Application of Deadlock Risk Evaluation of Architectural Models

Software architectural evaluation is a key discipline used to identify, at early stages of a real-time system (RTS) development, the problems that may arise during its operation. Typical mechanisms supporting concurrency, such as semaphores, mutexes or monitors, usually lead to concurrency problems in execution time that are difficult to be identified, reproduced and solved. For this reason, it is crucial to understand the root causes of these problems and to provide support to identify and mitigate them at early stages of the system lifecycle. This paper aims to present the results of a research work oriented to the development of the tool called ‘Deadlock Risk Evaluation of Architectural Models’ (DREAM) to assess deadlock risk in architectural models of an RTS. A particular architectural style, Pipelines of Processes in Object-Oriented Architectures–UML (PPOOA) was used to represent platform-independent models of an RTS architecture supported by the PPOOA –Visio tool. We validated the technique presented here by using several case studies related to RTS development and comparing our results with those from other deadlock detection approaches, supported by different tools. Here we present two of these case studies, one related to avionics and the other to planetary exploration robotics. Copyright © 2011 John Wiley & Sons, Ltd

Articular Chondrocyte Network Mediated by Gap Junctions: Role in Metabolic Cartilage Homeostasis

Objective This study investigated whether chondrocytes within the cartilage matrix have the capacity to communicate through intercellular connections mediated by voltage-gated gap junction (GJ) channels. Methods Frozen cartilage samples were used for immunofluorescence and immunohistochemistry assays. Samples were embedded in cacodylate buffer before dehydration for scanning electron microscopy. Co-immunoprecipitation experiments and mass spectrometry (MS) were performed to identify proteins that interact with the C-terminal end of Cx43. GJ communication was studied through in situ electroporation, electrophysiology and dye injection experiments. A transwell layered culture system and MS were used to identify and quantify transferred amino acids. Results Microscopic images revealed the presence of multiple cellular projections connecting chondrocytes within the matrix. These projections were between 5 and 150 μm in length. MS data analysis indicated that the C-terminus of Cx43 interacts with several cytoskeletal proteins implicated in Cx trafficking and GJ assembly, including α-tubulin and β-tubulin, actin, and vinculin. Electrophysiology experiments demonstrated that 12-mer oligonucleotides could be transferred between chondrocytes within 12 min after injection. Glucose was homogeneously distributed within 22 and 35 min. No transfer was detected when glucose was electroporated into A549 cells, which have no GJs. Transwell layered culture systems coupled with MS analysis revealed connexins can mediate the transfer of L-lysine and L-arginine between chondrocytes. Conclusions This study reveals that intercellular connections between chondrocytes contain GJs that play a key role in cell-cell communication and a metabolic function by exchange of nutrients including glucose and essential amino acids. A three-dimensional cellular network mediated through GJs might mediate metabolic and physiological homeostasis to maintain cartilage tissue

Characterization of Spatiooral Cardiac Action Potential Variability at Baseline and under ß-Adrenergic Stimulation by Combined Unscented Kalman Filter and Double Greedy Dimension Reduction

Objective: Elevated spatiooral variability of human ventricular repolarization has been related to increased risk for ventricular arrhythmias and sudden cardiac death, particularly under ß-adrenergic stimulation (ß-AS). This work presents a methodology for theoretical characterization of temporal and spatial repolarization variability at baseline conditions and in response to ß-AS. For any measured voltage trace, the proposed methodology estimates the parameters and state variables of an underlying human ventricular action potential (AP) model by combining Double Greedy Dimension Reduction (DGDR) with automatic selection of biomarkers and the Unscented Kalman Filter (UKF). Such theoretical characterization can facilitate subsequent characterization of underlying variability mechanisms. Material and Methods: Given an AP trace, initial estimates for the ionic conductances in a stochastic version of the baseline human ventricular O'Hara et al. model were obtained by DGDR. Those estimates served to initialize and update model parameter estimates by the UKF method based on formulation of an associated nonlinear state-space representation and joint estimation of model parameters and state variables. Similarly, ß-AS-induced phosphorylation levels of cellular substrates were estimated by the DGDR-UKF methodology. Performance was tested by building an experimentally-calibrated population of virtual cells, from which synthetic AP traces were generated for baseline and ß-AS conditions. Results: The combined DGDR-UKF methodology led to 25% reduction in the error associated with estimation of ionic current conductances at baseline conditions and phosphorylation levels under ß-AS with respect to individual DGDR and UKF methods. This improvement was not at the expense of higher computational load, which was diminished by 90% with respect to the individual UKF method. Both temporal and spatial AP variability of repolarization were accurately characterized by the DGDR-UKF methodology. Conclusions: A combined DGDR-UKF methodology is proposed for parameter and state variable estimation of human ventricular cell models from available AP traces at baseline and under ß-AS. This methodology improves the estimation performance and reduces the convergence time with respect to individual DGDR and UKF methods and renders a suitable approach for computational characterization of spatiooral repolarization variability to be used for ascertainment of variability mechanisms and its relation to arrhythmogenesis

