1,720,956 research outputs found
Developing an Oral-Insulin-Delivery System using GET-peptide-mediated transcytosis
Get PDFInsulin a peptide hormone regulates blood glucose levels and is considered a mainstay of treatment for diabetic patients. Oral insulin delivery still represents an overwhelming challenge due to its physio-chemical instability in gastro-intestinal tract (GIT) and poor intestinal permeability. A novel multidomain fusion-peptide system was employed to overcome these barriers termed Glycosaminoglycan (GAG)-binding enhanced transduction (GET) system, where GAG-binding motif promotes cell targeting and surface binding, whereas cell-penetrating-peptides (CPPs) region allows efficient cell entry. Here, potential of GET system in enhancing intestinal insulin permeation (transcytosis and translocation efficiency) was assessed across an in-vitro gut model system (Caco-2 cell monolayers). Insulin recycling was studied using different secretion regulators, moreover functional activity (by employing insulin-reporter cells) and stability of insulin-GET nanocomplexes (NCs) was also determined. In-house synthesised NHS-Fluorescein labelled insulin (Ins-F, non-quenchable) was used for studying internalisation, and transcytosis. Different stability assays were developed for GET system and insulin-GET NCs using quenchable proprietary FITC-insulin (Ins-F*). The difference in fluorescent behaviour of both insulins was studied using quenching and dequenching assays. pH-sensitive micro-particulates (MPs) based on Eudragit-L100 served as an enteric carrier system for insulin-GET NCs. These Eudragit-L100-MPs were characterised for their size, charge, morphology, drug release as a function of pH, and cellular uptake efficiency of released NCs across Caco-2 monolayers. Furthermore, enteric coated minicapsules were developed as an alternative to MPs for oral insulin delivery.
GET-peptide generates NCs with insulin and efficiently enhances its transport across differentiated model of intestinal epithelium (>8.7-fold greater translocation efficiency over un-modified insulin). Both the GET-system and insulin-GET NCs were resistant to proteolytic degradation, and NCs were stable and stayed intact even after being translocated inside cells. GET-peptide quenched the fluorescence of Ins-F*, which was successfully reversed using different proteolytic enzymes. Various studied inhibitors had insignificant effect on transcytosis and cellular uptake of NCs. Functional assessment using transcription reporter assays activated by insulin signalling (iLite-cells) revealed that NCs retain biological activity and may induce pharmacological response. Spherical Eudragit-L100-MPs (diameter 1250 nm & surface potential -8.3mV) displayed an entrapment efficiency of 77%. These MPs prevented insulin release at pH 1.2, with maximum release observed at pH 7.4. Likewise, enteric-coated minicapsules exhibited pH-dependent release in biorelevant media providing complete release in FaSSIF. The ability of this multidomain peptide sequence (GET) in promoting insulin permeation, transcytosis and intracellular uptake across in-vitro intestinal model while retaining insulin's functional activity might provide a step forward towards development of on oral insulin delivery system. Overall, this work underlines the application of non-viral vectors to overcome gastrointestinal barriers associated to oral insulin delivery. Current focus is to improve insulin bioavailability by formulating novel carrier system, which may possibly allow GET peptides to be an alternative approach in establishing effective oral peptide therapeutics for diabetes
Developing an Oral-Insulin-Delivery System using GET-peptide-mediated transcytosis
Get PDFInsulin a peptide hormone regulates blood glucose levels and is considered a mainstay of treatment for diabetic patients. Oral insulin delivery still represents an overwhelming challenge due to its physio-chemical instability in gastro-intestinal tract (GIT) and poor intestinal permeability. A novel multidomain fusion-peptide system was employed to overcome these barriers termed Glycosaminoglycan (GAG)-binding enhanced transduction (GET) system, where GAG-binding motif promotes cell targeting and surface binding, whereas cell-penetrating-peptides (CPPs) region allows efficient cell entry. Here, potential of GET system in enhancing intestinal insulin permeation (transcytosis and translocation efficiency) was assessed across an in-vitro gut model system (Caco-2 cell monolayers). Insulin recycling was studied using different secretion regulators, moreover functional activity (by employing insulin-reporter cells) and stability of insulin-GET nanocomplexes (NCs) was also determined. In-house synthesised NHS-Fluorescein labelled insulin (Ins-F, non-quenchable) was used for studying internalisation, and transcytosis. Different stability assays were developed for GET system and insulin-GET NCs using quenchable proprietary FITC-insulin (Ins-F*). The difference in fluorescent behaviour of both insulins was studied using quenching and dequenching assays. pH-sensitive micro-particulates (MPs) based on Eudragit-L100 served as an enteric carrier system for insulin-GET NCs. These Eudragit-L100-MPs were characterised for their size, charge, morphology, drug release as a function of pH, and cellular uptake efficiency of released NCs across Caco-2 monolayers. Furthermore, enteric coated minicapsules were developed as an alternative to MPs for oral insulin delivery.
GET-peptide generates NCs with insulin and efficiently enhances its transport across differentiated model of intestinal epithelium (>8.7-fold greater translocation efficiency over un-modified insulin). Both the GET-system and insulin-GET NCs were resistant to proteolytic degradation, and NCs were stable and stayed intact even after being translocated inside cells. GET-peptide quenched the fluorescence of Ins-F*, which was successfully reversed using different proteolytic enzymes. Various studied inhibitors had insignificant effect on transcytosis and cellular uptake of NCs. Functional assessment using transcription reporter assays activated by insulin signalling (iLite-cells) revealed that NCs retain biological activity and may induce pharmacological response. Spherical Eudragit-L100-MPs (diameter 1250 nm & surface potential -8.3mV) displayed an entrapment efficiency of 77%. These MPs prevented insulin release at pH 1.2, with maximum release observed at pH 7.4. Likewise, enteric-coated minicapsules exhibited pH-dependent release in biorelevant media providing complete release in FaSSIF. The ability of this multidomain peptide sequence (GET) in promoting insulin permeation, transcytosis and intracellular uptake across in-vitro intestinal model while retaining insulin's functional activity might provide a step forward towards development of on oral insulin delivery system. Overall, this work underlines the application of non-viral vectors to overcome gastrointestinal barriers associated to oral insulin delivery. Current focus is to improve insulin bioavailability by formulating novel carrier system, which may possibly allow GET peptides to be an alternative approach in establishing effective oral peptide therapeutics for diabetes
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
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