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Showing papers by "University of Oviedo published in 2019"


Journal ArticleDOI
Albert M. Sirunyan, Armen Tumasyan, Wolfgang Adam1, Federico Ambrogi1  +2265 moreInstitutions (153)
TL;DR: Combined measurements of the production and decay rates of the Higgs boson, as well as its couplings to vector bosons and fermions, are presented and constraints are placed on various two Higgs doublet models.
Abstract: Combined measurements of the production and decay rates of the Higgs boson, as well as its couplings to vector bosons and fermions, are presented. The analysis uses the LHC proton–proton collision data set recorded with the CMS detector in 2016 at $\sqrt{s}=13\,\text {Te}\text {V} $ , corresponding to an integrated luminosity of 35.9 ${\,\text {fb}^{-1}} $ . The combination is based on analyses targeting the five main Higgs boson production mechanisms (gluon fusion, vector boson fusion, and associated production with a $\mathrm {W}$ or $\mathrm {Z}$ boson, or a top quark-antiquark pair) and the following decay modes: $\mathrm {H} \rightarrow \gamma \gamma $ , $\mathrm {Z}\mathrm {Z}$ , $\mathrm {W}\mathrm {W}$ , $\mathrm {\tau }\mathrm {\tau }$ , $\mathrm {b} \mathrm {b} $ , and $\mathrm {\mu }\mathrm {\mu }$ . Searches for invisible Higgs boson decays are also considered. The best-fit ratio of the signal yield to the standard model expectation is measured to be $\mu =1.17\pm 0.10$ , assuming a Higgs boson mass of $125.09\,\text {Ge}\text {V} $ . Additional results are given for various assumptions on the scaling behavior of the production and decay modes, including generic parametrizations based on ratios of cross sections and branching fractions or couplings. The results are compatible with the standard model predictions in all parametrizations considered. In addition, constraints are placed on various two Higgs doublet models.

451 citations


Journal ArticleDOI
TL;DR: A brief insight into the materials and basics of sensors (methods of transduction, molecular recognition, and amplification) is provided followed by a comprehensive and critical overview of the disposable sensors currently used for medical diagnostics, food, and environmental analysis.
Abstract: Disposable sensors are low-cost and easy-to-use sensing devices intended for short-term or rapid single-point measurements. The growing demand for fast, accessible, and reliable information in a vastly connected world makes disposable sensors increasingly important. The areas of application for such devices are numerous, ranging from pharmaceutical, agricultural, environmental, forensic, and food sciences to wearables and clinical diagnostics, especially in resource-limited settings. The capabilities of disposable sensors can extend beyond measuring traditional physical quantities (for example, temperature or pressure); they can provide critical chemical and biological information (chemo- and biosensors) that can be digitized and made available to users and centralized/decentralized facilities for data storage, remotely. These features could pave the way for new classes of low-cost systems for health, food, and environmental monitoring that can democratize sensing across the globe. Here, a brief insight into the materials and basics of sensors (methods of transduction, molecular recognition, and amplification) is provided followed by a comprehensive and critical overview of the disposable sensors currently used for medical diagnostics, food, and environmental analysis. Finally, views on how the field of disposable sensing devices will continue its evolution are discussed, including the future trends, challenges, and opportunities.

444 citations


Journal ArticleDOI
Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam, Federico Ambrogi  +2298 moreInstitutions (160)
TL;DR: In this article, a search for invisible decays of a Higgs boson via vector boson fusion is performed using proton-proton collision data collected with the CMS detector at the LHC in 2016 at a center-of-mass energy root s = 13 TeV, corresponding to an integrated luminosity of 35.9fb(-1).

