1,721,103 research outputs found
PEPTIDOMIMETICS CONTAINING NEW BIFUNCTIONAL 2,5-DIKETOPIPERAZINE SCAFFOLDS: SYNTHESIS, CONFORMATIONAL ANALYSIS AND USE AS POTENT INTEGRIN LIGANDS
Full text linkA library of 11 bifunctional 2,5-diketopiperazine (DKP) scaffolds, derived from L- or D-Ser and either L- or D-Asp or D-Glu, was designed and synthesized. All the DKP scaffolds feature a carboxylic acid functionality and an amino group, either protected as Boc or masked as azide, which can be locked in a cis- or trans-relationship as a consequence of the absolute configurations of the two α-amino acids. Moreover, the DKP scaffolds differ from each other for the substitution at the intracyclic nitrogens (N-1, N-4), as they are either mono- or bis-benzylated. The DKP scaffolds, while being derived from α-amino acids, can be seen as constrained dipeptides formed by two β-amino acids or one β- and one γ-amino acid.
Two different synthetic strategies were devised to prepare the mono benzylated scaffolds, depending on the nitrogen substitution (N-1 or N-4). In particular, the synthesis of DKP scaffolds bearing a benzyl group at the serine-derived nitrogen N-4 was accomplished making use of a serine ligation strategy, via the isopeptide.[1] On the other hand, the synthesis of DKP scaffolds bearing a benzyl group at the aspartic acid-derived nitrogen N-1 occurred through the formation of a dipeptide intermediate. Bis N-benzyl substituted scaffolds were easily accessed benzylating mono-substituted advanced intermediates.
An efficient synthesis in solution of eight cyclic peptidomimetics containing a DKP scaffold and the Arg-Gly-Asp (RGD) motif[2] has been developed and optimized. The ligands were tested for their ability to inhibit biotinylated vitronectin binding to integrin αvβ3 and αvβ5 receptors. All the ligands, except for the one containing a cis-scaffold, displayed low nanomolar inhibitory activity for both αVβ3 and αVβ5 integrin receptors, with a slight selectivity in favour of the former receptor. In order to rationalize, on a molecular basis, the affinity of these cyclic RGD peptidomimetics for the αvβ3 receptor, conformational and docking studies were performed by NMR spectroscopy and computational methods.
Two cyclic peptidomimetics containing a DKP scaffold and the isoAsp-Gly-Arg (isoDGR) motif were prepared, combining a solid phase and a solution phase synthetic approach. Very promising results (low nanomolar inhibitory activity) were obtained for their ability to inhibit biotinylated vitronectin binding to the αvβ3 and αvβ5 integrin receptors.
Based on the good results recently obtained by the group of Prof. Oliver Reiser (Univ. Regensburg)[3] in the design of helices, alternating two α- and two β-amino acids, a linear pseudodecapeptide was prepared alternating a cis-DKP, which serves as a ββ-constrained dipeptide, and Ala-Ala as the αα-subunit. The folding properties of the αα,ββ-pseudodecapeptide were studied by NMR spectroscopy, CD spectroscopy and computational methods. The results obtained, though not exhaustive, are indicative of a turn-inducing ability of the cis-DKP.[4]
[1] M. Marchini, M. Mingozzi, R. Colombo, C. Gennari, M. Durini, U. Piarulli, Tetrahedron 2010, 66, 9528-9531.
[2] A. S. M. da Ressurreição, A. Vidu, M. Civera, L. Belvisi, D. Potenza, L. Manzoni, S. Ongeri, C. Gennari, U. Piarulli, Chem. Eur. J. 2009, 15, 12184-12188.
[3] L. Berlicki, L. Pilsl, E. Wéber, I. M. Mándity, C. Cabrele, T. A. Martinek, F. Fülöp, O. Reiser, Angew. Chem. Int. Ed., in press.
[4] a) A. S. M. Ressurreição, A. Bordessa, M. Civera, L. Belvisi, C. Gennari, U. Piarulli, J. Org. Chem. 2008, 73, 652-660; b) R. Delatouche, M. Durini, M. Civera, L. Belvisi, U. Piarulli, Tetrahedron Lett. 2010, 51, 4278-4280
Il calcolo delle conseguenze nell’analisi post-incidentale
No full textNel seguito delle presenti note si vuole dare testimonianza come l’uso post-dittivo degli strumenti propri
della analisi dei rischi possa non solo risultare utile, ma determinante nel razionalizzare il contesto di una
analisi tecnica a posteriori di un evento incidentale effettivamente verificatosi. Nel presente lavoro verrà
analizzato, con gli strumenti propri del calcolo delle conseguenze, un incidente avvenuto durante il travaso di
GPL da un’autocisterna ad un serbatoio fisso, che ha visto lo sviluppo di un incendio nei pressi
dell’autocisterna e la sua successiva esplosione. La disponibilità di testimonianze dirette e di riscontri
sperimentali, rappresentati dai danni provocati dai diversi fenomeni che si sono prodotti durante l’incidente,
ha consentito innanzitutto di individuare i modelli più accurati per la rappresentazione matematica dei
fenomeni incidentali. Inoltre, l’impiego combinato dei modelli selezionati, ha permesso poi di ricostruire in
maniera abbastanza accurata la dinamica dei fatti e di risalire all’evento iniziatore (la perdita di contenimento
dal sistema di travaso dell’autocisterna) ed alla sua quantificazione (in termini di portata effluente), anche se
non è stato possibile individuare in dettaglio la localizzazione specifica del punto di rilasci
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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