Inflammation, DNA-centered radicals, and oxidative genotoxicity: The role of HOCl produced by myeloperoxidase in carcinogenesis

Myeloid cells (macrophages and neutrophils) infiltrate and synthesize myeloperoxidase (MPO) in sites of inflammation, producing gentotoxicity. In RAW 264.7 macrophages, bacterial lipopolysaccharide (LPS) induces superoxide radical anion, nuclear deformation (nuclear protuberances), MPO synthesis, biomolecule oxidation and cell death. “Freezing” LPS-triggered macrophage activation with the nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) prevented cell activation and death. Oxidation of proteins and genomic DNA was also blocked, with formation of protein- and DNA-DMPO nitrone adducts, as analyzed by immuno-spin trapping with a polyclonal anti-DMPO serum. Interestingly, confocal microscopy analysis of these cells showed that MPO, genomic DNA, and DNA-DMPO nitrone adducts co-localized in the nuclear protuberances. These observations, and the fact that DNA is negatively charged and MPO is a cationic protein, suggest a role for uptaken or newly synthesized MPO in oxidative genotoxicity induced by myeloid cells in sites of inflammation. 
In order to understand MPO-induced formation of DNA-centered radicals, we studied DNA-DMPO nitrone adducts in calf thymus DNA treated with micromolar concentrations of hypochlorous acid (HOCl) added as a bolus or generated in situ by the MPO/H2O2/Cl- system in the presence of DMPO. We also investigated DNA-DMPO nitrone adducts inside living cells containing MPO. The cell models we used were: i) human leukemia (HL)-60 cells, which overexpress MPO, ii) RAW 264.7 macrophages activated with LPS (1 ng/ml for 24 h), to induce MPO, and iii) A549 human airway epithelial cells pre-loaded with human MPO. When these cells were activated with the phorbol ester PMA, the number of 6-thioguanine-resistant cells with the hypoxanthine-guanine phosphoribosyl transferase (HRPT) mutation increased. This mutation was prevented by each of the following: the NADPH oxidase inhibitor apocynin; the MPO inhibitors salicylhydroxamic acid and 4-aminobenzoic acid hydrazide; the cell-permeable HOCl scavenger resveratrol; and DMPO, which traps DNA-centered radicals and prevents further oxidation. 
Genomic DNA-centered radicals and further mutagenesis induced by activated myeloid cells in sites of inflammation can be prevented by blocking MPO activity, preventing formation of and/or scavenging HOCl, or trapping DNA-centered radicals. Our findings provide new therapeutic avenues for preventing carcinogenesis induced by infiltration and activation of myeloid cells in sites of inflammation, for example, in the lung exposed to particulate matter. SUPPORTED BY NIEHS 5R00ES015415-03
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Gradient Tracking for Coalitional Aggregation of Wind Power

In this work we study coalition formation for a set of independent wind power producers. The wind power producers bid a contract in a day-ahead market, and they wish to determine the optimal contract that maximizes their expected profit. To cope with the volatility of the wind, the producers can form coalitions and aggregate their power production. We consider a communication topology and we assume that each wind power producer gets information about the wind powers realisation in the network through the contracts bidden by its neighbours. To determine the optimal contract for each coalition, we use a data learning approach based on gradient tracking. We prove that, for each coalition, the producers converge to the optimal contract for such a coalition. From the optimal contract we obtain the profit of each coalition which represents the coalitions' values of the resulting coalitional game. Then, we design a stabilizing allocation mechanism based on the Shapley value.</p

Gradient Tracking for Coalitional Aggregation of Wind Power

In this work we study coalition formation for a set of independent wind power producers. The wind power producers bid a contract in a day-ahead market, and they wish to determine the optimal contract that maximizes their expected profit. To cope with the volatility of the wind, the producers can form coalitions and aggregate their power production. We consider a communication topology and we assume that each wind power producer gets information about the wind powers realisation in the network through the contracts bidden by its neighbours. To determine the optimal contract for each coalition, we use a data learning approach based on gradient tracking. We prove that, for each coalition, the producers converge to the optimal contract for such a coalition. From the optimal contract we obtain the profit of each coalition which represents the coalitions' values of the resulting coalitional game. Then, we design a stabilizing allocation mechanism based on the Shapley value.</p

Gradient Tracking for Coalitional Aggregation of Wind Power

In this work we study coalition formation for a set of independent wind power producers. The wind power producers bid a contract in a day-ahead market, and they wish to determine the optimal contract that maximizes their expected profit. To cope with the volatility of the wind, the producers can form coalitions and aggregate their power production. We consider a communication topology and we assume that each wind power producer gets information about the wind powers realisation in the network through the contracts bidden by its neighbours. To determine the optimal contract for each coalition, we use a data learning approach based on gradient tracking. We prove that, for each coalition, the producers converge to the optimal contract for such a coalition. From the optimal contract we obtain the profit of each coalition which represents the coalitions' values of the resulting coalitional game. Then, we design a stabilizing allocation mechanism based on the Shapley value.</p