347 citations


Journal ArticleDOI
Nabila Aghanim1, Yashar Akrami2, Yashar Akrami3, Yashar Akrami4  +213 moreInstitutions (66)
TL;DR: The 2018 Planck CMB likelihoods were presented in this paper, following a hybrid approach similar to the 2015 one, with different approximations at low and high multipoles, and implementing several methodological and analysis refinements.
Abstract: This paper describes the 2018 Planck CMB likelihoods, following a hybrid approach similar to the 2015 one, with different approximations at low and high multipoles, and implementing several methodological and analysis refinements. With more realistic simulations, and better correction and modelling of systematics, we can now make full use of the High Frequency Instrument polarization data. The low-multipole 100x143 GHz EE cross-spectrum constrains the reionization optical-depth parameter $\tau$ to better than 15% (in combination with with the other low- and high-$\ell$ likelihoods). We also update the 2015 baseline low-$\ell$ joint TEB likelihood based on the Low Frequency Instrument data, which provides a weaker $\tau$ constraint. At high multipoles, a better model of the temperature-to-polarization leakage and corrections for the effective calibrations of the polarization channels (polarization efficiency or PE) allow us to fully use the polarization spectra, improving the constraints on the $\Lambda$CDM parameters by 20 to 30% compared to TT-only constraints. Tests on the modelling of the polarization demonstrate good consistency, with some residual modelling uncertainties, the accuracy of the PE modelling being the main limitation. Using our various tests, simulations, and comparison between different high-$\ell$ implementations, we estimate the consistency of the results to be better than the 0.5$\sigma$ level. Minor curiosities already present before (differences between $\ell$ 800 parameters or the preference for more smoothing of the $C_\ell$ peaks) are shown to be driven by the TT power spectrum and are not significantly modified by the inclusion of polarization. Overall, the legacy Planck CMB likelihoods provide a robust tool for constraining the cosmological model and represent a reference for future CMB observations. (Abridged)

322 citations


Journal ArticleDOI
TL;DR: The most recent feature selection methods developed for and applied in medical problems are reviewed, covering prolific research fields such as medical imaging, biomedical signal processing, and DNA microarray data analysis.

320 citations


Journal ArticleDOI
TL;DR: This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated, to increase awareness and knowledge of adult ADHD in and outside Europe.

285 citations


Journal ArticleDOI
TL;DR: It is demonstrated that correction of the accelerated aging-associated intestinal dysbiosis is beneficial, suggesting the existence of a link between aging and the gut microbiota that provides a rationale for microbiome-based interventions against age-related diseases.
Abstract: The gut microbiome is emerging as a key regulator of several metabolic, immune and neuroendocrine pathways1,2. Gut microbiome deregulation has been implicated in major conditions such as obesity, type 2 diabetes, cardiovascular disease, non-alcoholic fatty acid liver disease and cancer3-6, but its precise role in aging remains to be elucidated. Here, we find that two different mouse models of progeria are characterized by intestinal dysbiosis with alterations that include an increase in the abundance of Proteobacteria and Cyanobacteria, and a decrease in the abundance of Verrucomicrobia. Consistent with these findings, we found that human progeria patients also display intestinal dysbiosis and that long-lived humans (that is, centenarians) exhibit a substantial increase in Verrucomicrobia and a reduction in Proteobacteria. Fecal microbiota transplantation from wild-type mice enhanced healthspan and lifespan in both progeroid mouse models, and transplantation with the verrucomicrobia Akkermansia muciniphila was sufficient to exert beneficial effects. Moreover, metabolomic analysis of ileal content points to the restoration of secondary bile acids as a possible mechanism for the beneficial effects of reestablishing a healthy microbiome. Our results demonstrate that correction of the accelerated aging-associated intestinal dysbiosis is beneficial, suggesting the existence of a link between aging and the gut microbiota that provides a rationale for microbiome-based interventions against age-related diseases.

279 citations


Journal ArticleDOI
TL;DR: It is recommended that the diagnosis of XLH is based on signs of rickets and/or osteomalacia in association with hypophosphataemia and renal phosphate wasting in the absence of vitamin D or calcium deficiency.
Abstract: X-linked hypophosphataemia (XLH) is the most common cause of inherited phosphate wasting and is associated with severe complications such as rickets, lower limb deformities, pain, poor mineralization of the teeth and disproportionate short stature in children as well as hyperparathyroidism, osteomalacia, enthesopathies, osteoarthritis and pseudofractures in adults. The characteristics and severity of XLH vary between patients. Because of its rarity, the diagnosis and specific treatment of XLH are frequently delayed, which has a detrimental effect on patient outcomes. In this Evidence-Based Guideline, we recommend that the diagnosis of XLH is based on signs of rickets and/or osteomalacia in association with hypophosphataemia and renal phosphate wasting in the absence of vitamin D or calcium deficiency. Whenever possible, the diagnosis should be confirmed by molecular genetic analysis or measurement of levels of fibroblast growth factor 23 (FGF23) before treatment. Owing to the multisystemic nature of the disease, patients should be seen regularly by multidisciplinary teams organized by a metabolic bone disease expert. In this article, we summarize the current evidence and provide recommendations on features of the disease, including new treatment modalities, to improve knowledge and provide guidance for diagnosis and multidisciplinary care. In this Evidence-Based Guideline on X-linked hypophosphataemia, the authors identify the criteria for diagnosis of this disease, provide guidance for medical and surgical treatment and explain the challenges of follow-up.

