132 research outputs found

    Supervisory Control Theory in System Safety Analysis

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    Development of safety critical systems requires a risk management strategy to identify and analyse hazards, and apply necessary actions to eliminate or control them as malfunctions could be catastrophic. Fault Tree Analysis (FTA) is one of the most widely used methods for safety analysis in industrial use. However, the standard FTA is manual, informal, and limited to static analysis of systems. In this paper, we present preliminary results from a model-based approach to address these limitations using Supervisory Control Theory. Taking an example from the Fault Tree Handbook, we present a systematic approach to incrementally obtain formal models from a fault tree and verify them in the tool Supremica. We present a method to calculate minimal cut sets using our approach. These compositional techniques could potentially be very beneficial in the safety analysis of highly complex safety critical systems, where several components interact to solve different tasks

    A case study of mesospheric planetary waves observed over a three-radar network using empirical mode decomposition

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    In this paper an attempt is made to study equatorial Kelvin waves using a network of three radars: Kototabang (0.204° S, 100.320° E) meteor radar, Pameungpeuk (7.646° S, 107.688° E) medium-frequency radar, and Pontianak (0.003° S, 109.367° E) medium-frequency radar. We have used the continuous data gathered from the three radars during April–May 2010. Empirical mode decomposition (EMD), Lomb–Scargle periodogram (LSP) analysis, and wavelet techniques are used to study the temporal and altitude structures of planetary waves. Here, we used a novel technique called EMD to extract the planetary waves from wind data. The planetary waves of  ∼  6.5 and  ∼  3.6 days periodicity are observed in all three radar stations with peak amplitudes of about 12 and 11 m s−1, respectively. The 3.6-day wave has an average vertical wavelength from the three radars of about 42 km. The 3.6- and 6.5-day planetary waves are particularly strong in the zonal wind component. We find that the two waves are present at the 84–94 km height region. The observed features of the 3.6- and 6.5-day waves at the three tropical-latitude stations show some correspondence with the results reported for the equatorial-latitude stations

    Quantitative Whole Body Biodistribution of Fluorescent-Labeled Agents by Non-Invasive Tomographic Imaging

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    When small molecules or proteins are injected into live animals, their physical and chemical properties will significantly affect pharmacokinetics, tissue penetration, and the ultimate routes of metabolism and clearance. Fluorescence molecular tomography (FMT) offers the ability to non-invasively image and quantify temporal changes in fluorescence throughout the major organ systems of living animals, in a manner analogous to traditional approaches with radiolabeled agents. This approach is best used with biotherapeutics (therapeutic antibodies, or other large proteins) or large-scaffold drug-delivery vectors, that are minimally affected by low-level fluorophore conjugation. Application to small molecule drugs should take into account the significant impact of fluorophore labeling on size and physicochemical properties, however, the presents studies show that this technique is readily applied to small molecule agents developed for far-red (FR) or near infrared (NIR) imaging. Quantification by non-invasive FMT correlated well with both fluorescence from tissue homogenates as well as with planar (2D) fluorescence reflectance imaging of excised intact organs (r2 = 0.996 and 0.969, respectively). Dynamic FMT imaging (multiple times from 0 to 24 h) performed in live mice after the injection of four different FR/NIR-labeled agents, including immunoglobulin, 20–50 nm nanoparticles, a large vascular imaging agent, and a small molecule integrin antagonist, showed clear differences in the percentage of injected dose per gram of tissue (%ID/g) in liver, kidney, and bladder signal. Nanoparticles and IgG1 favored liver over kidney signal, the small molecule integrin-binding agent favored rapid kidney and bladder clearance, and the vascular agent, showed both liver and kidney clearance. Further assessment of the volume of distribution of these agents by fluorescent volume added information regarding their biodistribution and highlighted the relatively poor extravasation into tissue by IgG1. These studies demonstrate the ability of quantitative FMT imaging of FR/NIR agents to non-invasively visualize and quantify the biodistribution of different agents over time

