Showing papers by "Aix-Marseille University published in 2011"
Institut Gustave Roussy1, University of South Florida2, University of Tübingen3, University of Paris4, Université catholique de Louvain5, Aix-Marseille University6, National Health Service7, University of Kiel8, McGill University9, University of Barcelona10, MedImmune11, Bristol-Myers Squibb12, Memorial Sloan Kettering Cancer Center13
TL;DR: Ipilimumab (at a dose of 10 mg per kilogram) in combination with dacarbazine, as compared with dACarbazine plus placebo, improved overall survival in patients with previously untreated metastatic melanoma.
Abstract: A B S T R AC T Background Ipilimumab monotherapy (at a dose of 3 mg per kilogram of body weight), as compared with glycoprotein 100, improved overall survival in a phase 3 study involving patients with previously treated metastatic melanoma. We conducted a phase 3 study of ipilimumab (10 mg per kilogram) plus dacarbazine in patients with previously untreated metastatic melanoma. Methods We randomly assigned 502 patients with previously untreated metastatic melanoma, in a 1:1 ratio, to ipilimumab (10 mg per kilogram) plus dacarbazine (850 mg per square meter of body-surface area) or dacarbazine (850 mg per square meter) plus placebo, given at weeks 1, 4, 7, and 10, followed by dacarbazine alone every 3 weeks through week 22. Patients with stable disease or an objective response and no doselimiting toxic effects received ipilimumab or placebo every 12 weeks thereafter as maintenance therapy. The primary end point was overall survival. Results Overall survival was significantly longer in the group receiving ipilimumab plus dacarbazine than in the group receiving dacarbazine plus placebo (11.2 months vs. 9.1 months, with higher survival rates in the ipilimumab–dacarbazine group at 1 year (47.3% vs. 36.3%), 2 years (28.5% vs. 17.9%), and 3 years (20.8% vs. 12.2%) (hazard ratio for death, 0.72; P<0.001). Grade 3 or 4 adverse events occurred in 56.3% of patients treated with ipilimumab plus dacarbazine, as compared with 27.5% treated with dacarbazine and placebo (P<0.001). No drug-related deaths or gastrointestinal perforations occurred in the ipilimumab–dacarbazine group. Conclusions Ipilimumab (at a dose of 10 mg per kilogram) in combination with dacarbazine, as compared with dacarbazine plus placebo, improved overall survival in patients with previously untreated metastatic melanoma. The types of adverse events were consistent with those seen in prior studies of ipilimumab; however, the rates of elevated liver-function values were higher and the rates of gastrointestinal events were lower than expected on the basis of prior studies. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00324155.)
4,069 citations
Daniel J. Eisenstein1, Daniel J. Eisenstein2, David H. Weinberg3, Eric Agol4 +260 more•Institutions (62)
TL;DR: SDSS-III as mentioned in this paper is a program of four spectroscopic surveys on three scientific themes: dark energy and cosmological parameters, the history and structure of the Milky Way, and the population of giant planets around other stars.
Abstract: Building on the legacy of the Sloan Digital Sky Survey (SDSS-I and II), SDSS-III is a program of four spectroscopic surveys on three scientific themes: dark energy and cosmological parameters, the history and structure of the Milky Way, and the population of giant planets around other stars. In keeping with SDSS tradition, SDSS-III will provide regular public releases of all its data, beginning with SDSS DR8 (which occurred in Jan 2011). This paper presents an overview of the four SDSS-III surveys. BOSS will measure redshifts of 1.5 million massive galaxies and Lya forest spectra of 150,000 quasars, using the BAO feature of large scale structure to obtain percent-level determinations of the distance scale and Hubble expansion rate at z 100 per resolution element), H-band (1.51-1.70 micron) spectra of 10^5 evolved, late-type stars, measuring separate abundances for ~15 elements per star and creating the first high-precision spectroscopic survey of all Galactic stellar populations (bulge, bar, disks, halo) with a uniform set of stellar tracers and spectral diagnostics. MARVELS will monitor radial velocities of more than 8000 FGK stars with the sensitivity and cadence (10-40 m/s, ~24 visits per star) needed to detect giant planets with periods up to two years, providing an unprecedented data set for understanding the formation and dynamical evolution of giant planet systems. (Abridged)
2,265 citations
TL;DR: Continuous daily administration of sunitinib at a dose of 37.5 mg improved progression-free survival, overall survival, and the objective response rate as compared with placebo among patients with advanced pancreatic neuroendocrine tumors.
Abstract: The multitargeted tyrosine kinase inhibitor sunitinib has shown activity against pancreatic neuroendocrine tumors in preclinical models and phase 1 and 2 trials.
2,192 citations
Hiroaki Aihara1, Carlos Allende Prieto2, Carlos Allende Prieto3, Deokkeun An4 +191 more•Institutions (58)
TL;DR: The first data release of SDSS-III is described in this article, which includes five-band imaging of roughly 5200 deg2 in the southern Galactic cap, bringing the total footprint of the Sloan Digital Sky Survey imaging to 14,555 deg2, or over a third of the Celestial Sphere.
Abstract: The Sloan Digital Sky Survey (SDSS) started a new phase in 2008 August, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Lyα forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg2 in the southern Galactic cap, bringing the total footprint of the SDSS imaging to 14,555 deg2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Exploration (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameter pipeline, which has better determination of metallicity for high-metallicity stars.
