Showing papers by "Pierre-and-Marie-Curie University published in 2011"

2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC)

Abstract: ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation : The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC).

phangorn: Phylogenetic analysis in R

Abstract: Summary: phangorn is a package for phylogenetic reconstruction and analysis in the R language. Previously it was only possible to estimate phylogenetic trees with distance methods in R. phangorn, now offers the possibility of reconstructing phylogenies with distance based methods, maximum parsimony or maximum likelihood (ML) and performing Hadamard conjugation. Extending the general ML framework, this package provides the possibility of estimating mixture and partition models. Furthermore, phangorn offers several functions for comparing trees, phylogenetic models or splits, simulating character data and performing congruence analyses. Availability: phangorn can be obtained through the CRAN homepage http://cran.r-project.org/web/packages/phangorn/index.html. phangorn is licensed under GPL 2. Contact: rf.ueissuj.vns@peilhcsk.sualk Supplementary information: Supplementary data are available at Bioinformatics online.

Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

Abstract: We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 - 10'8 and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.

The Joint UK Land Environment Simulator (JULES), model description – Part 1: Energy and water fluxes

Abstract: . This manuscript describes the energy and water components of a new community land surface model called the Joint UK Land Environment Simulator (JULES). This is developed from the Met Office Surface Exchange Scheme (MOSES). It can be used as a stand alone land surface model driven by observed forcing data, or coupled to an atmospheric global circulation model. The JULES model has been coupled to the Met Office Unified Model (UM) and as such provides a unique opportunity for the research community to contribute their research to improve both world-leading operational weather forecasting and climate change prediction systems. In addition JULES, and its forerunner MOSES, have been the basis for a number of very high-profile papers concerning the land-surface and climate over the last decade. JULES has a modular structure aligned to physical processes, providing the basis for a flexible modelling platform.

Effect of nesiritide in patients with acute decompensated heart failure.

Abstract: A b s t r ac t Background Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. Methods We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. Results Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P = 0.03) and 24 hours (68.2% vs. 66.1%, P = 0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, −0.7 percentage points; 95% confidence interval [CI], −2.1 to 0.7; P = 0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, −0.4 percentage points; 95% CI, −1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P = 0.11). Conclusions Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.)

Resolving Difficult Phylogenetic Questions: Why More Sequences Are Not Enough

Abstract: In the quest to reconstruct the Tree of Life, researchers have increasingly turned to phylogenomics, the inference of phylogenetic relationships using genome-scale data (Box 1). Mesmerized by the sustained increase in sequencing throughput, many phylogeneticists entertained the hope that the incongruence frequently observed in studies using single or a few genes [1] would come to an end with the generation of large multigene datasets. Yet, as so often happens, reality has turned out to be far more complex, as three recent large-scale analyses, one published in PLoS Biology [2]–[4], make clear. The studies, which deal with the early diversification of animals, produced highly incongruent (Box 2) findings despite the use of considerable sequence data (see Figure 1). Clearly, merely adding more sequences is not enough to resolve the inconsistencies.

A lateralized brain network for visuospatial attention

Abstract: Right hemisphere dominance for visuospatial attention is characteristic of most humans, but its anatomical basis remains unknown We report the first evidence in humans for a larger parieto-frontal network in the right than left hemisphere, and a significant correlation between the degree of anatomical lateralization and asymmetry of performance on visuospatial tasks Our results suggest that hemispheric specialization is associated with an unbalanced speed of visuospatial processing

Supernova constraints and systematic uncertainties from the first three years of the supernova legacy survey

Abstract: We combine high redshift Type Ia supernovae from the first 3 years of the Supernova Legacy Survey (SNLS) with other supernova (SN) samples, primarily at lower redshifts, to form a high-quality joint sample of 472 SNe (123 low-$z$, 93 SDSS, 242 SNLS, and 14 {\it Hubble Space Telescope}). SN data alone require cosmic acceleration at >99.9% confidence, including systematic effects. For the dark energy equation of state parameter (assumed constant out to at least $z=1.4$) in a flat universe, we find $w = -0.91^{+0.16}_{-0.20}(\mathrm{stat}) ^{+0.07}_{-0.14} (\mathrm{sys})$ from SNe only, consistent with a cosmological constant. Our fits include a correction for the recently discovered relationship between host-galaxy mass and SN absolute brightness. We pay particular attention to systematic uncertainties, characterizing them using a systematics covariance matrix that incorporates the redshift dependence of these effects, as well as the shape-luminosity and color-luminosity relationships. Unlike previous work, we include the effects of systematic terms on the empirical light-curve models. The total systematic uncertainty is dominated by calibration terms. We describe how the systematic uncertainties can be reduced with soon to be available improved nearby and intermediate-redshift samples, particularly those calibrated onto USNO/SDSS-like systems.

