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Simple Summary Hormonal treatments, especially those used to treat menopause symptoms are known to increase breast cancer risk. It is thus necessary to identify new formulations with a better benefit/risk profile. The aim of this translational study was to evaluate the breast cancer risk associated with a combination of a natural estrogen named estetrol, with progestogens such as natural progesterone and drospirenone. Since the assessment of breast cancer risk in patients during drug development is not possible given the requirement of long-term studies in large populations, this study provides new evidence that a therapeutic dose of estetrol for menopause treatment or contraception, combined with progesterone or drospirenone, may provide a better benefit/risk profile toward breast cancer risk compared to the hormonal treatments currently available for patients. Abstract Given the unequivocal benefits of menopause hormone therapies (MHT) and combined oral contraceptives (COC), there is a clinical need for new formulations devoid of any risk of breast cancer promotion. Accumulating data from preclinical and clinical studies support that estetrol (E4) is a promising natural estrogen for MHT and COC. Nevertheless, we report here that E4 remains active on the endometrium, even under a dose that is neutral on breast cancer growth and lung metastasis dissemination. This implies that a progestogen should be combined with E4 to protect the endometrium of non-hysterectomized women from hyperplasia and cancer. Through in vivo observations and transcriptomic analyses, our work provides evidence that combining a progestogen to E4 is neutral on breast cancer growth and dissemination, with very limited transcriptional impact. The assessment of breast cancer risk in patients during the development of new MHT or COC is not possible given the requirement of long-term studies in large populations. This translational preclinical research provides new evidence that a therapeutic dose of E4 for MHT or COC, combined with progesterone or drospirenone, may provide a better benefit/risk profile towards breast cancer risk compared to hormonal treatments currently available for patients.

Priority service and its generalization, multilevel demand subscription, have been proposed in the literature as alternatives to real-time pricing in residential demand response aggregation. This paper proposes a modeling approach for designing multilevel demand subscription menus that are comparable to priority service pricing menus. The menus are designed as the equilibrium solution to a Stackelberg game, which is modeled as a bilevel optimization problem involving a vertically integrated utility and consumers. The problem is reformulated and solved as a mixed integer linear program. The menus are compared in a realistic model of the Belgian power market.

The unprecedented growth of renewable energy has led to various challenges in power system operations. Demand response can provide additional flexibility to the system in order to balance the effects of the massive integration of renewable resources. This presentation focuses on the comparison of two approaches for enabling demand response, real-time pricing and priority service pricing. This analysis is centered on the impact to consumers by assessing the effects of these schemes on their comfort and bill. We use an example based on realistic electrical consumption of a household contained in the Pecan Street dataset. The example provides an end-to-end illustration of (i) how a household selects options from a priority service menu, (ii) how devices in the household are dispatched by a home energy router, and (iii) what consumer welfare losses are relative to the golden standard of real-time pricing with or without a battery.

Semiconductor nanocrystals have been intensively investigated in the past two decades because of the size dependent properties that they exhibit. These have tremen dous technological implications. In this presentation we focus on size dependent variation in the mechanical properties of carbon nanocrystals. The interest in these materials has been raised by the recent discovery that the strength of the legendary Damascus swords stems from the fact that they are made up of carbon nanotubes as well as other forms of carbon [1]. The basic issue of the enhancement of the mechanical properties is however not well understood and is still an open question. We have carried out first principles calculations for nanocrystals of carbon using a plane wave pseudopotential implementation of density functional theory. The carbon nanocrystals have been constructed keeping the bulk-like geometry. Spherical nanocrystals are constructed in this manner, and the to get rid of the surface dangling bonds, the surface atoms are connected to hydrogens. This approach allows us to handle nanocrystals upto 20 Ao diameter. The geometry of the nanocrystals is then fully optimised. In order to evaluate the bulk modulus, we expanded and contracted the nanocrystal about its equilibrium structure and determined the ensuing bulk modulus. A modest enhancement of the bulk modulus is found with respect to the bulk value for the largest nanocrystals considered here. We attempt to understand this enhancement in terms of modifications of the properties of the nanocrystals with respect to the bulk and contrast with existing theories explaining bulk modulus trends for semiconductors [2]. [1] M. Reibold, P. Paufler, A. A. Levin, W. Kochmann, N. Pätzke and D. C. Meyer, Nature 444, 286 (2006). [2] M.L. Cohen, Phys. Rev. B 32, 7988 (1985).

Colloque avec actes et comité de lecture. Internationale.; International audience; Les matériaux nanocomposites représentent un intérêt technologique majeur. Ils bénéficient en effet à la fois de la loi des mélanges des matériaux composites et de l’apport important des nanoparticules. Mais si leur bénéfice global a été largement noté, la modélisation de leur comportement mécanique reste limitée, du fait notamment d’une maîtrise insuffisante du comportement mécanique des phases nanométriques. Les investigations ici rapportées s’intéressent aux causes et mécanismes pouvant expliquer les variations de modules élastiques relevées notamment pour des nanoparticules semi-conductrices. La bibliographie actuellement disponible sur l’élasticité des nanoparticules est dispersée et contradictoire. Nous proposons donc ici sur un échantillon ciblé de matériaux (semi-conducteurs, de structure cristallographique cubique) des investigations approfondies au moyen d’une campagne de simulation ab initio performante, nous permettant un regard assez complet quant à différents facteurs envisagés : effet de surface, de taille, d’anisotropie. Les variations du module de compressibilité sont étudiées grâce à une approche premier principe utilisant l’approximation de la densité locale. Il est apporté un soin particulier à l’indépendance de l’analyse en regard de la question des conditions aux limites appliquées. Les résultats obtenus lors d’un chargement de type « pression hydrostatique » sont confrontés à des chargements plus proches des approches expérimentales. Un regard critique est également porté sur la description théorique de la surface des nanoparticules. L’objectif global de ce projet est de déterminer précisément la relation entre taille et élasticité des nanoparticules semi-conductrices, ouvrant la voie à une modélisation plus générale du comportement mécanique des nanomatériaux.

The plastic behaviour of FCC materials is studied under cyclic tensile-compression loading at room temperature. The material is an oxygen-free high conductivity copper. The purpose of the work is to model the onset of plasticity, then the cycle by cycle evolution of the localized strain, at grain scale and at mesoscopic scale. A polycrystalline aggregate taking into account the material microstructure is developped to perform Fnite element simulations corresponding to the experiments. Finite element calculations are carried out on this mesh, using a constitutive law which takes into account the crystallographic orientation of each grain. An analysis of the localisation scheme is performed at different steps of the cyclic loading.