1,578 citations
University of Erlangen-Nuremberg1, University College London2, University of Amsterdam3, Baylor College of Medicine4, University of California, Los Angeles5, Pontifícia Universidade Católica do Rio Grande do Sul6, Carlo Besta Neurological Institute7, University of California, San Francisco8, University of Bonn9, State University of Campinas10, University of Pennsylvania11, McGill University12, University of Florence13, University of Grenoble14, Cleveland Clinic15, Istanbul University16, University of Toronto17, Aix-Marseille University18, University of Florida19, University of Freiburg20, Mario Negri Institute for Pharmacological Research21
TL;DR: Focal cortical dysplasias (FCD) are localized regions of malformed cerebral cortex and are very frequently associated with epilepsy in both children and adults.
Abstract: Purpose Focal cortical dysplasias (FCD) are localized regions of malformed cerebral cortex and are very frequently associated with epilepsy in both children and adults. A broad spectrum of histopathology has been included in the diagnosis of FCD. An ILAE task force proposes an international consensus classification system to better characterize specific clinicopathological FCD entities. Methods Thirty-two Task Force members have reevaluated available data on electroclinical presentation, imaging, neuropathological examination of surgical specimens as well as postsurgical outcome. Key findings The ILAE Task Force proposes a three-tiered classification system. FCD Type I refers to isolated lesions, which present either as radial (FCD Type Ia) or tangential (FCD Type Ib) dyslamination of the neocortex, microscopically identified in one or multiple lobes. FCD Type II is an isolated lesion characterized by cortical dyslamination and dysmorphic neurons without (Type IIa) or with balloon cells (Type IIb). Hence, the major change since a prior classification represents the introduction of FCD Type III, which occurs in combination with hippocampal sclerosis (FCD Type IIIa), or with epilepsy-associated tumors (FCD Type IIIb). FCD Type IIIc is found adjacent to vascular malformations, whereas FCD Type IIId can be diagnosed in association with epileptogenic lesions acquired in early life (i.e., traumatic injury, ischemic injury or encephalitis). Significance This three-tiered classification system will be an important basis to evaluate imaging, electroclinical features, and postsurgical seizure control as well as to explore underlying molecular pathomechanisms in FCD.
1,395 citations
Paris Diderot University1, University of Crete2, Max Planck Society3, Institut d'Astrophysique de Paris4, California Institute of Technology5, Foundation for Research & Technology – Hellas6, European Space Agency7, University of Concepción8, Durham University9, Aix-Marseille University10, INAF11, University of Edinburgh12, UK Astronomy Technology Centre13, University of Arizona14, University of Hawaii15, University of Massachusetts Amherst16, University of British Columbia17, University of Paris-Sud18, Space Telescope Science Institute19, National Radio Astronomy Observatory20, Texas A&M University21
TL;DR: In this paper, the authors examined the infrared (IR) 3-500μm spectral energy distributions (SEDs) of galaxies at 0 < z < 2.5, supplemented by a local reference sample from IRAS, ISO, Spitzer, and AKARI data.
Abstract: We present the deepest 100 to 500 μm far-infrared observations obtained with the Herschel Space Observatory as part of the GOODS-Herschel key program, and examine the infrared (IR) 3–500 μm spectral energy distributions (SEDs) of galaxies at 0 < z < 2.5, supplemented by a local reference sample from IRAS, ISO, Spitzer, and AKARI data. We determine the projected star formation densities of local galaxies from their radio and mid-IR continuum sizes.
We find that the ratio of total IR luminosity to rest-frame 8 μm luminosity, IR8 (≡ L_(IR)^(tot)/L_8), follows a Gaussian distribution centered on IR8 = 4 (σ = 1.6) and defines an IR main sequence for star-forming galaxies independent of redshift and luminosity. Outliers from this main sequence produce a tail skewed toward higher values of IR8. This minority population ( 3 × 10^(10) L_⊙ kpc^(-2)) and a high specific star formation rate (i.e., starbursts). The rest-frame, UV-2700 A size of these distant starbursts is typically half that of main sequence galaxies, supporting the correlation between star formation density and starburst activity that is measured for the local sample.
Locally, luminous and ultraluminous IR galaxies, (U)LIRGs (L_(IR)^(tot)≥ 10^(11) L_☉), are systematically in the starburst mode, whereas most distant (U)LIRGs form stars in the “normal” main sequence mode. This confusion between two modes of star formation is the cause of the so-called “mid-IR excess” population of galaxies found at z > 1.5 by previous studies. Main sequence galaxies have strong polycyclic aromatic hydrocarbon (PAH) emission line features, a broad far-IR bump resulting from a combination of dust temperatures (T_(dust) ~ 15–50 K), and an effective T_(dust) ~ 31 K, as derived from the peak wavelength of their infrared SED. Galaxies in the starburst regime instead exhibit weak PAH equivalent widths and a sharper far-IR bump with an effective T_(dust)~ 40 K. Finally, we present evidence that the mid-to-far IR emission of X-ray active galactic nuclei (AGN) is predominantly produced by star formation and that candidate dusty AGNs with a power-law emission in the mid-IR systematically occur in compact, dusty starbursts. After correcting for the effect of starbursts on IR8, we identify new candidates for extremely obscured AGNs.
1,235 citations
Marcos Daniel Actis1, G. Agnetta2, Felix Aharonian3, A. G. Akhperjanian +682 more•Institutions (109)
TL;DR: The ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes as mentioned in this paper, which is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100GeV and above 100 TeV.
