60 research outputs found

    Production values as program quality signals in Spanish linear TV: A comparison of two periods

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    Technology disruption, digitalization and media convergence have triggered a profound crisis in the television industry. In this context, quality is an essential strategic element for success, especially when consumers have learned through their experience with VOD, becoming more demanding and less loyal customers. Then, has the importance of quality signals changed with the emergence of new online alternatives? And the quality perception among viewers? Our research explores four production values (the host, content, the set, and technical quality) as TV program quality signals and their effect on the quality perception of entertainment programs of Spanish broadcasters. We compare two years: 2012 and 2016, a period during which the Spanish television market changed due to appearance of OTT services. Using t-tests and regression models, we establish that the importance of quality signals varied over this period, with content proving more important and the set less so in 2016 as compared with 2012. Additionally, in 2016, the results show that the quality perception of linear TV entertainment programs depended more on subjective elements such as liking and satisfaction than on objective elements, as it was in 2012. Finally, our findings are discussed, and some managerial implications and future research are suggested

    Hooked on lit screens

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    The aim of this article is to trace new audiovisual consumption habits, analyzing which screens are preferred by people in Spain when watching different types of content online. In addition, we study the use of second screens, an increasingly common phenomenon. The main sources of data for this empirical study are two original surveys carried out online in May 2012 and in December 2016. The sample size was 1,200 in both cases, and interviews were conducted via the Internet. The target population consisted of Internet users in Spain and the sample distribution was designed to be representative of this population. Our results show that audiovisual consumption habits are changing dramatically, especially when looking at younger users, whose loyalty and attention is even more difficult to attract due to their disruptive practices. In this sense, great uncertainties and risks have emerged in the entertainment industry, although valuable opportunities may also arise.El objetivo de este artículo es descubrir nuevos hábitos de consumo audiovisual, analizando cuáles son las pantallas preferidas por los internautas españoles para ver contenidos audiovisuales online. Además, se analiza el uso de las segundas pantallas, práctica muy extendida entre la audiencia. La principal fuente de información es un estudio de campo basado en dos encuestas online originales lanzadas en mayo de 2012 y en diciembre de 2016. La muestra se compone en ambos casos de 1.200 personas y es representativa de la población internauta en España (universo). Los resultados apuntan a que los patrones de consumo audiovisual están cambiando drásticamente, especialmente en el caso de los usuarios más jóvenes, cuya fidelidad y atención es incluso más difícil de atraer debido a sus prácticas disruptivas. En este sentido, la industria del entretenimiento atraviesa una etapa repleta de importantes incertidumbres y riesgos, aunque al mismo tiempo se vislumbran valiosas oportunidade

    La televisión de los mileniales: una aproximación a sus hábitos de visionado

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    La televisión vive una etapa de transformación sin precedentes debido a la naturaleza disruptiva de las innovaciones tecnológicas derivadas de la digitalización y la convergencia del medio con internet. De un modelo televisivo lineal se ha pasado a una televisión conectada, multipantalla, interactiva y personalizada, en la que se han modificado radical- mente los procesos de producción, comercialización y visionado de los contenidos audio- visuales. Estos procesos se han visto potenciados por la irrupción de los usuarios mileniales, el público joven adulto, para quienes estos cambios son naturales. El presente artículo anali- za el impacto sobre el sector televisivo de los cambios en los hábitos de visionado generados por este grupo. Para ello, además de realizar una revisión bibliográfica, se ha recurrido a la encuesta como herramienta metodológica principal para conocer los nuevos hábitos de visionado. De este modo, se ha aplicado un cuestionario en línea a un panel de consumidores representativo de la población internauta española con edades comprendidas entre los 18 y los 35 años (mileniales), del que se ha obtenido una alta tasa de respuesta —cercana al 60%, porcentaje correspondiente a 518 encuestados—, con un error muestral del 3,1 % considerando una varianza máxima y un 95% de confianza. Se concluye que la competencia de las plataformas audiovisuales en línea disminuye el tiempo dedicado al consumo televisivo convencional, especialmente entre los sectores más jóvenes de la población, y que esto ha obligado a los operadores de televisión tradicionales a renovar su modelo y a apostar por nuevas estrategias y contenidos que cambian sustancialmente su propia identidad

    High-p_T pion and kaon production in relativistic nuclear collisions

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    High-p_T pion and kaon production is studied in relativistic proton-proton, proton-nucleus, and nucleus-nucleus collisions in a wide energy range. Cross sections are calculated based on perturbative QCD, augmented by a phenomenological transverse momentum distribution of partons (``intrinsic k_T''). An energy dependent width of the transverse momentum distribution is extracted from pion and charged hadron production data in proton-proton/proton-antiproton collisions. Effects of multiscattering and shadowing in the strongly interacting medium are taken into account. Enhancement of the transverse momentum width is introduced and parameterized to explain the Cronin effect. In collisions between heavy nuclei, the model over-predicts central pion production cross sections (more significantly at higher energies), hinting at the presence of jet quenching. Predictions are made for proton-nucleus and nucleus-nucleus collisions at RHIC energies.Comment: 26 pages in Latex, 19 EPS figure

