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Showing papers by "University of Geneva published in 2011"


Journal ArticleDOI
TL;DR: Four-dimensional covariant nonlinear theories of massive gravity are constructed which are ghost-free in the decoupling limit to all orders, and the Hamiltonian constraint is maintained at least up to and including quartic order in nonlinearities, hence excluding the possibility of the Boulware-Deser ghost up to this order.
Abstract: We construct four-dimensional covariant nonlinear theories of massive gravity which are ghost-free in the decoupling limit to all orders. These theories resum explicitly all the nonlinear terms of an effective field theory of massive gravity. We show that away from the decoupling limit the Hamiltonian constraint is maintained at least up to and including quartic order in nonlinearities, hence excluding the possibility of the Boulware-Deser ghost up to this order. We also show that the same remains true to all orders in a similar toy model.

1,909 citations


Journal ArticleDOI
Georg Ehret1, Georg Ehret2, Georg Ehret3, Patricia B. Munroe4  +388 moreInstitutions (110)
06 Oct 2011-Nature
TL;DR: A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function, and these findings suggest potential novel therapeutic pathways for cardiovascular disease prevention.
Abstract: Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

1,829 citations


Journal ArticleDOI
TL;DR: The epidemiology of endemic health-care-associated infection in developing countries is assessed and a need to improve surveillance and infection-control practices is indicated.

1,737 citations


Journal ArticleDOI
TL;DR: The theoretical and experimental status quo of this very active field of quantum repeater protocols is reviewed, and the potentials of different approaches are compared quantitatively, with a focus on the most immediate goal of outperforming the direct transmission of photons.
Abstract: The distribution of quantum states over long distances is limited by photon loss. Straightforward amplification as in classical telecommunications is not an option in quantum communication because of the no-cloning theorem. This problem could be overcome by implementing quantum repeater protocols, which create long-distance entanglement from shorter-distance entanglement via entanglement swapping. Such protocols require the capacity to create entanglement in a heralded fashion, to store it in quantum memories, and to swap it. One attractive general strategy for realizing quantum repeaters is based on the use of atomic ensembles as quantum memories, in combination with linear optical techniques and photon counting to perform all required operations. Here the theoretical and experimental status quo of this very active field are reviewed. The potentials of different approaches are compared quantitatively, with a focus on the most immediate goal of outperforming the direct transmission of photons.

1,603 citations


Journal ArticleDOI
TL;DR: An overview of the project and the resources it is generating and the application of ENCODE data to interpret the human genome are provided.
Abstract: The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The ENCODE Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and DNA methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of ENCODE data to interpret the human genome.

1,446 citations


Journal ArticleDOI
TL;DR: It is shown that mitochondrial morphology determines the cellular response to macroautophagy, and regulated changes in mitochondrial morphology determine the fate of the cell during autophagic degradation.
Abstract: A plethora of cellular processes, including apoptosis, depend on regulated changes in mitochondrial shape and ultrastructure. The role of mitochondria and of their morphology during autophagy, a bulk degradation and recycling process of eukaryotic cells' constituents, is not well understood. Here we show that mitochondrial morphology determines the cellular response to macroautophagy. When autophagy is triggered, mitochondria elongate in vitro and in vivo. During starvation, cellular cyclic AMP levels increase and protein kinase A (PKA) is activated. PKA in turn phosphorylates the pro-fission dynamin-related protein 1 (DRP1), which is therefore retained in the cytoplasm, leading to unopposed mitochondrial fusion. Elongated mitochondria are spared from autophagic degradation, possess more cristae, increased levels of dimerization and activity of ATP synthase, and maintain ATP production. Conversely, when elongation is genetically or pharmacologically blocked, mitochondria consume ATP, precipitating starvation-induced death. Thus, regulated changes in mitochondrial morphology determine the fate of the cell during autophagy.

