1,720,986 research outputs found
Nanoparticles, Their protein corona and impact on the immune function of human lung cells
No full textParticles with a single dimension smaller than 100 nm are called nanoparticles (NPs). There is a large amount of epidemiology that anthropogenic particles cause increased mortality, increased risk of asthma and increased incidence of lung adenocarcinoma.Inhaled NPs can reach the lung terminus, interacting with a lipid lining at the air-liquid interface (pulmonary surfactant (PSf)) and with an aqueous hydrophase beneath. Studies in serum have shown that upon contact with blood, proteins very rapidly adsorb to the particle surface, thus the particle accrues a biological identity. However, no such interaction studies have been performed in the pulmonary system, where there is a complex interplay of proteins and lipids. The interaction of NPs with PSf is poorly understood. Prior to reaching the lung epithelium, NPs must translocate through this layer.The aims of this thesis are to firstly explore the interactions of NPs with proteins and lipids in the lung and secondly investigate the toxicity and effect on the immunological action of lung cells.NPs were incubated with pulmonary lavage fluid and adsorbed proteins were analysed using state-of-the-art, high resolution, quantitative mass spectrometry. To investigate the interactions of NPs with PSf, particles were incubated with a porcine surfactant. The bound lipids were analysed by qualitative mass spectrometry. The effect of NPs and the NP-protein-corona was investigated in cell lines by a number of techniques.Unique proteins were observed on each particle type, however the main contributors contribution was from a few key proteins. There was no biophysical property of these bound proteins that could predict their affinity to a particle. Surfactant associated protein A, B and D (SP-A, B, D) were observed to be bound to the particle surface. SP-A was bound with high abundance, suggesting it is likely these particles may interfere with PSf in vivo. All particles retained lipids on their surface through binding mediated by electrostatic interactions. Aminated-polystyrene and titanium dioxide NPs were capable of interfering with PSf in vitro. There was little observed effect of the particles to induce inflammation.The key findings suggest that the protein corona does not predict particle toxicity. Any observed effect is due to the core particle chemistry, not an acquired bio-identity. The toxicity of particles observed through epidemiological surveys could be caused from the inhibition of pulmonary surfactant, not from direct toxicity of the particles themselves
Generation of novel trimeric fragments of human SP-A and SP-D after recombinant soluble expression in E. coli
Get PDFSurfactant treatment for neonatal respiratory distress syndrome has dramatically improved survival of preterm infants. However, this has resulted in a markedly increased incidence of sequelae such as neonatal chronic inflammatory lung disease. The current surfactant preparations in clinical use lack the natural lung defence proteins surfactant proteins (SP)-A and D. These are known to have anti-inflammatory and anti-infective properties essential for maintaining healthy non-inflamed lungs. Supplementation of currently available animal derived surfactant therapeutics with these anti-inflammatory proteins in the first few days of life could prevent the development of inflammatory lung disease in premature babies. However, current systems for production of recombinant versions of SP-A and SP-D require a complex solubilisation and refolding protocol limiting expression at scale for drug development. Using a novel solubility tag, we describe the expression and purification of recombinant fragments of human (rfh) SP-A and SP-D using Escherichia coli without the need for refolding. We obtained a mean (± SD) of 23.3 (± 5.4) mg and 86 mg (± 3.5) per litre yield of rfhSP-A and rfhSP-D, respectively. rfhSP-D was trimeric and 68% bound to a ManNAc-affinity column, giving a final yield of 57.5 mg/litre of highly pure protein, substantially higher than the 3.3 mg/litre obtained through the standard refolding protocol. Further optimisation of this novel lab based method could potentially make rfhSP-A and rfhSP-D production more commercially feasible to enable development of novel therapeutics for the treatment of lung infection and inflammation.</p
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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