Dynamique dans les fluides quantiques (Etude des excitations collectives dans un liquide de Fermi 2D)

L'4He et l'3He sont des systèmes modèles pour comprendre les propriétés quantiques de la matière fortement corrélée. C'est pour cette raison que plusieurs études ont été consacrées à la compréhension de leur dynamique. A basses températures où les effets quantiques jouent un rôle essentiel, les excitations élémentaires dans l'4He sont décrites par un mode collectif d'excitations: phonon-roton. Par contre pour un système d'3He la description est plus complexe, le spectre d'excitation a deux composantes: un mode collectif (zéro-son) et un continuum d'excitations incohérentes de type particule-trou. Les deux sont bien décrites par la théorie de Landau des liquides de Fermi qui trouve sa validité pour des petits vecteurs d'onde. Jusqu'à présent, on supposait que la dynamique dans les liquides de Fermi à vecteurs d'onde élevés était essentiellement incohérente. Cette thèse porte sur l'exploration, par diffusion inélastique de neutrons, des excitations collectives dans l'3He liquide 2D adsorbé sur un substrat de graphite. Un tel travail expérimental requiert trois ingrédients essentiels : un réfrigérateur à dilution afin de travailler à basses températures, un spectromètre temps de vol afin de mesurer le facteur de structure dynamique du système et un substrat solide (graphite exfolié ZYX) pour la préparation de films d'3He-2D par physisorption. Nos expériences sur ces films d'3He déposés en deuxième couche sur de l'4He solide adsorbé sur le graphite nous ont permis de faire les observations suivantes : à petit vecteur d'onde, le zéro-son est plus proche de la bande particule-trou que celui observé dans le cas de l'3He massif, tandis qu'à fort vecteur d'onde le mode collectif entre dans le continuum et réapparait de l'autre côté. Cette nouvelle branche, observée pour la première fois, est aujourd'hui décrite par la théorie dynamique à N-corps développée par nos collaborateurs de l'université Johannes Kepler de Linz, Autriche. Au cours de ce travail de thèse plusieurs techniques expérimentales ont été développées, en particulier, un réfrigérateur à dilution sans fluide cryogénique robuste adapté à des expériences de diffusion neutronique. Son optimisation a permis de réduire le temps de refroidissement de ce type de réfrigérateurs.4He and 3He are model systems for understanding quantum properties of strongly interacting matter. For this reason many studies have been devoted for the understanding of their dynamics. At low temperatures at which quantum effects play an essential role, the elementary excitations in 4He are described by a phonon-roton collective mode. For 3He, the physical description is more complicated, the spectrum has two components: collective excitations (zero-sound) and incoherent particle-hole excitations. Both are described by Landau's theory of Fermi liquids which is valid at low wave vectors. So far, it was thus believed that the dynamics at high wave vectors is essentially incoherent. This thesis is mainly concerned by exploring the collective excitations of a two dimensional 3He film adsorbed on graphite, using inelastic neutron scattering. Such an experiment has three main requirements: a dilution refrigerator in order to work at low temperatures, a time of flight spectrometer for measuring the dynamical structure factor of 3He and a solid substrate (exfoliated graphite ZYX) to obtain a two dimensional film by physical adsorption. Our investigations of the dynamics in two-dimensional 3He adsorbed on graphite preplated with 4He films have revealed important features: At low wave-vectors, the zero-sound mode is considerably depressed compared to bulk 3He. At higher wave vectors, the collective excitations branch enters the particle-hole continuum, and reappears at the lower energy branch of the continuum. This new branch, observed for the first time, is described by the dynamic many-body theory developed by our collaborators from Johannes Kepler University, Linz, Austria. During this work several low temperature techniques have been developed, in particular a robust, cryogen-free dilution refrigerator adapted to the demanding conditions of a neutron scattering experiments. Due to its efficient design, the cooling time has been considerably reduced compared to that of refrigerators of the same type developed in the past.SAVOIE-SCD - Bib.électronique (730659901) / SudocGRENOBLE1/INP-Bib.électronique (384210012) / SudocGRENOBLE2/3-Bib.électronique (384219901) / SudocSudocFranceF

