1,721,060 research outputs found
Domain Decomposition Methods and Scientific Computing Applications
No full textThis paper reviews the basic mathematical ideas and convergence analysis of domain decomposition methods. These are parallel and scalable iterative methods for the efficient numerical solution of partial differential equations. Two examples are then presented showing the application of domain decomposition methods to large-scale numerical simulations in computational mechanics and electrocardiology
Amino acid oxidases in red biotechnologies: a target and a tool.
No full textD-Amino acid oxidase (DAAO; EC 1.4.3.3) has been proposed to play a main role in the degradation of D-serine, an allosteric activator of the N-methyl-D-aspartate-type glutamate receptor in the human brain, associated with the onset of schizophrenia. To prevent excessive D-serine degradation, novel drugs for schizophrenia treatment based on DAAO inhibition were designed and tested on rats. The properties of rat DAAO (rDAAO) are unknown and various in vivo trials reported on the effects of DAAO inhibitors on D-serine concentration in rats. rDAAO was efficiently expressed in Escherichia coli. The recombinant enzyme was purified as an active, 40 kDa monomeric flavoenzyme showing the basic properties of the dehydrogenase-oxidase class of flavoproteins. rDAAO differs significantly from the human enzyme because it: 1)) possesses a different substrate specificity; 2) shows a lower kinetic efficiency (because of a low substrate affinity); 3) differs in affinity for binding of classical inhibitors; 4) is a stable monomer; 5) interacts with the mammalian protein modulator pLG72 yielding a 100 kDa complex in addition to the 200 kDa, as formed by the human DAAO. Interestingly, the concentration of endogenous D-serine in U87 glioblastoma cells was not affected by transfection with rDAAO whereas it was significantly decreased when expressing the human homologue. These results raise doubt on the use of rat as model system for testing new drugs against schizophrenia and indicate a different physiological function of DAAO in rodents and humans.
During past years, a number of variants of D-amino acid oxidase from the yeast Rhodotorula gracilis (RgDAAO) with altered substrate specificity (e.g., active on acidic, or hydrophobic, or on all D-amino acids) both by rational design and directed evolution methods have been produced in our laboratory. RgDAAO is the most suitable biotechnological tool for the detection of D-amino acids and in this work we evaluated the capability of some mutant forms of this flavoenzyme previously produced in our laboratory in order to determine D-amino acid content in different biological samples. The kinetic constants for a number of natural and unnatural D-amino acids have been investigated. This information constitutes the basis for considering potential analytical applications of these variants of RgDAAO.
Glycine is implicated in several physiological functions, e.g. as a biosynthetic precursor or neurotransmitter in the central nervous system. Glycine is an important coagonist of NMDA receptor and it is putatively involved in schizophrenia susceptibility and other neurological diseases, such as congenital nonketotic hyperglycinemia. With the final aim to produce an optimized enzyme that can be employed in a specific biosensor for glycine detection, glycine oxidase from Bacillus subtilis (GO) was engineered to improve its kinetic efficiency on this small amino acid. Based on in silico analysis, site saturation mutagenesis was independently performed at positions Met49, Gly51, Ala54, Met95, Tyr241, His244, Tyr246, Met261, Arg302, Arg329 and Asn330. The GO variants were screened by employing a rapid colorimetric assay on 96 well-plates based on the determination of hydrogen peroxide produced on glycine as substrate: seven GO variants were selected. Significant alteration of kinetic parameters was observed for H244K and H244R GO variants: kcat increased about twice and Km decreased 3-5-fold, yielding a 7-12-fold higher kinetic efficiency on glycine, as compared to the wild-type GO. Screening of GO variants at position 49 also identified an improved enzyme (M49I) showing a 1.4-fold decreased Km. Combination of information gathered from the site saturation mutagenesis approach could be useful to obtain an evolved GO variant suitable for biotechnological applications
Hybrid and Multiplicative Overlapping Schwarz Algorithms with Standard Coarse Spaces for Mixed Linear Elasticity and Stokes Problems
No full textParameter robust isogeometric methods for a four-field formulation of Biot’s consolidation model
No full textIn this paper, a novel isogeometric method for Biot's consolidation model is constructed and analyzed, using a four-field formulation where the unknown variables are the solid displacement, solid pressure, fluid flux, and fluid pressure. Mixed isogeometric spaces based on B-splines basis functions are employed in the space discretization, allowing a smooth representation of the problem geometry and solution fields. The main result of the paper is the proof of optimal error estimates that are robust with respect to material parameters for all solution fields, particularly in the case of nearly incompressible materials. The analysis does not require a uniformly positive storage coefficient. The results of numerical experiments in two and three dimensions confirm the theoretical error estimates and high-order convergence rates attained by the proposed isogeometric Biot discretization and assess its performance with respect to the mesh size, spline polynomial degree, spline regularity, and material parameters
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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