    Proteomic analysis of integrin-associated complexes from mesenchymal stem cells

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    PURPOSE: Multipotent mesenchymal stem cells (MSCs) have the capability to differentiate down adipocyte, osteocyte and chondrocyte lineages and as such offer a range of potential therapeutic applications. The composition and stiffness of the extracellular matrix (ECM) environment that surrounds cells dictates their transcriptional programme, thereby affecting stem cell lineage decision‐making. Cells sense force via linkages between themselves and their microenvironment, and this is transmitted by integrin receptors and associated adhesion signalling complexes. To identify regulators of MSC force sensing, we sought to catalogue MSC integrin‐associated adhesion complex composition. EXPERIMENTAL DESIGN: Adhesion complexes formed by MSCs plated on the ECM ligand fibronectin were isolated and characterised by MS. Identified proteins were interrogated by comparison to a literature‐based reference set of cell adhesion‐related components and using ontological and protein–protein interaction network analyses. RESULTS: Adhesion complex‐specific proteins in MSCs were identified that comprised predominantly cell adhesion‐related adaptors and actin cytoskeleton regulators. Furthermore, LIM domain‐containing proteins in MSC adhesion complexes were highlighted, which may act as force‐sensing components. CONCLUSION AND CLINICAL RELEVANCE: These data provide a valuable resource of information regarding the molecular connections that link integrins and adhesion signalling in MSCs, and as such may present novel opportunities for therapeutic intervention

    A substrate mimic allows high-throughput assay of the FabA protein and consequently the identification of a novel inhibitor of <i>Pseudomonas aeruginosa</i> FabA

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    The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 223461, Senior Investigator Award WT100209MA (JHN), Swedish Science Council (GS), Wellcome Trust Strategic grant 100476/Z/12/Z (DWG) and National Institutes of Health R01GM095970 (MB). JHN & ADS are Royal Society Wolfson Merit Award holders.Eukaryotes and prokaryotes possess fatty acid synthase (FAS) biosynthetic pathway(s) that comprise iterative chain elongation, reduction, and dehydration reactions. The bacterial FASII pathway differs significantly from human FAS pathways and is a long-standing target for antibiotic development against Gram-negative bacteria due to differences from the human FAS, and several existing antibacterial agents are known to inhibit FASII enzymes. N-acetylcysteamine (NAC) fatty acid thioesters have been used as mimics of the natural acyl carrier protein (ACP) pathway intermediates to assay FASII enzymes, and we now report an assay of FabV from Pseudomonas aeruginosa using (E)-2-decenoyl-NAC. In addition, we have converted an existing UV absorbance assay for FabA, the bifunctional dehydration/epimerization enzyme and key target in the FAS II pathway, into a high throughput enzyme coupled fluorescence assay that has been employed to screen a library of diverse small molecules. With this approach, N-(4-chlorobenzyl)-3-(2-furyl)-1H-1,2,4-triazol-5-amine (N42FTA) was found to competitively inhibit (pIC50 = 5.7 ± 0.2) the processing of 3-hydroxydecanoyl-NAC by P. aeruginosa FabA. N42FTA was shown to be potent in blocking crosslinking of E. coli ACP and FabA, a direct mimic of the biological process. The co-complex structure of N42FTA with P. aeruginosa FabA protein rationalizes affinity and suggests future design opportunities. Employing NAC fatty acid mimics to developing further high throughput assays for individual enzymes in the FASII pathway should aid in the discovery of new antimicrobials.Publisher PDFPeer reviewe

    Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

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    Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

    RNAi Effector Diversity in Nematodes

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    While RNA interference (RNAi) has been deployed to facilitate gene function studies in diverse helminths, parasitic nematodes appear variably susceptible. To test if this is due to inter-species differences in RNAi effector complements, we performed a primary sequence similarity survey for orthologs of 77 Caenorhabditis elegans RNAi pathway proteins in 13 nematode species for which genomic or transcriptomic datasets were available, with all outputs subjected to domain-structure verification. Our dataset spanned transcriptomes of Ancylostoma caninum and Oesophagostomum dentatum, and genomes of Trichinella spiralis, Ascaris suum, Brugia malayi, Haemonchus contortus, Meloidogyne hapla, Meloidogyne incognita and Pristionchus pacificus, as well as the Caenorhabditis species C. brenneri, C. briggsae, C. japonica and C. remanei, and revealed that: (i) Most of the C. elegans proteins responsible for uptake and spread of exogenously applied double stranded (ds)RNA are absent from parasitic species, including RNAi-competent plant-nematodes; (ii) The Argonautes (AGOs) responsible for gene expression regulation in C. elegans are broadly conserved, unlike those recruited during the induction of RNAi by exogenous dsRNA; (iii) Secondary Argonautes (SAGOs) are poorly conserved, and the nuclear AGO NRDE-3 was not identified in any parasite; (iv) All five Caenorhabditis spp. possess an expanded RNAi effector repertoire relative to the parasitic nematodes, consistent with the propensity for gene loss in nematode parasites; (v) In spite of the quantitative differences in RNAi effector complements across nematode species, all displayed qualitatively similar coverage of functional protein groups. In summary, we could not identify RNAi effector deficiencies that associate with reduced susceptibility in parasitic nematodes. Indeed, similarities in the RNAi effector complements of RNAi refractory and competent nematode parasites support the broad applicability of this research genetic tool in nematodes

    Genetic mechanisms of critical illness in COVID-19.

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    Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
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