Showing papers by "University of Oviedo published in 2013"

Signatures of mutational processes in human cancer

Abstract: All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.

Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease

Abstract: Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10−8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.

Supercomplex Assembly Determines Electron Flux in the Mitochondrial Electron Transport Chain

Abstract: The textbook description of mitochondrial respiratory complexes (RCs) views them as free-moving entities linked by the mobile carriers coenzyme Q (CoQ) and cytochrome c (cyt c). This model (known as the fluid model) is challenged by the proposal that all RCs except complex II can associate in supercomplexes (SCs). The proposed SCs are the respirasome (complexes I, III, and IV), complexes I and III, and complexes III and IV. The role of SCs is unclear, and their existence is debated. By genetic modulation of interactions between complexes I and III and III and IV, we show that these associations define dedicated CoQ and cyt c pools and that SC assembly is dynamic and organizes electron flux to optimize the use of available substrates.

Directrices para la traducción y adaptación de los tests: segunda edición

Abstract: Antecedentes: en los ultimos anos la adaptacion de los tests de unas culturas a otras se ha incrementado en todos los ambitos evaluativos. Vivimos en un entorno cada vez mas multicultural y multilingue en el que los tests se utilizan como apoyo en la toma de decisiones. El objetivo de este trabajo es presentar la segunda edicion de las directrices de la Comision Internacional de Tests (ITC) para la adaptacion de los tests de unas culturas a otras. Metodo: un grupo de seis expertos internacionales revisaron las directrices originales propuestas por la Comision Internacional de Tests, teniendo en cuenta los avances habidos en el campo desde su formulacion inicial. Resultados: la nueva edicion esta compuesta por veinte directrices agrupadas en seis apartados: directrices previas, desarrollo del test, confirmacion, aplicacion, puntuacion e interpretacion y documentacion. Se analizan los diferentes apartados, y se estudian las posibles fuentes de error que pueden influir en el proceso de traduccion y adaptacion de los tests. Conclusiones: se proponen veinte directrices para guiar la traduccion y adaptacion de los tests de unas culturas a otras. Se discuten las perspectivas futuras de las directrices en relacion con los nuevos desarrollos en el ambito de la evaluacion psicologica y educativa.

Observation of a new boson with mass near 125 GeV in pp collisions at $ \sqrt{s}=7 $ and 8 TeV

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.

Landscape of somatic mutations and clonal evolution in mantle cell lymphoma

Abstract: Mantle cell lymphoma (MCL) is an aggressive tumor, but a subset of patients may follow an indolent clinical course. To understand the mechanisms underlying this biological heterogeneity, we performed whole-genome and/or whole-exome sequencing on 29 MCL cases and their respective matched normal DNA, as well as 6 MCL cell lines. Recurrently mutated genes were investigated by targeted sequencing in an independent cohort of 172 MCL patients. We identified 25 significantly mutated genes, including known drivers such as ataxia-telangectasia mutated (ATM), cyclin D1 (CCND1), and the tumor suppressor TP53; mutated genes encoding the anti-apoptotic protein BIRC3 and Toll-like receptor 2 (TLR2); and the chromatin modifiers WHSC1, MLL2, and MEF2B. We also found NOTCH2 mutations as an alternative phenomenon to NOTCH1 mutations in aggressive tumors with a dismal prognosis. Analysis of two simultaneous or subsequent MCL samples by whole-genome/whole-exome (n = 8) or targeted (n = 19) sequencing revealed subclonal heterogeneity at diagnosis in samples from different topographic sites and modulation of the initial mutational profile at the progression of the disease. Some mutations were predominantly clonal or subclonal, indicating an early or late event in tumor evolution, respectively. Our study identifies molecular mechanisms contributing to MCL pathogenesis and offers potential targets for therapeutic intervention.

