Showing papers by "Vrije Universiteit Brussel published in 2013"
University of Copenhagen1, Institut national de la recherche agronomique2, Vrije Universiteit Brussel3, South China University of Technology4, Glostrup Hospital5, Aalborg University6, University of Southern Denmark7, Technical University of Denmark8, Wageningen University and Research Centre9, Pierre-and-Marie-Curie University10, French Institute of Health and Medical Research11, University of Helsinki12, Institut de recherche pour le développement13
TL;DR: The authors' classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities.
Abstract: We are facing a global metabolic health crisis provoked by an obesity epidemic. Here we report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. We find two groups of individuals that differ by the number of gut microbial genes and thus gut bacterial richness. They contain known and previously unknown bacterial species at different proportions; individuals with a low bacterial richness (23% of the population) are characterized by more marked overall adiposity, insulin resistance and dyslipidaemia and a more pronounced inflammatory phenotype when compared with high bacterial richness individuals. The obese individuals among the lower bacterial richness group also gain more weight over time. Only a few bacterial species are sufficient to distinguish between individuals with high and low bacterial richness, and even between lean and obese participants. Our classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities.
3,448 citations
TL;DR: The facile identification of antigen-specific VHHs and their beneficial biochemical and economic properties have encouraged antibody engineering of these single-domain antibodies for use as a research tool and in biotechnology and medicine.
Abstract: Sera of camelids contain both conventional heterotetrameric antibodies and unique functional heavy (H)-chain antibodies (HCAbs). The H chain of these homodimeric antibodies consists of one antigen-binding domain, the VHH, and two constant domains. HCAbs fail to incorporate light (L) chains owing to the deletion of the first constant domain and a reshaped surface at the VHH side, which normally associates with L chains in conventional antibodies. The genetic elements composing HCAbs have been identified, but the in vivo generation of these antibodies from their dedicated genes into antigen-specific and affinity-matured bona fide antibodies remains largely underinvestigated. However, the facile identification of antigen-specific VHHs and their beneficial biochemical and economic properties (size, affinity, specificity, stability, production cost) supported by multiple crystal structures have encouraged antibody engineering of these single-domain antibodies for use as a research tool and in biotechnology and medicine.
1,543 citations
University of Adelaide1, University of Wisconsin-Madison2, Ghent University3, University of Canterbury4, University of Geneva5, Humboldt University of Berlin6, University of California, Irvine7, University of Mainz8, University of California, Berkeley9, Ohio State University10, Université libre de Bruxelles11, Ruhr University Bochum12, University of Wuppertal13, University of Maryland, College Park14, University of Kansas15, Lawrence Berkeley National Laboratory16, RWTH Aachen University17, Uppsala University18, University of Alberta19, Stockholm University20, Vrije Universiteit Brussel21, University of Bonn22, École Polytechnique Fédérale de Lausanne23, Georgia Institute of Technology24, Pennsylvania State University25, Technical University of Dortmund26, Southern University and A&M College27
TL;DR: The presence of a high-energy neutrino flux containing the most energetic neutrinos ever observed is revealed, including 28 events at energies between 30 and 1200 TeV, although the origin of this flux is unknown and the findings are consistent with expectations for a neutRino population with origins outside the solar system.
Abstract: We report on results of an all-sky search for high-energy neutrino events interacting within the IceCube neutrino detector conducted between May 2010 and May 2012. The search follows up on the previous detection of two PeV neutrino events, with improved sensitivity and extended energy coverage down to about 30 TeV. Twenty-six additional events were observed, substantially more than expected from atmospheric backgrounds. Combined, both searches reject a purely atmospheric origin for the 28 events at the 4 sigma level. These 28 events, which include the highest energy neutrinos ever observed, have flavors, directions, and energies inconsistent with those expected from the atmospheric muon and neutrino backgrounds. These properties are, however, consistent with generic predictions for an additional component of extraterrestrial origin.