1,443 citations


Journal ArticleDOI
K. Abe1, N. Abgrall2, Yasuo Ajima, Hiroaki Aihara1  +413 moreInstitutions (53)
TL;DR: The T2K experiment observes indications of ν (μ) → ν(e) appearance in data accumulated with 1.43×10(20) protons on target, and under this hypothesis, the probability to observe six or more candidate events is 7×10(-3), equivalent to 2.5σ significance.
Abstract: The T2K experiment observes indications of nu(mu) -> nu(mu) e appearance in data accumulated with 1.43 x 10(20) protons on target. Six events pass all selection criteria at the far detector. In a three-flavor neutrino oscillation scenario with |Delta m(23)(2)| = 2.4 x 10(-3) eV(2), sin(2)2 theta(23) = 1 and sin(2)2 theta(13) = 0, the expected number of such events is 1.5 +/- 0.3(syst). Under this hypothesis, the probability to observe six or more candidate events is 7 x 10(-3), equivalent to 2.5 sigma significance. At 90% C.L., the data are consistent with 0.03(0.04) < sin(2)2 theta(13) < 0.28(0.34) for delta(CP) = 0 and a normal (inverted) hierarchy.

1,361 citations


Journal ArticleDOI
John K. Colbourne1, Michael E. Pfrender2, Michael E. Pfrender3, Donald L. Gilbert1, W. Kelley Thomas4, Abraham E. Tucker4, Abraham E. Tucker1, Todd H. Oakley5, Shin-ichi Tokishita6, Andrea Aerts7, Georg J. Arnold8, Malay Kumar Basu9, Malay Kumar Basu10, Darren J Bauer4, Carla E. Cáceres11, Liran Carmel12, Liran Carmel9, Claudio Casola1, Jeong Hyeon Choi1, John C. Detter7, Qunfeng Dong13, Qunfeng Dong1, Serge Dusheyko7, Brian D. Eads1, Thomas Fröhlich8, Kerry Geiler-Samerotte5, Kerry Geiler-Samerotte14, Daniel Gerlach15, Daniel Gerlach16, Phil Hatcher4, Sanjuro Jogdeo17, Sanjuro Jogdeo4, Jeroen Krijgsveld18, Evgenia V. Kriventseva15, Dietmar Kültz19, Christian Laforsch8, Erika Lindquist7, Jacqueline Lopez1, J. Robert Manak20, J. Robert Manak21, Jean Muller22, Jasmyn Pangilinan7, Rupali P Patwardhan23, Rupali P Patwardhan1, Samuel Pitluck7, Ellen J. Pritham24, Andreas Rechtsteiner1, Andreas Rechtsteiner25, Mina Rho1, Igor B. Rogozin9, Onur Sakarya26, Onur Sakarya5, Asaf Salamov7, Sarah Schaack1, Sarah Schaack24, Harris Shapiro7, Yasuhiro Shiga6, Courtney Skalitzky21, Zachary Smith1, Alexander Souvorov9, Way Sung4, Zuojian Tang1, Zuojian Tang27, Dai Tsuchiya1, Hank Tu7, Hank Tu26, Harmjan R. Vos18, Mei Wang7, Yuri I. Wolf9, Hideo Yamagata6, Takuji Yamada, Yuzhen Ye1, Joseph R. Shaw1, Justen Andrews1, Teresa J. Crease28, Haixu Tang1, Susan Lucas7, Hugh M. Robertson11, Peer Bork, Eugene V. Koonin9, Evgeny M. Zdobnov15, Evgeny M. Zdobnov29, Igor V. Grigoriev7, Michael Lynch1, Jeffrey L. Boore7, Jeffrey L. Boore30 
04 Feb 2011-Science
TL;DR: The Daphnia genome reveals a multitude of genes and shows adaptation through gene family expansions, and the coexpansion of gene families interacting within metabolic pathways suggests that the maintenance of duplicated genes is not random.
Abstract: We describe the draft genome of the microcrustacean Daphnia pulex, which is only 200 megabases and contains at least 30,907 genes. The high gene count is a consequence of an elevated rate of gene duplication resulting in tandem gene clusters. More than a third of Daphnia's genes have no detectable homologs in any other available proteome, and the most amplified gene families are specific to the Daphnia lineage. The coexpansion of gene families interacting within metabolic pathways suggests that the maintenance of duplicated genes is not random, and the analysis of gene expression under different environmental conditions reveals that numerous paralogs acquire divergent expression patterns soon after duplication. Daphnia-specific genes, including many additional loci within sequenced regions that are otherwise devoid of annotations, are the most responsive genes to ecological challenges.

