Showing papers by "Ghent University published in 2014"

Review of Particle Physics

Abstract: The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,283 new measurements from 899 Japers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as heavy neutrinos, supersymmetric and technicolor particles, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Supersymmetry, Extra Dimensions, Particle Detectors, Probability, and Statistics. Among the 112 reviews are many that are new or heavily revised including those on: Dark Energy, Higgs Boson Physics, Electroweak Model, Neutrino Cross Section Measurements, Monte Carlo Neutrino Generators, Top Quark, Dark Matter, Dynamical Electroweak Symmetry Breaking, Accelerator Physics of Colliders, High-Energy Collider Parameters, Big Bang Nucleosynthesis, Astrophysical Constants and Cosmological Parameters.

Pilon: An Integrated Tool for Comprehensive Microbial Variant Detection and Genome Assembly Improvement

Abstract: Advances in modern sequencing technologies allow us to generate sufficient data to analyze hundreds of bacterial genomes from a single machine in a single day. This potential for sequencing massive numbers of genomes calls for fully automated methods to produce high-quality assemblies and variant calls. We introduce Pilon, a fully automated, all-in-one tool for correcting draft assemblies and calling sequence variants of multiple sizes, including very large insertions and deletions. Pilon works with many types of sequence data, but is particularly strong when supplied with paired end data from two Illumina libraries with small e.g., 180 bp and large e.g., 3-5 Kb inserts. Pilon significantly improves draft genome assemblies by correcting bases, fixing mis-assemblies and filling gaps. For both haploid and diploid genomes, Pilon produces more contiguous genomes with fewer errors, enabling identification of more biologically relevant genes. Furthermore, Pilon identifies small variants with high accuracy as compared to state-of-the-art tools and is unique in its ability to accurately identify large sequence variants including duplications and resolve large insertions. Pilon is being used to improve the assemblies of thousands of new genomes and to identify variants from thousands of clinically relevant bacterial strains. Pilon is freely available as open source software.

ProteomeXchange provides globally coordinated proteomics data submission and dissemination

Abstract: 5. Tools available and ways to submit data to PX ............................................................. 11 5.1. MS/MS data submissions to PRIDE .................................................................................... 11 5.1.1. Creation of supported files for “Complete” submissions .................................................. 11 5.1.1.1. PRIDE XML .................................................................................................................................. 11 5.1.1.2. mzIdentML ................................................................................................................................. 13 5.1.2. Checking the files before submission (initial quality assessment) ..................................... 14 5.1.3. File submission to PRIDE: the PX submission tool ............................................................. 15 5.1.3.1. General Information ................................................................................................................... 15 5.1.3.2. Functionality, Design and Implementation Details .................................................................... 15 5.1.3.3. New open source libraries made available with PX submission tool ......................................... 18 5.1.3.4. PX Submission Tool Java Web Start ............................................................................................ 18 5.1.4. File submission to PRIDE: Command line support using Aspera ........................................ 19 5.1.5. Examples of Partial submissions to PRIDE ......................................................................... 19 5.2. SRM data submissions via PASSEL ..................................................................................... 20

The design and verification of MuMax3

Abstract: We report on the design, verification and performance of MUMAX3, an open-source GPU-accelerated micromagnetic simulation program. This software solves the time- and space dependent magnetization evolution in nano- to micro scale magnets using a finite-difference discretization. Its high performance and low memory requirements allow for large-scale simulations to be performed in limited time and on inexpensive hardware. We verified each part of the software by comparing results to analytical values where available and to micromagnetic standard problems. MUMAX3 also offers specific extensions like MFM image generation, moving simulation window, edge charge removal and material grains.

