18,031 research outputs found

    Sexuality, Identity and the Clothed Male Body

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    ‘Sexuality, Identity and the Clothed Male Body’ is a PhD by Published Work that draws together a collective body of work that deals specifically and significantly with the dressed male body. This thesis presents a case for the collection of publications included in the submission to be viewed as a coherent body of work which makes a contribution to knowledge in the fields of fashion studies and cultural studies, in which the works are situated. The body of work consists of two monographs - Don We Now Our Gay Apparel: Gay Men’s Dress in the Twentieth Century (Berg, 2000), and The Story of Men’s Underwear (Parkstone International Press, 2010) - and two chapters in edited books - ‘Butch Queens in Macho Drag: Gay Men, Dress and Subcultural Identity’ (2008) and ‘Hair and Male (Homo)Sexuality: Up-Top and Down Below’ (2008). Through an examination of the major themes addressed throughout the submitted body of work – sexuality, identity, subcultural formation, men’s dress and masculinities and clothes and the body - this thesis demonstrates that the published work contributes to knowledge through its two major foci. Firstly, the means by which gay men have utilised their dressed bodies as a situated and embodying practice to articulate identity, masculinity, and social and sexual interaction, and secondly an examination of men’s underwear’s specific function in the covering, exposing and representation of men’s bodies. These were, until recently, relatively neglected areas of fashion studies and dress history, and by explicitly bringing together these areas to present a comprehensive investigation this thesis serves to provide a new contribution to knowledge in these areas. Taking an interdisciplinary approach, that is common in both fashion studies and cultural studies, the specific combination of research methods that is employed throughout the body of work, has provided a unifying element that further enhances this contribution to knowledge

    The ownership of goods and cultures of consumption in Ludlow, Hereford and Tewkesbury, 1660-1760

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    A thesis submitted in fulfilment of the requirements of the University of Wolverhampton for the degree of Doctor of PhilosophyThis thesis examines how the lifestyles of the middling sorts evolved during the period 1660 and 1760 as reflected in their relationship to material goods in three contrasting, but geographically near towns. The towns are similar to the degree that their history and circumstances led to them being viewed as backwaters, and this may have influenced consumption practices. Ludlow had lost its importance as the Capital of Wales; it stagnated until its fortunes began to be revived by achieving leisure town status. Hereford was a cathedral city and a county town, but was mainly poorly built and congested. It was locally, rather than nationally important. Tewkesbury was an inland port and a manufacturing centre, but it had been eclipsed by the larger and more successful cities of Bristol and Gloucester. This study of household goods in the middling interiors of Ludlow, Hereford and Tewkesbury between 1660 and 1760 set out first to investigate the extent to which the possessions of the middling ranks reflected their social status. The second aspect is to analyse the geographical spread of new goods in the three towns to determine the extent to which economic circumstances and location influenced consumption. Thirdly, the intention is to determine how status and politeness was expressed in the early modern home. Finally, this study aimed to ascertain what these factors could tell us about early modern consumers in the three towns. A sample of the domestic goods of the middling ranks from Ludlow, Hereford and Tewkesbury is examined and compared. The material culture of the three towns has previously attracted little academic interest. It is my intention that this thesis on the three towns complements and contributes to the existing bodies of work on early modern regional culture studies

    Novel modulation of p53 activity in thyroid cancer

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    Thyroid cancer is responsible for more deaths than all other endocrine cancers combined, and its incidence is rising. In contrast to other cancers, thyroid carcinomas rarely display mutations in p53. p53 is a potent tumour suppressor, and serves to inhibit cell transformation. Interestingly, the thyroid gland is also sensitive to the effects of ionising radiation, where WT p53 would normally play a protective role. However, there is evidence to suggest that aberrant expression of cellular oncogenes can result in the functional inactivation of WT p53. PBF is a proto-oncogene found to be overexpressed in thyroid tumours. PBF overexpression causes transformation in vitro and tumourigenesis in vivo. Work within this thesis describes the functional relationship between PBF and p53 in thyroid cancer. We provide evidence for a direct interaction between PBF and p53 in thyroid cancer cells, and our data demonstrate that oncogenic expression of PBF adversely affects p53 homeostasis by increasing its degradation, with PBF potentially serving as a co-factor in a complex with p53 and HDM2. Surprisingly, PBF had no effect on p53-mediated transcription using focused microarrays. Nonetheless, overexpression of PBF conferred a significant survival advantage following DNA damage, indicating that PBF might potentially facilitate neoplastic growth and tumourigenesis. Besides regulation of transcription, p53 performs a wide range of biological functions. PBF may therefore serve to promote p53 inactivation independently of its role as a transcription factor. Overall, these data indicate that oncogenic expression of PBF may result in a novel mechanism of p53 inactivation, where PBF binds to p53 and accelerates its degradation in complex with HDM2. These events cause an increase in cell survival following DNA damage, thereby potentially promoting tumourigenesis in thyroid cancers expressing WT p53

