Multi-Sensor Fusion for Mono and Multi-Vehicle Localization using Bayesian Network

International audienc

Glutamate induces autophagy via the two-pore channels in neural cells

NAADP (nicotinic acid adenine dinucleotide phosphate) has been proposed as a second messenger for glutamate in neuronal and glial cells via the activation of the lysosomal Ca2+ channels TPC1 and TPC2. However, the activities of glutamate that are mediated by NAADP remain unclear. In this study, we evaluated the effect of glutamate on autophagy in astrocytes at physiological, non-toxic concentration. We found that glutamate induces autophagy at similar extent as NAADP. By contrast, the NAADP antagonist NED-19 or SiRNA-mediated inhibition of TPC1/2 decreases autophagy induced by glutamate, confirming a role for NAADP in this pathway. The involvement of TPC1/2 in glutamate-induced autophagy was also confirmed in SHSY5Y neuroblastoma cells. Finally, we show that glutamate leads to a NAADP-dependent activation of AMPK, which is required for autophagy induction, while mTOR activity is not affected by this treatment. Taken together, our results indicate that glutamate stimulates autophagy via NAADP/TPC/AMPK axis, providing new insights of how Ca2+ signalling glutamate-mediated can control the cell metabolism in the central nervous system

Effect of Grid Topology on Numerical Simulations of Flow Fields around Wind Turbine Nacelle Anemometer

In this paper, the effect of mesh topology on the numerical predictions of the immediate near wake region of a horizontal axis wind turbine is investigated. The present work focuses on the nacelle anemometry measurements. Steady Reynolds Averaged Navier-Stokes (RANS) equations are applied to describe the airflow around the wind turbine nacelle. The k-ε turbulence model is used. To model the turbine rotor, the approach based on the actuator disc concept is considered. The computational domain has been meshed with five different configurations of grid; namely, quasi-structured, unstructured and three different hybrid grids constituted of blending of quasi-structured and unstructured grids. The obtained results are compared to the available experimental data. The hybrid mesh with quasi-structured grid in the boundary layer region and unstructured grid in the vicinity of the nacelle is found to be more promising to simulate the near wake generated downstream of the wind turbine nacelle and to predict accurately the nacelle anemometry measurements

Numerical Investigations on the Fluid Behavior in the Near Wake of an Experimental Wind Turbine Model in the Presence of the Nacelle

Accurate predictions of the near wake of horizontal-axis wind turbines are critical in estimating and optimizing the energy production of wind farms. Consequently, accurate aerodynamic models of an isolated wind turbine are required. In this paper, the steady-state flow around an experimental horizontal-axis wind turbine (known as the MEXICO model) is investigated using full-geometry computational fluid dynamics (CFD) simulations. The simulations are performed using Reynolds-Averaged Navier-Stokes (RANS) equations in combination with the transitional k-kl-w turbulence model. The multiple reference frame (MRF) approach is used to allow the rotation of the blades. The impacts of the nacelle and blade rotation on the induction region and near wake are highlighted. Simulation cases under attached and detached flow conditions with and without the nacelle were compared to the detailed particle image velocimetry (PIV) measurements. The axial and radial flow behaviors at the induction region have been analyzed in detail. This study attempts to highlight the nacelle effects on the near wake flow and on numerical prediction accuracy under various conditions, as well as the possible reasons for these effects. According to simulation results, the rotation of blades dominates the near wake region, and including the nacelle geometry can improve both axial and radial flow prediction accuracy by up to 15% at high wind speeds. At low wind speeds, the nacelle effects can be ignored. The presence of the nacelle has also been shown to increase flow separation at the trailing edges of the blade airfoils, increasing both root and tip vorticities. Finally, small nacelle diameters are recommended to reduce flow separation on the blades and increase the average velocity downstream of the rotor, thereby optimizing wind farm output power

Synthesis of Spherical 4R Mechanism for Path Generation using Differential Evolution