Mepolizumab Treatment in Patients with Severe Eosinophilic Asthma

Abstract: BACKGROUND: Some patients with severe asthma have frequent exacerbations associated with persistent eosinophilic inflammation despite continuous treatment with high-dose inhaled glucocorticoids with or without oral glucocorticoids. METHODS: In this randomized, double-blind, double-dummy study, we assigned 576 patients with recurrent asthma exacerbations and evidence of eosinophilic inflammation despite high doses of inhaled glucocorticoids to one of three study groups. Patients were assigned to receive mepolizumab, a humanized monoclonal antibody against interleukin-5, which was administered as either a 75-mg intravenous dose or a 100-mg subcutaneous dose, or placebo every 4 weeks for 32 weeks. The primary outcome was the rate of exacerbations. Other outcomes included the forced expiratory volume in 1 second (FEV1) and scores on the St. George's Respiratory Questionnaire (SGRQ) and the 5-item Asthma Control Questionnaire (ACQ-5). Safety was also assessed. RESULTS: The rate of exacerbations was reduced by 47% (95% confidence interval [CI], 29 to 61) among patients receiving intravenous mepolizumab and by 53% (95% CI, 37 to 65) among those receiving subcutaneous mepolizumab, as compared with those receiving placebo (P<0.001 for both comparisons). Exacerbations necessitating an emergency department visit or hospitalization were reduced by 32% in the group receiving intravenous mepolizumab and by 61% in the group receiving subcutaneous mepolizumab. At week 32, the mean increase from baseline in FEV1 was 100 ml greater in patients receiving intravenous mepolizumab than in those receiving placebo (P=0.02) and 98 ml greater in patients receiving subcutaneous mepolizumab than in those receiving placebo (P=0.03). The improvement from baseline in the SGRQ score was 6.4 points and 7.0 points greater in the intravenous and subcutaneous mepolizumab groups, respectively, than in the placebo group (minimal clinically important change, 4 points), and the improvement in the ACQ-5 score was 0.42 points and 0.44 points greater in the two mepolizumab groups, respectively, than in the placebo group (minimal clinically important change, 0.5 points) (P<0.001 for all comparisons). The safety profile of mepolizumab was similar to that of placebo. CONCLUSIONS: Mepolizumab administered either intravenously or subcutaneously significantly reduced asthma exacerbations and was associated with improvements in markers of asthma control. (Funded by GlaxoSmithKline; MENSA ClinicalTrials.gov number, NCT01691521.).

A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis

Abstract: Objective Bacteria play an important role in the onset and perpetuation of intestinal inflammation in inflammatory bowel disease (IBD). Unlike in Crohn9s disease (CD), in which dysbiosis has been better characterised, in ulcerative colitis (UC), only small cohorts have been studied and showed conflicting data. Therefore, we evaluated in a large cohort if the microbial signature described in CD is also present in UC, and if we could characterise predominant dysbiosis in UC. To assess the functional impact of dysbiosis, we quantified the bacterial metabolites. Design The predominant microbiota from 127 UC patients and 87 age and sex-matched controls was analysed using denaturing gradient gel electrophoresis (DGGE) analysis. Differences were quantitatively validated using real-time PCR. Metabolites were quantified using gas chromatography–mass spectrometry. Results Based on DGGE analysis, the microbial signature previously described in CD was not present in UC. Real-time PCR analysis revealed a lower abundance of Roseburia hominis (p Faecalibacterium prausnitzii (p Conclusions The composition of the fecal microbiota of UC patients differs from that of healthy individuals: we found a reduction in R hominis and F prausnitzii, both well-known butyrate-producing bacteria of the Firmicutes phylum. These results underscore the importance of dysbiosis in IBD but suggest that different bacterial species contribute to the pathogenesis of UC and CD.

Concreteness ratings for 40 thousand generally known English word lemmas

Abstract: Concreteness ratings are presented for 37,058 English words and 2,896 two-word expressions (such as zebra crossing and zoom in), obtained from over 4,000 participants by means of a norming study using Internet crowdsourcing for data collection. Although the instructions stressed that the assessment of word concreteness would be based on experiences involving all senses and motor responses, a comparison with the existing concreteness norms indicates that participants, as before, largely focused on visual and haptic experiences. The reported data set is a subset of a comprehensive list of English lemmas and contains all lemmas known by at least 85 % of the raters. It can be used in future research as a reference list of generally known English lemmas.

Observation of high-energy astrophysical neutrinos in three years of icecube data

Abstract: A search for high-energy neutrinos interacting within the IceCube detector between 2010 and 2012 provided the first evidence for a high-energy neutrino flux of extraterrestrial origin. Results from an analysis using the same methods with a third year (2012-2013) of data from the complete IceCube detector are consistent with the previously reported astrophysical flux in the 100 TeV-PeV range at the level of 10(-8) GeV cm(-2) s(-1) sr(-1) per flavor and reject a purely atmospheric explanation for the combined three-year data at 5.7 sigma. The data are consistent with expectations for equal fluxes of all three neutrino flavors and with isotropic arrival directions, suggesting either numerous or spatially extended sources. The three-year data set, with a live time of 988 days, contains a total of 37 neutrino candidate events with deposited energies ranging from 30 to 2000 TeV. The 2000-TeV event is the highest-energy neutrino interaction ever observed.

