VictorJuiz/thesis huggingface dataset:
Engineering the surface properties of microbubbles for biomedical applications
Keywords: bubbles
microfluidics
membranes
ultrasound

Surfactant coated microbubbles are widely used as contrast agents (UCA) in medical ultrasound imaging, due to their high echogenicity and non-linear response to acoustic excitation. Controlling the stability of microbubbles in vivo represents a considerable challenge. Understanding the characteristics of the bubble surface and how they change with production method, composition and environment is key to addressing this problem. The aim of this thesis is to investigate viscosity, bubble dissolution, and acoustic response as functions of their composition, manufacturing method and environment.
Bubbles were made using combinations of phospholipid and an emulsifier in different molar ratios. Adding the emulsifier decreased both the size and the surface viscosity of the bubbles and caused changes in the scattered pressure amplitude of bubbles under ultrasound.
To increase microbubble stability, solid inorganic nanoparticles were adsorbed on to the microbubble surface. These particles behaved as Pickering stabilisers, and deterred Ostwald ripening. The nanoparticles also enhanced the nonlinear behaviour of bubbles at low acoustic pressures.
Three manufacturing methods (sonication, cross-flow and flow focusing) were investigated in order to verify stability differences. Sonication produced bubbles with surface viscosities hundreds of centipoise greater than those produced by microfluidics. Both pressure amplitude and harmonic content for sonicated bubbles were found to be much larger due to a higher liposomal adhesion rate at the surface.
Solution temperature and bubble age were also investigated. When the solutions were heated above the phospholipid gelling temperature, microfluidic bubbles showed an increased surface viscosity, due to increased liposome adhesion caused by the increased temperature.
Bubble composition, manufacturing method and environment were found to vary the surface characteristics of the microbubbles. Further investigations into the affects of the filling gas, in vitro studies, and low temperature TEM characterisation should be conducted to produce a microbubble with the full range of desired characteristics.
Investigation into the regulatory mechanism of BRCA2 stability
Keywords: APC/C
Ubiquitin
F-box proteins
cell cycle
SCF
BRCA2
DNA damage

Inherited mutations in the BRCA2 gene predispose individuals to the development of breast and ovarian cancers. The BRCA2 protein plays a fundamental role in the repair of DNA double strand breaks by homologous recombination (HR). BRCA2 mediates the recruitment of the RAD51 recombinase to DNA damage sites, which in turn promotes homologous pairing and strand exchange during HR.
It has been reported that increased BRCA2 mRNA levels correlate with poor cancer prognosis, and recently it has been shown that increased levels of BRCA2 suppress HR. As HR is regulated through the cell cycle and can only be employed during S and G2 phases of the cell cycle, in this study, the cell cycle-dependent regulation of BRCA2, as a key player of HR, was investigated.
In this study I report that BRCA2 stability is regulated by the ubiquitin-proteasome system (UPS), which has become increasingly evident as an important regulator of DNA repair. In line with this, I found that BRCA2 can be ubiquitylated in vivo and that it interacts with proteins of the UPS. Interestingly, I observed that BRCA2 levels and its ubiquitylation status change during the cell cycle. Using a siRNA-based approach, I identified a candidate E3 ubiquitin ligase, the SCFFBXW7 complex, which is also a known major cell cycle regulator. siRNA-mediated knockdown of FBXW7 led to stabilization of BRCA2 and overexpression of FBXW7 resulted in BRCA2 ubiquitylation in vivo. Furthermore, I have refined the regions that the SCFFBXW7 interacts with on BRCA2, which likely occurs in a phosphorylation-dependent manner.
Taken together, these observations suggest that BRCA2 stability is regulated by the UPS in a cell cycle-dependent manner, which may be an important regulatory mechanism for BRCA2 function.
Developments in social evolution and virulence in parasites
Keywords: phage
parasites
bacteria
evolution
virulence
social behaviour

The study of social evolution and virulence in parasites is concerned with fitness consequences of trade-offs between parasite life history traits and interactions between parasite species and/or genotypes with their hosts. I develop our understanding of social evolution and virulence in parasites in several ways. (1) I review empirical evidence for the fundamental predictions of virulence-transmission trade-off theory and demonstrate that the fit between theory and data is primarily qualitative rather than quantitative; that parasites differ in their degree of host generalism, and this is likely to impact virulence in four ways. (2) I take a comparative approach to examine the underlying causes of an observed statistical variation in the size of parasite infectious doses across taxa, revealing that mechanisms used by parasites to infect hosts are able to explain variation in both infectious dose and virulence. (3) I formally compare data on human pathogens to explain variation in virulence across taxa, revealing that immune subversion and not growth rate, explains variation in virulence. This allows me to predict that immune subverters and not fast growing parasites are likely to cause the most virulent clinical infections. (4) Using bacteria and their naturally infecting viruses (bacteriophage), I take an experimental approach to investigate the consequences of coinfection for parasite life history traits, and find that viruses cultured under a mix of single infections and coinfections evolved plasticity; they killed hosts more rapidly when coinfecting, and this resulted in high fitness under both single infection and coinfection conditions. (5) I experimentally investigate how selection within and between hosts and patches of hosts affects the fitness and virulence of populations of these viruses. I find that limited host availability favours virulent, faster killing parasites with reduced transmission; suggesting high, rather than low, virulence may be common in spatially structured host-parasite communities.
British politics and the post-war development of human rights
Keywords: Conservative Party History
Labour Party History
UK Constitutional Reform
European Human Rights Development
Human Rights
British Political History
Human Rights History

