VictorJuiz/thesis huggingface dataset:
The Greek hero Perseus : myths of maturation
Keywords: myths
hero
Greek heroes
Greek hero
heroes
Perseus

Owing to a certain fascination with the Gorgon and its origins, past scholarship has given less consideration to Perseus as a heroic figure in his own right than might be expected. He is generally thought of as colourless in comparison with heroes such as Heracles, Theseus and Jason. As a body, his myths have in any case received little attention in the last thirty years, and the thesis attempts to redress the balance, to ‘parse’ Perseus by ‘construing’ his myths. He is indispensable to all the myths. The initiatory schema, in terms both of a general rite of passage, and more specifically of ‘ephebic’ motifs, is central, and is established in the introductory chapter (I). The movement of the hero from οικος to πολις, is coextensive with his maturation. The remaining chapters (II-V), on Acrisius, the Gorgon, Andromeda and Dionysus, follow through the process of Perseus’ maturation, from his anomalous birth, exposure, his youthful exploits, acquisition of a wife, to his return to and defence of the πολις, Argos, from Dionysus and his θιασος. He returns to Argos with divine sanction despite all mortal attempts to prevent him: the preservation of the οικος, and by extension the πολις, is key to the characterization of Perseus. His myths are a particularly potent example of the tendency, and imperative for, Greek values of civilization, as represented by the οικος and πολις, to be perpetuated. In this sense, Perseus is a ‘political’ hero. An appendix on the fragmentary Perseus dramas performed in antiquity confirms his popularity throughout the whole of the fifth century and beyond, and shows that, contrary to what the relatively skeletal sources might suggest, he was not simply a cipher, but a fully characterized figure in the Greek imagination.
Influence of inherited genetic variants on risk, biology and prognosis of common cancers
Keywords: stratified GWAS
cancer prognosis
somatic driver mutations
cancer risk
p53 tumour suppressor
germline by somatic interaction
KRAS oncoprotein
adaptive immune response
inherited genetic variants

Cancer is a complex disease affected by both inherited risk variants and somatic alterations. Recent studies showed that inherited genetic variants and somatic driver mutations converge in cancer hallmark pathways, and that inherited genetic variants were associated with specific somatic driver mutations in tumours. However, it is unclear whether common inherited genetic variants interact with somatic driver mutations to influence cancer risk and prognosis.
In this study, I analyse multi-cancer datasets to investigate germline by somatic interaction in cancer and to evaluate the role of inherited genetic variants on risk, prognosis, nearby gene expression, response to anti-cancer therapy and adaptive immune response in common cancers. I describe how the p53 poly(A) SNP, rs78378222 (17p13.1; TP53), interacts with p53 mutational status in tumours to influence cancer risk, response to therapy and prognosis in common cancers. I find that a known colorectal cancer risk locus at 10p14 (rs10795668; ATP5C1) interacts with KRAS mutational status in tumours to associate with colorectal cancer risk. I identify two loci at 15q26.2 (rs72767781; NR2F2-AS1) and 15q22.2 (rs11447843; VPS13C) associated with prognosis in early-stage colorectal cancer at genome-wide significance, together with numerous suggestive loci. In particular, rs184423256 (8q22.3; RRM2B) and rs114887409 (4p16.1; ABLIM2) interact with KRAS mutational status in colorectal cancer to associate with clinical outcomes. Furthermore, I identify 22 loci associated with infiltrating CD8+ T cell density in colorectal cancer, which are used to infer the causal relationship between adaptive immune trait and prognosis in early-stage colorectal cancer.
In summary, this study constitutes an integrative analysis of germline by somatic interaction on risk, biology, and prognosis of common cancers. The findings provide supportive evidence that inherited genetic variants can play an active role during tumour development, thus offering insight into the genetic basis of cancer susceptibility and practical guidance for personalised disease prediction.
Extending the scope of covalent peptide-protein conjugation: from purification to expanded nanoassembly
Keywords: SpyCatcher
pH switch
Protein purification
Oligomerisation
Protein engineering