264 citations


Journal ArticleDOI
01 Jan 2019
TL;DR: The presented research reveals that coherent 3D data and spectral information, as provided by the SfM workflow, promote opportunities to derive both structural and physiological attributes at the individual tree crown (ITC) as well as stand levels.
Abstract: The adoption of Structure from Motion photogrammetry (SfM) is transforming the acquisition of three-dimensional (3D) remote sensing (RS) data in forestry. SfM photogrammetry enables surveys with little cost and technical expertise. We present the theoretical principles and practical considerations of this technology and show opportunities that SfM photogrammetry offers for forest practitioners and researchers. Our examples of key research indicate the successful application of SfM photogrammetry in forestry, in an operational context and in research, delivering results that are comparable to LiDAR surveys. Reviewed studies have identified possibilities for the extraction of biophysical forest parameters from airborne and terrestrial SfM point clouds and derived 2D data in area-based approaches (ABA) and individual tree approaches. Additionally, increases in the spatial and spectral resolution of sensors available for SfM photogrammetry enable forest health assessment and monitoring. The presented research reveals that coherent 3D data and spectral information, as provided by the SfM workflow, promote opportunities to derive both structural and physiological attributes at the individual tree crown (ITC) as well as stand levels. We highlight the potential of using unmanned aerial vehicles (UAVs) and consumer-grade cameras for terrestrial SfM-based surveys in forestry. Offering several spatial products from a single sensor, the SfM workflow enables foresters to collect their own fit-for-purpose RS data. With the broad availability of non-expert SfM software, we provide important practical considerations for the collection of quality input image data to enable successful photogrammetric surveys.

251 citations


Journal ArticleDOI
D. Blanco1, Pedro Fernández1, A. Noriega1, B.J. Alvarez1, G. Valiño1 
18 Dec 2019-Sensors
TL;DR: A new local distortion adjustment (LDA) method is proposed and its distortion correction capabilities are evaluated upon actual layer contours manufactured on a fused filament fabrication (FFF) machine, revealing quasi-systematic deformations of the images which could be minimized by means of distortion correction.
Abstract: Industrial adoption of additive manufacturing (AM) processes demands improvement in the geometrical accuracy of manufactured parts. One key achievement would be to ensure that manufactured layer contours match the correspondent theoretical profiles, which would require integration of on-machine measurement devices capable of digitizing individual layers. Flatbed scanners should be considered as serious candidates, since they can achieve high scanning speeds at low prices. Nevertheless, image deformation phenomena reduce their suitability as two-dimensional verification devices. In this work, the possibilities of using flatbed scanners for AM contour verification are investigated. Image distortion errors are characterized and discussed and special attention is paid to the plication effect caused by contact imaging sensor (CIS) scanners. To compensate this phenomena, a new local distortion adjustment (LDA) method is proposed and its distortion correction capabilities are evaluated upon actual layer contours manufactured on a fused filament fabrication (FFF) machine. This proposed method is also compared to conventional global distortion adjustment (GDA). Results reveal quasi-systematic deformations of the images which could be minimized by means of distortion correction. Nevertheless, the irregular nature of such a distortion and the superposition of different errors penalize the use of GDA, to the point that it should not be used with CIS scanners. Conclusions indicate that LDA-based correction would enable the use of flatbed scanners in AM for on-machine verification tasks.