Association of Atrial Tissue Fibrosis Identified by Delayed Enhancement MRI and Atrial Fibrillation Catheter Ablation The DECAAF Study

Abstract: Importance Left atrial fibrosis is prominent in patients with atrial fibrillation (AF). Extensive atrial tissue fibrosis identified by delayed enhancement magnetic resonance imaging (MRI) has been associated with poor outcomes of AF catheter ablation. Objective To characterize the feasibility of atrial tissue fibrosis estimation by delayed enhancement MRI and its association with subsequent AF ablation outcome. Design, Setting, and Participants Multicenter, prospective, observational cohort study of patients diagnosed with paroxysmal and persistent AF (undergoing their first catheter ablation) conducted between August 2010 and August 2011 at 15 centers in the United States, Europe, and Australia. Delayed enhancement MRI images were obtained up to 30 days before ablation. Main Outcomes and Measures Fibrosis quantification was performed at a core laboratory blinded to the participating center, ablation approach, and procedure outcome. Fibrosis blinded to the treating physicians was categorized as stage 1 ( Results Atrial tissue fibrosis estimation by delayed enhancement MRI was successfully quantified in 272 of 329 enrolled patients (57 patients [17%] were excluded due to poor MRI quality). There were 260 patients who were followed up after the blanking period (mean [SD] age of 59.1 [10.7] years, 31.5% female, 64.6% with paroxysmal AF). For recurrent arrhythmia, the unadjusted overall hazard ratio per 1% increase in left atrial fibrosis was 1.06 (95% CI, 1.03-1.08; P Conclusions and Relevance Among patients with AF undergoing catheter ablation, atrial tissue fibrosis estimated by delayed enhancement MRI was independently associated with likelihood of recurrent arrhythmia. The clinical implications of this association warrant further investigation.

SUBTLEX-UK: A new and improved word frequency database for British English

Abstract: We present word frequencies based on subtitles of British television programmes. We show that the SUBTLEX-UK word frequencies explain more of the variance in the lexical decision times of the British Lexicon Project than the word frequencies based on the British National Corpus and the SUBTLEX-US frequencies. In addition to the word form frequencies, we also present measures of contextual diversity part-of-speech specific word frequencies, word frequencies in children programmes, and word bigram frequencies, giving researchers of British English access to the full range of norms recently made available for other languages. Finally, we introduce a new measure of word frequency, the Zipf scale, which we hope will stop the current misunderstandings of the word frequency effect.

European Society of Hypertension practice guidelines for ambulatory blood pressure monitoring.

Abstract: Given the increasing use of ambulatory blood pressure monitoring (ABPM) in both clinical practice and hypertension research, a group of scientists, participating in the European Society of Hypertension Working Group on blood pressure monitoring and cardiovascular variability, in year 2013 published a comprehensive position paper dealing with all aspects of the technique, based on the available scientific evidence for ABPM. The present work represents an updated schematic summary of the most important aspects related to the use of ABPM in daily practice, and is aimed at providing recommendations for proper use of this technique in a clinical setting by both specialists and practicing physicians. The present article details the requirements and the methodological issues to be addressed for using ABPM in clinical practice, The clinical indications for ABPM suggested by the available studies, among which white-coat phenomena, masked hypertension, and nocturnal hypertension, are outlined in detail, and the place of home measurement of blood pressure in relation to ABPM is discussed. The role of ABPM in pharmacological, epidemiological, and clinical research is also briefly mentioned. Finally, the implementation of ABPM in practice is considered in relation to the situation of different countries with regard to the reimbursement and the availability of ABPM in primary care practices, hospital clinics, and pharmacies.

