105 research outputs found

    Intrapreneurship and the management of research centre growth in university art and design departments

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    The following is the first paragraph of the abstract: This thesis is an investigation of factors that influence the leadership and management of Research Centres during the early phases of growth. A small number of studies have specifically identified factors such as training, career development and business management but there is a dearth of empirical work to explain the causality of factors during origination, formation and development

    The business of research in art and design: Parallels between research centres and small businesses

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    This article provides a cross-case analysis of four art and design research centres operating within UK universities. Findings from autobiographical and semi-structured interviews with researchers, research managers, and research leaders indicate that they encounter similar issues in trying to establish internal legitimacy within the university alongside the need to gain external support and recognition. In dealing with these challenges, art and design research centres tend to pass through four broadly identifiable phases: (i) Origination (utilising credentials and leadership capacity), (ii) Establishment (securing resources and embedding dedicated systems and processes), (iii) Development (furthering profile, diversifying, and retaining autonomy), and (iv) Sustainability (enhancing research culture, networks, and influence).Many interesting parallels are evident with the way small businesses strive to establish themselves within competitive market environments. Lessons for research managers and directors are explored to consider such similarities in key areas of responsibility that cover leadership, managing people and processes, developing organisational capacity, and building external networks. The research suggests research centre directors must demonstrate many intrapreneurial qualities to overcome obstacles in the development of a successful research team and that university departments can make substantial organisational interventions to help them succeed

    Interpreting Ansiaux's Alexander, Apelles, and Campaspe

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    Includes bibliographical reference

    Tuberous sclerosis complex tumor suppressor–mediated S6 kinase inhibition by phosphatidylinositide-3-OH kinase is mTOR independent

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    The evolution of mitogenic pathways has led to the parallel requirement for negative control mechanisms, which prevent aberrant growth and the development of cancer. Principally, such negative control mechanisms are represented by tumor suppressor genes, which normally act to constrain cell proliferation (Macleod, K. 2000. Curr. Opin. Genet. Dev. 10:81–93). Tuberous sclerosis complex (TSC) is an autosomal-dominant genetic disorder, characterized by mutations in either TSC1 or TSC2, whose gene products hamartin (TSC1) and tuberin (TSC2) constitute a putative tumor suppressor complex (TSC1-2; van Slegtenhorst, M., M. Nellist, B. Nagelkerken, J. Cheadle, R. Snell, A. van den Ouweland, A. Reuser, J. Sampson, D. Halley, and P. van der Sluijs. 1998. Hum. Mol. Genet. 7:1053–1057). Little is known with regard to the oncogenic target of TSC1-2, however recent genetic studies in Drosophila have shown that S6 kinase (S6K) is epistatically dominant to TSC1-2 (Tapon, N., N. Ito, B.J. Dickson, J.E. Treisman, and I.K. Hariharan. 2001. Cell. 105:345–355; Potter, C.J., H. Huang, and T. Xu. 2001. Cell. 105:357–368). Here we show that loss of TSC2 function in mammalian cells leads to constitutive S6K1 activation, whereas ectopic expression of TSC1-2 blocks this response. Although activation of wild-type S6K1 and cell proliferation in TSC2-deficient cells is dependent on the mammalian target of rapamycin (mTOR), by using an S6K1 variant (GST-ΔC-S6K1), which is uncoupled from mTOR signaling, we demonstrate that TSC1-2 does not inhibit S6K1 via mTOR. Instead, we show by using wortmannin and dominant interfering alleles of phosphatidylinositide-3-OH kinase (PI3K) that increased S6K1 activation is contingent upon the suppression of TSC2 function by PI3K in normal cells and is PI3K independent in TSC2-deficient cells

    Tidal dynamics in the Gulf of Maine and New England Shelf : an application of FVCOM

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    Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 116 (2011): C12010, doi:10.1029/2011JC007054.The unstructured-grid, Finite-Volume Community Ocean Model (FVCOM) was used to simulate the tides in the Gulf of Maine (GoM) and New England Shelf (NES) for homogeneous and summer stratified conditions. FVCOM captures the near-resonant nature of the semidiurnal tide and energy flux in the GoM and the complex dynamics governing the tide in the NES. Stratification has limited impact on tidal elevation, but can significantly modify the tidal current profile. Internal tides are energetic in the stratified regions over steep bottom topography, but their contribution to the total tidal energy flux is only significant over the northeast flank of Georges Bank. The model suggests that the tidal flushing-induced eddy east of Monomoy Island is the dynamic basis for the locally observed phase lead of the M2 tide. The southward propagating tidal wave east of Cape Cod encounters the northeastward propagating tidal wave from the NES south of Nantucket Island, forming a zone of minimum sea level along a southeast-oriented line from Nantucket Island. These two waves are characterized by linear dynamics in which bottom friction and advection are negligible in the momentum balance, but their superposition leads to a strong nonlinear current interaction and large bottom stress in the zone of lowest sea elevation.This research is supported by the U.S. GLOBEC Northwest Atlantic/Georges Bank Program NSF (OCE-0234545, 0227679, 0606928, 0726851 and 0814505) to Changsheng Chen and Qixchun Xu and NSF grant (OCE-02-27679) and the WHOI Smith Chair to Robert Beardsley and Richard Limeburner. The tidal model-data comparison on Nantucket Sound/Shoals is partially the result of research sponsored by the MIT Sea Grant College Program, under NOAA grant NA06OAR4170019, MIT SG project 2006-R/RC-102, 2006-R/RC-103, 2006-R/RC-102, 2006-R/RC-107, 2008-R/RC-107), 2010-R/RC-116 and the NOAA NERACOOS Program for the UMASS team. C. Chen’s contribution is also supported by Shanghai Ocean University International Cooperation Program (A-2302-11-0003), the Program of Science and Technology Commission of Shanghai Municipality (09320503700), the Leading Academic Discipline Project of Shanghai Municipal Education Commission (project J50702), and Zhi jiang Scholar and 111 project funds of the State Key Laboratory for Estuarine and Coastal Research, East China Normal University (ECNU).2012-06-1