    Shakespeare and contemporary adaptation: the graphic novel

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    This thesis examines the process of adaptation of Shakespeare’s plays into the graphic novel medium. It traces the history of these adaptations from the first comic books produced in the mid-twentieth century to graphic novels produced in the twenty-first century. The editions used for examination have been selected as they are indicative of key developments in the history of adaptation of Shakespeare’s plays into the medium. This thesis explores how the plays are presented and the influences on the styles of presentation. It traces the history of the form and how the adaptations have been received in various periods. It also examines how the combination of illustrations and text and the conventions of the medium produce unique narrative capacities, how these have developed over time and how they used to present the plays. Sales data of Shakespeare graphic novels is presented and analysed to reveal the target audience is the education sector which in turn drives the publisher’s promotion of the authenticity and fidelity of their editions. How authenticity is claimed and invoked in the adaptation into graphic novels is also examined

    Regulation of the ATR signalling pathway by Adenovirus

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    Ad5 and Ad12 inhibit ATR-dependent Chk1 phosphorylation. Ad5 E4orf3 promotes the relocalization of the MRN complex in order to inhibit Chk1 activation during infection, whereas Ad12 E4orf3 is unable to inactivate MRN by this method. Here we show that Ad12 inhibits Chk1 phosphorylation by targeting TopBP1, Timeless and Tipin for degradation. We have determined that Ad12 E4orf6 associates with the cellular Cul2-containing ubiquitin ligase to promote TopBP1 degradation. We have shown that Ad5 and Ad12 differentially activate Cullin-containing ubiquitin ligase complexes during infection. Furthermore, we have also determined that Ad12 E4orf3 promotes the degradation of Timeless and Tipin in an Ad12E1B-55k/E4orf6-independent, and Cul2-dependent fashion, during infection. Previous research from our laboratory identified WDR62 as possible E1B-55K interacting protein. The second aim of this study was to expand our current knowledge of this protein and determine its role during infection. Here we show that E1B-55K interacts with WDR62 in vivo and colocalizes with it at centrosomes. We also provide evidence to show that WDR62 functions in the cellular DNA damage response. Indeed, cells depleted of WDR62 by RNA interference resulted in a UV-sensitive phenotype, defects in ATR activation and G2/M checkpoint control, as well as displaying supernumerary centrosome during mitosis

    The Role of the JNK/AP-1 Pathway in the Induction of iNOS and CATs in Vascular Cells