Adolescent subthreshold-depression and anxiety: psychopathology, functional impairment and increased suicide risk

Abstract: Background: Subthreshold-depression and anxiety have been associated with significant impairments in adults. This study investigates the characteristics of adolescent subthreshold-depression and anxiety with a focus on suicidality, using both categorical and dimensional diagnostic models. Methods: Data were drawn from the Saving and Empowering Young Lives in Europe (SEYLE) study, comprising 12,395 adolescents from 11 countries. Based on self-report, including Beck Depression Inventory-II (BDI-II), Zung Self-Rating Anxiety Scale (SAS), Strengths and Difficulties Questionnaire (SDQ) and Paykel Suicide Scale (PSS) were administered to students. Based on BDI-II, adolescents were divided into three groups: nondepressed, subthreshold-depressed and depressed; based on the SAS, they were divided into nonanxiety, subthreshold-anxiety and anxiety groups. Analyses of Covariance were conducted on SDQ scores to explore psychopathology of the defined groups. Logistic regression analyses were conducted to explore the relationships between functional impairments, suicidality and subthreshold and full syndromes. Results: Thirty-two percent of the adolescents were subthreshold-anxious and 5.8% anxious, 29.2% subthreshold-depressed and 10.5% depressed, with high comorbidity. Mean scores of SDQ of subthreshold-depressed/anxious were significantly higher than the mean scores of the nondepressed/nonanxious groups and significantly lower than those of the depressed/anxious groups. Both subthreshold and threshold-anxiety and depression were related to functional impairment and suicidality. Conclusions: Subthreshold-depression and subthreshold-anxiety are associated with an increased burden of disease and suicide risk. These results highlight the importance of early identification of adolescent subthreshold-depression and anxiety to minimize suicide. Incorporating these subthreshold disorders into a diagnosis could provide a bridge between categorical and dimensional diagnostic models. Keywords: Categorical diagnostic model, dimensional diagnostic model, subthreshold-depression, subthreshold-anxiety, adolescent, suicide, SEYLE.

Planck 2013 results. I. Overview of products and scientific results

Abstract: The ESA's Planck satellite, dedicated to studying the early Universe and its subsequent evolution, was launched 14 May 2009 and has been scanning the microwave and submillimetre sky continuously since 12 August 2009. This paper gives an overview of the mission and its performance, the processing, analysis, and characteristics of the data, the scientific results, and the science data products and papers in the release. The science products include maps of the CMB and diffuse extragalactic foregrounds, a catalogue of compact Galactic and extragalactic sources, and a list of sources detected through the SZ effect. The likelihood code used to assess cosmological models against the Planck data and a lensing likelihood are described. Scientific results include robust support for the standard six-parameter LCDM model of cosmology and improved measurements of its parameters, including a highly significant deviation from scale invariance of the primordial power spectrum. The Planck values for these parameters and others derived from them are significantly different from those previously determined. Several large-scale anomalies in the temperature distribution of the CMB, first detected by WMAP, are confirmed with higher confidence. Planck sets new limits on the number and mass of neutrinos, and has measured gravitational lensing of CMB anisotropies at greater than 25 sigma. Planck finds no evidence for non-Gaussianity in the CMB. Planck's results agree well with results from the measurements of baryon acoustic oscillations. Planck finds a lower Hubble constant than found in some more local measures. Some tension is also present between the amplitude of matter fluctuations derived from CMB data and that derived from SZ data. The Planck and WMAP power spectra are offset from each other by an average level of about 2% around the first acoustic peak.

Study of the Mass and Spin-Parity of the Higgs Boson Candidate via Its Decays to Z Boson Pairs

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.