Q-learning Based System for Path Planning with UAV Swarms in Obstacle Environments

Path Planning methods for autonomous control of Unmanned Aerial Vehicle (UAV) swarms are on the rise because of all the advantages they bring. There are more and more scenarios where autonomous control of multiple UAVs is required. Most of these scenarios present a large number of obstacles, such as power lines or trees. If all UAVs can be operated autonomously, personnel expenses can be decreased. In addition, if their flight paths are optimal, energy consumption is reduced. This ensures that more battery time is left for other operations. In this paper, a Reinforcement Learning based system is proposed for solving this problem in environments with obstacles by making use of Q-Learning. This method allows a model, in this particular case an Artificial Neural Network, to self-adjust by learning from its mistakes and achievements. Regardless of the size of the map or the number of UAVs in the swarm, the goal of these paths is to ensure complete coverage of an area with fixed obstacles for tasks, like field prospecting. Setting goals or having any prior information aside from the provided map is not required. For experimentation, five maps of different sizes with different obstacles were used. The experiments were performed with different number of UAVs. For the calculation of the results, the number of actions taken by all UAVs to complete the task in each experiment is taken into account. The lower the number of actions, the shorter the path and the lower the energy consumption. The results are satisfactory, showing that the system obtains solutions in fewer movements the more UAVs there are. For a better presentation, these results have been compared to another state-of-the-art approach

Self-report prevalence and associated factors to drug hypersensitivity in Mexican young adults

Background: Drug hypersensitivity is defined as any unfavorable reaction that occurs after the administration of any drug. It may or may not be mediated by the involvement of the immune system. Epidemiological data related to drug hypersensitivity reactions in our country are scarce. Objective: To determine the prevalence of drug hypersensitivity in a group of young adults, as well as to identify associated factors. Methods: A structured questionnaire was applied to young people aged 18 to 25 years. The instrument was oriented to identify reactions of drug hypersensitivity, as well as the most prevalent drugs involved. In addition, a personal and family history of atopic diseases was included. Analysis for associations between variables was been done through logistic regression. Results: The prevalence of drug hypersensitivity reactions was 12% (144 of 1,200). The antibiotics were the agents most related to hypersensitivity reactions (9.8%) followed by nonsteroidal anti-inflammatory drugs (1.6%). Factors associated with drug hypersensitivity were a personal history of asthma, odds ratio (OR) 3.15 (95% confidence interval [CI], 1.44–6.91), maternal and paternal history of drug hypersensitivity, OR 2.33 (95% CI, 1.21–4.48) and OR 3.11 (95% CI, 1.22–7.92), respectively. Conclusion: The results of this research show that drug hypersensitivity in young adults is a highly prevalent event and it is associated with personal history of asthma and history of drug hypersensitivity in parents

Time Course of Low-Frequency Oscillatory Behavior in Human Ventricular Repolarization Following Enhanced Sympathetic Activity and Relation to Arrhythmogenesis