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    Nitric oxide (NO) is an important biological molecule within the body, which over production of this molecule in response to different stimulations can cause various inflammatory diseases. Over production of this molecule is caused by the induction of the inducible nitric oxide synthase (iNOS) enzyme. This enzyme uses L-arginine as a substrate and therefore the presence and transport of this amino acid into the cells can be a key factor in regulating NO over production. Different signalling mechanisms have been implicated in the regulation of this pathway and one of which involves the Mitogen Activated Protein Kinases (MAPK). This family of proteins respond to inflammatory conditions and may mediate effects induced by inflammatory mediators. Of the MAPKs, the role of the c-Jun-N-terminal kinase (JNK) pathway in the induction of iNOS is still controversial. JNK and its downstream target, the transcription factor Activator Protein-1 (AP-1), have shown contradictory effects on iNOS induction leading to controversies over their role in regulating iNOS expression in different cell systems or with various stimuli. The studies described in this thesis have determined the role of JNK/AP-1 on iNOS expression, NO production, L-arginine uptake and also on the transporters responsible for L-arginine transport into the cells. The studies were carried out in two different cell types: rat aortic smooth muscle cells (RASMCs) and J774 macrophages which are both critically associated with the over production of NO in vascular inflammatory disease states. The first approach was to block the expression of the inducible L-arginine-NO pathway using SP600125 and JNK Inhibitor VIII which are both pharmacological inhibitors of JNK. The results from these studies showed that the pharmacological intervention was without effect in RASMCs, but inhibited iNOS, NO and L-arginine transport in J774 macrophages. In contrast, the molecular approach employed using two dominant negative constructs of AP-1 (TAM-67 and a-Fos) revealed a different profile of effects in RASMCs, where a-Fos caused an induction in iNOS and NO while TAM-67 had an inhibitory effect on iNOS, NO, L-arginine transport and CAT-2B mRNA expression. The latter was unaffected in RASMCs but suppressed in J774 macrophages by SP600125. Examination of JNK isoforms expression showed the presence of JNK1 and 2 in both cell systems. Moreover, stimulation with LPS/IFN- or LPS alone resulted in JNK phosphorylation which did not reveal any difference between smooth muscle cells and macrophages. In contrast, expression and activation of AP-1 subunits revealed differences between the two cell systems. Activation of cells with LPS and IFN- (RASMCs) or LPS alone (J774 macrophages) resulted in changes in the activated status of the different AP-1 subunit which was different for the two cell systems. In both cell types c-Jun, JunD and Fra-1 were increased and in macrophages, FosB activity was also enhanced. Inhibition of JNK with SP600125 caused down-regulation in c-Jun in both cell types. Interestingly this down-regulation was in parallel with increases in the subunits JunB, JunD, c-Fos and Fra-1 in RASMCs or JunB and Fra-1 in J774 macrophages. Since, SP600125 was able to exert inhibitory effects in the latter cell type but not in RASMCs, it is possible that the compensatory up-regulation of certain AP-1 subunits in the smooth muscle cells may compensate for c-Jun inhibition thereby preventing suppression of iNOS expression. This notion clearly needs to be confirmed but it is potentially likely that hetero-dimers formed between JunB, JunD, c-Fos and Fra-1 could sustain gene transcription in the absence of c-Jun. The precise dimer required has not been addressed but unlikely to exclusively involve JunB and Fra-1 as these are up-regulated in macrophages but did not sustain iNOS, NO or induced L-arginine transport in the presence of SP600125. To further support the argument above, the dominant negatives caused varied effects on the activation of the different subunits. a-Fos down-regulated c-Jun, c-Fos, FosB, Fra-1 whereas TAM-67 reduced c-Jun and c-Fos but marginally induced Fra-1 activity. Associated with these changes was an up-regulation of iNOS-NO by a-Fos and inhibition by TAM-67. Taken together, the data proposes a complex mechanism(s) that regulate the expression of the inducible L-arginine-NO pathway in different cell systems and the complexity may reflect diverse intracellular changes that may be different in each cell type and not always be apparent using one experimental approach especially where this is pharmacological. Moreover, these findings strongly suggest exercising caution when interpreting pure pharmacological findings in cell-based systems particularly where these are inconsistent or contradictory

    Computational Model-Based Functional Magnetic Resonance Imaging of Reinforcement Learning in Humans

