VictorJuiz/thesis huggingface dataset:
Isoenzyme specific PFK-2/FBPas-2 inhibition as an anti-cancer strategy 
Keywords: FBPase-2
Glycolysis
PFKFB3
Small Molecule Inhibitior
PFK-2
Hypoxia
Pentose Phosphate Pathway
Metabolism
PFKFB1
PFKFB4
PFKFB2

High aerobic glycolytic capacity is correlated with poor prognosis and increased tumour aggressiveness. 6Phosphofructo-1-kinase catalyses the first irreversible step of glycolysis, and is activated by fructose-2,6-bisphosphate, a product of the kinase activity of four bifunctional isoenzymes, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFK-2/FBPase-2:PFKFB1-4). These are potential anti-tumour targets, but their individual and collective role requires further investigation.
This thesis had three aims; to validate the PFK-2/FBPase-2 isoenzymes as anti-cancer targets, to investigate the requirement for isoenzyme-specific targeting, and to initiate assay development, enabling future identification of novel inhibitors.
A panel of cancer cell lines was examined and PFKFB3 and PFKFB4 were confirmed to be the most strongly induced isoenzymes in hypoxia, regulated by HIF-1α. Basal and hypoxic relative PFKFB3/PFKFB4 expression varied markedly, and three cell lines with varying expression ratios (MCF-7, U87, PC3) were selected for further study.
siRNA knockdown of each isoenzyme individually, markedly reduced 2D and 3D cell growth. The effect of PFKFB3 knockdown was consistently more pronounced, particularly in hypoxia. Double PFKFB3/PFKFB4 knockdown was significantly less effective than PFKFB3 knockdown alone. Direct antagonism of PFKFB3 and PFKFB4 on F-2,6-BP concentration was observed, with PFKFB3 exhibiting high kinase activity, as anticipated, and PFKFB4 exhibiting high bisphosphatase activity. The degree of antagonism was dependent on the relative PFKFB3/PFKFB4 expression ratio.
Extensive efforts were made to examine the wider metabolic effect of PFKFB3/PFKFB4 on flux towards glycolysis or the pentose phosphate pathway (PPP), including using metabolite, lipid droplet, 13C NMR and mass spectrometry assays. No significant change in metabolic flux was detected, the evidence presented therefore suggesting the impact of the antagonistic effects of the isoenzymes on [F-2,6-BP] extends beyond regulation of metabolic flux alone.
This study concluded that the most effective therapeutic strategy will be one that involves a PFKFB3-specific inhibitor, preferably hypoxia-targeted. Accordingly, steps were taken to validate and optimise a robust medium-throughput assay system.
Polyyne rotaxanes
Keywords: rotaxanes
Time-resolved spectroscopy
Polyynes
Photophysics

This thesis describes the synthesis of polyyne rotaxanes and an investigation of their excited state photophysical properties. The threading of dumbbell-shaped carbon chains with macrocyclic components is a way to mechanically insulate and control the environment around the carbon chains. The resulting polyyne rotaxanes can serve as model compounds for insulated carbyne. Different strategies have been tested for the synthesis of polyyne rotaxanes with different topologies and structures. Study of rotaxanes in the excited states reveals strong electronic communication between an acetylenic thread and a macrocycle.
Chapter 1 summarizes the field of acetylene scaffolding, introducing some recent achievements in acetylene chemistry. General synthetic methods for polyynes are discussed, and an introduction to active metal template synthesis of rotaxanes is given.
Chapter 2 describes the synthesis of a family of polyyne rotaxanes with different axle lengths and macrocycles, prepared by homocoupling of terminal alkynes. Synthesis of hexayne rotaxane with functional pyridine end-group is presented and a number of crystal structures of polyyne rotaxanes are analyzed.
Chapter 3 demonstrates the use of acetylene cross-coupling in the synthesis of rotaxanes. Synthesis of rotaxanes with different topological structure is provided.
Chapter 4 details the excited state properties of polyynes studied by time -resolved spectroscopy. The complexes of rhenium(I) carbonyls with rotaxanes is presented and the excited state energy transfer in rotaxanes is studied.
Chapter 5 explores new synthetic strategies for polyyne rotaxanes, using "masked" precursors. It also highlights the potential of carbenoid rearrangement of alkyliden es for the construction of linear and cyclic architectures.
Chapter 6 is the summary of the project and general discussion of future directions.
There are two appendices in the end of thesis: Appendix A covers the photophysics of rhenium tricarbonyl complex of the hexayne rotaxane with a small macrocycle and Appendix B reports work towards the synthesis of rotaxanes with platinum(II)-alkyne complexes.
Models of bilingual education in majority language contexts: an exploratory study of bilingual programmes in qatari primary schools
Keywords: language policy
language education
bilingual programmes
bilingual education

