VictorJuiz/thesis huggingface dataset:
Exploring the effects of symmetric arginine methylation readers on E2F1- dependent transcriptional output in vitro
Keywords: cell cycle control
apoptosis
cancer
E2F1
arginine methylation

E2F1 plays contrasting biological roles in both cellular proliferation and apoptosis. Recent studies have demonstrated that residue-specific arginine dimethylation marks deposited by PRMT1 and PRMT5 mediate the apoptotic and proliferative activity of E2F1 respectively. Two readers of the proliferative symmetric arginine dimethylation mark deposited by PRMT5 on E2F1 have since been identified: TSN and TDRD1. In this study, qRT-PCR analysis was used to validate the deregulation of candidate genes in response to TSN or TDRD1 knockdown in MCF7, SKBR3 and DuCaP cells. Transient siRNA co-depletion of readers along with E2F1 confirmed that the deregulation observed was achieved in an E2F1-mediated manner in MCF7 and SKBR3 cellular backgrounds. Furthermore, ChIP analysis revealed that the levels of E2F1 binding to target promoters were affected by reader knockdown. Moreover, E2F1-dependent and -independent recruitment of TSN was confirmed on the promoters of target genes in MCF7 cells. In addition to direct transcriptional effects, analysis of the splice variant expression of several target genes revealed that E2F1 could potentially play a role in TSN-associated splicing activity. The results obtained from this study implicate TSN and TDRD1 in mediating the proliferative activity of E2F1 through proposed regulatory roles in the transcription and alternative splicing of E2F1 targets. This study thus refines our current understanding of how symmetric arginine dimethylation mediates E2F1 proliferative activity, and forms the foundation for further research to strengthen and establish the mechanistic bridge between TSN, TDRD1 and the E2F1 symmetric arginine dimethylation mark.
Is Drosophila song amplitude structure a communication signal?
Keywords: signal
Amplitude
Drosophila
Modelling
SAS
Structure
Song
communication

Drosophila courtship song has been studied for over 60 years and remains an area of active research today. Several studies have investigated the physiological mechanisms for fly song production, but no unifying account exists. We review fly song production and integrate published data to a mathematical model of courtship song production.
We hypothesize that muscle dynamics underlie fluctuations in the amplitude of courtship song. Our model suggests that these fluctuations can be measured and we introduce the term 'song amplitude structure' (SAS) for those measurements. We predict that SAS signals muscle power and we validate our prediction in muscle mutants of the Drosophila myosin light chain (Dmlc2) gene.
We then investigate whether SAS is a communication signal in Drosophila. We show that the two species D. melanogaster and D. simulans differ in their SAS and that both females and males behaviourally discriminate their species SAS from other SAS. This suggests that SAS is a communication signal in Drosophila.
Perception of SAS may be affected by noise and we therefore examine the effect of noise on responses to SAS. We find that female auditory responses are not impaired by noise in SAS, however male auditory responses are impaired by noise in SAS. This suggests that males and females may be processing noise in SAS differently. Future work should investigate whether sexually dimorphic auditory neurons respond differently to noise in SAS.
We hope that our work will be helpful for investigating fluctuations in amplitude of fly song. We also wish that researchers can use our work for studying the mechanisms underlying both the production of SAS and the perception of SAS.
Soaring and gust response in the Steppe Eagle
Keywords: birds
soaring
flight
turbulence