1,490 citations
University of Düsseldorf1, Goethe University Frankfurt2, Vrije Universiteit Brussel3, University of Freiburg4, Leipzig University5, Dow Chemical Company6, University of Tübingen7, Durham University8, University of Turin9, Seoul National University10, University of Jena11, Charité12, University of Valencia13, Heidelberg University14, French Institute for Research in Computer Science and Automation15, University of Paris16, University of Liverpool17, University of Groningen18, Lund University19, University of Manchester20, South Valley University21, University Hospital Regensburg22, Merck KGaA23, Musashino University24, University of Kansas25, Ludwig Maximilian University of Munich26, Fresenius Medical Care27, University of Regensburg28, Merck & Co.29
TL;DR: This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro and how closely hepatoma, stem cell and iPS cell–derived hepatocyte-like-cells resemble real hepatocytes.
Abstract: This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4α, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4α), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell-derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun.
1,085 citations
Mayo Clinic1, University of Pittsburgh2, Autonomous University of Barcelona3, University of Alberta4, Karolinska University Hospital5, University of Florida6, New York Methodist Hospital7, United States Department of Veterans Affairs8, George Washington University9, University of Duisburg-Essen10, Albert Einstein College of Medicine11, Virginia Commonwealth University12, Otto-von-Guericke University Magdeburg13, Vrije Universiteit Brussel14, Ghent University Hospital15, Hospital of the University of Pennsylvania16, University of Chicago17, Duke University18, University of Maryland, Baltimore19, RWTH Aachen University20, St. John Providence Health System21, University of California, San Diego22, St Thomas' Hospital23, Beth Israel Deaconess Medical Center24, Medical University of Vienna25, Tampa General Hospital26, Goethe University Frankfurt27
TL;DR: Two novel markers for AKI have been identified and validated in independent multicenter cohorts and are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI.
Abstract: Introduction: Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. Methods: We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. Results: Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P 0.72. Furthermore, [TIMP2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method.
997 citations
Université libre de Bruxelles1, University of Exeter2, ETH Zurich3, University of Antwerp4, University of Hamburg5, University of California, San Diego6, University of Bristol7, University of North Carolina at Chapel Hill8, University of Liège9, Centre national de la recherche scientifique10, Bjerknes Centre for Climate Research11, Geophysical Institute, University of Bergen12, Max Planck Society13, University of Bern14, University of Southern California15, Vrije Universiteit Brussel16, Yale University17, University of East Anglia18, Helmholtz Centre for Environmental Research - UFZ19
TL;DR: This article showed that anthropogenic perturbation may have increased the flux of carbon to inland waters by as much as 1.0 Pg C yr−1 since pre-industrial times, mainly owing to enhanced carbon export from soils.
Abstract: A substantial amount of the atmospheric carbon taken up on land through photosynthesis and chemical weathering is transported laterally along the aquatic continuum from upland terrestrial ecosystems to the ocean. So far, global carbon budget estimates have implicitly assumed that the transformation and lateral transport of carbon along this aquatic continuum has remained unchanged since pre-industrial times. A synthesis of published work reveals the magnitude of present-day lateral carbon fluxes from land to ocean, and the extent to which human activities have altered these fluxes. We show that anthropogenic perturbation may have increased the flux of carbon to inland waters by as much as 1.0 Pg C yr−1 since pre-industrial times, mainly owing to enhanced carbon export from soils. Most of this additional carbon input to upstream rivers is either emitted back to the atmosphere as carbon dioxide (~0.4 Pg C yr−1) or sequestered in sediments (~0.5 Pg C yr−1) along the continuum of freshwater bodies, estuaries and coastal waters, leaving only a perturbation carbon input of ~0.1 Pg C yr−1 to the open ocean. According to our analysis, terrestrial ecosystems store ~0.9 Pg C yr−1 at present, which is in agreement with results from forest inventories but significantly differs from the figure of 1.5 Pg C yr−1 previously estimated when ignoring changes in lateral carbon fluxes. We suggest that carbon fluxes along the land–ocean aquatic continuum need to be included in global carbon dioxide budgets.
948 citations
TL;DR: A classification based on the principles through which the variable stiffness and damping are achieved is proposed and allows for designers of new devices to orientate and take inspiration and users of VIA's to be guided in the design and implementation process for their targeted application.
