271 research outputs found

    Contributing to the creative economy imaginary: universities and the creative sector

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    © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group. This paper explores the relationship between the creative economy and universities. As funders, educators and research bodies, universities have a complicated relationship with the creative economy. They propagate its practice, ‘buying-in’ to the rhetoric and models of creative value, particularly in teaching, research and knowledge exchange. Third mission activities also play a role, seeking to affect change in the world ‘outside’ academia through collaboration, partnerships, commercialisation and social action. For arts and humanities disciplines, these practices have focused almost exclusively on the creative sector in recent years. This paper asks how the third mission has been a site where universities have modified their function in relation to the creative economy. It considers the mechanisms by which universities have been complicit in propagating the notion of the creative economy, strengthening particular constructions of the idea at the level of policy and everyday practice. It also briefly asks how a focus on alternative academic practice and institutional forms might offer possibilities for developing a more critical creative economy. The argument made is that the university sector is an important agent in the shaping and performance of the creative economy, and that we should take action if we wish to produce a more diverse, equitable space for learning, researching, and being under the auspices of ‘creativity’

    A CRISPR Dropout Screen Identifies Genetic Vulnerabilities and Therapeutic Targets in Acute Myeloid Leukemia

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    Acute myeloid leukemia (AML) is an aggressive cancer with a poor prognosis, for which mainstream treatments have not changed for decades. To identify additional therapeutic targets in AML, we optimize a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening platform and use it to identify genetic vulnerabilities in AML cells. We identify 492 AML-specific cell-essential genes, including several established therapeutic targets such as DOT1L\textit{DOT1L}, BCL2\textit{BCL2}, and MEN1\textit{MEN1}, and many other genes including clinically actionable candidates. We validate selected genes using genetic and pharmacological inhibition, and chose KAT2A\textit{KAT2A} as a candidate for downstream study. KAT2A\textit{KAT2A} inhibition demonstrated anti-AML activity by inducing myeloid differentiation and apoptosis, and suppressed the growth of primary human AMLs of diverse genotypes while sparing normal hemopoietic stem-progenitor cells. Our results propose that KAT2A inhibition should be investigated as a therapeutic strategy in AML and provide a large number of genetic vulnerabilities of this leukemia that can be pursued in downstream studies.This work was funded by the Kay Kendall Leukaemia Fund (KKLF) and the Wellcome Trust (WT098051). G.S.V. is funded by a Wellcome Trust Senior Fellowship in Clinical Science (WT095663MA) and work in his laboratory is funded by Bloodwise. C.P. is funded by a Kay Kendall Leukaemia Fund Intermediate Fellowship (KKL888)

    Loss of Rassf1a cooperates with Apc(Min) to accelerate intestinal tumourigenesis

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    Promoter methylation of the RAS-association domain family 1, isoform A gene (RASSF1A) is one of the most frequent events found in human tumours. In this study we set out to test the hypothesis that loss of Rassf1a can co-operate with inactivation of the adenomatous polyposis coli (Apc) gene to accelerate intestinal tumourigenesis using the Apc-Min (Apc(Min/+)) mouse model, as mutational or deletional inactivation of APC is a frequent early event in the genesis of intestinal cancer. Further, loss of RASSF1A has also been reported to occur in premalignant adenomas of the bowel. RASSF1A has been implicated in an array of pivotal cellular processes, including regulation of the cell cycle, apoptosis, microtubule stability and most recently in the β-catenin signalling pathway. By interbreeding isoform specific Rassf1a knockout mice with Apc(+/Min) mice we showed that loss of Rassf1a results in a significant increase in adenomas of the small intestine and accelerated intestinal tumourigenesis leading to the earlier death of adenocarcinoma-bearing mice and decreased overall survival. Comparative genomic hybridization of adenomas from Rassf1a(−/−); Apc(+/Min) mice revealed no evidence of aneuploidy or gross chromosomal instability (no difference to adenomas from Rassf1a(+/+); Apc(+/Min) mice). Immunohistochemical analysis of adenomas revealed increased nuclear β-catenin accumulation in adenomas from Rassf1a(−/−); Apc(+/Min) mice, compared to those from Rassf1a(+/+); Apc(+/Min) mice, but no differences in proliferation marker (Ki67) staining patterns. Collectively these data demonstrate co-operation between inactivation of Rassf1a and Apc resulting in accelerated intestinal tumourigenesis, with adenomas showing increased nuclear accumulation of β-catenin, supporting a mechanistic link via loss of the known interaction of Rassf1 with β-TrCP that usually mediates degradation of β-catenin

