5,362 research outputs found

    Physical Characterization of Long-Lasting Hybrid Eruptions: The 2021 Tajogaite Eruption of Cumbre Vieja (La Palma, Canary Islands)

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    Long-lasting, hybrid eruptions can be of complex description and classification, especially when associated with multiple eruptive styles and multiple products. The 2021 Tajogaite eruption of La Palma, Canary Islands, was associated with a magma-gas decoupled system that resulted in the simultaneous emission of lava flows and tephra plumes from various vents. Even though the tephra blanket (∼2 × 107 m3) represents only 7%–16% of the total erupted volume, it provides fundamental insights into the overall eruptive dynamics. Tephra was mostly dispersed NE-SW due to a complex regional and local wind patterns and was subdivided into 3 units and 11 layers that well correlate at different distances from the vent and with both tremor data and lava emission rate. While plume height varied at the temporal scale of a few hours, the average mass eruption rate associated with the tephra blanket of the different units remained relatively constant (∼3–4 × 103 kg s−1). In contrast, the emission rate of lava largely increased after the first week and remained higher than the overall emission of tephra throughout the whole eruption (average value of ∼6 × 104 kg s−1). Based on a detailed characterization of the tephra blanket in combination with atmospheric wind, tremor, and lava emission trend, we demonstrate the need of (a) multidisciplinary strategies for the description of hybrid eruptions that account for both the duration of individual phases and the quantification of the mass of multiple products, and of (b) dedicated ash dispersal forecasting strategies that account for the frequent variations of eruptive and atmospheric conditions

    REGULATION OF BETA-ADRENOCEPTORS ACTIVITYUSING SYNTHETIC LIGHT-REGULATED MOLECULES

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    Beta-adrenoceptors (ß-AR) are prototypical G proteincoupled receptors and important pharmacological targets for many diseases. Indeed, a number of approved drugs target these receptors due to their key role on many physiological functions. Among other examples, we encounter ß1-AR antagonists (ß- Blockers), which constitute the first-line therapy for the treatment of heart diseases, and ß2-AR agonists, which act as bronchodilators for the treatment of breathing pathologies. Considering the relevance of these receptors, achieving a reversible and localised control of their activity would provide a powerful tool, both for its research applications and its clinical potential. In this context, photopharmacology arises as a potent approach. Photopharmacology is an emerging field based on the use of synthetic light-regulated molecules to allow reversible spatiotemporal control of target receptors in native tissues. These ligands have the potential to provide a precise and controllable therapeutic action with increased efficacy and reduced side effects. Moreover, the fine regulation on demand of the receptor activation state is of great interest for their study in non-modified cells, tissues and organisms. The present project provides the first proof of concept for beta-adrenoceptor photopharmacology. We first designed and synthesised libraries of lightregulated compounds in order to regulate ß-AR activity with spatiotemporal precision. Subsequent testing highlighted the successful development of compounds with promising pharmacological properties which can be reversibly and irreversibly controlled by light. The discovered molecules enable a fine control of ß-AR in their native environment that will certainly open the door to innovative research procedures and may inspire future personalized therapies targeting these receptors

    In vitro and in vivo regulation of ß-Adrenoceptors signaling using synthetic light-regulated molecules

