Potent Cardioprotective Effect of the 4-Anilinoquinazoline Derivative PD153035: Involvement of Mitochondrial K(ATP) Channel Activation

Background: The aim of the present study was to evaluate the protective effects of the 4-anilinoquinazoline derivative PD153035 on cardiac ischemia/reperfusion and mitochondrial function. Methodology/Principal Findings: Perfused rat hearts and cardiac HL-1 cells were used to determine cardioprotective effects of PD153035. Isolated rat heart mitochondria were studied to uncover mechanisms of cardioprotection. Nanomolar doses of PD153035 strongly protect against heart and cardiomyocyte damage induced by ischemia/reperfusion and cyanide/aglycemia. PD153035 did not alter oxidative phosphorylation, nor directly prevent Ca(2+) induced mitochondrial membrane permeability transition. The protective effect of PD153035 on HL-1 cells was also independent of AKT phosphorylation state. Interestingly, PD153035 activated K(+) transport in isolated mitochondria, in a manner prevented by ATP and 5-hydroxydecanoate, inhibitors of mitochondrial ATP-sensitive K(+) channels (mitoK(ATP)). 5-Hydroxydecanoate also inhibited the cardioprotective effect of PD153035 in cardiac HL-1 cells, demonstrating that this protection is dependent on mitoK(ATP) activation. Conclusions/Significance: We conclude that PD153035 is a potent cardioprotective compound and acts in a mechanism involving mitoK(ATP) activation.

Schistosoma mansoni Tegument Protein Sm29 Is Able to Induce a Th1-Type of Immune Response and Protection against Parasite Infection

Background: Schistosomiasis continues to be a significant public health problem. This disease affects 200 million people worldwide and almost 800 million people are at risk of acquiring the infection. Although vaccine development against this disease has experienced more failures than successes, encouraging results have recently been obtained using membrane-spanning protein antigens from the tegument of Schistosoma mansoni. Our group recently identified Sm29, another antigen that is present at the adult worm tegument surface. In this study, we investigated murine cellular immune responses to recombinant (r) Sm29 and tested this protein as a vaccine candidate. Methods and Findings: We first show that Sm29 is located on the surface of adult worms and lung-stage schistosomula through confocal microscopy. Next, immunization of mice with rSm29 engendered 51%, 60% and 50% reduction in adult worm burdens, in intestinal eggs and in liver granuloma counts, respectively (p<0.05). Protective immunity in mice was associated with high titers of specific anti-Sm29 IgG1 and IgG2a and elevated production of IFN-gamma, TNF-alpha and IL-12, a typical Th1 response. Gene expression analysis of worms recovered from rSm29 vaccinated mice relative to worms from control mice revealed a significant (q<0.01) down-regulation of 495 genes and up-regulation of only 22 genes. Among down-regulated genes, many of them encode surface antigens and proteins associated with immune signals, suggesting that under immune attack schistosomes reduce the expression of critical surface proteins. Conclusion: This study demonstrates that Sm29 surface protein is a new vaccine candidate against schistosomiasis and suggests that Sm29 vaccination associated with other protective critical surface antigens is the next logical strategy for improving protection.

Shelf and estuarine transport mechanisms affecting the supply of competent larvae in a suite of brachyuran crabs with different life histories

Supply of competent larvae to the benthic habitat is a major determinant of population dynamics in coastal and estuarine invertebrates with an indirect life cycle. Larval delivery may depend not only on physical transport mechanisms, but also on larval behavior and physiological progress to the competent stage. Yet, the combined analysis of such factors has seldom been attempted. We used time-series analyses to examine tide- and wind-driven mechanisms responsible for the supply of crab megalopae to an estuarine river under a major marine influence in SW Spain, and monitored the vertical distribution of upstream moving megalopae, their net flux and competent state. The species Panopeus africanus (estuarine), Brachynotus sexdentatus (euryhaline) and Nepinnotheres pinnotheres (coastal) comprised 80% of the whole sample, and responded in a similar way to tide and wind forcing. Tidal range was positively correlated to supply, with maxima 0 to 1 d after spring tides, suggesting selective tidal stream transport. Despite being extensively subjected to upwelling, downwind drift under the effect of westerlies, not Ekman transport, explained residual supply variation at our sampling area. Once in the estuary, net flux and competence state matched the expected trends. Net upstream flux increased from B. sexdentatus to P. africanus, favoring transport to a sheltered coastal habitat (N. pinnotheres), or to the upper estuary (P. africanus). Competence state was highest in N. pinnotheres, intermediate in B. sexdentatus and lowest in P. africanus, as expected if larvae respond to cues from adequate benthic habitat. P. africanus megalopae were found close to the bottom, not above, rendering slower upstream transport than anticipated.