This thesis explores how onboard instrumentation can be used to study how birds interact with the atmosphere, in particular to understand their soaring strategies and gust response mechanisms. The instrumentation unit consists of integrated sensors, including a GPS, IMU (inertial measurement unit) and pressure transducer, which provide accurate, high frequency measurements of the aerodynamics and kinematics of a free flying bird. The equipment development and derivation of parameters are initially presented. The data recorded from multiple flights of a steppe eagle (Aquila nipalensis) are then used to analyse the different aspects of its soaring flight throughout the rest of the thesis.
First, the occurrence and mechanism of the wing tuck manoeuvre is investigated and found to be a gust response, precipitated by a drop in aerodynamic loading. It is suggested that this reduction in loading results in a moment imbalance on the wings, and that ultimately the wings are pulled down by an internal musculoskeletal moment. The bird's slope soaring behaviour is then studied by using CFD analysis to model the local updrafts for comparison with the bird's performance. The analysis shows that the bird predominantly flew in the regions of strongest updraft along the ridge but did not attempt to maximise gravitational potential energy. This leads to gliding flight and a review of the theoretical derivation of the classic glide polar. A sensitivity analysis of the polar to different drag coeffcients highlights the need for more research into the selection of suitable values. The development of a new 'soaring optimisation' chart to include the effect of wind conditions on the selection of best glide speed is presented. This is then compared with experimental glide data from the bird and used to determine the optimal drag coeffcients for the polar model. Finally, a technique is developed for automatically identifying sections of thermalling flight and for removing the wind drift component to allow us to test thermalling behaviour. This exploratory analysis highlights the complexity of the flow structure within the thermal and the distinctly unsteady circling of the bird.
Fantasies of authenticity, anxieties of culture: global capital, entertainment and cultural nationalism in the contemporary popular cinemas of India and China since 1990
Keywords: Contemporary Motion Pictures
Contemporary India
Comparative Studies
Contemporary Cinema
Contemporary Film
Contemporary China

My thesis is dedicated to the study of popular, commercial cinema as a force within the discourse of national and personal identity in the rapidly changing mega-economies of India and China, and their diasporas, since the watershed year of 1990. Its purpose is to reveal the unique pattern of like and unlike that exists between the "Social Representations" (Serge Moscovici 2000) of contemporary India and China on screen through a juxtapositional comparative approach, close visual analysis, and the development of original theoretical tools. Tense networks of fantasy and anxiety emerge as popular culture actively circulates their shared experiences of changing global status, uneven economic growth (Gong Haomin 2012), and social change. Transnational subjects, Hua and Desi, arrive on screen ready to carve out culturally inflected modernities, in search of "tradition" and "values" to suit contemporary cultural-nations-beyond-borders.
I treat film as consumer product, diegetic entity, and text: hence narrative, visual, linguistic and contextual aspects of over fourteen popular commercial films ("Bollywood" and "Yulepian" 娱乐片), are explored. My analysis comprises two interlocking halves: the first two chapters focus chiefly on identities - Hua and Desi, and diasporic persons. The former, conduits for the cultural nation to re-think modernity, the latter a dreamed vanguard of "claim-staking" ethnicised global consumers, defenders of the cultural nation in the "host" country. Chapters Three and Four focus on genres - comedy and history films. Through comedy, these films create state-serving heterotopias or challenge the status quo; perhaps they build cultural nationalist mythos, or lace cynical questions through lavish history film. To understand internecine relationships between economics, society and the imagination, entertainment film cannot be dismissed – in India and China, where change has had intended and unintended consequences unfolding even as uncertainty looms, I show that fresh study, especially in comparison, is absolutely essential.
Investigating magnetically targeted microbubbles for ultrasound-enhanced thrombolysis
Keywords: Drug delivery
Microbubbles
Stroke
Therapeutic ultrasound
Sonothrombolysis
Thrombolysis
Magnetic targeting

