1,721,013 research outputs found

    Absorption-promoting effects of chitosan in airway and intestinal cell lines: A comparative study

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    This work explored the interaction of chitosan with Calu-3 and Caco-2 cell lines, as models of the airway and intestinal epithelium, respectively. The toxicity, tight junction opening and mucoadhesive effects of chitosan were compared in the two cell lines. Additionally, the role of mucus in the absorption-promoting activity of chitosan was studied systematically. Notably, chitosan exhibited a different degree of toxicity on the Calu-3 and Caco-2 cells. Chitosan's tight junction-opening effect, observed in terms of reduction of transepithelial electrical resistance and permeability enhancement, was apparent in both cell lines, though somewhat lower in Caco-2 compared to Calu-3 cell layers (though overall permeability was higher in the former). Tight junction opening and association of chitosan with the epithelial cell layers was more prominent in mucus-containing than in mucus-depleted Calu-3 cells and non mucus-excreting Caco-2 monolayers. Overall, the work suggests that chitosan exhibits a different level of toxicity in airway, as compared to intestinal cells and although absorption enhancement is apparent in both cell lines, enabling its potential use as an absorption-promoting excipient in both pulmonary and oral macromolecular delivery, the magnitude and the duration of the effect is dependent on the level of mucus present on the epithelial surfaces

    Study on Significance of Receptor Targeting in Killing of Intracellular Bacteria with Membrane-Impermeable Antibiotics

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    Water-soluble antibiotics are largely excluded from therapy of intracellular infections, such as Shigella spp., Listeria spp., or Salmonella spp., due to their inability to permeate mammalian cell membrane. Here, the authors study if targeting offers an advantage to deliver killing doses of membrane-impermeable antibiotics intracellularly to infected cells. Mannose-decorated liposomes, loaded with gentamicin, are fabricated to target mannose receptor, a recognition system of (infected) macrophages. Designing a family of liposomes with varying surface presentation of mannose ligand, the authors show a clear dependence of cellular internalization on the ligand surface presentation. Significantly for the killing of intracellular bacteria, the study demonstrates internalization of mannosylated liposomes by the entire population of macrophages, both Salmonella-infected and non-infected, resulting in an efficient treatment of intracellular infection. This contrasts with non-targeted liposomes, where internalization does not occur by a substantial subpopulation of infected cells. The study points to the significance of targeted delivery of antibiotics for treatment of intracellular infections

    Direct routes to functional RAFT agents from substituted N-alkyl maleimides

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    N-substituted maleimides have become an indispensable tool for the synthesis of bioconjugates and functional materials. Herein, we present three strategies for the incorporation of N-alkyl substituted maleimides into RAFT agents and show that these maleimide-derived CTAs can be used to easily introduce a range of chemical functionality at the β-position of polymer chains, resulting in α,β,ω-functional RAFT polymers. With both functional maleimides and RAFT agents that are increasingly available on the market, the approach presented in this study could facilitate the synthesis of end-functional macromolecules and will complement well the range of existing synthetic routes, including those utilising N-substituted maleimides, to functional polymeric materials

    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

    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

    Dispelling the Myths Behind First-author Citation Counts

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    We 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

    Targeted PEG-poly(glutamic acid) complexes for inhalation protein delivery to the lung

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    In this study, we designed novel vitamin B12-targeted PEG-poly(GA) copolymers, and evaluated the role of B12-receptor mediated transport in increased cellular internalization in differentiated, polarized Calu-3 cells epithelial model. The formulations generated showed no significant toxicity or lung inflammation following chronic treatment. Taken together the results presented in this study show that vitamin B12 targeted PEG-poly(glutamic acid) copolymers are a potential as a new class of targeted ‘excipients’ for inhalation delivery of protein drugs to the lungs. Data presented here includes: Real-time polymerase chain reaction (qPCR); Flow cytometry (FACs); Transmission electron microscopy (TEM); Fluorescence Spectrophotometer; Confocal Microscopy

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