VictorJuiz/thesis huggingface dataset:
Angiogenesis in human lung tumours

Angiogenesis, the growth of new blood vessels, is vital to tumour growth. Prevailing dogma has been that tumours cannot grow without angiogenesis. Based on this premise, anti-angiogenic drugs are used clinically. However, the principle of angiogenesis as an absolute requirement for tumour growth has been challenged with reports that many tumours are entirely or partially non-angiogenic.
This study describes and quantifies characteristics of non-angiogenic non-small cell lung tumours, demonstrates non-angiogenic growth in small-cell/neuroendocrine lung tumours and investigates the underlying pathogenetic processes by comparison with angiogenic lung tumours.
Hypoxia is an important stimulus for angiogenesis. Differences in response to hypoxia may determine whether a tumour produces new vessels. In order to test this, levels of. necrosis, often considered a surrogate marker of hypoxic stress, were quantified but no difference in quantity of necrosis was found Moreover, immunohistochemical investigation of hypoxia and angiogenesis factors provided no unambiguous explanation for the differences in angiogenesis. Significant differences were seen, however, in fibrosis and inflammation, which were both greater in angiogenic tumours. Differences were greater for lymphocytes rather than cells of the ‘innate’ immune system. This provided an alternative hypothesis: angiogenesis occurs during wound healing and in the growth of granulation tissue, so it is possible that tumour angiogenesis is a response to factors produced by immune cells rather than the tumour itself. A tumour’s angiogenic status may, therefore, be determined by the response it provokes from the immune system. Further work to test this theory would compare levels of immunogenic factors such as Tumour Necrosis Factor and tumour cell surface antigens such as the HLA class I molecules.
The study concludes with an investigation into the molecular basis of non-angiogenic growth using the technique of comparative genomic hybridisation (CGH) which allows amplifications and deletions of areas of DNA to be calculated. High-resolution array CGH was evaluated against conventional CGH, and the results compared with previous RNA studies from our laboratory. These revealed a set of genes with consistent changes in both RNA and DNA, several of which form part of known angiogenic and inflammatory pathways.

Keywords: CGH
Angiogenesis
Lung Cancer
small-cell/neuroendocrine lung tumours
Advisor: Pezzella, F
Gatter, K
Harris, A
Galaxy evolution with FMOS

This thesis is concerned with the targeting of emission line galaxies with FMOS (Fibre Multi-Object Spectrograph) to determine properties of star forming galaxies at redshift ~1.5, and provide measurements of the growth rate of large-scale structure through Redshift Space Distortions (RSDs). I also consider the opportunities of targeting the passive galaxy population at high redshift, through measurements of their continuum.
I start with the extensive broad-band photometric data available in the UKIDSS-UDS (United Kingdom Infrared Telescope Deep Sky Survey - Ultra-Deep Survey) field which is used to produce a band-merged catalogue, later used for determining photometric redshifts. In producing this catalogue, I approach the issue of source confusion present in the deep Spitzer imaging using z-band priors on profile position and shape and an iterative Expectation-Maximisation algorithm.
Photometric redshift estimates are compared against colour selections as potential targeting techniques for a wide-area redshift survey with FMOS. Different photometry survey areas are considered, and the quality of selection given the available broad-band data tested, by adjusting the photometric catalogue produced for the UDS. The results indicate that the SWIRE (Spitzer Wide area InfraRed Extragalactic Survey) fields are too small to provide adequate sources with a consistent selection mechanism. The CFHTLS (Canada-Frace-Hawaii Telescope Legacy Survey) would have a large enough area given deeper z'-band imaging, and SWIRE-depth coverage in the Spitzer 3.6μm and 4.5μm bands.
I present FMOS commissioning data obtained for the UDS field, including the spectroscopic targeting of sources form the High-Z Emission Line Survey (HiZELS). With this data, I am able to test the current quality of flux calibration using cool stars targeted simultaneously and the level of systematic errors left by sky-subtraction. The sample of HiZELS sources selected to place Hα at z~1.45 show low contamination from other emission lines, and only one out of 9 targets assigned a redshift has any indication of AGN activity.
Finally, I present longslit observations of faint, passive galaxies at redshift z~1.9, selected as members of a possible cluster, JKCS 041, selected from broad band colours. One object was observed with high enough signal to noise to constrain the position of the 4000 Å / Balmer break, providing a tighter constraint on the photometric redshift of 1.8867 +0.0034 -0.0117.