The purpose of this thesis was to explore and describe how bilingual programmes are organized and implemented within the unique linguistic and socio-economic case of Qatar. Specifically the thesis explored bilingual programs offered by two types of primary schools in Qatar: international schools and independent schools. Qatar launched a new initiative for educational development in 2001 but with hardly any research linked to these changes.
The study was positioned within a qualitative interpretive tradition drawing on elements of ethnography and grounded theory as tools of methodology. However, quantitative methods were also incorporated within the design. The research design is structured within two main phases: phase one included statistical analysis of secondary data investigating three variables: average teaching time in the first and the second language, students’ and teachers’ nationality. Phase two utilized a multi-case study design. One school from each type was examined in depth over a period of nine weeks. Data were collected by means of school documents, interviews, and non-participant observation of English and Arabic classes.
The first phase made an initial impression of the model of bilingual education followed by international and independent schools compared to bilingual typologies found in the literature. The analysis of the two cases examined revealed various differences across the two types. Findings reveal that the international school followed a partial immersion type of programme while the independent school followed a Content and Language Integrated Learning (CLIL) type of programme. The study reveals that the Qatari bilingual schools context was one of heteroglossia, with three codes in operation: Modern Standard Arabic, Colloquial Arabic dialects and English. Findings reveal that teachers and students in the international school adopt a strict separation policy between the two languages following a monoglossic belief. Language teachers and students in the independent school were found to apply a flexible language policy inside English and Arabic classes. The study revealed a gap between claimed programme features and implementation of these features. An absence of a clear language policy in the schools was also a main finding relating to the practice of these schools.
In light of these findings, adopting a clear and explicit language-in-education policy should be a priority for policy makers in Qatar. The study revealed how the diglossia situation in Qatari schools is unique and therefore schools must be aware of the languages at the disposal of students and teachers. Schools must also concentrate on developing academic language skills needed for success in L2 schooling.
The financing of entrepreneurial firms in the UK: a comparison of business angel and venture capitalist investment procedures
Keywords: investment
business angels
entrepreneurial firms
venture capitalists

Although just a minority of all small firms in the UK, high-growth entrepreneurial ventures are becoming widely recognised for their role in job growth and economic prosperity. However, due to their inherently high-risk nature, many of these early-stage firms experience difficulty in securing outside finance from institutional investors, which ultimately limits their growth and economic potential.
Fortunately, two investor types, business angels (BAs) and venture capitalists (VCs), do fund a small proportion of these entrepreneurial ventures, although they, especially BAs, often have much more financial capital available for such investments. Since many aspects of BA and VC investment processes remain unknown, it is hoped that a better understanding of how and why these investors fund particular investments may aid in further lessening the entrepreneurial funding problem.
This research study, therefore, conducts the first-ever detailed comparison of the investment criteria and procedures of these two financiers across the full investment process. To make the study more robust, a theoretical base is adopted (based on agency theory) to form research hypotheses which propose that BAs and VCs in the UK may use different approaches to limit potential agency risks in their investments (i.e. the risks associated with an entrepreneur's potential misuse of the investor's money). Utilising data from 40 personal interviews and 262 questionnaire responses, this study empirically supports the main hypothesised notion that, although both investors reduce agency risks at all stages of the investment process, BAs place more emphasis on doing so ex-post investment (the incomplete contracts approach), whilst VCs stress doing so more ex-ante investment (the principal-agent approach).
In supporting the hypothese, empirical information is gathered about each investment stage and each investor group's heterogeneity. Possible implications of these findings are then discussed in the hope of aiding, no matter how slightly, the funding efficiency of small entrepreneurial firms.
Algebraic modules for finite groups
Keywords: tensor product
representation theory
Algebraic modules

