1,720,992 research outputs found
Effects of a novel DNA-damaging agent on the budding yeast Saccharomyces cerevisiae cell cycle
No full textWe have investigated the effects on Saccharomyces cerevisiae of a novel antitumour agent (FCE24517 or Tallimustine) which causes selective alkylations to adenines in the minor groove of DNA. Tallimustine, added to wild-type cells for short periods, reduced the growth rate and increased the percentage of budded cells and delayed the cell cycle in the late S+G(2)+M phases. In the rad9 Delta null mutant cells, Tallimustine treatment did not affect growth rate and the percentage of budded cells but greatly reduced cell viability compared to isogenic cells. Consistent with a role of RAD9 in inducing a transient delay in G(2) phase which preserves cell viability, the potent cytotoxic effect of the drug on lad9 Delta cells was alleviated by treatment with nocodazole. Tallimustine was also found to delay the resumption from G, arrest of wild-type but not of lad9 Delta cells. These data indicate that the effects of Tallimustine on cell cycle progression in yeast are mediated by the RAD9 gene product. From our data it appears that yeast could be a valuable model system to study the mode of action of this alkylating drug and of minor groove alkylators in general
H-1 NMR investigations on the solution structure of the oligonucleotide 5 '-d(ACCT(5)GATGT)-3 '/5 '-d(ACATCA(5)GGT)-3 ' and its interaction with tallimustine
No full textThe conformation of the DNA duplex 5'-d(ACCT(5)GATGT)-3'/5'-(ACATCA(5)GGT)-3' has been studied by means of 2D H-1 NMR and restrained molecular mechanics and dynamics calculations, This sequence contains the tract 'T(4)GA', which has previously been proved to be the recognition sequence of tallimustine, a distamycin-A analogue, containing a nitrogen mustard moiety and with interesting anti-leukemia properties, The tridecamer has been found to possess a B-type DNA conformation with local variations in the helical parameters which may be related to the sequence, Guanine in position 9, a residue supposed to be a key point for tallimustine recognition, is at the end of a homopyrimidinic tract where the propeller twist is found to decrease down to 9 degrees at the flanking residue A(10). Analysis of the minor groove geometry has revealed an increase of the width up to G(9) and a return to average values at the level of residues A(10)-C-18. The reversible interaction of this oligonucleotide with tallimustine has also been investigated by NMR and UV spectroscopy, The association constant K-a is 2 x 10(7) dm(3) mol(-1). The off-rate constant is 1.5 +/- 0.5 s(-1) as measured by NOESY-exchange experiments performed at R = [drug]/[DNA] = 0.5. A multiple mode of binding of tallimustine with the oligomer has been detected by analysis of H-1 NMR spectra; however, the chemical shift analysis and several inter-molecular NOE interactions observed at low drug:DNA ratios have provided sufficient structural information to define the major orientation of the drug in the minor groove, The positively charged amidinic moiety is situated at the beginning of the AT-rich region and the phenyl group resides close to the T-8:A(19) base pair. The specificity of interaction of tallimustine depends on a favourable steric interaction at the T(8)G(9)A(10) tract, as a result of the widening of the minor groove allowing accommodation of the phenyl moiety in the floor of the groove, Under the conditions applied in the NMR studies, negligible alkylation has been detected by HPLC measurements, However, after nine days of incubation at T = 37 degrees C several peaks corresponding to alkylation products are detected giving further indications of a multiple mode of binding of tallimustine with the oligonucleotide
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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