1,204 citations


Journal ArticleDOI
TL;DR: Fission of mitochondria has been reported to participate in apoptosis in Drosophila and Caenorhabditis elegans, however, in these organisms, mitochondrial membrane permeabilization does not occur and the mechanism by which mitochondrial dynamics participates in cell death remains elusive.

1,204 citations


Journal ArticleDOI
Marcos Daniel Actis1, G. Agnetta2, Felix Aharonian3, A. G. Akhperjanian  +682 moreInstitutions (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


Journal ArticleDOI
TL;DR: In this paper, the authors highlight some of the exciting properties of complex transition metal oxides, including high dielectric permittivities, piezo-, pyro-, and ferroelectricity.
Abstract: Complex transition metal oxides span a wide range of crystalline structures and play host to an incredible variety of physical phenomena. High dielectric permittivities, piezo-, pyro-, and ferroelectricity are just a few of the functionalities offered by this class of materials, while the potential for applications of the more exotic properties like high temperature superconductivity and colossal magnetoresistance is still waiting to be fully exploited. With recent advances in deposition techniques, the structural quality of oxide heterostructures now rivals that of the best conventional semiconductors, taking oxide electronics to a new level. Such heterostructures have enabled the fabrication of artificial multifunctional materials. At the same time they have exposed a wealth of phenomena at the boundaries where compounds with different structural instabilities and electronic properties meet, giving unprecedented access to new physics emerging at oxide interfaces. Here we highlight some of these exciting...

Journal ArticleDOI
01 Apr 2011-Science
TL;DR: It is shown that dimers of the UVR8 protein perceive UV-B, probably by a tryptophan-based mechanism, which mediatesUV-B photomorphogenic responses securing plant acclimation and thus promotes survival in sunlight.
Abstract: To optimize their growth and survival, plants perceive and respond to ultraviolet-B (UV-B) radiation. However, neither the molecular identity of the UV-B photoreceptor nor the photoperception mechanism is known. Here we show that dimers of the UVR8 protein perceive UV-B, probably by a tryptophan-based mechanism. Absorption of UV-B induces instant monomerization of the photoreceptor and interaction with COP1, the central regulator of light signaling. Thereby this signaling cascade controlled by UVR8 mediates UV-B photomorphogenic responses securing plant acclimation and thus promotes survival in sunlight.

Journal ArticleDOI
24 Feb 2011-Neuron
TL;DR: The effects that addictive drugs leave on glutamatergic and GABAergic synaptic transmission in these three brain areas are reviewed, which outlasts the presence of the drug in the brain and contributes to the reorganization of neural circuits.

Journal ArticleDOI
TL;DR: The physics of one-dimensional interacting bosonic systems is reviewed in this paper, where the effects of various perturbations on the Tomonaga-Luttinger liquid state are discussed as well as extensions to multicomponent and out of equilibrium situations.
Abstract: The physics of one-dimensional interacting bosonic systems is reviewed. Beginning with results from exactly solvable models and computational approaches, the concept of bosonic Tomonaga-Luttinger liquids relevant for one-dimensional Bose fluids is introduced, and compared with Bose-Einstein condensates existing in dimensions higher than one. The effects of various perturbations on the Tomonaga-Luttinger liquid state are discussed as well as extensions to multicomponent and out of equilibrium situations. Finally, the experimental systems that can be described in terms of models of interacting bosons in one dimension are discussed.

