Label-free quantitative proteomics in Candida yeast species: technical and biological replicates to assess data reproducibility

International audienceObjective: Label-free quantitative proteomics has emerged as a powerful strategy to obtain high quality quantitative measures of the proteome with only a very small quantity of total protein extract. Because our research projects were requiring the application of bottom-up shotgun mass spectrometry proteomics in the pathogenic yeasts Candida glabrata and Candida albicans, we performed preliminary experiments to (i) obtain a precise list of all the proteins for which measures of abundance could be obtained and (ii) assess the reproducibility of the results arising respectively from biological and technical replicates. Data description: Three time-courses were performed in each Candida species, and an alkaline pH stress was induced for two of them. Cells were collected 10 and 60 min after stress induction and proteins were extracted. Samples were analysed two times by mass spectrometry. Our final dataset thus comprises label-free quantitative prot-eomics results for 24 samples (two species, three time-courses, two time points and two runs of mass spectrometry). Statistical procedures were applied to identify proteins with differential abundances between stressed and unstressed situations. Considering that C. glabrata and C. albicans are human pathogens, which face important pH fluctuations during a human host infection, this dataset has a potential value to other researchers in the field. which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/ publi cdoma in/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Objective Studying proteome dynamics is a key step in systems biology projects. In this context, label-free bottom-up shotgun MS-based proteomics produces quantitative analyses of proteomes. This technique has emerged from significant improvements achieved by mass spectrom-etry (MS) instrumentation, chromatographic separation systems and a stronger correlation between the relative measured ion intensity and the original molecule abundance in the electrospray ionization process [1-3]. Members of our research team were involved in functional genomics studies in pathogenic yeasts Candida glabrata and Candida albicans [4-8]. We observed how the experimental design is a critical step to empower the statistics used to assess the robustness of the results. "How many replicates is enough?" is certainly one of the most frequently asked questions in wet laboratories. This question is especially critical in situations where the experiments are expensive, and/or the preparation of the biological samples is challenging. Here, our objective was to assess the robustness of the results arising from label-free bottom-up shotgun MS-based proteom-ics performed in C. glabrata and C. albicans, in case of technical and biological replicates. If the importance of biological replicates was indisputable when we starte

Observations regarding 'quality of life' and 'comfort with food' after bariatric surgery: comparison between laparoscopic adjustable gastric banding and sleeve gastrectomy.

International audienceBACKGROUND: Although laparoscopic adjustable gastric banding (LAGB) and laparoscopic sleeve gastrectomy (LSG) are coexisting first-choice restrictive procedures for bariatric surgery candidates, it is possible, given their different modes of action, that these procedures have different effects on quality of life (QOL). We hypothesized that improvement of QOL and comfort with food could be better with LSG compared to LAGB. METHODS: This cohort study included 131 obese patients who had either LAGB (n = 102) or LSG (n = 29). Patients were assessed during preoperative and at 6- and 12-month postoperative visits. Five QOL dimensions were assessed using the 'Quality of Life, Obesity and Dietetics' rating scale: physical impact, psycho-social impact, impact on sex life, comfort with food and diet experience. We compared QOL evolution between LAGB and LSG using linear mixed models adjusted for gender and body mass index at each visit. RESULTS: Excess weight loss was 28.4 ± 14.7% and 34.8 ± 18.4% for LAGB and 35.7 ± 14.3% and 43.8 ± 17.8% for LSG at 6 and 12 months postoperatively, respectively. Both LAGB and LSG provided significant improvement in the physical, psycho-social, sexual and diet experience dimensions of QOL. LSG was associated with better improvement than LAGB in short-term (6-month) comfort with food. CONCLUSIONS: Our results add further evidence to the benefit of LSG and LAGB in obesity management. Within the first year of follow-up, there is no lasting difference in the comfort with food dimension between LSG and LABG