In this thesis I explore the attitudes, arguments, and actions of British political elites in connection with the development of human rights law in Europe and the UK. I do this by examining British input into five key episodes for the development of European supranational rights and their incorporation into domestic legal orders (namely the drafting of the European Convention on Human Rights 1950, the drafting of the European Social Charter 1961, the acceptance of individual petition in 1966, the failed 1970s Bill of Rights debate, the passing of the Human Rights Act 1998, and recent developments such as the UK ‘opt-out’ to the EU Charter of Fundamental Rights, and the emergence of a new ‘British Bill of Rights’ debate). Casting light on British involvement in less examined periods in European rights development, I challenge existing, isolated, explanations for the more focal episodes (such as Simpson’s rational-choice post-colonial thesis for individual petition acceptance, and ideological accounts for New Labour’s post-1997 constitutional reform). Responding to the most recent literature in the area, central to my analysis is the question of how rights progress relates to inter-party conflict. By considering continuities and discontinuities in elite political discussion of rights I argue that while conflict is a significant underlying feature of every major episode of rights progress during the last sixty years, and is less evident in less progressive periods, other factors have had a greater influence over the form, timing, and extent of rights progress. Most significant amongst these is the constitutional ideological development of the Labour party and the critical connection between Labour’s elevation of the Convention within the UK constitutional space and revisionist shifts in party thinking.
Heart valve tissue engineering
Keywords: Heart valve
PLGA microspheres
drug release
tissue engineering
mechanical property
Mesenchymal stem cells
scaffold
collagen

Since current prosthetic heart valve replacements are costly, cause medical complications, and lack the ability to regenerate, tissue-engineered heart valves are an attractive alternative. These could provide an unlimited supply of immunological-tolerated biological substitutes, which respond to patients' physiological condition and grow with them. Since collagen is a major extra cellular matrix component of the heart valve, it is ideal material for constructing scaffolds.
Collagen sources have been shown to influence the manufacturing of collagen scaffolds, and two commercial sources of collagen were obtained from Sigma Aldrich and Devro PLC for comparison. Consistencies between the collagens were shown in the primary and secondary structures of the collagen, while inconsistencies were shown at the tertiary level, when a higher level of natural crosslinking in the Sigma collagen and longer polymer chains in the Devro collagen were observed. These variations were reduced and the consistency increased by introducing crosslinking via dehydrothermal treatment (DHT).
Collagen scaffolds produced via freeze-drying (FD) and critical point-drying with cross-linking via DHT or 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide /N-hydroxysuccinimide (EDC/NHS) were investigated. All the scaffolds were compatible with mesenchymal stem cells (MSCs) according to the proliferation of the cells and their ability to produce ECM, without differentiating between osteogenic, chondrogenic or endothelial lineages. The FD EDC/NHS scaffold demonstrated the most suitable physical property of all. This result illustrates that FD EDC/NHS crosslinking is the most suitable scaffold investigated as a start for heart valve tissue engineering.
To prepare a scaffold with a controlled local, spatial and temporal delivery of growth factor, a composite scaffold comprising poly (lactic-co-glycolic acid) (PLGA) microspheres was developed. This composite scaffold demonstrated the same compatibility to the MSCs as untreated scaffold. However, the PLGA microspheres showed an increase in the deterioration rate of Young's modulus because of the detachment of the microspheres from the scaffold via cellular degradation.
bHLH and bHLH-LZ factor exchange at promoters
Keywords: MYC
bHLH-LZ
bHLH
USF2
USF1
HIF-1b
Transcription
HIF-2a
HIF-1a
MITF