213 citations


Journal ArticleDOI
TL;DR: This work proposes broadening the range of morphological, physiological and biochemical seed traits to add new understanding on plant niches, population dynamics and community assembly and lays the foundation for a seed-trait functional network which will underpin and facilitate trait-based inferences.
Abstract: Trait-based approaches have improved our understanding of plant evolution, community assembly and ecosystem functioning. A major challenge for the upcoming decades is to understand the functions and evolution of early life-history traits, across levels of organization and ecological strategies. Although a variety of seed traits are critical for dispersal, persistence, germination timing and seedling establishment, only seed mass has been considered systematically. Here we suggest broadening the range of morphological, physiological and biochemical seed traits to add new understanding on plant niches, population dynamics and community assembly. The diversity of seed traits and functions provides an important challenge that will require international collaboration in three areas of research. First, we present a conceptual framework for a seed ecological spectrum that builds upon current understanding of plant niches. We then lay the foundation for a seed-trait functional network, the establishment of which will underpin and facilitate trait-based inferences. Finally, we anticipate novel insights and challenges associated with incorporating diverse seed traits into predictive evolutionary ecology, community ecology and applied ecology. If the community invests in standardized seed-trait collection and the implementation of rigorous databases, major strides can be made at this exciting frontier of functional ecology.

Journal ArticleDOI
Albert M. Sirunyan, Armen Tumasyan, Wolfgang Adam1, Federico Ambrogi1  +2319 moreInstitutions (159)
TL;DR: In this article, the performance of missing transverse momentum (Tmiss) reconstruction algorithms for the CMS experiment is presented, using proton-proton collisions at a center of mass energy of 13 TeV, collected at the CERN LHC in 2016.
Abstract: The performance of missing transverse momentum (Tmiss) reconstruction algorithms for the CMS experiment is presented, using proton-proton collisions at a center-of-mass energy of 13 TeV, collected at the CERN LHC in 2016. The data sample corresponds to an integrated luminosity of 35.9 fb-1. The results include measurements of the scale and resolution of Tmiss, and detailed studies of events identified with anomalous Tmiss. The performance is presented of a Tmiss reconstruction algorithm that mitigates the effects of multiple proton-proton interactions, using the "pileup per particle identification" method. The performance is shown of an algorithm used to estimate the compatibility of the reconstructed Tmiss with the hypothesis that it originates from resolution effects.

Journal ArticleDOI
Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam, Federico Ambrogi  +2272 moreInstitutions (160)
TL;DR: A search for Higgs boson pair production using the combined results from four final states: bbγγ, bbττ, bbbb, and bbVV, where V represents a W or Z boson, is performed using data collected in 2016 by the CMS experiment from LHC proton-proton collisions.
Abstract: This Letter describes a search for Higgs boson pair production using the combined results from four final states: bbγγ, bbττ, bbbb, and bbVV, where V represents a W or Z boson. The search is performed using data collected in 2016 by the CMS experiment from LHC proton-proton collisions at s=13 TeV, corresponding to an integrated luminosity of 35.9 fb-1. Limits are set on the Higgs boson pair production cross section. A 95% confidence level observed (expected) upper limit on the nonresonant production cross section is set at 22.2 (12.8) times the standard model value. A search for narrow resonances decaying to Higgs boson pairs is also performed in the mass range 250–3000 GeV. No evidence for a signal is observed, and upper limits are set on the resonance production cross section.


Journal ArticleDOI
TL;DR: The sPlot database as mentioned in this paper contains 1,121,244 vegetation plots, which comprise 23,586,216 records of plant species and their relative cover or abundance in plots collected worldwide between 1885 and 2015.
Abstract: Aims :Vegetation-plot records provide information on the presence and cover or abundance of plants co-occurring in the same community. Vegetation-plot data are spread across research groups, environmental agencies and biodiversity research centers and, thus, are rarely accessible at continental or global scales. Here we present the sPlot database, which collates vegetation plots worldwide to allow for the exploration of global patterns in taxonomic, functional and phylogenetic diversity at the plant community level. Results: sPlot version 2.1 contains records from 1,121,244 vegetation plots, which comprise 23,586,216 records of plant species and their relative cover or abundance in plots collected worldwide between 1885 and 2015. We complemented the information for each plot by retrieving climate and soil conditions and the biogeographic context (e.g., biomes) from external sources, and by calculating community-weighted means and variances of traits using gap-filled data from the global plant trait database TRY. Moreover, we created a phylogenetic tree for 50,167 out of the 54,519 species identified in the plots. We present the first maps of global patterns of community richness and community-weighted means of key traits. Conclusions: The availability of vegetation plot data in sPlot offers new avenues for vegetation analysis at the global scale.

Journal ArticleDOI
TL;DR: The different salvage treatment options and associated prognostic factors for each of them are reviewed and a treatment algorithm based on the latest available evidence is proposed to discuss the future directions of treatment for locally recurrent NPC.