Planck intermediate results: V. Pressure profiles of galaxy clusters from the Sunyaev-Zeldovich effect

Abstract: Taking advantage of the all-sky coverage and broad frequency range of the Planck satellite, we study the Sunyaev-Zeldovich (SZ) and pressure profiles of 62 nearby massive clusters detected at high significance in the 14-month nominal survey. Careful reconstruction of the SZ signal indicates that most clusters are individually detected at least out to R500. By stacking the radial profiles, we have statistically detected the radial SZ signal out to 3R500, i.e., at a density contrast of about 50-100, though the dispersion about the mean profile dominates the statistical errors across the whole radial range. Our measurement is fully consistent with previous Planck results on integrated SZ fluxes, further strengthening the agreement between SZ and X-ray measurements inside R500. Correcting for the effects of the Planck beam, we have calculated the corresponding pressure profiles. This new constraint from SZ measurements is consistent with the X-ray constraints from xmm in the region in which the profiles overlap (i.e., [0.1-1] R500), and is in fairly good agreement with theoretical predictions within the expected dispersion. At larger radii the average pressure profile is shallower than the predictions. Combining the SZ and X-ray observed profiles into a joint fit to a generalised pressure profile gives best-fit parameters [P0, c500, gamma, alpha, beta] = [6.41, 1.81, 0.31, 1.33, 4.13]. Using a reasonable hypothesis for the gas temperature in the cluster outskirts we reconstruct from our stacked pressure profile the gas mass fraction profile out to 3R500. Within the temperature driven uncertainties, our Planck constraints are compatible with the cosmic baryon fraction and expected gas fraction in halos.

Measurement of the Bs0→μ+μ- branching fraction and search for B0→μ+μ- with the CMS experiment

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.

Search for top-squark pair production in the single-lepton final state in pp collisions at √s=8 TeV

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.

Support Vector Machines Used to Estimate the Battery State of Charge

Abstract: The aim of this study is to estimate the state of charge (SOC) of a high-capacity lithium iron manganese phosphate (LiFeMnPO4) battery cell from an experimental dataset using a support vector machine (SVM) approach. SVM is a type of learning machine based on statistical learning theory. Many applications require accurate measurement of battery SOC in order to give users an indication of available runtime. It is particularly important for electric vehicles or portable devices. In this paper, the proposed SOC estimator extracts model parameters from battery charging/discharging testing cycles, using cell current, cell voltage, and cell temperature as independent variables. Tests are carried out on a 60 Ah lithium-ion cell with the dynamic stress test cycle to set up the SVM model. The SVM SOC estimator maintains a high level of accuracy, better than 6% over all ranges of operation, whether the battery is charged/discharged at constant current or it is operating in a variable current profile.

A Meta-Analysis of State-of-the-Art Electoral Prediction From Twitter Data

Abstract: Electoral prediction from Twitter data is an appealing research topic. It seems relatively straightforward and the prevailing view is overly optimistic. This is problematic because while simple approaches are assumed to be good enough, core problems are not addressed. Thus, this article aims to (1) provide a balanced and critical review of the state of the art; (2) cast light on the presume predictive power of Twitter data; and (3) propose some considerations to push forward the field. Hence, a scheme to characterize Twitter prediction methods is proposed. It covers every aspect from data collection to performance evaluation, through data processing and vote inference. Using that scheme, prior research is analyzed and organized to explain the main approaches taken up to date but also their weaknesses. This is the first meta-analysis of the whole body of research regarding electoral prediction from Twitter data. It reveals that its presumed predictive power regarding electoral prediction has been somewhat exaggerated: Social media may provide a glimpse on electoral outcomes but, up to now, research has not provided strong evidence to support it can currently replace traditional polls. Nevertheless, there are some reasons for optimism and, hence, further work on this topic is required, along with tighter integration with traditional electoral forecasting research.

