1,721,714 research outputs found

    Effects of two L- to D-amino acid substitutions on the structural and functional properties of the antimicrobial peptide esculentin-1a(1-21)

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    During the last years, the excessive and improper use of commercially available antibiotics has contributed to the development of resistant microbial pathogens, which represent a serious problem for the world public health. Among these microorganisms, the Gram-negative bacterium Pseudomonas aeruginosa is one of the most difficult to eradicate due to its ability to form sessile communities, named biofilms, which cause chronic infections, especially in the lungs of cystic fibrosis (CF) patients. Naturally occurring antimicrobial peptides (AMPs), characterized by a different mechanism of action, represent a promising alternative to the commonly used drugs. AMPs are evolutionally conserved molecules produced by almost all living organisms as a first line of immune defense and amphibian skin is one of the richest sources. The studies carried out in this thesis focused on two peptides: Esculentin-1a(1-21)NH2, [Esc(1-21) GIFSKLAGKKIKNLLISGLKG-NH2], derived from the N-terminal region of the frog skin AMP esculentin-1a, and its diastereomer, Esc(1-21)-1c, containing two D-amino acids at positions 14 and 17 (i.e., D-Leu and D-Ser, respectively). This latter was designed with the purpose to reduce the peptide’s cytotoxicity and to increase its stability to proteolytic enzymes. The results achieved in this thesis have indicated that compared to Esc(1-21), the diastereomer is: i) significantly less toxic towards mammalian cells, in agreement with its lower α-helical structure, as determined by circular dichroism spectroscopy and nuclear magnetic resonance studies; ii) more effective against the biofilm form of P. aeruginosa (either reference or clinical isolates from CF patients) while maintaining high activity against the free-living form of this pathogen; iii) more effective in killing Pseudomonas cells once internalized into bronchial cells expressing either the functional or the ΔF508 mutant of the CF transmembrane conductance regulator; iv) more resistant to bacterial and human elastases, which are abundant in CF lungs. In addition, the diastereomer was found (i) to have a higher activity than the all-L peptide in promoting migration of bronchial epithelial cells and presumably in favoring re-epithelialization of damaged lung tissue; (ii) to disaggregate and detoxify the bacterial lipopolysaccharide (LPS) and to inhibit cyclooxygenase-2 (COX-2) synthesis, albeit less than the wild-type peptide. Based on its interesting biological properties, Esc(1-21)-1c is a promising candidate for the development of a new drug that not only eliminates microbial pathogens, but also restores the integrity of a damaged tissue, such as the lung of CF patients, following Pseudomonas respiratory infections

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

    Misurare il beneserre. La sfida degli indicatori alternativi al Pil

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    Da decenni si discute della comune pratica di misurare il benessere di una società, ed il progresso in generale, con il Pil pro capite, ma solo negli ultimi anni il dibattito è uscito dal confine scientifico-accademico per entrare in modo rilevante nel dibattito politico. Chiudendo la conferenza mondiale intitolata “Beyond Gdp” tenutasi a Bruxelles nel novembre 2007, il presidente della Commissione Europea Josè Maria Barroso affermava che “non è possibile affrontare le sfide del futuro con gli strumenti del passato: è ormai tempo di andare oltre il Pil”. E’ dunque possibile sostituire il Pil con una misura alternativa più direttamente focalizzata al benessere? Ma cosa significa esattamente misurare il benessere? E quali sono state le principali iniziative a livello internazionale e nazionale che coinvolgono la “statistica ufficiale”? Quali sono le difficoltà che si incontrano uscendo dalla metrica monetaria, tipica del sistema dei conti nazionali, e si cerca invece di ottenere una misura di sintesi dei diversi aspetti che contribuiscono al benessere di una collettività? Possiamo misurare il benessere di una società a partire dalla valutazione soggettiva che i cittadini danno della propria felicità o della propria soddisfazione di vita? Questo libro cerca di rispondere a queste domande, affrontando una serie di criticità, di natura logico-concettuale e di natura statistica, che si devono affrontare per andare “oltre il Pil”

    Variations on the Author

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    “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

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    We 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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