876 citations
TL;DR: These two neutrino-induced events could be a first indication of an astrophysical neutrinos flux; the moderate significance, however, does not permit a definitive conclusion at this time.
Abstract: We report on the observation of two neutrino-induced events which have an estimated deposited energy in the IceCube detector of 1.04 +/- 0.16 and 1.14 +/- 0.17 PeV, respectively, the highest neutrino energies observed so far. These events are consistent with fully contained particle showers induced by neutral-current nu(e,mu,tau) ((nu) over bar (e,mu,tau)) or charged-current nu(e) ((nu) over bar (e)) interactions within the IceCube detector. The events were discovered in a search for ultrahigh energy neutrinos using data corresponding to 615.9 days effective live time. The expected number of atmospheric background is 0.082 +/- 0.004(stat)(-0.057)(+0.041)(syst). The probability of observing two or more candidate events under the atmospheric background-only hypothesis is 2.9 x 10(-3) (2.8 sigma) taking into account the uncertainty on the expected number of background events. These two events could be a first indication of an astrophysical neutrino flux; the moderate significance, however, does not permit a definitive conclusion at this time.
786 citations
TL;DR: The structure of an agonist-bound, active state of the human M2 muscarinic acetylcholine receptor stabilized by a G-protein mimetic camelid antibody fragment isolated by conformational selection using yeast surface display reveals larger conformational changes in the extracellular region and orthosteric binding site than observed in the active states of the β2AR and rhodopsin.
Abstract: Despite recent advances in crystallography and the availability of G-protein-coupled receptor (GPCR) structures, little is known about the mechanism of their activation process, as only the β2 adrenergic receptor (β2AR) and rhodopsin have been crystallized in fully active conformations. Here we report the structure of an agonist-bound, active state of the human M2 muscarinic acetylcholine receptor stabilized by a G-protein mimetic camelid antibody fragment isolated by conformational selection using yeast surface display. In addition to the expected changes in the intracellular surface, the structure reveals larger conformational changes in the extracellular region and orthosteric binding site than observed in the active states of the β2AR and rhodopsin. We also report the structure of the M2 receptor simultaneously bound to the orthosteric agonist iperoxo and the positive allosteric modulator LY2119620. This structure reveals that LY2119620 recognizes a largely pre-formed binding site in the extracellular vestibule of the iperoxo-bound receptor, inducing a slight contraction of this outer binding pocket. These structures offer important insights into the activation mechanism and allosteric modulation of muscarinic receptors.
765 citations
TL;DR: In this article, a detailed description of the analysis used by the CMS Collaboration in the search for the standard model Higgs boson in pp collisions at the LHC, which led to the observation of a new boson.
Abstract: A detailed description is reported of the analysis used by the CMS Collaboration in the search for the standard model Higgs boson in pp collisions at the LHC, which led to the observation of a new boson. The data sample corresponds to integrated luminosities up to 5.1 inverse femtobarns at sqrt(s) = 7 TeV, and up to 5.3 inverse femtobarns at sqrt(s) = 8 TeV. The results for five Higgs boson decay modes gamma gamma, ZZ, WW, tau tau, and bb, which show a combined local significance of 5 standard deviations near 125 GeV, are reviewed. A fit to the invariant mass of the two high resolution channels, gamma gamma and ZZ to 4 ell, gives a mass estimate of 125.3 +/- 0.4 (stat) +/- 0.5 (syst) GeV. The measurements are interpreted in the context of the standard model Lagrangian for the scalar Higgs field interacting with fermions and vector bosons. The measured values of the corresponding couplings are compared to the standard model predictions. The hypothesis of custodial symmetry is tested through the measurement of the ratio of the couplings to the W and Z bosons. All the results are consistent, within their uncertainties, with the expectations for a standard model Higgs boson.
643 citations
TL;DR: By phylogenetic analysis, it is shown that system x(c)(-) is a rather evolutionarily new amino acid transport system and its diverse roles in the regulation of the immune response, in various aspects of cancer and in the eye and the CNS are highlighted.
