901 research outputs found

    An automatic approach for selecting new Hα emission-line galaxies

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    The most unambiguous way to discover new emission-line galaxies (ELGs) is directly by the presence of their lines, using objective-prism plates of adequate resolution. The first survey using this technique was developed by Smith in 1975 with the 0.6 m CTIO Curtis Schmidt Telescope. The Universidad Complutense de Madrid (UCM) is carrying out a survey of ELGs with the Schmidt Telescope at Calar Alto (AlmerĂ­a, Spain) using the presence of Ha in emission in IIIa-F prism plates as selection criterion. The observational procedure and results are described in Rego et al. 1989; Zamorano et al. 1990; Zamorano et al. 1993. The standard procedure is to scan the plates by eye, with a low-power binocular microscope. The use of different subjective criteria in the visual inspection can produce biased samples. Moreover, the visual scan does not produce any quantitative measure but only a sample of candidates. Therefore, in order to obtain an observer-independent sample and to extract the largest amount of information from the original plates, 2 plates have been scanned with the MAMA machine 1 (Guibert & Moreau 1991; Moreau 1992) with the aim of developing an automatic procedure to detect ELGs spectra

    Characteristics of Conservation Laws for Difference Equations

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    Each conservation law of a given partial differential equation is determined (up to equivalence) by a function known as the characteristic. This function is used to find conservation laws, to prove equivalence between conservation laws, and to prove the converse of Noether's Theorem. Transferring these results to difference equations is nontrivial, largely because difference operators are not derivations and do not obey the chain rule for derivatives. We show how these problems may be resolved and illustrate various uses of the characteristic. In particular, we establish the converse of Noether's Theorem for difference equations, we show (without taking a continuum limit) that the conservation laws in the infinite family generated by Rasin and Schiff are distinct, and we obtain all five-point conservation laws for the potential Lotka-Volterra equation

    Photomutagenicity of chlorpromazine and its N-demethylated metabolites assessed by NGS

