1,720,979 research outputs found
Different approaches to optimize the antimicrobial properties of cationic peptides: substitution by non-coded amino acids and conjugation to nanoparticles
Get PDFAntimicrobial peptides are small, cationic and amphipathic peptides produced by virtually all living organisms as key components of the innate immune system. Importantly, they hold promise for the development of new broad-spectrum anti-infective agents. These are urgently needed, due to the growing emergence of microorganisms that are resistant to the available therapeutic agents. In recent years, research has focused on the characterization and optimization of these molecules. Albeit thousands of peptides have been isolated and characterized, only a reduced number of them has entered into clinical phases, because of some limitations. Among them: (i) the poor peptide bioavailability, (ii) the toxicity at high doses (iii) the high susceptibility to proteolytic degradation (iv) the inefficient peptide delivery to the target site at high concentration.
Nowadays, thanks to advances in biochemical research, computational studies and nanotechnologies it has become possible to overcome some of these problems.
Recently, a frog-skin derived AMP, named Esc(1-21), has been investigated for its potent activity against the Gram-negative bacterium Pseudomonas aeruginosa and immunomodulatory properties. However, it showed a weaker activity against Gram-positive bacteria and some cytotoxic effect on mammalian cells.
In this thesis work, with the aim to optimize the biological properties of AMPs, e.g. Esc(1-21), three different approaches have been used:
- Design and synthesis of an analog of Esc(1-21) carrying three alpha-aminoisobutyric acid (Aib) residues. When inserted into the primary structure of
peptides, Aib residues are expected to increase the alpha-helical content of the peptides, due to their strong helicogenicity. Importantly, a stabilized alpha-helical structure is known to be a crucial parameter to improve the AMPs’ activity against Gram-positive bacteria but also to increase their toxicity against mammalian cells. The Aib-containing peptide has been studied for its structural and biological properties and compared with the parent peptide Esc(1-21).
- Design and synthesis of a diastereomer of Esc(1-21), named Esc(1-21)-1c, by replacing two L-amino acids in the C-terminal portion, i.e. L-Leu14 and L-Ser17, with the corresponding D-enantiomers. Besides making a peptide more resistant to proteolytic degradation, the insertion of D- amino acids is expected to disrupt the peptide’s alpha-helical content and to reduce its cytotoxicity. The effect(s) of D-amino acids incorporation on the structural/biological properties of the peptide have been investigated.
- Design and production of two different types of nanoparticles to protect the AMP from proteolytic degradation and to allow its delivery to the target site at high concentration without altering the antimicrobial properties: (i) inorganic gold nanoparticles (AuNPs) coated with Esc(1-21) and (ii) nano-embedded microparticles for pulmonary delivery of a model cationic antimicrobial peptide, i.e. colistin.
As expected, the Aib-analog of Esc(1-21) resulted to be more active against Gram-positive bacteria, but also more cytotoxic against mammalian cells, due to its higher alpha-helical content in the secondary structure.
Differently, the insertion of two D-amino acids provoked a disruption of the alpha-helix and, as a consequence, a significant reduction in the peptide’s cytotoxic effect. In addition, the diastereomer resulted to be more active against the biofilm form of P. aeruginosa and more stable in human serum.
The conjugation of Esc(1-21) to AuNPs, led to an increase of the antimicrobial activity of the peptide and to a greater stability to proteolytic degradation, without interfering with the mechanism of membrane perturbation. In addition, the conjugation onto AuNPs did not affect the wound-healing properties of the free peptide and AuNPs@Esc(1-21) were not found to be toxic against human keratinocytes.
Finally, the engineered biocompatible and biodegradable polymeric microparticles designed as a delivery system for an AMP model, i.e. colistin, resulted to have a prolonged activity against P. aeruginosa biofilm in comparison with the free peptide. This was likely due to their ability to penetrate into bacterial biofilm and to sustain colistin release inside it.
The promising results obtained by these different approaches, have made it possible to take a step forward in the optimization of a cationic peptide for the development of potential new antibacterial drugs
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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