Studies of molecular pathways associated with blood neutrophil corticosteroid insensitivity in equine asthma

L’asthme équin est caractérisé par une hyperactivité bronchique, une inflammation neutrophilique, et des altérations structurelles des voies aériennes. Chez les patients asthmatiques présentant une inflammation neutrophilique, les corticostéroïdes sont peu efficaces pour contrôler les signes cliniques. L’hypothèse de cette étude est que l’hypoxie et/ou le stress oxydatif dans le microenvironnement des poumons peuvent contribuer à une insensibilité des neutrophiles aux corticostéroïdes dans l’asthme. Les chevaux sont les meilleurs modèles animaux naturellement affectés par l’asthme neutrophilique et partagent plusieurs caractéristiques physiopathologiques avec l’humain. La viabilité, l’apoptose, l’expression génique d’IL-1, TNF- et IL-8 ont été mesurées dans des neutrophiles isolés à partir de sang périphérique de chevaux asthmatiques sévères (N=8) et de chevaux sains (N=8) en condition de culture stimulant l’hypoxie et le stress oxydatif, en présence ou non de corticostéroïdes (Dexamethason (Dex)). L’IL-1 et le TNF-, mais pas l’IL-8, ont été régulés négativement en présence de dexaméthasone dans des conditions de stress oxydatif induites par la pyocyanin. Bien que l’IL-17 et le LPS aient stimulé les neutrophiles équins, l’expression génique pro-inflammatoire n’a pas diminué après l’administration de Dex. En condition d’hypoxie induite par CoCl2, seulement l’expression génique de TNF- a considérablement été diminuée par la Dex, mais ceci a aussi été vrai en condition sans hypoxie. En conclusion, le stress oxydatif, mais pas l’hypoxie, entraîne une insensibilité aux corticostéroïdes, qui constitue une voie de régulation génique sélective (celle de l’IL-8). Les deux groupes de chevaux ont démontré une réponse similaire indiquant une réaction à la dexaméthasone et non liée à une inflammation asthmatique.Equine asthma is characterized by bronchial hyperactivity, neutrophilic inflammation, and structural alterations of the airways. Asthmatic patients with neutrophilic inflammation, are insensitive to corticosteroids. The hypothesis of this study is that hypoxia and/or oxidative stress in the microenvironment of the asthmatic lungs may contribute to this insensitivity of neutrophils to corticosteroids. Horses are unique animal models naturally affected by neutrophilic asthma and share several pathophysiological features with humans. Viability, apoptosis, IL-1, TNF- and IL-8 gene expression were measured in neutrophils isolated from peripheral blood of severe asthmatic horses (N = 8) and healthy horses (N = 8) in culture conditions stimulating hypoxia and oxidative stress, in the presence or absence of corticosteroids (Dexamethasone (Dex)). IL-1 and TNF- but not IL-8 were downregulated in the presence of Dex under pyocyanin-induced oxidative stress conditions. Also, in IL-17 and LPS stimulated equine neutrophils, pro-inflammatory gene expression did not decrease after Dex administration. In hypoxemic conditions induced by CoCl2, gene expression of TNF- was significantly reduced by Dex, this was also true in conditions without hypoxia. In conclusion, oxidative stress, but not hypoxia, leads to insensitivity to corticosteroids, which presents a selective gene regulatory pathway (that of IL-8). Both groups of horses demonstrated a similar response indicating a reaction to dexamethasone and not related to asthmatic inflammation

A Bayesian Approach to Sensor Placement and System Health Monitoring

System health monitoring and sensor placement are areas of great technical and scientific interest. Prognostics and health management of a complex system require multiple sensors to extract required information from the sensed environment, because no single sensor can obtain all the required information reliably at all times. The increasing costs of aging systems and infrastructures have become a major concern, and system health monitoring techniques can ensure increased safety and reliability of these systems. Similar concerns also exist for newly designed systems. The main objectives of this research were: (1) to find an effective way for optimal functional sensor placement under uncertainty, and (2) to develop a system health monitoring approach with both prognostic and diagnostic capabilities with limited and uncertain information sensing and monitoring points. This dissertation provides a functional/information --based sensor placement methodology for monitoring the health (state of reliability) of a system and utilizes it in a new system health monitoring approach. The developed sensor placement method is based on Bayesian techniques and is capable of functional sensor placement under uncertainty. It takes into account the uncertainty inherent in characteristics of sensors as well. It uses Bayesian networks for modeling and reasoning the uncertainties as well as for updating the state of knowledge for unknowns of interest and utilizes information metrics for sensor placement based on the amount of information each possible sensor placement scenario provides. A new system health monitoring methodology is also developed which is: (1) capable of assessing current state of a system's health and can predict the remaining life of the system (prognosis), and (2) through appropriate data processing and interpretation can point to elements of the system that have or are likely to cause system failure or degradation (diagnosis). It can also be set up as a dynamic monitoring system such that through consecutive time steps, the system sensors perform observations and send data to the Bayesian network for continuous health assessment. The proposed methodology is designed to answer important questions such as how to infer the health of a system based on limited number of monitoring points at certain subsystems (upward propagation); how to infer the health of a subsystem based on knowledge of the health of the main system (downward propagation); and how to infer the health of a subsystem based on knowledge of the health of other subsystems (distributed propagation)

Logarithmic entropy--corrected holographic dark energy with non--minimal kinetic coupling

In this paper, we have considered a cosmological model with the non--minimal kinetic coupling terms and investigated its cosmological implications with respect to the logarithmic entropy-- corrected holographic dark energy (LECHDE). The correspondence between LECHDE in flat FRW cosmology and the phantom dark energy model with the aim to interpret the current universe acceleration is also examined.Comment: 11 pages, 2 figures; Can. J. Phys. Vol. 90, 201

Relaxation of a steep density gradient in a simple fluid: comparison between atomistic and continuum modeling

We compare dynamical nonequilibrium molecular dynamics and continuum simulations of the dynamics of relaxation of a fluid system characterized by a non uniform density profile. Results match quite well as long as the lengthscale of density nonuniformities are greater than the molecular scale (10 times the molecular size). In presence of molecular scale features some of the continuum fields (e.g. density and momentum) are in good agreement with atomistic counterparts, but are smoother. On the contrary, other fields, such at the temperature field, present very large difference with respect to reference (atomistic) ones. This is due to the limited accuracy of some of the empirical relations used in continuum models, the equation of state of the fluid in the example considered

The Relationship between Investment Opportunity, Dividend Policy and Firm Value in Companies Listed in TSE: Evidence from IRAN

The purpose of this study is to examine of relationship between investment opportunity and dividend policy and firm value. The studied group included companies listed in TSE during 2009-2013. Using systematic elimination method, 88 firms (or 440 firm-years) were selected as samples. The methodology of this study is practical descriptive correlation. The required data are collected by library method; Excel software is used to calculate data from companies. To test the hypotheses, Eviews software and panel data method are used. Findings indicate a positive significant relationship between investment opportunities and dividend policy as well as investment opportunities and firm value