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    [EN] The human genome is constantly attacked by endogenous and exogenous agents (ultraviolet light, xenobiotics, reactive oxygen species), which can induce chemical transformations leading to DNA lesions. To combat DNA damage, cells have developed several repair mechanisms; however, if the repair is defective, DNA lesions lead to permanent mutations. Single-cell gel electrophoresis (COMET assay) is a sensitive and well-established technique for quantifying DNA damage in individual cells. Nevertheless, this tool lacks relationship with mutagenesis. Therefore, to identify errors that give rise to mutations it would be convenient to test an alternative known procedure, such as next generation sequencing (NGS). Thus, the present work aims to evaluate the photomutagenicity of neuroleptic drug chlorpromazine (CPZ), and its N-demethylated metabolites using COMET assay and to test NGS as an alternative method to assess photomutagenesis. In this context, upon exposure to UVA radiation, COMET assay reveals CPZ-photosensitized DNA damage partially repaired by cells. Conversely with this result, metabolites demethylchlorpromazine (DMCPZ) and didemethylchlorpromazine (DDMCPZ) promote extensive DNA-photodamage, hardly repaired under the same conditions. Parallel assessment of mutagenesis by NGS is consistent with these results with minor discrepancies for DDMCPZ. To our knowledge, this is the first example demonstrating the utility of NGS for evaluating drug-induced photomutagenicity.This study was funded by the Carlos III Institute (ISCIII) of Health (Grants: PI15/00303, PI18/00540, PI16/01877, CPII16/00052, the Thematic Networks and Co-operative Research Centres: ARADyAL RD16/0006/0004 and RD16/0006/0030), IB16170, GR18145 from Junta de Extremadura, Spain, co-funded by European Regional Development Fund and Generalitat Valenciana Prometeo/2017/075. We would also like to thank M. Dolores Coloma for technical assistance in the preliminary experiments.AgĂșndez, JA.; GarcĂ­a-MartĂ­n, E.; Garcia-Lainez, G.; Miranda Alonso, MÁ.; Andreu Ros, MI. (2020). Photomutagenicity of chlorpromazine and its N-demethylated metabolites assessed by NGS. Scientific Reports. 10(1):1-6. https://doi.org/10.1038/s41598-020-63651-yS16101Bjelland, S. & Seeberg, E. Mutagenicity, toxicity and repair of DNA base damage induced by oxidation. Mutat. Res. 531, 37–80 (2003).Friedberg, E. C. A brief history of the DNA repair field. Cell Res. 18, 3–7 (2008).Cadet, J. & Wagner, J. R. DNA base damage by reactive oxygen species, oxidizing agents, and UV radiation. Cold Spring Harb. Perspect. Biol. 5, (2013).Bauer, N. C., Corbett, A. H. & Doetsch, P. W. The current state of eukaryotic DNA base damage and repair. Nucleic Acids Res. 43, 10083–10101 (2015).Cadet, J. & Davies, K. J. A. Oxidative DNA damage & repair: An introduction. Free Radic. Biol. Med. 107, 2–12 (2017).Sancar, A., Lindsey-Boltz, L. A., Unsal-Kaçmaz, K. & Linn, S. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu. Rev. Biochem. 73, 39–85 (2004).Roos, W. P., Thomas, A. D. & Kaina, B. DNA damage and the balance between survival and death in cancer biology. Nat. Rev. Cancer 16, 20–33 (2016).MĂžller, P. Assessment of reference values for DNA damage detected by the comet assay in human blood cell DNA. Mutat. Res. 612, 84–104 (2006).Azqueta, A. & Collins, A. R. The essential comet assay: a comprehensive guide to measuring DNA damage and repair. Arch. Toxicol. 87, 949–968 (2013).Collins, A. R. et al. Controlling variation in the comet assay. Front. Genet. 5, 359 (2014).MĂžller, P. The comet assay: ready for 30 more years. Mutagenesis 33, 1–7 (2018).Shendure, J. & Ji, H. Next-generation DNA sequencing. Nat. Biotechnol. 26, 1135–1145 (2008).Metzker, M. L. Sequencing technologies—the next generation. Nat. Rev. Genet. 11, 31 (2010).Gawad, C., Koh, W. & Quake, S. R. Single-cell genome sequencing: current state of the science. Nat. Rev. Genet. 17, 175–188 (2016).Schwarz, U. I., Gulilat, M. & Kim, R. B. The Role of Next-Generation Sequencing in Pharmacogenetics and Pharmacogenomics. Cold Spring Harb. Perspect. Med. 9, (2019).Epstein, J. H., Brunsting, L. A., Petersen, M. C. & Schwarz, B. E. A study of photosensitivity occurring with chlorpromazine therapy. J. Invest. Dermatol. 28, 329–338 (1957).Kochevar, I. E., Chung, F. L. & Jeffrey, A. M. Photoaddition of chlorpromazine to DNA. Chem. Biol. Interact. 51, 273–284 (1984).Palumbo, F. et al. Enhanced photo(geno)toxicity of demethylated chlorpromazine metabolites. Toxicol. Appl. Pharmacol. 313, 131–137 (2016).Miki, Y. et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266, 66–71 (1994).Wooster, R. et al. Identification of the breast cancer susceptibility gene BRCA2. Nature 378, 789–792 (1995)

    Visual Ontology Cleaning: Cognitive Principles and Applicability

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    In this paper we connect two research areas, the Qualitative Spatial Reasoning and visual reasoning on ontologies. We discuss the logical limitations of the mereotopological approach to the visual ontology cleaning, from the point of view of its formal support. The analysis is based on three different spatial interpretations wich are based in turn on three different spatial interpretations of the concepts of an ontology.Ministerio de EducaciĂłn y Ciencia TIN2004-0388

    Gender and functional CYP2C and NAT2 polymorphisms determine the metabolic profile of metamizole