Abstract: Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.
1,006 citations
Kyoto University1, Brookhaven National Laboratory2, KEK3, Nagoya University4, Université Paris-Saclay5, University of Washington6, University of Connecticut7, University of Bern8, Spanish National Research Council9, University of Southern Denmark10, University of Rome Tor Vergata11, University of Wuppertal12, Forschungszentrum Jülich13, Osaka University14, San Francisco State University15, Indiana University16, Graduate University for Advanced Studies17, American Physical Society18, University of Edinburgh19, University of Southampton20, Aix-Marseille University21, National Chiao Tung University22, Roma Tre University23, Columbia University24, Autonomous University of Madrid25, University of Mainz26
TL;DR: The determination of the light-quark masses, the form factor, and the decay-constant ratio arising in semileptonic $$K \rightarrow \pi $$K→π transition at zero momentum transfer are reported on.
Abstract: We review lattice results related to pion, kaon, D- and B-meson physics with the aim of making them easily accessible to the particle physics community. More specifically, we report on the determination of the light-quark masses, the form factor f+(0), arising in semileptonic K -> pi transition at zero momentum transfer, as well as the decay constant ratio fK/fpi of decay constants and its consequences for the CKM matrix elements Vus and Vud. Furthermore, we describe the results obtained on the lattice for some of the low-energy constants of SU(2)LxSU(2)R and SU(3)LxSU(3)R Chiral Perturbation Theory and review the determination of the BK parameter of neutral kaon mixing. The inclusion of heavy-quark quantities significantly expands the FLAG scope with respect to the previous review. Therefore, for this review, we focus on D- and B-meson decay constants, form factors, and mixing parameters, since these are most relevant for the determination of CKM matrix elements and the global CKM unitarity-triangle fit. In addition we review the status of lattice determinations of the strong coupling constant alpha_s.
901 citations
University of Colorado Boulder1, University of Toronto2, Pierre-and-Marie-Curie University3, University of Oxford4, University of Paris5, Centre national de la recherche scientifique6, Aix-Marseille University7, INAF8, Las Cumbres Observatory Global Telescope Network9, University of California, Santa Barbara10, Defence Research and Development Canada11, University of Victoria12, California Institute of Technology13, Centra14, Lawrence Berkeley National Laboratory15, University of Waterloo16, Australian Astronomical Observatory17, University of California, Berkeley18
TL;DR: In this article, the authors 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-$z, 93 SDSS, 242 SNLS, and 14 {\it Hubble Space Telescope}).
Abstract: We combine high redshift Type Ia supernovae from the first 3 years of the Supernova Legacy Survey (SNLS) with other supernova (SN) samples, primarily at lower redshifts, to form a high-quality joint sample of 472 SNe (123 low-$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.
889 citations
Washington University in St. Louis1, Rush University Medical Center2, University of California, San Francisco3, University of Cambridge4, University of Cincinnati5, University of California, Los Angeles6, Aix-Marseille University7, Columbia University8, University of Virginia9, University of Düsseldorf10, University of Florida11, Mayo Clinic12, University of Pennsylvania13, Innsbruck Medical University14, University of Milan15, Baylor College of Medicine16, Nottingham University Hospitals NHS Trust17, Utrecht University18, Free University of Berlin19
TL;DR: Recommendations were developed based on literature review using the GRADE system, discussion integrating the literature with the collective experience of the participants and critical review by an impartial jury and emphasis was placed on the principle that recommendations should be based not only on the quality of the data but also tradeoffs and translation into practice.
Abstract: Subarachnoid hemorrhage (SAH) is an acute cerebrovascular event which can have devastating effects on the central nervous system as well as a profound impact on several other organs SAH patients are routinely admitted to an intensive care unit and are cared for by a multidisciplinary team A lack of high quality data has led to numerous approaches to management and limited guidance on choosing among them Existing guidelines emphasize risk factors, prevention, natural history, and prevention of rebleeding, but provide limited discussion of the complex critical care issues involved in the care of SAH patients The Neurocritical Care Society organized an international, multidisciplinary consensus conference on the critical care management of SAH to address this need Experts from neurocritical care, neurosurgery, neurology, interventional neuroradiology, and neuroanesthesiology from Europe and North America were recruited based on their publications and expertise A jury of four experienced neurointensivists was selected for their experience in clinical investigations and development of practice guidelines Recommendations were developed based on literature review using the GRADE system, discussion integrating the literature with the collective experience of the participants and critical review by an impartial jury Recommendations were developed using the GRADE system Emphasis was placed on the principle that recommendations should be based not only on the quality of the data but also tradeoffs and translation into practice Strong consideration was given to providing guidance and recommendations for all issues faced in the daily management of SAH patients, even in the absence of high quality data
884 citations
Uppsala University1, University of Hamburg2, Aix-Marseille University3, Stanford University4, Swedish University of Agricultural Sciences5, Arizona State University6, Lawrence Berkeley National Laboratory7, Lawrence Livermore National Laboratory8, Max Planck Society9, Technical University of Berlin10
TL;DR: This work shows that high-quality diffraction data can be obtained with a single X-ray pulse from a non-crystalline biological sample, a single mimivirus particle, which was injected into the pulsed beam of a hard-X-ray free-electron laser, the Linac Coherent Light Source.