Mammalian promoters often contain DNA-elements that can be bound by a number of closely related transcription factors (TFs) that cannot bind to the same DNA-element simultaneously. It is possible that each TF responds to distinct cues, allowing the gene to be activated in response to multiple stimuli. An alternative possibility is that each TF binds sequentially, each contributing to the pre-initiation events leading up to transcription.
Here, we explore the exchange of basic-Helix-Loop-Helix-Leucine-Zipper (bHLH-LZ) factors, USF1, USF2 and MITF at the TYROSINASE promoter following induction by UVB-irradiation and methotrexate-administration. We demonstrate, for the first time in human melanoma, differential induction kinetics of TYROSINASE gene in response to an initial or re-induction, a phenomenon akin to "transcription memory" previously described in yeast.
We also show that USF2, specifically detected by two different antibodies targeting the N-terminal region, is largely cytoplasmic, at least in the cell lines we have investigated. We also showed that nucleo-cytoplasmic shuttling of these USF2 species is partly regulated by glucose. Using deletion mutants, we demonstrated the requirement of the amino-acids surrounding the USF-specific region and the basic domain in nuclear localisation of USF2, and that amino-acids 1−193 appear to enhance dimerization of USF2 in addition to the classical HLH-LZ dimerization domain.
We will further investigate the role(s) played by MYC, MITF, HIF and USF exchange at common targets (which we identified through our ChIP-seq analysis) in gene activation and the effect on the (re)activation potential of these genes when DNA-binding by one or more of these factors are abolished, as well as when the promoter is monopolised by one of these factors through overexpression using cell lines expressing one of the bHLH-TFs under a tet-inducible promoter. In the long run, we aim to understand the potential differences in the role(s) of each bHLH-factors co-occupying E-box elements.
The dragon and the lamb: Christianity and political engagement in China
Keywords: China
Nationalism
Public opinion
Politics
Political engagement
Christianity
Protestantism

This thesis examines political engagement amongst young urban Chinese Protestants. Based on 100 interviews in Beijing and Shenzhen, 50 with Protestants, and 50 with non-Protestants, it focuses on three areas: national narratives (what individuals think about China, its current situation and its future direction), political opinions, and social and political activity.
I firstly argue that Protestants generally adhere to a relatively ‘critical’ national narrative, one that is more divergent from the Party-state’s nationalist discourse than that of their demographic peers. I then argue that in causal terms, it is primarily individuals who hold these critical values who are most drawn to Christianity, rather than developing the values as a result of their faith.
Secondly, Protestants do not just hold more negative opinions of China's political regime, but that the criteria by which they judge it are different. In contrast to their demographic peers, Protestants do not base their judgements of the regime on its performance at delivering on everyday political issues.
Thirdly, Protestantism catalyses the development of a sense of agency in its adherents: a sense of moral responsibility towards China and a desire to bring change through transformative activism. However, factors in China's cultural, historical, social and political context serve to steer Protestants' activism away from engagement with secular society and inward towards the church community.
I conclude by arguing that Protestantism poses two challenges to China's Party-state: Firstly, it is symptomatic of an underlying sense of social and political malaise, of scepticism towards the primacy of economic enrichment and towards the Party-state’s attempt to legitimise its rule based upon this. Secondly, Protestantism catalyses the emergence of a critical, morally agentic individualism that anchors its worldview in a discourse outside the control of the Party-state. Adapting to these social shifts presents a major future challenge for the CCP.
An investigation into the biology and function of protein Icb-1
Keywords: BCR signalling
Themis2
B lymphocyte
Icb-1
Themis1

In this thesis I describe an investigation into the function of the protein Icb-1, a homologue of Themis1 in B cells and monocytes. Themis1 is important for T cell positive and negative selections. Yet its function in T cell development is not clear. Although it shows characteristics of an adaptor protein and involvement in TCR-induced signalling, the exact signalling defects in Themis1-/- T cells remain obscure. Icb-1 is similar to Themis1 in sequence, function and binding partners. It has been studied in human tumour and macrophage cell lines, leading to limited conclusions. Its role in B cells has never been published. Given the link with Themis1, it is of great interest to investigate the function of Icb-1.
My study has been focused on the comparison between Icb-1 knockout mice with wild-type controls. I characterised the B cell development in Icb-1-/- mice, either naturally born or produced as mixed adult bone marrow chimeras reconstituted from WT and Icb-1-/- donor cells. I examined the possible compensation and redundancy of Themis1 and Icb-1, by characterising Thems1/Icb-1 double knockout mice. The Ig-HEL mouse models were used to examine the change in B cell repertoire due to negative and positive selections. The mice were challenged with SRBCs or NP-CGG to examine the germinal centre response to foreign antigen when Icb-1 is absent. In vitro stimulation of B cells with soluble and membrane-bound antigens was used to investigate early B cell responses in detail and to give insights into the defects found in in vivo challenges. Finally, I examined the BCR-induced phosphorylation of key signalling molecules and Ca2+ flux in splenic B cells.
The study revealed largely normal B cell development with subtle selection impairments, but a partially defected B cell immune response to antigens in Icb-1-/- mice. The marginal zone B cell population was enlarged in the absence of Icb-1, while the positive selection of B1 B cells induced by intracellular self-antigen was impaired. The deficient mice showed a reduction in germinal centre B cell generation. The defects are associated with impaired BCR-induced cell signalling to low abundance and/or low avidity antigens. In particular, Ca2+ flux and Erk1/2 phosphorylation were clearly reduced under certain conditions. The results shine a light on the function of protein Icb-1, and also improve our knowledge of Themis1 and the Themis family. They provide a new avenue of investigation into the regulation of BCR signalling, especially in Ca2+ flux induction and Erk1/2 activation. They also provide insight into how differential signalling is controlled within cells during activation and differentiation in response to antigens that vary in terms of affinity, avidity and frequency.
How do Bilateral Investment Treaties work? Evidence from highly regulated industries
Keywords: Bilateral Investment Treaties
Foreign Investment