Using bi-fluxon tunneling to protect the Fluxonium qubit

Encoding quantum information in quantum states with disjoint wave-function support and noise insensitive energies is the key behind the idea of qubit protection. While fully protected qubits are expected to offer exponential protection against both energy relaxation and pure dephasing, simpler circuits may grant partial protection with currently achievable parameters. Here, we study a fluxonium circuit in which the wave-functions are engineered to minimize their overlap while benefiting from a first-order-insensitive flux sweet spot. Taking advantage of a large superinductance ($L\sim 1~\mu \rm{H}$), our circuit incorporates a resonant tunneling mechanism at zero external flux that couples states with the same fluxon parity, thus enabling bifluxon tunneling. The states $|0\rangle$ and $|1\rangle$ are encoded in wave-functions with parities 0 and 1, respectively, ensuring a minimal form of protection against relaxation. Two-tone spectroscopy reveals the energy level structure of the circuit and the presence of $4 \pi$ quantum-phase slips between different potential wells corresponding to $m=\pm 1$ fluxons, which can be precisely described by a simple fluxonium Hamiltonian or by an effective bifluxon Hamiltonian. Despite suboptimal fabrication, the measured relaxation ($T_1 = 177\pm 3 ~\mu s$) and dephasing ($T_2^E = 75\pm 5~\mu \rm{s}$) times not only demonstrate the relevance of our approach but also opens an alternative direction towards quantum computing using partially-protected fluxonium qubits.Comment: 14 pages, 12 figure

: Rapport final du projet ANR 2006-2008 (annexes scientifiques)

