VictorJuiz/thesis huggingface dataset:
Video camera monitoring to detect changes in haemodynamics

Patients in hospital can be prone to sudden, life-threatening changes in their cardiovascular state. Haemodynamic parameters such as blood pressure, pulse transit time (PTT) and perfusion can be monitored in clinical situations to identify these changes as early as possible. Continuous blood pressure is usually monitored using a catheter placed into a major artery, but this is invasive and involves risk to the patient. In the last decade, the field of non-contact vital sign monitoring has emerged, with growing evidence that the remote photoplethysmogram (rPPG) signal can be used to estimate vital signs using video cameras. If the analysis of the rPPG signal can be expanded to include the estimation of haemodynamic parameters, it could result in methods for the continuous, non-contact monitoring of a subject's haemodynamic state.
In a physiology study, a series of video recordings were made of 43 healthy volunteers. The subjects sat in a purpose-built chamber, and the composition of the air was carefully adjusted to cause the subjects to experience large, controlled changes in blood oxygen levels. To validate the video camera algorithms, reference data were also collected. Along with the volunteer study, a clinical study was performed to acquire data in a challenging clinical environment. Data were collected from patients on haemodialysis in the Renal Unit, a population likely to experience sudden changes in haemodynamics.
The reference data from the Renal Unit study were analysed to determine the extent to which PTT and mean arterial pressure (MAP) are related. The correlation coefficients and linear fits were found on a global and a per-subject basis. In addition, the video recordings from the Physiology study were processed to derive rPPG signals, and these signals were analysed to obtain estimates for PTT. Local rPPG signals were also derived for different regions of interest, and the waveforms were analysed using a novel application of the technique of signal averaging to produce spatial maps of perfusion and blood flow.
The correlation between conventionally measured PTT and MAP was found to be weaker in the haemodialysis population than has been shown elsewhere in the literature, except for a sub-set of patients. The results of the video analysis showed that PTT could be estimated robustly and consistently, although direct validation of these estimates was not possible because of the different method used to calculate the reference PTT. For most subjects, the spatial mapping methods produced robust maps that were consistent over time. These results suggest that it is possible to detect changes in haemodynamics using a video camera, and that this could have applications in healthcare, providing that challenges such as subject movement and clinical validation can be overcome.

Keywords: Patient monitoring
Signal processing
Advisor: Tarassenko, L
Algorithms and computer code for ab initio path integral molecular dynamics simulations

This thesis presents i-PI, a new path integral molecular dynamics code designed to capture nuclear quantum effects in ab initio electronic structure calculations of condensed phase systems. This software has an implementation of estimators used to calculate a wide range of static and dynamical properties and of state-of-the-art techniques used to increase the computational efficiency of path integral simulations. i-PI has been designed in a highly modular fashion, to ensure that it is as simple as possible to develop and implement new algorithms to keep up with the research frontier, and so that users can take maximum advantage of the numerous electronic structure programs which are freely available without needing to rewrite large amounts of code.
Among the functionality of the i-PI code is a novel integrator for constant pressure dynamics, which is used to investigate the properties of liquid water at 750 K and 10 GPa, and efficient estimators for the calculation of single particle momentum distri- butions, which are used to study the properties of solid and liquid ammonia. These show respectively that i-PI can be used to make predictions about systems which are both difficult to study experimentally and highly non-classical in nature, and that it can illustrate the relative advantages and disadvantages of different theoretical methods and their ability to reproduce experimental data.