The problem of path generation for the spherical 4R mechanism is solved using the Differential Evolution algorithm (DE). Formulas for the spherical geodesics are employed in order to obtain the parametric equation for the generated trajectory. Direct optimization of the objective function gives the solution to the path generation task without prescribed timing. Therefore, there is no need to separate this task into two stages to make the optimization. Moreover, the order defect problem can be solved without difficulty by means of manipulations of the individuals in the DE algorithm. Two examples of optimum synthesis showing the simplicity and effectiveness of this approach are included.Comment: Submitted to Mechanism and Machine Theor

A cyclopalladated complex interacts with mitochondrial membrane thiol-groups and induces the apoptotic intrinsic pathway in murine and cisplatin-resistant human tumor cells

<p>Abstract</p> <p>Background</p> <p>Systemic therapy for cancer metastatic lesions is difficult and generally renders a poor clinical response. Structural analogs of cisplatin, the most widely used synthetic metal complexes, show toxic side-effects and tumor cell resistance. Recently, palladium complexes with increased stability are being investigated to circumvent these limitations, and a biphosphinic cyclopalladated complex {Pd₂[<it>S_(-)</it>C², N-dmpa]₂(μ-dppe)Cl₂} named C7a efficiently controls the subcutaneous development of B16F10-Nex2 murine melanoma in syngeneic mice. Presently, we investigated the melanoma cell killing mechanism induced by C7a, and extended preclinical studies.</p> <p>Methods</p> <p>B16F10-Nex2 cells were treated <it>in vitro </it>with C7a in the presence/absence of DTT, and several parameters related to apoptosis induction were evaluated. Preclinical studies were performed, and mice were endovenously inoculated with B16F10-Nex2 cells, intraperitoneally treated with C7a, and lung metastatic nodules were counted. The cytotoxic effects and the respiratory metabolism were also determined in human tumor cell lines treated <it>in vitro </it>with C7a.</p> <p>Results</p> <p>Cyclopalladated complex interacts with thiol groups on the mitochondrial membrane proteins, causes dissipation of the mitochondrial membrane potential, and induces Bax translocation from the cytosol to mitochondria, colocalizing with a mitochondrial tracker. C7a also induced an increase in cytosolic calcium concentration, mainly from intracellular compartments, and a significant decrease in the ATP levels. Activation of effector caspases, chromatin condensation and DNA degradation, suggested that C7a activates the apoptotic intrinsic pathway in murine melanoma cells. In the preclinical studies, the C7a complex protected against murine metastatic melanoma and induced death in several human tumor cell lineages <it>in vitro</it>, including cisplatin-resistant ones. The mitochondria-dependent cell death was also induced by C7a in human tumor cells.</p> <p>Conclusions</p> <p>The cyclopalladated C7a complex is an effective chemotherapeutic anticancer compound against primary and metastatic murine and human tumors, including cisplatin-resistant cells, inducing apoptotic cell death via the intrinsic pathway.</p

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

14-3-3theta Protects against Neurotoxicity in a Cellular Parkinson's Disease Model through Inhibition of the Apoptotic Factor Bax

Disruption of 14-3-3 function by alpha-synuclein has been implicated in Parkinson's disease. As 14-3-3s are important regulators of cell death pathways, disruption of 14-3-3s could result in the release of pro-apoptotic factors, such as Bax. We have previously shown that overexpression of 14-3-3θ reduces cell loss in response to rotenone and MPP+ in dopaminergic cell culture and reduces cell loss in transgenic C. elegans that overexpress alpha-synuclein. In this study, we investigate the mechanism for 14-3-3θ's neuroprotection against rotenone toxicity. While 14-3-3s can inhibit many pro-apoptotic factors, we demonstrate that inhibition of one factor in particular, Bax, is important to 14-3-3s' protection against rotenone toxicity in dopaminergic cells. We found that 14-3-3θ overexpression reduced Bax activation and downstream signaling events, including cytochrome C release and caspase 3 activation. Pharmacological inhibition or shRNA knockdown of Bax provided protection against rotenone, comparable to 14-3-3θ's neuroprotective effects. A 14-3-3θ mutant incapable of binding Bax failed to protect against rotenone. These data suggest that 14-3-3θ's neuroprotective effects against rotenone are at least partially mediated by Bax inhibition and point to a potential therapeutic role of 14-3-3s in Parkinson's disease