VictorJuiz/thesis huggingface dataset:
The revival of Sphoṭa in early modern Benares: Śeṣakṛṣṇa's Sphoṭatattvanirūpaṇa
Keywords: Śeṣakṛṣṇa
Sphotatattvanirupana
Sphota
Sphoṭa
Sesakrsna
Sphoṭatattvanirūpaṇa
Early Modern India

This thesis examines the revival of the sphoṭa doctrine in early modern Benares and &Sacute;eṣakṛṣṇa's Sphoṭatattvanir&umacr;paṇa as an influential work in that revival. The sphoṭa doctrine is the richest contribution of the grammarians to the philosophy of language, but its semantic significance was not highlighted until late, because its theological implication was stronger. &Sacute;eṣakṛṣṇa was a renowned Sanskrit grammarian who flourished in sixteenth-century Benares. He also wrote poetry and Dharma&sacute;āstric works, and played an important role as a juridical authority. Despite his illustrious career, &Sacute;eṣakṛṣṇa encountered criticism for his works from contemporary critics. The only work he wrote solely on the philosophy of language was the Sphoṭatattvanir&umacr;paṇa. As the first discrete work on sphoṭa by a grammarian, the Sphoṭatattvanir&umacr;paṇa represented an important landmark in the later expositions of the doctrine of sphoṭa particularly because it renewed the later grammarians' interest in sphoṭa, which then resulted in a series of individual works of a similar sort. The revival of the sphoṭa doctrine in early modern Benares coincided with that of the philosophy of language, which was caused by a number of social and intellectual factors in different proportions and phases. &Sacute;eṣakṛṣṇa's Sphoṭatattvanir&umacr;paṇa emerged on the eve of that revival, and can be recognized as a pioneer work in terms of its revitalization of the grammarians' interpretation of sphoṭa after a period of dormancy, and its influence on later works on sphoṭa.
Rational Cherednik algebras and link invariants
Keywords: Non-commutative resolutions
Knot theory
Symplectic reflection algebras
Quantisation
Rational Cherednik algebras
D-modules

Motivated by homological mirror symmetry, Smith and Thomas tried to construct a link invariant considering the derived category of coherent sheaves on the Hilbert scheme of n points on the minimal resolution of the Klenian singularity of type A, and an object ℒ(n) thereof. The braid group acts on this category by spherical twists, so one obtains a braid invariant by taking the Ext between ℒ(n) and its image under the braid group action. Smith and Thomas proved that taking the plat closure of the braid, this cohomology does not produce a link invariant but is close to doing so, and they conjectured that, in order to fix the one knot relation that is not satisfied, one has to consider a deformation of the Hilbert scheme.
In this thesis, we give a non-commutative approach to this problem: the commutative picture can be quantised by considering modules for the rational Cherednik algebra of cyclotomic type. This algebra gives a quantisation of the Hilbert scheme and there is a localisation theorem which allows one to work in the algebraic setting. In this context, the role of ℒ(n) turns out to be played by a certain module for the rational Cherednik algebra which we define for k=0. We then show that this module deforms to non-zero values of k. There is an action of the braid group on the derived category of category 𝒪 by twisting functors, which is defined at all deformation parameters, whereas the existence of the action on deformed Hilbert schemes in the commutative setting has not been rigorously established. We prove the analogue of the Smith-Thomas theorem, and conjecture that the braid invariant given by the algebraic analogue of the Smith-Thomas construction yields a link invariant for certain non-zero values of the deformation parameter.
Mid-infrared laser spectroscopy for trace gas detection
Keywords: trace gas detection
modulation spectroscopy
infrared spectroscopy