Chronic Stress Is Associated with High Cortisol Levels and Emotional Coping Mechanisms in Amnestic Mild Cognitive Impairment

Background/Aims: To investigate the association between cortisol levels, chronic stress and coping in subjects with amnestic-type mild cognitive impairment (aMCI). Methods: Cortisol levels were measured using morning saliva samples from 33 individuals with aMCI and from 41 healthy elderly. Chronic stress was evaluated with the Stress Symptoms List (SSL), whereas coping strategies were assessed using the Jalowiec Coping Scale. Results: aMCI subjects with high SSL scores presented higher cortisol levels (p = 0.045). Furthermore, aMCI subjects who employed emotion-focused coping had higher SSL scores (p = 0.023). Conclusion: The association between increased cortisol secretion, chronic stress and coping strategies may be modulated by the presence or absence of cognitive impairment, where memory deficit awareness constitutes an additional potential factor involved in high stress severity. Copyright (C) 2009 S. Karger AG, Basel

Intracellular mechanisms of specific beta-adrenoceptor antagonists involved in improved cardiac function and survival in a genetic model of heart failure

beta-blockers, as class, improve cardiac function and survival in heart failure (HF). However, the molecular mechanisms underlying these beneficial effects remain elusive. In the present study, metoprolol and carvedilol were used in doses that display comparable heart rate reduction to assess their beneficial effects in a genetic model of sympathetic hyperactivity-induced HF (alpha(2A)/alpha(2C)-ARKO mice). Five month-old HF mice were randomly assigned to receive either saline, metoprolol or carvedilol for 8 weeks and age-matched wild-type mice (WT) were used as controls. HF mice displayed baseline tachycardia, systolic dysfunction evaluated by echocardiography, 50% mortality rate, increased cardiac myocyte width (50%) and ventricular fibrosis (3-fold) compared with WT. All these responses were significantly improved by both treatments. Cardiomyocytes from HF mice showed reduced peak [Ca(2+)](i) transient (13%) using confocal microscopy imaging. Interestingly, while metoprolol improved [Ca(2+)](i) transient, carvedilol had no effect on peak [Ca(2+)](i) transient but also increased [Ca(2+)] transient decay dynamics. We then examined the influence of carvedilol in cardiac oxidative stress as an alternative target to explain its beneficial effects. Indeed, HF mice showed 10-fold decrease in cardiac reduced/oxidized glutathione ratio compared with WT, which was significantly improved only by carvedilol treatment. Taken together, we provide direct evidence that the beneficial effects of metoprolol were mainly associated with improved cardiac Ca(2+) transients and the net balance of cardiac Ca(2+) handling proteins while carvedilol preferentially improved cardiac redox state. (C) 2008 Elsevier Inc. All rights reserved.

Test of a Modular Fault Current Limiter for 220 V Line Using YBCO Coated Conductor Tapes With Shunt Protection

A modular superconducting fault current limiter (SFCL) consisting of 16 elements was constructed and tested in a 220 V line for a fault current between 1 kA to 7.4 kA. The elements are made up of second generation (2G) YBCO-coated conductor tapes with stainless steel reinforcement. For each element four tapes were electrically connected in parallel with effective length of 0.4 m per element, totaling 16 elements connected in series. The evaluation of SFCL performance was carried out under DC and AC tests. The DC test was performed through pulsed current tests and its recovery characteristics under load current were analysed by changing the shunt resistor value. The AC test performed using a 3 MVA/220 V/60 Hz transformer has shown the current limiting ratio achieved a factor higher than 10 during fault of up to five cycles without conductor degradation. The measurement of the voltage for each element during the AC test showed that in this modular SFCL the quench is homogeneous and the transition occurs similarly in all the elements.