    Implementation of multimodal computed tomography in a telestroke network : five-year experience

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    Aims: Penumbral selection is best-evidence practice for thrombectomy in the 6-24 hour window. Moreover, it helps to identify the best responders to thrombolysis. Multimodal computed tomography (mCT) at the primary centre—including noncontrast CT, CT perfusion, and CT angiography—may enhance reperfusion therapy decision-making. We developed a network with five spoke primary stroke sites and assessed safety, feasibility, and influence of mCT in rural hospitals on decision-making for thrombolysis. Methods: Consecutive patients assessed via telemedicine from April 2013 to June 2018. Clinical outcomes were measured, and decision-making compared using theoretical models for reperfusion therapy applied without mCT guidance. Symptomatic intracranial hemorrhage (sICH) was assessed according to Safe Implementation of Treatments in Stroke Thrombolysis Registry criteria. Results: A total of 334 patients were assessed, 240 received mCT, 58 were thrombolysed (24.2%). The mean age of thrombolysed patients was 70 years, median baseline National Institutes of Health Stroke Scale was 10 (IQR 7-18) and 23 (39.7%) had a large vessel occlusion. 1.7% had sICH and 3.5% parenchymal hematoma. Three months poststroke, 55% were independent, compared with 70% in the non-thrombolysed group. Conclusion: Implementation of CTP in rural centers was feasible and led to high thrombolysis rates with low rates of sICH. © 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd

    p53 modeling as a route to mesothelioma patients stratification and novel therapeutic identification

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    Background Malignant pleural mesothelioma (MPM) is an orphan disease that is difficult to treat using traditional chemotherapy, an approach which has been effective in other types of cancer. Most chemotherapeutics cause DNA damage leading to cell death. Recent discoveries have highlighted a potential role for the p53 tumor suppressor in this disease. Given the pivotal role of p53 in the DNA damage response, here we investigated the predictive power of the p53 interactome model for MPM patients’ stratification. Methods We used bioinformatics approaches including omics type analysis of data from MPM cells and from MPM patients in order to predict which pathways are crucial for patients’ survival. Analysis of the PKT206 model of the p53 network was validated by microarrays from the Mero-14 MPM cell line and RNA-seq data from 71 MPM patients, whilst statistical analysis was used to identify the deregulated pathways and predict therapeutic schemes by linking the affected pathway with the patients’ clinical state. Results In silico simulations demonstrated successful predictions ranging from 52 to 85% depending on the drug, algorithm or sample used for validation. Clinical outcomes of individual patients stratified in three groups and simulation comparisons identified 30 genes that correlated with survival. In patients carrying wild-type p53 either treated or not treated with chemotherapy, FEN1 and MMP2 exhibited the highest inverse correlation, whereas in untreated patients bearing mutated p53, SIAH1 negatively correlated with survival. Numerous repositioned and experimental drugs targeting FEN1 and MMP2 were identified and selected drugs tested. Epinephrine and myricetin, which target FEN1, have shown cytotoxic effect on Mero-14 cells whereas marimastat and batimastat, which target MMP2 demonstrated a modest but significant inhibitory effect on MPM cell migration. Finally, 8 genes displayed correlation with disease stage, which may have diagnostic implications. Conclusions Clinical decisions related to MPM personalized therapy based on individual patients’ genetic profile and previous chemotherapeutic treatment could be reached using computational tools and the predictions reported in this study upon further testing in animal models

    Maria Cosway’s Hours: Cosmopolitan and Classical Visual Culture in Thomas Macklin’s Poets Gallery

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    Thomas Macklin’s Gallery of Poets opened at the Mitre Tavern in Fleet Street in 1788 with the aim to ‘display British Genius’ through ‘Prints Illustrative of the Most Celebrated British Poets’. Early newspaper coverage promised ‘a monument of the powers of the pencil in England, as the Vatican is at Rome’. The incongruous juxtaposition between Fleet Street and the Vatican spells out the cosmopolitan ambition of the literary gallery phenomenon through its real and imagined geographies of display. Through the format of the paper gallery of prints, Macklin’s Poets offered the inventions of British Poets as a repository of painting. This chapter examines how the cosmopolitan idiom of the paper gallery is negotiated in the first number of Macklin’s Poets. This essay examines the extent to which this ambition was achieved in the first Number of Macklin’s Poets which carried an engraving of Maria Cosway’s The Hours, originally a painting with an impressively European iconographic heritage. The painting was first exhibited at the Royal Academy in 1783, and was retroactively associated by Macklin with Thomas Gray’s ‘Ode on the Spring’. The trope of the Hours brought with it a weighty provenance derived from classical marble bas-relief, through the antiquarian pages of Pietro Santi Bartoli and Bernard de Montfaucon to Flaxman’s designs for Wedgwood plaques and vases. Cosway’s name also imported into Gray’s poem her reputation as a cosmopolitan, cultured woman who had completed the Grand Tour and who moved in elite circles including those of the Prince of Wales in London and the Duke of Orleans, Pierre d’Hancarville and Thomas Jefferson in Paris. The iconographies of the painting, the print, and the poem articulate a European cosmopolitan tradition for British Art
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