Reactive Oxygen Species via Redox Signaling to PI3K/AKT Pathway Contribute to the Malignant Growth of 4-Hydroxy Estradiol-Transformed Mammary Epithelial Cells

The purpose of this study was to investigate the effects of 17-β-estradiol (E2)-induced reactive oxygen species (ROS) on the induction of mammary tumorigenesis. We found that ROS-induced by repeated exposures to 4-hydroxy-estradiol (4-OH-E2), a predominant catechol metabolite of E2, caused transformation of normal human mammary epithelial MCF-10A cells with malignant growth in nude mice. This was evident from inhibition of estrogen-induced breast tumor formation in the xenograft model by both overexpression of catalase as well as by co-treatment with Ebselen. To understand how 4-OH-E2 induces this malignant phenotype through ROS, we investigated the effects of 4-OH-E2 on redox-sensitive signal transduction pathways. During the malignant transformation process we observed that 4-OH-E2 treatment increased AKT phosphorylation through PI3K activation. The PI3K-mediated phosphorylation of AKT in 4-OH-E2-treated cells was inhibited by ROS modifiers as well as by silencing of AKT expression. RNA interference of AKT markedly inhibited 4-OH-E2-induced in vitro tumor formation. The expression of cell cycle genes, cdc2, PRC1 and PCNA and one of transcription factors that control the expression of these genes – nuclear respiratory factor-1 (NRF-1) was significantly up-regulated during the 4-OH-E2-mediated malignant transformation process. The increased expression of these genes was inhibited by ROS modifiers as well as by silencing of AKT expression. These results indicate that 4-OH-E2-induced cell transformation may be mediated, in part, through redox-sensitive AKT signal transduction pathways by up-regulating the expression of cell cycle genes cdc2, PRC1 and PCNA, and the transcription factor – NRF-1. In summary, our study has demonstrated that: (i) 4-OH-E2 is one of the main estrogen metabolites that induce mammary tumorigenesis and (ii) ROS-mediated signaling leading to the activation of PI3K/AKT pathway plays an important role in the generation of 4-OH-E2-induced malignant phenotype of breast epithelial cells. In conclusion, ROS are important signaling molecules in the development of estrogen-induced malignant breast lesions.

Direct power control with common mode voltage elimination for open-winding brushless doubly-fed wind power generators

In this paper, a new open-winding control strategy is proposed for a brushless doubly-fed reluctance generator (BDFRG) applicable for wind turbines. The BDFRG control winding is fed via a dual two-level three-phase converter using a single dc bus. Direct power control based on maximum power point tracking with common mode voltage elimination is designed, which not only the active and reactive power is decoupled, but the reliability and redundancy are all improved greatly by increasing the switching modes of operation, while DC-link voltage and rating of power devices decreased by 50% comparing to the traditional three-level converter systems. Consequently its effectiveness is evaluated by simulation tests based on a 42-kW prototype generator.

System operational costs reduction with non-conventional reactive power sources

Wind energy installations are increasing in power systems worldwide and wind generation capacity tends to be located some distance from load centers. A conflict may arise at times of high wind generation when it becomes necessary to curtail wind energy in order to maintain conventional generators on-line for the provision of voltage control support at load centers. Using the island of Ireland as a case study and presenting commercially available reactive power support devices as possible solutions to the voltage control problems in urban areas, this paper explores the reduction in total generation costs resulting from the relaxation of the operational constraints requiring conventional generators to be kept on-line near load centers for reactive power support. The paper shows that by 2020 there will be possible savings of 87€m per annum and a reduction in wind curtailment of more than a percentage point if measures are taken to relax these constraints.