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    Beta-adrenoceptors (ß-AR) are prototypical G protein-coupled receptors (GPCR) and important pharmacological targets for numerous diseases. Indeed, a number of approved drugs target ß-AR, which are key regulators of many physiological functions. Among other examples, ß1-AR antagonists (known as ß-Blockers) are first-line therapies for the treatment of heart failure, and ß2-AR agonists, which act as bronchodilators, are widely used for the treatment of breathing pathologies. Considering the medical relevance of these receptors, achieving a reversible and localized control of their activity would provide a powerful research and clinical tool. GPCR signaling is currently recognized as a multidimensional process governed by molecular, spatial and temporal components. Uncovering the role of each of these dimensions is crucial to improve our knowledge on cell communication, to understand how different pathways give rise to cellular and physiological effects, and to know how can we interact with biological systems with precision using drugs. Photopharmacology is an emerging field in which light-sensitive molecules are used to control the function of a given target protein in native tissues. The modulation of the target activity is achieved by small, drug-like, photoregulated ligands. By the use of light, both spatial and temporal control of the compound activity can be achieved in unprecedented manners compared to conventional pharmacology. These ligands have the potential to provide highly precise and controllable therapeutic actions that may result in increased efficacies and reduced side effects. Importantly, photopharmacology may allow to gain mechanistic insight on the interplay between the activation time and the receptor location during signaling processes in non-modified cells, tissues and whole organisms. Our research focused on the generation of new molecular tools for beta-adrenoceptors photopharmacology will be presented in this communication. First, several libraries of light-sensitive compounds with the aim to regulate ß-AR activity with spatiotemporal precision were designed and synthesized. Subsequent testing in cell preparations demonstrated the successful development of compounds with promising pharmacological properties, which can be reversibly and irreversibly controlled by light. Among those, several hit compounds were identified as ligands for beta-1 and beta-2 adrenoceptors with low nanomolar activities. These libraries compounds were found to be active enough to become useful photopharmacological tools, so we also performed in vivo experiments to determine their research potential in physiological environments. Indeed, the discovered molecules enabled a fine control of ß-AR in their native environment. We believe that the results of these studies will certainly open the door to innovative research procedures and may inspire future therapies targeting ß-AR

    Tephra sedimentation and grainsize associated with pulsatory activity: the 2021 Tajogaite eruption of Cumbre Vieja (La Palma, Canary Islands, Spain)

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    Long-lasting eruptions are of complex characterization and are typically associated with challenging risk assessment and crisis management due to the usual occurrence of multiple interacting hazards evolving at different temporal and spatial scales (e.g., lava, tephra, and gas). The 2021 Tajogaite eruption of Cumbre Vieja (La Palma) demonstrated how even hybrid events that are mostly effusive can be associated with widespread and impacting tephra deposits as a result of a complex interplay among gas flux, conduit geometry, and magma feeding rate. In this novel study, direct observations, syn-eruptive and post-eruptive sampling, and statistical analysis of pulsatory activity have been combined to provide new insights into eruption dynamics. They show how rapid gas segregation and high magma ascent rate modulated the gas flux at multiple vents, resulting in short-time fluctuations among the different explosive styles (ash-poor gas puffing, Strombolian, violent Strombolian, and lava fountaining) and unsteady tephra ground accumulation. Various size-selective sedimentation processes were also observed, including particle aggregation and ash fingers, which have impacted the overall tephra dispersal. In fact, even though both local and total grainsize distributions of selected layers, units, and of the whole tephra blanket are unimodal with a low fine-ash content, grainsize analysis of 154 samples suggests no correlation of particles <63 μm with distance from vents. Our analyses demonstrate the need to include a detailed characterization of all products of hybrid eruptions for a comprehensive interpretation of eruptive dynamics and to use multiple classification strategies that can capture eruptive styles at different temporal scales

    NG2 antigen is involved in leukemia invasiveness and central nervous system infiltration in MLL-rearranged infant B-ALL