Keywords: galaxy evolution
Advisor: Dalton, G
Ammonia borane and its derivatives: high weight percentage hydrogen storage materials

Ammonia borane and ammonium borohydride have been considered extensively as potential hydrogen storage materials. This thesis reports their structure and functional properties, emphasising the key role that dihydrogen bonding plays in both materials.
The formation of a 'mobile phase' is considered to be the preliminary step in the decomposition of ammonia borane. The formation of this mobile phase has been studied using neutron diffraction, inelastic neutron spectroscopy and NMR. It has been found that in the mobile phase, 'end-to-end' flipping of the ammonia borane molecule occurs. This is an important precursor to the next step in the decomposition: the formation of the diammoniate of diborane. The dihydrogen bonding networks which occur in both the orthorhombic and the tetragonal phases of ammonia borane, and are the controlling factor in the decomposition process, were investigated using Density Functional Theory Molecular Dynamics (DFT-MD) simulations. It was hence shown that in the high-temperature tetragonal phase of ammonia borane, dihydrogen bonding is still an important stabilising interaction and there is little to distinguish between the three crystallographically distinct dihydrogen bonds.
A closely related hydrogen storage material, ammonium borohydride, was also studied using the same techniques. Its low temperature phase progression was examined using variable temperature neutron diffraction. The vibrational modes of ammonium borohydride were assigned by comparing vibrational spectra determined using inelastic neutron spectroscopy with the results of DFT-MD simulations. Quasielastic neutron spectroscopy was used to show that both the ammonium and borohydride groups in ammonium borohydride perform discrete 'hopping' reorientational motions at a wide range of temperatures, and that the ammonium group has a mean residence time approximately 100 times less than that of the borohydride group. Hydrogen atom densities in the ammonium group were determined from DFT-MD simulations, and from refinements of high-resolution neutron diffraction data using cubic harmonic basis functions.

Keywords: ammonium borohydride
ammonia borane
hydrogen storage
Advisor: Edwards, P
David, B
Targeting EGFR signalling pathway in triple negative breast cancer 

Epidermal growth factor receptor (EGFR) is frequently overexpressed in the majority of triple negative breast cancer patients (TNBC). However, the molecular determinants behind their limited response to EGFR-targeted therapies are poorly understood. Here, both the acute and chronic responses of TNBC to the EGFR-targeted therapy, cetuximab (CTX), have been investigated.
The expression of EGFR has been analyzed in a cohort of 2000 breast cancer tumours from the public dataset as well as in a panel of breast cancer cell lines. Furthermore, the response of TNBC cell lines to CTX has been investigated using conventional biochemical methods. Finally, a comprehensive transcriptomic profiling of an acquired CTX-resistant TNBC model by RNA sequencing has been performed to understand the molecular determinants of acquired CTX resistance.
The results confirmed that EGFR is highly expressed in TNBC in comparison to non-TNBC breast cancer tumours and cell lines, which was associated with adverse clinical outcomes. Targeting EGFR in TNBC cell lines using CTX failed to completely inhibit the EGFR signalling pathway and was associated with an increase in ADAMs-mediated release of endogenous EGFR ligands, EGF and TGFα. Inhibition of ADAMs (ADAM10 and ADAM17) significantly enhanced the anti tumour efficacy of CTX both in vitro and in vivo. Furthermore, transcriptomic profiling of the acquired CTX-resistant TNBC cell line (MDA-MB-468CR) revealed an activation of several key oncogenic pathways and genes, including the TGFβ/BMP pathway. Blocking BMP receptors (BMPRs) restored the sensitivity of resistant cells to CTX treatment.
Collectively, current findings offer alternative strategies that could enhance the CTX response in TNBC. We further reported that simultaneous targeting of both EGFR and BMPR pathways could overcome CTX resistance, which might have important implications for the treatment of TNBC.

Keywords: genomics
cell biology
Cetuximab
drug resistance
EGFR
Triple negative breast cancer
Advisor: Ahmed, A
Kong, A
Investigating a role of ASPP2 in the cellular response to infection