As a 24 months platform project, Lutin Game Lab was designed for making academic researchers and game companies cooperate in order to reach a new stage in the process of game quality assessment, before and after they are available on the market. The project was organized along 6 WP, all of them having fulfilled their specific goals, although we had to endure some delays due to the time required for settling the technical platform and due to the lack of time available for the companies to collaborate during the year 2008.The project results can be summed up in 4 different aspects:* A platform is now open to companies as well as to academic labs, equipped with all the devices and the softwares needed for conducting evaluation of gamers behaviour, including all game platforms, excepted for on-line games. Two eye-tracking devices and sensorial analysis tools are part of the equipment of the platform. This technical platform is operated by the UMS CNRS Lutin at the Cité des Sciences in Paris.* The methods created for analyzing the existing games and the ones in development phase were scientifically validated and adapted to the requirements of companies (time needed, display of the results, prerequisites and modes of cooperation with developers). These methods have not yet been tested in the developing phase of real games except for one of them (QRC), due to the workload of developers during this period. * The methods are the following:o Artificial expert for the prediction of gamers judgments based on a description framework of game properties. A subjective evaluation database has been designed using the data collected during the tests of 240 gamers (experts and naives) expressing judgments in a 11 items questionnaire, using the data from an objective description of game properties and the data obtained through an "objectivated subjective" description of games qualities retrieved from experts who designed and filled up a framework of 56 items per game genre (126 iterations). This expert allows companies to test their games while they are still in the design phase through the description framework in order to predict the judgments from the gamers and to optimize their various choices in game design using the 15 fuzzy models selected for each game genre.o Usability testing method adapted specifically to videogames (Quick Reality Check, QRC), based on a test protocol involving 10 gamers, on logs tracking the gamer behaviour (implemented by the developers in their prototype), on synthetic visualization tools displaying the results, and on remediation method in cooperation with game designers (game doctor). This method focuses on ergonomics features and acceptability issues.o An eyetracking method dedicated to gamers behaviour analysis. It helps to explore in-depth the areas or phases of concern discovered with the previous method. This allows the game designers to reshape some features in the interfaces and to compare their results with the patterns of each game genre that the research was able to modelize.o A method for tracking emotional states during the game, through sensors placed on the gamers bodies, in order to explore and better understand the reasons of the problems pointed out by the other methods. This is a much more innovative methodology and field of research and this explains the need for focusing on specific features in order to validate the whole framework with the existing scientific state of the art. This is a very promising field and a very attractive one for the game designers, one that would require much more research efforts.o An artificial expert providing diagnosis through the gathering of every piece of data collected during the various tests, with added results from on line questionnaires. The expert software provides an integrative view of the results for a specific game and can refer it to the various models available in the literature.* In the gameplay evaluation field, the project evolves from a review of literature to the design of a wiki open to the community of game designers, which aim is to create de knowledge database about gameplay qualities for each game genre. The wiki includes a list of rules shared by the community and examples of games displaying the uses of these rules, extracted from a corpus of the most famous games. The database can be enriched with new cases, rules can be adapted, through the revision process of the wiki which includes collective validation. Developers can access the wiki as a resource for validation of their choices.In brief, the platform offers a set of devices, a set of methods, available for the game industry, operated by Lutin experts, and a website including the wiki. Lutin Game lab platform represents an European reference center in the field of game evaluation. Lutin plans to design a quality label for games that could be used before the games are placed on the market. LUtin Game Lab requires a new research project devoted to the extension of the methods to on-line games (Lutin Game Lab on line). The next year will be devoted to dissemination and validation on real game being developed.Le projet annonçait ainsi ses objectifs en 2006 : " Lutin Game Lab, projet de plate-forme de 24 mois, se propose de fédérer les forces de recherche académiques et de développement des entreprises pour faire faire un pas significatif aux méthodologies d'évaluation de la qualité d'un jeu vidéo fini ou en cours de développement. " Le travail a comporté 6 sous -projets qui ont tous été menés à bien conformément au programme prévu avec des décalages non négligeables dus notamment au temps nécessaire au montage technique de la plate-forme et à la difficulté des entreprises à dégager du temps pour leur collaboration au moment voulu alors qu'elles sont sous haute pression concurrentielle. Le bilan du projet peut se résumer en 4 points : * il existe désormais en France une plate-forme ouverte aux entreprises et aux laboratoires, équipée de tous les matériels et logiciels nécessaires pour faire l'évaluation des comportements des joueurs de jeux vidéo, toutes plates-formes de jeu confondus, à l'exception des jeux multi joueurs en ligne. Cette plate-forme technique, comportant notamment des dispositifs d'oculométrie opérationnels de divers types, et des dispositifs d'analyse sensorielle, est opérationnelle en permanence dans le cadre des missions de l'UMS CNRS Lutin 2803 à la Cité des Sciences. * Les méthodes élaborées pour l'analyse des jeux existants et des jeux en cours de développement ont été validées scientifiquement et opérationnellement selon les critères des entreprises de jeux vidéo (délais, présentation des résultats, prérequis et formes de coopération). Ces méthodes devront cependant être validées en situation de jeux en cours de développement car les délais de coopération avec les entreprises n'ont permis de mettre en œuvre cette étape que pour une seule de ces méthodes (dite QRC)* Les méthodes comportent 5 volets : o un expert artificiel prédictif qui permet de prédire l'appréciation subjective des joueurs à partir d'une description formalisée des propriétés d'un jeu. Une base de données d'évaluation subjective a été constituée à partir de tests réalisés par 240 joueurs de tous niveaux et de leur appréciation subjective (11 items), à partir de description des propriétés objectives du jeu (106 items) et à partir d'une description subjective objectivée des qualités d'un jeu par genre (56 items par genre de jeu) et de 126 itérations de cette grille réalisée à partir d'une extraction d'expertise auprès de game designers et élèves game designers. Il est proposé aux entreprises de jeux vidéo de tester leur jeu dans une phase amont du développement pour prédire les scores de leurs jeux et ensuite optimiser les choix effectués, en exploitant les 15 modèles en logique floue sélectionnés pour chaque genre de jeu. o Une méthode en usability (Quick Reality Check) qui comporte un protocole de tests auprès de 10 joueurs minimum, des outils de suivi des déplacements par implantation de logs dans le jeu en cours de développement, de modes de visualisation synthétique des résultats et une méthode de correction associant les développeurs (Game Doctor). Cette méthode traite avant tout les questions d'ergonomie et d'acceptabilité. o Une méthode de suivi du regard des joueurs permettant d'affiner les résultats de la méthode précédente, sur des zones ou des phases problématiques pour repositionner le game design et l'ergonomie en fonction des patterns, ou signatures, identifiés par la recherche pour chaque type de jeux. o Une méthode de suivi de l'engagement émotionnel durant le jeu à partir de capteurs d'analyse sensorielle placés sur les joueurs, permettant là aussi d'affiner la recherche éventuelle de problèmes pour des phases plus précises selon les stratégies du game designer. Cette méthode est la plus innovante en termes de recherche et nos résultats restent donc limités à certains points précis qui sont cependant très prometteurs et nécessiteraient des travaux supplémentaires.o Un expert artificiel diagnostic permettant de traiter et de synthétiser toutes les données recueillies lors des tests des autres méthodes, de les compléter par des questionnaires en ligne si nécessaire et de les rapporter à des modèles issus de la littérature pour proposer un diagnostic intégré sur les qualités d'un jeu donné. * Dans le domaine du gameplay, le projet a évolué à partir d'un recensement exhaustif de la littérature sur la mise en place d'un wiki permettant à toute la communauté des développeurs de constituer une base de connaissances partagées sur les qualités du gameplay selon les genres. Ce wiki comporte un énoncé de règles reconnues par la communauté mais aussi leur exemplification à partir d'un corpus de jeux parmi les plus connus dans tous les genres. La base peut être enrichie par d'autres études de cas, les règles peuvent être affinées, et les développeurs peuvent la consulter en tant que de besoin pour valider les choix qu'ils effectuent. La mise en place de la plate-forme comporte ainsi une partie d'équipements localisés à la cité des sciences, une expertise en méthodes, directement opérationnelles et proposées déjà aux entreprises par les différents partenaires membres de Lutin, et un site collaboratif qui rassemble la communauté autour de son expertise propre. Lutin Game Lab peut ainsi prétendre devenir un centre de références européen en termes de méthodes qualité pour les jeux vidéo et nous prévoyons de travailler à proposer un label pour qualifier les jeux vidéo avant leur mise sur le marché, ainsi qu'à une extension de ses compétences pour les jeux vidéo multi joueurs en ligne (Lutin Game Lab on line). Le projet a ainsi atteint son objectif général ainsi que ses objectifs particuliers, à l'exception du temps de validation encore nécessaire auprès des entreprises qui n'a pu être pris en compte durant le projet