Abstract: The start-up of the Linac Coherent Light Source (LCLS), the new femtosecond hard X-ray laser facility in Stanford, California, has brought high expectations of a new era for biological imaging. The intense, ultrashort X-ray pulses allow diffraction imaging of small structures before radiation damage occurs. Two papers in this issue of Nature present proof-of-concept experiments showing the LCLS in action. Chapman et al. tackle structure determination from nanocrystals of macromolecules that cannot be grown in large crystals. They obtain more than three million diffraction patterns from a stream of nanocrystals of the membrane protein photosystem I, and assemble a three-dimensional data set for this protein. Seibert et al. obtain images of a non-crystalline biological sample, mimivirus, by injecting a beam of cooled mimivirus particles into the X-ray beam. The start-up of the new femtosecond hard X-ray laser facility in Stanford, the Linac Coherent Light Source, has brought high expectations for a new era for biological imaging. The intense, ultrashort X-ray pulses allow diffraction imaging of small structures before radiation damage occurs. This new capability is tested for the problem of imaging a non-crystalline biological sample. Images of mimivirus are obtained, the largest known virus with a total diameter of about 0.75 micrometres, by injecting a beam of cooled mimivirus particles into the X-ray beam. The measurements indicate no damage during imaging and prove the concept of this imaging technique. X-ray lasers offer new capabilities in understanding the structure of biological systems, complex materials and matter under extreme conditions1,2,3,4. Very short and extremely bright, coherent X-ray pulses can be used to outrun key damage processes and obtain a single diffraction pattern from a large macromolecule, a virus or a cell before the sample explodes and turns into plasma1. The continuous diffraction pattern of non-crystalline objects permits oversampling and direct phase retrieval2. Here we show that high-quality diffraction data can be obtained with a single X-ray pulse from a non-crystalline biological sample, a single mimivirus particle, which was injected into the pulsed beam of a hard-X-ray free-electron laser, the Linac Coherent Light Source5. Calculations indicate that the energy deposited into the virus by the pulse heated the particle to over 100,000 K after the pulse had left the sample. The reconstructed exit wavefront (image) yielded 32-nm full-period resolution in a single exposure and showed no measurable damage. The reconstruction indicates inhomogeneous arrangement of dense material inside the virion. We expect that significantly higher resolutions will be achieved in such experiments with shorter and brighter photon pulses focused to a smaller area. The resolution in such experiments can be further extended for samples available in multiple identical copies.
TL;DR: Dense suspension and granular media are unified under a common framework and the results are shown to be compatible with classical empirical models of suspension rheology and provide a clear determination of constitutive laws close to the jamming transition.
Abstract: Using an original pressure-imposed shear cell, we study the rheology of dense suspensions. We show that they exhibit a viscoplastic behavior similarly to granular media successfully described by a frictional rheology and fully characterized by the evolution of the friction coefficient μ and the volume fraction ϕ with a dimensionless viscous number I(v). Dense suspension and granular media are thus unified under a common framework. These results are shown to be compatible with classical empirical models of suspension rheology and provide a clear determination of constitutive laws close to the jamming transition.
TL;DR: The existence in Chlamydomonas of complex interplays between oil synthesis, genetic background and stress conditions is suggested and the importance of using direct progenitors as control strains when assessing the effect of mutations on oil content is highlighted.
Abstract: When cultivated under stress conditions, many microalgae species accumulate both starch and oil (triacylglycerols). The model green microalga Chlamydomonas reinhardtii has recently emerged as a model to test genetic engineering or cultivation strategies aiming at increasing lipid yields for biodiesel production. Blocking starch synthesis has been suggested as a way to boost oil accumulation. Here, we characterize the triacylglycerol (TAG) accumulation process in Chlamydomonas and quantify TAGs in various wild-type and starchless strains. In response to nitrogen deficiency, Chlamydomonas reinhardtii produced TAGs enriched in palmitic, oleic and linoleic acids that accumulated in oil-bodies. Oil synthesis was maximal between 2 and 3 days following nitrogen depletion and reached a plateau around day 5. In the first 48 hours of oil deposition, a ~80% reduction in the major plastidial membrane lipids occurred. Upon nitrogen re-supply, mobilization of TAGs started after starch degradation but was completed within 24 hours. Comparison of oil content in five common laboratory strains (CC124, CC125, cw15, CC1690 and 11-32A) revealed a high variability, from 2 μg TAG per million cell in CC124 to 11 μg in 11-32A. Quantification of TAGs on a cell basis in three mutants affected in starch synthesis (cw15sta1-2, cw15sta6 and cw15sta7-1) showed that blocking starch synthesis did not result in TAG over-accumulation compared to their direct progenitor, the arginine auxotroph strain 330. Moreover, no significant correlation was found between cellular oil and starch levels among the twenty wild-type, mutants and complemented strains tested. By contrast, cellular oil content was found to increase steeply with salt concentration in the growth medium. At 100 mM NaCl, oil level similar to nitrogen depletion conditions could be reached in CC124 strain. A reference basis for future genetic studies of oil metabolism in Chlamydomonas is provided. Results highlight the importance of using direct progenitors as control strains when assessing the effect of mutations on oil content. They also suggest the existence in Chlamydomonas of complex interplays between oil synthesis, genetic background and stress conditions. Optimization of such interactions is an alternative to targeted metabolic engineering strategies in the search for high oil yields.
