VictorJuiz/thesis huggingface dataset:
Functional dyes as tools for neurophysiology
Keywords: Second Harmonic Generation
non-linear optics
Porphyrin
SHG

The aim of the project described in this thesis is to synthesise new functional molecules which interact with light for neurophysiological applications. In particular, I describe a family of amphiphilic porphyrins with large first hyperpolarisabilities which are used as SHG contrast agents and voltage-sensitive probes. In addition I detail a methodological microscopy tool and a novel caged form of a neuronal ion-channel antagonist.
Chapter 1 introduces the key concepts underlying the use of dyes as SHG contrast agents. In particular it focuses on aspects of molecular design, covering both the amphiphilicity and nolinearity required by the target molecule. It covers quantification of the nonlinear properties of SHG stains, then surveys a number of examples which showcase the flexibility of SHG imaging as a biomedical technique.
Chapter 2 describes a family of amphiphilic porphyrins with large first hyperpolarisabilities. Working from the structure-property relationships identified in Chapter 1, we fully characterise these dyes and demonstrate that they can be used in SHG imaging. We demonstrate that these molecules may also be tuned by complexation of a metal ion which can modulate their photophysical and solubility behaviour.
Chapter 3 provides a description of how to determine the orientational distribution of dipolar dyes in a membrane by multiphoton microscopy. We measure the signal intensity of the dye in a model membrane system then find distributional moments which lead to the distribution itself.
Chapter 4 explores whether off-axis contributions to the first hyperpolarisability tensor can significantly augment the dominant on-axis contribution from the main dipolar charge-transfer band. We synthesise and characterise a series of cis-donor cis-acceptor porphyrin compounds and explore their biophysical characteristics.
Chapter 5 is the culmination of this project and after discussing method development, goes on to show how we measure the voltage sensitivity of an amphiphilic porphyrin SHG dye. We compare the archetypal porphyrin dye chromophore with three commercially available styryl dyes and demonstrate that our dye has greater sensitivity and a more rapid response.
Chapter 6 describes a side project, the use of a photolabile cage to protect MK801, a neuronal ion-channel antagonist. By developing a water soluble photolabile cage using molecular design techniques, we are able to release MK801 in neurons with precise spatiotemporal control, allowing us to pinpoint the locus of two key neurophysiological processes.
The Armenian merchants of New Julfa, Isfahan: a study in pre-modern Asian trade
Keywords: trade
merchants
historiography
Armenians
New Julfa
Europeans
Safavi Iran

In the sixteenth and seventeenth centuries the merchants of Julfa, a town on the trade routes linking the Mediterranean with Iran, developed an extensive international trade network reaching from the Atlantic coast of Europe to the Indian Ocean. Part 1 of the dissertation traces the history of Julfa and examines the factors contributing to the Armenians' success - among them the significant growth of Iranian raw silk exports to Europe; the stimulus to East-West trade given by the influx of American silver to Europe and the consequent imbalance in the value of bullion between Europe, the Middle East and South Asia; the forced resettlement of the Julfans in Isfahan and the formation of a close economic relationship with the Safavi court.
Part 2 concentrates on social and economic organisation, examining the structure of the Armenian patriarchal household and its commercial operation as family firm, and the community and its provision of the institutions that upheld commercial law and the merchants' system of values and standards of behaviour. The discussion in Chapters 4 and 5 of partnership and agency and the credit system operated by the Julfans is based on research into surviving contracts and credit instruments.
These documents also provide the material for Part 3. The Julfan mercantile documents are a unique record of the commercial world of an Asian trading community in the sixteenth to eighteenth centuries. They also present numerous technical difficulties, which are discussed through the presentation of examples of documents in the original, with translation, notes and a glossary.
The history of the Julfa merchants affords a rare opportunity for close examination of the organisation and techniques of trade in Asia and provides a basis for comparison with other Asian merchants.
Understanding the evolutionary ecology of dispersal
Keywords: experimental evolution
bacterial motility
kin competition

