1,721,043 research outputs found
Stability-Capacity Diagram of a Neural Network with Ising Bonds
No full textThe stability-capacity diagram of a fully connected neural network, whose bonds take the values 1 and -1 with equal probability, is determined numerically. Two different optimization methods (simulated annealing and tabu search) are used and their relevant features are discussed. The results indicate the existence of a region, in the stability-capacity plane, where replica-symmetry should be broken, within the replica-symmetric phase found by previous, analytical, computations. The critical capacity, consistent with simple arguments on information storage, is found to be less than one.Le diagramme stabilité — capacité d'un réseau de neurones totalement connecté, dont les liens synaptiques ne peuvent prendre que deux valeurs 1 ou — 1, avec la même probabilité, est déterminé par simulations numériques. Deux différentes méthodes d'optimisation ont été utilisées (recuit simulé et recherche tabou) et nous discutons leurs aspects les plus importants. Les résultats indiquent l'existence d'une région, dans le plan stabilité — capacité, où la symétrie des répliques devrait être brisée, à l'intérieur de la phase symétrique trouvée précédemment par des calculs analytiques. La capacité critique, en accord avec des arguments simples, est trouvée inférieure à un
Oxidase reactivity of cuii bound to n-truncated aβ peptides promoted by dopamine
No full textThe redox chemistry of copper(II) is strongly modulated by the coordination to amyloid-β peptides and by the stability of the resulting complexes. Amino-terminal copper and nickel binding motifs (ATCUN) identified in truncated Aβ sequences starting with Phe4 show very high affinity for copper(II) ions. Herein, we study the oxidase activity of [Cu–Aβ4−x ] and [Cu–Aβ1−x ] complexes toward dopamine and other catechols. The results show that the CuII–ATCUN site is not redox-inert; the reduction of the metal is induced by coordination of catechol to the metal and occurs through an inner sphere reaction. The generation of a ternary [CuII–Aβ–catechol] species determines the efficiency of the oxidation, although the reaction rate is ruled by reoxidation of the CuI complex. In addition to the N-terminal coordination site, the two vicinal histidines, His13 and His14, provide a second Cu-binding motif. Catechol oxidation studies together with structural insight from the mixed dinuclear complexes Ni/Cu–Aβ4−x reveal that the His-tandem is able to bind CuII ions independently of the ATCUN site, but the N-terminal metal complexation reduces the conformational mobility of the peptide chain, preventing the binding and oxidative reactivity toward catechol of CuII bound to the secondary site
Human plasma retinol-binding protein (RBP4) is also a fatty acid-binding protein
Full text linkRBP4 (plasma retinol-binding protein) is the 21 kDa transporter of all-trans retinol that circulates in plasma as a moderately tight 1:1 molar complex of the vitamin with the protein. RBP4 is primarily synthesised in the liver but is also produced by adipose tissue and circulates bound to a larger protein, transthyretin, TTR, that serves to increase its molecular mass and thus avoid its elimination by glomerular filtration. This paper reports the high resolution three-dimensional structures of human RBP4 naturally lacking bound retinol purified from plasma, urine and amniotic fluid. In all these crystals we found a fatty acid molecule bound in the hydrophobic ligand-binding site, a result confirmed by mass spectrometry measurements. In addition we also report the 1.5 Å resolution structures of human holo-RBP4 and of the protein saturated with palmitic and lauric acid and discuss the interaction of the fatty acids and retinol with the protein
Increased Sp1 binding mediates erythroid-specific overexpression of a mutated (HPFH) gamma-globulin promoter
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The reactivity of copper complexes with neuronal peptides promoted by catecholamines and its impact on neurodegeneration
No full textIn this review we give an updated outlook of the reactivity of catecholamines, particularly dopamine, and the redox effects produced by their interaction with copper(II) and dioxygen, with emphasis to the extensive studies carried out by our group. The interaction between copper(II) ions and neuronal proteins and peptides can contribute to neurodegeneration because in many cases the peptide fragments contain high affinity binding sites and the resulting complexes exhibit increased redox reactivity. It has become apparent in recent years that the redox reactivity of Cu-peptide complexes can be substantially improved by catecholamines, which are redox reactive molecules by themselves but also relatively good ligands for copper ions. Therefore, the toxic effects of copper dyshomeostasis will be particularly harmful in the brain areas producing and releasing catecholamines, i.e. the axon terminals of the substantia nigra and locus coeruleus. These are the brain regions which become affected in the early stages of Parkinson and Alzheimer's disease, indicating that copper neurotoxicity may contribute to the outset of the diseases. Copper-β-amyloid and copper-prion complexes exhibit the highest redox activity induced by catecholamines; their reactivity is modulated by interaction with membranes, which tend to depress the reactivity unless the peptides interact with each other strengthening the binding of copper(II)
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
Human plasma retinol-binding protein can physiologically be bound to palmitic acid; new information from old crystals
Full text linkRBP4 (plasma retinol-binding protein) is the 21 kDa transporter of all-trans retinol that circulates in serum as a moderately tight 1:1 molar complex of the vitamin with the protein. RBP4 is primarily synthesised in the liver but is also produced by adipose tissue (about 20-40 % of the amounts released by the liver) and circulates bound to a larger protein, transthyretin, TTR, that serves to increase its molecular mass to about 80,000 and thus avoid its elimination by glomerular filtration. The RBP-TTR complex dissociates readily upon interaction with the RBP receptor, STRA6, that removes the vitamin from the transporter and facilitates its entrance into the cell. When retinol is not present in the complex, RBP dissociates from TTR and is eliminated in urine. We previously reported the X-ray structure of human holo RBP4 and what we expected to be the apo form, i.e. after the loss of retinol, to 2.5 Å resolution. Our most important finding was the observation of a well-defined conformational transition involving a loop at the entrance of the ligand binding site. We also reported that the protein molecule without retinol contained residual electron density in the central cavity that we interpreted as ordered solvent molecules. This job reports the three-dimensional structure of human holo-RBP and of the protein naturally deprived from retinol purified from plasma, urine and amniotic fluid determined to resolutions of 1.5, 2.0, 1.5 and 1.7 Å respectively. It is remarkable that the crystals used in this study of the plasma RBP4 holo and deprived from the retinol molecule are of the same batch as those used to determine the 2.5 Å resolution structure more than 20 years ago. In all the crystal forms of the RBP4 naturally deprived from the ligand we found palmitic acid bound in the hydrophobic ligand-binding site, a result that we confirmed by mass spectrometry measurements. The interactions of all-trans retinol with the protein at this significantly improved resolution as well as the conformational changes induced by vitamin deprivation are discussed in detail as is the structure of the complex of human RBP4 with palmitic acid
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
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