Institut national de la recherche agronomique1, Harvard University2, United States Department of Energy3, University of Upper Alsace4, Natural Resources Canada5, Max Planck Society6, Aix-Marseille University7, University of British Columbia8, Hoffmann-La Roche9, University of Göttingen10, Commonwealth Scientific and Industrial Research Organisation11, University of Sydney12, Oak Ridge National Laboratory13, North Dakota State University14, University of Minnesota15
TL;DR: The dramatic up-regulation of transcripts coding for small secreted proteins, secreted hydrolytic enzymes, and transporters in planta suggests that they play a role in host infection and nutrient acquisition.
Abstract: Rust fungi are some of the most devastating pathogens of crop plants. They are obligate biotrophs, which extract nutrients only from living plant tissues and cannot grow apart from their hosts. Their lifestyle has slowed the dissection of molecular mechanisms underlying host invasion and avoidance or suppression of plant innate immunity. We sequenced the 101-Mb genome of Melampsora larici-populina, the causal agent of poplar leaf rust, and the 89-Mb genome of Puccinia graminis f. sp. tritici, the causal agent of wheat and barley stem rust. We then compared the 16,399 predicted proteins of M. larici-populina with the 17,773 predicted proteins of P. graminis f. sp tritici. Genomic features related to their obligate biotrophic lifestyle include expanded lineage-specific gene families, a large repertoire of effector-like small secreted proteins, impaired nitrogen and sulfur assimilation pathways, and expanded families of amino acid and oligopeptide membrane transporters. The dramatic up-regulation of transcripts coding for small secreted proteins, secreted hydrolytic enzymes, and transporters in planta suggests that they play a role in host infection and nutrient acquisition. Some of these genomic hallmarks are mirrored in the genomes of other microbial eukaryotes that have independently evolved to infect plants, indicating convergent adaptation to a biotrophic existence inside plant cells.
11 Nov 2011-Nuclear Instruments & Methods in Physics Research Section A-accelerators Spectrometers Detectors and Associated Equipment
TL;DR: The ANTARES Neutrino Telescope was completed in May 2008 and is the first operational neutrino telescope in the Mediterranean Sea as mentioned in this paper, where the main purpose of the detector is to perform neutrinos astronomy and the apparatus also offers facilities for marine and Earth sciences.
Abstract: The ANTARES Neutrino Telescope was completed in May 2008 and is the first operational Neutrino Telescope in the Mediterranean Sea. The main purpose of the detector is to perform neutrino astronomy and the apparatus also offers facilities for marine and Earth sciences. This paper describes the design, the construction and the installation of the telescope in the deep sea, offshore from Toulon in France. An illustration of the detector performance is given.
University of Oxford1, Pierre-and-Marie-Curie University2, University of Toronto3, University of Colorado Boulder4, University of Paris5, Centre national de la recherche scientifique6, Aix-Marseille University7, INAF8, Las Cumbres Observatory Global Telescope Network9, University of California, Santa Barbara10, Defence Research and Development Canada11, University of Victoria12, California Institute of Technology13, Lawrence Berkeley National Laboratory14, Perimeter Institute for Theoretical Physics15, University of Waterloo16, Australian Astronomical Observatory17, Centra18, University of California, Berkeley19
TL;DR: In this article, the authors 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., and they find that the cosmological constraints derived from these different subsamples are consistent.
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.
TL;DR: This study suggests that growth inhibition and cell damage can be directly attributed either to the nanoparticles themselves or to the ability of AgNPs to deliver dissolved Ag to critical biotic receptors.
Abstract: Silver nanoparticles (AgNPs) are increasingly used as antimicrobial additives in consumer products and may have adverse impacts on organisms when they inadvertently enter ecosystems. This study investigated the uptake and toxicity of AgNPs to the common grass, Lolium multiflorum. We found that root and shoot Ag content increased with increasing AgNP exposures. AgNPs inhibited seedling growth. While exposed to 40 mg L(-1) GA-coated AgNPs, seedlings failed to develop root hairs, had highly vacuolated and collapsed cortical cells and broken epidermis and rootcap. In contrast, seedlings exposed to identical concentrations of AgNO(3) or supernatants of ultracentrifuged AgNP solutions showed no such abnormalities. AgNP toxicity was influenced by total NP surface area with smaller AgNPs (6 nm) more strongly affecting growth than did similar concentrations of larger (25 nm) NPs for a given mass. Cysteine (which binds Ag(+)) mitigated the effects of AgNO(3) but did not reduce the toxicity of AgNP treatments. X-ray spectro-microscopy documented silver speciation within exposed roots and suggested that silver is oxidized within plant tissues. Collectively, this study suggests that growth inhibition and cell damage can be directly attributed either to the nanoparticles themselves or to the ability of AgNPs to deliver dissolved Ag to critical biotic receptors.
TL;DR: ALDH and CD133 are defined as a functionally significant set of markers to identify ovarian CSCs and the presence of ALDH(+)CD133(+) cells in debulked primary tumor specimens correlated with reduced disease-free and overall survival in ovarian cancer patients.