    Large-Scale Cortical Dynamics of Sleep Slow Waves

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    Slow waves constitute the main signature of sleep in the electroencephalogram (EEG). They reflect alternating periods of neuronal hyperpolarization and depolarization in cortical networks. While recent findings have demonstrated their functional role in shaping and strengthening neuronal networks, a large-scale characterization of these two processes remains elusive in the human brain. In this study, by using simultaneous scalp EEG and intracranial recordings in 10 epileptic subjects, we examined the dynamics of hyperpolarization and depolarization waves over a large extent of the human cortex. We report that both hyperpolarization and depolarization processes can occur with two different characteristic time durations which are consistent across all subjects. For both hyperpolarization and depolarization waves, their average speed over the cortex was estimated to be approximately 1 m/s. Finally, we characterized their propagation pathways by studying the preferential trajectories between most involved intracranial contacts. For both waves, although single events could begin in almost all investigated sites across the entire cortex, we found that the majority of the preferential starting locations were located in frontal regions of the brain while they had a tendency to end in posterior and temporal regions

    Sub region-specific modulation of synchronous neuronal burst firing after a kainic acid insult in organotypic hippocampal cultures

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    <p>Abstract</p> <p>Background</p> <p>Excitotoxicity occurs in a number of pathogenic states including stroke and epilepsy. The adaptations of neuronal circuits in response to such insults may be expected to play an underlying role in pathogenesis. Synchronous neuronal firing can be induced in isolated hippocampal slices and involves all regions of this structure, thereby providing a measure of circuit activity. The effect of an excitotoxic insult (kainic acid, KA) on Mg<sup>2+</sup>-free-induced synchronized neuronal firing was tested in organotypic hippocampal culture by measuring extracellular field activity in CA1 and CA3.</p> <p>Results</p> <p>Within 24 hrs of the insult regional specific changes in neuronal firing patterns were evident as: (i) a dramatic <it>reduction </it>in the ability of CA3 to generate firing; and (ii) a contrasting <it>increase </it>in the frequency and duration of synchronized neuronal firing events in CA1. Two distinct processes underlie the increased propensity of CA1 to generate synchronized burst firing; a lack of ability of the CA3 region to 'pace' CA1 resulting in an increased frequency of synchronized events; and a change in the 'intrinsic' properties limited to the CA1 region, which is responsible for increased event duration. Neuronal quantification using NeuN immunoflurescent staining and stereological confocal microscopy revealed no significant cell loss in hippocampal sub regions, suggesting that changes in the properties of neurons within this region were responsible for the KA-mediated excitability changes.</p> <p>Conclusion</p> <p>These results provide novel insight into adaptation of hippocampal circuits following excitotoxic injury. KA-mediated disruption of the interplay between CA3 and CA1 clearly increases the propensity to synchronized firing in CA1.</p

    Early phase of plasticity-related gene regulation and SRF dependent transcription in the hippocampus

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    Hippocampal organotypic cultures are a highly reliable in vitro model for studying neuroplasticity: in this paper, we analyze the early phase of the transcriptional response induced by a 20 \ub5M gabazine treatment (GabT), a GABA-Ar antagonist, by using Affymetrix oligonucleotide microarray, RT-PCR based time-course and chromatin-immuno-precipitation. The transcriptome profiling revealed that the pool of genes up-regulated by GabT, besides being strongly related to the regulation of growth and synaptic transmission, is also endowed with neuro-protective and pro-survival properties. By using RT-PCR, we quantified a time-course of the transient expression for 33 of the highest up-regulated genes, with an average sampling rate of 10 minutes and covering the time interval [10 3690] minutes. The cluster analysis of the time-course disclosed the existence of three different dynamical patterns, one of which proved, in a statistical analysis based on results from previous works, to be significantly related with SRF-dependent regulation (p-value<0.05). The chromatin immunoprecipitation (chip) assay confirmed the rich presence of working CArG boxes in the genes belonging to the latter dynamical pattern and therefore validated the statistical analysis. Furthermore, an in silico analysis of the promoters revealed the presence of additional conserved CArG boxes upstream of the genes Nr4a1 and Rgs2. The chip assay confirmed a significant SRF signal in the Nr4a1 CArG box but not in the Rgs2 CArG box
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