1,721,163 research outputs found
Rationalisation of decision support for integrated coastal zone management
EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Shining a light on the FCGR Locus: Deconvoluting the challenging genomic organisation and consequences in immune oncology
The majority of therapeutic monoclonal antibodies (mAbs) educe their functional response by interfacing with a family of cell-surface proteins called the Fc gamma receptors (FcγRs), comprising a single high-affinity and five low-affinity receptors. The low-affinity receptors are encoded by the FCGR2A, FCGR2B, FCGR2C, FCGR3A and FCGR3B genes, positioned within a highly homologous 200kb locus on chromosome 1q23-24 that is subject to numerous single nucleotide polymorphisms (SNPs) and regions of copy number variation (CNRs). Resulting from multiple recombination and segmental duplication events, the high sequence homology represents a unique challenge for the genetic analyses of this cluster as the traditional short-read technologies often fail to produce reads that can be adequately aligned or assembled. However, the Oxford Nanopore Technologies (ONT) sequencing platform introduces the exciting opportunity to accurately resolve this locus and generate highly-detailed genomic maps of the region under different copy number states.Previously generated nanopore sequencing data of long-range (LR)-PCR products from the low- affinity FCGR genes (n=4) were analysed and led to the development of a bioinformatic pipeline to remove spurious alignments and identify single nucleotide variation. This analysis revealed that while nanopore sequenced LR-PCR products can be utilised to analyse the low-affinity FCGR genes to some extent, they are restricted by their gene-centric nature and generating reliable sequencing reads from the FCGR2C gene proved to be difficult.To address this challenge, ONT long-read sequencing and Bionano optical mapping were performed on peripheral blood mononuclear cell (PBMC) samples from healthy donors (n=22). The project involved the optimisation of multiple amplification-independent ONT approaches; i) whole genome sequencing (WGS) ii) cas9-mediated targeting and iii) computational enrichment with adaptive sampling. The cas9 and adaptive sampling techniques resulted in a 450- and 10-fold enrichment of the FCGR locus respectively. The newly generated nanopore data was then used to provide extensive phasing, CNR breakpoint and variant characterisation. A total of 16,326 high-quality small variants, corresponding to 2,296 unique locations, were detected. This enabled the genotyping of clinically-relevant SNPs of interest, identification of extended haplotypes and successful phasing across the 200kb region. Eight polymorphic short tandem repeat (STR) regions were found that have the potential to be of functional relevance to FcγR expression. Breakpoints for CNR1, CNR2, CNR3 and CNR4 were refined to regions of 5.4kb, 14.5kb, 7.9kb and 4.7kb respectively. A novel case of CNR4 duplication was reported and CNR4, in addition to CNR3, was shown to be more prevalent than previously suggested. In conclusion, ONT presents the possibility to overcome the inherent difficulties of characterising genomic variation in the complex FCGR locus, thereby permitting a more holistic view of the region and its regulation. Ultimately this data provides a fuller understanding of the genomic variation at the FCGR locus providing the basis for further research into the regulation of these genes, with the potential to improve risk-adapted patient stratification and offer more targeted therapeutic approaches for cancer patients
Going Beyond Counting First Authors in Author Co-citation Analysis
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
Three Memory Frameworks on Chernobyl
This case study explores three narratives – and attendant spatial manifestations – that, after emerging in the aftermath of the Chernobyl accident, foreground different aspects of the disaster’s legacy: the “hazard” story, the “national martyrdom” story, and the “lost paradise” story. Each of these narratives manifests itself spatially, from the iconic site of the power plant with the nearby ghost town of Pripyat, now the epicentre of an international disaster tourism industry, to Kyiv’s Chernobyl Museum and the related lieux de memoire that perpetuate national storytelling. The “paradise lost” narrative finds its spatial manifestation in the colourful cemeteries that stud the Chernobyl Exclusion Zone. Ethnographic analysis shows that as the ruins of former settlements become engulfed in vegetation, Chernobyl survivors keep returning to their ancestral burial grounds to carry out maintenance and perform rituals, thereby giving life to places of the dead and turning a landscape of loss into one of remembrance and hope
Variations on the Author
“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
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
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
We 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
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