1,721,059 research outputs found
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
Towards personalised medicine - developing a 3D leukaemia biomimicry
No full textLeukaemia is a form of cancer that affects cells of the haematopoietic lineage. Acute myeloid leukaemia (AML) and chronic lymphocytic leukaemia (CLL) are the two most common types, accounting for 31% and 38% of all leukaemia diagnoses in the United Kingdom.
The study of leukaemia has been traditionally conducted in two-dimensional (2D) cultures or resorting to animal models, both systems failing to recapitulate the physiological parameters of the disease. A three-dimensional (3D) bone marrow model comprised of polyurethane (PU) scaffolds coated with Collagen I has been shown to allow the culture of leukaemic cell lines, showing potential towards the culture of primary cells. In this thesis, this 3D model was tailored to the culture of primary bone marrow (BM) and peripheral blood (PB) cells of patients with leukaemia, using serum-free cytokine-free conditions and enabling a long-term culture (>28 days). Scaffold dimensions, geometry, cell seeding methods, extraction methods, coating proteins and storage protocols were studied and optimised.
The study of AML in this platform allowed the xenofree culture of PB and BM cells for up to 6 weeks, maintaining >80% viability, 30 days longer than the previously reported primary AML culture. The long-term viable cultures allowed the study of population dynamics through flow cytometry, measurement of cell expansion and delivery of chemotherapy, highlighting higher susceptibility of primary cells to drugs. The study of CLL allowed for long-term cultures of up to 8 weeks of cells derived from PB and BM, demonstrating that 3D and serum-free conditions reduced CLL cell apoptosis in vitro, allowing the delivery of a novel BCL2 inhibitor. This is the first long-term serum-free, cytokine-free and feeder-cell free culture to be reported.
In summary, this thesis reports the long-term xenofree study of primary leukaemia in a PU scaffold, allowing the study of population dynamics and drug delivery.Open Acces
Synthesis and characterisation of bio-inspired polymers for pH-mediated intracellular delivery and therapeutic applications
No full textEffective intracellular delivery remains a significant challenge in the development of non-viral delivery systems. Endosomal entrapment, which results in enzymatic degradation of bioactive compounds in lysosomes, is one of the main barriers. This thesis outlines endeavours to develop biomimetic nanoscale systems tailored for pH-triggered intracellular delivery.
A library of innovative pH-responsive polymers was developed to mimic fusogenic viral peptides. They were synthesized by grafting fatty acids to the pendant carboxyl groups along the backbone of the pseudopeptide poly (L-lysine iso-phthalamide) (PLP) at varying degrees of grafting. The effects of hydrophobic chains on pH-responsive properties in aqueous solution, cell membrane destabilization activity, and in vitro cytotoxicity were examined. The synthesized and characterized 12-aminododecanoic acid-grafted PLP (PLP-ADA) exhibited minimal cytotoxicity toward different mammalian cell lines. The polymer-mediated translocation of model payloads into cells was demonstrated. The mechanism behind membrane destabilization was elucidated, showing the superior endosomal-escape ability of the polymer to release endocytosed materials into the cytoplasm. Under mildly acidic extracellular conditions, its intracellular delivery was significantly enhanced. The thesis systematically explores the effects of side chain, polymer concentration, treatment time, extracellular pH, and payload size on delivery efficiency across various cell types, demonstrating its broad applicability in drug delivery. Furthermore, PLP-ADA has shown the capability to enhance the internalization of the ribosome-inactivating protein Saporin, inducing cell death in cancer cells, suggesting its potential for cancer therapy applications.