Ethanol-induced vasoconstriction is mediated via redox-sensitive cyclo-oxygenase-dependent mechanisms

The present study investigated the role of ROS (reactive oxygen species) and COX (cyclooxygenase) in ethanol-induced contraction and elevation of [Ca(2+)](i) (intracellular [Ca(2+)]). Vascular reactivity experiments, using standard muscle bath procedures, showed that ethanol (1-800 mmol/l) induced contraction in endothelium-intact (EC(50): 306 +/- 34 mmol/l) and endothelium-denuded (EC(50): 180 +/- 40 mmol/l) rat aortic rings. Endothelial removal enhanced ethanol-induced contraction. Preincubation of intact rings with L-NAME [N(G)-nitro-L-arginine methyl ester; non-selective NOS (NO synthase) inhibitor, 100 mu mol/l], 7-nitroindazole [selective nNOS (neuronal NOS) inhibitor, 100 mu mol/l], oxyhaemoglobin (NO scavenger, 10 mu mol/l) and ODQ (selective inhibitor of guanylate cyclase enzyme, 1 mu mol/l) increased ethanol-induced contraction. Tiron [O(2)(-) (superoxide anion) scavenger, 1 mmol/l] and catalase (H(2)O(2) scavenger, 300 units/ml) reduced ethanol-induced contraction to a similar extent in both endothelium-intact and denuded rings. Similarly, indomethacin (non-selective COX inhibitor, 10 mu mol/l), SC560 (selective COX- I inhibitor, 1 mu mol/l), AH6809 [PGF(2 alpha) (prostaglandin F(2 alpha))] receptor antagonist, 10 mu mol/l] or SQ29584 [PGH(2)(prostaglandin H(2))/TXA(2) (thromboxane A(2)) receptor antagonist, 3 mu mol/l] inhibited ethanol-induced contraction in aortic rings with and without intact endothelium. In cultured aortic VSMCs (vascular smooth muscle cells), ethanol stimulated generation of O(2)(-) and H(2)O(2). Ethanol induced a transient increase in [Ca(2+)](i), which was significantly inhibited in VSMCs pre-exposed to tiron or indomethacin. Our data suggest that ethanol induces vasoconstriction via redox-sensitive and COX-dependent pathways, probably through direct effects on ROS production and Ca(2+) signalling. These findings identify putative molecular mechanisms whereby ethanol, at high concentrations, influences vascular reactivity. Whether similar phenomena occur in vivo at lower concentrations of ethanol remains unclear.

Power Transformer Differential Protection Based on Clarke`s Transform and Fuzzy Systems

The power transformer is a piece of electrical equipment that needs continuous monitoring and fast protection since it is very expensive and an essential element for a power system to perform effectively. The most common protection technique used is the percentage differential logic, which provides discrimination between an internal fault and different operating conditions. Unfortunately, there are some operating conditions of power transformers that can affect the protection behavior and the power system stability. This paper proposes the development of a new algorithm to improve the differential protection performance by using fuzzy logic and Clarke`s transform. An electrical power system was modeled using Alternative Transients Program (ATP) software to obtain the operational conditions and fault situations needed to test the algorithm developed. The results were compared to a commercial relay for validation, showing the advantages of the new method.

Power imbalance application region method for distributed synchronous generator anti-islanding protection design and evaluation

This paper presents a novel graphical approach to adjust and evaluate frequency-based relays employed in anti-islanding protection schemes of distributed synchronous generators, in order to meet the anti-islanding and abnormal frequency variation requirements, simultaneously. The proposed method defines a region in the power mismatch space, inside which the relay non-detection zone should be located, if the above-mentioned requirements must be met. Such region is called power imbalance application region. Results show that this method can help protection engineers to adjust frequency-based relays to improve the anti-islanding capability and to minimize false operation occurrences, keeping the abnormal frequency variation utility requirements satisfied. Moreover, the proposed method can be employed to coordinate different types of frequency-based relays, aiming at improving overall performance of the distributed generator frequency protection scheme. (C) 2011 Elsevier B.V. All rights reserved.

Failure Mechanisms in Sand over a Deep Active Trapdoor

An experimental testing program was undertaken to investigate failure mechanisms induced by the active movement of a deep rectangular trapdoor underlying a granular soil. Reduced-scale models were tested under normal gravity as well as under an increased gravitational field using a centrifuge facility. Some models were used to evaluate the performance of both flexible and rigid pipes undergoing a localized loss of support. Failure mechanisms in the longitudinal direction of the models were characterized by a single, well-defined failure surface that developed within the limits of the trapdoor. However, failure mechanisms in the transverse direction of the models were characterized by multiple failure surfaces extending outside the limits of the trapdoor. Significant dilation of the soil located immediately above the trapdoor was identified in the failure of the models. The pattern of the failure mechanisms was found to be affected by the stress level and backfill density. Higher stress levels were found to lead to well-developed failure zones. The influence of backfill density was found to be more relevant in models involving flexible pipes. Pipes embedded within loose backfill were severely damaged after loss of support, while pipes embedded in dense backfill experienced negligible deformations. These results indicate that damage to pipelines caused by ground loss of support can be significantly minimized by controlling the compaction of the fill.