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    The aim of this thesis is to determine the changes in BOLD signal of the human brain during various stages of reinforcement learning. In order to accomplish that goal two probabilistic reinforcement-learning tasks were developed and assessed with healthy participants by using functional magnetic resonance imaging (fMRI). For both experiments the brain imaging data of the participants were analysed by using a combination of univariate and model–based techniques. In Experiment 1 there were three types of stimulus-response pairs where they predict either a reward, a neutral or a monetary loss outcome with a certain probability. The Experiment 1 tested the following research questions: Where does the activity occur in the brain for expecting and receiving a monetary reward and a punishment ? Does avoiding a loss outcome activate similar brain regions as gain outcomes and vice a verse does avoiding a reward outcome activate similar brain regions as loss outcomes? Where in the brain prediction errors, and predictions for rewards and losses are calculated? What are the neural correlates of reward and loss predictions for reward and loss during early and late phases in learning? The results of the Experiment 1 have shown that expectation for reward and losses activate overlapping brain areas mainly in the anterior cingulate cortex and basal ganglia but outcomes of rewards and losses activate separate brain regions, outcomes of losses mainly activate insula and amygdala whereas reward activate bilateral medial frontal gyrus. The model-based analysis also revealed early versus late learning related changes. It was found that predicted-value in early trials is coded in the ventro-medial orbito frontal cortex but later in learning the activation for the predicted value was found in the putamen. The second experiment was designed to find out the differences in processing novel versus familiar reward-predictive stimuli. The results revealed that dorso-lateral prefrontal cortex and several regions in the parietal cortex showed greater activation for novel stimuli than for familiar stimuli. As an extension to the fourth research question of Experiment 1, reward predictedvalues of the conditional stimuli and prediction errors of unconditional stimuli were also assessed in Experiment 2. The results revealed that during learning there is a significant activation of the prediction error mainly in the ventral striatum with extension to various cortical regions but for familiar stimuli no prediction error activity was observed. Moreover, predicted values for novel stimuli activate mainly ventro-medial orbito frontal cortex and precuneus whereas the predicted value of familiar stimuli activates putamen. The results of Experiment 2 for the predictedvalues reviewed together with the early versus later predicted values in Experiment 1 suggest that during learning of CS-US pairs activation in the brain shifts from ventro-medial orbito frontal structures to sensori-motor parts of the striatum

    Constraints on a Minimal Hidden Photon with Kaluza-Klein Excitations in Large Extra Dimensions

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    The major purpose of this work is to combine the minimal-hidden-photon model with Large Extra Dimensions (LED). This involves confining the Standard- Model photon to a 3-brane, whilst allowing the hidden photon and graviton to occupy the higher-dimensional bulk. After integrating out the extra dimensions both the hidden photon and graviton obtain a tower of massive Kaluza-Klein (KK) modes. The Standard-Model photon obtains no KK modes, in accordance with experiment. The work begins with a discussion of the minimal hidden photon with-out KK modes, including the current constraints. In most cases existing constraints are simply quoted or rederived, but for some experiments original constraints are produced. For example new constraints from atomic spectra are produced. Significant modifications are also made to the published constraint from the SN1987a energy-loss experiment. This means properly accounting for the plasma mass of the electron, and also accounting for the modification of the kinetic-mixing parameter in a plasma. Finally constraints are produced for the minimal-hidden-photon model with KK modes

    Receptivity and transition to turbulence of supersonic boundary layers with surface roughness

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    A deeper understanding of the different factors that influence the laminar-turbulent transition in supersonic boundary layers will help the design of efficient high-speed vehicles. In this work we study the effects of surface roughness on the stability and transition to turbulence of supersonic boundary layers. The investigation is carried out by direct numerical simulations (DNS) of the compressible Navier-Stokes equations and focuses on the modifications introduced in the transition process by localised roughness elements, for Mach numbers M? = 6.0 and M? = 2.5, and distributed slender pores at M? = 6.0. The first part of the investigation into the effects of localised roughness deals with the receptivity and initial exponential amplification of disturbances in boundary layers subjected to small external perturbations. Different transition scenarios are investigated by considering different free-stream disturbances and roughness elements with different heights. The results show that, for roughness heights approaching the local displacement thickness, transition is dominated by the growth of a number of instability modes in the roughness wake. These modes are damped by wall cooling and their receptivity is found to be more efficient in the case of free-stream disturbances dominated by sound. At M? = 6 the growth of Mack modes in the boundary layer is found to play a crucial role in the excitation of the most unstable wake modes. An investigation into the nonlinear stages of transition shows that the breakdown to turbulence starts with nonlinear interactions of the wake instability modes. This leads to the formation of a turbulent wedge behind the roughness element, which spreads laterally following mechanisms similar to those observed for the evolution of compressible turbulent spots. An oblique shock impinging on the transitional boundary layer significantly accelerates the breakdown process and leads to a wider turbulent wedge. The study ends with an analysis of porous walls as a passive method for transition control, which is carried out using a temporal DNS approach. The results show damping of both the primary, of second or Mack mode type, and secondary instabilities and indicate that, despite the high Mack number, first mode waves regain importance in this modified transition scenario
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