While much has been written on whether signing bilateral investment treaties (BITs) actually leads to greater inward foreign direct investment (FDI), relatively little attention has been paid to understanding the underlying question of how BITs attract investment. This thesis helps to fill this gap, both theoretically and empirically. It develops a rational choice account of why a government that has signed many BITs will be incentivized to adopt marginally more investor-friendly regulation, a benefit which will be of particular value to one specific group of investors: those in highly regulated industries that do not have easy access to BIT substitutes, most importantly state contracts. Econometric analysis of the effects of BITs on industry-level FDI provides strong support for this model: BITs are associated with an increase in FDI in finance and business services, but not in other industries.
Tandem catalytic processes involving Rhodium-catalysed intermolecular hydroacylation
Keywords: heterocycles
catalysis
rhodium
hydroacylation
chemistry

This work describes the extension of rhodium-catalysed intermolecular hydroacylation to encompass some tandem catalytic processes, wherein a further catalytic process is enacted on the product of an intermolecular hydroacylation reaction in “one pot”.
Chapter 1 entails an overview of the development of hydroacylation chemistry, with a focus on the different types of catalytic systems which have been used to facilitate this transformation. A brief description of some precedented examples of tandem catalytic processes which include a hydroacylation reaction is also included.
Chapter 2 describes the intermolecular hydroacylation of chelating aldehydes and propargylic alkynes to form γ-hydroxy-α,β-enones, and their subsequent acid-catalysed cyclisation to form substituted furans in a "one-pot" procedure. Additionally, a tandem intermolecular hydroacylation/double-bond isomerisation protocol for the synthesis of 1,4-dicarbonyl compounds is detailed, and the subsequent transformation of this class of compounds to heterocycles is included.
Chapter 3 focuses on the development of tandem catalytic hydroacylation/reductive processes, wherein a hydroacylation product undergoes a reduction which is catalysed by the hydroacylation catalyst.
Chapter 4 describes an attempt to utilise the rhodium-catalysed conjugate addition of arylmetal species to enomes to create a tandem alkyne hydroacylation/conjugate addition process.
Chapter 5 encompasses the use of a small range of different solvents in rhodium-catalysed hydroacylation, in an attempt to find higher-boiling alternatives to acetone and a "green" alternative to the commonly used DCE.
Art, ceremony and the British monarchy, 1689-1714
Keywords: ceremony
art
history of the British monarchy

This thesis investigates the ceremonial and artistic strategies of the British monarchy in the years following the Glorious Revolution. By adopting a range of methodologies used in the study of visual culture, the thesis considers royal ceremonies as channels for conveying political messages non-verbally. These could affect attitudes to the monarchy, and inform artistic output. By paying particular attention to the way royal participants performed ceremonially in relation to the various formal and informal architectural settings for the court, the thesis highlights the process of seeing as a communicative act. Being alert to the impact of royal ceremonial and artistic activities on contemporary audiences, the thesis also considers the dissemination of royal imagery in England by commercial means. The thesis surveys paintings, prints and medals produced in England, and places the intended audiences at the centre of the analysis. It also pays keen attention to the impact of war on royal image making, and highlights the political context of continental Europe, especially in relation to William’s role as Stadholder-King but also the exiled Stuart court at St Germain near Paris.
The evidence presented here supports a number of conclusions. Firstly, war had a profound impact on all aspects of royal image making. Secondly, royal behaviour and involvement in ceremony were vital elements in the visual presentation of monarchy. Kings and queens were of paramount importance, but their consorts were highly significant. Art was also taken seriously by the monarchy and the Crown tightened controls on royal image making during the period in question. The thesis also concludes that the nationalities of the incumbent monarchs and their consorts, along with their previous experiences and personalities, influenced their individual approach to visual representation. These approaches could shift depending on political circumstances and the personal inclinations of the person concerned.