Background and Objectives: Recent studies in humans and dogs have shown that ventricular repolarization exhibits a low-frequency (LF) oscillatory pattern following enhanced sympathetic activity, which has been related to arrhythmic risk. The appearance of LF oscillations in ventricular repolarization is, however, not immediate, but it may take up to some minutes. This study seeks to characterize the time course of the action potential (AP) duration (APD) oscillatory behavior in response to sympathetic provocations, unveil its underlying mechanisms and establish a potential link to arrhythmogenesis under disease conditions. Materials and Methods: A representative set of human ventricular computational models coupling cellular electrophysiology, calcium dynamics, β-adrenergic signaling, and mechanics was built. Sympathetic provocation was modeled via phasic changes in β-adrenergic stimulation (β-AS) and mechanical stretch at Mayer wave frequencies within the 0.03–0.15 Hz band. Results: Our results show that there are large inter-individual differences in the time lapse for the development of LF oscillations in APD following sympathetic provocation, with some cells requiring just a few seconds and other cells needing more than 3 min. Whereas, the oscillatory response to phasic mechanical stretch is almost immediate, the response to β-AS is much more prolonged, in line with experimentally reported evidences, thus being this component the one driving the slow development of APD oscillations following enhanced sympathetic activity. If β-adrenoceptors are priorly stimulated, the time for APD oscillations to become apparent is remarkably reduced, with the oscillation time lapse being an exponential function of the pre-stimulation level. The major mechanism underlying the delay in APD oscillations appearance is related to the slow IKs phosphorylation kinetics, with its relevance being modulated by the IKs conductance of each individual cell. Cells presenting short oscillation time lapses are commonly associated with large APD oscillation magnitudes, which facilitate the occurrence of pro-arrhythmic events under disease conditions involving calcium overload and reduced repolarization reserve. Conclusions: The time course of LF oscillatory behavior of APD in response to increased sympathetic activity presents high inter-individual variability, which is associated with different expression and PKA phosphorylation kinetics of the IKs current. Short time lapses in the development of APD oscillations are associated with large oscillatory magnitudes and pro-arrhythmic risk under disease conditions

Bronchial Thermoplasty Global Registry (BTGR): 2-year results

Asma; Broncoscòpia; Termoplàstia bronquialAsma; Broncoscopia; Termoplastia bronquialAsthma; Bronchoscopy; Bronchial ThermoplastyObjectives: Bronchial thermoplasty (BT) is a device-based treatment for subjects ≥18 years with severe asthma not well controlled with inhaled corticosteroids and long-acting beta-agonists. The Bronchial Thermoplasty Global Registry (BTGR) collected real-world data on subjects undergoing this procedure. Design: The BTGR is an all-comer, prospective, open-label, multicentre study enrolling adult subjects indicated for and treated with BT. Setting: Eighteen centres in Spain, Italy, Germany, the UK, the Netherlands, the Czech Republic, South Africa and Australia PARTICIPANTS: One hundred fifty-seven subjects aged 18 years and older who were scheduled to undergo BT treatment for asthma. Subjects diagnosed with other medical conditions which, in the investigator's opinion, made them inappropriate for BT treatment were excluded. Primary and secondary outcome measures: Baseline characteristics collected included demographics, Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Test (ACT), medication usage, forced expiratory volume in one second and forced vital capacity, medical history, comorbidities and 12-month baseline recall data (severe exacerbations (SE) and healthcare utilisation). SE incidence and healthcare utilisation were summarised at 1 and 2 years post-BT. Results: Subjects' baseline characteristics were representative of persons with severe asthma. A comparison of the proportion of subjects experiencing events during the 12 months prior to BT to the 2-year follow-up showed a reduction in SE (90.3% vs 56.1%, p<0.0001), emergency room visits (53.8% vs 25.5%, p<0.0001) and hospitalisations (42.9% vs 23.5 %, p=0.0019). Reductions in asthma maintenance medication dosage were also observed. AQLQ and ACT scores improved from 3.26 and 11.18 at baseline to 4.39 and 15.54 at 2 years, respectively (p<0.0001 for both AQLQ and ACT). Conclusions: The BTGR demonstrates sustained improvement in clinical outcomes and reduction in asthma medication usage 2 years after BT in a real-world population. This is consistent with results from other BT randomised controlled trials and registries and further supports improvement in asthma control after BT.This study was sponsored by Boston Scientific Corporation, Marlborough, MA, USA

Time Course of Low-Frequency Oscillatory Behavior in Human Ventricular Repolarization Following Enhanced Sympathetic Activity and Relation to Arrhythmogenesis

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