The surprising discovery of intramolecular isopeptide bonds within Gram-positive bacteria pili and surface adhesins gave rise to the development of a new type of protein conjugation method, namely the Tag/Catcher system. Among the different kinds of Tag/Catcher platforms, SpyTag/SpyCatcher is the leading system with more than 200 articles utilising the technology due to the rapid and buffer-independent nature of the reaction. In this thesis, I have developed a purification method called Spy&Go to complement the SpyTag/SpyCatcher platform. Spy&Go enables the purification of proteins using SpyTag as the affinity peptide tag. Spy&Go thereby eliminates the dependence on extraneous tags for purification of proteins intended for SpyCatcher-based protein conjugation reactions. Spy&Go was developed by engineering SpyCatcher2.1, a fast reacting variant of SpyCatcher, to become SpyDock by removing reactivity whilst maintaining tight binding to SpyTag. The purity of proteins purified through Spy&Go was comparable to the purity of proteins purified by Ni-NTA using a polyhistidine tag. Subsequently, a different route for elution of SpyTag-proteins was explored by conferring pH-sensitivity to a SpyDock variant through the introduction of histidine residues at the SpyTag003-binding interface. With the combined effects of three histidine mutations, SpySwitch was developed, which can bind SpyTag003 at pH 8.0 and release at pH 5.0. SpyTag/SpyCatcher has been used to modularly multimerise proteins for vaccination, nanomedicine and making enzymatic nanoreactors. To extend the scope of SpyCatcher-based protein multimerisation platforms, I developed a Spy oligomerisation toolbox composed of SpyCatcher002 fused to coiled coils, to multimerise SpyTag-proteins into dimer, trimer, tetramer, pentamer, hexamer and heptamer assemblies. The SpyCatcher002-oligomers enable a rapid and scalable route to multimerise different proteins into defined assemblies. An agonistic nanobody against Death Receptor 5 was multimerised through SpyCatcher002-oligomers and showed a stoichiometry-dependent effect on breast cancer cell line apoptosis upon receptor activation.
John Ashenden and the Scientia astrorum Mertonensis : with an edition of Ashenden's Pronosticationes
Keywords: astronomy
Scientia astrorum Mertonensis
Pronosticationes
medieval astronomy
John Ashenden
medieval
astrology

John Ashenden, who flourished between the years 1336and 1365, was a fellow of Merton College,Oxford, and an astrologer. In the later Middle Ages the science of the stars, or scientia astrorum, comprised both astronomy and astrology. Merton College is well known for the school of natural philosophy which prospered there in the first half of the fourteenth century. At the same time, a group of Merton fellows and their acquaintances specialized in the scientia astrorum. Ashenden’s writings are illustrative of the scholarship of this Merton circle. The circulation and copying of astronomical and astrological texts played a major part in their studies. Ashenden compiled a large Summa of astrological theory from nearly one hundred sources. He also made predictions on the basis of reputed influences of eclipses and planetary conjunctions. Coincidental events, which appeared to follow what he had predicted, greatly encouraged him. He composed his predictions out of academic interest rather than for personal gain. His writings continued to be read for 400 years; yet by the Age of Enlightenment his learning had lost its value. Ashenden’'s scholarship was indicative of the weaknesses of medieval scientific enquiry--it was mostly qualitative rather than quantitative;and assertions were never put to real experimental tests. Astrology had as much to do with theology as it had with science. The questions of determinism, natural causation,and numerological prophecy excited Oxford theologians. On these issues Ashenden stood on an orthodox middle-ground.
The examination of marriage ritual among selected groups in South India
Keywords: marriage ritual
caste
ritual
India
South India

This thesis is concerned with variations in the traditional Hindu marriage ceremony as practiced by the several Tamil-speaking castes on the east coast of South India, The primary objective is to survey the descriptions of marriage ritual which are available in the current literature, rather than to attempt a sociological analysis of any particular problem. The intention has been to organize and examine the existing material with a view to additional field research in person in the near future. In the following pages we point out several significant differences in the nuptial rituals as they are performed at different levels in the caste hierarchy and these facts are interspersed with a discussion of the relation of the marriage ceremony to South Indian ritual in general. Because information on this topic is relatively abundant, the area to be considered in detail has been limited to three districts of Madras State: South Arcot, Tiruchirappalli and Thanjavur.
Continued in thesis ...
Understanding the mechanism of Adenovirus endosomal escape
Keywords: protein structure
protein characterisation
liposomes
viral entry
protein purification
endocytosis
electron microscopy
adenovirus

Adenoviruses (AdV) are non-enveloped dsDNA viruses that cause respiratory and gastrointestinal diseases and are commonly used as vaccine and gene therapy vectors. In order to replicate inside a host cell, AdV must first penetrate the endosomal membrane and gain access to the cytosol. A highly conserved amphiphilic alpha helix within AdV protein VI (pVI) has been proposed as the membrane-lytic factor that is necessary for endosomal escape. However, the precise mechanism of endosomal membrane disruption is uncertain. This investigation aimed to characterise pVI and investigate the contribution of different domains using several biophysical techniques and electron microscopy. Firstly, a purification protocol was developed for recombinant wild type pVI and two loss of function mutants. The three pVI proteins, along with a synthetic peptide composed of the suggested membrane-lytic domain of pVI, were then examined using circular dichroism and analytical ultracentrifugation in order to further understand their secondary structure and oligomeric state. The effect of pVI on liposomes was then investigated using dynamic light scattering and a dye release assay and visualised using electron cryo-microscopy (cryoEM). Finally, electron cryo-tomography (cryoET) was used to examine membrane disruption events in 3D. The activity of pVI constructs upon liposomes was observed to be highly dependent on the membrane composition, with phosphatidylethanolamine reducing the activity of pVI.
The annexation of populations: a new state strategy?
Keywords: Citizenship
Realism
Constructivism
Politics
Power politics
State strategy
Hungary
Nationalism
Ethnicity
Extraterritorial naturalisation
Russia
Foreign policy
International Relations
Identity