Despite therapeutic advances, ischaemic stroke remains one of the leading causes of mortality and disability worldwide. Microbubble-enhanced sonothrombolysis is an advantageous method to accelerate the reopening of occluded arteries, but further improvements in safety and efficacy are required to attain widespread clinical implementation. This thesis investigates the potential of magnetically targeted microbubbles to enhance sonothrombolysis. First, a computational and experimental model of a thrombosed vascular network was developed. It showed that magnetic targeting considerably increases the number of microbubbles delivered to the thrombus, a key element for effective sonothrombolysis. The effect of these magnetically targeted microbubbles on rates of thrombus breakdown was then investigated in vitro, first with ultrasound and microbubbles alone (mechanical sonothrombolysis), then with the addition of fibrinolytic drugs (enzymatic sonothrombolysis). Magnetic targeting was not found to affect mechanical treatment, and mechanical lysis rates were highly variable. On the other hand, magnetic targeting significantly accelerated enzymatic treatment, even with low concentrations of fibrinolytic drugs. The mechanisms underlying both treatments were discussed. In addition, treatment safety was examined. Specifically, the risk of secondary embolism and the feasibility of real-time treatment monitoring were assessed. Neither treatment increased the risk of downstream vascular embolism with large clot fragments. Acoustic monitoring of enzymatic sonothrombolysis was feasible, as a strong correlation was found between lysis rates and the energy of acoustic emissions near the clot surface. There was no strong correlation in mechanical sonothrombolysis. Magnetic targeting may therefore be regarded as a promising adjuvant to enzymatic sonothrombolysis, improving microbubble delivery to the clot, accelerating its breakdown, and reducing injected drug doses. It is hoped that targeted treatment and real-time monitoring will enhance safety and efficacy in the management of acute and chronic thrombosis, and ultimately improve patient outcomes.
From the Ritz to the rubble? The asistente of Seville, urban government and disaster, 1621-1700
Keywords: spain
disaster
asistente
seville
environment
flooding
urban
natural disaster

Seventeenth-century Seville, one of early modern Spain's most populous cities and the mercantile hub of its imperial trade, endured repeated and severe flooding of the Guadalquivir River, events that have been largely overlooked by historians. Additionally, Seville's boom-then-bust history and the allure of the ‘decline of Spain’ thesis have ensured that the second half of the seventeenth century for both the urban and the national context remains similarly neglected. This thesis, by conducting research into the city’s flooding from 1621 to 1700 presents an alternative narrative of continuity, at the same time as asserting the value to be gained from a historical study of the environment and disasters. I argue that urban responses – political and cultural – to disaster provide fundamental evidence of the impact of wider historical processes and structures.
The asistente – the royal governor – of Seville likewise lacks sustained or detailed study. These men, as the king's appointees, had a vital role in the performance of the government of the Habsburg monarchy. The city’s equivalent of the corregidor in other Spanish cities and towns, and previously understood as a legal and administrative official, the asistente was, I argue, responded to a broader set of political attitudes, which prioritised conservation and discouraged novelty. I also stress the hands-on and practical aspects to the post, which demanded a working appreciation of urban space.
By connecting a study of royal government in one of the most significant of early modern Spanish cities to an environmental history of flooding, I address important gaps in the scholarship and suggest new avenues of research into the history of environmental disaster. Spanish 'decline' might be reinterpreted as a failure to deal with specific local environmental issues, and environmental disaster acknowledged as an issue of central political importance.
Keeping the faith: church and community in Alresford c. 1780-1939
Keywords: Hampshire
Secularisation
Church
Anglican

The Religious Census of 1851 revealed the registration district of Alresford in Hampshire to be a particular bastion of the Church of England. This study considers the basis of this Anglican strength and how the established Church managed to retain its dominance against the challenge from Nonconformity in the context of an apparent waning of religious commitment nationally. Starting from c.1780 to pick up the roots of any early signs of local dissent, the thesis considers the evolving relationship between church and community in this rural part of southern England which comprised a small but prosperous market town surrounded by a variety of agricultural parishes. The study is positioned in the national context of the major political, social and economic upheaval of the nineteenth and early twentieth centuries, concluding with the period between the two world wars. The research consists primarily, but not exclusively, of qualitative analysis, which draws on a rich variety of primary sources including clerical service registers, vestry minutes, churchwarden and overseer accounts, school, court and parish records, enclosure and tithe agreements, parish magazines, local and national newspapers and private correspondence. The general historiography to which the work contributes is around secularisation and denominational rivalry, and regular reference is made to this and more specific sub-themes throughout the thesis. I will argue that the enduring local dominance of the Church of England was due to its enormous financial strength, its central involvement in the provision of charity and welfare, a re-invigorated commitment to pastoral care and the absence of any senior local sponsorship for Nonconformity. Underpinning everything was the formation of a particularly tight nexus between church and parish elites which served to preserve effective Anglican hegemony well beyond the First World War. It was not until the 1920s and 1930s, when the church started to lose its social relevance in welfare and education nationally, that the cracks in the façade of local dominance became irrefutable.
Optimal control and stability of four-wheeled vehicles
Keywords: Fuel minimisation
Stability
Flywheels
Suspension
Optimal Control
Sum of Squares
Pseudo-spectral
Parameter Optimisaiton
Vehicle dynamics
3D routing
Minimum lap time
Hybrid Vehicles
Lyapunov stability
Formula One