Shallow Gas Hydrate Accumulations at a Nigerian Deepwater Pockmark—Quantities and Dynamics

The evolution of submarine pockmarks is often related to the ascent of fluid from the subsurface. For pockmarks located within the gas hydrate stability zone, methane oversaturation can result in the formation of gas hydrates in the sediment. An ~600 m‐wide sea floor depression in deep waters offshore Nigeria, Pockmark A, was investigated for distributions and quantities of shallow gas hydrates, origins of hydrocarbons, and time elapsed since the last major fluid ascent event. For the first time, pressure coring of shallow sediments and drilling of more than 50 m‐long cores with the sea floor drill rig MARUM‐MeBo70 were conducted in this pockmark. Unusually, high hydrate saturations of up to 51% of pore volume in the uppermost 2.5 m of sediment in the pockmark center substantiate that deepwater pockmarks are a relevant methane reservoir. Molecular and stable C and H isotopic compositions suggest that thermogenic hydrocarbons and secondary microbial methane resulting from petroleum biodegradation are injected into shallower sediments and mixed with primary microbial hydrocarbons. Two independent pore water chloride and sulfate modeling approaches suggest that a major methane migration event occurred during the past one to three centuries. A rough sea floor topography within the pockmark most likely results from combined sediment removal through ascending gas bubbles, hydrate clogging and deflection of migration pathways, gas pressure build‐up, and hydrate sea floor detachment. This study shows for the first time the chronological interrelationship between gas migration events, hydrate formation, and sea floor shaping in a deep sea pockmark

Sen2Like: Paving the Way towards Harmonization and Fusion of Optical Data

Satellite Earth Observation (EO) sensors are becoming a vital source of information for land surface monitoring. The concept of the Virtual Constellation (VC) is gaining interest within the science community owing to the increasing number of satellites/sensors in operation with similar characteristics. The establishment of a VC out of individual missions offers new possibilities for many application domains, in particular in the fields of land surface monitoring and change detection. In this context, this paper describes the Copernicus Sen2Like algorithms and software, a solution for harmonizing and fusing Landsat 8/Landsat 9 data with Sentinel-2 data. Developed under the European Union Copernicus Program, the Sen2Like software processes a large collection of Level 1/Level 2A products and generates high quality Level 2 Analysis Ready Data (ARD) as part of harmonized (Level 2H) and/or fused (Level 2F) products providing high temporal resolutions. For this purpose, we have re-used and developed a broad spectrum of data processing and analysis methodologies, including geometric and spectral co-registration, atmospheric and Bi-Directional Reflectance Distribution Function (BRDF) corrections and upscaling to 10 m for relevant Landsat bands. The Sen2Like software and the algorithms have been developed within a VC establishment framework, and the tool can conveniently be used to compare processing algorithms in combinations. It also has the potential to integrate new missions from spaceborne and airborne platforms including unmanned aerial vehicles. The validation activities show that the proposed approach improves the temporal consistency of the multi temporal data stack, and output products are interoperable with the subsequent thematic analysis processes

Consolidation of an Olfactory Memory Trace in the Olfactory Bulb Is Required for Learning-Induced Survival of Adult-Born Neurons and Long-Term Memory

Background: It has recently been proposed that adult-born neurons in the olfactory bulb, whose survival is modulated by learning, support long-term olfactory memory. However, the mechanism used to select which adult-born neurons following learning will participate in the long-term retention of olfactory information is unknown. We addressed this question by investigating the effect of bulbar consolidation of olfactory learning on memory and neurogenesis. Methodology/Principal Findings: Initially, we used a behavioral ecological approach using adult mice to assess the impact of consolidation on neurogenesis. Using learning paradigms in which consolidation time was varied, we showed that a spaced (across days), but not a massed (within day), learning paradigm increased survival of adult-born neurons and allowed long-term retention of the task. Subsequently, we used a pharmacological approach to block consolidation in the olfactory bulb, consisting in intrabulbar infusion of the protein synthesis inhibitor anisomycin, and found impaired learning and no increase in neurogenesis, while basic olfactory processing and the basal rate of adult-born neuron survival remained unaffected. Taken together these data indicate that survival of adult-born neurons during learning depends on consolidation processes taking place in the olfactory bulb. Conclusion/Significance: We can thus propose a model in which consolidation processes in the olfactory bulb determine both survival of adult-born neurons and long-term olfactory memory. The finding that adult-born neuron survival durin

