Purinergic Signalling in Immune System Regulation in Health and Disease

The concept of a purinergic signalling system was first proposed by Professor Geoffrey Burnstock over 30 years ago. This includes the cellular responses to purine nucleotides, such as ATP, and nucleosides, such as adenosine, that act as extracellular messengers playing a role through specific nucleotide and adenosine receptors in all systems. Indeed, in addition to their role in cellular metabolism, nucleotides as well as nucleosides are extracellular mediators that activate biological responses in all cells. Cells subjected to activation or shear or mechanical stress release nucleotides such as ATP, ADP, UTP, and UDP in large amounts. All cells can release nucleotides in a controlled fashion [1]. The mechanisms of nucleotide release have been the focus of intense research activities but are still not fully understood. While activated platelets and neurons release nucleotides by exocytosis, neutrophils, and T lymphocytes use pannexin-1 hemichannels for nucleotide efflux, some cells also constitutively release nucleotides

Correlations for the ignition characteristics of six different fuels and their application to predict ignition delays under transient thermodynami conditions

[EN] The ignition characteristics of six different fuels have been correlated as a function of the temperature, pressure, equivalence ratio and oxygen molar fraction in this investigation. More specifically, the ignition delay referred to cool flames, the high-temperature ignition delay and the critical concentrations and ignition times of HO2 and CH2O have been parameterized for n-dodecane, PRFO, PRF25, PRF50, PRF75 and PRF100. To do so, a wide database of ignition data of the aforementioned fuels has been generated by means of chemical simulations in CHEMKIN, solving a detailed mechanism for PRF mixtures and a reduced mechanism for n-dodecane. In fact, in cylinder engine-like conditions reached in a Rapid Compression Expansion Machine (RCEM) have been replicated. The mathematical correlations have shown a relative deviation around 20% with the database in the low-temperature, low-pressure zone, which is the typical accuracy of usual correlations for the ignition delay. Finally, the ignition delay under transient conditions measured in the RCEM has been predicted by means of different integral methods coupled to both the proposed correlations and the generated database. It has been found that deviations between the predictions obtained with the correlations or with the database are lower than 1%. This means that the correlations are accurate enough to predict the ignition time in spite of showing high deviation with the database, since the low-temperature, low-pressure zone has a minor contribution to the ignition delay.The authors would like to thank different members of the CMT-Motores Termicos team of the Universitat Politecnica de Valencia for their contribution to this work. The authors would also like to thank the Spanish Ministry of Education for financing the PhD. Studies of Dario Lopez-Pintor (grant FPU13/02329). This research has been partially funded by FEDER and the Spanish Government through project TRA2015-67136-R.Desantes, J.; Bermúdez, V.; López, JJ.; López-Pintor, D. (2017). Correlations for the ignition characteristics of six different fuels and their application to predict ignition delays under transient thermodynami conditions. Energy Conversion and Management. 152:124-135. https://doi.org/10.1016/j.enconman.2017.09.030S12413515

Sensitivity analysis and validation of a predictive procedure for high and low-temperature ignition delays under engine conditions for n-dodecane using a Rapid Compression-Expansion Machine

[EN] A predictive procedure for cool flames and high-temperature ignition delays based on the accumulation and consumption of chain carriers has been validated for n-dodecane under engine conditions. To do so, an experimental parametric study has been carried out in a Rapid Compression-Expansion Machine, measuring the ignition times for different compression ratios (14 and 19), initial temperatures (from 403 K to 463 K), O-2 molar fractions (from 0.21 to 0.16) and equivalence ratios (from 0.4 to 0.7). The measured ignition delays have been compared to results from chemical kinetic simulations performed in CHEMKIN using a 0-D reactor that replicates the experimental conditions by solving five different chemical kinetic mechanisms, as a way to evaluate the mechanisms accuracy and variability. In general, all chemical kinetic mechanisms are able to accurately replicate the experimental ignition delays, being the mean relative deviation lower than 1.9% and 1.6% for both ignition stages, cool flames and the high-temperature ignition respectively. Furthermore, small differences have been appreciated between mechanisms in terms of ignition delay. Then, the predictive method has been applied using different databases obtained from each mechanism and a sensitivity analysis has been performed in order to evaluate the effects of the selected database on the predicted ignition delay. It has been found that while cool flames seems to be independent on the selected mechanism, the predicted high-temperature ignition delay is very sensitive to the species selected as chain carrier. Thus, if formaldehyde is assumed as ignition tracer, the predicted ignition time can vary up to 3%, while this percent decreases up to 1.3% when hydrogen peroxide takes the role of chain carrier. (C) 2017 Elsevier Ltd. All rights reserved.The authors are grateful to the Generalitat Valenciana for the financial support to acquire the RCEM (references PPC/2013/011 and FEDER Operativo 2007/2013 F07010203PCI00CIMETUPV001). Finally, the authors would like to thank the Spanish Ministry of Education for financing the PhD. Studies of Darío López-Pintor (grant FPU13/02329).Desantes, J.; Bermúdez, V.; López, JJ.; López-Pintor, D. (2017). Sensitivity analysis and validation of a predictive procedure for high and low-temperature ignition delays under engine conditions for n-dodecane using a Rapid Compression-Expansion Machine. Energy Conversion and Management. 145:64-81. https://doi.org/10.1016/j.enconman.2017.04.092S648114

