1,721,068 research outputs found
Structure and dynamics of intercalation complexes of anthracyclines with d(CGATCG)2 and d(CGTACG)2. 2D-1H and 31P NMR investigations
No full textThe interaction of (2S )-2-methoxymorpholinodoxorubicin 4 and morpholinodoxorubicin 5 with the hexanucleotides d(CGATCG)2 and d(CGTACG)2 has been studied by a combined use of 2D-1H and 31P NMR techniques and molecular dynamics (MD) calculations, in comparison with doxorubicin 1, daunorubicin 2 and idarubicin 3. Both 1H and 31P chemical shifts of imino protons and phosphates respectively have been shown to be a sensitive probe for the intercalation sites (two anthracycline molecules at the CpG sites). A relevant number of NOE interactions allowed the structure of the complexes in solution to be derived through restrained MD calculations, which were compared with those obtained by X-ray analysis. In all the complexes the aglycone was shown to be located in the middle of the double helix, orthogonally oriented with respect to the base pairs, with ring D extending out of the helix on the major groove and ring A, with 9H8 conformation, between guanines G2 and G12. The daunosamine and morpholino moieties lie in the center of the minor groove, with slightly different positions than in the X-ray structures. In all the complexes the daunosamine ring is located at the A3 (T3) level, while the morpholino ring displays NOE interactions with the fourth unit T4 (A4). The deformations of the double helix are revealed by an increased distance between protons of the C5 and G6 units and by conformational changes at the level of the α, ζ, Îμ and δ angles of the phosphoribose backbone. The variation of the 31P chemical shifts is interpreted in terms of conformational equilibria leading to different populations of conformers. This is clearly shown from the values of the α and ζ torsion angles, monitored during the MD, which indicate a relevant population of trans forms for ζ and also for α angles of C5pG6 and G2pT3 (G2pA3) units, while the other phosphates exist entirely in the α, ζ, gauche,gauche conformation. The dissociation rate constants were measured by 2D 31P NOESY-exchange experiments for 1 and 4. The decrease of koff for 4, corresponding to a ten-fold increase of the residence time of the drug in the intercalation sites, is in line with the higher activity found for methoxymorpholinodoxorubicin 4
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
Conformation and tautomerism of hypocrellins. Revised structure of shiraiachrome A
No full textHypocrellins, natural perylenequinones from the fungi Hypocrella bambusae and Shiraia bambusicola, are being intensively studied for their photodynamic activity. As a recent paper reported the existence of a slow tautomeric equilibrium for hypocrellin A, the behaviour in solution of hypocrellin and hypocrellin A was reinvestigated by NMR. 1D and 2D ROESY spectra at different temperatures and in different solvents have been measured and quantitative NOE experiments have been performed to obtain the cross-relaxation rates and then the interproton distances, to be used for MM and MD calculations. This allowed us to confirm that tautomerism in these compounds is a fast process on the NMR time scale, and to establish the relative population of the two principal tautomers and the preferred conformation of hypocrellin, hypocrellin A and of their atropisomers. The atropisomeric interconversion process is fast enough to be studied by NMR; the rate constants, obtained by ROESY-exchange experiments, gave the activation parameters. The helix inversion also induces the inversion of the seven-membered ring, which adopts a twist–boat conformation in both atropisomers. The values of the dihedral angle C(1)–C(12b)–C(12a)–C(12), which shows the distortion of the perylenequinone system, have been obtained from energy minimisation of the structures derived from NOE data. They are in the range 25–29° for all stereoisomers. The structure of shiraiachrome A, another member of the series, has been revised to M(R),14S,16S. The conformation and the tautomeric equilibrium of this compound have been similarly determined
Structural Features and Reversible Association of Different Quaternary Structures of β-Lactoglobulin
No full textStructural and functional features were studied on the native dimeric form of β-lactoglobulin at neutral pH and on the monomeric forms obtained either by raising the pH to 9.0 or by blocking the thiol group of Cys121 with iodoacetamide under bland dissociating conditions. The thiol blocked monomer did not reassociate to native-like dimers, it retained retinol-binding ability, and it was found to display many of the structural features of the monomer obtained at pH 9, but differed in several structural features from the native dimer. The supramolecular associative properties of the proteins were studied by measuring concentration dependence of the accessibility of the backbone exchangeable amide protons in 1H NMR H/D exchange experiments, of their ligand-binding properties, and of their intrinsic fluorescence features. Evidence of reversible association was found for all the proteins with a very similar concentration dependence, indicating that the weak forces involved in this association were different from those stabilizing the native dimer
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