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    Metamizole is a pain-killer drug that has been banned in some countries because of its toxicity, but it is still used in many countries due to its effective analgesic and antispasmodic properties. Although large variability in the biodisposition and adverse effects of metamizole are known, factors underlying this variability are poorly understood. We analyzed the urinary recovery of metabolites, as well as the association of these profiles with genetic and non-genetic factors, in a group of 362 healthy individuals. Gender and functional polymorphisms are strongly related to metabolic profiles. N-demethylation of the active metabolite MAA is diminished in carriers of the CYP2C19*2 allele and in NAT2-slow acetylators. Acetylation of the secondary metabolite AA is decreased in men, in drinkers and in NAT2-slow acetylators with a differential effect of NAT2*5 and NAT2*6 alleles. The formylation of MAA is diminished in older subjects and in carriers of defect CYP2C9 and CYP2C19 alleles. Two novel arachidonoyl metabolites were identified for the first time in humans. Women and NAT2-slow acetylators show higher concentrations, whereas the presence of the rapid CYP2C19*17 allele is associated with lower concentrations of these metabolites. All genetic associations show a gene-dose effect. We identified for the first time genetic and non-genetic factors related to the oxidative metabolism of analgesic drug metamizole, as well as new active metabolites in humans. The phenotypic and genetic factors identified in this study have a potential application as biomarkers of metamizole biotransformation and toxicity.We are grateful to Prof. James McCue for assistance in language editing. Financed by grants PS09/00943, PS09/00469, PI12/00241, PI12/00324 and RETICS RD07/0064/0016 and RD12/0013/0002 and RD12/0013/0009 from Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III, Madrid, Spain; GR10068 from Junta de Extremadura, Spain. Financed in part with FEDER funds from the European Union. I.A. is supported by a Servet Contract CP11/00154.Martínez, C.; Andreu Ros, MI.; Amo, G.; Miranda Alonso, MÁ.; Esguevillas, G.; Torres, MJ.; Blanca López, N.... (2014). Gender and functional CYP2C and NAT2 polymorphisms determine the metabolic profile of metamizole. Biochemical Pharmacology. 92(3):457-466. https://doi.org/10.1016/j.bcp.2014.09.005S45746692

    Supergravity brane worlds and tachyon potentials

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    We study massless and massive graviton modes that bind on thick branes which are supergravity domain walls solutions in DD-dimensional supergravity theories where only the supergravity multiplet and the scalar supermultiplet are turned on. The domain walls are bulk solutions provided by tachyon potentials. Such domain walls are regarded as BPS branes of one lower dimension that are formed due to tachyon potentials on a non-BPS D-brane.Comment: RevTex4, 6 pages; version to appear in Phys. Rev.

    Complete solutions to the metric of spherically collapsing dust in an expanding spacetime with a cosmological constant

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    We present semi-analytical solutions to the background equations describing the Lema\^itre-Tolman-Bondi (LTB) metric as well as the homogeneous Friedmann equations, in the presence of dust, curvature and a cosmological constant Lambda. For none of the presented solutions any numerical integration has to be performed. All presented solutions are given for expanding and collapsing phases, preserving continuity in time and radius. Hence, these solutions describe the complete space time of a collapsing spherical object in an expanding universe. In the appendix we present for completeness a solution of the Friedmann equations in the additional presence of radiation, only valid for the Robertson-Walker metric.Comment: 23 pages, one figure. Numerical module for evaluation of the solutions released at http://web.physik.rwth-aachen.de/download/valkenburg/ColLambda/ Matches published version, published under Open Access. Note change of titl