Two vehicular optimal control problems are visited. The first relates to the minimum lap time problem, which is of interest in racing and the second the minimum fuel problem, which is of great importance in commercial road vehicles. Historically, minimum lap time problems were considered impractical due to their slow solution times compared with the quasi-steady static (QSS) simulations. However, with increasing computational power and advancement of numerical algorithms, such problems have become an invaluable tool for the racing teams. To keep the solution times reasonable, much attention still has to be paid to the problem formulation. The suspension of a Formula One car is modelled using classical mechanics and a meta-model is proposed to enable its incorporation in the optimal control problem. The interactions between the aerodynamics and the suspension are thereby studied and various related parameters are optimised.
Aerodynamics plays a crucial role in the performance of Formula One cars. The influence of a locally applied perturbation to the aerodynamic balance is investigated to determine if a compromise made in design can actually lead to lap time improvements. Various issues related to minimum lap time calculations are then discussed.
With the danger of climate change and the pressing need to reduce emissions, improvements in fuel consumption are presently needed more than ever. A methodology is developed for fuel performance optimisation of a hybrid vehicle equipped with an undersized engine, battery and a flywheel. Rather than using the widely used driving cycles, a three-dimensional route is chosen and the optimal driving and power management strategy is found with respect to a time of arrival constraint. The benefits of a multi-storage configuration are thereby demonstrated.
Finally, the nonlinear stability of a vehicle model described by rational vector fields is investigated using region of attraction (RoA) analysis. With the aid of sum-of-squares programming techniques, Lyapunov functions are found whose level sets act as an under-approximation to the RoA. The influence of different vehicle parameters and driving conditions on the RoA is studied.
The media and cultural productions in the context of the “Third Chimurenga” in Zimbabwe, 2000 to 2005
Keywords: Patriotic History
Media
Framing the "Third Chimurenga" in Zimbabwe

This thesis explores the role of the media in a "hybrid regime". Taking post-2000 Zimbabwe as a "hybrid regime" in flux over time, the thesis explores the media policies and strategies deployed by the ruling Zimbabwe African National Union - Patriotic Front (ZANU-PF) party in the context of the "revolutionary" seizure of white-owned farms in Zimbabwe in the early 2000s, what became known as the "Third Chimurenga". I examine how the ZANU (PF) media strategy was developed under the newly created Ministry/Department of Information and Publicity in line with the hegemonic ambitions and legitimation needs of the hybrid system that the party built during this period. Through this, the thesis exposes the shortcomings in the literature on hybrid regimes and a Zimbabweanist scholarly literature on the media and 'patriotic history', which both overly emphasise the formal media, and argues for a much deeper understanding of the role of the 'non-traditional' media and political practices that are historically and culturally constituted in the survival or persistence of these regimes. By showing the importance of history and culture in practices of regime legitimation and survival, the thesis challenges much of the assumptions within the literature on hybrid regimes which is largely quantitative and electoralist in approach. This thesis explores: i) the means and mechanisms of media control in a hybrid regime; ii) the tensions and contradictions that characterise a hybrid media system; iii) the role of the media in legitimacy construction, specifically how journalists framed events, and; iv) the role of the 'non-traditional' media or the forms of media drawn from history and culture in regime legitimation and survival. The thesis is based on interviews with ZANU (PF) elites, senior government officials, journalists, artists and a media content analysis as well as a variety of political actors in Murewa, a particularly violent and contested district in Zimbabwe.
Immune responses to vaccines against malaria
Keywords: Viral vector
in vitro assay optimisation
T cell mediated parasite inhibition
Liver stage malaria
Transgenic sporozoite
Malaria vaccines
Flow cytometry
T cell responses
Malaria clinical vaccine trials
Adult and paediatric immunogenicity
Vaccine immunogenicity

