Development and evaluation of a building energy model integrated in the TEB scheme

The use of air-conditioning systems is expected to increase as a consequence of global-scale and urban-scale climate warming. In order to represent future scenarios of urban climate and building energy consumption, the Town Energy Balance (TEB) scheme must be improved. This paper presents a new building energy model (BEM) that has been integrated in the TEB scheme. BEM-TEB makes it possible to represent the energy effects of buildings and building systems on the urban climate and to estimate the building energy consumption at city scale (~10 km) with a resolution of a neighbourhood (~100 m). The physical and geometric definition of buildings in BEM has been intentionally kept as simple as possible, while maintaining the required features of a comprehensive building energy model. The model considers a single thermal zone, where the thermal inertia of building materials associated with multiple levels is represented by a generic thermal mass. The model accounts for heat gains due to transmitted solar radiation, heat conduction through the enclosure, infiltration, ventilation, and internal heat gains. BEM allows for previously unavailable sophistication in the modelling of air-conditioning systems. It accounts for the dependence of the system capacity and efficiency on indoor and outdoor air temperatures and solves the dehumidification of the air passing through the system. Furthermore, BEM includes specific models for passive systems, such as window shadowing devices and natural ventilation. BEM has satisfactorily passed different evaluation processes, including testing its modelling assumptions, verifying that the chosen equations are solved correctly, and validating the model with field data.French National Research Agency (ANR). MUSCADE project (ANR-09-VILL-003)European Commission Framework Program (FP7/2007–2013) (BRIDGE Project grant 211345

Evolution of the calcium-based intracellular signalling system

To progress our understanding of molecular evolution from a collection of well-studied genes toward the level of the cell, we must consider whole systems. Here, we reveal the evolution of an important intracellular signaling system. The calcium-signaling toolkit is made up of different multidomain proteins that have undergone duplication, recombination, sequence divergence, and selection. The picture of evolution, considering the repertoire of proteins in the toolkit of both extant organisms and ancestors, is radically different from that of other systems. In eukaryotes, the repertoire increased in both abundance and diversity at a far greater rate than general genomic expansion. We describe how calcium-based intracellular signaling evolution differs not only in rate but in nature, and how this correlates with the disparity of plants and animals

Use of a differential pressure transducer for the monitoring of soil volume change in cyclic triaxial test on unsaturated soils

A new experimental set-up using a differential pressure transducer was developed, that enables the monitoring of volume changes in cyclic triaxial tests on unsaturated soils. Calibration tests were performed in order to analyze the performance of the set-up, especially in terms of loading frequencies. Based on calibration results, a low frequency of 0.05 Hz was adopted for the tests carried out on the unsaturated loess from northern France. Five water contents were considered in the tests. The obtained results have confirmed the efficiency of the new system for volume change monitoring under cyclic loading. The effect of water content on the cyclic behavior of loess was clearly evidenced. Finally, some suggestions were made to improve the accuracy of the system

Gene Therapy in a Humanized Mouse Model of Familial Hypercholesterolemia Leads to Marked Regression of Atherosclerosis

Familial hypercholesterolemia (FH) is an autosomal codominant disorder caused by mutations in the low-density lipoprotein receptor (LDLR) gene. Homozygous FH patients (hoFH) have severe hypercholesterolemia leading to life threatening atherosclerosis in childhood and adolescence. Mice with germ line interruptions in the Ldlr and Apobec1 genes (Ldlr(-/-)Apobec1(-/-)) simulate metabolic and clinical aspects of hoFH, including atherogenesis on a chow diet.In this study, vectors based on adeno-associated virus 8 (AAV8) were used to deliver the gene for mouse Ldlr (mLDLR) to the livers of Ldlr(-/-)Apobec1(-/-) mice. A single intravenous injection of AAV8.mLDLR was found to significantly reduce plasma cholesterol and non-HDL cholesterol levels in chow-fed animals at doses as low as 3×10(9) genome copies/mouse. Whereas Ldlr(-/-)Apobec1(-/-) mice fed a western-type diet and injected with a control AAV8.null vector experienced a further 65% progression in atherosclerosis over 2 months compared with baseline mice, Ldlr(-/-)Apobec1(-/-) mice treated with AAV8.mLDLR realized an 87% regression of atherosclerotic lesions after 3 months compared to baseline mice. Immunohistochemical analyses revealed a substantial remodeling of atherosclerotic lesions.Collectively, the results presented herein suggest that AAV8-based gene therapy for FH may be feasible and support further development of this approach. The pre-clinical data from these studies will enable for the effective translation of gene therapy into the clinic for treatment of FH

Combining narratives and modelling approaches to simulate fine scale and long-term urban growth scenarios for climate adaptation

International audienceAlthough climate scientists explore the effects of climate change for 2100, it is a challenging time frame for urban modellers to foresee the future of cities. The question addressed in this paper is how to improve the existing methodologies in order to build scenarios to explore urban climate impacts in the long term and at a fine scale. This study provides a structural framework in six steps that combines narratives and model-based approaches. The results present seven scenarios of urban growth based on land use strategies and technological and socio-economic trends. These contrasted scenarios span the largest possible world of futures for the city under study. Urban maps for 2010, 2040 and 2100 were used to assess the impacts on the Urban Heat Island. The comparison of these scenarios and related outputs allowed some levers to be evaluated for their capacity to limit the increase of air temperature

Identification of the Active Form of Endothelial Lipase, a Homodimer in a Head-to-Tail Conformation*

Endothelial lipase (EL) is a member of a subfamily of lipases that act on triglycerides and phospholipids in plasma lipoproteins, which also includes lipoprotein lipase and hepatic lipase. EL has a tropism for high density lipoprotein, and its level of phospholipase activity is similar to its level of triglyceride lipase activity. Inhibition or loss-of-function of EL in mice results in an increase in high density lipoprotein cholesterol, making it a potential therapeutic target. Although hepatic lipase and lipoprotein lipase have been shown to function as homodimers, the active form of EL is not known. In these studies, the size and conformation of the active form of EL were determined. Immunoprecipitation experiments suggested oligomerization. Ultracentrifugation experiments showed that the active form of EL had a molecular weight higher than the molecular weight of a simple monomer but less than a dimer. A construct encoding a covalent head-to-tail homodimer of EL (EL-EL) was expressed and had similar lipolytic activity to EL. The functional molecular weights determined by radiation inactivation were similar for EL and the covalent homodimer EL-EL. We previously showed that EL could be cleaved by proprotein convertases, such as PC5, resulting in loss of activity. In cells overexpressing PC5, the covalent homodimeric EL-EL appeared to be more stable, with reduced cleavage and conserved lipolytic activity. A comparative model obtained using other lipase structures suggests a structure for the head-to-tail EL homodimer that is consistent with the experimental findings. These data confirm the hypothesis that EL is active as a homodimer in head-to-tail conformation