Searches for long-lived charged particles in pp collisions at sqrt(s) = 7 and 8 TeV

Abstract: Results of searches for heavy stable charged particles produced in pp collisions at sqrt(s) = 7 and 8 TeV are presented corresponding to an integrated luminosity of 5.0 inverse femtobarns and 18.8 inverse femtobarns, respectively. Data collected with the CMS detector are used to study the momentum, energy deposition, and time-of-flight of signal candidates. Leptons with an electric charge between e/3 and 8e, as well as bound states that can undergo charge exchange with the detector material, are studied. Analysis results are presented for various combinations of signatures in the inner tracker only, inner tracker and muon detector, and muon detector only. Detector signatures utilized are long time-of-flight to the outer muon system and anomalously high (or low) energy deposition in the inner tracker. The data are consistent with the expected background, and upper limits are set on the production cross section of long-lived gluinos, scalar top quarks, and scalar tau leptons, as well as pair produced long-lived leptons. Corresponding lower mass limits, ranging up to 1322 GeV for gluinos, are the most stringent to date.

Epigenetic regulation of adaptive responses of forest tree species to the environment.

Abstract: Epigenetic variation is likely to contribute to the phenotypic plasticity and adaptative capacity of plant species, and may be especially important for long-lived organisms with complex life cycles, including forest trees. Diverse environmental stresses and hybridization/polyploidization events can create reversible heritable epigenetic marks that can be transmitted to subsequent generations as a form of molecular “memory”. Epigenetic changes might also contribute to the ability of plants to colonize or persist in variable environments. In this review, we provide an overview of recent data on epigenetic mechanisms involved in developmental processes and responses to environmental cues in plant, with a focus on forest tree species. We consider the possible role of forest tree epigenetics as a new source of adaptive traits in plant breeding, biotechnology, and ecosystem conservation under rapid climate change.

POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia

Abstract: Carlos Lopez-Otin and colleagues report recurrent mutations in POT1 in chronic lymphocytic leukemia. This is the first member of the telomeric shelterin complex reported to be mutated in human cancer.

Surgical margins in head and neck cancer: A contemporary review

Abstract: Adequate resection margins are critical to the treatment decisions and prognosis of patients with head and neck squamous cell carcinoma (HNSCC). However, there are numerous controversies regarding reporting and interpretation of the status of resection margins. Fundamental issues relating to the basic definition of margin adequacy, uniform reporting standards for margins, optimal method of specimen dissection, and the role of intraoperative frozen section evaluation, all require further clarification and standardization. Future horizons for margin surveillance offer the possible use of novel methods such as "molecular margins" and contact microscopic endoscopy, However, the limitations of these approaches need to be understood. The goal of this review was to evaluate these issues to define a more rational, standardized approach for achieving resection margin adequacy for patients with HNSCC undergoing curative resection.

Air pollution and respiratory infections during early childhood: an analysis of 10 European birth cohorts within the ESCAPE Project

Abstract: Background: Few studies have investigated traffic-related air pollution as a risk factor for respiratory infections during early childhood. Objectives: We aimed to investigate the association between air pollution and pneumonia, croup, and otitis media in 10 European birth cohorts—BAMSE (Sweden), GASPII (Italy), GINIplus and LISAplus (Germany), MAAS (United Kingdom), PIAMA (the Netherlands), and four INMA cohorts (Spain)—and to derive combined effect estimates using meta-analysis. Methods: Parent report of physician-diagnosed pneumonia, otitis media, and croup during early childhood were assessed in relation to annual average pollutant levels [nitrogen dioxide (NO2), nitrogen oxide (NOx), particulate matter ≤ 2.5 μm (PM2.5), PM2.5 absorbance, PM10, PM2.5–10 (coarse PM)], which were estimated using land use regression models and assigned to children based on their residential address at birth. Identical protocols were used to develop regression models for each study area as part of the ESCAPE project. Logistic regression was used to calculate adjusted effect estimates for each study, and random-effects meta-analysis was used to calculate combined estimates. Results: For pneumonia, combined adjusted odds ratios (ORs) were elevated and statistically significant for all pollutants except PM2.5 (e.g., OR = 1.30; 95% CI: 1.02, 1.65 per 10-μg/m3 increase in NO2 and OR = 1.76; 95% CI: 1.00, 3.09 per 10-μg/m3 PM10). For otitis media and croup, results were generally null across all analyses except for NO2 and otitis media (OR = 1.09; 95% CI: 1.02, 1.16 per 10-μg/m3). Conclusion: Our meta-analysis of 10 European birth cohorts within the ESCAPE project found consistent evidence for an association between air pollution and pneumonia in early childhood, and some evidence for an association with otitis media.