BIDIRECTIONAL AC-DC CONVERTERS USING ONE CYCLE CONTROL (OCC) FOR ELECTRIC VEHICLES

The electric vehicle (EV) market has seen a rapid growth in the recent past. With an increase in the number of electric vehicles on road, there is an increase in the number of high capacity battery banks interfacing the grid. The battery bank of an EV, besides being the fuel tank, is also a huge energy storage unit. Presently, it is used only when the vehicle is being driven and remains idle for rest of the time, rendering it underutilized. Whereas on the other hand, there is a need of large energy storage units in the grid to filter out the fluctuations of supply and demand during a day. EVs can help bridge this gap. The EV battery bank can be used to store the excess energy from the grid to vehicle (G2V) or supply stored energy from the vehicle to grid (V2G ), when required. To let power flow happen, in both directions, a bidirectional AC-DC converter is required. This thesis concentrates on the bidirectional AC-DC converters which have a control on power flow in all four quadrants for the application of EV battery interfacing with the grid. This thesis presents a bidirectional interleaved full bridge converter topology. This helps in increasing the power processing and current handling capability of the converter which makes it suitable for the purpose of EVs. Further, the benefit of using the interleaved topology is that it increases the power density of the converter. This ensures optimization of space usage with the same power handling capacity. The proposed interleaved converter consists of two full bridges. The corresponding gate pulses of each switch, in one cell, are phase shifted by 180 degrees from those of the other cell. The proposed converter control is based on the one-cycle controller. To meet the challenge of new requirements of reactive power handling capabilities for grid connected converters, posed by the utilities, the controller is modified to make it suitable to process the reactive power. A fictitious current derived from the grid voltage is introduced in the controller, which controls the converter performance. The current references are generated using the second order generalized integrators (SOGI) and phase locked loop (PLL). A digital implementation of the proposed control ii scheme is developed and implemented using DSP hardware. The simulated and experimental results, based on the converter topology and control technique discussed here, are presented to show the performance of the proposed theory.

Development of Effortful Control as a Moderator of the Longitudinal Relations of Negative Reactivity and Symptoms in Preschool

Thesis (Ph.D.)--University of Washington, 2016-08

Reactive clusters on a membrane

We investigate the reaction dynamics of diffusive molecules with immobile binding partners. The fixed reactants build clusters that comprise just a few tens of molecules, which leads to small cluster sizes. These molecules participate in the reaction only if they are activated. The dynamics of activation is mapped to a time-dependent size of an active region within the cluster. We focus on the deterministic description of the dynamics of a single cluster. The spatial setup accounts for one of the most important determinants of the dynamics of a cluster, i.e. diffusional transport of reaction partners toward or away from the active region of the cluster. We provide numerical and analytical evidence that diffusion influences decisively the dynamic regimes of the reactions. The application of our methods to intracellular Ca²⁺ dynamics shows that large local concentrations saturate the Ca²⁺ feedback to the channel state control. That eliminates oscillations depending on this feedback.

An experimental study of adaptive control for evolutionary algorithms

International audience

Quality control of gamma irradiated dwarf mallow (Malva neglecta Wallr.) based on color, organic acids, total phenolics and antioxidant parameters

This study addresses the effects of gamma irradiation (1, 5 and 8 kGy) on color, organic acids, total phenolics, total flavonoids, and antioxidant activity of dwarf mallow (Malva neglecta Wallr.). Organic acids were analyzed by ultra fast liquid chromatography (UFLC) coupled to a photodiode array (PDA) detector. Total phenolics and flavonoids were measured by the Folin-Ciocalteu and aluminium chloride colorimetric methods, respectively. The antioxidant activity was evaluated based on the DPPH(•) scavenging activity, reducing power, β-carotene bleaching inhibition and thiobarbituric acid reactive substances (TBARS) formation inhibition. Analyses were performed in the non-irradiated and irradiated plant material, as well as in decoctions obtained from the same samples. The total amounts of organic acids and phenolics recorded in decocted extracts were always higher than those found in the plant material or hydromethanolic extracts, respectively. The DPPH(•) scavenging activity and reducing power were also higher in decocted extracts. The assayed irradiation doses affected differently the organic acids profile. The levels of total phenolics and flavonoids were lower in the hydromethanolic extracts prepared from samples irradiated at 1 kGy (dose that induced color changes) and in decocted extracts prepared from those irradiated at 8 kGy. The last samples also showed a lower antioxidant activity. In turn, irradiation at 5 kGy favored the amounts of total phenolics and flavonoids. Overall, this study contributes to the understanding of the effects of irradiation in indicators of dwarf mallow quality, and highlighted the decoctions for its antioxidant properties.