Journal ArticleDOI
22 Apr 2011-Science
TL;DR: This work established various gene trap cell lines and transgenic cell lines expressing a short-lived luciferase protein from an unstable mRNA, and recorded bioluminescence in real time in single cells, demonstrating that bursting kinetics are highly gene-specific.
Abstract: In prokaryotes and eukaryotes, most genes appear to be transcribed during short periods called transcriptional bursts, interspersed by silent intervals. We describe how such bursts generate gene-specific temporal patterns of messenger RNA (mRNA) synthesis in mammalian cells. To monitor transcription at high temporal resolution, we established various gene trap cell lines and transgenic cell lines expressing a short-lived luciferase protein from an unstable mRNA, and recorded bioluminescence in real time in single cells. Mathematical modeling identified gene-specific on- and off-switching rates in transcriptional activity and mean numbers of mRNAs produced during the bursts. Transcriptional kinetics were markedly altered by cis-regulatory DNA elements. Our analysis demonstrated that bursting kinetics are highly gene-specific, reflecting refractory periods during which genes stay inactive for a certain time before switching on again.

Journal ArticleDOI
TL;DR: Structural, mechanistic and molecular biological studies have started to reveal how these conserved proteins can perform such diverse functions and how accessory proteins have a central role in their regulation.
Abstract: RNA helicases of the DEAD box family are present in all eukaryotic cells and in many bacteria and Archaea. These highly conserved enzymes are required for RNA metabolism from transcription to degradation and are therefore important players in gene expression. DEAD box proteins use ATP to unwind short duplex RNA in an unusual fashion and remodel RNA-protein complexes, but they can also function as ATP-dependent RNA clamps to provide nucleation centres that establish larger RNA-protein complexes. Structural, mechanistic and molecular biological studies have started to reveal how these conserved proteins can perform such diverse functions and how accessory proteins have a central role in their regulation.

Journal ArticleDOI
01 Dec 2011-Genetics
TL;DR: The yeast Saccharomyces cerevisiae has played a prominent role in both the discovery of TOR and the elucidation of its function, and the TOR signaling network in S. cerevisia is reviewed.
Abstract: TOR (Target Of Rapamycin) is a highly conserved protein kinase that is important in both fundamental and clinical biology. In fundamental biology, TOR is a nutrient-sensitive, central controller of cell growth and aging. In clinical biology, TOR is implicated in many diseases and is the target of the drug rapamycin used in three different therapeutic areas. The yeast Saccharomyces cerevisiae has played a prominent role in both the discovery of TOR and the elucidation of its function. Here we review the TOR signaling network in S. cerevisiae.

Journal ArticleDOI
S. Chatrchyan, Vardan Khachatryan, Albert M. Sirunyan, A. Tumasyan  +2268 moreInstitutions (158)
TL;DR: In this article, the transverse momentum balance in dijet and γ/Z+jets events is used to measure the jet energy response in the CMS detector, as well as the transversal momentum resolution.
Abstract: Measurements of the jet energy calibration and transverse momentum resolution in CMS are presented, performed with a data sample collected in proton-proton collisions at a centre-of-mass energy of 7TeV, corresponding to an integrated luminosity of 36pb−1. The transverse momentum balance in dijet and γ/Z+jets events is used to measure the jet energy response in the CMS detector, as well as the transverse momentum resolution. The results are presented for three different methods to reconstruct jets: a calorimeter-based approach, the ``Jet-Plus-Track'' approach, which improves the measurement of calorimeter jets by exploiting the associated tracks, and the ``Particle Flow'' approach, which attempts to reconstruct individually each particle in the event, prior to the jet clustering, based on information from all relevant subdetectors

Journal ArticleDOI
TL;DR: Interleukin-6 mediates crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand and suggests that drugs modulating this loop may be useful in type 2 diabetes.
Abstract: Exercise, obesity and type 2 diabetes are associated with elevated plasma concentrations of interleukin-6 (IL-6). Glucagon-like peptide-1 (GLP-1) is a hormone that induces insulin secretion. Here we show that administration of IL-6 or elevated IL-6 concentrations in response to exercise stimulate GLP-1 secretion from intestinal L cells and pancreatic alpha cells, improving insulin secretion and glycemia. IL-6 increased GLP-1 production from alpha cells through increased proglucagon (which is encoded by GCG) and prohormone convertase 1/3 expression. In models of type 2 diabetes, the beneficial effects of IL-6 were maintained, and IL-6 neutralization resulted in further elevation of glycemia and reduced pancreatic GLP-1. Hence, IL-6 mediates crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand. This previously unidentified endocrine loop implicates IL-6 in the regulation of insulin secretion and suggests that drugs modulating this loop may be useful in type 2 diabetes.

