1,317 research outputs found

    p38ő≥ is essential for cell cycle progression and liver tumorigenesis

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    The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)‚Äďcyclin protein complex1. However, control of the G0-to-G1 transition is not completely understood. Here we demonstrate that p38 MAPK gamma (p38ő≥) acts as a CDK-like kinase and thus cooperates with CDKs, regulating entry into the cell cycle. p38ő≥ shares high sequence homology, inhibition sensitivity and substrate specificity with CDK family members. In mouse hepatocytes, p38ő≥ induces proliferation after partial hepatectomy by promoting the phosphorylation of retinoblastoma tumour suppressor protein at known CDK target residues. Lack of p38ő≥ or treatment with the p38ő≥ inhibitor pirfenidone protects against the chemically induced formation of liver tumours. Furthermore, biopsies of human hepatocellular carcinoma show high expression of p38ő≥, suggesting that p38ő≥ could be a therapeutic target in the treatment of this disease

    Measurement of the cosmic ray spectrum above 4√ó10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

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    A measurement of the cosmic-ray spectrum for energies exceeding 4√ó10184{\times}10^{18} eV is presented, which is based on the analysis of showers with zenith angles greater than 60‚ąė60^{\circ} detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above 5.3√ó10185.3{\times}10^{18} eV, the "ankle", the flux can be described by a power law E‚ąíő≥E^{-\gamma} with index ő≥=2.70¬Ī0.02‚ÄČ(stat)¬Ī0.1‚ÄČ(sys)\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)} followed by a smooth suppression region. For the energy (EsE_\text{s}) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find Es=(5.12¬Ī0.25‚ÄČ(stat)‚ąí1.2+1.0‚ÄČ(sys))√ó1019E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19} eV.Comment: Replaced with published version. Added journal reference and DO

    Credit Supply: Identifying Balance-Sheet Channels with Loan Applications and Granted Loans

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    The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

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    Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

    Outreach activities at the Pierre Auger Observatory

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    CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

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    Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

    Event-by-event reconstruction of the shower maximum XmaxX_{\mathrm{max}} with the Surface Detector of the Pierre Auger Observatory using deep learning

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