Evaluation of Mucociliary Clearance by Three Dimension Micro-CT-SPECT in Guinea Pig: Role of Bitter Taste Agonists

Different image techniques have been used to analyze mucociliary clearance (MCC) in humans, but current small animal MCC analysis using in vivo imaging has not been well defined. Bitter taste receptor (T2R) agonists increase ciliary beat frequency (CBF) and cause bronchodilation but their effects in vivo are not well understood. This work analyzes in vivo nasal and bronchial MCC in guinea pig animals using three dimension (3D) micro-CT-SPECT images and evaluates the effect of T2R agonists. Intranasal macroaggreggates of albumin-Technetium 99 metastable (MAA-Tc99m) and lung nebulized Tc99m albumin nanocolloids were used to analyze the effect of T2R agonists on nasal and bronchial MCC respectively, using 3D micro-CT-SPECT in guinea pig. MAA-Tc99m showed a nasal mucociliary transport rate of 0.36 mm/min that was increased in presence of T2R agonist to 0.66 mm/min. Tc99m albumin nanocolloids were homogeneously distributed in the lung of guinea pig and cleared with time-dependence through the bronchi and trachea of guinea pig. T2R agonist increased bronchial MCC of Tc99m albumin nanocolloids. T2R agonists increased CBF in human nasal ciliated cells in vitro and induced bronchodilation in human bronchi ex vivo. In summary, T2R agonists increase MCC in vivo as assessed by 3D micro-CT-SPECT analysis

Cigarette smoke exposure up-regulates endothelin receptor B in human pulmonary artery endothelial cells: molecular and functional consequences

BACKGROUND AND PURPOSEPulmonary arteries from smokers and chronic obstructive pulmonary disease patients show abnormal endothelium-dependent vascular reactivity. We studied the effect of cigarette smoke extract (CSE) on endothelin receptor B (ETB) expression in human pulmonary artery endothelial cells (HPAECs) and its role in endothelial dysfunction.EXPERIMENTAL APPROACHETB receptor expression was measured by real time RT-PCR, Western blot and immunofluorescence. Cell contraction, intracellular Ca2+, F/G-actin, RhoA activity, myosin light chain phosphorylation, ET, NO, thromboxane (Tx)A2 and reactive oxygen species (ROS) were measured by traction microscopy, fluorescence microscopy, phalloidin fluorescence, colorimetric assay, Western blot, elisa and DCFDA fluorescence respectively.KEY RESULTSCigarette smoke extract dose-dependently increased ETB receptor expression in HPAECs after 24 h incubation. CSE-induced ETB expression was attenuated by bosentan, the ETB receptor antagonist BQ788, the Rho kinase antagonist Y27632 and the antioxidant N-acetylcysteine. A monoclonal antibody to ET-1 prevented CSE-induced ETB receptor overexpression. Twenty-four hour exposure to ET-1 dose-dependently increased ETB receptor expression, mimicking the effect of CSE. CSE-induced ETB receptor overexpression caused greater cell contraction; increased intracellular Ca2+; increased F/G-actin and RhoA activity; increased myosin light chain phosphorylation; augmented TxA2 and ROS production; and decreased NO after acute ET-1 (10 nM). These effects were attenuated by bosentan, BQ788, Y27632 and N-acetylcysteine.CONCLUSIONS AND IMPLICATIONCigarette smoke extract induced ETB receptor overexpression by a feed forward mechanism mediated partly by ET release, promoting HPAEC dysfunction and attenuated by ETB receptor blockade, Rho kinase and ROS inhibition. These results provide support for the use of bosentan in CS-related endothelial dysfunction

Cryo-CMOS Interfaces for Large-Scale Quantum Computers

Cryogenic CMOS (cryo-CMOS) is a viable technology for the control interface of the large-scale quantum computers able to address non-trivial problems. In this paper, we demonstrate state-of-the-art cryo-CMOS circuits and systems for such application and we discuss the challenges still to be faced on the path towards practical quantum computers.AQU

Multiplexed quantum transport using commercial off-the-shelf CMOS at sub-kelvin temperatures