Purinergic receptors in ocular inflammation

Inflammation is a complex process that implies the interaction between cells and molecular mediators, which, when not properly 'tuned,' can lead to disease. When inflammation affects the eye, it can produce severe disorders affecting the superficial and internal parts of the visual organ. The nucleoside adenosine and nucleotides including adenine mononucleotides like ADP and ATP and dinucleotides such as P(1),P(4)-diadenosine tetraphosphate (Ap4A), and P(1),P(5)-diadenosine pentaphosphate (Ap5A) are present in different ocular locations and therefore they may contribute/modulate inflammatory processes. Adenosine receptors, in particular A2A adenosine receptors, present anti-inflammatory action in acute and chronic retinal inflammation. Regarding the A3 receptor, selective agonists like N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine (CF101) have been used for the treatment of inflammatory ophthalmic diseases such as dry eye and uveoretinitis. Sideways, diverse stimuli (sensory stimulation, large intraocular pressure increases) can produce a release of ATP from ocular sensory innervation or after injury to ocular tissues. Then, ATP will activate purinergic P2 receptors present in sensory nerve endings, the iris, the ciliary body, or other tissues surrounding the anterior chamber of the eye to produce uveitis/endophthalmitis. In summary, adenosine and nucleotides can activate receptors in ocular structures susceptible to suffer from inflammatory processes. This involvement suggests the possible use of purinergic agonists and antagonists as therapeutic targets for ocular inflammation

Insights on the use of wind speed vertical extrapolation methods

The present work aims to study the influence of using different methods for wind speed extrapolation in energy production calculations. A dataset of 21 meteorological masts from several landscape characteristics and locations, with at least one year of 10-minute wind speed/direction data, was used as the basis for calculations. Both the power law through estimation of wind shear coefficients, and the logarithmic-based profile using WAsP, were used as mathematical models for predicting wind shear. Wind speed extrapolation was performed either from the top-most height, using a distance method that incorporated all measurement heights, or using the function for wind shear coefficient prediction. It was found that using the logarithmicbased profile was the less reliable of all studied methods. The study showed that the most accurate method was the power law with wind shear coefficients estimated from the two upper heights closest to the extrapolation height, by wind direction sector of 30º, and the wind speeds extrapolation from the topmost height of the two. It is suggested that the use of this method reduces uncertainty in AEP estimates.info:eu-repo/semantics/publishedVersio

Structure–activity relationships of dinucleotides: Potent and selective agonists of P2Y receptors

Dinucleoside polyphosphates act as agonists on purinergic P2Y receptors to mediate a variety of cellular processes. Symmetrical, naturally occurring purine dinucleotides are found in most living cells and their actions are generally known. Unsymmetrical purine dinucleotides and all pyrimidine containing dinucleotides, however, are not as common and therefore their actions are not well understood. To carry out a thorough examination of the activities and specificities of these dinucleotides, a robust method of synthesis was developed to allow manipulation of either nucleoside of the dinucleotide as well as the phosphate chain lengths. Adenosine containing dinucleotides exhibit some level of activity on P2Y1 while uridine containing dinucleotides have some level of agonist response on P2Y2 and P2Y6. The length of the linking phosphate chain determines a different specificity; diphosphates are most accurately mimicked by dinucleoside triphosphates and triphosphates most resemble dinucleoside tetraphosphates. The pharmacological activities and relative metabolic stabilities of these dinucleotides are reported with their potential therapeutic applications being discussed