Intracellular pathogens such as Epstein-Barr virus (EBV) and Mycobacterium tuberculosis (Mtb), the causative agents of nasopharyngeal cancer (NPC) and tuberculosis (TB), respectively, can establish lifelong persistent infection in their respective host cells and have a profound effect on the dynamics of the host microenvironment. Studies have explored the molecular components and mechanisms that are involved in complex host-pathogen interactions that lead to infection and cancer. In particular, the transcription factor (TF) p53 plays a critical role in protecting the host against cancer and infectious agents by inducing cell cycle arrest and apoptosis. Dysregulation of p53 pathways contributes to the pathogenesis of cancer and inflammatory diseases. Here, it is investigated whether regulators of p53, such as p63 and ASPP2, can link infection, immune activation and their involvement in NPC and TB. Both p63 and ASPP2 are determinants of epithelial integrity and cell apoptosis. In addition, ASPP2 has been shown to interact with members of the p53 family and the pro-inflammatory TF NF-KB. Notably, an inverse relationship is shown between the expression levels of p63 and EBV infection in vitro. Moreover, EBV-infected NPC cells exhibit features of epithelial-to-mesenchymal transition (EMT), and a lack of p63 may play a role in NPC progression by improving tumour motility and invasion. Interestingly, human NPC biopsies exhibit nuclear p63, which contradicts the in vitro data outlined in this report. It is postulated that the histology analyses in this study are more likely to accurately reflect the intrinsic environment of tumourigenesis, which are in agreement with the published literature. Induction of ASPP2 in vivo is shown in NPC, as well as BCG- and Mtb-infected lung biopsies. Furthermore, examination of these samples revealed aberrant accumulation of immune cells at the lesion site. Administration of inflammatory agonists, such as lipopolysaccharide (LPS), triggerred up-regulation of ASPP2 in macrophage-like THP-1 cells. This differential expression indicates that ASPP2 may be involved in the immunological eradication of cancerous or granulomatous lesions. Understanding the interplay between regulators of p53 and the anti-inflammatory responses will shed light on the complexity of the host’s immune surveillance system.

Keywords: p53
Epstein-Barr Virus
nasopharyngeal
ASPP2
tuberculosis
p63
Advisor: Lu, X
Beyond schools and monasteries: literate education in late Roman Syria (350-450 AD)

The subject of the present work is the provision of higher literate education in late Roman Syria (c. 350 - c. 450). The difference that Christianity made to literate education has always been in danger of being explained with the introduction and the development of a new kind of instruction provided in monasteries. A rigid dichotomy between secular schools and Christian monasteries, however, finds limited validation in our sources for literate education. While early Christian literature often presented monasteries as providers of education, documentary evidence offers a more blurred picture. On the one hand, studentsʼ papyri show the penetration of Christianity into schools, and, on the other, secular instructional texts have been found in the excavations of early monasteries in Egypt.
This thesis presents a neglected corpus of Christian instructional texts that call into question an oppositional understanding of scholastic and monastic education in the Syrian region during late Antiquity. The corpus consists of the Syriac translations of six literary pieces by (or attributed to) Plutarch, Lucian, and Themistius that bring together features of rhetorical education with an interest in Christian asceticism (ch. 2). While the contents and the transmission of the Syriac translations reveal the link to Christianity and Christian ascetic practice (ch. 3), the textual form and the choice of the texts unearths the underlying connection to traditional literate education (ch. 4).
These documents, which will be put in relation to instructional literature composed in Greek, Latin, and Syriac in the same period, challenge the existence of a neat line dividing scholastic and monastic education in the Syrian region during late Antiquity. A fresh analysis that is not constrained by a preconceived model of monastic instruction better accounts for the involvement of early Christian leaders in higher education and prompts a new investigation of their conduct on the social scene. Their agency now appears much closer to that of their non-Christian counterparts, sophists in primis, and raises the broader question of the extent to which they owed their considerable success to the implementation of strategies ultimately derived from the world of professional paideia.

Keywords: Syriac
Syriac Translations from Greek
Classics
Greek Literature
Late Antiquity
Advisor: McLynn, N
Taylor, D
The authority of church and party among London Anglo-Catholics, 1880-1914, with special reference to the Church Crisis, 1898-1904

Anglo-Catholicism was the major occasion of strife within the Church of England, 1880-1914. Between 1898 and 1904 Protestant agitators made their last serious attempt to invent laws to put down ritualism. This thesis describes that church crisis, as London Anglo- Catholics experienced it. Particular attention is paid to the ways in which the authorities tried to establish control over ritualists, and to the different reactions to the crisis within the Catholic party.
Anglo-Catholic ecclesiology was not so much a dogmatic package as a theological method - the application of an organic church principle to all doctrine and practice. Anglo-Catholics used a distinctive hermeneutic, taken over from Pusey and Bishop Forbes, to neutralize offensive aspects of the thirty-nine articles and Prayer Book. Pressure from their bishops before and during the crisis stimulated distinctive doctrines of episcopacy and magisterium among them. Against all opposition, they continued to postulate a special affinity between the churches of England and Rome, secured by a particlar concept of holiness.
Radical Anglo-Catholics who came to the fore in the church crisis turned the concept that the Church of England was but two provinces of the Catholic church from a passive assumption into the basis of a radical critique of other Anglican doctrine and practice.
They responded to being under pressure in two kinds of way. Some sought security in formally reactionary postures which they hoped would make their position impregnable. Others saw the crisis as an opportunity for all involved to re-think their perceptions of their own positions and of the nature of authority.
Although Anglo-Catholics did not always face up to the ecclesiological implications of their behaviour, they did manage to defend and define their approach between 1880 and 1914 well enough for it to make a major impact upon the twentieth century Church of England.
Hemispheric asymmetries in human beings and monkeys