Journal ArticleDOI
K. Abe1, N. Abgrall2, Hiroaki Aihara1, Yasuo Ajima  +533 moreInstitutions (53)
TL;DR: The T2K experiment as discussed by the authors is a long-baseline neutrino oscillation experiment whose main goal is to measure the last unknown lepton sector mixing angle by observing its appearance in a particle beam generated by the J-PARC accelerator.
Abstract: The T2K experiment is a long-baseline neutrino oscillation experiment Its main goal is to measure the last unknown lepton sector mixing angle {\theta}_{13} by observing { u}_e appearance in a { u}_{\mu} beam It also aims to make a precision measurement of the known oscillation parameters, {\Delta}m^{2}_{23} and sin^{2} 2{\theta}_{23}, via { u}_{\mu} disappearance studies Other goals of the experiment include various neutrino cross section measurements and sterile neutrino searches The experiment uses an intense proton beam generated by the J-PARC accelerator in Tokai, Japan, and is composed of a neutrino beamline, a near detector complex (ND280), and a far detector (Super-Kamiokande) located 295 km away from J-PARC This paper provides a comprehensive review of the instrumentation aspect of the T2K experiment and a summary of the vital information for each subsystem

Journal ArticleDOI
TL;DR: E-cigarettes were used much as people would use nicotine replacement medications: by former smokers to avoid relapse or as an aid to cut down or quit smoking, and for quitting and relapse prevention.
Abstract: Aims To assess the profile, utilization patterns, satisfaction and perceived effects among users of electronic cigarettes (‘e-cigarettes’). Design and Setting Internet survey in English and French in 2010. Measurements Online questionnaire. Participants Visitors of websites and online discussion forums dedicated to e-cigarettes and to smoking cessation. Findings There were 3587 participants (70% former tobacco smokers, 61% men, mean age 41 years). The median duration of electronic cigarette use was 3 months, users drew 120 puffs/day and used five refills/day. Almost all (97%) used e-cigarettes containing nicotine. Daily users spent $33 per month on these products. Most (96%) said the e-cigarette helped them to quit smoking or reduce their smoking (92%). Reasons for using the e-cigaretteincludedtheperceptionthatitwaslesstoxicthantobacco(84%),todealwithcravingfortobacco(79%)and withdrawal symptoms (67%), to quit smoking or avoid relapsing (77%), because it was cheaper than smoking (57%) and to deal with situations where smoking was prohibited (39%). Most ex-smokers (79%) feared they might relapse to smoking if they stopped using the e-cigarette. Users of nicotine-containing e-cigarettes reported better relief of withdrawalandagreatereffectonsmokingcessationthanthoseusingnon-nicotinee-cigarettes.Conclusions E-cigarettes were used much as people would use nicotine replacement medications: by former smokers to avoid relapse or as an aid tocutdownorquitsmoking.Furtherresearchshouldevaluatethesafetyandefficacyof e-cigarettesforadministration of nicotine and other substances, and for quitting and relapse prevention.

Journal ArticleDOI
TL;DR: In this article, the authors review studies of the electromagnetic response of various classes of correlated electron materials including transition metal oxides, organic and molecular conductors, intermetallic compounds with $d$- and $f$-electrons as well as magnetic semiconductors.
Abstract: We review studies of the electromagnetic response of various classes of correlated electron materials including transition metal oxides, organic and molecular conductors, intermetallic compounds with $d$- and $f$-electrons as well as magnetic semiconductors. Optical inquiry into correlations in all these diverse systems is enabled by experimental access to the fundamental characteristics of an ensemble of electrons including their self-energy and kinetic energy. Steady-state spectroscopy carried out over a broad range of frequencies from microwaves to UV light and fast optics time-resolved techniques provide complimentary prospectives on correlations. Because the theoretical understanding of strong correlations is still evolving, the review is focused on the analysis of the universal trends that are emerging out of a large body of experimental data augmented where possible with insights from numerical studies.

