272 research outputs found
Developing strategic learning alliances: partnerships for the provision of global education and training solutions
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
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
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Comparison of different trap designs for capture of noctuid moths (Lepidoptera: Noctuidae) with pheromone and floral odor attractants
Six trap designs were assessed for capturing noctuid moths in field trials in the UK and Argentina. The traps were baited with either a sex pheromone for Autographa gamma in the UK trials and Helicoverpa gelotopoeon in Argentina, or a floral odor blend. In the UK trials the Universal Trap and a funnel sleeve trap were compared; in Argentina the funnel sleeve trap, a homemade bucket trap, and three sticky traps: LepTrap, wing trap, and delta trap were compared. Comparisons were made between the traps and attractants and captures of noctuid moths and non-target insects. Traps baited with the floral attractant caught a lower number but a wider range of noctuid species including Helicoverpa, Spodoptera, Rachiplusia, Dargida, Mythimna, Chrysodeixis, Agrotis, and Autographa spp, and non-target insects. In the UK trials, the funnel sleeve trap caught significantly more A. gamma than the Universal Trap. The addition of an insecticide to the Universal Trap marginally increased trap catches. In the Argentinian trials, the homemade bucket and the sleeve traps outperformed all sticky traps in most situations regardless of crop environment and attractant type. The homemade bucket and the funnel sleeve traps are also considerably cheaper than the other trap designs. Of the sticky traps the LepTrap caught more noctuids than the wing and delta traps. The results suggest that the bucket trap and the sleeve trap have a much greater maximum capacity and possibly a greater retention efficiency for noctuid moths compared to the sticky traps
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The Right to the Sustainable Smart City
Environmental concerns have driven an interest in sustainable smart cities, through the monitoring and optimisation of networked infrastructures. At the same time, there are concerns about who these interventions and services are for, and who benefits. HCI researchers and designers interested in civic life have started to call for the democratisation of urban space through resistance and political action to challenge state and corporate claims. This paper contributes to an emerging body of work that seeks to involve citizens in the design of sustainable smart cities, particularly in the context of marginalised and culturally diverse urban communities. We present a study involving co- designing Internet of Things with urban agricultural communities and discuss three ways in which design can participate in the right to the sustainable smart city through designing for the commons, care, and biocultural diversity
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Solvent-Free Continuous Operations Using Small Footprint Reactors: A Key Approach for Process Intensification
A solvent-free approach to intensification of chemical processes is reported. This concept, in which reactions are carried out solvent-free, without the need for further downstream processing, was highlighted first with a full reduction of ethyl nicotinate to ethylpiperidine-3-carboxylate under continuous flow conditions. Using a small footprint reactor, a throughput of 26.4 g h–1 was achieved. Similarly, this approach was used for the telescoped two-step synthesis of 2-propyl phenol (productivity 120 g h–1) and 2-propyl cyclohexanone (productivity 30 g h–1), starting from the commercially available allyl phenol ether via Claisen rearrangement and subsequent reduction.We would like to thank Pfizer Worldwide Research & Development (CB), the EPSRC (RJM, SVL, Grant Codes EP/K009494/1, EP/M004120/1 and EP/K039520/1) and the Woolf Fisher Trust (DEF) for financial support.This is the final version of the article. It first appeared from the American Chemical Society via https://doi.org/10.1021/acssuschemeng.6b0028
Chapitre 25 - One Health dans l’élaboration des politiques : une approche intégrée pour traduire la science en politique
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
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?
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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