Keywords: AIPIMD
Constant pressure simulations
density functional theory
PIMD
Advisor: Manolopoulos, D
The impact of HLA-driven escape mutation on viral replicative capacity and immune control in HIV infection

Despite the introduction of antiretroviral therapy, the HIV/HIV epidemic remains an unsolved global health problem. Amongst all the host defence mechanisms, HLA class I molecules have shown the strongest genetic association with delayed disease progression, in particular HLA-B alleles. Numerous studies have shown that the HLAmediated CD8+ T cell responses play a central role in the immune control of HIV. Yet our understanding of HLA-mediated immune control of HIV remains incomplete, even when considering the best-defined epitopes restricted by the protective HLA alleles at a population level.
The studies I have conducted and describe herein focus on two well-charaterised protective HLA-B molecules, HLA-B*81:01 and HLA-B*27:05; a third protective molecule, HLA-B*52:01, that has not been well-studied hitherto; and finally the most prevalent HLAB allele in many Asian populations such as Taiwan, HLA-B*40:01, which has an apparently neutral effect on viral replication. This thesis is centred on the Gag-specific immune response, since previous studies have shown the benefits of CD8+ T-cell responses targeting this conserved and immunogenic region of the HIV proteome, in particular the p24 capsid protein. I have investigated here HLA footprints driven by CD8+ T-cell pressure on HIV that are evident in the viral sequences of individuals expressing these HLA molecules. These footprints include novel escape and putative compensatory mutations. The impact of these variants on viral replicative capacity (VRC) and on HIV disease outcome clinical outcomes was examined via fitness assays. These studies identified several escape mutations that effectively cripple HIV. The distinct compensatory pathways available to the virus to mitigate the fitness cost of particular escape mutations were evaluated. In the course of these analyses I have demonstrated the critical influence of the viral backbone, including HIV clade, in combination with particular viral variants, on VRC. Computational modelling analysis has been applied to facilitate understanding of the mechanism by which certain mutants affect the stability of interactions between HLA and viral capsid protein. This thesis offers novel insights into immune control of the key HIV subtypes – B- and C-clade – and of the most severely affected populations – in Africa (South Africa) and Asia (India and Taiwan) – within the global epidemic. This work helps to better define the viral mutation landscape that is essential both for future vaccines designed to corner the virus, and for successful HIV cure strategies.

Keywords: HLA-B*81:01
HLA-B*52:01
CTL response
viral replicative capacity
escape mutation
HLA-B*27:05
HLA-B*40:01
HIV
cellular immunity
HLA footprint
compensatory mutation
Gag
Advisor: Goulder, P
Investigating resistance of glioblastoma multiforme to radiotherapy and chemotherapy

Glioblastoma multiforme (GBM) is the most common and aggressive type of brain tumour. Despite treatment with surgery, radiotherapy and temozolomide (TMZ) chemotherapy, patient survival remains poor, suggesting that GBM cells evade and resist these therapies. The insulin-like growth factor 1 receptor (IGF-1R) is a receptor tyrosine kinase that signals towards cellular survival, proliferation and motility. Previous work from our laboratory showed that IGF-1R inhibition sensitises other tumour types to ionising radiation (IR) and TMZ. The first aim of this project was to assess IGF-1R expression in brain tumour tissue microarrays by immunohistochemistry. IGF-1R was found to be upregulated in adult and paediatric tumours relative to normal brain. In paediatric brain tumour patients, higher IGF-1R expression was found to associate with reduced patient survival, but no association was observed for adult brain tumour patients. The second aim sought to assess the effect of IGF-1R inhibition on the sensitivities of GBM cell lines to IR and TMZ. Adult and paediatric GBM cells showed varied expression and activation of IGF-1R and downstream signalling components. Use of two IGF-1R axis inhibitors showed that paediatric, but not adult GBM cells were sensitive to IGF-1R inhibition. In addition, there was evidence that IGF-1R inhibition sensitised paediatric GBM cells to IR. These results suggest that the IGF-1R could be an important target in paediatric GBM. However, sensitisation to TMZ was not observed. The third aim of this project was to assess the effects of repeated TMZ or IR treatment on adult GBM cells in order to identify mediators of treatment resistance. Repeated treatment with TMZ allowed previously sensitive cells that lacked O6-alkylguanine-DNA alkyltransferase (MGMT) to acquire different degrees of resistance to TMZ. Characterisation of the induced resistance sublines showed detectable MGMT expression. However, unlike the TMZ resistance detected in two cell lines that expressed endogenous MGMT, the induced TMZ resistance in the repeatedly treated cells did not depend on MGMT activity. These MGMT-independent resistant cells may be useful to investigate novel strategies to overcome TMZ resistance. Finally, two repeatedly irradiated GBM sublines were established and characterised. One subline developed relative resistance to IR, the other developed a more motile phenotype. Microarray analysis showed differential expression of 122 genes across both cell line pairs, including upregulation of the stem cell marker CD24 in the more motile repeatedly irradiated subline. CD24 upregulation was validated at the mRNA and protein levels. Further investigation of differentially expressed genes may provide insights into novel mechanisms by which GBM cells evade or resist radiotherapy, and may help to guide development of new targeted treatments for GBM patients.