New insights into plant salt acclimation: the roles of vesicle trafficking and reactive oxygen species signalling in mitochondria and the endomembrane system

In this study, we investigated the cellular and molecular mechanisms that regulate salt acclimation. The main objective was to obtain new insights into the molecular mechanisms that control salt acclimation. Therefore, we carried out a multidisciplinary study using proteomic, transcriptomic, subcellular and physiological techniques. We obtained a Nicotiana tabacum BY-2 cell line acclimated to be grown at 258 mM NaCl as a model for this study. The proteomic and transcriptomic data indicate that the molecular response to stress (chaperones, defence proteins, etc.) is highly induced in these salt-acclimated cells. The subcellular results show that salt induces sodium compartmentalization in the cell vacuoles and seems to be mediated by vesicle trafficking in tobacco salt-acclimated cells. Our results demonstrate that abscisic acid (ABA) and proline metabolism are crucial in the cellular signalling of salt acclimation, probably regulating reactive oxygen species (ROS) production in the mitochondria. ROS may act as a retrograde signal, regulating the cell response. The network of endoplasmic reticulum and Golgi apparatus is highly altered in salt-acclimated cells. The molecular and subcellular analysis suggests that the unfolded protein response is induced in salt-acclimated cells. Finally, we propose that this mechanism may mediate cell death in salt-acclimated cells.

Real-time load-side control of electric power systems

Two trends are emerging from modern electric power systems: the growth of renewable (e.g., solar and wind) generation, and the integration of information technologies and advanced power electronics. The former introduces large, rapid, and random fluctuations in power supply, demand, frequency, and voltage, which become a major challenge for real-time operation of power systems. The latter creates a tremendous number of controllable intelligent endpoints such as smart buildings and appliances, electric vehicles, energy storage devices, and power electronic devices that can sense, compute, communicate, and actuate. Most of these endpoints are distributed on the load side of power systems, in contrast to traditional control resources such as centralized bulk generators. This thesis focuses on controlling power systems in real time, using these load side resources. Specifically, it studies two problems.

(1) Distributed load-side frequency control: We establish a mathematical framework to design distributed frequency control algorithms for flexible electric loads. In this framework, we formulate a category of optimization problems, called optimal load control (OLC), to incorporate the goals of frequency control, such as balancing power supply and demand, restoring frequency to its nominal value, restoring inter-area power flows, etc., in a way that minimizes total disutility for the loads to participate in frequency control by deviating from their nominal power usage. By exploiting distributed algorithms to solve OLC and analyzing convergence of these algorithms, we design distributed load-side controllers and prove stability of closed-loop power systems governed by these controllers. This general framework is adapted and applied to different types of power systems described by different models, or to achieve different levels of control goals under different operation scenarios. We first consider a dynamically coherent power system which can be equivalently modeled with a single synchronous machine. We then extend our framework to a multi-machine power network, where we consider primary and secondary frequency controls, linear and nonlinear power flow models, and the interactions between generator dynamics and load control.

(2) Two-timescale voltage control: The voltage of a power distribution system must be maintained closely around its nominal value in real time, even in the presence of highly volatile power supply or demand. For this purpose, we jointly control two types of reactive power sources: a capacitor operating at a slow timescale, and a power electronic device, such as a smart inverter or a D-STATCOM, operating at a fast timescale. Their control actions are solved from optimal power flow problems at two timescales. Specifically, the slow-timescale problem is a chance-constrained optimization, which minimizes power loss and regulates the voltage at the current time instant while limiting the probability of future voltage violations due to stochastic changes in power supply or demand. This control framework forms the basis of an optimal sizing problem, which determines the installation capacities of the control devices by minimizing the sum of power loss and capital cost. We develop computationally efficient heuristics to solve the optimal sizing problem and implement real-time control. Numerical experiments show that the proposed sizing and control schemes significantly improve the reliability of voltage control with a moderate increase in cost.

A second order control-volume finite-element least-squares strategy for simulating diffusion in strongly anisotropic media

An unstructured mesh �nite volume discretisation method for simulating di�usion in anisotropic media in two-dimensional space is discussed. This technique is considered as an extension of the fully implicit hybrid control-volume �nite-element method and it retains the local continuity of the ux at the control volume faces. A least squares function recon- struction technique together with a new ux decomposition strategy is used to obtain an accurate ux approximation at the control volume face, ensuring that the overall accuracy of the spatial discretisation maintains second order. This paper highlights that the new technique coincides with the traditional shape function technique when the correction term is neglected and that it signi�cantly increases the accuracy of the previous linear scheme on coarse meshes when applied to media that exhibit very strong to extreme anisotropy ratios. It is concluded that the method can be used on both regular and irregular meshes, and appears independent of the mesh quality.