Histopathologic-Based Prognostic Factors of Colorectal Cancers Are Associated With the State of the Local Immune Reaction

Abstract: Purpose The prognosis of patients with colorectal cancer has sometimes proved uncertain; thus, the prognostic significance of immune criteria was compared with that of the tumor extension criteria using the American Joint Committee on Cancer/International Union Against Cancer–TNM (AJCC/UICC-TNM) staging system. Patients and Methods We studied the intratumoral immune infiltrates in the center of the tumor and in the invasive margin of 599 specimens of stage I to IV colorectal cancers from two independent cohorts. We analyzed these findings in relation to the degree of tumor extension and to the frequency of recurrence. Results Growth of the primary tumor and metastatic spread were associated with decreased intratumoral immune T-cell densities. Sixty percent of patients with high densities of CD8+ cytotoxic T-lymphocyte infiltrate presented with stage Tis/T1 tumor, whereas no patients with low densities presented with such early-stage tumor. In patients who did not relapse, the density of CD8 infiltrates wa...

The HadGEM2-ES implementation of CMIP5 centennial simulations

Abstract: . The scientific understanding of the Earth's climate system, including the central question of how the climate system is likely to respond to human-induced perturbations, is comprehensively captured in GCMs and Earth System Models (ESM). Diagnosing the simulated climate response, and comparing responses across different models, is crucially dependent on transparent assumptions of how the GCM/ESM has been driven – especially because the implementation can involve subjective decisions and may differ between modelling groups performing the same experiment. This paper outlines the climate forcings and setup of the Met Office Hadley Centre ESM, HadGEM2-ES for the CMIP5 set of centennial experiments. We document the prescribed greenhouse gas concentrations, aerosol precursors, stratospheric and tropospheric ozone assumptions, as well as implementation of land-use change and natural forcings for the HadGEM2-ES historical and future experiments following the Representative Concentration Pathways. In addition, we provide details of how HadGEM2-ES ensemble members were initialised from the control run and how the palaeoclimate and AMIP experiments, as well as the "emission-driven" RCP experiments were performed.

Global dust model intercomparison in AeroCom phase I

Abstract: . This study presents the results of a broad intercomparison of a total of 15 global aerosol models within the AeroCom project. Each model is compared to observations related to desert dust aerosols, their direct radiative effect, and their impact on the biogeochemical cycle, i.e., aerosol optical depth (AOD) and dust deposition. Additional comparisons to Angstrom exponent (AE), coarse mode AOD and dust surface concentrations are included to extend the assessment of model performance and to identify common biases present in models. These data comprise a benchmark dataset that is proposed for model inspection and future dust model development. There are large differences among the global models that simulate the dust cycle and its impact on climate. In general, models simulate the climatology of vertically integrated parameters (AOD and AE) within a factor of two whereas the total deposition and surface concentration are reproduced within a factor of 10. In addition, smaller mean normalized bias and root mean square errors are obtained for the climatology of AOD and AE than for total deposition and surface concentration. Characteristics of the datasets used and their uncertainties may influence these differences. Large uncertainties still exist with respect to the deposition fluxes in the southern oceans. Further measurements and model studies are necessary to assess the general model performance to reproduce dust deposition in ocean regions sensible to iron contributions. Models overestimate the wet deposition in regions dominated by dry deposition. They generally simulate more realistic surface concentration at stations downwind of the main sources than at remote ones. Most models simulate the gradient in AOD and AE between the different dusty regions. However the seasonality and magnitude of both variables is better simulated at African stations than Middle East ones. The models simulate the offshore transport of West Africa throughout the year but they overestimate the AOD and they transport too fine particles. The models also reproduce the dust transport across the Atlantic in the summer in terms of both AOD and AE but not so well in winter-spring nor the southward displacement of the dust cloud that is responsible of the dust transport into South America. Based on the dependency of AOD on aerosol burden and size distribution we use model bias with respect to AOD and AE to infer the bias of the dust emissions in Africa and the Middle East. According to this analysis we suggest that a range of possible emissions for North Africa is 400 to 2200 Tg yr−1 and in the Middle East 26 to 526 Tg yr−1.

