Endocannabinoids, FOXO and the metabolic syndrome: redox, function and tipping point--the view from two systems

The endocannabinoid system (ECS) was only 'discovered' in the 1990s. Since then, many new ligands have been identified, as well as many new intracellular targets--ranging from the PPARs, to mitochondria, to lipid rafts. It was thought that blocking the CB-1 receptor might reverse obesity and the metabolic syndrome. This was based on the idea that the ECS was dysfunctional in these conditions. This has met with limited success. The reason may be that the ECS is a homeostatic system, which integrates energy seeking and storage behaviour with resistance to oxidative stress. It could be viewed as having thrifty actions. Thriftiness is an innate property of life, which is programmed to a set point by both environment and genetics, resulting in an epigenotype perfectly adapted to its environment. This thrifty set point can be modulated by hormetic stimuli, such as exercise, cold and plant micronutrients. We have proposed that the physiological and protective insulin resistance that underlies thriftiness encapsulates something called 'redox thriftiness', whereby insulin resistance is determined by the ability to resist oxidative stress. Modern man has removed most hormetic stimuli and replaced them with a calorific sedentary lifestyle, leading to increased risk of metabolic inflexibility. We suggest that there is a tipping point where lipotoxicity in adipose and hepatic cells induces mild inflammation, which switches thrifty insulin resistance to inflammation-driven insulin resistance. To understand this, we propose that the metabolic syndrome could be seen from the viewpoint of the ECS, the mitochondrion and the FOXO group of transcription factors. FOXO has many thrifty actions, including increasing insulin resistance and appetite, suppressing oxidative stress and shifting the organism towards using fatty acids. In concert with factors such as PGC-1, they also modify mitochondrial function and biogenesis. Hence, the ECS and FOXO may interact at many points; one of which may be via intracellular redox signalling. As cannabinoids have been shown to modulate reactive oxygen species production, it is possible that they can upregulate anti-oxidant defences. This suggests they may have an 'endohormetic' signalling function. The tipping point into the metabolic syndrome may be the result of a chronic lack of hormetic stimuli (in particular, physical activity), and thus, stimulus for PGC-1, with a resultant reduction in mitochondrial function and a reduced lipid capacitance. This, in the context of a positive calorie environment, will result in increased visceral adipose tissue volume, abnormal ectopic fat content and systemic inflammation. This would worsen the inflammatory-driven pathological insulin resistance and inability to deal with lipids. The resultant oxidative stress may therefore drive a compensatory anti-oxidative response epitomised by the ECS and FOXO. Thus, although blocking the ECS (e.g. via rimonabant) may induce temporary weight loss, it may compromise long-term stress resistance. Clues about how to modulate the system more safely are emerging from observations that some polyphenols, such as resveratrol and possibly, some phytocannabinoids, can modulate mitochondrial function and might improve resistance to a modern lifestyle.

Anticipatory engineering: anticipation in sensory-motor systems of human

In visual tracking experiments, distributions of the relative phase be-tween target and tracer showed positive relative phase indicating that the tracer precedes the target position. We found a mode transition from the reactive to anticipatory mode. The proposed integrated model provides a framework to understand the antici-patory behaviour of human, focusing on the integration of visual and soma-tosensory information. The time delays in visual processing and somatosensory feedback are explicitly treated in the simultaneous differential equations. The anticipatory behaviour observed in the visual tracking experiments can be ex-plained by the feedforward term of target velocity, internal dynamics, and time delay in somatosensory feedback.

Quenching of Photoactivity in Phthalocyanine Copper(II)-Titanate Nanotube Hybrid Systems

Titanate nanotubes (TiNTs) were obtained by hydrothermal treatment of anatase powder in aqueous NaOH solution and then modified with 2,9,16,23-tertracarboxyl phthalocyanine copper(H) (CuPc). This hybrid organic inorganic nanoscopic system was characterized by X-ray diffraction, microscopy, and spectroscopy. Transmission electron microscopy (TEM) images of pure and modified TiNTs revealed multiwall structures with an average outer diameter of 9 nm and a length of several hundred nanometers. The tubular morphology of the TiNTs was covered with CuPc-film. The amount of CuPc adsorbed onto the TiNTs was quantified by electron paramagnetic resonance (EPR). Using the same technique and spin-trapping methodology, the photogeneration of reactive oxygen species (ROS) from the TiNTs was systematically investigated. A drastic quenching of photoactivity was observed in the CuPc/TiNT hybrid system. Electron transfer from excited CuPc states to the TiNT conduction band followed by electron recombination may be the cause of this quenching.