The main focus of this thesis is algebraic modules---modules that satisfy a polynomial equation with integer co-efficients in the Green ring---in various finite groups, as well as their general theory. In particular, we ask the question `when are all the simple modules for a finite group G algebraic?' We call this the (p-)SMA property. The first chapter introduces the topic and deals with preliminary results, together with the trivial first results. The second chapter provides the general theory of algebraic modules, with particular attention to the relationship between algebraic modules and the composition factors of a group, and between algebraic modules and the Heller operator and Auslander--Reiten quiver. The third chapter concerns itself with indecomposable modules for dihedral and elementary abelian groups. The study of such groups is both interesting in its own right, and can be applied to studying simple modules for simple groups, such as the sporadic groups in the final chapter. The fourth chapter analyzes the groups PSL(2,q); here we determine, in characteristic 2, which simple modules for PSL(2,q) are algebraic, for any odd q. The fifth chapter generalizes this analysis to many groups of Lie type, although most results here are in defining characteristic only. Notable exceptions include the small Ree groups, which have the 2-SMA property for all q. The sixth and final chapter focuses on the sporadic groups: for most groups we provide results on some simple modules, and some of the groups are completely analyzed in all characteristics. This is normally carried out by restricting to the Sylow p-subgroup. This thesis develops the current state of knowledge concerning algebraic modules for finite groups, and particularly for which simple groups, and for which primes, all simple modules are algebraic.
Genetic regulation of Kranz anatomy
Keywords: Setaria
rice
C4
leaf development
Kranz
maize
transcriptomics

The C₄ photosynthetic cycle acts to concentrate CO₂ around the enzyme Rubisco. By doing so, C₄ photosynthesis leads to increased radiation, water and nitrogen use efficiencies. As such, C₄ photosynthesis is the most productive form of photosynthesis known. Because it enables such high levels of productivity there are large international efforts to introduce C₄ photosynthesis into non-C₄ crop species such as rice. Kranz anatomy is a characteristic leaf cellular arrangement of concentric rings of bundle sheath and mesophyll cells around closely spaced veins and is crucial to C₄ photosynthesis in almost all known examples. Despite the fact that Kranz has evolved on over 60 times independently little is known about the genetic regulation of Kranz development, as attempts to elucidate Kranz regulators using conventional mutagenesis screens have provided few insights. However, the advent of next generation DNA sequencing technologies has enabled the interrogation of genetic networks at a previously unprecedented scale. The work in this thesis describes a genome-wide transcriptomic analysis of leaf development in maize, a C₄ species, that develops both Kranz-type and non-Kranz-type leaves. Detailed bioinformatics analyses identified candidate regulators of both Kranz development and additional aspects of maize leaf development. Three of the identified Kranz candidates were functionally characterised in both C₄ and non-C₄ species. Furthermore, expression and phylogenetic analyses of GOLDEN2-LIKE (GLK) genes, a small transcription factor family previously implicated in C₄ development in maize, were extended to determine the generality of GLK function in C₄ evolution.
The role of LATS1 in DNA damage signalling
Keywords: DNA Damage Repair
Cancer Research
LATS1
Tumour Suppressor
Replication Fork Stabilisation