Laser spectroscopy offers a powerful and adaptable toolkit of techniques for sensitive and selective gas detection. New semiconductor laser sources that can emit high power midinfrared radiation at room temperature have reawakened interest in exploiting the spectrally separated, strongly absorbing ro-vibrational transitions in this region. The aim of this thesis is the demonstration of absorption spectroscopy methods with interband cascade lasers (ICLs) and quantum cascade lasers (QCLs) to detect gases relevant to physiology and atmospheric science.
Modulation of laser frequency via the injection current can increase instrument performance and prevent long-term drifts in laser output. An 8.2 μm QCL was locked to a CH4 rovibrational line using a 3f signal, limiting the laser frequency deviation to 3 MHz over 120 s. Frequency modulation spectroscopy (FMS) at 20 MHz demonstrated a twofold improvement for NO measured with a 5.3 μm QCL despite residual amplitude modulation. Broadband RF current perturbation of a 5.3 μm QCL was shown to broaden the laser linewidth and enhance the sensitivity of off-axis cavity-enhanced absorption spectroscopy (CEAS) tenfold.
Optical-feedback CEAS (OF-CEAS), which achieves high intracavity power and elongated periods of resonant cavity excitation, was performed using V-shaped and linear optical cavities. ICL and EC-QCL sources were utilized for the first time for sensitive OF-CEAS detection of VOCs and N2O. OF-CEAS using a V-shaped cavity and 3.2 μm ICL achieved an αmin of 2:5x10-8 cm-1 for N2O measurements. While the 5 μm EC-QCL achieved similar single-scan precision, mode-hopping prevented consistent measurements. The novel use of a linear optical cavity for OF-CEAS was demonstrated theoretically and experimentally with a 5.3 μm QCL to achieve excellent sensitivities (4 x 10-9 cm-1 Hz-1/2). The successful demonstration of these techniques paves the way for new QCL and ICL technology to be incorporated in future laser absorption spectrometers for the laboratory, field, and clinic.
Examining the contribution of dentate gyrus granule cells and ambiguity toward the stress response and behaviour of the rodent
Keywords: stress
neuroscience
psychology
dentate gyrus

The hippocampus and adult-born neurons have been implicated in regulating the stress response and disambiguating conflicting goal-related information. How these functions interact to promote adaptive behaviour has not been investigated. In this thesis, hippocampal lesions or pharmaco-genetic ablation of adult neurogenesis in mice ('TK mice') was used to dissect this relationship. Hippocampal lesions or selectively ablating adult neurogenesis decreased defensive behaviours toward a partially reinforced fear conditioned cue ('ambiguous fear conditioning'). Conversely, these animals did not show these impairments when a cue reliably predicted a footshock ('reliable fear conditioning'). In TK mice, this same pattern of results was also seen in Fos expression levels in the dentate gyrus and CA3. In additional experiments, baseline novelty-suppressed feeding behaviour (latency to eat a familiar food) did not differ between genotypes. After reliable fear conditioning, TK mice took longer to eat the food, suggesting increased anxiodepressive-like behaviour. After ambiguous fear conditioning, however, TK showed quicker latencies to eat, suggesting decreased anxiodepressive-like behaviour, as compared to wildtype mice. Clamping corticosterone levels was used to determine its role in adaptive responding to prior stress. Preventing experience-induced increases in corticosterone did decrease the latency for wildtype mice to eat after ambiguous fear conditioning, whereas TK mice were unaffected. Finally, another set of experiments were designed to see if ambiguity would affect appetitive behaviour in a non-spatial T-maze task with conflicting goal responses. It was found that mice with hippocampal lesions, but not TK mice, tended to choose an arm associated with a large reward less often if the other arm contained a small reward, as compared to their respective control groups. Similarly, hippocampal-lesioned mice, but not TK mice, chose an arm that was always associated with the presence of a reward less often if the other arm ambiguously predicted a reward. All of the above results suggest that the hippocampus, especially adult-born neurons, is necessary to disambiguate salient conflicting memories that underlie goal responses and that this disambiguation biases goal-related behaviour in an adaptive manner.
Models of men: The construction and problematization of masculinities in the Islendingasogur
Keywords: Sagas of Icelanders
Íslendingasögur
Old Norse