Journal ArticleDOI
TL;DR: The molecular and cellular mechanisms through which WNT signaling influences cancer immunosurveillance are discussed and potential therapeutic avenues to harness currently available WNT modulators for cancer immunotherapy are presented.

Journal ArticleDOI
Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam, Federico Ambrogi  +2382 moreInstitutions (209)
TL;DR: In this paper, a search for supersymmetric particles in the final state with multiple jets and large missing transverse momentum was performed using a sample of proton-proton collisions collected with the CMS detector.
Abstract: Results are reported from a search for supersymmetric particles in the final state with multiple jets and large missing transverse momentum. The search uses a sample of proton-proton collisions at $ \sqrt{s} $ = 13 TeV collected with the CMS detector in 2016–2018, corresponding to an integrated luminosity of 137 fb$^{−1}$, representing essentially the full LHC Run 2 data sample. The analysis is performed in a four-dimensional search region defined in terms of the number of jets, the number of tagged bottom quark jets, the scalar sum of jet transverse momenta, and the magnitude of the vector sum of jet transverse momenta. No significant excess in the event yield is observed relative to the expected background contributions from standard model processes. Limits on the pair production of gluinos and squarks are obtained in the framework of simplified models for supersymmetric particle production and decay processes. Assuming the lightest supersymmetric particle to be a neutralino, lower limits on the gluino mass as large as 2000 to 2310 GeV are obtained at 95% confidence level, while lower limits on the squark mass as large as 1190 to 1630 GeV are obtained, depending on the production scenario.

Journal ArticleDOI
TL;DR: In this article, the light-by-light scattering process in ultra-peripheral PbPb collisions at a centre-of-mass energy per nucleon pair of 5.02 TeV is reported.

Journal ArticleDOI
TL;DR: The importance of the epigenetic alterations identified in human cancer, which have led to the appearance of biomarkers or epigenetic drugs in precision medicine, are summarized, and the transport and release systems of theigenetic drugs that have been developed to date are described.
Abstract: The emergence of nanotechnology applied to medicine has revolutionized the treatment of human cancer. As in the case of classic drugs for the treatment of cancer, epigenetic drugs have evolved in terms of their specificity and efficiency, especially because of the possibility of using more effective transport and delivery systems. The use of nanoparticles (NPs) in oncology management offers promising advantages in terms of the efficacy of cancer treatments, but it is still unclear how these NPs may be affecting the epigenome such that safe routine use is ensured. In this work, we summarize the importance of the epigenetic alterations identified in human cancer, which have led to the appearance of biomarkers or epigenetic drugs in precision medicine, and we describe the transport and release systems of the epigenetic drugs that have been developed to date.

Journal ArticleDOI
TL;DR: Following the ten proposed steps, objective tests can be developed with adequate psychometric properties based on empirical evidence.
Abstract: Background: Tests are the measurement instruments most used by psychologists to obtain data about people, both in professional and research contexts. The main goal of this paper is to synthesize in ten steps the fundamental aspects that must be taken into account when building a test in a rigorous way. Method: For the elaboration of the ten proposed phases, the specialized psychometric literature was revised, and previous works by the authors on the subject were updated. Results: Ten steps are proposed for the objective development of a test: delimitation of the general framework, defi nition of the variable to be measured, specifi cations, items development, edition of the test, pilot studies, selection of other measurement instruments, test administration, psychometric properties, and development of the fi nal version. Conclusion: Following the ten proposed steps, objective tests can be developed with adequate psychometric properties based on empirical evidence

Journal ArticleDOI
TL;DR: The algorithm combines time series analysis methods to forecast the values of the predictor variables with machine learning techniques to predict RUL from those variables, and shows a high prediction capability, far greater than that provided by the VARMA model.

