VictorJuiz/thesis huggingface dataset:
The molecular basis of tick-host interactions

Ticks are obligate haematophagous arthropods that represent a major economic drain upon the world's livestock as well being a significant medical and veterinary risk through the transmission of tick-borne pathogens such as Borrelia burgdorferi, the causative agent of Lyme disease.
The tick-host relationship is a function of both ecological and physiological factors. Successful feeding requires the effective acquisition and digestion of a bloodmeal by the tick. Acquisition relies upon the ability of the tick to counteract host immune responses induced by the extended feeding periods of ixodid ticks (up to 2 weeks). The host response to tick infestation and the consequent countermeasures employed by the tick, constitute the tick-host interface.
The immune response of hosts to Ixodes ricinus infestations was examined through antigenic profiling. The antigens exposed to the host were shown to vary throughout the feeding period and differed between the different development stages of I. ricinus. It was also shown that different host species infested with I. ricinus recognised different antigens. This was true of both natural and non-natural hosts, and even closely related species.
Anti-complement activity was investigated in the salivary glands of Ixodes ticks. This activity was shown to inhibit some host species but not others. The pattern of inhibitory activity varied between the tick species tested in a way that was consistent with known tick host-preferences. The mechanisms of anti-complement activity in I. ricinus salivary glands were explored. The alternative but not the classical pathway of complement was inhibited. Activity was present in unfed ticks and throughout the feeding period. Three targets of the complement system were identified as being modulated by the tick.
Digestion of the bloodmeal was explored and a haemolytic activity was associated with the salivary glands of I. ricinus ticks. The activity was demonstrated to be Mg2+- dependent.
In addition, a subtractive cDNA library enriched for saliva-associated transcripts was successfully produced. Random sampling identified putative differentially expressed genes.
The results of this thesis illustrate the complexity of tick-host interactions at the molecular level. It is apparent that the research described poses many more questions than answers.
Musical thought and the early German Reformation

German musicology has customarily situated a paradigm shift in musical aesthetics some time during the first half of the sixteenth century. This dissertation examines the suggestion that German Reformation theology inspired a modern musical aesthetic. In Part One, the existing narrative of relationship between theological and musical thought is tested and rejected. Chapter 1 analyses twentieth-century music historians' positive expectation of commensurability between Luther's theological ideas and the sixteenth-century concepts of the musical work and musical rhetoric, concluding that their positive expectation was dependent on a Germanocentric modernity narrative. Chapter 2 assesses Listenius' Musica (1537), the textbook in which the concepts of the musical work and musica poetica were expounded for the first time. I argue that, since Listenius' textbook was intended as a pedagogical tool, it is inappropriate to read his exposition of musica poetica and opus as if logical sentences on musical aesthetics. Part Two investigates the treatment of musica in the theology of early German Reformation disputants. Chapter 3 finds that Luther's early musical thought was borrowed from the late mediæval mystics, and resisted the influence of the Renaissance Platonists. Chapter 4 shows that, far from embracing humanist ideas of musical rhetoric, Luther's Reformed musical aesthetic became increasingly anti-rational and sceptical of music's relation to verbal meaning. Chapter 5 examines the discussions of music by the German Romanist polemicists. It finds that their music-aesthetic assertions were opportunistic attempts to situate the Lutherans outside the bounds of orthodoxy. The dissertation concludes that the discussions of music in early German Reformation texts ran counter to the general sixteenth-century trajectory towards a humanistic or modern aesthetic of music. It further argues that the aesthetic proposals of sixteenth-century German theologians should be taken seriously in the formation of our present-day picture of sixteenth-century musical thought.

