1,089 research outputs found
Fibroblast mediated dynamics in diffusively uncoupled myocytes -- a simulation study using 2-cell motifs
In healthy hearts myocytes are typically coupled to nearest neighbours
through gap junctions. Under pathological conditions such as fibrosis, or in
scar tissue, or across ablation lines myocytes can uncouple from their
neighbours. Electrical conduction may still occur via fibroblasts that not only
couple proximal myocytes but can also couple otherwise unconnected regions. We
hypothesise that such coupling can alter conduction between myocytes via
introduction of delays or by initiation of premature stimuli that can
potentially result in reentry or conduction blocks. To test this hypothesis we
have developed several -cell motifs and investigated the effect of
fibroblast mediated electrical coupling between uncoupled myocytes. We have
identified various regimes of myocyte behaviour that depend on the strength of
gap-junctional conductance, connection topology, and parameters of the myocyte
and fibroblast models. These motifs are useful in developing a mechanistic
understanding of long-distance coupling on myocyte dynamics and enable the
characterisation of interaction between different features such as myocyte and
fibroblast properties, coupling strengths and pacing period. They are
computationally inexpensive and allow for incorporation of spatial effects such
as conduction velocity. They provide a framework for constructing scar tissue
boundaries and enable linking of cellular level interactions with scar induced
arrhythmia
s-Process Studies In the Light of New Experimental Cross Sections: Distribution of Neutron Fluences and r-Process Residuals
A best set of neutron-capture cross sections has been evaluated for the most important s-process isotopes. With this data base, s-process studies have been carried out using the traditional model which assumes a steady neutron flux and an exponential distribution of neutron irradiations. The calculated sigma-N curve is in excellent agreement with the empirical sigma-N-values of pure s-process nuclei. Simultaneously, good agreement is found between the difference of solar and s-process abundances and the abundances of pure r-process nuclei. The abundance pattern of the iron group elements where s-process results complement the abundances obtained from explosive nuclear burning is discussed. The results obtained from the traditional s-process model such as seed abundances, mean neutron irradiations, or neutron densities are compared to recent stellar model calculations which assume the He-burning shells of red giant stars as the site for the s-process
Prospectus, February 13, 1973
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Determinants of carotid microembolization
AbstractPurpose: Earlier studies have highlighted risk factors for perioperative stroke after carotid endarterectomy, such as female sex, preoperative symptoms, and cerebral infarction. In this study, we investigated the relationship between these factors and perioperative microembolization. Methods: A total of 235 patients were entered in the study at two centers. Transcranial Doppler ultrasound scanning was possible in 190 patients (81%) and was performed for 1 hour preoperatively and continuously intraoperatively as a means of detecting microemboli and monitoring mean middle cerebral artery velocity. The findings of transcranial Doppler ultrasound scanning were related to perioperative risk factors by means of univariate analysis. Results: Microemboli were detected in 28 (15%), 79 (42%), and 98 (52%) patients preoperatively, during carotid artery dissection, and after closure of the artery, respectively. Having 10 or more emboli after carotid artery closure was more common in women (P =.04) and in patients with symptomatic carotid artery disease (P =.04) and was demonstrated in three of the six patients who had a perioperative stroke. These three patients also had preoperative evidence of cerebral infarction and an intraoperative middle cerebral artery velocity less than 40 cm/s. Conclusion: In this study, perioperative microembolization was more common in women and patients with symptomatic carotid artery disease. These findings may explain the increased risk of carotid surgery in these patients. (J Vasc Surg 2001;34:1060-4.
Regional differences in APD restitution can initiate wavebreak and re-entry in cardiac tissue: A computational study
Background
Regional differences in action potential duration (APD) restitution in the heart favour arrhythmias, but the mechanism is not well understood.
Methods
We simulated a 150 Ă— 150 mm 2D sheet of cardiac ventricular tissue using a simplified computational model. We investigated wavebreak and re-entry initiated by an S1S2S3 stimulus protocol in tissue sheets with two regions, each with different APD restitution. The two regions had a different APD at short diastolic interval (DI), but similar APD at long DI. Simulations were performed twice; once with both regions having steep (slope > 1), and once with both regions having flat (slope < 1) APD restitution.