Genomic DNA is constantly exposed to assaults, which if not dealt with, can lead to genomic instability and carcinogenesis. In response to stress including either Ionising Radiation (IR) or replication stress, ATM and ATR promote the activation of cell cycle checkpoints and initiate repair of DNA damage. Recent studies have revealed that ATM signalling can activate LATS1 via a cascade through RASSF1A and MST2. LATS1 is a tumour suppressor, which forms a barrier to carcinogenesis restricting cell proliferation and promoting apoptosis by stabilising a YAP/p73 transcriptional complex, hence upregulating p73 responsive genes. LATS1 is inactivated through promoter hypermethylation in a number of cancer types including breast cancer and soft tissue sarcoma. This research project seeks to define the mechanism through which LATS1 is involved in IR-induced DNA damage signalling. The data presented in this thesis shows that LATS1 controls CDK2 and regulates phosphorylation of S3291 on BRCA2. Cells lacking LATS1 exhibited enhanced accumulation of damage-induced Rad51 foci leading to cell cycle arrest at the G2/M checkpoint. Furthermore, the data presented here suggests that LATS1 may not be required for homologous recombination. This work supports the hypothesis that LATS1 inhibits CDK2-dependent phosphorylation of BRCA2 at S3291, hence protecting stalled replication forks from nucleolytic degradation.
Riparian reserves in oil palm plantations: biodiversity, ecological processes and ecosystem services
Keywords: ants
conservation
Palm oil
dung beetles
riparian zones

As the human population expands, agricultural expansion and intensification will exert an increasing pressure on remaining habitats, especially in the tropics. Oil palm is one of the most rapidly expanding crops in these regions, and identifying management strategies that conserve biodiversity and ecosystem services in these landscapes is therefore a priority.
I assess whether riparian forest fragments (riparian reserves) conserve species and the functions they support within oil palm landscapes. Riparian forests are legally required for their beneficial impact on hydrological dynamics and their potential to contribute to the conservation of terrestrial species is poorly documented.
I focussed on two ecologically important indicator groups (ants and dung beetles) and the ecosystem processes that they support.
Whilst protecting primary forest will remain the most important strategy for biodiversity conservation, I found that riparian reserves do support species of ants and dung beetles that would not otherwise persist in oil palm landscapes. However, the extent to which riparian reserves maintained key ecological functions differed between these two taxa. The amount of nutrient distribution carried out by ants in riparian reserves was similar to logged forest areas, and higher than in oil palm. In contrast, dung removal functions did not vary between these land uses.
I also investigated how the vegetation structure and landscape context of riparian reserves affects the dung beetle communities they support. Increasing reserve width and proximity to other forest fragments had a positive impact on the species richness and diversity of dung beetles in riparian reserves.
There was little evidence that riparian reserves enhance the provision of dung removal or pest control services in adjacent areas of oil palm.
The results provide evidence to support the introduction and/or enforcement of legislation to protect riparian forest reserves in order to conserve biodiversity and ecological processes in oil palm landscapes.
Muon-spin relaxation and its application in the study of molecular quantum magnets
Keywords: Muon-spin relaxation
density-functional theory
molecular magnetism

