1,720,979 research outputs found
Peptidyl 3-substituted 1-hydroxyureas as isosteric analogues of succinylhydroxamate MMP inhibitors
No full textTo evaluate N-hydroxyurea as zinc binding group in the design of MMP inhibitors, two peptidyl 1-hydroxyureas were prepared by N-hydroxycarbamoylation
of the diastereomeric dipeptides H-Leu-Phe-NHMe and H-D-Leu-Phe-NHMe. Peptidyl 1-hydroxyureas were more potent than
the parent peptides, but dramatically weaker (4e5 orders of magnitude) than the isosteric (R)-succinylhydroxamate analogue, which displays
IC50 in the range of nM vs MMP-1, -3, -7 and sub-nM vs MMP-2, -8, and -9. The peptidyl 1-hydroxyurea 1a attained an IC50 of 20 mM vs
MMP-9, and substantially approaches inhibition of known N-hydroxyureas based on aminoacids or peptides against other zinc metalloenzymes
and non-peptidic N-hydroxyureas against MMPs. Strong preference of the OeN1eC]O unit for the antiperiplanar amide bond conformation
seems to be the major limit for more effective zinc chelation. Methylation of a peptidyl 1-hydroxyurea at N3, to promote the synperiplanar
OeN1eC]O conformation required for zinc chelation and improve affinity, resulted in release of a methylimidazolidine-2,4-dione through
an undesired intramolecular reaction reminiscent of the Edman peptide degradation
Peptidyl 3-Substituted 1-Hydroxyureas as Isosteric Analogues of Succinylhydroxamate MMP Inhibitors
No full textTo evaluate N-hydroxyurea as zinc binding group in the design of MMP inhibitors, two peptidyl 1-hydroxyureas were prepared by N-hydroxycarbamoylation of the diastereomeric dipeptides H-Leu-Phe-NHMe and H-d-Leu-Phe-NHMe. Peptidyl 1-hydroxyureas were more potent than the parent peptides, but dramatically weaker (4-5 orders of magnitude) than the isosteric (R)-succinylhydroxamate analogue, which displays IC(50) in the range of nM vs MMP-1, -3, -7 and sub-nM vs MMP-2, -8, and -9. The peptidyl 1-hydroxyurea 1a attained an IC(50) of 20muM vs MMP-9, and substantially approaches inhibition of known N-hydroxyureas based on aminoacids or peptides against other zinc metalloenzymes and non-peptidic N-hydroxyureas against MMPs. Strong preference of the O-N1-CO unit for the antiperiplanar amide bond conformation seems to be the major limit for more effective zinc chelation. Methylation of a peptidyl 1-hydroxyurea at N3, to promote the synperiplanar O-N1-CO conformation required for zinc chelation and improve affinity, resulted in release of a methylimidazolidine-2,4-dione through an undesired intramolecular reaction reminiscent of the Edman peptide degradation
Turistas de las raíces ascendencia italiana. La investigación cualitativa
No full textEn esta etapa de la investigación se realizó un estudio cumulativo de tpo exploratorio con el fin de analizar las características del segmento de domanda del turismo de las raíces. Teniendo en cuenta la falta de conocimientos disponibles sobre este fenómeno y la necesidad de adquirirlos y de profundizar en algunas dinámicas, la investigación cumulativa tuvo como objetivo explorar el tema y ofrecer una primera aproximaciòn cognitiva acerca de características, orientaciones y acciones de emigrantes y sus descendientes. Es más, se dedicó una sección de la investigación, descrita en el siguiente párrafo, a spectos relativos a la sutantabilidad del turismo de las raíces en términos socioculturales, es decir, al impacto del fenómeno en el entramado social y cultural de la comunidad de acogida. Se trata de un tema que resulta nuevo también en las publicaciones a nivel internacional y de gran interésy novedad. Finalmente, se abordó la temática de la actual pandemia de Covid-19 y de aquello que podría suceder cuando ésta termine, siempre en referencia al turismo de las raíces. Este estudio exploratorio inicial permitió obtener lineamientos para futuras implementaciones de la investigación, en particular para el abordaje estadistico realizado posteriormente
Peptidyl 3-substituted 1-hydroxyureas as isosteric analogues of succinylhydroxamate MMP inhibitors
No full textTo evaluate N-hydroxyurea as zinc binding group in the design of MMP inhibitors, two peptidyl 1-hydroxyureas were prepared by N-hydroxycarbamoylation of the diastereomeric dipeptides H-Leu-Phe-NHMe and H-D-Leu-Phe-NHMe. Peptidyl 1-hydroxyureas were more potent than the parent peptides, but dramatically weaker (4e5 orders of magnitude) than the isosteric (R)-succinylhydroxamate analogue, which displays IC50 in the range of nM vs MMP-1, -3, -7 and sub-nM vs MMP-2, -8, and -9. The peptidyl 1-hydroxyurea 1a attained an IC50 of 20 mM vs MMP-9, and substantially approaches inhibition of known N-hydroxyureas based on aminoacids or peptides against other zinc metalloenzymes and non-peptidic N-hydroxyureas against MMPs. Strong preference of the OeN1eC]O unit for the antiperiplanar amide bond conformation seems to be the major limit for more effective zinc chelation. Methylation of a peptidyl 1-hydroxyurea at N3, to promote the synperiplanar O-N1-C=O conformation required for zinc chelation and improve affinity, resulted in release of a methylimidazolidine-2,4-dione through an undesired intramolecular reaction reminiscent of the Edman peptide degradation
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
I turisti delle radici di origini italiane. L'indagine qualitativa.
No full textIn questa fase della ricerca si è realizzata un’indagine qualitativa di tipo esplorativo per studiare le caratteristiche del segmento di domanda del turismo delle radici. Considerate le lacune nelle conoscenze disponibili sul fenomeno e la necessità di acquisirle e di approfondirne alcune dinamiche, la ricerca qualitativa ha inteso esplorare il tema ed offrire un primo approccio conoscitivo su caratteristiche, orientamenti ed azioni di emigrati e loro discendenti. Inoltre, una sezione della ricerca, descritta nel successivo paragrafo, è stata dedicata ad aspetti relativi alla sostenibilità del roots tourism in termini socio-culturali, quindi all’impatto del fenomeno sul tessuto sociale e culturale della comunità ospitante. Si tratta di un tema che appare nuovo anche nella letteratura internazionale e di grande interesse ed attualità. Infine, si è affrontato la tematica dell’attuale pandemia da Covid-19 e di ciò che potrebbe succedere al termine della stessa, sempre con riferimento al turismo delle radici. Questa indagine esplorativa iniziale ha consentito di fornire indicazioni per le future implementazioni della ricerca, in particolare per l’indagine statistica condotta successivamente
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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