A phenomenological explanation of the autoignition propagation under HCCI conditions

[EN] A phenomenological explanation about the autoignition propagation under HCCI conditions is developed in this paper. To do so, diffusive effects from the burned zones to the fresh mixture, pressure waves based effects and expansion effects caused by combustion are taken into account. Additionally, different Damkohler numbers have been defined and evaluated in order to characterize the phenomenon and quantify the relevance of each effect. The theoretical explanation has been evaluated by means of chemiluminescence measurements performed in a Rapid Compression Expansion Machine (RCEM), which allow to estimate the velocity of propagation of the autoignition front. The results showed that under HCCI conditions the autoignition propagation is controlled, in general, by the pressure waves established in the combustion chamber, since the characteristic time of the autoignition propagation is too short to assume the absence of pressure gradients in the chamber. Thus, the thermodynamic conditions reached behind the pressure wave promote the autoignition and explain the high propagation velocities associated to the reaction front. Besides, the results also showed that the contribution of diffusive phenomena on the propagation is negligible, since the characteristic time of diffusion is too long compared to the characteristic time of the autoignition propagation. Finally, the experimental measurements showed that the autoignition propagation is affected by a really relevant cycle-to-cycle variation. The turbulence generated by the combustion has, by definition, an aleatory behavior, leading to random heterogeneity distribution and, therefore, to somewhat random autoignition propagation.The authors would like to thank different members of the CMT-Motores TTrmicos team of the Universitat Politecnica de Valencia for their contribution to this work. The authors would also like to thank the Spanish Ministry of Education for financing the PhD. Studies of Dario Lopez-Pintor (grant FPU13/02329). This research has been partially funded by FEDER and the Spanish Government through project TRA2015-67136-R.Desantes, J.; López, JJ.; García-Oliver, JM.; López-Pintor, D. (2017). A phenomenological explanation of the autoignition propagation under HCCI conditions. Fuel. 206:43-57. https://doi.org/10.1016/j.fuel.2017.05.075S435720

Experimental validation and analysis of seven different chemical kinetic mechanisms for n-dodecane using a Rapid Compression-Expansion Machine

[EN] Seven different chemical kinetic mechanisms for n-dodecane, two detailed and five reduced, have been evaluated under Engine Combustion Network (ECN) thermodynamic conditions by comparison to experimental measurements in a Rapid Compression-Expansion Machine (RCEM). The target ECN conditions are imposed at Top Dead Center (TDC), which cover a wide range of temperatures (from 850 K to 1000 K), oxygen molar fractions (0.21 and 0.15) and equivalence ratios (0.8, 0.9 and 1), while the pressure is fixed to keep a constant density at TDC equal to 22.8 kg/m(3). The results obtained have been used to validate the chemical kinetic simulations, which have been performed with CHEMKIN, by comparing both cool flames and high temperature ignition delays, as well as the heat released in each stage of the combustion process in case of having a two-stage ignition pattern. The experimental results show good agreement with the chemical kinetic simulations. In fact, the mean relative deviation in ignition delay between experiments and simulations among all the chemical mechanisms is equal to 18.0% (3 CAD) for both cool flames and high temperature ignition. In general, closer correspondence has been obtained for the ignition delay referred to the high-temperature stage of the process, being the cool flames phenomenon more difficult to reproduce. Moreover, the differences between the reduced mechanisms and the most detailed one have been analyzed, concluding that the enhanced specific reaction rates of the most reduced mechanisms cause differences not only on the ignition delays, but also on the Negative Temperature Coefficient (NTC) behavior and on the heat released during cool flames. (C) 2017 The Combustion Institute. Published by Elsevier Inc. All rights reserved.The authors would also like to thank the Spanish Ministry of Education for financing the PhD. Studies of Dario Lopez-Pintor (grant FPU13/02329). This study was partially funded by the Spanish Ministry of Economy and Competitiveness in the frame of the COMEFF (TRA2014-59483-R) project.Desantes, J.; López, JJ.; García-Oliver, JM.; López-Pintor, D. (2017). Experimental validation and analysis of seven different chemical kinetic mechanisms for n-dodecane using a Rapid Compression-Expansion Machine. Combustion and Flame. 182:76-89. https://doi.org/10.1016/j.combustflame.2017.04.004S768918

A new method to predict high and low-temperature ignition delays under transient thermodynamic conditions and its experimental validation using a Rapid Compression-Expansion Machine