Clinical, Biological and Genetic Analysis of Prepubertal Isolated Ovarian Cyst in 11 Girls

BACKGROUND: The cause of isolated gonadotropin-independent precocious puberty (PP) with an ovarian cyst is unknown in the majority of cases. Here, we describe 11 new cases of peripheral PP and, based on phenotypes observed in mouse models, we tested the hypothesis that mutations in the GNAS1, NR5A1, LHCGR, FSHR, NR5A1, StAR, DMRT4 and NOBOX may be associated with this phenotype. METHODOLOGY/PRINCIPAL FINDINGS: 11 girls with gonadotropin-independent PP were included in this study. Three girls were seen for a history of prenatal ovarian cyst, 6 girls for breast development, and 2 girls for vaginal bleeding. With one exception, all girls were seen before 8 years of age. In 8 cases, an ovarian cyst was detected, and in one case, suspected. One other case has polycystic ovaries, and the remaining case was referred for vaginal bleeding. Four patients had a familial history of ovarian anomalies and/or infertility. Mutations in the coding sequences of the candidate genes GNAS1, NR5A1, LHCGR, FSHR, NR5A1, StAR, DMRT4 and NOBOX were not observed. CONCLUSIONS/SIGNIFICANCE: Ovarian PP shows markedly different clinical features from central PP. Our data suggest that mutations in the GNAS1, NR5A1, LHCGR, FSHR StAR, DMRT4 and NOBOX genes are not responsible for ovarian PP. Further research, including the identification of familial cases, is needed to understand the etiology of ovarian PP

The clinical and genetic spectrum of autosomal-recessive TOR1A-related disorders.

In the field of rare diseases, progress in molecular diagnostics led to the recognition that variants linked to autosomal-dominant neurodegenerative diseases of later onset can, in the context of biallelic inheritance, cause devastating neurodevelopmental disorders and infantile or childhood-onset neurodegeneration. TOR1A-associated arthrogryposis multiplex congenita 5 (AMC5) is a rare neurodevelopmental disorder arising from biallelic variants in TOR1A, a gene that in the heterozygous state is associated to torsion dystonia-1 (DYT1 or DYT-TOR1A), an early-onset dystonia with reduced penetrance. While 15 individuals with TOR1A-AMC5 have been reported (less than 10 in detail), a systematic investigation of the full disease-associated spectrum has not been conducted. Here, we assess the clinical, radiological and molecular characteristics of 57 individuals from 40 families with biallelic variants in TOR1A. Median age at last follow-up was 3 years (0-24 years). Most individuals presented with severe congenital flexion contractures (95%) and variable developmental delay (79%). Motor symptoms were reported in 79% and included lower limb spasticity and pyramidal signs, as well as gait disturbances. Facial dysmorphism was an integral part of the phenotype, with key features being a broad/full nasal tip, narrowing of the forehead and full cheeks. Analysis of disease-associated manifestations delineated a phenotypic spectrum ranging from normal cognition and mild gait disturbance to congenital arthrogryposis, global developmental delay, intellectual disability, absent speech and inability to walk. In a subset, the presentation was consistent with fetal akinesia deformation sequence with severe intrauterine abnormalities. Survival was 71% with higher mortality in males. Death occurred at a median age of 1.2 months (1 week - 9 years) due to respiratory failure, cardiac arrest, or sepsis. Analysis of brain MRI studies identified non-specific neuroimaging features, including a hypoplastic corpus callosum (72%), foci of signal abnormality in the subcortical and periventricular white matter (55%), diffuse white matter volume loss (45%), mega cisterna magna (36%) and arachnoid cysts (27%). The molecular spectrum included 22 distinct variants, defining a mutational hotspot in the C-terminal domain of the Torsin-1A protein. Genotype-phenotype analysis revealed an association of missense variants in the 3-helix bundle domain to an attenuated phenotype, while missense variants near the Walker A/B motif as well as biallelic truncating variants were linked to early death. In summary, this systematic cross-sectional analysis of a large cohort of individuals with biallelic TOR1A variants across a wide age-range delineates the clinical and genetic spectrum of TOR1A-related autosomal-recessive disease and highlights potential predictors for disease severity and survival