Understanding dispersal is a central aim of evolutionary ecology. Theoretical analyses of dispersal have been crucial in identifying key variables which contribute to its evolution and maintenance, but the supporting empirical data remains elusive. Microbes offer a powerful model system on which ecological and evolutionary theory can be experimentally tested with controlled and replicated experiments, and with the convenient malleability of selective pressures and bacterial genomics. Pseudomonas aeruginosa is an ubiquitous, opportunistic pathogen that is able to induce acute or chronic infections in a broad array of hosts. As well as in vivo environments, P. aeruginosa can be found in a range of ecological habitats, from solid to aqueous, and as such requires a variety of dispersal mechanisms (including swimming, gliding on a surfactant and ‘crawling’) for effective colonisation and infectivity. In this thesis, I present a collection of papers which outline empirical ecological and evolutionary experiments to identify the abiotic and biotic forces that shape the evolution of these different dispersal mechanisms, with particular focus on the theoretically important role of kin competition and the structure of the abiotic environment.
Free will in device-independent cryptography
Keywords: device-independent cryptography
Bell inequalities
Bell nonlocality
quantum cryptography
determinism
free will

Device-independent cryptography provides security in various tasks whilst removing an assumption that cryptographers previously thought of as crucial -- complete trust in the machinations of their experimental apparatus. The theory of Bell inequalities as a proof of indeterminism within nature allows for secure device-independent schemes requiring neither trust in the cryptographers' devices nor reliance on the completeness of quantum mechanics. However, the extreme paranoia attributable to the relaxed assumptions within device independence requires an explicit consideration of the previously assumed ability of the experimenters to freely make random choices. This thesis addresses the so-called `free will loophole', presenting Bell tests and associated cryptographic protocols robust against adversarial manipulation of the random number generators with which measurements in a Bell test are selected.
We present several quantitative measures for this experimental free will, otherwise known as measurement dependence. We discuss how an eavesdropper maliciously preprogramming the experimenters' untrusted devices can falsely simulate the violation of a Bell inequality. We also bound the amount of Bell violation achievable within a certain degree of measurement dependence. This analysis extends to device-independent randomness expansion, bounding the guessing probability and estimating the amount of privacy amplification required to distil private randomness. The protocol is secure against either arbitrary no-signalling or quantum adversaries. We also consider device-independent key distribution, studying adversarial models that exploit the free will loophole.
Finally, we examine a model correlated between the random number generators and Bell devices across multiple runs of a Bell test. This enables an explicit exposition of the optimal cheating strategy and how the correlations manifest themselves within this strategy. We prove that there remain Bell violations for a sufficiently high, yet non-maximal degree of measurement dependence which cannot be simulated by a classical attack, regardless of how many runs of the experiment those choices are correlated over.
“Better” regulation through social entrepreneurship? - innovative and market-based approaches to address the digital challenge to copyright regulation
Keywords: social entrepreneurship
creative commons
legal innovation
China
blanket license
self-regulation
co-regulation
copyright regulation
copyright law
better regulation
legal entrepreneurship

