1,721,025 research outputs found
REVERSIBLY STABLE THIOPOLYPLEXES FOR INTRACELLULAR DELIVERY OF GENES
No full textNovel polyaspartamide non-viral carriers for gene therapy were synthesized by introducing, on the same polymer backbone, positively charged
groups, for electrostatic interactions with DNA, and thiol groups for the formation of disulfide bridges between polymer chains. The introduction
of thiols was aimed to have a vector with low redox potential sensitivity: disulfide crosslinking in fact, being stable in extracellular environment,
allowed either to have stable complexes in plasma, that can protect DNA from metabolism, or to be reduced inside the cell, where the excess of
glutathion in reduced form maintains a low redox potential. The consequent destabilization of the complex after disulfide cleavage can release
DNA selectively inside the cells.
α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) was used as starting polymer being a highly water-soluble synthetic polymer, already
proposed with success as therapeutic carrier by our group. In this study, PHEA was firstly functionalised with ethylendiamine, obtaining a well
defined copolymer with pendant primary amine groups (PHEA-EDA), to which N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) and 3-
(carboxypropyl)trimethyl-ammonium chloride (CPTA) were linked in two subsequent steps, allowing the introduction of thiol and cationic groups
respectively. Finally DTT treatment lead to the final PHEA-EDA-SH-CPTA thiopolycation, named PESC.
The present work describes the synthesis and characterization of the thiopolycation PESC. 1H NMR spectroscopy detected the derivatization
molar degrees in SPDP and CPTA; the formation of DNA complexes (thiopolyplexes), their stability in the presence of polyanions and the ability
to release DNA under reductive conditions were studied by agarose gel electrophoresis. DNase II degradation study was carried out to detect the
ability of thiopolyplex to stabilize DNA towards enzymatic metabolism. Thiopolyplexes were then characterized by Dynamic Light Scattering
(DLS) and Zeta Potential analysis. Finally, in vitro toxicity profile (MTT) and gene transfer efficiency (Luciferase assay) were carried out to
evaluate thiopolyplex biocompatibility, safety and efficacy to be used as gene delivery system.
© 2006 Elsevier B.V. All rights reserved
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
Polyhydroxyethylaspartamide-spermine copolymers: Efficient vectors for gene delivery
No full textAim of this paper was that to prepare biocompatible, polyaspartamide based copolymers containing spermine
or spermine/hydrophobic side chains able to condense nucleic acids and to transfect mammalian cells.
Copolymers were prepared starting from α,β-poly-(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) and exploiting
the reactive hydroxyl groups in the polymeric side chains by subsequent activation reactions to obtain PHEASpermine
(PHEA-Spm) and PHEA-Spermine-Butyramide (PHEA-Spm-C4). Molecular, physico-chemical and
biological characterization of copolymers and interpolyelectrolyte complexes with plasmid DNAwas performed.
Experimental results evidenced that these copolymers are able to form complexes with plasmid DNA already at
low polycation/DNAweight ratio ranging from 0.75/1 to 2/1. Interpolyelectrolyte complexes with decreased size
were obtained when increasing the polycation/DNA weight ratio, until nanosized dimensions were reached.
Copolymers aswell as complexeswere not haemolytic and non toxic in vitro. In vitro cell transfection with PHEA
derivatives showed good biocompatibility and high transfection efficiency (luciferase) in cancer cells in
comparison with commercially available, but toxic transfection agents
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