VCSEL Based on InAs Quantum-Dashes With a Lasing Operation Over a 117-nm Wavelength Span

International audienceWe report an InP based vertical cavity surface emitting laser (VCSEL) achieving a lasing operation between 1529 and 1646 nm. This optically-pumped VCSEL includes a wide-gain bandwidth active region based on InAs quantum dashes and wideband dielectric Bragg mirrors. Based on a wedge microcavity design, we obtain a spatial dependence of the resonant wavelength along the wafer, enabling thus to monitor the gain material bandwidth. We demonstrate a 117 nm continuous wavelength variation of the VCSEL emission, a consequence of the important and wide gain afforded by the use of optimized quantum dashes

VCSEL à fils quantiques présentant une émission laser de 1647 à 1542 nm

National audienceLes lasers à cavité verticale émettant par la surface (VCSEL) présentent de grands intérêts pour des applications variées (télécommunication, capteurs, ..), d'autant plus si ces derniers s'avèrent stables et accordables en longueur d'onde. Au-delà du procédé technologique utilisé, cette dernière propriété est aussi très limitée par l'extension du gain spectral de la zone active. Nous présentons ici la réalisation d'un VCSEL émettant à 1.55 μm, et présentant une émission laser sur une plage en longueur d'onde de 105 nm

VCSEL à fils quantiques présentant une émission laser de 1647 à 1542 nm

National audienceLes lasers à cavité verticale émettant par la surface (VCSEL) présentent de grands intérêts pour des applications variées (télécommunication, capteurs, ..), d'autant plus si ces derniers s'avèrent stables et accordables en longueur d'onde. Au-delà du procédé technologique utilisé, cette dernière propriété est aussi très limitée par l'extension du gain spectral de la zone active. Nous présentons ici la réalisation d'un VCSEL émettant à 1.55 μm, et présentant une émission laser sur une plage en longueur d'onde de 105 nm