After the initial excitement about the Internet as a space outside of governmental control has evaporated and courts in several states have applied national laws to ‘Cyberspace’, there is now a consensus among scholars that regulators have in principle the authority and capacity to regulate the Internet. Nevertheless, the application of the established tools of regulation - legislation and adjudication - to the current challenges to copyright regulation posed by the Internet has proven to be ineffective and produced undesirable side effects. Although market self-regulation has been suggested as a more efficacious approach to regulating the Internet and has proven effective in content regulation and Internet governance, the market has so far been unsuccessful in providing an effective and efficient remedy to the challenges to copyright regulation. The purpose of this thesis is to examine a novel approach to regulation and analyse its benefits and limitations. The novel approach defies the conceptualisation as co- and self-regulation, but introduces the solution from outside the regulated environment through entrepreneurship and innovation, and relies on the forces of the market to become effective. In this thesis, I analyse the regulatory systems implemented by two private organisations, Noank Media and Creative Commons, in China’s reportedly ineffective copyright law environment and find that their market-based and innovative approach to regulation can be understood as a form of social entrepreneurship. Social enterprises have been claimed to deliver social goods more effectively and efficiently than governmental intervention, because they are said to rely on local knowledge, to be driven by the demand of the stakeholders, and to be focused on social value creation. Based on quantitative and qualitative fieldwork with Noank Media’s and Creative Common’s stakeholders in China I analyse to what extent these two enterprises managed to successfully leverage the assets of social entrepreneurship. I conclude that while the novel approach has demonstrated the potential to produce more effective and more efficient regulation, it does not automatically result in Better Regulation. Further efforts are required to ensure participation, transparency, and public accountability, and to avoid regulatory fragmentation.
Comparison of the effects of vitamin D metabolites on osteoblast and osteocyte bone cells
Keywords: Osteocyte
1
25(OH)D2
Osteoblast
25(OH)D3
25(OH)2D2
25(OH)2D3

While the major source of vitamin D is D3 from ultraviolet exposure, some supplements supply D2. The relative potency of vitamin D2 versus vitamin D3 remains controversial.
The aims of the current study were, 1. To optimize the in vitro model, including use of cell lines, vitamin D concentrations, and outcome biomarkers. 2. To compare the potency of vitamin D2 and D3 metabolites on mouse and human bone cellular activity. 3. To explore the expression of VDR in osteoarthritic (OA) bone tissues as well as cellular responses to vitamin D2 and D3 metabolites ex-vivo.
In mouse 2T3 osteoblasts, at physiological doses, both vitamin D2 and D3 metabolites increased ALP activity and mineralisation and up-regulated osteoblastic signature genes and proteins. At supra-physiological doses D3 metabolites were more potent inhibitors of 2T3 function than D2 metabolites. Although hBMS cell proliferation was inhibited by both 25(OH)D2 and D3, ALP activity was enhanced by both metabolites. However, 25(OH)D3 was a more potent stimulator of ALP and mineralisation of hBMSCs. D2 and D3 equally stimulated expression of CX43 and PHEX markers in osteocytic cell lines. Immunohistochemistry of femoral heads showed much reduced VDR expression in OA osteocytes and osteoclasts, yet both 25(OH)D2 and D3 increased OA-hBMSCs mineralisation more than non-OA-hBMSCs ex-vivo.
While vitamin D2 or D3 increased mouse 2T3 osteoblastic activity at physiological doses, OA and non-OA hBMSCs differentiation was more responsive to 25(OH)D3. Key bone cells such as osteocyte and osteoclasts expressed less VDR in OA. For the first time vitamin D2 metabolites have been thoroughly examined and emerged as a potent stimulator of bone cell differentiation, at least in vitro. Vitamin D3 in contrast is confirmed as highly potent in bone cells, but with toxicity at much lower doses than D2.
Long term appearance-based mapping with vision and laser
Keywords: computer vision
mobile robotics
autonomous systems
machine learning

