43 research outputs found

    Vibration control of bridges under simultaneous effects of earthquake and moving loads using steel pipe dampers

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    This study aims to develop a practical methodology based on the eigenfunction expansion method to assess the effects of simultaneous action of vertical earthquake excitation and moving vehicle loads in single-span and multi-span simply-supported bridges. While the effects of vertical earthquake ground motions are generally ignored in common design practice, it is shown that the influence of simultaneous vertical earthquake excitation and vehicle loads can considerably affect the structural response of the bridge, especially in near-field earthquakes with high amplitude vertical components. To address this issue, a novel vibration suppression system is proposed using steel pipe dampers and its reliability is investigated for a wide range of bridge flexural rigidity under seven different earthquake records. The results indicate that the proposed system can significantly (up to 75%) suppress the vertical vibrations generated in the bridge, especially for the systems with lower flexural rigidity. For the same maximum deflection limits, application of pipe dampers could reduce the required flexural rigidity of the bridge (up to 50%), and therefore, lead to more economic design solutions with lower structural weight

    Feedback control architecture and the bacterial chemotaxis network.

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    PMCID: PMC3088647This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Bacteria move towards favourable and away from toxic environments by changing their swimming pattern. This response is regulated by the chemotaxis signalling pathway, which has an important feature: it uses feedback to 'reset' (adapt) the bacterial sensing ability, which allows the bacteria to sense a range of background environmental changes. The role of this feedback has been studied extensively in the simple chemotaxis pathway of Escherichia coli. However it has been recently found that the majority of bacteria have multiple chemotaxis homologues of the E. coli proteins, resulting in more complex pathways. In this paper we investigate the configuration and role of feedback in Rhodobacter sphaeroides, a bacterium containing multiple homologues of the chemotaxis proteins found in E. coli. Multiple proteins could produce different possible feedback configurations, each having different chemotactic performance qualities and levels of robustness to variations and uncertainties in biological parameters and to intracellular noise. We develop four models corresponding to different feedback configurations. Using a series of carefully designed experiments we discriminate between these models and invalidate three of them. When these models are examined in terms of robustness to noise and parametric uncertainties, we find that the non-invalidated model is superior to the others. Moreover, it has a 'cascade control' feedback architecture which is used extensively in engineering to improve system performance, including robustness. Given that the majority of bacteria are known to have multiple chemotaxis pathways, in this paper we show that some feedback architectures allow them to have better performance than others. In particular, cascade control may be an important feature in achieving robust functionality in more complex signalling pathways and in improving their performance

    Membrane Properties and the Balance between Excitation and Inhibition Control Gamma-Frequency Oscillations Arising from Feedback Inhibition

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    Computational studies as well as in vivo and in vitro results have shown that many cortical neurons fire in a highly irregular manner and at low average firing rates. These patterns seem to persist even when highly rhythmic signals are recorded by local field potential electrodes or other methods that quantify the summed behavior of a local population. Models of the 30ā€“80 Hz gamma rhythm in which network oscillations arise through ā€˜stochastic synchronyā€™ capture the variability observed in the spike output of single cells while preserving network-level organization. We extend upon these results by constructing model networks constrained by experimental measurements and using them to probe the effect of biophysical parameters on network-level activity. We find in simulations that gamma-frequency oscillations are enabled by a high level of incoherent synaptic conductance input, similar to the barrage of noisy synaptic input that cortical neurons have been shown to receive in vivo. This incoherent synaptic input increases the emergent network frequency by shortening the time scale of the membrane in excitatory neurons and by reducing the temporal separation between excitation and inhibition due to decreased spike latency in inhibitory neurons. These mechanisms are demonstrated in simulations and in vitro current-clamp and dynamic-clamp experiments. Simulation results further indicate that the membrane potential noise amplitude has a large impact on network frequency and that the balance between excitatory and inhibitory currents controls network stability and sensitivity to external inputs

    Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles

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    Release of membrane vesicles, a process conservedĀ in bothĀ prokaryotes and eukaryotes, represents an evolutionary link, and suggests essential functions of a dynamic extracellular vesicular compartment (including exosomes, microparticles or microvesicles and apoptotic bodies). Compelling evidence supports the significance of this compartment in a broad range of physiological and pathological processes. However, classification of membrane vesicles, protocols of their isolation and detection, molecular details of vesicular release, clearance and biological functions are still under intense investigation. Here, we give a comprehensive overview of extracellular vesicles. After discussing the technical pitfalls and potential artifacts of the rapidly emerging field, we compare results from meta-analyses of published proteomic studies on membrane vesicles. We also summarize clinical implications of membrane vesicles. Lessons from this compartment challenge current paradigms concerning the mechanisms of intercellular communication and immune regulation. Furthermore, its clinical implementation may open new perspectives in translational medicine both in diagnostics and therapy

    JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies

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    BACKGROUND. Monogenic IFNā€“mediated autoinflammatory diseases present in infancy with systemic inflammation, an IFN response gene signature, inflammatory organ damage, and high mortality. We used the JAK inhibitor baricitinib, with IFN-blocking activity in vitro, to ameliorate disease. METHODS. Between October 2011 and February 2017, 10 patients with CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures), 4 patients with SAVI (stimulator of IFN genesā€“associated [STING-associated] vasculopathy with onset in infancy), and 4 patients with other interferonopathies were enrolled in an expanded access program. The patients underwent dose escalation, and the benefit was assessed by reductions in daily disease symptoms and corticosteroid requirement. Quality of life, organ inflammation, changes in IFN-induced biomarkers, and safety were longitudinally assessed. RESULTS. Eighteen patients were treated for a mean duration of 3.0 years (1.5ā€“4.9 years). The median daily symptom score decreased from 1.3 (interquartile range [IQR], 0.93ā€“1.78) to 0.25 (IQR, 0.1ā€“0.63) (P < 0.0001). In 14 patients receiving corticosteroids at baseline, daily prednisone doses decreased from 0.44 mg/kg/day (IQR, 0.31ā€“1.09) to 0.11 mg/kg/day (IQR, 0.02ā€“0.24) (P < 0.01), and 5 of 10 patients with CANDLE achieved lasting clinical remission. The patientsā€™ quality of life and height and bone mineral density Z-scores significantly improved, and their IFN biomarkers decreased. Three patients, two of whom had genetically undefined conditions, discontinued treatment because of lack of efficacy, and one CANDLE patient discontinued treatment because of BK viremia and azotemia. The most common adverse events were upper respiratory infections, gastroenteritis, and BK viruria and viremia. CONCLUSION. Upon baricitinib treatment, clinical manifestations and inflammatory and IFN biomarkers improved in patients with the monogenic interferonopathies CANDLE, SAVI, and other interferonopathies. Monitoring safety and efficacy is important in benefit-risk assessment

    Comparison of Dynamic Positioning Systems

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    Lambda Matrices and General Eigenvalue Problems

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