BIOTIC AND ABIOTIC EVENTS IN A SHALLOW CARBONATE PLATFORM (UPPER CRETACEOUS, SOUTH PYRENEAN MARGIN)

Πραγματοποιήθηκε μία λεπτoμεpής ιζηματολογική και παλαιοντολογική μελέτη των αποθέσεων ανθρακικής πλατφόρμας της περιοχής Serres Marginals (νότιο περιθώριο της Λεκάνης των Πυρρηναίων) και αναγνωρίσθηκαν τρεις ακολουθίες ρηχών ανθρακικών αποθέσεων (Cl, C2 και C3). Εντός των αποθέσεων ρηχής πλατφόρμας περιγράφονται ενδιάμεσης ενέργειας υποπαλιρροιακές έως ενδοπαλιρροιακές φάσεις, αβαθείς άμμοι υψηλής ενέργειας καθώς και λιμνοθαλάσσια έως λιμναία περιβάλλοντα.A detailed sedimentological and paleontological study of the Late Santonian-Late Campanian carbonate platform deposits of the Serres Marginals area (South margin of the Pyrenean Basin) has been performed. Three depositional shallow carbonate sequences have been distinguished (CI, C2 and C3). Within the shallow platform sequences moderate energy subtidal to intertidal, high energy sand-shoal, protected lagoon and restricted lagoon to lacustrine fades have been identified

A Light Calibration System for the ProtoDUNE-DP Detector

A LED-based fiber calibration system for the ProtoDUNE-Dual Phase (DP) photon detection system (PDS) has been designed and validated. ProtoDUNE-DP is a 6x6x6 m3 liquid argon time-projection-chamber currently being installed at the Neutrino Platform at CERN. The PDS is based on 36 8-inch photomultiplier tubes (PMTs) and will allow triggering on cosmic rays. The system serves as prototype for the PDS of the final DUNE DP far detector in which the PDS also has the function to allow the 3D event reconstruction on non-beam physics. For this purpose an equalized PMT response is desirable to allow using the same threshold definition for all PMT groups, simplifying the determination of the trigger efficiency. The light calibration system described in this paper is developed to provide this and to monitor the PMT performance in-situ.Comment: 15 pages, 5 figure

MicroRNA-mediated differential expression of TRMU, GTPBP3 and MTO1 in cell models of mitochondrial-DNA diseases

Mitochondrial diseases due to mutations in the mitochondrial (mt) DNA are heterogeneous in clinical manifestations but usually include OXPHOS dysfunction. Mechanisms by which OXPHOS dysfunction contributes to the disease phenotype invoke, apart from cell energy deficit, maladaptive responses to mitochondria-to-nucleus retrograde signaling. Here we used five different cybrid models of mtDNA diseases to demonstrate that the expression of the nuclear-encoded mt-tRNA modification enzymes TRMU, GTPBP3 and MTO1 varies in response to specific pathological mtDNA mutations, thus altering the modification status of mt-tRNAs. Importantly, we demonstrated that the expression of TRMU, GTPBP3 and MTO1 is regulated by different miRNAs, which are induced by retrograde signals like ROS and Ca2+ via different pathways. Our data suggest that the up- or down-regulation of the mt-tRNA modification enzymes is part of a cellular response to cope with a stoichiometric imbalance between mtDNA- and nuclear-encoded OXPHOS subunits. However, this miRNA-mediated response fails to provide full protection from the OXPHOS dysfunction; rather, it appears to aggravate the phenotype since transfection of the mutant cybrids with miRNA antagonists improves the energetic state of the cells, which opens up options for new therapeutic approaches

Tuning the Endocytosis Mechanism of Zr-Based Metal–Organic Frameworks through Linker Functionalization

A critical bottleneck for the use of metal-organic frameworks (MOFs) as drug delivery systems has been allowing them to reach their intracellular targets without being degraded in the acidic environment of the lysosomes. Cells take up particles by endocytosis through multiple biochemical pathways, and the fate of these particles depends on these routes of entry. Here, we show the effect of functional group incorporation into a series of Zr-based MOFs on their endocytosis mechanisms, allowing us to design an effi-cient drug delivery system. In particular, naphthalene-2,6-dicarboxylic acid and 4,4'-biphenyldicarboxylic acid ligands promote entry through the caveolin-pathway, allowing the particles to avoid lysosomal degradation and be delivered into the cytosol, en-hancing their therapeutic activity when loaded with drugs.C.A.O. thanks Becas Chile and the Cambridge Trust for funding. S.H. thanks the Cambridge Trust for funding. R.S.F. and D.F.-J. thank the Royal Society for the receipt of University Research Fellowships. D.F.-J. thanks financial support from ERC-2016-COG 726380. R.S.F., R.J.M., and I.A.L. thank the University of Glasgow and the EPSRC (EP/L004461/1) for funding. G.B., I.I., and D.M. acknowledge the financial support from 2014-SGR-80, MAT2015-65354-C2-1-R and EU FP7 ERC-Co 615954. ICN2 received support from the Spanish MINECO through the Severo Ochoa Centers of Excellence Program, under Grant No. SEV-2013-0295

A Study of Concurrency Bugs and Advanced Development Support for Actor-based Programs

The actor model is an attractive foundation for developing concurrent applications because actors are isolated concurrent entities that communicate through asynchronous messages and do not share state. Thereby, they avoid concurrency bugs such as data races, but are not immune to concurrency bugs in general. This study taxonomizes concurrency bugs in actor-based programs reported in literature. Furthermore, it analyzes the bugs to identify the patterns causing them as well as their observable behavior. Based on this taxonomy, we further analyze the literature and find that current approaches to static analysis and testing focus on communication deadlocks and message protocol violations. However, they do not provide solutions to identify livelocks and behavioral deadlocks. The insights obtained in this study can be used to improve debugging support for actor-based programs with new debugging techniques to identify the root cause of complex concurrency bugs.Comment: - Submitted for review - Removed section 6 "Research Roadmap for Debuggers", its content was summarized in the Future Work section - Added references for section 1, section 3, section 4.3 and section 5.1 - Updated citation