This thesis aims to analyse the extraterritorial naturalisation practices of Russia and Hungary to determine the states’ motivation and the domestic and international consequences of the policies. At the individual level, it remains a state’s legal prerogative to confer citizenship upon whomever it wishes consensually. When done to an extraterritorial collective, the practice can and has caused disputes between states. Russian and Hungarian state officials defend the practice by arguing the conferral of citizenship is a legal manifestation of a responsibility to privilege co-nationals, wherever they may reside. While this position cannot be entirely dismissed, it is argued that it lacks sufficient explanatory power and that strategic and instrumental motivations are fundamental to the practice. Research in International Relations has so far neglected to investigate citizenship policies from a strategic foreign policy perspective, a shortcoming this thesis seeks to address. Using a case study qualitative research design involving fifty-two interviews with political stakeholders and an official state discourse analysis, it shows that Russia and Hungary have made international and domestic gains by naturalising targeted populations in their contiguous states, which can be metaphorically described as an annexation of populations. The official state discourse from the leaders of Russia and Hungary relating to external populations and territory are found to exhibit similarities. This thesis offers an emotive analogue that the extraterritorial naturalisations are justified as a means to rectify perceived injustices at historical losses caused by external rivals. The significance of this study is that it informs our theoretical understandings of key concepts of International Relations by focussing on the implications of extraterritorial naturalisation on sovereign territorial integrity, the nation, (dual) citizenship and will interest constructivists and realists and those interested in international law.
Elucidating the molecular mechanism of TET2 function in hematopoiesis
Keywords: Gene regulation
DNA methylation
Tet2

DNA modifications are epigenetic marks deposited throughout the mammalian genome and play an important role in gene regulation in normal and malignant biological processes. Biological DNA modifications are introduced by DNA methyltransferases (DNMT) and dioxygenases of ten- eleven translocation (TET) family. DNMT proteins can convert cytosine into 5-methylcytosine. TET proteins catalyze the oxidation of 5mC to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. These oxidized forms of cytosine stay in the DNA or result in DNA demethylation. TET2, a member of TET family proteins, is one of the most frequently mutated genes in hematological malignancies. While TET2 has roles in normal hematopoiesis, including stem cell self-renewal and specific lineage commitment, the exact molecular mechanism of its function still remains unknown. The aims of the project are to identify the role of TET2 in regulating hematopoietic gene expression and to identify the molecular partners of TET2 in the hematopoietic-associated context, thus to arrive at the mechanism of action of TET2 in normal hematopoiesis.
To study the Tet2 function in a hematopoietic context, I chose the mouse hematopoietic progenitor cell line, HPC-7, as a model system. I constructed the Tet2-knock-out (KO) HPC-7 cell and characterized the cell differentiation phenotype caused by Tet2 depletion. To understand the role of Tet2 in gene regulation, I firstly identified genes affected by Tet2 depletion. Then I mapped the Tet2 binding profile in HPC-7 and discovered genes directly targeted by Tet2. Finally, I assessed the contribution of DNA demethylation in Tet2-mediated gene regulation. The results revealed that Tet2 deficiency caused a block of cell differentiation in the Colony-forming-unit assay. Genes involved in hematopoiesis were differentially expressed upon Tet2 deficiency. Surprisingly, Tet2 binding is associated with both gene activation and gene repression. Tet2 binds to the hematopoietic-enhancers together with many hematopoietic transcription factors, and leads to DNA demethylation at enhancers, thus activates the expression of essential hematopoietic genes, such as csf1R, Cebpa, Cebpe. The mechanism by which Tet2 negatively regulates its targeted gene expression needs further investigation.
To identify Tet2 molecular partners in the hematopoietic-associated context, I mapped the TET2 interactome in HPC-7 cells by immunoprecipitation coupled to mass spectrometry. Our data suggests that polycomb repressive complex 2 (PRC2) physically interacts with Tet2 via the C- terminus of Tet2 protein. The functional importance of Tet2-PRC2 interaction in gene regulation and cell differentiation remain further explored.
Taken together, this study systematically investigated the Tet2-mediated gene regulation and identified new Tet2 binding partner, PRC2 complex, suggesting a novel mechanism of Tet2 function in hematopoiesis.
Roll-to-Roll processable organic thin film transistor based circuits and their sensory application
Keywords: Roll to Roll
Flexible electronics
Sensors
Organic Thin Film Transistor
Healthcare application

