272 research outputs found

    Developing strategic learning alliances: partnerships for the provision of global education and training solutions

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    The paper describes a comprehensive model for the development of strategic alliances between education and corporate sectors, which is required to ensure effective provision of education and training programmes for a global market. Global economic forces, combined with recent advances in information and communication technologies, have provided unprecedented opportunities for education providers to broaden the provision of their programmes both on an international scale and across new sectors. Lifelong learning strategies are becoming increasingly recognized as an essential characteristic of a successful organization and therefore large organizations have shown a preparedness to invest in staff training and development. The demands for lifelong learning span a wide range of training and educational levels from school-level and vocational courses to graduate-level training for senior executive

    A study to investigate the expression, structure and function of alternatively spliced progesterone receptor variants in breast cancer cells

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    The progesterone receptor (PR) gene consists of eight exons and encodes the functionally distinct PR-A and B isoforms. PR alternative splicing events involving deletion of internal exons or intron retention have been reported, potentially generating proteins which lack various internal functional domains or are N-terminally truncated. PR status in breast cancer may be predictive of the efficacy of endocrine therapy and is measured using N-terminally targeted antibodies which detect both PR-A and B. In this study PR mRNA expression was assessed in breast cancer (MCF-7, T47-D and MDA-MB-231) and non-tumourigenic breast (MCF-10A) cell lines using an RT-PCR based gene walking assay. PR mRNA resulting from alternative splicing was detected in reportedly PR negative MDA-MB-231 cells using this assay. These mRNA could encode the low molecular weight nuclear and cytoplasmic PR proteins which are detected in this cell line using the C-terminal PR antibody C19. Ligand blotting, co-immunoprecipitation and DNA affinity precipitation assays demonstrated the ability of these proteins to bind progesterone, interact with the PR nuclear co-factor PSF, dimerise and bind DNA; thus potentially to function as ligand activated nuclear transcription factors. Validation studies using the gene walking assay demonstrate that alternatively spliced PR mRNA was also present in breast tumours originally characterised using N-terminal antibodies as being both PR+ and PR-. Using a novel non N-terminal PR antibody developed in this study, the nuclear PR status differed from the original status for 2 of 14 tumours examined, and cytoplasmic PR was detected. The results presented in this thesis suggest that PR undergoes extensive alternative splicing, generating potentially functional isoforms, and that expression of variant PR isoforms may affect the PR status of a tumour as determined using antibodies targeting different epitopes. PR exons 4 and 6 are flanked by consensus 5′ and 3′ splice sites and contain cryptic 3′ splice sites, as well as potential binding sites for a range of RNA binding splicing factors. siRNA knockdown of the individual SR proteins SRSF1, SRSF2, SRSF5 and SRSF6 identified potentially antagonistic roles for SRSF1 and SRSF2 in influencing the inclusion/skipping of PR exons 4 and 6, and also for SRSF6 in regulating exon 6 splicing.EThOS - Electronic Theses Online ServiceRVI Breast Cancer AppealGBUnited Kingdo

    Chapitre 25 - One Health dans l’élaboration des politiques : une approche intégrée pour traduire la science en politique

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    Introduction L’application du concept One Health à l’élaboration et à la mise en œuvre de politiques fondées sur la science n’est pas nouvelle, mais elle a été relancée au cours de la dernière décennie avec une prise de conscience croissante de la nécessité d’engager des équipes transdisciplinaires pour résoudre des problèmes complexes. La composition de ces équipes dépend dans une large mesure de la ou des questions à traiter, ..

    Development and exploitation of a novel mutant androgen receptor modelling strategy to identify new targets for advanced prostate cancer therapy

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    The persistence of androgen receptor (AR) signalling in castrate-resistant prostate cancer (CRPC) highlights the unmet clinical need for the development of more effective AR targeting therapies. A key mechanism of therapy-resistance is by selection of AR mutations that convert anti-androgens to agonists enabling the retention of androgenic signalling in CRPC. To improve our understanding of these receptors in advanced disease we developed a physiologically-relevant model to analyse the global functionality of AR mutants in CRPC. Using the bicalutamide-activated ARW741L/C mutation as proof of concept, we demonstrate that this mutant confers an androgenic-like signalling programme and growth promoting phenotype in the presence of bicalutamide. Transcriptomic profiling of ARW741L highlighted key genes markedly up-regulated by the mutant receptor, including TIPARP, RASD1 and SGK1. Importantly, SGK1 expression was found to be highly expressed in the KUCaP xenograft model and a CRPC patient biopsy sample both of which express the bicalutamide-activated receptor mutant. Using an SGK1 inhibitor, ARW741L transcriptional and growth promoting activity was reduced indicating that exploiting functional distinctions between receptor isoforms in our model may provide new and effective therapies for CRPC patients

    Football: a counterpoint to the procession of pain on the Western Front, 1914-1918?

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    In this article, three artworks of the First World War containing images of recreational football are analysed. These three images, In the Wings of the Theatre of War, Artillery Men at Football and Gassed, span the war from its beginning to its conclusion and are discussed in relationship to the development of recreational football in the front-line area, the evolving policies of censorship and propaganda and in consideration of the national mood in Britain. The paper shows how football went from being a spontaneous and improvised pastime in the early stages of the war to a well organized entertainment by war’s end. The images demonstrate how the war was portrayed as a temporary affair by a confident nation in 1914 to a more resigned acceptance of a semi-permanent event to be endured by 1918; however, all three artworks show that the sporting spirit, and hence the fighting spirit, of the British soldier was intact
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