Progress in Atomic Fountains at LNE-SYRTE

We give an overview of the work done with the Laboratoire National de M\'etrologie et d'Essais-Syst\`emes de R\'ef\'erence Temps-Espace (LNE-SYRTE) fountain ensemble during the last five years. After a description of the clock ensemble, comprising three fountains, FO1, FO2, and FOM, and the newest developments, we review recent studies of several systematic frequency shifts. This includes the distributed cavity phase shift, which we evaluate for the FO1 and FOM fountains, applying the techniques of our recent work on FO2. We also report calculations of the microwave lensing frequency shift for the three fountains, review the status of the blackbody radiation shift, and summarize recent experimental work to control microwave leakage and spurious phase perturbations. We give current accuracy budgets. We also describe several applications in time and frequency metrology: fountain comparisons, calibrations of the international atomic time, secondary representation of the SI second based on the 87Rb hyperfine frequency, absolute measurements of optical frequencies, tests of the T2L2 satellite laser link, and review fundamental physics applications of the LNE-SYRTE fountain ensemble. Finally, we give a summary of the tests of the PHARAO cold atom space clock performed using the FOM transportable fountain.Comment: 19 pages, 12 figures, 5 tables, 126 reference

Competitive segmentation of the hippocampus and the amygdala from MRI scans

The hippocampus and the amygdala are two brain structures which play a central role in several fundamental cognitive processes. Their segmentation from Magnetic Resonance Imaging (MRI) scans is a unique way to measure their atrophy in some neurological diseases, but it is made difficult by their complex geometry. Their simultaneous segmentation is considered here through a competitive homotopic region growing method. It is driven by relational anatomical knowledge, which enables to consider the segmentation of atrophic structures in a straightforward way. For both structures, this fast algorithm gives results which are comparable to manual segmentation with a better reproducibility. Its performances regarding segmentation quality, automation and computation time, are amongst the best published data.L’hippocampe et l’amygdale sont deux structures cérébrales intervenant dans plusieurs fonctions cognitives fondamentales. Leur segmentation, à partir de volumes d’imagerie par résonance magnétique (IRM), est un outil essentiel pour mesurer leur atteinte dans certaines pathologies neurologiques, mais elle est rendue difficile par leur géométrie complexe. Nous considérons leur segmentation simultanée par une méthode de déformation homotopique compétitive de régions. Celle-ci est guidée par des connaissances anatomiques relationnelles ; ceci permet de considérer directement des structures atrophiées. Rapide, l’algorithme donne, pour les deux structures, des résultats comparables à la segmentation manuelle avec une meilleure reproductibilité. Ses performances, concernant la qualité de la segmentation, le degré d’automatisation et le temps de calcul, sont parmi les meilleures de la littérature

Atomic fountains and optical clocks at SYRTE: status and perspectives

In this article, we report on the work done with the LNE-SYRTE atomic clock ensemble during the last 10 years. We cover progress made in atomic fountains and in their application to timekeeping. We also cover the development of optical lattice clocks based on strontium and on mercury. We report on tests of fundamental physical laws made with these highly accurate atomic clocks. We also report on work relevant to a future possible redefinition of the SI second

Development of the concept of an innovative laboratory installation for the study of dust-forming surfaces

Currently, the determination of the emission rate of suspended solids from a unit of the surface area of a man-made mass at various parameters of the wind flow is not sufficiently described. The analysis of the world experience of researchers shows that existing laboratory installations have various design features that do not allow to correctly determine the mass of the dust being flapped and wind-blown. Based on the analysis results, the concept of an innovative laboratory installation for the study of dust-forming surfaces has been developed. It takes into account the influence of wind shadows, the deturbulization of an artificially created air flow, the possibility of regulating not only the flow velocity mode, but also the creation of a vacuum or disturbance in the area of sample placement, as well as the formation of a certain angle of wind flow attack relative to the surface. The concept provides for the possibility of determining the volume of dust emissions by the values of the lost dust masses in the sample and by the values of dust concentrations in the outgoing stream. The calculation of the main basic elements of the installation using the ANSYS FLUENT software package was carried out. The model and configuration of the wind tunnel have been developed and calculated, the main geometric parameters and functional elements for the possibility of use in scientific work have been determined. For practical use of the empirical roughness value of the underlying surface, its values are recommended in a wide range – from zero for the water surface to 0.44 for large cities with tall buildings and skyscrapers

Segmentation compétitive de l'hippocampe et de l'amygdale à partir de volumes IRM

L'hippocampe et l'amygdale sont deux structures cérébrales intervenant dans plusieurs fonctions cognitives fondamentales. Leur segmentation est un outil essentiel pour mesurer leur atteinte dans certaines pathologies neurologiques, mais elle est rendue difficile par leur complexité. Nous considérons leur segmentation simultanée par une méthode de déformation homotopique compétitive de régions. celle-ci est guidée par des connaissances anatomiques relationnelles, et non des a priori statistiques, pour pouvoir considérer des structures atrophiées. Rapide, l'algorithme donne des résultats satisfaisants pour les deux structures par rapport à la segmentation manuelle et à la littérature

Lipidomics Reveals Triacylglycerol Accumulation Due to Impaired Fatty Acid Flux in Opa1-Disrupted Fibroblasts

