VictorJuiz/thesis huggingface dataset:
Ultraselective nanocatalysts in fine chemical and pharmaceutical synthesis
Keywords: alkynes
liquid phase
formic acid
subsurface
interstitial
2-chloronitrobenzene
selective hydrogenation
heterogeneous catalyst
nuclear magnetic resonance
kinetic modelling

Surface catalysed reactions play an important role in chemical productions. Developments of catalyst requiring high activity whilst improving on product selectivity can potentially have a profound effect in the chemical industry. Traditional catalyst modifications were focused on tuning the size, shape and foreign metal doping to form well defined metal nanoparticles of unique functionalities. Here, we show new approach to engineering of metal nanocatalysts via a subsurface approach can modify the chemisorption strength of adsorbates on the surface. Carbon modified nanoparticles were synthesised using glucose to stabilise Pd nanoparticles at a molecular level. Upon heat treatment, the carbonised glucose encapsulated the Pd nanoparticles with carbon atoms take residence in the octahedral holes (15 at.%). These materials were tested in liquid phase stereoselective hydrogenations of 3-hexyn-1-ol and 4-octyne. The former has importance in the fragrance industry towards the production of leaf fragrance alcohol. It was shown for the first time that the geometrically and electronically modified Pd with interstitial carbon atoms reduced the adsorption energy of alkenes, ultimately leading to higher reaction selectivity. Boron modified Pd nanoparticles was synthesised using BH3.THF in the liquid phase. The material possess high B interstitial saturation (20 at.%), which can be synthesised for the first time below 100°C. These materials were tested in the liquid phase selective hydrogenation of various alkynes and 2-chloronitrobenzene, of which the latter has importance in the pesticides industry. Kinetic modelling on the hydrogenation of 4-octyne suggests these subsurface occupied B does play a pivotal role on increasing the reaction selectivity, as removal of these species lead to decreased selectivity. Au nanoparticles were synthesised and characterised using H13COOH NMR. The new liquid NMR characterisation method is successfully applied to examine the chemisorption strength of metal nanoparticles. An attempt to synthesise PVP capped B modified Pd nanoparticles with the above NMR characterisation was investigated. It is believed the examples of subsurface atom modifications as shown here may offer future catalyst developments in this area.
Angiogenesis in human lung tumours
Keywords: CGH
Angiogenesis
Lung Cancer
small-cell/neuroendocrine 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.
Galaxy evolution with FMOS
Keywords: galaxy evolution

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.
Ammonia borane and its derivatives: high weight percentage hydrogen storage materials
Keywords: ammonium borohydride
ammonia borane
hydrogen storage

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.
Targeting EGFR signalling pathway in triple negative breast cancer 
Keywords: genomics
cell biology
Cetuximab
drug resistance
EGFR
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.
Investigating a role of ASPP2 in the cellular response to infection
Keywords: p53
Epstein-Barr Virus
nasopharyngeal
ASPP2
tuberculosis
p63

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.
Beyond schools and monasteries: literate education in late Roman Syria (350-450 AD)
Keywords: Syriac
Syriac Translations from Greek
Classics
Greek Literature
Late Antiquity

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.
Characterisation of the immune response to PARV4
Keywords: PARV4
HCV
HIV
CD8
T cell
immune response
parvovirus

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.
The emergence of a medical exception from patentability in the 20th century
Keywords: law
patent
exception
medical
profession
history

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.
Fourier transform ion cyclotron resonance mass spectrometry for petroleomics
Keywords: artificial neural networks
mass spectrometry
machine learning
FT-ICR-MS
data modelling
genetic algorithms
petroleomics

The past two decades have witnessed tremendous advances in the field of high accuracy, high mass resolution data acquisition of complex samples such as crude oils and the human proteome. With the development of Fourier transform ion cyclotron resonance mass spectrometry, the rapidly growing field of petroleomics has emerged, whose goal is to process and analyse the large volumes of complex and often poorly understood data on crude oils generated by mass spectrometry.
As global oil resources deplete, oil companies are increasingly moving towards the extraction and refining of the still plentiful reserves of heavy, carbon rich and highly contaminated crude oil. It is essential that the oil industry gather the maximum possible amount of information about the crude oil prior to setting up the drilling infrastructure, in order to reduce processing costs.
This project describes how machine learning can be used as a novel way to extract critical information from complex mass spectra which will aid in the processing of crude oils.
The thesis discusses the experimental methods involved in acquiring high accuracy mass spectral data for a large and key industry-standard set of crude oil samples. These data are subsequently analysed to identify possible links between the raw mass spectra and certain physical properties of the oils, such as pour point and sulphur content.
Methods including artificial neural networks and self organising maps are described and the use of spectral clustering and pattern recognition to classify crude oils is investigated. The main focus of the research, the creation of an original simulated annealing genetic algorithm hybrid technique (SAGA), is discussed in detail and the successes of modelling a number of different datasets using all described methods are outlined.
Despite the complexity of the underlying mass spectrometry data, which reflects the considerable chemical diversity of the samples themselves, the results show that physical properties can be modelled with varying degrees of success. When modelling pour point temperatures, the artificial neural network achieved an average prediction error of less than 10% while SAGA predicted the same values with an average accuracy of more than 85%. It did not prove possible to model any of the other properties with such statistical significance; however improvements to feature extraction and pre-processing of the spectral data as well as enhancement of the modelling techniques should yield more consistent and statistically reliable results.
These should in due course lead to a comprehensive model which the oil industry can use to process crude oil data using rapid and cost effective analytical methods.