A new procedure to predict both high-temperature stage and cool flames ignition delays under transient thermodynamic conditions has been developed in this paper. The results obtained have been compared with those obtained from the Livengood & Wu integral method, as well as with other predictive methods and with direct chemical kinetic simulations and experimental data. All simulations have been performed with CHEMKIN, employing a detailed chemical kinetic mechanism. The simulations and predictions have been validated in the working range versus experimental results obtained from a Rapid CompressionExpansion Machine (RCEM). The study has been carried out with n-heptane and iso-octane, as diesel and gasoline fuel surrogates, under a wide range of initial temperatures (from 358 K to 458 K), initial pressures (0.14 MPa and 0.17 MPa), compression ratios (15 and 17), EGR rates (from 0% to 50%) and equivalence ratios (from 0.3 to 0.8). The experimental results show good agreement with the direct chemical kinetic simulations and with the new predictive method proposed. In fact, the mean relative deviation between experiments and simulations is equal to 1.719% for n-heptane and equal to 1.504% for iso-octane. Besides, the new method has shown good predictive capability not only for the hightemperature stage of the process but also for cool flames, being the mean relative deviation versus the experimental data lower than 2.900%. Better predictions of the ignition delay have been obtained with the new procedure than the ones obtained with the classic Livengood & Wu expression, especially in those cases showing a two-stage ignition pattern.The authors would like to thank different members of the CMT-Motores Termicos team of the Universitat Politecnica de Valencia for their contribution to this work. The authors would also like to thank the director of LAV-ETH, Konstantinos Boulouchos, for the Dario Lopez-Pintor's internship at LAV. Finally, the authors would like to thank the Spanish Ministry of Education for financing the PhD. Studies of Dario Lopez-Pintor (grant FPU13/02329).Desantes Fernández, JM.; Bermúdez, V.; López, JJ.; López Pintor, D. (2016). A new method to predict high and low-temperature ignition delays under transient thermodynamic conditions and its experimental validation using a Rapid Compression-Expansion Machine. Energy Conversion and Management. 123:512-522. https://doi.org/10.1016/j.enconman.2016.06.051S51252212

Experimental validation of an alternative method to predict high and low-temperature ignition delays under transient thermodynamic conditions for PRF mixtures using a Rapid Compression-Expansion Machine

An alternative procedure to predict both high-temperature stage and cool flames ignition delays under transient thermodynamic conditions is intended to be validated in this paper. An experimental study has been carried out in a Rapid Compression-Expansion Machine (RCEM), using different iso-octane/nheptane blends in order to cover a wide range of octane numbers (from 25 to 75) under a wide range of initial temperatures (from 363 K to 423 K), compression ratios (14 and 19), O2 molar rates (from 21% to 16%) and equivalence ratios (from 0.4 to 0.8). The results obtained have been used to validate direct chemical kinetic simulations, as well as to evaluate the alternative predictive method and the Livengood & Wu integral method. Simulations have been performed solving a detailed chemical kinetic mechanism in CHEMKIN. The experimental results show good agreement with the chemical kinetic simulations and with the alternative predictive method. In fact, the mean relative deviation between experiments and simulations is equal to 1.7%, 2.2% and 3.1% for PRF25, PRF50 and PRF75, respectively. Besides, the alternative method has shown good predictive capability not only for the high-temperature stage of the process, but also for cool flames, being the mean relative deviation versus the experimental data lower than 3.3% for all fuels. Better predictions of the ignition delay have been obtained with the alternative procedure than the ones obtained with the classic Livengood & Wu expression, especially in those cases showing a two-stage ignition pattern, in which the Livengood & Wu integral method is not able to predict the high-temperature stage of the process.The authors would like to thank different members of the CMT-Motores Termicos team of the Universitat Politecnica de Valencia for their contribution to this work. The authors would also like to thank the Spanish Ministry of Education for financing the PhD. Studies of Dario Lopez-Pintor (Grant FPU13/02329). This work was partly funded by the Spanish Ministry of Economy and Competitiveness, project TRA2015-67136-R.Desantes Fernández, JM.; Bermúdez, V.; López, JJ.; López Pintor, D. (2016). Experimental validation of an alternative method to predict high and low-temperature ignition delays under transient thermodynamic conditions for PRF mixtures using a Rapid Compression-Expansion Machine. Energy Conversion and Management. 129:23-33. https://doi.org/10.1016/j.enconman.2016.09.089S233312