37 research outputs found

    Experimentally-calibrated population of models predicts and explains inter-subject variability in cardiac cellular\ud electrophysiology

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    Cellular and ionic causes of variability in the electrophysiological activity of hearts from individuals of the same species are unknown. However, improved understanding of this variability is key to enable prediction of the response of specific hearts to disease and therapies. Limitations of current mathematical modeling and experimental techniques hamper our ability to provide insight into variability. Here we describe a methodology to unravel the ionic determinants of inter-subject variability exhibited in experimental recordings, based on the construction and calibration of populations of models. We illustrate the methodology through its application to rabbit Purkinje preparations, due to their importance in arrhythmias and safety pharmacology assessment. We consider a set of equations describing the biophysical processes underlying rabbit Purkinje electrophysiology and we construct a population of over 10,000 models by randomly assigning specific parameter values corresponding to ionic current conductances and kinetics. We calibrate the model population by closely comparing simulation output and experimental recordings at three pacing frequencies. We show that 213 of the 10,000 candidate models are fully consistent with the experimental dataset. Ionic properties in the 213 models cover a wide range of values, including differences up to ±100% in several conductances. Partial correlation analysis shows that particular combinations of ionic properties determine the precise shape, amplitude and rate dependence of specific action potentials. Finally, we demonstrate that the population of models calibrated using data obtained under physiological conditions quantitatively predicts the action potential duration prolongation caused by exposure to four concentrations of the potassium channel blocker dofetilide

    Measurement of absolute Îł-ray emission probabilities in the decay of 227Ac in equilibrium with its progeny

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    Abstract The emission probabilities of Îł rays produced in the 227Ac decay series were determined by high-resolution Îł-ray spectrometry of sources with standardised activity. The sources were prepared quantitatively on glass discs by drop deposition of a solution with 227Ac in radioactive equilibrium with its daughter nuclides. Their activity was measured by a primary standardisation technique based on alpha-particle counting at a defined low solid angle. Four laboratories performed Îł-ray spectrometry and derived absolute Îł-ray intensities. Mean values were calculated and compared with literature data and the currently recommended evaluated data. New values on certain Îł-ray emission probabilities are proposed

    measurement of absolute Îł ray emission probabilities in the decay of 235u

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    Abstract Accurate measurements were performed of the photon emission probabilities following the α decay of 235U to 231Th. Sources of highly enriched 235U were characterised in terms of isotopic composition by mass spectrometry and their activities were standardised by means of alpha-particle counting at a low defined solid angle. The standardised sources were subsequently measured by high-resolution γ-ray spectrometry with calibrated high-purity germanium detectors to determine the photon emission probabilities. Four laboratories participated in this work and reported emission probabilities for 33 γ-ray lines. Most of them agree with previously published evaluated data. In addition, new values are proposed for γ-lines which have been measured only once in the past

    Adsorption of cesium on different types of activated carbon

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    The optimal conditions to remove radiocesium from water by adsorption on activated carbon (AC) were investigated. Two commercial ACs were compared to ACs prepared by steam activation of brewers’ spent grain. The influence of pH and loading AC with Prussian Blue were studied. 134Cs, measured by gamma-ray spectroscopy, served as a tracer for the Cs concentration. Column experiments showed that a neutral to acidic pH enhanced adsorption compared to high pH. Norit GAC 1240 had the highest adsorption capacity, 8.5 µg Cs g-1 AC for a column filtration. Sequential columns of Norit GAC 1240 removed 28.1 ± 2.8 % of Cs per column.JRC.D.4-Standards for Nuclear Safety, Security and Safeguard

    Qualification of a precision pattern dispenser

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    In order to automate sample preparation processes, a precision pattern dispenser was designed to reproducibly dispense radioactive solutions at pre-defined positions. It is composed of an automatic liquid sample handling unit coupled to an XYZ table. Qualification tests were conducted to evaluate the performance of the instrument and to assess the compliance with the requirements, in particular trueness (< 2%) and repeatability (< 1%). The instrument allows preparing sources in different source holders and on air filters, in a fast and accurate way.JRC.G.2-Standards for Nuclear Safety, Security and Safeguard

    Measurement of absolute Îł-ray emission probabilities in the decay of 235 U

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    Abstract Accurate measurements were performed of the photon emission probabilities following the α decay of 235U to 231Th. Sources of highly enriched 235U were characterised in terms of isotopic composition by mass spectrometry and their activities were standardised by means of alpha-particle counting at a low defined solid angle. The standardised sources were subsequently measured by high-resolution γ-ray spectrometry with calibrated high-purity germanium detectors to determine the photon emission probabilities. Four laboratories participated in this work and reported emission probabilities for 33 γ-ray lines. Most of them agree with previously published evaluated data. In addition, new values are proposed for γ-lines which have been measured only once in the past
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