Abstract: Markers that reliably identify cancer stem cells (CSC) in ovarian cancer could assist prognosis and improve strategies for therapy CD133 is a reported marker of ovarian CSC Aldehyde dehydrogenase (ALDH) activity is a reported CSC marker in several solid tumors, but it has not been studied in ovarian CSC Here we report that dual positivity of CD133 and ALDH defines a compelling marker set in ovarian CSC All human ovarian tumors and cell lines displayed ALDH activity ALDH+ cells isolated from ovarian cancer cell lines were chemoresistant and preferentially grew tumors, compared with ALDH− cells, validating ALDH as a marker of ovarian CSC in cell lines Notably, as few as 1,000 ALDH+ cells isolated directly from CD133− human ovarian tumors were sufficient to generate tumors in immunocompromised mice, whereas 50,000 ALDH− cells were unable to initiate tumors Using ALDH in combination with CD133 to analyze ovarian cancer cell lines, we observed even greater growth in the ALDH+CD133+ cells compared with ALDH+CD133− cells, suggesting a further enrichment of ovarian CSC in ALDH+CD133+ cells Strikingly, as few as 11 ALDH+CD133+ cells isolated directly from human tumors were sufficient to initiate tumors in mice Like other CSC, ovarian CSC exhibited increased angiogenic capacity compared with bulk tumor cells Finally, the presence of ALDH+CD133+ cells in debulked primary tumor specimens correlated with reduced disease-free and overall survival in ovarian cancer patients Taken together, our findings define ALDH and CD133 as a functionally significant set of markers to identify ovarian CSCs Cancer Res; 71(11); 3991–4001 ©2011 AACR
Centre Hospitalier Universitaire de Nice1, International Agency for Research on Cancer2, University of Nice Sophia Antipolis3, University of Strasbourg4, Institut Gustave Roussy5, French Institute of Health and Medical Research6, University of Paris-Sud7, University of Paris8, University of Burgundy9, Claude Bernard University Lyon 110, Curie Institute11, University of Genoa12, University of Barcelona13, Lund University14, Aix-Marseille University15, Joseph Fourier University16, University of Bordeaux17, Centre Hospitalier Universitaire de Toulouse18, University of Évry Val d'Essonne19
TL;DR: A germline missense substitution in MITF (Mi-E318K) is identified that occurred at a significantly higher frequency in genetically enriched patients affected with melanoma, RCC or both cancers, when compared with controls and provides insights into the link between SUMOylation, transcription and cancer.
Abstract: So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes; risk factors associated with RCC include smoking, obesity and hypertension. A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers. The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene; it also stimulates the transcription of hypoxia inducible factor (HIF1A), the pathway of which is targeted by kidney cancer susceptibility genes. We therefore proposed that MITF might have a role in conferring a genetic predisposition to co-occurring melanoma and RCC. Here we identify a germline missense substitution in MITF (Mi-E318K) that occurred at a significantly higher frequency in genetically enriched patients affected with melanoma, RCC or both cancers, when compared with controls. Overall, Mi-E318K carriers had a higher than fivefold increased risk of developing melanoma, RCC or both cancers. Codon 318 is located in a small-ubiquitin-like modifier (SUMO) consensus site (ΨKXE) and Mi-E318K severely impaired SUMOylation of MITF. Mi-E318K enhanced MITF protein binding to the HIF1A promoter and increased its transcriptional activity compared to wild-type MITF. Further, we observed a global increase in Mi-E318K-occupied loci. In an RCC cell line, gene expression profiling identified a Mi-E318K signature related to cell growth, proliferation and inflammation. Lastly, the mutant protein enhanced melanocytic and renal cell clonogenicity, migration and invasion, consistent with a gain-of-function role in tumorigenesis. Our data provide insights into the link between SUMOylation, transcription and cancer.
Goddard Institute for Space Studies1, Max Planck Society2, National Center for Atmospheric Research3, Aix-Marseille University4, University of Edinburgh5, Joseph Fourier University6, Oeschger Centre for Climate Change Research7, University of Bern8, Lund University9, Swiss Federal Institute of Aquatic Science and Technology10, University of Orléans11
TL;DR: In this article, the authors describe the approach taken in defining the scenarios used in the PMIP3, document the forcing reconstructions and discuss likely implications and discuss the likely implications.
Abstract: Simulations of climate over the Last Millennium (850-1850 CE) have been incorporated into the third phase of the Paleoclimate Modelling Intercomparison Project (PMIP3). The drivers of climate over this period are chiefly orbital, solar, volcanic, changes in land use/land cover and some variation in greenhouse gas levels. While some of these effects can be easily defined, the reconstructions of solar, volcanic and land use-related forcing are more uncertain. We describe here the approach taken in defining the scenarios used in PMIP3, document the forcing reconstructions and discuss likely implications.
TL;DR: In this article, a search for squarks and gluinos in final states containing jets, missing transverse momentum and no electrons or muons is presented, and the data were recorded by the ATLAS experiment in sqrt(s) = 7 TeV proton-proton collisions at the Large Hadron Collider.
TL;DR: In this paper, the particle multiplicity, its dependence on transverse momentum and pseudorapidity and the relationship between the mean transversal momentum and the charged-particle multiplicity are measured.
Abstract: Measurements are presented from proton-proton collisions at centre-of-mass energies of root s = 0.9, 2.36 and 7 TeV recorded with the ATLAS detector at the LHC. Events were collected using a single-arm minimum-bias trigger. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity and the relationship between the mean transverse momentum and charged-particle multiplicity are measured. Measurements in different regions of phase space are shown, providing diffraction-reduced measurements as well as more inclusive ones. The observed distributions are corrected to well-defined phase-space regions, using model-independent corrections. The results are compared to each other and to various Monte Carlo (MC) models, including a new AMBT1 pythia6 tune. In all the kinematic regions considered, the particle multiplicities are higher than predicted by the MC models. The central charged-particle multiplicity per event and unit of pseudorapidity, for tracks with p(T) > 100 MeV, is measured to be 3.483 +/- 0.009 (stat) +/- 0.106 (syst) at root s = 0.9 TeV and 5.630 +/- 0.003 (stat) +/- 0.169 (syst) at root s = 7 TeV.