The Joint UK Land Environment Simulator (JULES), model description – Part 2: Carbon fluxes and vegetation dynamics

Abstract: . The Joint UK Land Environment Simulator (JULES) is a process-based model that simulates the fluxes of carbon, water, energy and momentum between the land surface and the atmosphere. Many studies have demonstrated the important role of the land surface in the functioning of the Earth System. Different versions of JULES have been employed to quantify the effects on the land carbon sink of climate change, increasing atmospheric carbon dioxide concentrations, changing atmospheric aerosols and tropospheric ozone, and the response of methane emissions from wetlands to climate change. This paper describes the consolidation of these advances in the modelling of carbon fluxes and stores, in both the vegetation and soil, in version 2.2 of JULES. Features include a multi-layer canopy scheme for light interception, including a sunfleck penetration scheme, a coupled scheme of leaf photosynthesis and stomatal conductance, representation of the effects of ozone on leaf physiology, and a description of methane emissions from wetlands. JULES represents the carbon allocation, growth and population dynamics of five plant functional types. The turnover of carbon from living plant tissues is fed into a 4-pool soil carbon model. The process-based descriptions of key ecological processes and trace gas fluxes in JULES mean that this community model is well-suited for use in carbon cycle, climate change and impacts studies, either in standalone mode or as the land component of a coupled Earth system model.

Zagros orogeny: a subduction-dominated process

Abstract: This paper presents a synthetic view of the geodynamic evolution of the Zagros orogen within the frame of the Arabia-Eurasia collision. The Zagros orogen and the Iranian plateau preserve a record of the long-standing convergence history between Eurasia and Arabia across the Neo-Tethys, from subduction/obduction processes to present-day collision (from ~ 150 to 0 Ma). We herein combine the results obtained on several geodynamic issues, namely the location of the oceanic suture zone, the age of oceanic closure and collision, the magmatic and geochemical evolution of the Eurasian upper plate during convergence (as testified by the successive Sanandaj-Sirjan, Kermanshah and Urumieh-Dokhtar magmatic arcs), the P-T-t history of the few Zagros blueschists, the convergence characteristics across the Neo-Tethys (kinematic velocities, tomographic constraints, subduction zones and obduction processes), together with a survey of recent results gathered by others. We provide lithospheric-scale reconstructions of the Zagros orogen from ~ 150 to 0 Ma across two SW-NE transects. The evolution of the Zagros orogen is also compared to those of the nearby Turkish and Himalayan orogens. In our geotectonic scenario for the Zagros convergence, we outline three main periods/regimes: (1) the Mid to Late Cretaceous (115-85 Ma) corresponds to a distinctive period of perturbation of subduction processes and interplate mechanical coupling marked by blueschist exhumation and upper-plate fragmentation, (2) the Paleocene-Eocene (60-40 Ma) witnesses slab break-off, major shifts in arc magmatism and distributed extension within the upper plate, and (3) from the Oligocene onwards (~ 30-0 Ma), collision develops with a progressive SW migration of deformation and topographic build-up (Sanandaj-Sirjan Zone: 20-15 Ma, High Zagros: ~12-8 Ma; Simply Folded Belt: 5-0 Ma) and with partial slab tear at depths (~10 Ma to present). Our reconstructions underline the key role played by subduction throughout the whole convergence history. We finally stress that such a long-lasting subduction system with changing boundary conditions also makes the Zagros orogen an ideal natural laboratory for subduction processes.

Na2Ti3O7: Lowest voltage ever reported oxide insertion electrode for sodium ion batteries

Abstract: Na2Ti3O7 is found to reversibly uptake 2 Na ions per formula unit (200 mA h/g) at an average potential of 0.3 V and is hence a very promising negative electrode material for building sodium ion bat...

The Cryptochromes: Blue Light Photoreceptors in Plants and Animals

Abstract: Cryptochromes are flavoprotein photoreceptors first identified in Arabidopsis thaliana, where they play key roles in growth and development. Subsequently identified in prokaryotes, archaea, and many eukaryotes, cryptochromes function in the animal circadian clock and are proposed as magnetoreceptors in migratory birds. Cryptochromes are closely structurally related to photolyases, evolutionarily ancient flavoproteins that catalyze light-dependent DNA repair. Here, we review the structural, photochemical, and molecular properties of cry-DASH, plant, and animal cryptochromes in relation to biological signaling mechanisms and uncover common features that may contribute to better understanding the function of cryptochromes in diverse systems including in man.

Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis.

Abstract: Background Patients with vasculitis induced by the hepatitis C virus (HCV) have reduced levels of regulatory T cells (Tregs). Resolution of HCV infection correlates with cure of vasculitis and the recovery of Treg levels. We reasoned that interleukin-2, a cytokine that promotes Treg survival and function, could be beneficial for patients with vasculitis that is resistant to HCV therapy. Methods We investigated the safety and immunologic effects of the administration of low-dose interleukin-2 in a prospective open-label, phase 1–phase 2a study. Ten patients with HCV-induced vasculitis that was refractory to conventional antiviral therapy, rituximab therapy, or both and who were not receiving glucocorticoid or immunosuppressant therapy received one course of interleukin-2 (1.5 million IU per day) for 5 days, followed by three 5-day courses of 3 million IU per day at weeks 3, 6, and 9. Both the safety of the treatment and its effectiveness were evaluated, the latter by monitoring the Treg response and the cl...

The European Nitrogen Assessment. Sources, Effects and Policy Perspectives

Abstract: List of contributors Preface Summary for policymakers Technical summary 1. Assessing our nitrogen inheritance Part I. Nitrogen in Europe: The Present Position: 2. The European nitrogen problem in a global perspective 3. Benefits of nitrogen for food fibre and industrial production 4. Nitrogen in current European policies 5. The challenge to integrate nitrogen science and policies Part II. Nitrogen Processing in the Biosphere: 6. Nitrogen processes in terrestrial ecosystems 7. Nitrogen processes in aquatic ecosystems 8. Nitrogen processes in coastal and marine ecosystems 9. Nitrogen processes in the atmosphere Part III. Nitrogen Flows and Fate at Multiple Scales: 10. Nitrogen flows in farming systems across Europe 11. Nitrogen flows and fate in rural landscapes 12. Nitrogen flows and fate in urban landscapes 13. Nitrogen flows from European watersheds to coastal marine waters 14. Atmospheric transport and deposition of nitrogen in Europe 15. Geographic variation in terrestrial nitrogen budgets across Europe 16. Integrating nitrogen fluxes at the European scale Part IV. Key Societal Threats of Nitrogen: 17. Nitrogen as a threat to European water quality 18. Nitrogen as a threat to European air quality 19. Nitrogen as a threat to the European greenhouse balance 20. Nitrogen as a threat to European terrestrial biodiversity 21. Nitrogen as a threat to European soil quality Part V. European Nitrogen Policies and Future Challenges: 22. Costs and benefits of nitrogen in the environment 23. Developing integrated approaches to nitrogen management 24. Future scenarios of nitrogen in Europe 25. Coordinating European nitrogen policies between directives and international conventions 26. Societal choice and communicating the European nitrogen challenge Glossary Index.

Spinning conformal correlators

Abstract: We develop the embedding formalism for conformal field theories, aimed at doing computations with symmetric traceless operators of arbitrary spin. We use an index-free notation where tensors are encoded by polynomials in auxiliary polarization vectors. The efficiency of the formalism is demonstrated by computing the tensor structures allowed in n-point conformal correlation functions of tensors operators. Constraints due to tensor conservation also take a simple form in this formalism. Finally, we obtain a perfect match between the number of independent tensor structures of conformal correlators in d dimensions and the number of independent structures in scattering amplitudes of spinning particles in (d+1)-dimensional Minkowski space.

Krüppel-like factor 4 regulates macrophage polarization

Abstract: Current paradigms suggest that two macrophage subsets, termed M1 and M2, are involved in inflammation and host defense. While the distinct functions of M1 and M2 macrophages have been intensively studied - the former are considered proinflammatory and the latter antiinflammatory - the determinants of their speciation are incompletely understood. Here we report our studies that identify Kruppel-like factor 4 (KLF4) as a critical regulator of macrophage polarization. Macrophage KLF4 expression was robustly induced in M2 macrophages and strongly reduced in M1 macrophages, observations that were recapitulated in human inflammatory paradigms in vivo. Mechanistically, KLF4 was found to cooperate with Stat6 to induce an M2 genetic program and inhibit M1 targets via sequestration of coactivators required for NF-κB activation. KLF4-deficient macrophages demonstrated increased proinflammatory gene expression, enhanced bactericidal activity, and altered metabolism. Furthermore, mice bearing myeloid-specific deletion of KLF4 exhibited delayed wound healing and were predisposed to developing diet-induced obesity, glucose intolerance, and insulin resistance. Collectively, these data identify KLF4 as what we believe to be a novel regulator of macrophage polarization.