Diseño de un controlador de seguimiento para un sistema SISO de servoposicionamiento neumático

Pneumatic systems have many advantages, such as simplicity, reliability, low-cost, long life, etc. making them attractive for rapid development and widespread application, but the complexity of the airflow through the valve port and the friction between the cylinder and piston make it difficult to establish an exact mathematical model and control the pneumatic system with high precision. Experiments were conducted with a 25 mm bore rod-less pneumatic cylinder and a 5/3 way proportional control valve. In this contribution, I propose a nonlinear robust tracking control strategy to solve the tracking problem of the servo pneumatic positioning system. The approach is novel in the sense that it takes into account the nonlinearities inherent to pneumatic servo positioning systems and considers position, velocity and pressure difference in the chambers of the pneumatic cylinder as feedback states. The suggested control strategy is implemented in simulation and on the real system. Experimental results from an implementation on a test ring show a high position tracking control performance.Los sistemas neumáticos tienen varias ventajas que permitieron su rápido desarrollo y uso generalizado, tales como: simplicidad, confiabilidad, bajo costo, larga vida etc. Sin embargo, la complejidad del flujo de aire a través de los orificios de la válvula y la naturaleza de la fuerza de fricción entre las paredes del cilindro y el pistón, dificultan la obtención de modelos matemáticos exactos y el control de los sistemas neumáticos con alta precisión. Experimentos fueron llevados a cabo con un cilindro sin vástago de 25 mm de diámetro y una válvula de control proporcional de 5 puertos -3 vías. En este artículo, proponemos una estrategia de control de posicionamiento robusta para solucionar el problema de un sistema de servo posicionamiento neumático. El enfoque es novedoso en el sentido de que tiene en cuenta las no linealidades inherentes a los sistemas de servo posicionamiento neumático y considera posición, velocidad y diferencia de presiones en las cámaras del cilindro neumático como estados de retroalimentación.  La estrategia de control propuesta es implementada en simulación y sobre el sistema real. Los resultados experimentales de la implementación de la estrategia en el sistema de servo-posicionamiento  neumático muestran un alto desempeño en el control de seguimiento de posición

Dynamic Coordination Games with Activation Costs

Motivated by inventory control problems with set-up costs, we consider a coordination game where each player’s dynamics is an inventory model characterized by a controlled input and an uncontrolled output. An activation cost is shared among active players, namely players who control their dynamics at a given time. At each time, each player decides to be active or not depending on its inventory level. The main contribution of this paper is to show that strategies at a Nash equilibrium have a threshold structure on the number of active players. Furthermore, we provide an explicit expression for the lower and upper threshold is given both in the deterministic case, namely when the exogenous signal is known, and in the single-stage game. The relevance of the above results is discussed in the context of inventory control where Nash equilibrium reordering strategies imply that a single retailer reorders only if jointly with a number of other retailers and will reorder to restore a pre-assigned inventory level

Computing DSGE Models with Recursive Preferences

This paper compares different solution methods for computing the equilibrium of dynamic stochastic general equilibrium (DSGE) models with recursive preferences such as those in Epstein and Zin (1989 and 1991). Models with these preferences have recently become popular, but we know little about the best ways to implement them numerically. To fill this gap, we solve the stochastic neoclassical growth model with recursive preferences using four different approaches: second and third-order perturbation, Chebyshev polynomials, and value function iteration. We document the performance of the methods in terms of computing time, implementation complexity, and accuracy. Our main finding is that a third-order perturbation is competitive in terms of accuracy with Chebyshev polynomials and value function iteration, while being an order of magnitude faster to run. Therefore, we conclude that perturbation methods are an attractive approach for computing this class of problems.DSGE Models, Recursive Preferences, Perturbation

Cascading failures: dynamics, stability and control

We develop a dynamic model of cascading failures in a financial network whereby cross-holdings are viewed as feedback, external assets investments as inputs and failure penalties as static nonlinearities. We provide sufficient milder and stronger conditions for the system to be a positive one, and study equilibrium points and stability. Stability implies absence of cascades and convergence of market values to constant values. We provide a constructive method for control design to obtain stabilizing market investments in the form of feedback-feedforward control inputs

Coordinated maintenance in a multi-component system with compound Poisson deterioration

This paper proposes a coordinated maintenance model in a multi-component system with compound Poisson deterioration. The main contribution is a policy-iteration approach for Semi-Markov processes that optimizes the threshold at which the component is eligible for preventive maintenance if another component requires corrective maintenance. The methodology is novel as we develop explicit expressions for the policy evaluation and prove these expressions to satisfy the set of linear equations which characterize traditional policy evaluation. By doing so, long-run average cost savings are achieved, since setup costs can be shared