Abstract: The antiporter system xc− imports the amino acid cystine, the oxidized form of cysteine, into cells with a 1:1 counter-transport of glutamate. It is composed of a light chain, xCT, and a heavy chain, 4F2 heavy chain (4F2hc), and, thus, belongs to the family of heterodimeric amino acid transporters. Cysteine is the rate-limiting substrate for the important antioxidant glutathione (GSH) and, along with cystine, it also forms a key redox couple on its own. Glutamate is a major neurotransmitter in the central nervous system (CNS). By phylogenetic analysis, we show that system xc− is a rather evolutionarily new amino acid transport system. In addition, we summarize the current knowledge regarding the molecular mechanisms that regulate system xc−, including the transcriptional regulation of the xCT light chain, posttranscriptional mechanisms, and pharmacological inhibitors of system xc−. Moreover, the roles of system xc− in regulating GSH levels, the redox state of the extracellular cystine/cysteine re...
TL;DR: In this paper, two-particle angular correlations for charged particles emitted in pPb collisions at a nucleon-nucleon center-of-mass energy of 5.02 TeV are presented.
Dartmouth College1, Uppsala University2, Nagaoka University of Technology3, University of Copenhagen4, Heidelberg University5, Natural Resources Canada6, Oregon State University7, Centre national de la recherche scientifique8, Korean Ocean Research and Development Institute9, Swansea University10, University of Bern11, British Antarctic Survey12, University of Kansas13, National Institute of Polar Research14, University of Iceland15, Stockholm University16, Vrije Universiteit Brussel17, University of Colorado Boulder18, Alfred Wegener Institute for Polar and Marine Research19, University of Washington20, Arctic and Antarctic Research Institute21, Desert Research Institute22, Hokkaido University23, University of Grenoble24, University of California, San Diego25, Université libre de Bruxelles26, Utrecht University27, Oeschger Centre for Climate Change Research28, Max Planck Society29, Swiss Federal Institute for Forest, Snow and Landscape Research30, ETH Zurich31, United Arab Emirates University32, Paul Scherrer Institute33, École Polytechnique Fédérale de Lausanne34, University of East Anglia35, Geological Survey of Canada36
TL;DR: In this paper, the North Greenland Eemian Ice Drilling (NEEM) ice core was extracted from folded Greenland ice using globally homogeneous parameters known from dated Greenland and Antarctic ice-core records.
Abstract: Efforts to extract a Greenland ice core with a complete record of the Eemian interglacial (130,000 to 115,000 years ago) have until now been unsuccessful. The response of the Greenland ice sheet to the warmer-than-present climate of the Eemian has thus remained unclear. Here we present the new North Greenland Eemian Ice Drilling ('NEEM') ice core and show only a modest ice-sheet response to the strong warming in the early Eemian. We reconstructed the Eemian record from folded ice using globally homogeneous parameters known from dated Greenland and Antarctic ice-core records. On the basis of water stable isotopes, NEEM surface temperatures after the onset of the Eemian (126,000 years ago) peaked at 8 +/- 4 degrees Celsius above the mean of the past millennium, followed by a gradual cooling that was probably driven by the decreasing summer insolation. Between 128,000 and 122,000 years ago, the thickness of the northwest Greenland ice sheet decreased by 400 +/- 250 metres, reaching surface elevations 122,000 years ago of 130 +/- 300 metres lower than the present. Extensive surface melt occurred at the NEEM site during the Eemian, a phenomenon witnessed when melt layers formed again at NEEM during the exceptional heat of July 2012. With additional warming, surface melt might become more common in the future.
TL;DR: It is reported that the Wnt pathway is robustly activated upon injury by partial duct ligation (PDL), concomitant with the appearance of Lgr5 expression in regenerating pancreatic ducts.