Keywords: Temozolomide
CD24
Radio-resistance
MGMT
Glioblastoma multiforme
Radiation
IGF-1R
Chemo-resistance
Advisor: Macaulay, V
Non-discrimination in international economic law

This thesis examines the jurisprudence of the World Trade Organization (WTO) Panels and Appellate Body (AB) and investment tribunals on non-discrimination clauses contained in the WTO agreements and investment agreements respectively. The thesis puts forward an alternative conceptual perspective through which the interpretation of non-discrimination provisions in international economic law could be analysed. It is argued that nondiscrimination obligations (as every legal rule to a greater or lesser extent) are inherently indeterminate. This is a fortiori the case in regard to non-discrimination provisions due to their link to the concept of equality. The concept of equality is open-ended and value-laden: its content depends on the prioritisation of different values. Thus, equality in the economic sphere can accommodate different conceptions which reflect different ideological approaches in relation to regulation, economic development and the proper role of the State in the economy. International courts and tribunals enjoy broad discretion in selecting which conception of equality to adopt when interpreting non-discrimination clauses. This indeterminacy is a positive characteristic of international economic regimes. Both the WTO and the investment arbitration regime are equipped with institutional characteristics which enable the contestation of different ideological approaches and promote pluralism. In the WTO context, this role is fulfilled by the institutional structure of the organization which facilitates the dialogue between the WTO members and the WTO Dispute Settlement System. In the realm of international investment arbitration, the mechanism of party-appointed arbitrators, despite its shortcomings which can be addressed, ensures value pluralism.

Advisor: Sarooshi, D
Characterisation of placental and platelet exosome-bound cardiotrophin-1 in cardiomyocyte and endothelial cell function

Maternal cardiovascular adaptions during pregnancy have been well described and include characteristic changes in cardiac morphology and function. The mechanisms behind these changes remain largely unknown but are tied to the developing feto-placental unit. Extracellular vesicles are membrane-encapsulated particles carrying cargo originating from their parental cells and are critical mediators of intercellular communication. Syncytiotrophoblast extracellular vesicles (STB-EV), comprising of microvesicles and exosomes, are released by the placenta into the maternal circulation throughout pregnancy. We hypothesized that there might be molecules on the STB-EV that had cardiac effects. In this thesis, we characterised the expression of Cardiotrophin 1 (CT-1), a known potent inducer of cardiac hypertrophy and regulator of cardiac physiology, as being present on the human placenta. Importantly, we demonstrated that CT-1 is present on both microvesicles and exosomes, with a greater expression on exosomes. Furthermore, we show that CT-1 is biologically active and can phosphorylate its cognate receptor gp130/LIFR. Moreover, we demonstrate downstream signaling pathways that are mediated by STB-EV, most notably STAT 3 and ERK 1/2. We subsequently conducted a transcriptomic analysis using microarrays to investigate the effects of CT-1 positive STB-EV on cardiomyocytes derived from human induced pluripotent stem cells. This analysis showed significantly upregulated and downregulated genes involved in cardiovascular function. Furthermore, gene networking using Ingenuity Pathway Analysis (IPA) revealed STAT 3 as the most likely mediator of these gene changes. Intriguingly, real-time quantitative PCR validation confirmed the vesicular changes seen in the array but revealed that while some of the gene changes are directly due to CT-1, some are almost certainly due to the cargo within the vesicles. As a corollary to our experimental investigations we also identified, for the first time that CT-1 was present in platelets and platelet extracellular vesicles (PEV). We found in vitro evidence that PEV-bound CT-1 phosphorylated gp130 signaling leading to the activation of STAT 3 and ERK 1/2. Furthermore, we demonstrated that CT-1 positive vesicles protect against cytotoxicity in endothelial cells raising the possibility that this cytokine performs a cellular protective role.
This thesis thus reports the first observation of active CT-1 expressed in STB-EV from normal placentae and points to a novel finding that the placenta may well play a role in the orchestration of cardiovascular adaptation in pregnancy. Moreover, our results suggest that the placenta can communicate with the maternal heart. Additionally, it places CT-1 in vesicles as playing a significant role in both cardiomyocyte and vascular biology. Finally, the finding that platelets contain Cardiotrophin-1 positive vesicles suggests that this cytokine may well have a role in cellular protection outside pregnancy.

