\u3ci\u3eThe Coming of the Sea-Elves (Unto the World)\u3c/i\u3e

As motes of dust were the ships of the Sea-Elves, far out upon the boundless blue sea, at the very limits of visibility

Saturation of the Human Phenome

The phenome is the complete set of phenotypes resulting from genetic variation in populations of an organism. Saturation of a phenome implies the identification and phenotypic description of mutations in all genes in an organism, potentially constrained to those encoding proteins. The human genome is believed to contain 20-25,000 protein coding genes, but only a small fraction of these have documented mutant phenotypes, thus the human phenome is far from complete. In model organisms, genetic saturation entails the identification of multiple mutant alleles of a gene or locus, allowing a consistent description of mutational phenotypes for that gene. Saturation of several model organisms has been attempted, usually by targeting annotated coding genes with insertional transposons (Drosophila melanogaster, Mus musculus) or by sequence directed deletion (Saccharomyces cerevisiae) or using libraries of antisense oligonucleotide probes injected directly into animals (Caenorhabditis elegans, Danio rerio). This paper reviews the general state of the human phenome, and discusses theoretical and practical considerations toward a saturation analysis in humans. Throughout, emphasis is placed on high penetrance genetic variation, of the kind typically asociated with monogenic versus complex traits

BIOMECHANICS OF THE LONGSWING PRECEDING THE TKACHEV

The aim of this study was to compare the longswing preceding the straddle, straight and full twisting Tkachev with the central aim of establishing whether a Tkachev specific longswing exists that can be used for the development of different versions of the skill. Twin video images of Tkachevs (straddle n=6; straight n=10; and full twisting n=2) were collected at the 2000 Sydney Olympics, digitised and analysed using DLT techniques. The functional phases (Irwin and Kerwin, 2005) were determined from hip and shoulder angular velocity profiles. Differences between the angular positions of the gymnasts during the functional phases highlighted that a generic Tkachev preparatory longswing did not appear to exist and that more specific preparatory drills are required to develop complex versions of this skill

Reconsidering the superstore workplace : A Sheffield case study of segmentation and technology.

Retailing is back on the research agenda and the analysis of consumption processes is providing a fertile source of insightful geographical literature. Yet despite this interest, the retail workplace remains on the margins of disciplinary concerns. Given this situation, it is time that the retail workplace was reconsidered. The reconsideration within this thesis concentrates on the superstore workplace and attempts to challenge existing applications of labour market segmentation theory. This challenge is driven by an interest in information and communication technology (ICT) and a realisation that these technologies must be understood with reference to human interaction. The empirical analysis centres on one case study, a food-selling superstore in Sheffield. As an empirical link between theory and qualitative analysis, secondary human resource statistics are analysed to provide a guide to segmentation within the store. Qualitative research techniques are used to build an in-depth understanding of different employees activities and experiences. The secondary data suggests that segmentation remains an important framework for organisation within the retail superstore. However, qualitative research illustrates how existing theoretical conceptualisations of the segmented superstore might be problematised by a series of power relationships (dictation, delegation and authority) that are, in part, facilitated by the use of ICTs. These power relationships are in turn reinterpreted within individual worker strategies of manipulation and resistance. Here, workers regularly use ICTs in different ways than the remote head office might have originally intended. It is also suggested that the consent to work for many disadvantaged workers has to be understood by reference to a series of social concerns from outside the workplace (childcare, other domestic relationships, financial survival, lifestyle choice, social experience and self-esteem). These findings suggest a rich vein for additional research and the retail workplace should be pushed to the centre of geographical debate for further analysis

Reconstituting immune surveillance in breast cancer: molecular pathophysiology and current immunotherapy strategies

Over the past 50 years, breast cancer immunotherapy has emerged as an active field of research, generating novel, targeted treatments for the disease. Immunotherapies carry enormous potential to improve survival in breast cancer, particularly for the subtypes carrying the poorest prognoses. Here, we review the mechanisms by which cancer evades immune destruction as well as the history of breast cancer immunotherapies and recent developments, including clinical trials that have shaped the treatment of the disease with a focus on cell therapies, vaccines, checkpoint inhibitors, and oncolytic viruses

Extracellular vesicles as mediators of therapy resistance in breast cancer microenvironment

Resistance to various therapies, including novel immunotherapies, poses a major challenge in the management of breast cancer and is the leading cause of treatment failure. Bidirectional communication between breast cancer cells and the tumour microenvironment is now known to be an important contributor to therapy resistance. Several studies have demonstrated that crosstalk with the tumour microenvironment through extracellular vesicles is an important mechanism employed by cancer cells that leads to drug resistance via changes in protein, lipid and nucleic acid cargoes. Moreover, the cargo content enables extracellular vesicles to be used as effective biomarkers for predicting response to treatments and as potential therapeutic targets. This review summarises the literature to date regarding the role of extracellular vesicles in promoting therapy resistance in breast cancer through communication with the tumour microenvironment