Part I. Patients with unilateral brain damage were given a number of tests to investigate the nature of left hemisphere specialization for complex sequential movements of the hand and arm. It was concluded that the left hemisphere deficit was one of memory rather than performance. There was no specific left hemisphere deficit in the ordering of multiple motor acts. Traditional apraxia tests produced results consistent with the interpretation of normal left hemisphere specialization for memory (but not ordering or execution) of motor acts. There was no left hemisphere deficit in producing a large number of different positions when there were no constraints on the exact positions produced. Firm conclusions could not be drawn to questions regarding the importance or relevance to the asymmetry of the motor nature of the tasks, the inclusion of more than one element or motion in motor memory tasks, or the involvement of proximal v. distal muscles in motor memory tasks. Little information was found on the relationship between motor and language functions of the left hemisphere. It was hypothesized that there are two broad stages of motor function: generation of motor "target" acts (which is lateralized to the left hemisphere) and the ordering and execution of these acts (which is not lateralized).
Part II. The hypothesis that functional neural asymmetries exist in rhesus monkeys was tested using a task which in human beings is lateralized to the right hemisphere: the task required discrimination between two squares, one containing a dot located exactly in the centre, and the other containing a dot displaced vertically from centre. Pre- and post-operative threshold measures were taken. Animals with a left occipital lobectomy combined with a splenial section were worse post- operatively than pre-operatively; animals with similar right-sided lesions were better. Hand preference was probably unrelated to this asymmetry, and to hand competence on a visually-guided reaching task.

Advisor: Weiskrantz, L
Warrington, E
Characterisation of the immune response to PARV4

PARV4 is a novel human parvovirus initially identified in an intravenous drug user at risk of HIV infection. PARV4 is a small single stranded DNA virus principally absent from the general population, but common in HCV- and HIV-infected individuals. Until 2009, most published PARV4 studies related to the prevalence of PARV4 in various risk groups. PARV4 has been detected in the liver of HCV-patients and the bone marrow of HIV-patients. Parvovirus B19, the closest related virus, elicits a strong immune response and can cause serious disease. Thus, this project was initiated to characterise the immune response to PARV4, and investigate the clinical significance of this virus.
Cohorts of HCV-infected, HIV-infected, HCV-HIV co-infected, healthy and acute parvovirus B19-infected individuals were screened for humoral and cellular responses in both acute and chronic PARV4 infection. HCV- and HIV-related disease progression was also assessed relative to PARV4 infection. This study demonstrates that the highest prevalence of PARV4 infection is found in HCV-HIV co-infected intravenous drug users, and provides additional evidence for parenteral transmission. I present here the first data on the cellular immune response to PARV4 in acute and chronic infection and define PARV4 as a persistent virus. Although no clear correlation could be found between PARV4 and HCV or HIV disease progression, the high prevalence rates emphasize the importance of investigations into emerging infections such as PARV4.

Keywords: PARV4
HCV
HIV
CD8
T cell
immune response
parvovirus
Advisor: Klenerman, P
Bowness, P
The emergence of a medical exception from patentability in the 20th century

Many patent law dilemmas arise from a failure to understand technologies as embedded in broader social, economic and political realities and to contextually analyze these legal phenomena. This narrowness leads to poor legal development, of which the modern medical exception from patentability is one example. Judges have difficulty interpreting it, patentees do not understand its purpose and it does not protect the important medical technologies to which the public would like access. This thesis applies a legal pluralist analysis to examine the emergence of the medical methods exception in order to understand why it was created and legislated. It starts by examining the origins of the exception in the caselaw, and the informal, concurrent norm established by the emerging medical profession in the early 20th century. It then proceeds to examine why the medical profession might have sought and enforced a norm prohibiting its members from patenting, and concludes that this arose from the need of the medical profession to distance itself from the patent law. As a result, professionalizing physicians established an internal normative order that mimicked and in many cases replaced the effect of the formal law. The thesis then proceeds to examine how the form of the informal norm evolved in the period between WWI and WWII, finding that the profession’s norm transformed and broke down concurrently with its efforts to achieve external legitimacy through legislation. That breakdown arose from factors which included growing labour mobility, greater understanding of the benefits of patents, and a growing role of science and industry in medicine that threatened the profession’s access to valuable medical innovation. The thesis concludes with a study of a current case (Myriad Genetics) that applies the thesis’ theoretical framework to a present dispute over the role the law should play in regulating genetic diagnostic tests.

Keywords: law
patent
exception
medical
profession
history
Advisor: Vaver, D