Journal ArticleDOI
TL;DR: In vivo imaging and pharmacological experiments show that macrophage-derived reactive oxygen and nitrogen species (ROS and RNS) can trigger mitochondrial pathology and initiate FAD, and suggest that inflammatory axon damage might be spontaneously reversible and thus a potential target for therapy.
Abstract: In multiple sclerosis, a common inflammatory disease of the central nervous system, immune-mediated axon damage is responsible for permanent neurological deficits. How axon damage is initiated is not known. Here we use in vivo imaging to identify a previously undescribed variant of axon damage in a mouse model of multiple sclerosis. This process, termed 'focal axonal degeneration' (FAD), is characterized by sequential stages, beginning with focal swellings and progressing to axon fragmentation. Notably, most swollen axons persist unchanged for several days, and some recover spontaneously. Early stages of FAD can be observed in axons with intact myelin sheaths. Thus, contrary to the classical view, demyelination-a hallmark of multiple sclerosis-is not a prerequisite for axon damage. Instead, focal intra-axonal mitochondrial pathology is the earliest ultrastructural sign of damage, and it precedes changes in axon morphology. Molecular imaging and pharmacological experiments show that macrophage-derived reactive oxygen and nitrogen species (ROS and RNS) can trigger mitochondrial pathology and initiate FAD. Indeed, neutralization of ROS and RNS rescues axons that have already entered the degenerative process. Finally, axonal changes consistent with FAD can be detected in acute human multiple sclerosis lesions. In summary, our data suggest that inflammatory axon damage might be spontaneously reversible and thus a potential target for therapy.

Journal ArticleDOI
TL;DR: The manuscript describes the “digital transcriptome atlas” of the developing mouse embryo, a powerful resource to determine co-expression of genes, to identify cell populations and lineages and to identify functional associations between genes relevant to development and disease.
Abstract: Ascertaining when and where genes are expressed is of crucial importance to understanding or predicting the physiological role of genes and proteins and how they interact to form the complex networks that underlie organ development and function. It is, therefore, crucial to determine on a genome-wide level, the spatio-temporal gene expression profiles at cellular resolution. This information is provided by colorimetric RNA in situ hybridization that can elucidate expression of genes in their native context and does so at cellular resolution. We generated what is to our knowledge the first genome-wide transcriptome atlas by RNA in situ hybridization of an entire mammalian organism, the developing mouse at embryonic day 14.5. This digital transcriptome atlas, the Eurexpress atlas (http://www.eurexpress.org), consists of a searchable database of annotated images that can be interactively viewed. We generated anatomy-based expression profiles for over 18,000 coding genes and over 400 microRNAs. We identified 1,002 tissue-specific genes that are a source of novel tissue-specific markers for 37 different anatomical structures. The quality and the resolution of the data revealed novel molecular domains for several developing structures, such as the telencephalon, a novel organization for the hypothalamus, and insight on the Wnt network involved in renal epithelial differentiation during kidney development. The digital transcriptome atlas is a powerful resource to determine co-expression of genes, to identify cell populations and lineages, and to identify functional associations between genes relevant to development and disease.

Journal ArticleDOI
TL;DR: In this article, the authors studied the effect of collision centrality on the transverse momentum of PbPb collisions at the LHC with a data sample of 6.7 inverse microbarns.
Abstract: Jet production in PbPb collisions at a nucleon-nucleon center-of-mass energy of 2.76 TeV was studied with the CMS detector at the LHC, using a data sample corresponding to an integrated luminosity of 6.7 inverse microbarns. Jets are reconstructed using the energy deposited in the CMS calorimeters and studied as a function of collision centrality. With increasing collision centrality, a striking imbalance in dijet transverse momentum is observed, consistent with jet quenching. The observed effect extends from the lower cut-off used in this study (jet transverse momentum = 120 GeV/c) up to the statistical limit of the available data sample (jet transverse momentum approximately 210 GeV/c). Correlations of charged particle tracks with jets indicate that the momentum imbalance is accompanied by a softening of the fragmentation pattern of the second most energetic, away-side jet. The dijet momentum balance is recovered when integrating low transverse momentum particles distributed over a wide angular range relative to the direction of the away-side jet.