    Talking alone : Reality TV, emotions and authenticity

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    This article examines reality TV as an illustration of contemporary confessional culture in which the key attraction is the disclosure of true emotions. This article hopes to contribute to the understanding of the production of self-disclosure through a formal analysis of international and domestic dating, adventure and lifestyle-oriented reality shows broadcast on Finnish television between 2002 and 2004. The diverse programmes verify that reality TV shows capitalize on a variety of talk situations within one programme, but it is the monologue that is used as a truth-sign of direct access to the authentic. We also suggest that the power of monologue in the reality genre promotes the transformation of television from a mass medium to first-person medium addressing masses of individuals.Peer reviewe

    Lowering β-Amyloid Levels Rescues Learning and Memory in a Down Syndrome Mouse Model

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    β-amyloid levels are elevated in Down syndrome (DS) patients throughout life and are believed to cause Alzheimer's disease (AD) in adult members of this population. However, it is not known if β-amyloid contributes to intellectual disability in younger individuals. We used a γ-secretase inhibitor to lower β-amyloid levels in young mice that model DS. This treatment corrected learning deficits characteristic of these mice, suggesting that β-amyloid-lowering therapies might improve cognitive function in young DS patients

    Kita Driven Expression of Oncogenic HRAS Leads to Early Onset and Highly Penetrant Melanoma in Zebrafish

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    Melanoma is the most aggressive and lethal form of skin cancer. Because of the increasing incidence and high lethality of melanoma, animal models for continuously observing melanoma formation and progression as well as for testing pharmacological agents are needed.Using the combinatorial Gal4-UAS system, we have developed a zebrafish transgenic line that expresses oncogenic HRAS under the kita promoter. Already at 3 days transgenic kita-GFP-RAS larvae show a hyper-pigmentation phenotype as earliest evidence of abnormal melanocyte growth. By 2-4 weeks, masses of transformed melanocytes form in the tail stalk of the majority of kita-GFP-RAS transgenic fish. The adult tumors evident between 1-3 months of age faithfully reproduce the immunological, histological and molecular phenotypes of human melanoma, but on a condensed time-line. Furthermore, they show transplantability, dependence on mitfa expression and do not require additional mutations in tumor suppressors. In contrast to kita expressing melanocyte progenitors that efficiently develop melanoma, mitfa expressing progenitors in a second Gal4-driver line were 4 times less efficient in developing melanoma during the three months observation period.This indicates that zebrafish kita promoter is a powerful tool for driving oncogene expression in the right cells and at the right level to induce early onset melanoma in the presence of tumor suppressors. Thus our zebrafish model provides a link between kita expressing melanocyte progenitors and melanoma and offers the advantage of a larval phenotype suitable for large scale drug and genetic modifier screens

    Negotiating the modern cross-class ‘model home’:domestic experiences in Basil Spence’s Claremont Court

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    This article investigates the spatial articulation of architecture and home through the exploration of current domestic experiences in Basil Spence’s Claremont Court housing scheme (1959-1962), Edinburgh. How architecture and home are both idealized and lived is the backdrop for a discussion that draws on the concept of “model home,” or physical representation of a domestic ideal. The article reads Claremont Court as an architectural prototype of the modern domestic ideal, before exploring its reception by five of its households through the use of visual methods and semistructured interviews. Receiving the model home involves negotiating between ideal and lived homes. Building on this idea, the article contributes with a focus on the spatiality of such reception, showing how it is modulated according to the architectural affordances that the “model home” represents. The article expands on scholarship on architecture and home with empirical evidence that argues the reciprocal spatiality of home

    The Longitudinal Relationship Between Satisfaction with Transitional Care and Social and Emotional Quality of Life Among Chronically Ill Adolescents

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    This study aimed to identify the relationship between satisfaction with transitional care and quality of life of chronically ill adolescents over time. This longitudinal study included adolescents with type I diabetes, juvenile idiopathic arthritis (JIA), and neuromuscular disorders (NMD). At baseline 138 respondents (response rate 31 %) filled in a questionnaire and 188 about 1 year later (response rate 43 %). Analysis of variance showed that adolescents with diabetes reported the highest physical quality of life, followed in order by those with NMD and JIA (p ≤ 0.01). Adolescents with diabetes reported the highest social quality of life, followed in order by those with JIA and NMD (both at p ≤ 0.001). Univariate analyses showed that satisfaction with transitional care at T0 was significantly related to emotional and physical quality of life at T1 (both at p ≤ 0.05). At T1, satisfaction with transitional care was significantly related to the emotional, physical, and social domains of quality of life (all at p ≤ 0.001). Multiple regression analyses revealed that satisfaction with transitional care at T1 was related to emotional (β -0.20; p ≤ 0.05) and social (β -0.35; p ≤ 0.01) quality of life domains over time. This indicates that lower gap scores, which measured differences between 'best care' and 'current care,' are associated with better social and emotional quality of life in this sample of adolescents. Satisfaction with transitional care and social and emotional quality of life are related over time
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