Advisor: Vatish, M
Sargent, I
Remedies and international private law

This thesis seeks to determine how remedies inter-relate with the European rules on international private law. The thesis is broadly separated into two Parts, the first Part discussing the relationship between remedies and the general part of European international private law, and the second Part discussing the relationship between remedies and the specific parts of European international private law.
From this analysis, three threads can be drawn. First, primary right, secondary right and the court order vindicating them are so closely related that, ideally, the same law ought to apply to all. They form a unit which should remain unbroken.
Second, the distinction between substantive and ancillary rights is of crucial importance for remedies in the context of both jurisdiction and choice of law. Ancillary rights are those which arise by virtue of the trial process itself, whereas substantive rights are, or are perceived to be, created prior to the trial. The orthodox jurisdictional and choice of law rules only apply to substantive rights. Ancillary rights have their own, separate, rules. With one exception, the only court with jurisdiction over those ancillary rights is the court with jurisdiction over the substantive right to which they are ancillary. Furthermore, the lex fori must be applied to determine the nature of the ancillary right.
Third, there exists a rule of exclusion which is of crucial importance for remedies in the context of both the enforcement of foreign judgments and choice of law. This rule of exclusion applies where the application of the foreign court order, whether applied by virtue of enforcing a foreign judgment, or applied by virtue of applying a foreign governing law under the choice of law process, would be too inconvenient for the forum court’s machinery. Under such circumstances, the forum court can disapply the foreign law and substitute the closest order it can from its own legal system.

Advisor: Peel, E
Music-making in the English parish church from the 1760s to 1860s, with particular reference to Hertfordshire

This dissertation focuses on a previously unexplored aspect of music-making in the English parish church during the 1760s to 1860s, namely its local development in response to inter-related episcopal, elite, clerical and economic influences.
The historiography suggests ineffectual episcopal leadership and little gentry engagement with parochial church music-making during this period. By contrast, this study presents evidence of their influence, particularly during the late eighteenth to early nineteenth centuries. Elite support for Sunday and charity schools was allied with a desire to improve congregational psalmody, and church organs and barrel-organs were given with this objective in mind. Gentry involvement with amateur military bands of music also influenced the instrumentation of choir-bands. These actions were mirrored by those further down the social scale, and formed part of a complex pattern of support for church music-making.
This dissertation argues that methods adopted to improve congregational singing in one generation were reviled in the next. The suggestion that teaching charity school children to sing would result in a congregation of singing adults became a recurring theme, yet time and again it met with little success. Nineteenth-century reform of church music-making has often been presented as a clear-cut progression, with the replacement of choir-bands by a barrel-organ or harmonium, but this dissertation argues that these phases were sometimes parallel rather than sequential, with no inevitable outcome. Furthermore, new evidence reveals that nineteenth-century church rate disputes had a profound effect on church music-making, an area of research neglected in modern literature.
Lack of available seating became a significant problem in parish churches owing to the often compulsory attendance of schoolchildren, which opens up another new area of research. This dissertation argues that attempts to reform music-making contributed to alterations in the church fabric long before ecclesiological reorderings, and had long-lasting repercussions.

