8 resultados para Scratch

em CentAUR: Central Archive University of Reading - UK


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Purpose – Mergers and acquisitions are among the most intensely used strategic decisions. Yet research by both academics and consulting groups suggests that many mergers and acquisitions fail to add value. On the other hand there are many companies that successfully use mergers and acquisition to grow and add shareholder value. One such company is WPP. The aim of this paper is to explore why WPP has been successful in its acquisition strategy while so many other companies fail. Design/methodology/approach – The paper draws on documentary evidence and a semi-structured interview with Sir Martin Sorrell – Chief Executive and founder of WPP. Research limitations/implications – The case study offers a unique insight into thinking of a successful acquirer and sheds light on how mergers and acquisitions are managed by WPP. However, because of its design the findings are not generalisable. Originality/value – This case study sheds light on how mergers and acquisitions can be used to create a £9 billion company from a standing start. Furthermore, very few case studies offer insight into the thinking of entrepreneurial Chief Executives who established the business, grew it to become the largest and most profitable marketing services company in the world and engineered close to 300 acquisitions.

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Cloud imagery is not currently used in numerical weather prediction (NWP) to extract the type of dynamical information that experienced forecasters have extracted subjectively for many years. For example, rapidly developing mid-latitude cyclones have characteristic signatures in the cloud imagery that are most fully appreciated from a sequence of images rather than from a single image. The Met Office is currently developing a technique to extract dynamical development information from satellite imagery using their full incremental 4D-Var (four-dimensional variational data assimilation) system. We investigate a simplified form of this technique in a fully nonlinear framework. We convert information on the vertical wind field, w(z), and profiles of temperature, T(z, t), and total water content, qt (z, t), as functions of height, z, and time, t, to a single brightness temperature by defining a 2D (vertical and time) variational assimilation testbed. The profiles of w, T and qt are updated using a simple vertical advection scheme. We define a basic cloud scheme to obtain the fractional cloud amount and, when combined with the temperature field, we convert this information into a brightness temperature, having developed a simple radiative transfer scheme. With the exception of some matrix inversion routines, all our code is developed from scratch. Throughout the development process we test all aspects of our 2D assimilation system, and then run identical twin experiments to try and recover information on the vertical velocity, from a sequence of observations of brightness temperature. This thesis contains a comprehensive description of our nonlinear models and assimilation system, and the first experimental results.

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Purpose: Retinoic acid (RA) is a metabolite of vitamin A that plays a fundamental role in the development and function of the human eye. The purpose of this study was to investigate the effects of RA on the phenotype of corneal stromal keratocytes maintained in vitro for extended periods under serum-free conditions. Methods: Keratocytes isolated from human corneas were cultured up to 21 days in serum-free media supplemented with RA or DMSO vehicle. The effects of RA and of its removal after treatment on cell proliferation and morphology were evaluated. In addition, the expression of keratocyte markers was quantified at the transcriptional and protein levels by quantitative PCR and immunoblotting or ELISA, respectively. Furthermore, the effects of RA on keratocyte migration were tested using scratch assays. Results: Keratocytes cultured with RA up to 10×10-6 M showed enhanced proliferation and stratification, and reduced mobility. RA also promoted the expression of keratocyte-characteristic proteoglycans such as keratocan, lumican, and decorin, and increased the amounts of collagen type-I in culture while significantly reducing the expression of matrix metalloproteases 1, 3, and 9. RA effects were reversible, and cell phenotype reverted to that of control after removal of RA from media. Conclusions: RA was shown to control the phenotype of human corneal keratocytes cultured in vitro by regulating cell behaviour and extracellular matrix composition. These findings contribute to our understanding of corneal stromal biology in health and disease, and may prove useful in optimizing keratocyte cultures for applications in tissue engineering, cell biology, and medicine.

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Alkyl esters of p–hydroxybenzoic acid (parabens) are widely used as preservatives in personal care products, foods and pharmaceuticals. Their oestrogenic activity, their measurement in human breast tissue and their ability to drive proliferation of oestrogen-responsive human breast cancer cells has opened a debate on their potential to influence breast cancer development. Since proliferation is not the only hallmark of cancer cells, we have investigated the effects of exposure to parabens at concentrations of maximal proliferative response on migratory and invasive properties using three oestrogen-responsive human breast cancer cell lines (MCF-7, T-47-D, ZR-75-1). Cells were maintained short-term (1 week) or long-term (20±2 weeks) in phenol-red-free medium containing 5% charcoal-stripped serum with no addition, 10-8M 17-oestradiol, 1-5x10-4M methylparaben, 10-5M n-propylparaben or 10-5M n-butylparaben. Long-term exposure (20±2 weeks) of MCF-7 cells to methylparaben, n-propylparaben or n-butylparaben increased migration as measured using a scratch assay, time-lapse microscopy and xCELLigence technology: invasive properties were found to increase in matrix degradation assays and migration through matrigel on xCELLigence. Western immunoblotting showed an associated downregulation of E-cadherin and -catenin in the long-term paraben-exposed cells which could be consistent with a mechanism involving epithelial to mesenchymal transition. Increased migratory activity was demonstrated also in long-term paraben-exposed T-47-D and ZR-75-1 cells using a scratch assay and time-lapse microscopy. This is the first report that in vitro, parabens can influence not only proliferation but also migratory and invasive properties of human breast cancer cells.