This thesis examines masculinities in the Íslendingasögur. It attempts to uncover the dominant model of masculinity that operates in the sagas, outlines how masculinities and masculine characters function within these texts, and investigates the means by which the sagas, and saga characters, may subvert masculine dominance. The thesis applies to men and masculinities in saga literature the same scrutiny traditionally used to study women and femininities.
The first – introductory – chapter reviews the limited scholarship that presently exists on masculinities in Old Norse literature. It then proposes a new model for the critical study of saga masculinities, drawing on sociological theories of hegemonic and subordinated masculinities. The second chapter ranges across the entire Íslendingasaga corpus in order to demonstrate how masculinity inflects homosocial relationships (and thus virtually all aspects of saga texts). It also suggests that almost all masculine characters have a problematic relationship with masculinity as a result of the intersectional nature of subject formation. The third chapter, focusing on Njáls saga, argues that the male body is used to undermine the prevailing model of masculinity. It is argued that the Njála author purposefully deploys somatic indices that have gendered significance to show embodied resistance to the demands of masculinity. The fourth chapter examines the representation and treatment of a character (Grettir Ásmundarson) that embodies masculinity to an exceptional degree, but who nevertheless – or perhaps for that reason – experiences a problematic relationship with masculinity. Finally, an epilogue briefly investigates some of the ways in which female characters may undermine and problematize the masculinity of men and the category of masculinity itself. Ultimately, this thesis shows that masculinity is not simply glorified in the sagas, but is represented as being both inherently fragile and a burden to all characters, masculine and non-masculine alike.
The dynamics of a changing arctic ocean
Keywords: Arctic dynamics

The Arctic Ocean is undergoing a period of rapid transition, and many different aspects of its environment (ocean, sea ice, and atmosphere) are changing faster than has ever previously been observed. Motivated by the role that the Arctic plays in the global climate and ocean circulation, the aim of this thesis is to investigate how the changing environment is affecting the dynamics and circulation of the Arctic Ocean.
Observations show that freshwater accumulation in the Beaufort Gyre of the western Arctic Ocean has accelerated over the past decade. First, a simple process model and idealised perturbations to the annual cycle in ocean surface stress are used to show that the decline in Arctic sea ice cover and an increase in the annual mean momentum flux can explain this accelerated accumulation. The adjustment timescale and quantity of freshwater accumulated are determined by a balance between Ekman pumping and an eddy-induced volume flux, highlighting the importance of eddies in the changing Arctic.
Sea ice decline may also drive periodic increases in vertical mixing. Using a 1D model of the Arctic Ocean water column, the competing effects of elevated vertical mixing and enhanced freshwater input on the stratification, the stability of the cold halocline, and the sea ice cover at the surface are explored. An elevated diffusive heat flux driven by stronger vertical mixing has little effect on the sea ice. Instead, the erosion of the cold halocline, which isolates the sea ice from the warm Atlantic water, represents the most important feedback for ongoing sea ice melt.
The changing Arctic Ocean will further affect the freshwater export to either side of Greenland; however, local dynamics will also be important. In this chapter, the vertical structure of the tides in Nares Strait in the Canadian Arctic Archipelago are explored, as tidal turbulence may represent an important frictional constraint for the freshwater flow in this region. The tides propagate as either standing or progressive waves, and the vertical structure is set by the proximity of the semi-diurnal critical latitude, the requirement of no normal flow through the coast, and the strong stratification at the surface. There is little temporal variability in the vertical structure, and tidal dissipation is comparable in magnitude to that over the highly dissipative region of the northwest European Shelf.
Effects of beta-2 adrenergic receptor agonists in DOK7 congenital myasthenic syndrome
Keywords: DOK7
beta-2 adrenergic receptor agonist
salbutamol
neuromuscular junction
congenital myasthenic syndrome
acetylcholine receptor

