Ivabradine Induces Cardiac Protection against Myocardial Infarction by Preventing Cyclophilin-A Secretion in Pigs under Coronary Ischemia/Reperfusion

In response to cardiac ischemia/reperfusion, proteolysis mediated by extracellular matrix metalloproteinase inducer (EMMPRIN) and its secreted ligand cyclophilin-A (CyPA) significantly contributes to cardiac injury and necrosis. Here, we aimed to investigate if, in addition to the effect on the funny current (I(f)), Ivabradine may also play a role against cardiac necrosis by reducing EMMPRIN/CyPA-mediated cardiac inflammation. In a porcine model of cardiac ischemia/reperfusion (IR), we found that administration of 0.3 mg/kg Ivabradine significantly improved cardiac function and reduced cardiac necrosis by day 7 after IR, detecting a significant increase in cardiac CyPA in the necrotic compared to the risk areas, which was inversely correlated with the levels of circulating CyPA detected in plasma samples from the same subjects. In testing whether Ivabradine may regulate the levels of CyPA, no changes in tissue CyPA were found in healthy pigs treated with 0.3 mg/kg Ivabradine, but interestingly, when analyzing the complex EMMPRIN/CyPA, rather high glycosylated EMMPRIN, which is required for EMMPRIN-mediated matrix metalloproteinase (MMP) activation and increased CyPA bonding to low-glycosylated forms of EMMPRIN were detected by day 7 after IR in pigs treated with Ivabradine. To study the mechanism by which Ivabradine may prevent secretion of CyPA, we first found that Ivabradine was time-dependent in inhibiting co-localization of CyPA with the granule exocytosis marker vesicle-associated membrane protein 1 (VAMP1). However, Ivabradine had no effect on mRNA expression nor in the proteasome and lysosome degradation of CyPA. In conclusion, our results point toward CyPA, its ligand EMMPRIN, and the complex CyPA/EMMPRIN as important targets of Ivabradine in cardiac protection against IR.     

Ethylene and Nitric Oxide Involvement in the Regulation of Fe and P Deficiency Responses in Dicotyledonous Plants

Iron (Fe) and phosphorus (P) are two essential elements for plant growth. Both elements are abundant in soils but with poor availability for plants, which favor their acquisition by developing morphological and physiological responses in their roots. Although the regulation of the genes related to these responses is not totally known, ethylene (ET) and nitric oxide (NO) have been involved in the activation of both Fe-related and P-related genes. The common involvement of ET and NO suggests that they must act in conjunction with other specific signals, more closely related to each deficiency. Among the specific signals involved in the regulation of Fe- or P-related genes have been proposed Fe-peptides (or Fe ion itself) and microRNAs, like miR399 (P), moving through the phloem. These Fe- or P-related phloem signals could interact with ET/NO and confer specificity to the responses to each deficiency, avoiding the induction of the specific responses when ET/NO increase due to other nutrient deficiencies or stresses. Besides the specificity conferred by these signals, ET itself could confer specificity to the responses to Fe- or P-deficiency by acting through different signaling pathways in each case. Given the above considerations, there are preliminary results suggesting that ET could regulate different nutrient responses by acting both in conjunction with other signals and through different signaling pathways. Because of the close relationship among these two elements, a better knowledge of the physiological and molecular basis of their interaction is necessary to improve their nutrition and to avoid the problems associated with their misuse. As examples of this interaction, it is known that Fe chlorosis can be induced, under certain circumstances, by a P over- fertilization. On the other hand, Fe oxides can have a role in the immobilization of P in soils. Qualitative and quantitative assessment of the dynamic of known Fe- and P-related genes expression, selected ad hoc and involved in each of these deficiencies, would allow us to get a profound knowledge of the processes that regulate the responses to both deficiencies. The better knowledge of the regulation by ET of the responses to these deficiencies is necessary to properly understand the interactions between Fe and P. This will allow the obtention of more efficient varieties in the absorption of P and Fe, and the use of more rational management techniques for P and Fe fertilization. This will contribute to minimize the environmental impacts caused by the use of P and Fe fertilizers (Fe chelates) in agriculture and to adjust the costs for farmers, due to the high prices and/or scarcity of Fe and P fertilizers. This review aims to summarize the latest advances in the knowledge about Fe and P deficiency responses, analyzing the similarities and differences among them and considering the interactions among their main regulators, including some hormones (ethylene) and signaling substances (NO and GSNO) as well as other P- and Fe-related signals.     