This thesis is about appearance-based topological mapping for mobile robots using vision and laser. Our goal is life-long continual operation in outdoor unstruc- tured workspaces.
We present a new probabilistic framework for appearance-based mapping and navigation incorporating spatial and visual appearance. Locations are encoded prob- abilistically as random graphs possessing latent distributions over visual features and pair-wise euclidean distances generating observations modeled as 3D constellations of features observed via noisy range and visual detectors. Multi-modal distributions over inter-feature distances are learnt using non-parametric kernel density estima- tion. Inference is accelerated by executing a Delaunay tessellation of the observed graph with minimal loss in performance, scaling log-linearly with scene complexity.
Next, we demonstrate how a robot can, through introspection and then targeted data retrieval, improve its own place recognition performance. We introduce the idea of a dynamic sampling set, the onboard workspace representation, that adapts with increasing visual experience of continually operating robot. Based on a topic based probabilistic model of images, we use a measure of perplexity to evaluate how well a working set of background images explains the robot’s online view of the world. O/ine, the robot then searches an external resource to seek additional background images that bolster its ability to localize in its environment when used next.
Finally, we present an online and incremental approach allowing an exploring robot to generate apt and compact summaries of its life experience using canon- ical images that capture the essence of the robot’s visual experience-illustrating both what was ordinary and what was extraordinary. Leveraging probabilistic topic models and an incremental graph clustering technique we present an algorithm that scales well with time and variation of experience, generating a summary that evolves incrementally with the novelty of data.
A critical study of the life of the 13th-century Tibetan monk U rgyan pa Rin chen dpal based on his biographies
Keywords: Tibetan history
U rgyan pa Rin chen dpal
Tibetan biography

U rgyan pa Rin chen dpal (1230-1309) was a great adept of the bKa' brgyud school of Tibetan Buddhism, particularly renowned for his knowledge of the Kālacakra tantra and the unique teaching known as the Approach and Attainment of the Three Vajras (rDo rje gsum gyi bsnyen sgrub), said to have been given to him in his vision by Vajrayoginī (rDo rje rnal 'byor ma) in the Miraculous Land (sprul pa'i zhing) of U rgyan. He was the student of the 2nd Karma pa, who entrusted him with the Black Hat, which he passed to the 3rd Karma pa. He was also a great traveller who journeyed widely across and beyond Tibet. He met Qubilai Khan in the capital of Yuan China and visited sacred Buddhist sites in South India. He has been aptly described by van der Kuijp as "the great Tibetan yogi, thaumaturge, scholar, alchemist, and traveler".
Thanks to the availability of a large amount of hitherto unknown materials from eleven biographies, the thesis has put considerable weight on the bibliographical comparison and analysis of the different works in an attempt to establish the possible relationship between them. This is supplemented by summaries of the biographies, to give an overview of the protagonist's life in Part One of the thesis. Part Two consists of a critical study of the different phases and aspects of U rgyan pa's life in the unique historical, political and religious context of each phase, drawing materials from the corpus of biographies and in the light of other primary and secondary sources in Tibetan, Chinese and Western languages. In Chapter I, U rgyan pa's family lineage, childhood and early studies are discussed in order to find out how his innate propensities and early studies are represented as having influenced his character. In Chapter II, the account of U rgyan pa's journey to West Tibet and U rgyan is studied. A sixteen-stanza song in his own words epitomising this journey, supplemented by route maps, will be used as a framework to illustrate and reconstruct his journey to the Land of the Ḍākinīs. In Chapter III, the teachings he received and the subsequent transformation of his character and status, are explored. In Chapter IV, his career as a tantric master, his other pilgrimages and benediction trips, and his conflicts with various religious and political authorities, are examined. The materials will be scrutinised in the hope of separating as far as possible fact from fiction.
Genetic, socio-ecological and fitness correlates of extra-group paternity in the European badger (Meles meles)
Keywords: extra-group paternity
heterozygosity-fitness correlations
inbreeding depression
pairwise relatedness
capture-mark-recapture survival analysis
european badger
Meles meles
lifetime reproductive success
paternal effects
sexually antagonistic genetic effects
local density effects