Economic impact of improving patient safety using Sugammadex for routine reversal of neuromuscular blockade in Spain

Background: Neuromuscular blocking (NMB) agents are often administered to facilitate tracheal intubation and prevent patient movement during surgical procedures requiring the use of general anesthetics. Incomplete reversal of NMB, can lead to residual NMB, which can increase the risk of post-operative pulmonary complications. Sugammadex is indicated to reverse neuromuscular blockade induced by rocuronium or vecuronium in adults. The aim of this study is to estimate the clinical and economic impact of introducing sugammadex to routine reversal of neuromuscular blockade (NMB) with rocuronium in Spain. Methods: A decision analytic model was constructed reflecting a set of procedures using rocuronium that resulted in moderate or deep NMB at the end of the procedure. Two scenarios were considered for 537, 931 procedures using NMB agents in Spain in 2015: a scenario without sugammadex versus a scenario with sugammadex. Comparators included neostigmine (plus glycopyrrolate) and no reversal agent. The total costs for the healthcare system were estimated from the net of costs of reversal agents and overall cost offsets via reduction in postoperative pneumonias and atelectasis for which incidence rates were based on a Spanish real-world evidence (RWE) study. The model time horizon was assumed to be one year. Costs were expressed in 2019 euros (€) and estimated from the perspective of a healthcare system. One-way sensitivity analysis was carried out by varying each parameter included in the model within a range of +/- 50%. Results: The estimated budget impact of the introduction of sugammadex to the routine reversal of neuromuscular blockade in Spanish hospitals was a net saving of €57.1 million annually. An increase in drug acquisition costs was offset by savings in post-operative pulmonary events, including 4806 post-operative pneumonias and 13, 996 cases of atelectasis. The total cost of complications avoided was €70.4 million. All parameters included in the model were tested in sensitivity analysis and were favorable to the scenario with sugammadex. Conclusions: This economic analysis shows that sugammadex can potentially lead to cost savings for the reversal of rocuronium-induced moderate or profound NMB compared to no reversal and reversal with neostigmine in the Spanish health care setting. The economic model was based on data obtained from Spain and from assumptions from clinical practice and may not be valid for other countries

Thinking like a consumer: Linking aquatic basal metabolism and consumer dynamics

The increasing availability of high-frequency freshwater ecosystem metabolism data provides an opportunity to identify links between metabolic regimes, as gross primary production and ecosystem respiration patterns, and consumer energetics with the potential to improve our current understanding of consumer dynamics (e.g., population dynamics, community structure, trophic interactions). We describe a conceptual framework linking metabolic regimes of flowing waters with consumer community dynamics. We use this framework to identify three emerging research needs: (1) quantifying the linkage of metabolism and consumer production data via food web theory and carbon use efficiencies, (2) evaluating the roles of metabolic dynamics and other environmental regimes (e.g., hydrology, light) in consumer dynamics, and (3) determining the degree to which metabolic regimes influence the evolution of consumer traits and phenology. Addressing these needs will improve the understanding of consumer biomass and production patterns as metabolic regimes can be viewed as an emergent property of food webs

Deep subcutaneous application of poly-L-lactic acid as a filler for facial lipoatrophy in HIV-infected patients

Introduction: Facial lipoatrophy is a crucial problem of HIV-infected patients undergoing highly active antiretroviral therapy (HAART). Poly-L-lactic acid (PLA), provided as New-Fill(R)/Sculptra(TM), is known as one possible treatment option. In 2004 PLA was approved by the FDA as Sculptra(TM) for the treatment of lipoatrophy of the face in HIV-infected patients. While the first trials demonstrated relevant efficacy, this was to some extent linked to unwanted effects. As the depth of injection was considered relevant in this context, the application modalities of the preparation were changed. The preparation was to be injected more deeply into subcutaneous tissue, after increased dilution. Material and Methods: To test this approach we performed a pilot study following the new recommendations in 14 patients. Results: While the efficacy turned out to be about the same, tolerability was markedly improved. The increase in facial dermal thickness was particularly obvious in those patients who had suffered from lipoatrophy for a comparatively small period of time. Conclusion: With the new recommendations to dilute PLA powder and to inject it into the deeper subcutaneous tissue nodule formation is a minor problem. However, good treatment results can only be achieved if lipoatrophy is not too intense; treatment intervals should be about 2 - 3 weeks. Copyright (C) 2005 S. Karger AG, Basel

Magnetically treated water on phytochemical compounds of Rosmarinus officinalis L.

Irrigation using water treated with static magnetic field (SMF) has recently been used as a strategy to stimulate the growth and development of different plant species. The aim of this study was to characterize the bioactive compounds and evaluate the anatomical structure of Rosmarinus officinalis L. irrigated with SMF-treated water. Results demonstrate that the treatment promoted plant growth, the number of trichomes and increased concentrations of secondary metabolites. Methanol-extracted leaves revealed that rosmarinic acid was detected in both experimental groups, without a difference in the level. Camphor, α-terpineol and verbenone were determined as the most abundant compounds present in these leaf extracts and were strongly increased in plants irrigated with SMF-treated water. Similar results were also observed for endo-borneol, bornyl acetate and β-amyrin concentrations.Taken together, these results indicate that irrigation with SMF-treated water can be used to improve the production of rosemary to obtain pharmaceutical products with an increased antioxidative activity