AbstractContinuing advancements in quantum information processing have caused a paradigm shift from research mainly focused on testing the reality of quantum mechanics to engineering qubit devices with numbers required for practical quantum computation. One of the major challenges in scaling toward large-scale solid-state systems is the limited input/output (I/O) connectors present in cryostats operating at sub-kelvin temperatures required to execute quantum logic with high fidelity. This interconnect bottleneck is equally present in the device fabrication-measurement cycle, which requires high-throughput and cryogenic characterization to develop quantum processors. Here we multiplex quantum transport of two-dimensional electron gases at sub-kelvin temperatures. We use commercial off-the-shelf CMOS multiplexers to achieve an order of magnitude increase in the number of wires. Exploiting this technology, we accelerate the development of 300 mm epitaxial wafers manufactured in an industrial CMOS fab and report a remarkable electron mobility of (3.9 ± 0.6) × 105 cm2/Vs and percolation density of (6.9 ± 0.4) × 1010 cm−2, representing a key step toward large silicon qubit arrays. We envision that the demonstration will inspire the development of cryogenic electronics for quantum information, and because of the simplicity of assembly and versatility, we foresee widespread use of similar cryo-CMOS circuits for high-throughput quantum measurements and control of quantum engineered systems.</jats:p

How holistic approaches of activity analysis in ergonomics renew training design?

International audienceThis communication presents the benefit of holistic approaches of work analysis in ergonomics and professional didactics in the field of occupational training. The research-intervention processes discussed have the originality aiming to conduct jointly learning questions, conditions of training and prevention of occupational risks. Its specificities are presented from three research-interventions in the field of aeronautics industry, agriculture and education. We stress questions that are emerging, such as the design of digital tools for training, the importance of subjective commitment at work and the identity transformations and we precise how the holistic approach advocated, based on a model of operator development that articulates mastery of tasks and work and the construction of health and safety over the long term, may be used to treat these questions.

Evaluation d’impact sur la santé et évaluation d’impact sur l’équité en santé : éventail de pratiques et questions de recherche

International audienceL’Evaluation d’Impact sur la Santé (EIS) se développe au niveau international et est encore au stade émergent en France. Elle vise à évaluer les effets positifs et négatifs potentiels d’un projet, d’un programme ou d’une politique sur la santé. L’objectif est de produire des recommandations en direction des décideurs, afin d’en maximiser les effets positifs et d’en diminuer les effets négatifs. L’EIS est un moyen particulièrement intéressant d’action sur les déterminants de la santé au-delà des comportements individuels et du système de santé. Les politiques de logement, de transport, de solidarité, économiques, etc. ont, en effet, des impacts souvent non prévus sur la santé. Au-delà des effets sur la santé, l’EIS doit aussi permettre d’apprécier la distribution de ces effets dans la population. Si la préoccupation pour l’équité en santé est centrale dans l’EIS, elle reste cependant difficilement traduite en pratique. Face à cette difficulté, des démarches d’évaluation d’impact ont été développées pour renforcer la prise en compte de l’équité à chaque étape de l’EIS ou « Equity Focused Health Impact Assessment », ou prendre en compte les impacts sur les inégalités de santé de façon spécifique. Ainsi, l’Evaluation de l’Impact sur l’Equité en Santé (EIES) semble, par exemple, particulièrement intéressante pour évaluer l’impact sur les inégalités de projets dans le champ sanitaire. L’EIS et l’EIES posent de nombreuses questions de recherche, notamment autour de la réunion, dans une même démarche, du politique, du citoyen et de l’expert. La participation des populations vulnérables potentiellement affectées par la politique évaluée est une valeur centrale de l’EIS, mais pose des questions d’acceptabilité sociale. La collaboration avec les décideurs politiques est également un enjeu majeur. Les difficultés méthodologiques, notamment de quantification des impacts, peuvent constituer des freins à la promotion de la démarche auprès des décideurs

Psychological research on homelessness in Western Europe: A review from 1970 to 2001

The rapidly growing, but still small, research literature on homelessness in Europe has often been provided by non-academics, using qualitative methods, and has been published in sources that are not widely available. This article summarizes definitions employed, observed prevalence, the socio-demographic characteristics, and the physical and mental health status of the homeless in Western Europe. Research pertaining to the causes of homelessness and the societal response to the problem are also reviewed, and the ethical and methodological questions raised by European researchers are debated. A critical analysis of the largely descriptive European research is provided, and some noteworthy exceptions are described. We also discuss a number of promising theoretical models, including those that focus on learned helplessness, social strain, and social stress