OPA1 is a dynamin GTPase implicated in mitochondrial membrane fusion. Despite its involvement in lipid remodeling, the function of OPA1 has never been analyzed by whole-cell lipidomics. We used a nontargeted, reversed-phase lipidomics approach, validated for cell cultures, to investigate OPA1-inactivated mouse embryonic fibroblasts ( Opa1 MEFs). This led to the identification of a wide range of 14 different lipid subclasses comprising 212 accurately detected lipids. Multivariate and univariate statistical analyses were then carried out to assess the differences between the Opa1 and Opa1 genotypes. Of the 212 lipids identified, 69 were found to discriminate between Opa1 MEFs and Opa1 MEFs. Among these lipids, 34 were triglycerides, all of which were at higher levels in Opa1 MEFs with fold changes ranging from 3.60 to 17.93. Cell imaging with labeled fatty acids revealed a sharp alteration of the fatty acid flux with a reduced mitochondrial uptake. The other 35 discriminating lipids included phosphatidylcholines, lysophosphatidylcholines, phosphatidylethanolamine, and sphingomyelins, mainly involved in membrane remodeling, and ceramides, gangliosides, and phosphatidylinositols, mainly involved in apoptotic cell signaling. Our results show that the inactivation of OPA1 severely affects the mitochondrial uptake of fatty acids and lipids through membrane remodeling and apoptotic cell signaling

Warburg-like effect is a hallmark of complex I assembly defects

Due to its pivotal role in NADH oxidation and ATP synthesis, mitochondrial complex I (CI) emerged as a crucial regulator of cellular metabolism. A functional CI relies on the sequential assembly of nuclear- and mtDNA-encoded subunits; however, whether CI assembly status is involved in the metabolic adaptations in CI deficiency still remains largely unknown. Here, we investigated the relationship between CI functions, its structure and the cellular metabolism in 29 patient fibroblasts representative of most CI mitochondrial diseases. Our results show that, contrary to the generally accepted view, a complex I deficiency does not necessarily lead to a glycolytic switch, i.e. the so-called Warburg effect, but that this particular metabolic adaptation is a feature of CI assembly defect. By contrast, a CI functional defect without disassembly induces a higher catabolism to sustain the oxidative metabolism. Mechanistically, we demonstrate that reactive oxygen species overproduction by CI assembly intermediates and subsequent AMPK-dependent Pyruvate Dehydrogenase inactivation are key players of this metabolic reprogramming. Thus, this study provides a two-way-model of metabolic responses to CI deficiencies that are central not only in defining therapeutic strategies for mitochondrial diseases, but also in all pathophysiological conditions involving a CI deficiency

Population gene introgression and high genome plasticity for the zoonotic pathogen Streptococcus agalactiae

The influence that bacterial adaptation (or niche partitioning) within species has on gene spillover and transmission among bacteria populations occupying different niches is not well understood. Streptococcus agalactiae is an important bacterial pathogen that has a taxonomically diverse host range making it an excellent model system to study these processes. Here we analyze a global set of 901 genome sequences from nine diverse host species to advance our understanding of these processes. Bayesian clustering analysis delineated twelve major populations that closely aligned with niches. Comparative genomics revealed extensive gene gain/loss among populations and a large pan-genome of 9,527 genes, which remained open and was strongly partitioned among niches. As a result, the biochemical characteristics of eleven populations were highly distinctive (significantly enriched). Positive selection was detected and biochemical characteristics of the dispensable genes under selection were enriched in ten populations. Despite the strong gene partitioning, phylogenomics detected gene spillover. In particular, tetracycline resistance (which likely evolved in the human-associated population) from humans to bovine, canines, seals, and fish, demonstrating how a gene selected in one host can ultimately be transmitted into another, and biased transmission from humans to bovines was confirmed with a Bayesian migration analysis. Our findings show high bacterial genome plasticity acting in balance with selection pressure from distinct functional requirements of niches that is associated with an extensive and highly partitioned dispensable genome, likely facilitating continued and expansive adaptation

Simultaneous segmentation and grading of anatomical structures for patient's classification: application to Alzheimer's Disease

Data used in the preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (www.loni.ucla.edu/ADNI).In this paper, we propose an innovative approach to robustly and accurately detect Alzheimer's disease (AD) based on the distinction of specific atrophic patterns of anatomical structures such as hippocampus (HC) and entorhinal cortex (EC). The proposed method simultaneously performs segmentation and grading of structures to efficiently capture the anatomical alterations caused by AD. Known as SNIPE (Scoring by Non-local Image Patch Estimator), the novel proposed grading measure is based on a nonlocal patch-based frame-work and estimates the similarity of the patch surrounding the voxel under study with all the patches present in different training populations. In this study, the training library was composed of two populations: 50 cognitively normal subjects (CN) and 50 patients with AD, randomly selected from the ADNI database. During our experiments, the classification accuracy of patients (CN vs. AD) using several biomarkers was compared: HC and EC volumes, the grade of these structures and finally the combination of their volume and their grade. Tests were completed in a leave-one-out framework using discriminant analysis. First, we showed that biomarkers based on HC provide better classification accuracy than biomarkers based on EC. Second, we demonstrated that structure grading is a more powerful measure than structure volume to distinguish both populations with a classification accuracy of 90%. Finally, by adding the ages of subjects in order to better separate age-related structural changes from disease-related anatomical alterations, SNIPE obtained a classification accuracy of 93%Data collection and sharing for this project were funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Insti- tute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., as well as non-profit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the U.S. Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30AG010129, K01 AG030514, and the Dana Foundation.Coupé, P.; Eskildsen, SF.; Manjón Herrera, JV.; Fonov, VS.; Collins, DL.; Alzheimer's Dis Neuroimaging (2012). Simultaneous segmentation and grading of anatomical structures for patient's classification: application to Alzheimer's Disease. NeuroImage. 59(4):3736-3747. https://doi.org/10.1016/j.neuroimage.2011.10.080S3736374759