Observability of linear systems with commensurate delays and unknown inputs

This paper investigates the observability analysis for linear time systems whose outputs are affected by unknown inputs. Three different definitions of observability are proposed. By introducing the Smith form and comparing the invariant factors, a sufficient condition is deduced for each proposed observability definition. Three examples are given for the purpose of highlighting the effectiveness of the proposed approach.     

Application of the classical levels of intelligence to structuring the control system in an automated distribution centre

Traditional management and control models can benefit from added levels of intelligence to increase their capability to adapt to the continuous changes in global markets. After reviewing the classical definition of intelligence and its levels, this paper provides a new approach to help increase the responsiveness of management and control to changes and disturbances in the manufacturing supply chain. The ancient concept of the “Tertium Quid” has inspired a three-level community of agents (MAS-TRIO) that is proposed to improve the coordination of all actors involved. The proposed model combines Multi-Agent Systems (MAS) with Radio-Frequency Identification (RFID) to make possible a certain level of Autonomous Intelligence in the decision-taking process. This paper analyses how these levels of intelligence can be applied to management and control, and the performance of the proposed model has been tested at low and mid-levels on an experimental platform representing the facilities of a distribution centre controlled by a network of programmable logic controllers (PLCs).     

A stochastic controller for a scalar linear system with additive Cauchy noise

A stochastic control scheme is developed for scalar, discrete-time, and linear-dynamic systems driven by Cauchy distributed process and measurement noises. When addressing the optimal control problem for such systems, the standard quadratic cost criteria cannot be used. In this study we introduce a new objective function that is functionally similar to the Cauchy probability density function. The performance index, defined as the expectation of this objective function with respect to the Cauchy densities, exists. The dynamic programming solution to the fixed and finite horizon optimal control problem that uses this performance index appears to be intractable. Therefore, a moving horizon optimal model predictive control problem is implemented, for which the conditional expected value of the objective function and its gradients can be computed in closed   form and without assumptions such as certainty equivalence. Numerical results are shown for this m$m$-step model predictive optimal controller and compared to a similar, Linear-Exponential-Gaussian model predictive controller. An essential difference between the Cauchy and Gaussian controllers when applied to a system with Cauchy noises is that, while the Gaussian controller is linear and reacts strongly to all noise pulses, the Cauchy controller can differentiate between measurement and process noise pulses by ignoring the former while responding to the latter. This property of the Cauchy controller occurs when an impulsive measurement noise is more likely than an impulsive process noise. The Cauchy and Gaussian controllers react similarly when applied to a system with Gaussian noises, demonstrating the robustness of the proposed control scheme.     

Event-driven,pattern-based methodology for cost-effective development of standardized personal health devices

Experiences applying standards in personal health devices (PHDs) show an inherent trade-off between interoperability and costs (in terms of processing load and development time). Therefore, reducing hardware and software costs as well as time-to-market is crucial for standards adoption. The ISO/IEEE11073 PHD family of standards (also referred to as X73PHD) provides interoperable communication between PHDs and aggregators. Nevertheless, the responsibility of achieving inexpensive implementations of X73PHD in limited resource microcontrollers falls directly on the developer. Hence, the authors previously presented a methodology based on patterns to implement X73-compliant PHDs into devices with low-voltage low-power constraints. That version was based on multitasking, which required additional features and resources. This paper therefore presents an event-driven evolution of the patterns-based methodology for cost-effective development of standardized PHDs. The results of comparing between the two versions showed that the mean values of decrease in memory consumption and cycles of latency are 11.59% and 45.95%, respectively. In addition, several enhancements in terms of cost-effectiveness and development time can be derived from the new version of the methodology. Therefore, the new approach could help in producing cost-effective X73-compliant PHDs, which in turn could foster the adoption of standards.     