This thesis is trying to explore a possible routine to manufacture flexible sensor via vacuum-based processes. It starts with an exploration of a route to manufacture Organic Thin Film Transistors (OTFTs) and then a series of stabilization methods are discussed to reduce the probability of short circuit, current leakage and improve the performance of OTFTs, i.e., increasing mobility and decreasing threshold voltage. In addition, a possible mechanism of bias stress is investigated with a model and the relevant evolution of trapping state and trapping energy is plotted over time and distance from the dielectric/semiconductor interface. Next, a short-time bias scheme is demonstrated to reduce error of bias stress during strain tests. A first example of a strain sensor is based on the architecture of floating gate OTFTs, i.e., a PVDF coated floating gate that transfers the signal of charge imbalance from the ferroelectric effect to transistors, and then the OTFT will output the amplified signal. The advantage of floating gate structure is the separation of the transistor and sensor part to avoid interference between transistor and sensing reaction and giving the option for the transistor to be encapsulated from the environment. However, the bias voltage is a key parameter to control the floating gate sensor, with the sensitivity of the device dependant on it, i.e., it is very difficult to obtain both a sensitive signal at same time as one unaffected by bias stress. In order to obtain a sensitive and stable signal, a series of OTFT-based functional circuits are developed and a transimpedance converter is fabricated to convert nano-scale input current to a readable voltage output (0 – 3V). After encapsulation, the linear converting relationship is maintained and the mechanical flexibility is not affected. Finally, a series of sensors are built with the OTFT-based signal conditioning circuit to detect arterial pulse from human body, pH, hydrogen peroxide and glucose from solution. Conclusively, this thesis demonstrates a new architecture of OTFT-based sensing system, and that can work as a versatile platform to integrate with different functionalized sensing electrodes to process signals to a readable level and visualized with smartphone via Bluetooth microcontroller.
Phase-dependent closed-loop modulation of beta-frequency network oscillations in parkinsonian rats
Keywords: Parkinson's disease
closed-loop stimulation

Normal brain function is associated with an assortment of oscillations of various frequencies, each reflecting the timing of separate computational processes and levels of synchronization within and between brain areas. Stimulation accurately delivered on a specified phase of a given oscillation provides the opportunity to target individual aspects of brain function. To achieve this, we have developed a highly responsive system to produce a continuous online phase-estimate. In addition to stable oscillations, the system accurately tracks the early cycles of short, transient oscillations and can operate across the frequency range of most established neuronal oscillations (4 to 250 Hz).
Here we demonstrate bidirectional modulation of the pathologically elevated parkinsonian beta-band oscillation (around 35 Hz) in 6-OHDA hemi-lesioned rats. Beta phase, monitored using a single channel electrocorticogram above secondary motor cortex, was used to drive electrical stimulation of the globus pallidus or subthalamic nucleus on one of eight phases spanning the oscillation cycle. Stimulation of the early ascending phase suppressed the oscillation whereas stimulation of the early descending phase was amplifying. By implementing a rule that prevented stimulation when the phase estimate was unstable, we achieved a system that could adapt stimulation rate and pattern to respond to the changes produced in the target oscillation. This allowed the electronic system to create and maintain a state of equilibrium with the biological system resulting in continuous stable modulation of the target oscillation over time.
Elevated beta-band activity correlates with motor impairment in humans, primates, and rodents. In an attempt to establish a causal relationship, we used phase-locked stimulation to modulate ongoing cortical beta activity during concurrent assessment of spontaneous forelimb use or goal-directed walking. Despite large deficits in paw use on the injured side during the cylinder task, phase-locked stimulation was unable to modulate forelimb asymmetry. In contrast, consistent reductions in average speed were produced when amplifying beta activity that were driven by a change in running style preference that favoured smaller and slower steps. Altered stand time variance was also observed during individual runs, suggesting that beta-band amplification impaired interlimb coordination. Locomotor deficits were phase-dependent and only present when targeting amplifying phases, thus supporting the functional role of beta-band oscillations in parkinsonian motor impairment.
The results in this study demonstrate the feasibility of phase locked stimulation as a more refined strategy for remediation of pathological beta oscillations in the treatment of the motor symptoms of Parkinson’s disease. Furthermore, they establish the utility of our algorithm and allow for the potential to assess the contribution of rhythmic activity in neuronal computation across a number of brain systems.