In Vivo Anomalous Diffusion and Weak Ergodicity Breaking of Lipid Granules

Abstract: Combining extensive single particle tracking microscopy data of endogenous lipid granules in living fission yeast cells with analytical results we show evidence for anomalous diffusion and weak ergodicity breaking. Namely we demonstrate that at short times the granules perform subdiffusion according to the laws of continuous time random walk theory. The associated violation of ergodicity leads to a characteristic turnover between two scaling regimes of the time averaged mean squared displacement. At longer times the granule motion is consistent with fractional Brownian motion.

Real-time quantum feedback prepares and stabilizes photon number states

Abstract: Feedback loops are central to most classical control procedures A controller compares the signal measured by a sensor (system output) with the target value or set-point It then adjusts an actuator (system input) to stabilize the signal around the target value Generalizing this scheme to stabilize a micro-system's quantum state relies on quantum feedback, which must overcome a fundamental difficulty: the sensor measurements cause a random back-action on the system An optimal compromise uses weak measurements, providing partial information with minimal perturbation The controller should include the effect of this perturbation in the computation of the actuator's operation, which brings the incrementally perturbed state closer to the target Although some aspects of this scenario have been experimentally demonstrated for the control of quantum or classical micro-system variables, continuous feedback loop operations that permanently stabilize quantum systems around a target state have not yet been realized Here we have implemented such a real-time stabilizing quantum feedback scheme following a method inspired by ref 13 It prepares on demand photon number states (Fock states) of a microwave field in a superconducting cavity, and subsequently reverses the effects of decoherence-induced field quantum jumps The sensor is a beam of atoms crossing the cavity, which repeatedly performs weak quantum non-demolition measurements of the photon number The controller is implemented in a real-time computer commanding the actuator, which injects adjusted small classical fields into the cavity between measurements The microwave field is a quantum oscillator usable as a quantum memory or as a quantum bus swapping information between atoms Our experiment demonstrates that active control can generate non-classical states of this oscillator and combat their decoherence, and is a significant step towards the implementation of complex quantum information operations

SNLS3: Constraints on dark energy combining the supernova legacy survey three-year data with other probes

Abstract: We present observational constraints on the nature of dark energy using the Supernova Legacy Survey three-year sample (SNLS3) of Guy et al. and Conley et al. We use the 472 Type Ia supernovae (SNe Ia) in this sample, accounting for recently discovered correlations between SN Ia luminosity and host galaxy properties, and include the effects of all identified systematic uncertainties directly in the cosmological fits. Combining the SNLS3 data with the full WMAP7 power spectrum, the Sloan Digital Sky Survey luminous red galaxy power spectrum, and a prior on the Hubble constant H_0 from SHOES, in a flat universe we find Ω_m = 0.269 ± 0.015 and w = –1.061^(+0.069)_(–0.068) (where the uncertainties include all statistical and SN Ia systematic errors)—a 6.5% measure of the dark energy equation-of-state parameter w. The statistical and systematic uncertainties are approximately equal, with the systematic uncertainties dominated by the photometric calibration of the SN Ia fluxes—without these calibration effects, systematics contribute only a ~2% error in w. When relaxing the assumption of flatness, we find Ω_m = 0.271 ± 0.015, Ω_k = –0.002 ± 0.006, and w = –1.069^(+0.091)_(–0.092). Parameterizing the time evolution of w as w(a) = w_0 + w_a (1–a) gives w_0 = –0.905 ± 0.196, w_a = –0.984^(+1.094)_(– 1.097) in a flat universe. All of our results are consistent with a flat, w = –1 universe. The size of the SNLS3 sample allows various tests to be performed with the SNe segregated according to their light curve and host galaxy properties. We find that the cosmological constraints derived from these different subsamples are consistent. There is evidence that the coefficient, β, relating SN Ia luminosity and color, varies with host parameters at >4σ significance (in addition to the known SN luminosity-host relation); however, this has only a small effect on the cosmological results and is currently a subdominant systematic.