Abstract: Lgr5 marks adult stem cells in multiple adult organs and is a receptor for the Wnt-agonistic R-spondins (RSPOs). Intestinal, stomach and liver Lgr5(+) stem cells grow in 3D cultures to form ever-expanding organoids, which resemble the tissues of origin. Wnt signalling is inactive and Lgr5 is not expressed under physiological conditions in the adult pancreas. However, we now report that the Wnt pathway is robustly activated upon injury by partial duct ligation (PDL), concomitant with the appearance of Lgr5 expression in regenerating pancreatic ducts. In vitro, duct fragments from mouse pancreas initiate Lgr5 expression in RSPO1-based cultures, and develop into budding cyst-like structures (organoids) that expand five-fold weekly for >40 weeks. Single isolated duct cells can also be cultured into pancreatic organoids, containing Lgr5 stem/progenitor cells that can be clonally expanded. Clonal pancreas organoids can be induced to differentiate into duct as well as endocrine cells upon transplantation, thus proving their bi-potentiality.
TL;DR: A unique chytrid fungus is isolated and characterized, Batrachochytrium salamandrivorans sp.
Abstract: The current biodiversity crisis encompasses a sixth mass extinction event affecting the entire class of amphibians. The infectious disease chytridiomycosis is considered one of the major drivers of global amphibian population decline and extinction and is thought to be caused by a single species of aquatic fungus, Batrachochytrium dendrobatidis. However, several amphibian population declines remain unexplained, among them a steep decrease in fire salamander populations (Salamandra salamandra) that has brought this species to the edge of local extinction. Here we isolated and characterized a unique chytrid fungus, Batrachochytrium salamandrivorans sp. nov., from this salamander population. This chytrid causes erosive skin disease and rapid mortality in experimentally infected fire salamanders and was present in skin lesions of salamanders found dead during the decline event. Together with the closely related B. dendrobatidis, this taxon forms a well-supported chytridiomycete clade, adapted to vertebrate hosts and highly pathogenic to amphibians. However, the lower thermal growth preference of B. salamandrivorans, compared with B. dendrobatidis, and resistance of midwife toads (Alytes obstetricans) to experimental infection with B. salamandrivorans suggest differential niche occupation of the two chytrid fungi.
Harvard University1, University College London2, Vrije Universiteit Brussel3, University of Alabama at Birmingham4, Princess Margaret Cancer Centre5, Henry Ford Health System6, Cedars-Sinai Medical Center7, St. Joseph's Hospital and Medical Center8, University of Texas MD Anderson Cancer Center9, University of Melbourne10, Royal Melbourne Hospital11, Medical University of Graz12, AstraZeneca13, Erasmus University Rotterdam14
TL;DR: This study did not meet its primary end point of PFS prolongation with cediranib either as monotherapy or in combination with lomustine versus lomUSTine in patients with recurrent glioblastoma, although cedIRanib showed evidence of clinical activity on some secondary end points including time to deterioration in neurologic status and corticosteroid-sparing effects.
Abstract: Purpose A randomized, phase III, placebo-controlled, partially blinded clinical trial (REGAL [Recentin in Glioblastoma Alone and With Lomustine]) was conducted to determine the efficacy of cediranib, an oral pan–vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, either as monotherapy or in combination with lomustine versus lomustine in patients with recurrent glioblastoma. Patients and Methods Patients (N = 325) with recurrent glioblastoma who previously received radiation and temozolomide were randomly assigned 2:2:1 to receive (1) cediranib (30 mg) monotherapy; (2) cediranib (20 mg) plus lomustine (110 mg/m2); (3) lomustine (110 mg/m2) plus a placebo. The primary end point was progression-free survival based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted magnetic resonance imaging (MRI) brain scans. Results The primary end point of progression-free survival (PFS) was not significantly different for either cediranib alone...
TL;DR: It is reported that hypoxia-induced Semaphorin 3A (Sema3A) acts as an attractant for TAMs by triggering vascular endothelial growth factor receptor 1 phosphorylation through the associated holoreceptor, composed of Neuropilin-1 (Nrp1) and PlexinA1/PlexinA4.
TL;DR: A systematic review of cycling-related sport-science literature shows the large variety in the description of female subject groups in the existing literature, and proposes a standardized preexperimental testing protocol and guidelines to classifyfemale subject groups into 5 PLs based on relative VO2max, relative PPO, training status, absolute VO2 max, and absolute PPO.