This thesis is concerned with the muon-spin relaxation (musr) technique and its application in the study of a number of molecular magnetic systems that may be driven through a quantum phase transition at low temperatures through the application of a magnetic field or hydrostatic pressure.
Musr is a highly sensitive probe of magnetism, but its utility can be severely limited by the lack of knowledge of the muon implantation site and the extent to which the muon perturbs its host. In a system of ionic fluorides, where partial information about the muon site is experimentally available, I demonstrate systematically that these problems can be addressed accurately using electronic-structure calculations. The F--mu--F complex formed by muons in many fluorides can be understood as an exotic molecule-in-a-crystal defect with a zero-point energy larger than that of any naturally-occurring triatomic molecule.
I demonstrate the interesting possibility of controlling the magnetic dimensionality in a molecular magnet using applied pressure. musr and high-field magnetisation experiments under applied pressure on the coordination polymer CuF2(H2O)2(pyrazine) show a transition from a quasi-two-dimensional to a quasi-one-dimensional antiferromagnetic phase. Density-functional theory calculations and calculations of the dipolar anisotropy complement the experiments.
I describe how subtle differences in chemical composition can lead to starkly different structural and magnetic properties. [Cu(pyz)(H2O)(gly)2](ClO4)2 may be considered an antiferromagnetic chain that orders below 50 mK while the related compound [Cu(pyz)(gly)](ClO4) is formed from Cu2+ dimers and remains disordered down to 30 mK in zero field, but displays a field-temperature phase diagram consistent with the Bose-Einstein condensation of triplons. I also describe musr measurements on the strong-leg spin ladder DIMPY and on the molecular nanomagnets Cr8Cd and Cr8Mn which highlight some of the remaining challenges for longitudinal-field musr experiments.
The effect of relatedness on sexual dynamics. Studies of red junglefowl and fruit flies
Keywords: sexual conflict
Coolidge effect
kin selection
senescence
inbreeding

In this thesis, I explore four different ways in which relatedness affects sexual interactions in the red junglefowl Gallus gallus ssp., and the fruit fly Drosophila melanogaster. First, I show that in both species, inbreeding depression is sex-specific and modulated by parental age and gametic age. However, the sex that suffers higher inbreeding depression was trait- and species-dependent. Second, I examined patterns of inbreeding avoidance. I found no evidence of inbreeding avoidance in the fruit fly, but in the red junglefowl both males and females avoided mating with relatives, independently from sex-ratio of the social group. Third, I investigated whether relatedness amongst members of one sex affects mate choice in members of the opposite sex. Male fruit flies preferentially courted females unrelated to females with whom they had previously mated, while female flies displayed a weak preference for males related to their previous mates. In the red junglefowl, females exposed to male trios of two males related to each other and one unrelated male, displayed a marked preference for mating with the male unrelated to the other two males, and might also bias postcopulatory sperm utilization in favour of the unrelated male. Fourth, I explored the implications of male relatedness on the intensity of male-male competition. Male red junglefowl were less aggressive towards related competitors, but invested more sperm in females that had previously mated with a related male rather than with an unrelated male. In fruit flies, male relatedness had a strong impact on female life-history and offspring viability, although I found no evidence that these effects were modulated by changes in male-male competition. Collectively, the findings of these studies demonstrate the complex relationship between relatedness and other important biological phenomena as such senescence and sexual conflict.
Narconovela: four case studies of the representation of drug trafficking in Mexican fiction
Keywords: Mexican Literature
Latin American Literature
Mexico
Narconovela
Drug Trafficking

In addition to coverage in the national and international media of the ongoing violence in Mexico related to the drug trade, there has been growing interest in fictional representations of the Mexican drug trade, its origins and social context. There is now a considerable body of written narratives that have been christened narconovelas. A small number of academic works has charted the emergence of the narconovela and sought to examine how drug traffickers have been represented and evaluated in fiction. However, very little attention has been paid to the aesthetic qualities of ‘narco-literature’. This study examines four of the most highly-regarded works in detail: Balas de plata (2008), by Élmer Mendoza; Los minutos negros (2006), by Martín Solares; Contrabando (2008), by Víctor Hugo Rascón Banda; and Trabajos del reino (2004), by Yuri Herrera. So embedded is the phenomenon of drug trafficking in northern Mexican culture, so suffused with cliché is its representation in other media, that to write about the topic with originality and ethical nuance is difficult. This thesis accounts for the distinct choices made by the four authors in question to address this difficulty of representation in the structure, style and tone of their novels. The self-awareness exhibited by these works of fiction regarding the challenges of representing their subject matter render them the most sophisticated examples yet created of the so-called narconovela.