Energy calibration and resolution of the CMS electromagnetic calorimeter in pp collisions at √s = 7 TeV

Abstract: The article is the pre-print version of the final publishing paper that is available from the link below.

The pre-launch Planck Sky Model: a model of sky emission at submillimetre to centimetre wavelengths

Abstract: We present the Planck Sky Model (PSM), a parametric model for the generation of all-sky, few arcminute resolution maps of sky emission at submillimetre to centimetre wavelengths, in both intensity and polarisation. Several options are implemented to model the cosmic microwave background, Galactic diffuse emission (synchrotron, free-free, thermal and spinning dust, CO lines), Galactic H-II regions, extragalactic radio sources, dusty galaxies, and thermal and kinetic Sunyaev-Zeldovich signals from clusters of galaxies. Each component is simulated by means of educated interpolations/extrapolations of data sets available at the time of the launch of the Planck mission, complemented by state-of-the-art models of the emission. Distinctive features of the simulations are: spatially varying spectral properties of synchrotron and dust; different spectral parameters for each point source; modeling of the clustering properties of extragalactic sources and of the power spectrum of fluctuations in the cosmic infrared background. The PSM enables the production of random realizations of the sky emission, constrained to match observational data within their uncertainties, and is implemented in a software package that is regularly updated with incoming information from observations. The model is expected to serve as a useful tool for optimizing planned microwave and sub-millimetre surveys and to test data processing and analysis pipelines. It is, in particular, used for the development and validation of data analysis pipelines within the planck collaboration. A version of the software that can be used for simulating the observations for a variety of experiments is made available on a dedicated website.

Measurement of the elliptic anisotropy of charged particles produced in PbPb collisions at √sNN=2.76 TeV

Abstract: The anisotropy of the azimuthal distributions of charged particles produced in √s_(NN)=2.76 TeV PbPb collisions is studied with the CMS experiment at the LHC. The elliptic anisotropy parameter, v_2, defined as the second coefficient in a Fourier expansion of the particle invariant yields, is extracted using the event-plane method, two- and four-particle cumulants, and Lee-Yang zeros. The anisotropy is presented as a function of transverse momentum (p_T), pseudorapidity (η) over a broad kinematic range, 0.3

Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy.

Abstract: Francisco Real and colleagues report exome sequencing in urothelial bladder tumors. They show that STAG2, a subunit of the cohesin complex, is recurrently mutated and provide evidence that STAG2 loss does not lead to increases in aneuploidy. Urothelial bladder cancer (UBC) is heterogeneous at the clinical, pathological and genetic levels. Tumor invasiveness (T) and grade (G) are the main factors associated with outcome and determine patient management1. A discovery exome sequencing screen (n = 17), followed by a prevalence screen (n = 60), identified new genes mutated in this tumor coding for proteins involved in chromatin modification (MLL2, ASXL2 and BPTF), cell division (STAG2, SMC1A and SMC1B) and DNA repair (ATM, ERCC2 and FANCA). STAG2, a subunit of cohesin, was significantly and commonly mutated or lost in UBC, mainly in tumors of low stage or grade, and its loss was associated with improved outcome. Loss of expression was often observed in chromosomally stable tumors, and STAG2 knockdown in bladder cancer cells did not increase aneuploidy. STAG2 reintroduction in non-expressing cells led to reduced colony formation. Our findings indicate that STAG2 is a new UBC tumor suppressor acting through mechanisms that are different from its role in preventing aneuploidy.