Abstract: Aim: To review current cycling-related sport-science literature to formulate guidelines to classify female subject groups and to compare this classification system for female subject groups with the classification system for male subject groups. Methods: A database of 82 papers that described female subject groups containing information on preexperimental maximal cycle-protocol designs, terminology, biometrical and physiological parameters, and cycling experience was analyzed. Subject groups were divided into performance levels (PLs), according to the nomenclature. Body mass, body-mass index, maximal oxygen consumption (VO2max), peak power output (PPO), and training status were compared between PLs and between female and male PLs. Results: Five female PLs were defined, representing untrained, active, trained, well-trained, and professional female subjects. VO2max and PPO significantly increased with PL, except for PL3 and PL4 (P < .01). For each PL, significant differences were observed in absolute and re...
TL;DR: In this paper, measurements of two-and four-particle angular correlations for charged particles emitted in pPb collisions are presented over a wide range in pseudorapidity and full azimuth.
TL;DR: A search for muon neutrinos from dark matter annihilation in the center of the Sun with the 79-string configuration of the IceCube neutrino telescope is performed, lowering the energy threshold and extending the search to the austral summer.
Abstract: We have performed a search for muon neutrinos from dark matter annihilation in the center of the Sun with the 79-string configuration of the IceCube neutrino telescope. For the first time, the DeepCore subarray is included in the analysis, lowering the energy threshold and extending the search to the austral summer. The 317 days of data collected between June 2010 and May 2011 are consistent with the expected background from atmospheric muons and neutrinos. Upper limits are set on the dark matter annihilation rate, with conversions to limits on spin-dependent and spin-independent scattering cross sections of weakly interacting massive particles (WIMPs) on protons, for WIMP masses in the range 20-5000 GeV=c(2). These are the most stringent spin-dependent WIMP-proton cross section limits to date above 35 GeV=c(2) for most WIMP models.
TL;DR: It is demonstrated that consumption of raw milk poses a realistic health threat due to a possible contamination with human pathogens and it is therefore strongly recommended that milk should be heated before consumption.
TL;DR: The detection of enterotypes suggests a common ecological cause, possibly low-grade inflammation that might drive differences among gut microbiota composition in mammals, and has important consequences for experimental design in mouse microbiome research.
Abstract: Background
Murine models are a crucial component of gut microbiome research. Unfortunately, a multitude of genetic backgrounds and experimental setups, together with inter-individual variation, complicates cross-study comparisons and a global understanding of the mouse microbiota landscape. Here, we investigate the variability of the healthy mouse microbiota of five common lab mouse strains using 16S rDNA pyrosequencing.
TL;DR: A landslide susceptibility map is prepared on the basis of available digital data of topography, geology, land-use and hydrology and reveals that the predicted susceptibility levels are found to be in good agreement with the past landslide occurrences, and, hence, the map is trustworthy for future land- use planning.
TL;DR: The present data are consistent with the pure scalar hypothesis, while disfavoring the pure pseudoscalar hypothesis.
Abstract: A study is presented of the mass and spin-parity of the new boson recently observed at the LHC at a mass near 125 GeV. An integrated luminosity of 17.3 fb^(-1), collected by the CMS experiment in proton-proton collisions at center-of-mass energies of 7 and 8 TeV, is used. The measured mass in the ZZ channel, where both Z bosons decay to e or μ pairs, is 126.2±0.6(stat)±0.2(syst) GeV. The angular distributions of the lepton pairs in this channel are sensitive to the spin-parity of the boson. Under the assumption of spin 0, the present data are consistent with the pure scalar hypothesis, while disfavoring the pure pseudoscalar hypothesis.
TL;DR: The gene composition of human gut microbiome in a large and deeply sequenced cohort highlighted an overall non-redundant genome size 150 times larger than the human genome.