Keywords: charity schools
organ (musical instrument)
Hertfordshire
barrel organ
Advisor: Smith, M
Global fabric bazaar: an Indian trading economy in a Chinese county

This thesis is primarily based on ethnographic fieldwork that lasted fifteen months, between 2010 and 2012, in Keqiao, a municipal county in eastern Zhejiang Province, China. Despite its inferior administrative status and rather inland location, Keqiao is China’s trading frontier for fabrics, which are the semifinished textiles that are industrially weaved, knitted, dyed, and printed in bulk before being exported. Contributing to the turnover of more than one-third of all fabric produced in China, the county’s fabric wholesale market is not only the mainstay of Keqiao’s economy. It is also the world’s centre for fabric supplies, and where around 10,000 Indians have flocked to start their intermediary trading businesses.
The major aim of this thesis is to examine the everyday encounters between Indians and Chinese in the local fabric market. It begins by exploring how Keqiao emerged as the global distribution centre for a wide variety of cheap fabrics. It also shows how Keqiao becomes characterized by the growing importance of low-end fabric sales and the influx of Indian traders, who specialize in exporting these fabrics. The thesis then describes the encounters between Indians and local Chinese in the fabric market, addressing the challenges and difficulties that these Indians, especially the newcomers, confront when dealing with the Chinese suppliers. Focusing on novice traders, the thesis turns to investigate the internal dynamics of Indian trading companies. Remarkably, novice Indian traders successfully learn several strategies to counteract their precarious position in the workplace. These strategies leverage the accumulation of work experience and expanding social networks. These insights bring the thesis to chapters that highlight other strategies, particularly those created from encounters between Indian traders and Chinese clerks, as well as those between Indian traders and Chinese salespersons.
Taken together, this thesis illustrates how transnational and local actors team up to create their own, locally based, intermediary economy within a small Chinese county, and how such a collaborative economy, which I term a ‘global fabric bazaar,’ sustains these actors. Without this collaborative economy, these players would otherwise be vulnerable within the fabric wholesale industry because this supply chain is increasingly polarized and weakened by today’s global capitalism.

Keywords: Social and cultural anthropology
Advisor: Xiang, B
Banks, M
Sedes et rura: landownership and the Roman peasantry in the Late Republic

This thesis reconsiders the cultural and economic relevance of landownership for the Roman republican peasants. In the Introduction, I define direct agricultural producers (hereafter “peasants”) as the object of my investigation. In Chapter 1, I argue that throughout the republic peasants owned little or no land, and private landholdings had a marginal role in peasants' production strategies. The frequent land schemes did not make the distribution of property more egalitarian, because they were not designed for that purpose, and due to their poverty peasants were unable to maintain control of the allotments.
In Chapter 2, I explain that in ancient literature peasants were idealized as symbols of complete independence and self-sufficiency, and in political reflection they were considered the most perfect citizens. In accordance with the widespread view that Roman power had peaked and was now declining, already by the time of Fabius Pictor early and middle republican Rome was idealized as a society of peasants, whose supposed decline was threatening the republic. I conclude that in the Gracchan period peasants' discontent may have been a consequence of growing inequality, rather than utter impoverishment.
In Chapter 3, I argue that in order to understand whether the free peasantry was actually declining we should consider variations in peasants' opportunities for dependent labour on the one hand, marketing on the other. Therefore, I reconsider the available data on the demography of Roman Italy and on commercial agriculture. I conclude that, while peasants could profit from increased access to markets, there is no conclusive evidence that competition for labour grew.
In Chapter 4 I explain that the late republican peasants were perfectly aware that land had an economic value, and were even able to carry out evaluations. I suggest that this was a consequence of census procedures.

Advisor: Purcell, N