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The formation of new blood vessels from the pre-existing vasculature (angiogenesis) is a crucial stage in cancer progression and, indeed, angiogenesis inhibitors are now used as anticancer agents, clinically. Here we have explored the potential of flavonoid derivatives as antiangiogenic agents. Specifically, we have synthesised methoxy and 4-thio derivatives of the natural flavones quercetin and luteolin, two of which (4-thio quercetin and 4-thio luteolin) had never been previously reported. Seven of these compounds showed significant (P<0.05) antiangiogenic activity in an in vitro scratch assay. Their activity ranged from an 86% inhibition of the vascular endothelium growth factor (VEGF)-stimulated migration (observed for methoxyquercetin at 10 µM and for luteolin at 1 µM) to a 36% inhibition (for thiomethoxy quercetin at 10 µM). Western blotting studies showed that most (4 out of 7) compounds inhibited phosphorylation of the VEGF receptor-2 (VEGFR2), suggesting that the antiangiogenic activity was due to an interference with the VEGF/VEGFR2 pathway. Molecular modelling studies looking at the affinity of our compounds towards VEGFR and/or VEGF confirmed this hypothesis, and indeed the compound with the highest antiangiogenic activity (methoxyquercetin) showed the highest affinity towards VEGFR and VEGF. As reports from others have suggested that structurally similar compounds can elicit biological responses via a non-specific, promiscuous membrane perturbation, potential interactions of the active compounds with a model lipid bilayer were assessed via DSC. Luteolin and its derivatives did not perturb the model membrane even at concentrations 10 times higher than the biologically active concentration and only subtle interactions were observed for quercetin and its derivatives. Finally, cytotoxicity assessment of these flavonoid derivatives against MCF-7 breast cancer cells demonstrated also a direct anticancer activity albeit at generally higher concentrations than those required for an antiangiogenic effect (10 fold higher for the methoxy analogues). Taken together these results show promise for flavonoid derivatives as antiangiogenic agents.

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Objectives: The search for agents that are capable of preventing restenosis and reduce the risk of late thrombosis is of utmost importance. In this study we aim to evaluate the in vitro effects of ibuprofen on proliferation and migration of human coronary artery smooth muscle cells (HCASMCs) and on human coronary artery endothelial cells (HCAECs) migration. Methods: Cell proliferation was evaluated by direct cell counting using trypan blue exclusion. Cell migration was assessed by wound healing “scratch” assay and by time lapse video-microscopy. Protein expression was assessed by immunoblotting, and morphological changes were studied by immunocytochemistry. The involvement of the PPARγ pathway was studied with the selective agonist troglitazone, and the use of highly selective antagonists of PPARγ such as PGF2α and GW9662. Results: We demonstrate that ibuprofen inhibits proliferation and migration of HCASMCs and induces a switch in HCASMCs towards a differentiated and contractile phenotype, and that these effects are mediated through the PPARγ pathway. Importantly we also show that the effects of ibuprofen are cell type specific as it does not affect migration and proliferation of endothelial cells. Conclusions: Taken together, our results suggest that ibuprofen could be an effective drug for the development of novel drug eluting stents, which could lead reduced rates of restenosis and potentially other complications of DES stent implantation.

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In an era of fragmenting audience and diversified viewing platforms, youth television needs to move fast and make a lot of noise in order to capture and maintain the attention of the teenage viewer. British ensemble youth drama Skins (E4, 2007-2013) calls attention to itself with its high doses of drugs, chaotic parties and casual attitudes towards sexuality. It also moves quickly, shedding its cast every two seasons as they graduate from school, then renewing itself with a fresh generation of 16 year old characters - three cycles in total. This essay will explore the challenges of maintaining audience connections whilst resetting the narrative clock with each cycle. I suggest that the development of the Skins brand was key to the programme’s success. Branding is particularly important for an audience demographic who increasingly consume their television outside of broadcast flow and essential for a programme which renews its cast every two years. The Skins brand operate as a framework, as the central audience draw, have the strength to maintain audience connections when it ‘graduates’ those characters they identify with at the close of each cycle and starts again from scratch. This essay will explore how the Skins brand constructs a cohesive identity across its multiple generations, yet also consider how the cyclic form poses challenges for the programme’s representations and narratives. This cyclic form allows Skins to repeatedly reach out to a new audience who comes of age alongside each new generation and to reflect shifts in British youth culture. Thus Skins remains ever-youthful, seeking to maintain an at times painfully hip identity. Yet the programme has a somewhat schizophrenic identity, torn between its roots in British realist drama and surrealist comedy and an escapist aspirational glamour that shows the influence of US Teen TV. This combination results in a tendency towards a heightened melodrama at odds with Skins claims for authenticity - its much vaunted teenage advisors and young writers - with the cyclic structure serving to amplify the programme’s excessive tendencies. Each cycle wrestles with a need for continuity and familiarity - partly maintained through brand, aesthetic and setting - yet a desire for freshness and originality, to assert difference from what has gone before. I suggest that the inevitable need for each cycle to ‘top’ what has gone before results in a move away from character-based intimacy and the everyday to high-stakes drama and violence which sits uncomfortably within British youth television.

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The outcome of the UK’s referendum on continued EU membership is at the time of writing uncertain, and the consequences of a vote to remain (‘Bremain’) or leave (‘Brexit’) difficult to predict. Polarised views have been voiced about the impact of Brexit on UK agriculture, and on the nature and level of funding, of future policy. Policymakers would not have the luxury of devising a new policy from scratch. WTO rules and commitments, the nature of any future accord with the EU, budget constraints, the rather different perspectives of the UK’s devolved administrations in Scotland, Wales and Northern Ireland, and the expectations of farmers, landowners and the environmental lobby, will all impact the policymaking process. The WTO dimension, and the UK’s future relationship with the EU, are particularly difficult to predict, and – some commentators believe – may take years to resolve. Brexit’s impact on the future CAP is also unclear. A vote to remain within the EU would not necessarily assuage the Eurosceptics’ criticisms of the EU, or the UK’s perception of the CAP. Whatever the outcome, future agricultural, food and rural land use policies will remain key preoccupations of European governments.