A versatile Plasmodium falciparum reporter line expressing NanoLuc enables highly sensitive multi-stage drug assays

Presentation of a versatile Plasmodium falciparum dual reporter line, expressing both a fluorescent protein and NanoLuc under a constitutive promoter, that can be used to screen for novel anti-malarial drugs effective against multiple stages of the parasite.Transgenic luciferase-expressing Plasmodium falciparum parasites have been widely used for the evaluation of anti-malarial compounds. Here, to screen for anti-malarial drugs effective against multiple stages of the parasite, we generate a P. falciparum reporter parasite that constitutively expresses NanoLuciferase (NanoLuc) throughout its whole life cycle. The NanoLuc-expressing P. falciparum reporter parasite shows a quantitative NanoLuc signal in the asexual blood, gametocyte, mosquito, and liver stages. We also establish assay systems to evaluate the anti-malarial activity of compounds at the asexual blood, gametocyte, and liver stages, and then determine the 50% inhibitory concentration (IC50) value of several anti-malarial compounds. Through the development of this robust high-throughput screening system, we identify an anti-malarial compound that kills the asexual blood stage parasites. Our study highlights the utility of the NanoLuc reporter line, which may advance anti-malarial drug development through the improved screening of compounds targeting the human malarial parasite at multiple stages.Host-parasite interactio

A tailored multi-model ensemble for air traffic management: Demonstration and evaluation for the Eyjafjallajökull eruption in May 2010

High quality volcanic ash forecasts are crucial to minimize the economic impact of volcanic hazards on air traffic. Decision-making is usually based on numerical dispersion modeling with only one model realization. Given the inherent uncertainty of such approach, a multi-model multi-source term ensemble has been designed and evaluated for the Eyjafjallaj&ouml;kull eruption in May 2010. Its use for air traffic management is discussed. Two multi-model ensembles were built: the first is based on the output of four dispersion models and their own implementation of ash ejection. All a priori model source terms were constrained by observational evidence of the volcanic ash cloud top as a function of time. The second ensemble is based on the same four dispersion models, which were run with three additional source terms: (i) a source term obtained with background modeling constrained with satellite data (a posteriori source term), (ii) its lower bound estimate, and (iii) its upper bound estimate. The a priori ensemble gives valuable information about the probability of ash dispersion during the early phase of the eruption, when observational evidence is limited. However, its evaluation with observational data reveals lower quality compared to the second ensemble. While the second ensemble ash column load and ash horizontal location compare well to satellite observations, 3D ash concentrations are negatively biased. This might be caused by the vertical distribution of ash, which is too much diluted in all model runs, probably due to defaults in the a posteriori source term and vertical transport and/or diffusion processes in all models. Relevant products for the air traffic management are horizontal maps of ash concentration quantiles (median, 75 %, 99 %) at a fine-resolved flight level grid. These maps can be used for route optimization in the areas where ash does not pose a direct and urgent threat to aviation. Cost-optimized consideration of such hazards will result in much less impact on flight cancellations, reroutings, and traffic flow congestions.</p

Adaptation d'un spectromètre de masse à l'analyse des particules instables et à la mesure des pressions d'oxygène élevées

L'ouverture de la chambre d'ionisation, la stabilisation du canon à électrons en émission totale et l'adjonction d'un deuxième collecteur dans un spectromètre de masse Veeco GA 5, nous ont permis de détecter des oxydes volatils, de mesurer des potentiels d'ionisation et des pressions d'oxygène allant jusqu'à 10-6 torr

Adaptation d'un spectromètre de masse à l'analyse des particules instables et à la mesure des pressions d'oxygène élevées

With a mass spectrometer Veeco GA 5, by opening the ionization chamber, stabilization of the total emission of the electron gun and adding a second collector, we have been able to analyze volatile oxides, to measure ionization potentials and to measure oxygen pressure down to 10-6 torr.L'ouverture de la chambre d'ionisation, la stabilisation du canon à électrons en émission totale et l'adjonction d'un deuxième collecteur dans un spectromètre de masse Veeco GA 5, nous ont permis de détecter des oxydes volatils, de mesurer des potentiels d'ionisation et des pressions d'oxygène allant jusqu'à 10-6 torr

An ensemble of state-of-the-art ash dispersion models: towards probabilistic forecasts to increase the resilience of air traffic against volcanic eruptions

High-quality volcanic ash forecasts are crucial to minimize the economic impact of volcanic hazards on air traffic. Decision-making is usually based on numerical dispersion modelling with only one model realization. Given the inherent uncertainty of such an approach, a multi-model multi-source term ensemble has been designed and evaluated for the Eyjafjallajökull eruption in May 2010. Its use for flight planning is discussed. Two multi-model ensembles were built: the first is based on the output of four dispersion models and their own implementation of ash ejection