Matter-wave laser Interferometric Gravitation Antenna (MIGA): New perspectives for fundamental physics and geosciences

The MIGA project aims at demonstrating precision measurements of gravity with cold atom sensors in a large scale instrument and at studying the associated applications in geosciences and fundamental physics. The first stage of the project (2013-2018) will consist in building a 300-meter long optical cavity to interrogate atom interferometers and will be based at the low noise underground laboratory LSBB in Rustrel, France. The second stage of the project (2018-2023) will be dedicated to science runs and data analyses in order to probe the spatio-temporal structure of the local gravity field of the LSBB region, a site of high hydrological interest. MIGA will also assess future potential applications of atom interferometry to gravitational wave detection in the frequency band $\sim 0.1-10$ Hz hardly covered by future long baseline optical interferometers. This paper presents the main objectives of the project, the status of the construction of the instrument and the motivation for the applications of MIGA in geosciences. Important results on new atom interferometry techniques developed at SYRTE in the context of MIGA and paving the way to precision gravity measurements are also reported.Comment: Proceedings of the 50th Rencontres de Moriond "100 years after GR", La Thuile (Italy), 21-28 March 2015 - 10 pages, 5 figures, 23 references version2: added references, corrected typo

The effects of juridification on states exiting international institutions

This article complements the doctrine of termination of membership by arguing that at times international organizations (IOs) can still exert considerable normative effects on states that withdraw or express the intent to withdraw from them. We capture this continuing influence, which can collide with the exiting state’s intended goal of regaining control over specific issues, with a theoretical framework based on juridification as a socio-legal concept of systems theory in the international legal context. The aim is to explain the endogenous process of legal growth within the IO via bureaucratization and expert rule, which eventually affects the norms of the wider legal regime where the IO operates. With three case studies of IO exits, we illustrate the continuation of normative structures promoted directly or indirectly by the IO, according to two legal techniques of juridification: third-party interpretation on the one hand, and the extended reach of norms and processes through the work of non-state actors on the other. Overall, widening the theoretical perspective on state exits under systems theory can lead to more complete judgements on the tensions between domestic and supranational systems in the expansion of global normative regimes

Albums de littérature de jeunesse et mathématiques. L'exemple des albums codés: typologie, savoirs et tâches

National audienceL'album codé fait partie du paysage de littérature de jeunesse. Nous montrons ici l'intérêt de l'étude d'albums codés en classe pour des apprentissages en mathématiques. Afin de situer l'album codé, nous présentons une typologie des albums de littérature de jeunesse pour la classe de mathématiques. Ensuite, nous analysons les savoirs mathématiques sous-jacents à l'étude d'albums codés (codage, symbolisme, logique en particulier) en montrant l'intérêt pour l'apprentissage de la schématisation en résolution de problèmes. Nous présentons également des pistes d'activités pour la classe qui comprennent des tâches de lecture et des tâches de création d'albums codés

Nested R^\widehat R: Assessing the convergence of Markov chain Monte Carlo when running many short chains

The growing availability of hardware accelerators such as GPUs has generated interest in Markov chains Monte Carlo (MCMC) workflows which run a large number of chains in parallel. Each chain still needs to forget its initial state but the subsequent sampling phase can be almost arbitrarily short. To determine if the resulting short chains are reliable, we need to assess how close the Markov chains are to convergence to their stationary distribution. The $\widehat R$ statistic is a battle-tested convergence diagnostic but unfortunately can require long chains to work well. We present a nested design to overcome this challenge, and introduce tuning parameters to control the reliability, bias, and variance of convergence diagnostics

Preferential binding of a G-quadruplex ligand to human chromosome ends

The G-overhangs of telomeres are thought to adopt particular conformations, such as T-loops or G-quadruplexes. It has been suggested that G-quadruplex structures could be stabilized by specific ligands in a new approach to cancer treatment consisting in inhibition of telomerase, an enzyme involved in telomere maintenance and cell immortality. Although the formation of G-quadruplexes was demonstrated in vitro many years ago, it has not been definitively demonstrated in living human cells. We therefore investigated the chromosomal binding of a tritiated G-quadruplex ligand, (3)H-360A (2,6-N,N′-methyl-quinolinio-3-yl)-pyridine dicarboxamide [methyl-(3)H]. We verified the in vitro selectivity of (3)H-360A for G-quadruplex structures by equilibrium dialysis. We then showed by binding experiments with human genomic DNA that (3)H-360A has a very potent selectivity toward G-quadruplex structures of the telomeric 3′-overhang. Finally, we performed autoradiography of metaphase spreads from cells cultured with (3)H-360A. We found that (3)H-360A was preferentially bound to chromosome terminal regions of both human normal (peripheral blood lymphocytes) and tumor cells (T98G and CEM1301). In conclusion, our results provide evidence that a specific G-quadruplex ligand interacts with the terminal ends of human chromosomes. They support the hypothesis that G-quadruplex ligands induce and/or stabilize G-quadruplex structures at telomeres of human cells

Drivers of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) in nine southern African countries: a modelling study.

INTRODUCTION: The rise of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTI) threatens antiretroviral therapy's long-term success (ART). NNRTIs will remain an essential drug for the management of HIV-1 due to safety concerns associated with integrase inhibitors. We fitted a dynamic transmission model to historical data from 2000 to 2018 in nine countries of southern Africa to understand the mechanisms that have shaped the HIV-1 epidemic and the rise of pretreatment NNRTI resistance. METHODS: We included data on HIV-1 prevalence, ART coverage, HIV-related mortality, and survey data on pretreatment NNRTI resistance from nine southern Africa countries from a systematic review, UNAIDS and World Bank. Using a Bayesian hierarchical framework, we developed a dynamic transmission model linking data on the HIV-1 epidemic to survey data on NNRTI drug resistance in each country. We estimated the proportion of resistance attributable to unregulated, off-programme use of ART. We examined each national ART programme's vulnerability to NNRTI resistance by defining a fragility index: the ratio of the rate of NNRTI resistance emergence during first-line ART over the rate of switching to second-line ART. We explored associations between fragility and characteristics of the health system of each country. RESULTS: The model reliably described the dynamics of the HIV-1 epidemic and NNRTI resistance in each country. Predicted levels of resistance in 2018 ranged between 3.3% (95% credible interval 1.9-7.1) in Mozambique and 25.3% (17.9-33.8) in Eswatini. The proportion of pretreatment NNRTI resistance attributable to unregulated antiretroviral use ranged from 6% (2-14) in Eswatini to 64% (26-85) in Mozambique. The fragility index was low in Botswana (0.01; 0.0-0.11) but high in Namibia (0.48; 0.16-10.17), Eswatini (0.64; 0.23-11.8) and South Africa (1.21; 0.83-9.84). The combination of high fragility of ART programmes and high ART coverage levels was associated with a sharp increase in pretreatment NNRTI resistance. CONCLUSIONS: This comparison of nine countries shows that pretreatment NNRTI resistance can be controlled despite high ART coverage levels. This was the case in Botswana, Mozambique, and Zambia, most likely because of better HIV care delivery, including rapid switching to second-line ART of patients failing first-line ART