Novozymes1, United States Department of Energy2, Concordia University3, Aix-Marseille University4, University of New Mexico5, Utrecht University6, Centraalbureau voor Schimmelcultures7, Sandia National Laboratories8, Macquarie University9, Pacific Northwest National Laboratory10, McGill University11, University of Glasgow12, Broad Institute13
TL;DR: These genomes are the first described for thermophilic eukaryotes and the first complete telomere-to-telomere genomes for filamentous fungi and suggest that both thermophiles are capable of hydrolyzing all major polysaccharides found in biomass.
Abstract: Thermostable enzymes and thermophilic cell factories may afford economic advantages in the production of many chemicals and biomass-based fuels. Here we describe and compare the genomes of two thermophilic fungi, Myceliophthora thermophila and Thielavia terrestris. To our knowledge, these genomes are the first described for thermophilic eukaryotes and the first complete telomere-to-telomere genomes for filamentous fungi. Genome analyses and experimental data suggest that both thermophiles are capable of hydrolyzing all major polysaccharides found in biomass. Examination of transcriptome data and secreted proteins suggests that the two fungi use shared approaches in the hydrolysis of cellulose and xylan but distinct mechanisms in pectin degradation. Characterization of the biomass-hydrolyzing activity of recombinant enzymes suggests that these organisms are highly efficient in biomass decomposition at both moderate and high temperatures. Furthermore, we present evidence suggesting that aside from representing a potential reservoir of thermostable enzymes, thermophilic fungi are amenable to manipulation using classical and molecular genetics.
TL;DR: This tutorial chapter is intended to give an "hands on" view of FCS, including calibration, measurement, and data treatment, and the major difficulties that are encountered when performing for the first time FCS.
Abstract: Fluorescence correlation spectroscopy (FCS), implemented in microscopy, relies on performing an autocorrelation of the time fluctuating intensity arising from individual molecules diffusing through a confocal volume. It allows us to investigate a large variety of dynamic processes and to quantify photophysical, photochemical, interaction, diffusion, and transport properties of molecules. This tutorial chapter is intended to give an "hands on" view of FCS. After a brief introduction on the principle of FCS, the major theoretical assumptions are emphasized, and the main analytical expression are given. Then the key parameters that have to be considered when building a FCS system are discussed. The complete method of operation is described, including calibration, measurement, and data treatment. The major difficulties that are encountered when performing for the first time FCS are illustrated by examples of measurements, and possible solutions are proposed.
TL;DR: The analyses revealed that differentially calcified species and morphotypes are distributed in the ocean according to carbonate chemistry, and the discovery of a heavily calcified Emiliania huxleyi morphotype in modern waters with low pH highlights the complexity of assemblage-level responses to environmental forcing factors.
Abstract: About one-third of the carbon dioxide (CO(2)) released into the atmosphere as a result of human activity has been absorbed by the oceans(1), where it partitions into the constituent ions of carbonic acid. This leads to ocean acidification, one of the major threats to marine ecosystems(2) and particularly to calcifying organisms such as corals(3,4), foraminifera(5-7) and coccolithophores(8). Coccolithophores are abundant phytoplankton that are responsible for a large part of modern oceanic carbonate production. Culture experiments investigating the physiological response of coccolithophore calcification to increased CO(2) have yielded contradictory results between and even within species(8-11). Here we quantified the calcite mass of dominant coccolithophores in the present ocean and over the past forty thousand years, and found a marked pattern of decreasing calcification with increasing partial pressure of CO(2) and concomitant decreasing concentrations of CO(3)(2-). Our analyses revealed that differentially calcified species and morphotypes are distributed in the ocean according to carbonate chemistry. A substantial impact on the marine carbon cycle might be expected upon extrapolation of this correlation to predicted ocean acidification in the future. However, our discovery of a heavily calcified Emiliania huxleyi morphotype in modern waters with low pH highlights the complexity of assemblage-level responses to environmental forcing factors.
TL;DR: The quality of 454 GS-FLX sequencing data is analyzed and the pattern identified here calls for the use of internal controls and error-correcting base callers, to correct for errors, when available (e.g. when sequencing amplicons).
Abstract: The rapid evolution of 454 GS-FLX sequencing technology has not been accompanied by a reassessment of the quality and accuracy of the sequences obtained. Current strategies for decision-making and error-correction are based on an initial analysis by Huse et al. in 2007, for the older GS20 system based on experimental sequences. We analyze here the quality of 454 sequencing data and identify factors playing a role in sequencing error, through the use of an extensive dataset for Roche control DNA fragments. We obtained a mean error rate for 454 sequences of 1.07%. More importantly, the error rate is not randomly distributed; it occasionally rose to more than 50% in certain positions, and its distribution was linked to several experimental variables. The main factors related to error are the presence of homopolymers, position in the sequence, size of the sequence and spatial localization in PT plates for insertion and deletion errors. These factors can be described by considering seven variables. No single variable can account for the error rate distribution, but most of the variation is explained by the combination of all seven variables. The pattern identified here calls for the use of internal controls and error-correcting base callers, to correct for errors, when available (e.g. when sequencing amplicons). For shotgun libraries, the use of both sequencing primers and deep coverage, combined with the use of random sequencing primer sites should partly compensate for even high error rates, although it may prove more difficult than previous thought to distinguish between low-frequency alleles and errors.