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Regulation by learning of adult neurogenesis in the olfactory bulb and role of newborn neurons

Le bulbe olfactif est le siège d’une neurogenèse adulte permanente. Le nombre de nouveaux neurones issus de cette neurogenèse adulte est modulé par l’apprentissage, ce qui suggère un rôle des néoneurones dans la mémoire olfactive. Au cours de ce travail, nous avons montré que l’apprentissage olfactif associatif recrute des nouveaux neurones granulaires dans des régions de la couche granulaire du bulbe olfactif spécifiques à l’odeur apprise. Nous avons également mis en évidence un lien entre la force de l’apprentissage olfactif, sa rétention et la modulation de la neurogenèse qui en résulte. En bloquant la neurogenèse bulbaire à l’aide d’un agent antimitotique nous avons montré que les nouveaux interneurones ne sont pas indispensables à l’acquisition d’une tâche olfactive associative, mais le sont pour sa rétention à long terme. Puis, en utilisant une approche comportementale, nous avons aboli l’association olfactive acquise lors d’un apprentissage et nous avons observé que les nouveaux neurones initialement sauvés dans le bulbe olfactif par cet apprentissage disparaissaient prématurément, confirmant ainsi leur rôle dans le support de la mémoire olfactive. Enfin, nous avons montré que suite à un apprentissage olfactif, une régulation locale de la mort cellulaire est mise en jeu qui pourrait être à l’origine de la sélection des néoneurones dans les régions traitant l’odeur apprise. Dans l’ensemble nos données indiquent un rôle crucial des neurones formés à l’âge adulte dans le bulbe olfactif dans la mémoire olfactiveAdult-born neurons are added to the mammalian olfactory bulb, and their number is modulated by learning suggesting that they could play a role in olfactory memory. In this work, we demonstrate that retrieval of an associative olfactory task recruits newborn neurons in odor-specific areas of the olfactory bulb and in a manner that depends on the strength of learning. By blocking neurogenesis during this olfactory task, we then demonstrate that acquisition is not dependent on neurogenesis while long-term retention of the task is abolished by neurogenesis blockade. In a second part, using an ecological approach, we show that behaviorally breaking a previously learned odor-reward association prematurely suppresses newborn neurons selected to survive during initial learning. Our results indicate that the newborn neurons saved by olfactory learning die when the odor looses its associative value, thus confirming that these newborn neurons support the memory trace. Finally, during and after learning, cell death and BrdU positive cells were mapped in the granule cell layer. We find that regions showing high BrdU-positive cell density exhibit the lowest rate of cell death indicating local regulation of cell death shaping the spatial distribution of newborn neurons in the granule cell layer of the olfactory bulb. Taken together, our findings reveal the crucial role of bulbar adult born neurons in olfactory memor

Evaluation and design of heteropolycompound catalysts for the selective oxidation of isobutane into methacrylic acid

International audienc

Taurine increases hippocampal neurogenesis in aging mice

Aging is associated with increased inflammation and reduced hippocampal neurogenesis, which may in turn contribute to cognitive impairment. Taurine is a free amino acid found in numerous diets, with anti-inflammatory properties. Although abundant in the young brain, the decrease in taurine concentration with age may underlie reduced neurogenesis. Here, we assessed the effect of taurine on hippocampal neurogenesis in middle-aged mice. We found that taurine increased cell proliferation in the dentate gyrus through the activation of quiescent stem cells, resulting in increased number of stem cells and intermediate neural progenitors. Taurine had a direct effect on stem/progenitor cells proliferation, as observed in vitro, and also reduced activated microglia. Furthermore, taurine increased the survival of newborn neurons, resulting in a net increase in adult neurogenesis. Together, these results show that taurine increases several steps of adult neurogenesis and support a beneficial role of taurine on hippocampal neurogenesis in the context of brain aging