Efficacy of surface hydrophobic agents in reducing water and chloride ion penetration in concrete

Hydrophobic agents are surface protection materials capable of increasing the angle of contact between the water and the concrete surface. For this reason, hydrophobic agents reduce water (in liquid form) penetration in concrete. Therefore, many European construction regulating agencies recommend this treatment in their maintenance policy. Nonetheless, there continues to be a gap in the understanding about which transport mechanisms of the concrete are modified by the hidrophobic agents. The aim of this study was to fill this gap in regards to reinforced concrete structures inserted in a marine environment. To this end, certain tests were used: Two involving permeability mechanism, one determining capillary absorption, and the last, a migration test used to estimate the chloride diffusion coefficient in saturated condition. Results indicated the efficacy of the hydrophobic agents in cases where capillary suction is the mechanism of water penetration (reduced by 2.12 and 7.0 times, depending of the product). However, when the transport mechanism is permeability this product is not advisable. Moreover, it was demonstrated that the chloride diffusion coefficient (in saturated condition) is reduced by the hydrophobic agents, however, the magnitude of this reduction is minor (reduced by 11% and 17%, depending on the product).

A survey on key management mechanisms for distributed Wireless Sensor Networks

Wireless Sensor Networks (WSNs) have a vast field of applications, including deployment in hostile environments. Thus, the adoption of security mechanisms is fundamental. However, the extremely constrained nature of sensors and the potentially dynamic behavior of WSNs hinder the use of key management mechanisms commonly applied in modern networks. For this reason, many lightweight key management solutions have been proposed to overcome these constraints. In this paper, we review the state of the art of these solutions and evaluate them based on metrics adequate for WSNs. We focus on pre-distribution schemes well-adapted for homogeneous networks (since this is a more general network organization), thus identifying generic features that can improve some of these metrics. We also discuss some challenges in the area and future research directions. (C) 2010 Elsevier B.V. All rights reserved.

Transmission lines distance protection using artificial neural networks

This work presents the development and implementation of an artificial neural network based algorithm for transmission lines distance protection. This algorithm was developed to be used in any transmission line regardless of its configuration or voltage level. The described ANN-based algorithm does not need any topology adaptation or ANN parameters adjustment when applied to different electrical systems. This feature makes this solution unique since all ANN-based solutions presented until now were developed for particular transmission lines, which means that those solutions cannot be implemented in commercial relays. (c) 2011 Elsevier Ltd. All rights reserved.

Wear mechanisms and microstructure of pulsed plasma nitrided AISI H13 tool steel

AISI H13 tool steel discs were pulsed plasma minded during different times at a constant temperature of 400 degrees C Wear tests were performed in order to study the acting wear mechanisms The samples were characterized by X-ray diffraction, scanning electron microscopy and hardness measurements The results showed that longer nitriding times reduce the wear volumes. The friction coefficient was 0.20 +/- 0 05 for all tested conditions and depends strongly on the presence of debris After wear tests, the wear tracks were characterized by optical and scanning electron microscopy and the wear mechanisms were observed to change from low cycle fatigue or plastic shakedown to long cycle fatigue These mechanisms were correlated to the microstructure and hardness of the nitrided layer (C) 2010 Elsevier B V All rights reserved

Design of compliant mechanisms considering thermal effect compensation and topology optimization

Compliant mechanisms can achieve a specified motion as a mechanism without relying on the use of joints and pins. They have broad application in precision mechanical devices and Micro-Electro Mechanical Systems (MEMS) but may lose accuracy and produce undesirable displacements when subjected to temperature changes. These undesirable effects can be reduced by using sensors in combination with control techniques and/or by applying special design techniques to reduce such undesirable effects at the design stage, a process generally termed ""design for precision"". This paper describes a design for precision method based on a topology optimization method (TOM) for compliant mechanisms that includes thermal compensation features. The optimization problem emphasizes actuator accuracy and it is formulated to yield optimal compliant mechanism configurations that maximize the desired output displacement when a force is applied, while minimizing undesirable thermal effects. To demonstrate the effectiveness of the method, two-dimensional compliant mechanisms are designed considering thermal compensation, and their performance is compared with compliant mechanisms designs that do not consider thermal compensation. (C) 2010 Elsevier B.V. All rights reserved.