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    Mixed-lineage leukemia (MLL)-rearranged (MLLr) infant B-cell acute lymphoblastic leukemia (iMLLr-B-ALL) has a dismal prognosis and is associated with a pro-B/mixed phenotype, therapy refractoriness and frequent central nervous system (CNS) disease/relapse. Neuron-glial antigen 2 (NG2) is specifically expressed in MLLr leukemias and is used in leukemia immunophenotyping because of its predictive value for MLLr acute leukemias. NG2 is involved in melanoma metastasis and brain development; however, its role in MLL-mediated leukemogenesis remains elusive. Here we evaluated whether NG2 distinguishes leukemia-initiating/propagating cells (L-ICs) and/or CNS-infiltrating cells (CNS-ICs) in iMLLr-B-ALL. Clinical data from the Interfant cohort of iMLLr-B-ALL demonstrated that high NG2 expression associates with lower event-free survival, higher number of circulating blasts and more frequent CNS disease/relapse. Serial xenotransplantation of primary MLL-AF4 + leukemias indicated that NG2 is a malleable marker that does not enrich for L-IC or CNS-IC in iMLLr-B-All. However, NG2 expression was highly upregulated in blasts infiltrating extramedullar hematopoietic sites and CNS, and specific blockage of NG2 resulted in almost complete loss of engraftment. Indeed, gene expression profiling of primary blasts and primografts revealed a migratory signature of NG2 + blasts. This study provides new insights on the biology of NG2 in iMLLr-B-ALL and suggests NG2 as a potential therapeutic target to reduce the risk of CNS disease/relapse and to provide safer CNS-directed therapies for iMLLr-B-ALL

    The initial phase of the 2021 Cumbre Vieja ridge eruption (Canary Islands): Products and dynamics controlling edifice growth and collapse

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    Tajogaite cone in the Cumbre Vieja ridge (La Palma, Canary Islands) erupted between 19 September and 13 December 2021. The tephra and lava sourced from the newly formed fissure rapidly built a pyroclastic cone. During the early days of eruption and after several small-scale landslides, the west flank of the edifice partially collapsed on 25 September, breaching the cone and emplacing a prominent raft-bearing lava flow. Our research combines direct observations, digital elevation models, thermal and visible imaging, and textural and compositional investigation of the explosive products to describe and characterize the edifice growth and collapse. The cone built over a steep slope (26°) and its failure occurred after an intense phase of lava fountaining (up to 30 m3 s−1) that produced rapid pyroclastic accumulation. We suggest that an increased magma supply, to an ascent rate of 0.30 m s−1, led to the rapid growth of the cone (at 2.4 × 106 m3 day−1). Simultaneously, the SW lava flow reactivated and formed a lava ‘seep’ that undercut the flank of the cone, triggering a lateral collapse via rotational rockslide that moved at minimum speeds of 34–70 m h−1. The lateral collapse formed a ~ 200 m wide scar, involving 5.5 × 106 m3 of material, and covered 1.17 km2 with decametric edifice portions and raft-bearing lava. The collapse produced a modest change in the vent geometry, but did not affect eruptive activity long term. A short pause in the eruption after the collapse may have been favored by rapid emptying of the shallower magma system, reducing ascent rates and increasing crystallization times. These results reveal the complex chain of events related to the growth and destruction of newly formed volcanic cones and highlight hazards when situated close to inhabited areas

    The templated growth of a chiral transition metal chalcogenide

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    We demonstrate that an intrinsically chiral, high Miller index surface of an achiral metal can be used to template the enantioselective growth of chiral transition metal chalcogenide films. Specifically, Cu(643)R can be used as a template for the enantioselective growth of a chiral copper telluride alloy surface. Beyond a critical alloy thickness the chiral influence of the Cu(643)R surface diminishes and an achiral surface forms. Our work demonstrates a new method of producing chiral transition metal chalcogenide surfaces, with potential applications in the study of structurally chiral topological insulators