Results
Wavebreak and re-entry were readily initiated using the S1S2S3 protocol in tissue sheets with two regions having different APD restitution properties. Initiation occurred irrespective of whether the APD restitution slopes were steep or flat. With steep APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms with S1S2 of 250 ms, to 75 ms (S1S2 180 ms). With flat APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms (S1S2 250 ms), to 21 ms (S1S2 340 ms) and then 11 ms (S1S2 400 ms).
Conclusion
Regional differences in APD restitution are an arrhythmogenic substrate that can be concealed at normal heart rates. A premature stimulus produces regional differences in repolarisation, and a further premature stimulus can then result in wavebreak and initiate re-entry. This mechanism for initiating re-entry is independent of the steepness of the APD restitution curve
Convergence, sampling and total order estimator effects on parameter orthogonality in global sensitivity analysis
Dynamical system models typically involve numerous input parameters whose “effects” and orthogonality need to be quantified through sensitivity analysis, to identify inputs contributing the greatest uncertainty. Whilst prior art has compared total-order estimators’ role in recovering “true” effects, assessing their ability to recover robust parameter orthogonality for use in identifiability metrics has not been investigated. In this paper, we perform: (i) an assessment using a different class of numerical models representing the cardiovascular system, (ii) a wider evaluation of sampling methodologies and their interactions with estimators, (iii) an investigation of the consequences of permuting estimators and sampling methodologies on input parameter orthogonality, (iv) a study of sample convergence through resampling, and (v) an assessment of whether positive outcomes are sustained when model input dimensionality increases. Our results indicate that Jansen or Janon estimators display efficient convergence with minimum uncertainty when coupled with Sobol and the lattice rule sampling methods, making them prime choices for calculating parameter orthogonality and influence. This study reveals that global sensitivity analysis is convergence driven. Unconverged indices are subject to error and therefore the true influence or orthogonality of the input parameters are not recovered. This investigation importantly clarifies the interactions of the estimator and the sampling methodology by reducing the associated ambiguities, defining novel practices for modelling in the life sciences
Downtown Los Angeles 52-Story High-Rise and Free-Field Response to an Oil Refinery Explosion
The ExxonMobil Corp. oil refinery in Torrance, California experienced an explosion on February 18, 2015 causing ground shaking equivalent to a magnitude 2.0 earthquake. The impulse response for the source was computed from Southern California Seismic Network data for a single force system with a value of 2Ă—10^5 kN vertically downward. The refinery explosion produced an air pressure wave that was recorded 22.8 km away in a 52-story high-rise building in downtown Los Angeles by a dense accelerometer array that is a component of the Community Seismic Network. The array recorded anomalous waveforms on each floor displaying coherent arrivals that are consistent with the building's elastic response to a pressure wave caused by the refinery explosion. Using a finite-element model of the building, the force on the building on a floor-by-floor scale was found to range up to 1.42 kN, corresponding to a pressure perturbation of 7.7 Pa
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Gladstone and Scott: Family, identity, and nation
In the 175 years since his death, Walter Scott has regularly been hailed as an influence by politicians. Amongst the poet-novelist's nineteenth-century political admirers, William Ewart Gladstone was possibly the most ardent, genuine, and significant. Scott's poems and novels were amongst the earliest texts Gladstone read; he read no works (in English), except the Bible, so consistently or completely over such a length of time. They offered him a plethora of inspirations, ideas, and language, which he imbibed and appropriated into his public and private lives. His concept of self, his understanding of family, and his sense of home, were all forged and conducted within a Scottian frame of reference. Scott's life and works also crucially influenced Gladstone's political understanding of the Scottish nation and its people, and his conception of how he could best serve their political interests. This article casts new light on an important and influential relationship in Gladstone's life, establishing that it was neither the superficial and recreational association some have described, nor simply a ploy of an astute politician. The article falls into three parts. The first elucidates how Gladstone's consumption of Scott's writings was seminal in the formation of his private identity, both individual and familial. The second explains how Gladstone's readings of Scott fitted into the specific and serious character of his other reading and knowledge-gathering, and the third shows how the details of Gladstone's response to Scott related to the broader intellectual and cultural context of his public life. By placing Gladstone within his Scottish context, this article shows how frequently and significantly his private and public worlds intersected
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