The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling

Abstract: Despite an enormous interest in the role of extracellular vesicles, including exosomes, in cancer and their use as biomarkers for diagnosis, prognosis, drug response and recurrence, there is no consensus on dependable isolation protocols. We provide a comparative evaluation of 4 exosome isolation protocols for their usability, yield and purity, and their impact on downstream omics approaches for biomarker discovery. OptiPrep density gradient centrifugation outperforms ultracentrifugation and ExoQuick and Total Exosome Isolation precipitation in terms of purity, as illustrated by the highest number of CD63-positive nanovesicles, the highest enrichment in exosomal marker proteins and a lack of contaminating proteins such as extracellular Argonaute-2 complexes. The purest exosome fractions reveal a unique mRNA profile enriched for translation, ribosome, mitochondrion and nuclear lumen function. Our results demonstrate that implementation of high purification techniques is a prerequisite to obtain reliable omics data and identify exosome-specific functions and biomarkers.

Synchronized renal tubular cell death involves ferroptosis

Abstract: Receptor-interacting protein kinase 3 (RIPK3)-mediated necroptosis is thought to be the pathophysiologically predominant pathway that leads to regulated necrosis of parenchymal cells in ischemia-reperfusion injury (IRI), and loss of either Fas-associated protein with death domain (FADD) or caspase-8 is known to sensitize tissues to undergo spontaneous necroptosis. Here, we demonstrate that renal tubules do not undergo sensitization to necroptosis upon genetic ablation of either FADD or caspase-8 and that the RIPK1 inhibitor necrostatin-1 (Nec-1) does not protect freshly isolated tubules from hypoxic injury. In contrast, iron-dependent ferroptosis directly causes synchronized necrosis of renal tubules, as demonstrated by intravital microscopy in models of IRI and oxalate crystal-induced acute kidney injury. To suppress ferroptosis in vivo, we generated a novel third-generation ferrostatin (termed 16-86), which we demonstrate to be more stable, to metabolism and plasma, and more potent, compared with the first-in-class compound ferrostatin-1 (Fer-1). Even in conditions with extraordinarily severe IRI, 16-86 exerts strong protection to an extent which has not previously allowed survival in any murine setting. In addition, 16-86 further potentiates the strong protective effect on IRI mediated by combination therapy with necrostatins and compounds that inhibit mitochondrial permeability transition. Renal tubules thus represent a tissue that is not sensitized to necroptosis by loss of FADD or caspase-8. Finally, ferroptosis mediates postischemic and toxic renal necrosis, which may be therapeutically targeted by ferrostatins and by combination therapy.

The genome of Eucalyptus grandis

Abstract: Eucalypts are the world's most widely planted hardwood trees. Their outstanding diversity, adaptability and growth have made them a global renewable resource of fibre and energy. We sequenced and assembled >94% of the 640-megabase genome of Eucalyptus grandis. Of 36,376 predicted protein-coding genes, 34% occur in tandem duplications, the largest proportion thus far in plant genomes. Eucalyptus also shows the highest diversity of genes for specialized metabolites such as terpenes that act as chemical defence and provide unique pharmaceutical oils. Genome sequencing of the E. grandis sister species E. globulus and a set of inbred E. grandis tree genomes reveals dynamic genome evolution and hotspots of inbreeding depression. The E. grandis genome is the first reference for the eudicot order Myrtales and is placed here sister to the eurosids. This resource expands our understanding of the unique biology of large woody perennials and provides a powerful tool to accelerate comparative biology, breeding and biotechnology.

Breast-Cancer Risk in Families with Mutations in PALB2

Abstract: The risk of breast cancer for female PALB2 mutation carriers, as compared with the general population, was eight to nine times as high among those younger than 40 years of age, six to eight times as high among those 40 to 60 years of age, and five times as high among those older than 60 years of age. The estimated cumulative risk of breast cancer among female mutation carriers was 14% (95% confidence interval [CI], 9 to 20) by 50 years of age and 35% (95% CI, 26 to 46) by 70 years of age. Breast-cancer risk was also significantly influenced by birth cohort (P < 0.001) and by other familial factors (P = 0.04). The absolute breast-cancer risk for PALB2 female mutation carriers by 70 years of age ranged from 33% (95% CI, 25 to 44) for those with no family history of breast cancer to 58% (95% CI, 50 to 66) for those with two or more first-degree relatives with breast cancer at 50 years of age. CONCLUSIONS Loss-of-function mutations in PALB2 are an important cause of hereditary breast cancer, with respect both to the frequency of cancer-predisposing mutations and to the risk associated with them. Our data suggest the breast-cancer risk for PALB2 mutation carriers may overlap with that for BRCA2 mutation carriers. (Funded by the European Research Council and others.) abstr act

Consensus guidelines for the detection of immunogenic cell death

Abstract: Apoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named "immunogenic cell death" (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defects in the components that underlie the capacity of the immune system to perceive cell death as immunogenic negatively influence disease outcome among cancer patients treated with ICD inducers. Thus, ICD has profound clinical and therapeutic implications. Unfortunately, the gold-standard approach to detect ICD relies on vaccination experiments involving immunocompetent murine models and syngeneic cancer cells, an approach that is incompatible with large screening campaigns. Here, we outline strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine.