    Allergic Reactions to Metamizole: Immediate and Delayed Responses

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    [EN] Background: Pyrazolones are the most common causes of selective nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. We studied a large group of patients with immediate and delayed selective responses to metamizole. Methods: Patients with suspicion of hypersensitivity to metamizole were evaluated. We verified acetylsalicylic acid tolerance and classified patients as immediate or delayed responders if they showed symptoms less or more than 24 h after metamizole administration. Skin tests were performed and if negative, a basophil activation test (BAT) was performed on immediate responders. If it was negative, we performed a drug provocation test (DPT) with metamizole. Results: A total of 137 patients were included: 132 reacted within 24 h (single NSAID-induced urticaria/angioedema/ anaphylaxis; SNIUAA) and 5 after 24 h (single NSAID-induced delayed hypersensitivity reaction; SNIDHR). Most SNIUAA patients developed anaphylaxis (60.60%); for SNIDHR, maculopapular exanthema was the most frequent entity (60%). Skin testing was positive in 62.04% of all cases and BAT in 28% of the SNIUAA patients with negative skin tests. In 5.1% of the cases, DPT with metamizole was needed to establish the diagnosis. In 22.62% of the cases, diagnosis was established by consistent and unequivocal history of repeated allergic episodes in spite of a negative skin test and BAT. Conclusions: SNIUAA to metamizole is the most frequent type of selective NSAID hypersensitivity, with anaphylaxis being the most common clinical entity. It may occur within 1 h after drug intake. SNIDHR occurs in a very low percentage of cases. The low sensitivity of diagnostic tests may be due to incomplete characterization of the chemical structures of metamizole and its metabolites.The present study has been supported by the Institute of Health ‘Carlos III’ of the Ministry of Economy and Competitiveness [grants cofounded by European Regional Development Fund (ERDF), Red de Reacciones Adversas a Alergenos y Farmacos (RD12/0013/0001 and PI15/01317)] and by Consejeria de Salud de la Junta de AndalucĂ­a (PI-0463-2013).Blanca-LĂłpez, N.; PĂ©rez-Sanchez, N.; AgĂșndez, JA.; GarcĂ­a-MartĂ­n, E.; Torres, MJ.; Cornejo-Garcia, JA.; Perkins, JR.... (2016). Allergic Reactions to Metamizole: Immediate and Delayed Responses. International Archives of Allergy and Immunology. 169(4):223-230. https://doi.org/10.1159/000444798S223230169

    Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB

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    Polycomb group (PcG) proteins are transcriptional repressors that control processes ranging from the maintenance of cell fate decisions and stem cell pluripotency in animals to the control of flowering time in plants 1-6. In Drosophila, genetic studies identified more than 15 different PcG proteins that are required to repress homeotic (HOX) and other developmental regulator genes in cells where they must stay inactive 1,7,8. Biochemical analyses established that these PcG proteins exist in distinct multiprotein complexes that bind to and modify chromatin of target genes. Among those, Polycomb repressive complex 1 (PRC1) and the related dRing-associated factors (dRAF) complex contain an E3 ligase activity for monoubiquitination of histone H2A (refs 1-4). Here we show that the uncharacterized Drosophila PcG gene calypso encodes the ubiquitin carboxy-terminal hydrolase BAP1. Biochemically purified Calypso exists in a complex with the PcG protein ASX, and this complex, named Polycomb repressive deubiquitinase (PR-DUB), is bound at PcG target genes in Drosophila. Reconstituted recombinant Drosophila and human PR-DUB complexes remove monoubiquitin from H2A but not from H2B in nucleosomes. Drosophila mutants lacking PR-DUB show a strong increase in the levels of monoubiquitinated H2A. A mutation that disrupts the catalytic activity of Calypso, or absence of the ASX subunit abolishes H2A deubiquitination in vitro and HOX gene repression in vivo. Polycomb gene silencing may thus entail a dynamic balance between H2A ubiquitination by PRC1 and dRAF, and H2A deubiquitination by PR-DUB

    Soil-landscape and climatic relationships in the middle Miocene of the Madrid Basin

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    The Miocene alluvial-lacustrine sequences of the Madrid Basin, Spain, formed in highly varied landscapes. The presence of various types of palaeosols allows assessment of the effects of local and external factors onsedimentation, pedogenesis and geomorphological development. In the northern, more arid, tectonicallyactive arca, soils were weakly developed in aggrading alluvial fans, dominated by mass flows. reflecting high sedimentation rates. In more distal parts of the fans and in playa lakes calcretes and dolocretes developed: the former were associated with Mg-poor fan sediments whitc: the latter formed on Mg-rich lake clays exposed during minar lake lowstands. The nonh-east part of the basin had a less arid climate. Alluvial fans in this area were dominated by stream Aood deposits, sourced by carbonate terrains. Floodplain and freshwater lakc deposits formed in distal areas. The high local supply of calcium carbonate may have contributed to the preferential developmenl on calcretes on the fans. Both the fan and floodplain palaeosols exhibit pedofacies relationships and more mature soils developed in settings more distant from the sediment sources. Palaeosols also developed on pond and lake margin carbonates, and led to the formation of palustrine limestones. The spatial distributions and stratigraphies of palaeosols in the Madrid Basin alluvial fans suggest that soil formation was controlled by local factors. These palaeosols differ from those seen in Quatemary fans. Which are characterized by climatically induced periods of stability and instability
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