Congenital myasthenic syndromes (CMS) are a rare group of heterogeneous disorders, characterised by compromised neuromuscular transmission and symptoms of fatiguable muscle weakness. CMS is caused by mutations in genes that affect the structure and function of the neuromuscular junction (NMJ). In about 20% of CMS cases, patients have mutations in the gene DOK7; the protein product, DOK7, is crucial for maintaining the dense aggregation of acetylcholine receptor (AChR) clusters at the NMJ. DOK7-CMS patients do not respond to treatment with acetylcholinesterase inhibitors which are the first line treatment for most forms of CMS. Instead, a dramatic response to beta-2 adrenergic receptor (ADRB2) agonists, such as salbutamol, is observed. The aim of this project was to investigate the molecular mechanisms that underlie the beneficial effects of ADRB2 agonists.
Firstly, NMJ functioning was modelled in vitro by studying AChR clusters formed on cultured C2C12 mouse myotubes in the presence of WT DOK7. Overexpression of mutant DOK7 led to a significant reduction in the number of AChR clusters, explaining the pathogenic effect of the mutation. Importantly, incubation of myotubes with salbutamol increased the number of AChR clusters and their stability. The results provide the first evidence that ADRB2 agonists directly affect proteins located at the NMJ. However, this disease model suffers from limitations.
The rest of the thesis focussed on developing alternative cell culture models to explore the AChR clustering pathway. The first model combined optogenetics and fluorescence lifetime microscopy to study the effects of ADRB2 activation on AChR cluster stability in single live cells. The second used CRISPR/Cas9 genome editing tools to directly introduce Dok7 mutations to the genome of C2C12 cells, thereby overcoming some of the drawbacks associated with DOK7 overexpression. Further manipulations of these novel model systems will be used in the future to examine in more detail the molecular events underlying the pathogenic effects of DOK7 mutations and the mechanisms of ADRB2 agonists.
The role of religion in shaping women's family and employment patterns in Britain and France
Keywords: fertility
western Europe
religion

The current study examines the influence of religious affiliation and practice on family patterns and labour market activity for women in Western Europe, focusing on Britain and France. While both countries have experienced a sharp decline in institutionalized forms of religion over the past decades, differences in family and fertility behaviour on the basis of religiosity seem to persist. Although previous studies documented a positive correlation between religion and both intended and actual family size, there is still uncertainty about the different routes through which religion affects fertility, how structural factors are involved in this relationship and whether and how this relationship has changed along with the process of religious decline. This study aims to fill this gap by exploring the interrelationships between religion, educational attainment, female labour force participation, union formation and fertility levels. The data come from the British Household Panel Survey (BHPS), which contains 18 waves from 1991 to 2008, and the French survey of the Generations and Gender Programme (GGP), which was initially conducted in 2005. By following trends in fertility differences by religious affiliation and practice across birth cohorts of women, it is found that religious differences in fertility are not only persistent across birth cohorts, there is also a growing divide between non-affiliated and religiously practicing women who maintain higher fertility levels. Religious differences in family formation patterns and completed fertility are also explored, taking into account the interaction between education and religiosity. It appears that the effect of education on fertility differs by level of religiosity, as higher education is less likely to lead to childlessness or to a smaller family size among more religious women. The findings on the relationships between family and work trajectories by level of religiosity also point to a reduced conflict between paid employment and childbearing among actively religious women, although these patterns vary by religious denomination and by country.
Progress towards a demonstration of multi-pulse laser wakefield acceleration and implementation of a single-shot wakefield diagnostic
Keywords: frequency-domain holography
Wakefields
pulse trains
LWFA
FDH