TL;DR: Family history, illness course, and clinical status, in addition to DSM-IV-TR criteria, may provide useful information for physicians when assessing evidence of bipolarity in patients with major depressive episodes, and is recommended before deciding on treatment.
Abstract: Context Major depressive disorder, the most common psychiatric illness, is often chronic and a major cause of disability. Many patients with major depressive episodes who have an underlying but unrecognized bipolar disorder receive pharmacologic treatment with ineffective regimens that do not include mood stabilizers. Objective To determine the frequency of bipolar disorder symptoms in patients seeking treatment for a major depressive episode. Design Multicenter, multinational, transcultural, cross-sectional, diagnostic study. The study arose from the initiative Bipolar Disorders: Improving Diagnosis, Guidance and Education (BRIDGE). Setting Community and hospital psychiatry departments. Patients Participants included 5635 adults with an ongoing major depressive episode. Main Outcome Measures The frequency of bipolar disorder was determined by applying both DSM-IV-TR criteria and previously described bipolarity specifier criteria. Variables associated with bipolarity were assessed using logistic regression. Results A total of 903 patients fulfilled DSM-IV-TR criteria for bipolar disorder (16.0%; 95% confidence interval, 15.1%-17.0%), whereas 2647 (47.0%; 95% confidence interval, 45.7%-48.3%) met the bipolarity specifier criteria. Using both definitions, significant associations (odds ratio > 2; P Conclusions The bipolar-specifier criteria in comparison with DSM-IV-TR criteria were valid and identified an additional 31% of patients with major depressive episodes who scored positive on the bipolarity criteria. Family history, illness course, and clinical status, in addition to DSM-IV-TR criteria, may provide useful information for physicians when assessing evidence of bipolarity in patients with major depressive episodes. Such an assessment is recommended before deciding on treatment.
European Bioinformatics Institute1, Spanish National Research Council2, Centre national de la recherche scientifique3, École Normale Supérieure4, Pierre-and-Marie-Curie University5, Vrije Universiteit Brussel6, University of Arizona7, University of Milano-Bicocca8, Aix-Marseille University9, Massachusetts Institute of Technology10, Stazione Zoologica Anton Dohrn11, Commissariat à l'énergie atomique et aux énergies alternatives12, University of Bremen13, University College Dublin14, Bigelow Laboratory For Ocean Sciences15, IFREMER16
TL;DR: The structure, robustness, and dynamics of ocean plankton ecosystems remain poorly understood due to sampling, analysis, and computational limitations, and the Tara Oceans consortium organizes expeditions to help fill this gap.
Abstract: With biology becoming quantitative, systems-level studies can now be performed at spatial scales ranging from molecules to ecosystems. Biological data generated consistently across scales can be integrated with physico-chemical contextual data for a truly holistic approach, with a profound impact on our understanding of life [1]–[5]. Marine ecosystems are crucial in the regulation of Earth's biogeochemical cycles and climate [6],[7]. Yet their organization, evolution, and dynamics remain poorly understood [8],[9]. The Tara Oceans project was launched in September 2009 for a 3-year study of the global ocean ecosystem aboard the ship Tara. A unique sampling programme encompassing optical and genomic methods to describe viruses, bacteria, archaea, protists, and metazoans in their physico-chemical environment has been implemented. Starting as a grassroots initiative of a few scientists, the project has grown into a global consortium of over 100 specialists from diverse disciplines, including oceanography, microbial ecology, genomics, molecular, cellular, and systems biology, taxonomy, bioinformatics, data management, and ecosystem modeling. This multidisciplinary community aims to generate systematic, open access datasets usable for probing the morphological and molecular makeup, diversity, evolution, ecology, and global impacts of plankton on the Earth system.
TL;DR: The aim of this tutorial review is to highlight the synergistic effect of the combined use of MCRs and ILs for the development of new eco-compatible methodologies for heterocyclic chemistry.
Abstract: The efficiency of a chemical synthesis can be nowadays measured, not only by parameters like selectivity and overall yield, but also by its raw material, time, human resources and energy requirements, as well as the toxicity and hazard of the chemicals and the protocols involved. The development of multicomponent reactions (MCRs) in the presence of task-specific ionic liquids (ILs), used not only as environmentally benign reaction media, but also as catalysts, is a new approach that meet with the requirements of sustainable chemistry. The aim of this tutorial review is to highlight the synergistic effect of the combined use of MCRs and ILs for the development of new eco-compatible methodologies for heterocyclic chemistry.
TL;DR: Remarkably, the growth demonstrated on a metal surface can be extended onto a thin insulating film and the intrinsic properties to be preserved, and the system should be easily transferable to real devices.
Abstract: Supramolecular chemistry on a surface has produced a large variety of atomically controlled systems, but practical applications are seriously restricted by the use of weakly cohesive non-covalent bonds and by the confinement to a metal surface. Here we report on the formation of a well-ordered organometallic sheet consisting of two-dimensional polymeric phthalocyanine. Remarkably, the growth demonstrated on a metal surface can be extended onto a thin insulating film. We thus expect the intrinsic properties to be preserved, and the system should be easily transferable to real devices.