precise than the current PDG average. Combined with 1% determinations of the charm quark mass now possible this gives $\bar{m}_s(2{\rm GeV}) =$ 92.4(1.5) MeV. The MILC result for $m_s/m_l = 27.2(3)$ yields $\bar{m}_l(2{\rm GeV})$ = 3.40(7) MeV for the average of $u$ and $d$ quark masses.Comment: 4 pages, 2 figures. Version accepted by Physical Review Letters. Changes include modifying the title, using the MILC value for m_s/m_l which changes slightly the resulting up and down quark masses and their average, adding some references and making other small adjustments to the text for space reasons

Unification of bulk and interface electroresistive switching in oxide systems

We demonstrate that the physical mechanism behind electroresistive switching in oxide Schottky systems is electroformation, as in insulating oxides. Negative resistance shown by the hysteretic current-voltage curves proves that impact ionization is at the origin of the switching. Analyses of the capacitance-voltage and conductance-voltage curves through a simple model show that an atomic rearrangement is involved in the process. Switching in these systems is a bulk effect, not strictly confined at the interface but at the charge space region.Comment: 4 pages, 3 figures, accepted in PR