An ongoing experiment is described to demonstrate the principle of multi-pulse laser wakefield acceleration, in which a plasma wakefield is resonantly excited by a train of laser pulses, spaced by the plasma wavelength. Particle-in-cell simulations of the initial single-pulse experimental setup are presented, in order to calculate the expected signal. Preliminary results are presented and future plans, based on work done so far, are discussed.
Part of this work involves the implementation of a single-shot wakefield diagnostic — frequency-domain holography, which records the phase shift caused by passage of a probe pulse through the plasma. This implementation is described in detail, along with the associated analysis procedure. Practical difficulties encountered while implementing the diagnostic are discussed, along with possible ways of mitigating them in the future. A method is presented by which the noise level in the resulting phase measurements can be predicted, much more accurately than any previously published method for this technique.
Methods of generating pulse trains for use in future multi-pulse laser wakefield acceleration experiments are presented. These include techniques proposed for use in this demonstration experiment, as well as one intended for use in a dedicated high-efficiency, high repetition-rate, multi-pulse driver laser. This last method, based on programmable pulse shaping using a spatial light modulator, requires a suitable mask to be computed based on the parameters of the required pulse train; an algorithm is described to perform this computation.
Precipitation pattern as a proxy for protein crystallization
Keywords: machine learning
pattern recognition
protein crystallization
precipitation pattern

X-ray crystallography has been the workhorse behind most 3D protein structures, which are crucial in the understanding of their biological function and interaction with other molecules. However, a major rate-limiting step in X-ray crystallography remains obtaining suitable protein crystals. The best approach to crystallise a protein can be summarized as a random-screen-and-wait procedure, with little to no readout from experiments that do not produce crystals. This project aims to make the most out of present screening practice, by establishing objective analyses of sparse-matrix screening experiments that extract informative readouts from this standard front-line experiment, independent of whether it yields visible crystals or not.
We have developed methods to objectively characterize crystallization outcome based on image analysis, enabling several things. Firstly, the ranking of droplets based on their likelihood of crystallinity to increase the efficiency and accuracy of human visual identification of crystals. Secondly, fingerprints of the collective precipitation behaviour of a protein across standard sparse-matrix can be generalised, and compared objectively to fingerprints of historical experiments, to assess crystallizability and infer optimization strategies based on past successes. Thirdly, clear drops can be automatically identified, and mapped to chemical components in a sparse-matrix screen to suggest alternative buffers for protein formulation. Fourthly, TeXRank, a user interface could be developed to present and make all algorithm output accessible for daily use. Fifthly, the associated data mining led us to evaluate the strategies for setting up screening experiments with limited protein samples, based on over ten years of crystallization data at the Structural Genomics Consortium, Oxford. Our methods capitalizes on present day standard screening procedure and hardware to extract useful information, bypassing laborious and subjective evaluation of each droplet.
Novel approaches for targeting BRCA2-deficient tumour cells
Keywords: BRCA2-deficient tumours
Targeted cancer therapies
HR-deficient tumours
BRCA2

Defects in homologous recombination (HR) repair are associated with significant mortality and improved therapies for HR-deficient tumours are therefore urgently needed. This work aimed to address this unmet need and utilised pharmacological approaches to investigate several methods for the targeting of BRCA2-deficient tumour cells. Parallel lines of investigation demonstrated the selective and effective targeting of BRCA2-deficient cells via both chemical G-quadruplex stabilisation and ERK inhibition. These studies provide impetus for the further development of specific and clinically relevant inhibitors. Further, pharmacological screens generated a body of data relevant to the selective targeting of BRCA2-deficiency. In particular, screening studies demonstrated that targeting the kinase GSK3 selectively kills BRCA2-deficient cells. Moreover, pharmacological screens revealed for the first time that disulfiram, an aldehyde dehydrogenase inhibitor currently in clinical use as an alcohol-aversive agent, induces replicative stress and DNA damage, selectively reducing the viability of BRCA2-deficient human tumour cells. Together, these data reveal a greater dependency of BRCA2-deficient human tumour cells on certain pro-proliferative pathways than their wild type counterparts and demonstrate the vulnerability of BRCA2-deficient cells to replicative stress. Importantly, this work delivers clear rationale for the further study and clinical development of several novel approaches relevant to the treatment of HR-deficient tumours and thus has the potential to help reduce the burden of these devastating diseases in the future.