Low-cost sensor to detect overtaking based on optical flow

The automotive industry invests substantial amounts of money in driver-security and driver-assistance systems. We propose an overtaking detection system based on visual motion cues that combines feature extraction, optical flow, solid-objects segmentation and geometry filtering, working with a low-cost compact architecture based on one focal plane and an on-chip embedded processor. The processing is divided into two stages: firstly analog processing on the focal plane processor dedicated to image conditioning and relevant image-structure selection, and secondly, vehicle tracking and warning-signal generation by optical flow, using a simple digital microcontroller. Our model can detect an approaching vehicle (multiple-lane overtaking scenarios) and warn the driver about the risk of changing lanes. Thanks to the use of tightly coupled analog and digital processors, the system is able to perform this complex task in real time with very constrained computing resources. The proposed method has been validated with a sequence of more than 15,000 frames (90 overtaking maneuvers) and is effective under different traffic situations, as well as weather and illumination conditions.     

The effectiveness of the combined use of VIX and Support Vector Machines on the prediction of S&P 500

The aim of this research is to analyse the effectiveness of the Chicago Board Options Exchange Market Volatility Index (VIX) when used with Support Vector Machines (SVMs) in order to forecast the weekly change in the S&P 500 index. The data provided cover the period between 3 January 2000 and 30 December 2011. A trading simulation is implemented so that statistical efficiency is complemented by measures of economic performance. The inputs retained are traditional technical trading rules commonly used in the analysis of equity markets such as Relative Strength Index, Moving Average Convergence Divergence, VIX and the daily return of the S&P 500. The SVM identifies the best situations in which to buy or sell in the market. The two outputs of the SVM are the movement of the market and the degree of set membership. The obtained results show that SVM using VIX produce better results than the Buy and Hold strategy or SVM without VIX. The influence of VIX in the trading system is particularly significant when bearish periods appear. Moreover, the SVM allows the reduction in the Maximum Drawdown and the annualised standard deviation.     

Calmodulin Supports TRPA1 Channel Association with Opioid Receptors and Glutamate NMDA Receptors in the Nervous Tissue

Transient receptor potential ankyrin member 1 (TRPA1) belongs to the family of thermo TRP cation channels that detect harmful temperatures, acids and numerous chemical pollutants. TRPA1 is expressed in nervous tissue, where it participates in the genesis of nociceptive signals in response to noxious stimuli and mediates mechanical hyperalgesia and allodynia associated with different neuropathies. The glutamate N-methyl-d-aspartate receptor (NMDAR), which plays a relevant role in allodynia to mechanical stimuli, is connected via histidine triad nucleotide-binding protein 1 (HINT1) and type 1 sigma receptor (σ1R) to mu-opioid receptors (MORs), which mediate the most potent pain relief. Notably, neuropathic pain causes a reduction in MOR antinociceptive efficacy, which can be reversed by blocking spinal NMDARs and TRPA1 channels. Thus, we studied whether TRPA1 channels form complexes with MORs and NMDARs that may be implicated in the aforementioned nociceptive signals. Our data suggest that TRPA1 channels functionally associate with MORs, delta opioid receptors and NMDARs in the dorsal root ganglia, the spinal cord and brain areas. These associations were altered in response to pharmacological interventions and the induction of inflammatory and also neuropathic pain. The MOR-TRPA1 and NMDAR-TRPA1 associations do not require HINT1 or σ1R but appear to be mediated by calcium-activated calmodulin. Thus, TRPA1 channels may associate with NMDARs to promote ascending acute and chronic pain signals and to control MOR antinociception.     

Al ionic radius influence on molecular dynamics simulations ofγ-Al2O3

Molecular dynamics (MD) simulations of-Al₂O₃, using a pairwise additive interaction potential of Pauling's type with four different radii for aluminum atoms, were analysed in order to determine the influence of the radius on the modification of coordination numbers of A1 relative to the ideal structure, at two different temperatures of 300 and 1500 K. It is found that the best choice is the radius of penta-coordinated aluminum, reproducing structural and vibrational properties of the compound in excellent agreement with experimentally observed properties.