Journal ArticleDOI
TL;DR: In this paper, the authors show that the planar free energy of ABJM theory matches the classical IIA supergravity action on a zero-dimensional super-matrix model and gives the correct N 3/2 scaling for the number of degrees of freedom of M2 brane theory.
Abstract: The partition function of $${\mathcal{N}=6}$$ supersymmetric Chern–Simons-matter theory (known as ABJM theory) on $${\mathbb{S}^3}$$ , as well as certain Wilson loop observables, are captured by a zero dimensional super-matrix model. This super–matrix model is closely related to a matrix model describing topological Chern–Simons theory on a lens space. We explore further these recent observations and extract more exact results in ABJM theory from the matrix model. In particular we calculate the planar free energy, which matches at strong coupling the classical IIA supergravity action on $${{\rm AdS}_4\times\mathbb{C}\mathbb{P}^3}$$ and gives the correct N 3/2 scaling for the number of degrees of freedom of the M2 brane theory. Furthermore we find contributions coming from world-sheet instanton corrections in $${\mathbb{C}\mathbb{P}^3}$$ . We also calculate non-planar corrections, both to the free energy and to the Wilson loop expectation values. This matrix model appears also in the study of topological strings on a toric Calabi–Yau manifold, and an intriguing connection arises between the space of couplings of the planar ABJM theory and the moduli space of this Calabi–Yau. In particular it suggests that, in addition to the usual perturbative and strong coupling (AdS) expansions, a third natural expansion locus is the line where one of the two ’t Hooft couplings vanishes and the other is finite. This is the conifold locus of the Calabi–Yau, and leads to an expansion around topological Chern–Simons theory. We present some explicit results for the partition function and Wilson loop observables around this locus.

Journal ArticleDOI
21 Apr 2011-Nature
TL;DR: The retroviral restriction factor TRIM5 has two additional activities that are linked to restriction: it constitutively promotes innate immune signalling and it acts as a pattern recognition receptor specific for the retrovirus capsid lattice.
Abstract: TRIM5 is a RING domain-E3 ubiquitin ligase that restricts infection by human immunodeficiency virus (HIV)-1 and other retroviruses immediately following virus invasion of the target cell cytoplasm. Antiviral potency correlates with TRIM5 avidity for the retrovirion capsid lattice and several reports indicate that TRIM5 has a role in signal transduction, but the precise mechanism of restriction is unknown. Here we demonstrate that TRIM5 promotes innate immune signalling and that this activity is amplified by retroviral infection and interaction with the capsid lattice. Acting with the heterodimeric, ubiquitin-conjugating enzyme UBC13-UEV1A (also known as UBE2N-UBE2V1), TRIM5 catalyses the synthesis of unattached K63-linked ubiquitin chains that activate the TAK1 (also known as MAP3K7) kinase complex and stimulate AP-1 and NFκB signalling. Interaction with the HIV-1 capsid lattice greatly enhances the UBC13-UEV1A-dependent E3 activity of TRIM5 and challenge with retroviruses induces the transcription of AP-1 and NF-κB-dependent factors with a magnitude that tracks with TRIM5 avidity for the invading capsid. Finally, TAK1 and UBC13-UEV1A contribute to capsid-specific restriction by TRIM5. Thus, the retroviral restriction factor TRIM5 has two additional activities that are linked to restriction: it constitutively promotes innate immune signalling and it acts as a pattern recognition receptor specific for the retrovirus capsid lattice.