Journal ArticleDOI
TL;DR: Results are consistent with most of the associations previously found between these patterns and breast, prostate and gastric cancer risk and indicate that consuming whole fruits, vegetables, legumes, olive oil, nuts, and fish and avoiding red and processed meat, refined grains, sweets, caloric drinks, juices, convenience food, and sauces might reduce CRC risk.
Abstract: To assess if the associations found between three previously identified dietary patterns with breast, prostate and gastric cancer are also observed for colorectal cancer (CRC). MCC-Spain is a multicase-control study that collected information of 1629 incident cases of CRC and 3509 population-based controls from 11 Spanish provinces. Western, Prudent and Mediterranean data-driven dietary patterns—derived in another Spanish case-control study—were reconstructed in MCC-Spain. Their association with CRC was assessed using mixed multivariable logistic regression models considering a possible interaction with sex. Risk by tumor site (proximal colon, distal colon, and rectum) was evaluated using multinomial regression models. While no effect of the Prudent pattern on CRC risk was observed, a high adherence to the Western dietary pattern was associated with increased CRC risk for both males [ORfourth(Q4) vs. first(Q1)quartile (95% CI): 1.45 (1.11;1.91)] and females [ORQ4 vs. Q1 (95% CI): 1.50 (1.07;2.09)] but seem to be confined to distal colon [ORfourth(Q4) vs. first(Q1)quartile (95% CI): 2.02 (1.44;2.84)] and rectal [ORQ4 vs. Q1 (95% CI): 1.46 (1.05;2.01)] tumors. The protective effect of the Mediterranean dietary pattern against CRC was observed for both sexes [males: ORQ4 vs. Q1 (95% CI): 0.71 (0.55;0.92); females: ORQ4 vs. Q1 (95% CI): 0.56 (0.40;0.77)] and for all cancer sites: proximal colon [ORQ4 vs. Q1 (95% CI): 0.70 (0.51;0.97)], distal colon [ORQ4 vs. Q1 (95% CI): 0.65 (0.48;0.89)], and rectum (ORQ4 vs. Q1 (95% CI): 0.60 (0.45;0.81)]. Our results are consistent with most of the associations previously found between these patterns and breast, prostate and gastric cancer risk and indicate that consuming whole fruits, vegetables, legumes, olive oil, nuts, and fish and avoiding red and processed meat, refined grains, sweets, caloric drinks, juices, convenience food, and sauces might reduce CRC risk.

Journal ArticleDOI
TL;DR: This review focuses on major physiological changes such as aging and essential pathologies including cancer, neurodegenerative diseases, viral infections and obesity, and document the essential role of melatonin in the regulation of autophagy in each of these different situations.
Abstract: There are several pathologies, syndromes, and physiological processes in which autophagy is involved. This process of self-digestion that cells trigger as a survival mechanism is complex and tightly regulated, according to the homeostatic conditions of the organ. However, in all cases, its relationship with oxidative stress alterations is evident, following a pathway that suggests endoplasmic reticulum stress and/or mitochondrial changes. There is accumulating evidence of the beneficial role that melatonin has in the regulation and restoration of damaged autophagic processes. In this review, we focus on major physiological changes such as aging and essential pathologies including cancer, neurodegenerative diseases, viral infections and obesity, and document the essential role of melatonin in the regulation of autophagy in each of these different situations.

Journal ArticleDOI
31 Oct 2019-Nature
TL;DR: These U1 snRNA mutations provide an example of highly recurrent and tissue-specific mutations of a non-protein-coding gene in cancer, which result in disrupted RNA splicing and the activation of oncogenes.
Abstract: In cancer, recurrent somatic single-nucleotide variants-which are rare in most paediatric cancers-are confined largely to protein-coding genes1-3. Here we report highly recurrent hotspot mutations (r.3A>G) of U1 spliceosomal small nuclear RNAs (snRNAs) in about 50% of Sonic hedgehog (SHH) medulloblastomas. These mutations were not present across other subgroups of medulloblastoma, and we identified these hotspot mutations in U1 snRNA in only <0.1% of 2,442 cancers, across 36 other tumour types. The mutations occur in 97% of adults (subtype SHHδ) and 25% of adolescents (subtype SHHα) with SHH medulloblastoma, but are largely absent from SHH medulloblastoma in infants. The U1 snRNA mutations occur in the 5' splice-site binding region, and snRNA-mutant tumours have significantly disrupted RNA splicing and an excess of 5' cryptic splicing events. Alternative splicing mediated by mutant U1 snRNA inactivates tumour-suppressor genes (PTCH1) and activates oncogenes (GLI2 and CCND2), and represents a target for therapy. These U1 snRNA mutations provide an example of highly recurrent and tissue-specific mutations of a non-protein-coding gene in cancer.