Mega-heatwave temperatures due to combined soil desiccation and atmospheric heat accumulation

Abstract: Extreme heatwave events are expected to become increasingly common as a consequence of climate change. Analyses of the 2003 and 2010 mega-heatwaves in Europe suggest that atmospheric boundary-layer dynamics and feedbacks with the drying land surface lead to the build-up of heat in the atmosphere and extremely hot temperatures.

Experimental demonstration of reservoir computing on a silicon photonics chip

Abstract: Reservoir computing uses computational techniques related to neural networks to perform certain computing tasks. Here, the authors implement a passive optical reservoir computing scheme integrated on a silicon chip, operating at speeds up to 12.5 Gbit s−1.

Is there new hope for therapeutic matrix metalloproteinase inhibition

Abstract: Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that form a family of 24 members in mammals. Evidence of the pathological roles of MMPs in various diseases, combined with their druggability, has made them attractive therapeutic targets. Initial drug discovery efforts focused on the roles of MMPs in cancer progression, and more than 50 MMP inhibitors have been investigated in clinical trials in various cancers. However, all of these trials failed. Reasons for failure include the lack of inhibitor specificity and insufficient knowledge about the complexity of the disease biology. MMPs are also known to be involved in several inflammatory processes, and there are new therapeutic opportunities for MMP inhibitors to treat such diseases. In this Review, we discuss the recent advances made in understanding the role of MMPs in inflammatory diseases and the therapeutic potential of MMP inhibition in those conditions.

Hydrous mantle transition zone indicated by ringwoodite included within diamond

Abstract: X-ray diffraction, Raman and infrared spectroscopic evidence for the inclusion of water-rich ringwoodite in diamond from Juina, Brazil, indicates that, at least locally, the Earth’s transition zone is hydrous to about 1 weight per cent. It is not clear just how much water resides within the solid Earth, and where it is to be found, with many indirect measurements yielding conflicting results. Here Graham Pearson and co-authors present evidence from a diamond inclusion from Juina, Brazil, for the first known terrestrial occurrence of ringwoodite — a high-pressure polymorph of olivine first identified in meteorites and thought to be a major constituent of the Earth's mantle transition zone. The water-rich nature of this inclusion provides direct evidence that, at least locally, the transition zone is hydrous, to about 1 weight per cent. The ultimate origin of water in the Earth’s hydrosphere is in the deep Earth—the mantle. Theory1 and experiments2,3,4 have shown that although the water storage capacity of olivine-dominated shallow mantle is limited, the Earth’s transition zone, at depths between 410 and 660 kilometres, could be a major repository for water, owing to the ability of the higher-pressure polymorphs of olivine—wadsleyite and ringwoodite—to host enough water to comprise up to around 2.5 per cent of their weight. A hydrous transition zone may have a key role in terrestrial magmatism and plate tectonics5,6,7, yet despite experimental demonstration of the water-bearing capacity of these phases, geophysical probes such as electrical conductivity have provided conflicting results8,9,10, and the issue of whether the transition zone contains abundant water remains highly controversial11. Here we report X-ray diffraction, Raman and infrared spectroscopic data that provide, to our knowledge, the first evidence for the terrestrial occurrence of any higher-pressure polymorph of olivine: we find ringwoodite included in a diamond from Juina, Brazil. The water-rich nature of this inclusion, indicated by infrared absorption, along with the preservation of the ringwoodite, is direct evidence that, at least locally, the transition zone is hydrous, to about 1 weight per cent. The finding also indicates that some kimberlites must have their primary sources in this deep mantle region.

2013 ESH/ESC Practice guidelines for the management of arterial hypertension

Abstract: ABPMambulatory blood pressure monitoringACEangiotensin converting enzymeARBangiotensin receptor blockerA-Vatrio-ventricularBBbeta-blockerBPblood pressureCHDcoronary heart diseaseCKDchronic kidney d...