Revealing the finite-frequency response of a bosonic quantum impurity

Quantum impurities are ubiquitous in condensed matter physics and constitute the most stripped-down realization of many-body problems. While measuring their finite-frequency response could give access to key characteristics such as excitations spectra or dynamical properties, this goal has remained elusive despite over two decades of studies in nanoelectronic quantum dots. Conflicting experimental constraints of very strong coupling and large measurement bandwidths must be met simultaneously. We get around this problem using cQED tools, and build a precisely characterized quantum simulator of the boundary sine-Gordon model, a non-trivial bosonic impurity problem. We succeeded to fully map out the finite frequency linear response of this system. Its reactive part evidences a strong renormalisation of the nonlinearity at the boundary in agreement with non-perturbative calculations. Its dissipative part reveals a dramatic many-body broadening caused by multi-photon conversion. The experimental results are matched quantitatively to a resummed diagrammatic calculation based on a microscopically calibrated model. Furthermore, we push the device into a regime where diagrammatic calculations break down, which calls for more advanced theoretical tools to model many-body quantum circuits. We also critically examine the technological limitations of cQED platforms to reach universal scaling laws. This work opens exciting perspectives for the future such as quantifying quantum entanglement in the vicinity of a quantum critical point or accessing the dynamical properties of non-trivial many-body problems.Comment: 39 pages, 14 figure

A SAP30 Complex Inhibits IFN-β Expression in Rift Valley Fever Virus Infected Cells

Rift Valley fever virus (RVFV) nonstructural protein NSs acts as the major determinant of virulence by antagonizing interferon β (IFN-β) gene expression. We demonstrate here that NSs interacts with the host protein SAP30, which belongs to Sin3A/NCoR/HDACs repressor complexes and interacts with the transcription factor YY1 that regulates IFN-β gene expression. Using confocal microscopy and chromatin immunoprecipitation, we show that SAP30, YY1, and Sin3A-associated corepressor factors strongly colocalize with nuclear NSs filaments and that NSs, SAP30 and Sin3A-associated factors are recruited on the IFN-β promoter through YY1, inhibiting CBP recruitment, histone acetylation, and transcriptional activation. To ascertain the role of SAP30, we produced, by reverse genetics, a recombinant RVFV in which the interacting domain in NSs was deleted. The virus was unable to inhibit the IFN response and was avirulent for mice. We discuss here the strategy developed by the highly pathogenic RVFV to evade the host antiviral response, affecting nuclear organization and IFN-β promoter chromatin structure

Continuous Monitoring of Cerebral Autoregulation in Children Supported by Extracorporeal Membrane Oxygenation: A Pilot Study.

OBJECTIVE: Cerebral autoregulation (CA) impairment may pose a risk factor for neurological complications among children supported by extracorporeal membrane oxygenation (ECMO). Our first objective was to investigate the feasibility of CA continuous monitoring during ECMO treatment and to describe its evolution over time. The second objective was to analyze the association between CA impairment and neurological outcome. DESIGN: Observational prospective study. PATIENTS AND SETTING: Twenty-nine children treated with veno-arterial or veno-venous ECMO in the PICU of Nantes University Hospital, France, and the PICU of the IRCCS Giannina Gaslini Institute in Genoa, Italy. MEASUREMENTS: A correlation coefficient between the variations of regional cerebral oxygen saturation and the variations of mean arterial blood pressure (MAP) was calculated as an index of CA (cerebral oxygenation reactivity index, COx). A COx > 0.3 was considered as indicative of autoregulation impairment. COx-MAP plots were investigated allowing determining optimal MAP (MAPopt) and limits of autoregulation: lower (LLA) and upper (ULA). Neurological outcome was assessed by the onset of an acute neurological event (ANE) after ECMO start. RESULTS: We included 29 children (median age 84 days, weight 4.8 kg). MAPopt, LLA, and ULA were detected in 90.8% (84.3-93.3) of monitoring time. Mean COx was significantly higher during day 1 of ECMO compared to day 2 [0.1 (0.02-0.15) vs. 0.01 (- 0.05 to 0.1), p = 0.002]. Twelve children experienced ANE (34.5%). The mean COx and the percentage of time spent with a COx > 0.3 were significantly higher among ANE+ compared to ANE- patients [0.09 (0.01-0.23) vs. 0.04 (- 0.02 to 0.06), p = 0.04 and 33.3% (24.8-62.1) vs. 20.8% (17.3-23.7) p = 0.001]. ANE+ patients spent significantly more time with MAP below LLA [17.2% (6.5-32.9) vs. 5.6% (3.6-9.9), p = 0.02] and above ULA [13% (5.3-38.4) vs. 4.2% (2.7-7.4), p = 0.004], respectively. CONCLUSION: CA assessment is feasible in pediatric ECMO. The first 24 h following ECMO represents the most critical period regarding CA. Impaired autoregulation is significantly more severe among patients who experience ANE