In addition, the optimal pH-responsive polymer was utilized to facilitate intracellular loading of membrane-impermeable trehalose for cryoprotection of mammalian cells. This could avoid the use of toxic dimethyl sulfoxide (DMSO). With the assistance of PLP-ADA, efficient delivery of trehalose into red blood cells (RBCs) and an immortalized line Jurkat cells was achieved. The successful cryopreservation of cells was demonstrated, which addresses a crucial aspect in emerging fields of cell therapy and biobanking.Open Acces
Cryopreservation of mammalian cells based on intracellular saccharide delivery using membrane-permeabilising biopolymers
No full textCell cryopreservation is a key process for fields including cell therapy and biobanking. The toxicity concerns around currently standard cryoprotective agents (CPAs) such as dimethylsulfoxide (DMSO) and glycerol are limiting the development of cell cryopreservation. This thesis presents the work on developing and optimising a glycerol-free and DMSO-free cryopreservation method for mammalian cells using saccharides solely as the CPA with saccharides delivered into cells by a novel pH-responsive polymer for the maximal cryoprotection and minimal cell damage.
The polymer PLP-NDA18 displayed negligible cytotoxicity to different mammalian cells after being synthesised and characterised. Different saccharides, including trehalose, sucrose, glucose, and dextran 40 kDa, were delivered into mammalian cells successfully with the assistance of PLP-NDA18. The PLP-NDA18-mediated intracellular saccharide delivery was proven rapid and efficient with negligible cytotoxicity for different mammalian cells.
The cryopreservation process of saccharide-loaded red blood cells (RBCs) was investigated and optimised. Compared with other commonly-used CPAs, saccharides displayed significantly more effective cryoprotection according to the cryosurvival rates and post-thaw cell characterisation.
In addition, the optimal condition for saccharide-loaded RBC cryopreservation was tested on immortalised and primary human T cells. Key parameters of each step were investigated and optimised using immortalised T cells which led to the preliminary success of the primary T-cell cryopreservation using saccharides as the sole CPA without any other excipient.
Overall, intracellular saccharides have been rapidly delivered into RBCs and T cells using the PLP-NDA18 polymer with minimal cell damage. The cryopreservation protocol with saccharides solely as the CPA presenting at both sides of cells has been successfully developed and optimised for RBCs and immortalised T cells, with preliminary success on primary T-cell observed. This DMSO-free and glycerol-free cryopreservation method for mammalian cells can be used as a platform for cellular products to prompt the development of biobanking and wider application of cell therapy.Open Acces
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
Synthesis and characterisation of stimuli-responsive amino acid-based polymeric materials for drug delivery
Get PDFThe delivery of cell-targeted therapeutics, particularly macrodrugs such as proteins and nucleic acids, is of great importance for modern therapy. However, there are many different barriers in the complex bio-environment, which significantly limit the drug availability and efficacy. Herein, this thesis presents the work on development of smart amino acid-based polymeric materials for drug delivery. Specifically, drug delivery vehicles at different length scales with different stimuli-responsive behaviour have been systematically investigated. A library of anionic, cell penetrating peptide-mimicking, lysine-based hyperbranched polymers have been developed for intracellular drug delivery. Results showed that these polymers destabilised membranes significantly at late endosomal pH, but remained non-lytic at physiological pH. The multivalency effect of the hyperbranched structure further effectively promoted the membrane interactions. Further investigation into endosomal release showed that the hyperbranched polymers could facilitate intracellular payload delivery in Hela cells.
A series of amphiphilic hydrogels have been developed for oral drug delivery. The effects of crosslinking ratio, solid contents and molecular weights of crosslinkers on hydrogels’ behaviour were investigated. Also, the in vitro model drug loading and release was evaluated. Results suggested that hydrophobic payloads could be successfully incorporated into the hydrogels, and the release in biorelevant buffers was triggered by pH stimulus. Furthermore, by using disulfide-bond containing crosslinkers, the hydrogels responded to the redox trigger in the colon, which led to a faster and more efficient release. For intracellular drug delivery via an oral route, nanogels were prepared using membrane-active polymers by either physical or chemical crosslinking. The physically crosslinked nanogels were designed to have pH-responsive dissociation. So they could retain model drugs in the acidic gastric fluid, but release them in the neutral intestinal fluid. After dissociation, the polymers were membrane-lytic at slight acidic pH (5.5), which could probably permeabilise cell membranes for intracellular delivery.Open Acces
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