The evolution of extra-group paternity (EGP) is a contentious issue in evolutionary biology. This thesis examines the factors and adaptive benefits driving EGP in a high-density, group-living population of European badgers (Meles meles).
To improve power to assign parentage, I isolated and characterised 21 new polymorphic microsatellite markers. I genotyped 83% of 1410 badger trapped 1987‒2010 using 35 autosomal microsatellite markers. Maternity and paternity were assigned at 80% confidence ca. 82% of individuals. 48% of paternities were extra-group, where 85% were attributable to neighbouring-group males and EGP was detected in 47% of litters; thus badger social group do not correspond with a breeding unit.
I tested whether indirect genetic benefits explain these high EGP rates. (1) ‘Good-gene-as-heterozygosity Hypothesis’: Paternal heterozygosity, but not maternal or an individual’s own heterozygosity, associated positively with first-year survival probability. Under benign environmental conditions, cubs fathered by more heterozygous males had a higher first year survival probability. Despite this correlation, the EGP rate per litter correlated with neither average nor maximum within-group heterozygosity of candidate fathers. (2) Fitness benefit Hypothesis: Extra-group offspring (EGO) had lower first-year survival probability and lived 1.3 years less than within-group offspring (WGO). Female WGO produced more litters and offspring over their lifetime than female EGO, whereas male EGO produced more offspring than male WGO. (3) Inbreeding avoidance hypothesis: The EGP rate within a litter increased with greater average pair-wise relatedness between mothers and within-group candidate fathers. No inbreeding depression on first-year survival probability was detected, but small sample sizes limited statistical power. Socio-ecologically, at the litter level, EGP correlated negatively with the number of within-group candidate fathers, and positively with neighbouring-group candidate fathers.
In conclusion, EGP in badgers may reduce inbreeding and be maintained in the population through a sex-specific antagonistic selection and indirect genetic benefits may occur when the total fitness benefits of producing extra-group sons outweigh the costs of producing extra-group daughters. These indirect genetic benefits only partially explain the evolution of promiscuity in European badgers, highlighting that evolutionary factors underlying promiscuity remain unclear.
Structural and functional magnetic resonance imaging (MRI) in the prediction and characterization of mild cognitive impairment (MCI) and Alzheimer's disease (AD)
Keywords: imaging
MRI
Alzheimer's disease
mild cognitive impairment

The aim of the research presented in this thesis was to improve the characterisation of the changes in brain structure and function that occur at different stages of Alzheimer’s disease (AD) progression, from pre-symptomatic AD, to mild cognitive impairment (MCI), to clinically evident dementia, using magnetic resonance imaging (MRI) techniques.
Baseline structural MRI data from a cohort of healthy older adults who were followed prospectively for ten years, during which time some developed MCI and some AD, were analysed. It was found that structural MRI could detect volume loss in medial-temporal lobes up to 7-10 years before clinical symptoms of AD appear. In addition, volumetric variability of medial-temporal regions detected by structural MRI across cognitively healthy older adults correlated with their performance on a task of visuospatial associative memory, and functional activation of the same regions occurred during successful performance of the same task on functional MRI (fMRI).
Three groups of participants - cognitively healthy controls, people with MCI, and patients with probable AD - were then recruited and underwent a multimodal MRI protocol, which included functional sequences acquired at rest and during the execution of two different cognitive tasks (visuospatial associative memory and self-appraisal). Cross-sectional comparisons showed: (i) that successful visuospatial associative memory performance was associated with increased functional activity (measured with task fMRI) in lateral prefrontal regions in AD patients relative to controls and (ii) that increased functional activity overlapped with frontal brain networks showing increased functional connectivity (measured with resting fMRI) in the same AD patients. Further, by demonstrating group- and condition-specific decreased frontal activity in AD patients relative to controls during a self-appraisal fMRI task, it was shown the specific utility of fMRI to unravel cognitive mechanisms underlying specific neuropsychological symptoms such as unawareness of cognitive impairment (anosognosia) in MCI and AD.
In conclusion, structural MRI can detect morphological changes in the preclinical stage of AD, possibly earlier than previously described, and these reliably match cognitive functioning in older adults. In the MCI and AD stages, once symptoms of cognitive impairment are clinically evident and measurable, task-related and resting functional MRI can inform on residual brain function detectable over and above the known changes in brain morphology and cognitive performance that have already occurred at these stages, emerging as a sensitive marker of residual ability that could potentially be used to measure the effect of new treatments.