Abstract: Advances in sequencing technology and the development of metagenomic and bioinformatics methods have opened up new ways to investigate the 10(14) microorganisms inhabiting the human gut. The gene composition of human gut microbiome in a large and deeply sequenced cohort highlighted an overall nonredundant genome size 150 times larger than the human genome. The in silico predictions based on metagenomic sequencing are now actively followed, compared and challenged using additional 'omics' technologies. Interactions between the microbiota and its host are of key interest in several pathologies and applying metaomics to describe the human gut microbiome will give a better understanding of this crucial crosstalk at mucosal interfaces. Adding to the growing appreciation of the importance of the microbiome is the discovery that numerous phages, that is, viruses of prokaryotes infecting bacteria (bacteriophages) or archaea with a high host specificity, inhabit the human gut and impact microbial activity. In addition, gene exchanges within the gut microbiota have proved to be more frequent than anticipated. Taken together, these innovative exploratory technologies are expected to unravel new information networks critical for gut homeostasis and human health. Among the challenges faced, the in vivo validation of these networks, together with their integration into the prediction and prognosis of disease, may require further working hypothesis and collaborative efforts.
TL;DR: These newly postulated AOPs can serve a number of ubiquitous purposes, including the establishment of (quantitative) structure-activity relationships, the development of novel in vitro toxicity screening tests and the elaboration of prioritization strategies.
TL;DR: In this article, it was shown that the Jacobiator of generalised diffeomorphisms gives such a reducibility transformation, i.e., the tower of ghosts for ghosts is infinite.
Abstract: We investigate the generalised diffeomorphisms in M-theory, which are gauge transformations unifying diffeomorphisms and tensor gauge transformations. After giving an En(n)-covariant description of the gauge transformations and their commutators, we show that the gauge algebra is infinitely reducible, i.e., the tower of ghosts for ghosts is infinite. The Jacobiator of generalised diffeomorphisms gives such a reducibility transformation. We give a concrete description of the ghost structure, and demonstrate that the infinite sums give the correct (regularised) number of degrees of freedom. The ghost towers belong to the sequences of rep- resentations previously observed appearing in tensor hierarchies and Borcherds algebras. All calculations rely on the section condition, which we reformulate as a linear condition on the cotangent directions. The analysis holds for n < 8. At n = 8, where the dual gravity field becomes relevant, the natural guess for the gauge parameter and its reducibility still yields the correct counting of gauge parameters.
TL;DR: An unbinned maximum-likelihood fit to the dimuon invariant mass distribution gives a branching fraction B(Bs(0)→μ+ μ-)=(3.0(-0.9)(+1.0))×10(-9), where the uncertainty includes both statistical and systematic contributions.
Abstract: Results are presented from a search for the rare decays B0s→μ+μ− and B0→μ+μ− in pp collisions at s√=7 and 8 TeV, with data samples corresponding to integrated luminosities of 5 and 20 fb−1, respectively, collected by the CMS experiment at the LHC. An unbinned maximum-likelihood fit to the dimuon invariant mass distribution gives a branching fraction B(B0s→μ+μ−)=(3.0+1.0−0.9)×10−9, where the uncertainty includes both statistical and systematic contributions. An excess of B0s→μ+μ− events with respect to background is observed with a significance of 4.3 standard deviations. For the decay B0→μ+μ− an upper limit of B(B0→μ+μ−)<1.1×10−9 at the 95% confidence level is determined. Both results are in agreement with the expectations from the standard model.
S. Chatrchyan1, Vardan Khachatryan1, Albert M. Sirunyan1, Armen Tumasyan1 +3948 more•Institutions (144)
TL;DR: In this article, a search for the pair production of top squarks in events with a single isolated electron or muon, jets, large missing transverse momentum, and large transverse mass is presented.
Abstract: This paper presents a search for the pair production of top squarks in events with a single isolated electron or muon, jets, large missing transverse momentum, and large transverse mass. The data sample corresponds to an integrated luminosity of 19.5 inverse femtobarns of pp collisions collected in 2012 by the CMS experiment at the LHC at a center-of-mass energy of sqrt(s) = 8 TeV. No significant excess in data is observed above the expectation from standard model processes. The results are interpreted in the context of supersymmetric models with pair production of top squarks that decay either to a top quark and a neutralino or to a bottom quark and a chargino. For small mass values of the lightest supersymmetric particle, top-squark mass values up to around 650 GeV are excluded.
TL;DR: Geriatric screening and assessment in older patients with cancer is feasible at large scale and has a significant impact on the detection of unknown geriatric problems, leading to geriatric interventions and adapted treatment.