Optimal reactive power flow via the modified barrier Lagrangian function approach

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Parameterized fast decoupled power flow methods for obtaining the maximum loading point of power systems. Part I. Mathematical modeling

The conventional Newton and fast decoupled power flow (FDPF) methods have been considered inadequate to obtain the maximum loading point of power systems due to ill-conditioning problems at and near this critical point. It is well known that the PV and Q-theta decoupling assumptions of the fast decoupled power flow formulation no longer hold in the vicinity of the critical point. Moreover, the Jacobian matrix of the Newton method becomes singular at this point. However, the maximum loading point can be efficiently computed through parameterization techniques of continuation methods. In this paper it is shown that by using either theta or V as a parameter, the new fast decoupled power flow versions (XB and BX) become adequate for the computation of the maximum loading point only with a few small modifications. The possible use of reactive power injection in a selected PV bus (Q(PV)) as continuation parameter (mu) for the computation of the maximum loading point is also shown. A trivial secant predictor, the modified zero-order polynomial which uses the current solution and a fixed increment in the parameter (V, theta, or mu) as an estimate for the next solution, is used in predictor step. These new versions are compared to each other with the purpose of pointing out their features, as well as the influence of reactive power and transformer tap limits. The results obtained with the new approach for the IEEE test systems (14, 30, 57 and 118 buses) are presented and discussed in the companion paper. The results show that the characteristics of the conventional method are enhanced and the region of convergence around the singular solution is enlarged. In addition, it is shown that parameters can be switched during the tracing process in order to efficiently determine all the PV curve points with few iterations. (C) 2003 Elsevier B.V. All rights reserved.

Load compensation in four-wire electrical power systems

This work describes a methodology for power factor control and correction of the unbalanced currents in four-wire electric circuits. The methodology is based on the insertion of two compensation networks, one wye-grounded neutral and another in delta, in parallel to the load. The mathematical development has been proposed in previous work [3]. In this paper, however, the methodology was adapted to accept different power factors for the system to be compensated. on the other hand, the determination of the compensation susceptances is based on the instantaneous values of the load currents. The results are obtained using the MatLab - Simulink environment.

Parameterized fast decoupled power flow methods for obtaining the maximum loading point of power systems. Part II. Performance evaluation

The parameterized fast decoupled power flow (PFDPF), versions XB and BX, using either theta or V as a parameter have been proposed by the authors in Part I of this paper. The use of reactive power injection of a selected PVbus (Q(PV)) as the continuation parameter for the computation of the maximum loading point (MLP) was also investigated. In this paper, the proposed versions obtained only with small modifications of the conventional one are used for the computation of the MLP of IEEE test systems (14, 30, 57 and 118 buses). These new versions are compared to each other with the purpose of pointing out their features, as well as the influence of reactive power and transformer tap limits. The results obtained with the new approaches are presented and discussed. The results show that the characteristics of the conventional FDPF method are enhanced and the region of convergence around the singular solution is enlarged. In addition, it is shown that these versions can be switched during the tracing process in order to efficiently determine all the PV curve points with few iterations. A trivial secant predictor, the modified zero-order polynomial, which uses the current solution and a fixed increment in the parameter (V, theta, or mu) as an estimate for the next solution, is used for the predictor step. (C) 2003 Elsevier B.V. All rights reserved.

Reactive power dispatch and planning using a non-linear branch-and-bound algorithm

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Reactive Control for Transmission Overload Relief Based on Sensitivity Analysis and Cooperative Game Theory

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Primary power distribution systems planning taking into account reliability, operation and expansion costs

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Primal-dual logarithmic barrier and augmented Lagrangian function to the loss minimization in power systems

This article presents a new approach to minimize the losses in electrical power systems. This approach considers the application of the primal-dual logarithmic barrier method to voltage magnitude and tap-changing transformer variables, and the other inequality constraints are treated by augmented Lagrangian method. The Lagrangian function aggregates all the constraints. The first-order necessary conditions are reached by Newton's method, and by updating the dual variables and penalty factors. Test results are presented to show the good performance of this approach.

A heuristic method for reactive power planning

An approach for solving reactive power planning problems is presented, which is based on binary search techniques and the use of a special heuristic to obtain a discrete solution. Two versions were developed, one to run on conventional (sequential) computers and the other to run on a distributed memory (hypercube) machine. This latter parallel processing version employs an asynchronous programming model. Once the set of candidate buses has been defined, the program gives the location and size of the reactive sources needed(if any) in keeping with operating and security constraints.

Incorporating voltage/reactive representation to short-term generation scheduling models

This paper proposes a methodology to incorporate voltage/reactive representation to Short Term Generation Scheduling (STGS) models, which is based on active/reactive decoupling characteristics of power systems. In such approach STGS is decoupled in both Active (AGS) and Reactive (RGS) Generation Scheduling models. AGS model establishes an initial active generation scheduling through a traditional dispatch model. The scheduling proposed by AGS model is evaluated from the voltage/reactive points of view, through the proposed RGS model. RGS is formulated as a sequence of T nonlinear OPF problems, solved separately but taking into account load tracking between consecutive time intervals. This approach considerably reduces computational effort to perform the reactive analysis of the RGS problem as a whole. When necessary, RGS model is capable to propose active generation redispatches, such that critical reactive problems (in which all reactive variables have been insufficient to control the reactive problems) can be overcome. The formulation and solution methodology proposed are evaluated in the IEEE30 system in two case studies. These studies show that the methodology is robust enough to incorporate reactive aspects to STGS problem.

A decentralized approach for optimal reactive power dispatch using a Lagrangian decomposition method

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Optimized Allocation of Control and Protective Devices in Electric Distribution Systems

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)