    Two-dimensional multi-component photometric decomposition of CALIFA galaxies

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    We present a two-dimensional multi-component photometric decomposition of 404 galaxies from the Calar Alto Legacy Integral Field Area Data Release 3 (CALIFA-DR3). They represent all possible galaxies with no clear signs of interaction and not strongly inclined in the final CALIFA data release. Galaxies are modelled in the g, r, and i Sloan Digital Sky Survey (SDSS) images including, when appropriate, a nuclear point source, bulge, bar, and an exponential or broken disc component. We use a human-supervised approach to determine the optimal number of structures to be included in the fit. The dataset, including the photometric parameters of the CALIFA sample, is released together with statistical errors and a visual analysis of the quality of each fit. The analysis of the photometric components reveals a clear segregation of the structural composition of galaxies with stellar mass. At high masses (log(M⋆/M⊙) > 11), the galaxy population is dominated by galaxies modelled with a single Sérsic or a bulge+disc with a bulge-to-total (B/T) luminosity ratio B/T > 0.2. At intermediate masses (9.5 < log(M⋆/M⊙) < 11), galaxies described with bulge+disc but B/T < 0.2 are preponderant, whereas, at the low mass end (log(M⋆/M⊙)< 9.5), the prevailing population is constituted by galaxies modelled with either pure discs or nuclear point sources+discs (i.e., no discernible bulge). We obtain that 57% of the volume corrected sample of disc galaxies in the CALIFA sample host a bar. This bar fraction shows a significant drop with increasing galaxy mass in the range 9.5 < log(M⋆/M⊙) < 11.5. The analyses of the extended multi-component radial profile result in a volume-corrected distribution of 62%, 28%, and 10% for the so-called Type I (pure exponential), Type II (down-bending), and Type III (up-bending) disc profiles, respectively. These fractions are in discordance with previous findings. We argue that the different methodologies used to detect the breaks are the main cause for these differences.PostprintPeer reviewe

    Matrix metalloproteinase-9, -10, and tissue inhibitor of matrix metalloproteinases-1 blood levels as biomarkers of severity and mortality in sepsis

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    INTRODUCTION: Matrix metalloproteinases (MMPs) play a role in infectious diseases through extracellular matrix (ECM) degradation, which favors the migration of immune cells from the bloodstream to sites of inflammation. Although higher levels of MMP-9 and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) have been found in small series of patients with sepsis, MMP-10 levels have not been studied in this setting. The objective of this study was to determine the predictive value of MMP-9, MMP-10, and TIMP-1 on clinical severity and mortality in a large series of patients with severe sepsis. METHODS: This was a multicenter, observational, and prospective study carried out in six Spanish Intensive Care Units. We included 192 (125 surviving and 67 nonsurviving) patients with severe sepsis and 50 age- and sex-matched healthy controls in the study. Serum levels of MMP-9, MMP-10, TIMP-1, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-10 were measured in patients with severe sepsis at the time of diagnosis and in healthy controls. RESULTS: Sepsis patients had higher levels of MMP-10 and TIMP-1, higher MMP-10/TIMP-1 ratios, and lower MMP-9/TIMP-1 ratios than did healthy controls (P < 0.001). An association was found between MMP-9, MMP-10, TIMP-1, and MMP-9/TIMP-1 ratios and parameters of sepsis severity, assessed by the SOFA score, the APACHE-II score, lactic acid, platelet count, and markers of coagulopathy. Nonsurviving sepsis patients had lower levels of MMP-9 (P = 0.037), higher levels of TIMP-1 (P < 0.001), lower MMP-9/TIMP-1 ratio (P = 0.003), higher levels of IL-10 (P < 0.001), and lower TNF-alpha/IL-10 ratio than did surviving patients. An association was found between MMP-9, MMP-10, and TIMP-1 levels, and TNF-alpha and IL-10 levels. The risk of death in sepsis patients with TIMP-1 values greater than 531 ng/ml was 80% higher than that in patients with lower values (RR = 1.80; 95% CI = 1.13 to 2.87;P = 0.01; sensitivity = 0.73; specificity = 0.45). CONCLUSIONS: The novel findings of our study on patients with severe sepsis (to our knowledge, the largest series reporting data about MMP levels in sepsis) are that reduced MMP-9/TIMP-1 ratios and increased MMP-10 levels may be of great pathophysiologic significance in terms of severity and mortality, and that TIMP-1 levels may represent a biomarker to predict the clinical outcome of patients with sepsis

    Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

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    This paper presents measurements of the W+μ+νW^+ \rightarrow \mu^+\nu and WμνW^- \rightarrow \mu^-\nu cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13
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