Journal ArticleDOI
TL;DR: Recommendations included a call for more specific language that clarifies conceptual differences between frailty definitions and measurement tools and the development of randomized controlled trials to test whether specific intervention strategies for a variety of conditions differently affect frail and non‐frail individuals.
Abstract: Frailty has long been an important concept in the practice of geriatric medicine and in gerontological research, but integration and implementation of frailty concepts into clinical practice in the United States has been slow. The National Institute on Aging (NIA) Intramural Research Program and the Johns Hopkins Older Americans Independence Center sponsored a symposium to identify potential barriers that impede the movement of frailty into clinical practice and to highlight opportunities to facilitate the further integration of frailty into clinical practice. Primary and subspecialty care providers, and investigators working to integrate and translate new biological aging knowledge into more specific preventive and treatment strategies for frailty provided the meeting content. Recommendations included a call for more specific language that clarifies conceptual differences between frailty definitions and measurement tools; the development of randomized controlled trials to test whether specific intervention strategies for a variety of conditions differently affect frail and non-frail individuals; development of implementation studies and therapeutic trials aimed at tailoring care as a function of pragmatic frailty markers; the use of deep learning and dynamic systems approaches to improve the translatability of findings from epidemiological studies; and the incorporation of advances in aging biology, especially focused on mitochondria, stem cells, and senescent cells, toward the further development of biologically targeted intervention and prevention strategies that can be used to treat or prevent frailty. J Am Geriatr Soc 67:1559-1564, 2019.

Journal ArticleDOI
01 Oct 2019-Nature
TL;DR: This study demonstrates a noncoding driver in spliceosomal RNAs, reveals a mechanism of aberrant splicing in cancer and may represent a new target for treatment, and suggests that driver discovery should be extended to a wider range of genomic regions.
Abstract: Cancers are caused by genomic alterations known as drivers. Hundreds of drivers in coding genes are known but, to date, only a handful of noncoding drivers have been discovered—despite intensive searching1,2. Attention has recently shifted to the role of altered RNA splicing in cancer; driver mutations that lead to transcriptome-wide aberrant splicing have been identified in multiple types of cancer, although these mutations have only been found in protein-coding splicing factors such as splicing factor 3b subunit 1 (SF3B1)3–6. By contrast, cancer-related alterations in the noncoding component of the spliceosome—a series of small nuclear RNAs (snRNAs)—have barely been studied, owing to the combined challenges of characterizing noncoding cancer drivers and the repetitive nature of snRNA genes1,7,8. Here we report a highly recurrent A>C somatic mutation at the third base of U1 snRNA in several types of tumour. The primary function of U1 snRNA is to recognize the 5′ splice site via base-pairing. This mutation changes the preferential A–U base-pairing between U1 snRNA and the 5′ splice site to C–G base-pairing, and thus creates novel splice junctions and alters the splicing pattern of multiple genes—including known drivers of cancer. Clinically, the A>C mutation is associated with heavy alcohol use in patients with hepatocellular carcinoma, and with the aggressive subtype of chronic lymphocytic leukaemia with unmutated immunoglobulin heavy-chain variable regions. The mutation in U1 snRNA also independently confers an adverse prognosis to patients with chronic lymphocytic leukaemia. Our study demonstrates a noncoding driver in spliceosomal RNAs, reveals a mechanism of aberrant splicing in cancer and may represent a new target for treatment. Our findings also suggest that driver discovery should be extended to a wider range of genomic regions. A highly recurrent A>C somatic mutation in U1 small nuclear RNA, which alters the splicing pattern of genes that include known drivers of cancer, is identified in several types of tumour.

Journal ArticleDOI
TL;DR: In this article, a search for direct production of the supersymmetric partners of electrons or muons is presented in final states with two opposite-charge, same-flavour leptons (electrons and muons), no jets, and large missing transverse momentum.