The development of a malaria vaccine is necessary for disease eradication. Successful vaccine candidates to date have targeted the asymptomatic, pre-erythrocytic stage of the disease, however even the most efficacious vaccines are only partially protective. Research undertaken in our laboratory has demonstrated that one such regimen, using an 8 week prime-boost viral vector approach of ChAd63 ME-TRAP and MVA ME-TRAP, induces sterile efficacy in 21% of vaccinees, with a key role identified for TRAP-specific CD8+ T cells. The work described in this thesis explores the most immunogenic regimen by which to administer these two pre-erythrocytic malaria vaccines. A shortening of the prime-boost interval from 8 to 4 weeks, and the addition of an extra ChAd63 ME-TRAP priming vaccination, both demonstrated improved T cell immunogenicity over the standard 8 week regimen. Further to this, novel assays were developed to aid the evaluation of vaccine-induced immune responses. Adaptations of the existing methodology for ELISpot analysis and to whole blood flow cytometry techniques, enabled more detailed analyses of paediatric vaccine-induced T cell responses in The Gambia. This work also permitted the comparison of vaccine immunogenicity in this paediatric population, with malaria-naïve and malaria-exposed adult vaccinees. The results suggest that vaccine-induced T cell responses in infants of 8 weeks and older are comparable to that of adults. A second approach involved the development of a novel functional assay. This assay quantitatively measured the in vitro inhibition of intrahepatic Plasmodium parasite development using T cells from ChAd63.MVA ME-TRAP vaccinated volunteers. The assay demonstrated the ability of CD8+ T cells to inhibit parasite development in a TRAP-specific manner, and provides a platform with which to further explore pre-erythrocytic immune responses.
On the interaction of DNA nanostructures with lipid bilayers
Keywords: Cryo-EM
Triskelion
confocal microscopy
Fluorescence microscopy
cholesterol anchors
DNA origami
membrane bending
biomimetic
TEM

Much of our knowledge of cellular biology arises from direct observation of active cellular functions. Tools and techniques have steadily developed over the past several hundreds of years to aid in our understanding and control of the nanoworld and are referred to as nanotechnologies. In the context of nanotechnology, DNA is not used as a carrier for genetic information (as it is in cell), but as a construction material. DNA offers unprecedented control over the construction of simplified biomimetic models for the study of biological processes. This thesis first introduces and defines the field of DNA nanotechnology, with particular emphasis on the interaction of snthetic DNA nanostructures with biological membranes. Inspired by the protein clathrin, three-fold symmetric DNA tile made of eight, short DNA strands and capable of polymerising is described and studied, with the aim to interact with and controllably bend a membrane bilayer. This structure presented challenges during construction so an enhanced three-armed DNA structure built with DNA origami was designed. The succesful assembly of a rigid and functionalisable nanostructure is described. This origami structure was polymerised into large constructs in solution and on a supported lipid membrane. The shape of the structure was modulated to vary its curvature and apply a bending force to a lipid vesicle when anchored to it. Following the conclusion of this study, we present the construction of a small, unique DNA structure for enhanced electron microscopy imaging in cell lysate. This project is part of a developing technique to couple the interaction specificity of dyes in super-resolution microscopy and the high-resolution output of electron microscopy. Finally, the optimisation procedures and recommendations for TEM imaging of samples of DNA origami and lipid structures are discussed.