Journal ArticleDOI
TL;DR: Methods to analyze the brain's electric fields recorded with multichannel Electroencephalogram (EEG) and their implementation in the software CARTOOL, designed to visualize the data and the analysis results using 3-dimensional display routines that allow rapid manipulation and animation of 3D images.
Abstract: This paper describes methods to analyze the brain's electric fields recorded with multichannel Electroencephalogram (EEG) and demonstrates their implementation in the software CARTOOL. It focuses on the analysis of the spatial properties of these fields and on quantitative assessment of changes of field topographies across time, experimental conditions, or populations. Topographic analyses are advantageous because they are reference independents and thus render statistically unambiguous results. Neurophysiologically, differences in topography directly indicate changes in the configuration of the active neuronal sources in the brain. We describe global measures of field strength and field similarities, temporal segmentation based on topographic variations, topographic analysis in the frequency domain, topographic statistical analysis, and source imaging based on distributed inverse solutions. All analysis methods are implemented in a freely available academic software package called CARTOOL. Besides providing these analysis tools, CARTOOL is particularly designed to visualize the data and the analysis results using 3-dimensional display routines that allow rapid manipulation and animation of 3D images. CARTOOL therefore is a helpful tool for researchers as well as for clinicians to interpret multichannel EEG and evoked potentials in a global, comprehensive, and unambiguous way.

Journal ArticleDOI
07 Apr 2011-Nature
TL;DR: It is found that natural and experimentally induced variants in ONSEN insertions confer heat responsiveness to nearby genes, and therefore mobility bursts may generate novel, stress-responsive regulatory gene networks.
Abstract: Eukaryotic genomes consist to a significant extent of retrotransposons that are suppressed by host epigenetic mechanisms, preventing their uncontrolled propagation. However, it is not clear how this is achieved. Here we show that in Arabidopsis seedlings subjected to heat stress, a copia-type retrotransposon named ONSEN (Japanese 'hot spring') not only became transcriptionally active but also synthesized extrachromosomal DNA copies. Heat-induced ONSEN accumulation was stimulated in mutants impaired in the biogenesis of small interfering RNAs (siRNAs); however, there was no evidence of transposition occurring in vegetative tissues. After stress, both ONSEN transcripts and extrachromosomal DNA gradually decayed and were no longer detected after 20-30 days. Surprisingly, a high frequency of new ONSEN insertions was observed in the progeny of stressed plants deficient in siRNAs. Insertion patterns revealed that this transgenerational retrotransposition occurred during flower development and before gametogenesis. Therefore in plants with compromised siRNA biogenesis, memory of stress was maintained throughout development, priming ONSEN to transpose during differentiation of generative organs. Retrotransposition was not observed in the progeny of wild-type plants subjected to stress or in non-stressed mutant controls, pointing to a crucial role of the siRNA pathway in restricting retrotransposition triggered by environmental stress. Finally, we found that natural and experimentally induced variants in ONSEN insertions confer heat responsiveness to nearby genes, and therefore mobility bursts may generate novel, stress-responsive regulatory gene networks.

Journal ArticleDOI
Peter A. R. Ade1, Nabila Aghanim, Monique Arnaud, M. Ashdown2  +291 moreInstitutions (57)
TL;DR: The European Space Agency's Planck satellite was launched on 14 May 2009, and has been surveying the sky stably and continuously since 13 August 2009 as mentioned in this paper, and it will continue to gather scientific data until the end of its cryogenic lifetime.
Abstract: The European Space Agency's Planck satellite was launched on 14 May 2009, and has been surveying the sky stably and continuously since 13 August 2009. Its performance is well in line with expectations, and it will continue to gather scientific data until the end of its cryogenic lifetime. We give an overview of the history of Planck in its first year of operations, and describe some of the key performance aspects of the satellite. This paper is part of a package submitted in conjunction with Planck's Early Release Compact Source Catalogue, the first data product based on Planck to be released publicly. The package describes the scientific performance of the Planck payload, and presents results on a variety of astrophysical topics related to the sources included in the Catalogue, as well as selected topics on diffuse emission.