Journal ArticleDOI
Rafael Luque1, Rafael Luque2, Enric Palle2, Enric Palle1, Diana Kossakowski3, Stefan Dreizler4, J. Kemmer5, Néstor Espinoza3, Jennifer Burt6, Guillem Anglada-Escudé1, Guillem Anglada-Escudé7, Víctor J. S. Béjar2, Víctor J. S. Béjar1, Jose A. Caballero1, Karen A. Collins8, Kevin I. Collins9, M. Cortés-Contreras1, E. Díez-Alonso10, E. Díez-Alonso11, Fabo Feng12, Artie P. Hatzes, Coel Hellier13, Thomas Henning3, S. V. Jeffers4, Lisa Kaltenegger14, Martin Kürster3, J. Madden14, Karan Molaverdikhani3, D. Montes10, Norio Narita, Grzegorz Nowak1, Grzegorz Nowak2, Aviv Ofir15, Mahmoudreza Oshagh4, Hannu Parviainen2, Hannu Parviainen1, Andreas Quirrenbach5, Sabine Reffert5, Ansgar Reiners4, Cristina Rodríguez-López1, Martin Schlecker3, S. Stock5, Trifon Trifonov3, Joshua N. Winn16, M. R. Zapatero Osorio1, Mathias Zechmeister4, Pedro J. Amado1, David R. Anderson13, Natasha E. Batalha17, F. F. Bauer1, P. Bluhm5, Christopher J. Burke6, R. P. Butler12, Douglas A. Caldwell18, Douglas A. Caldwell19, Guo Chen20, Jeffrey D. Crane12, Diana Dragomir6, Courtney D. Dressing21, Scott Dynes6, Jon M. Jenkins19, A. Kaminski5, Hubert Klahr3, Takayuki Kotani, M. Lafarga22, David W. Latham8, Pablo Lewin, Scott McDermott, Pilar Montañés-Rodríguez2, Pilar Montañés-Rodríguez1, Juan Carlos Morales22, Felipe Murgas1, Felipe Murgas2, Evangelos Nagel23, S. Pedraz1, Ignasi Ribas22, George R. Ricker6, Pamela Rowden24, Sara Seager6, S. Shectman12, Motohide Tamura25, Johanna Teske12, J. D. Twicken18, J. D. Twicken19, R. Vanderspeck6, Sharon X. Wang12, Bill Wohler19, Bill Wohler18 
TL;DR: In this paper, a transiting Earth-size planet around GJ 357, a nearby M2.5 V star, was detected using data from the Transiting Exoplanet Survey Satellite (TESS).
Abstract: We report the detection of a transiting Earth-size planet around GJ 357, a nearby M2.5 V star, using data from the Transiting Exoplanet Survey Satellite (TESS). GJ 357 b (TOI-562.01) is a transiting, hot, Earth-sized planet (T eq = 525 ± 11 K) with a radius of R b = 1.217 ± 0.084 R ⊕ and an orbital period of P b = 3.93 d. Precise stellar radial velocities from CARMENES and PFS, as well as archival data from HIRES, UVES, and HARPS also display a 3.93-day periodicity, confirming the planetary nature and leading to a planetary mass of M b = 1.84 ± 0.31 M ⊕ . In addition to the radial velocity signal for GJ 357 b, more periodicities are present in the data indicating the presence of two further planets in the system: GJ 357 c, with a minimum mass of M c = 3.40 ± 0.46 M ⊕ in a 9.12 d orbit, and GJ 357 d, with a minimum mass of M d = 6.1 ± 1.0 M ⊕ in a 55.7 d orbit inside the habitable zone. The host is relatively inactive and exhibits a photometric rotation period of P rot = 78 ± 2 d. GJ 357 b isto date the second closest transiting planet to the Sun, making it a prime target for further investigations such as transmission spectroscopy. Therefore, GJ 357 b represents one of the best terrestrial planets suitable for atmospheric characterization with the upcoming JWST and ground-based ELTs.

Journal ArticleDOI
TL;DR: Friction is characterized at the nanoscale using AFM experiments with the same tip sliding over graphene, MoS2, and a graphene/MoS2 heterostructure in a single measurement, repeated hundreds of times, and also measured with a slowly varying normal force.
Abstract: Ultralow friction can be achieved with 2D materials, particularly graphene and MoS2. The nanotribological properties of these different 2D materials have been measured in previous atomic force microscope (AFM) experiments sequentially, precluding immediate and direct comparison of their frictional behavior. Here, friction is characterized at the nanoscale using AFM experiments with the same tip sliding over graphene, MoS2, and a graphene/MoS2 heterostructure in a single measurement, repeated hundreds of times, and also measured with a slowly varying normal force. The same material systems are simulated using molecular dynamics (MD) and analyzed using density functional theory (DFT) calculations. In both experiments and MD simulations, graphene consistently exhibits lower friction than the MoS2 monolayer and the heterostructure. In some cases, friction on the heterostructure is lower than that on the MoS2 monolayer. Quasi-static MD simulations and DFT calculations show that the origin of the friction contrast is the difference in energy barriers for a tip sliding across each of the three surfaces.