Keywords: Conrad Wimpina
Johannes Cochlaeus
Luther
Listenius
Georg Witzel
Musica poetica
Advisor: Rees, O
Biak morphosyntax

This thesis is a general description of the morphology and syntax of the Biak language. The Biak language belongs to the West New Guinea subgroup of the Austronesian language family and is spoken by around 50,000 to 70,000 speakers in West Papua in the northern part of the Geelvink Bay. The thesis consists of 7 main chapters that cover demographic and ethnographic information of the language, morphology, grammatical categories, basic constituent order, noun compounding and denominalization, relative clauses, and predicate nominal constructions.
The main findings of the thesis are:
The Biak language is predominantly a head-initial language.
The Biak language has morphological variation from monomorphemic to polymorphemic with the polymorphemic being the dominant pattern in the language.
Inflectional patterns on verbal and prepositional predicates, demonstratives, and possessive pronouns are divided into two patterns: the consonantal pattern and the vocal pattern.,/li>
Biak has alienable and inalienable nouns. Alienability in Biak is a syntactic distinction, not exactly corresponding to the semantic distinction.
The basic constituent order is SVO or AVP. Variations occur with predicate nominal (OV) and internally headed relative clause which uses SOV pattern.
Three types of relative clauses were identified:
Post nominal relative clause;
Headless relative clause; and
Internally headed relative clause.
The Biak language allows stacked and nested relative clauses.
Two kinds of predicate nominal constructions were identified:
copular clitics (clitic –ri, -s-, and free pronoun clitics) and
copular verbs –iri and iso. The two kinds of predicate nominal constructions can be distinguished syntactically.

Keywords: morphology
syntax
Biak language
Advisor: Dalrymple, M
Investigating non-image forming photoreception in a mouse model of autosomal dominant optic atrophy

Autosomal Dominant Optic Atrophy (ADOA) is a progressive optic neuropathy affecting mainly the retinal ganglion cells (RGCs). It is associated with mutations in the Opa1 gene and is phenotypically characterized by decreased visual acuity, central field deficits and colour vision defects. Experimental work on Opa1 mutant mice (B6; C3-Opa1Q285STOP) has permitted further characterisation of the pathophysiology of the disease. A specific functional visual deficit in the photopic negative response of the electroretinogram has been described in these mice, possibly due to altered dendritic pruning of RGCs. However, non-image-forming (NIF) visual function, which is regulated by a subset of RGCs that express the photopigment melanopsin, has not yet been extensively investigated in Opa1 mutant mice. We were interested in whether RGC dysfunction in Opa1 mutants affects NIF behaviours. We evaluated circadian behaviour, sleep behaviour and melanopsin expression in Opa1 mutant mice (Opa1+/-) and littermate controls (Opa1+/+). Opa1 mutant mice were able to entrain their behaviour rhythm to a normal 12:12 hr light/dark cycle, confining their activity to the dark phase. The suppression of activity by acute light exposure at night (negative masking) was equivalent between genotypes. Circadian phase shift responses to 480 nm or 520 nm light pulses during the subjective night were preserved in Opa1+/- mice relative to wildtype controls. The acute induction of sleep by light exposure at night was also present in Opa1+/- mice and not significantly different to Opa1+/+ animals. Immunohistochemical characterisation of melanopsin cells in flatmount retinae revealed no significant differences in cell numbers betweeen genotypes. Melanopsin (Opn4) transcript levels were also equivalent between Opa1 wildtype and mutant mice. There was also no obvious difference in melanopsin cell stratification patterns. The data overwhelmingly support the preservation of the NIF visual system in Opa1 mutant mice. The findings are consistent with patient studies suggesting increased resistance of melanopsin-expressing RGCs in conditions of mitochondrial optic atrophy. Further work is needed to extend our understanding of the possible neuroprotective mechanism involved which could lead to exciting therapeutic strategies.

Keywords: neuroprotection
retinal ganglion cells
dominant optic atrophy
melanopsin
Advisor: MacLaren, RE
Sekaran, S
The role of ultraviolet light in the image and non-image forming visual systems of mice

Long thought to be absent from mammals, UV sensitivity has now been established in many species, including mice, where it has been found to provide visual sensitivity and drive circadian responses. Compared to closely related species, the murine UVS cone photopigment is both in relatively high abundance and is associated with a unique expression gradient across the retina, raising questions concerning the function of UV sensitivity that may be relevant to other mammals. Here we investigate the non-image and image forming roles of UV light in mice. Phase-shifting sensitivity changes in rod and cone photoreceptor mutants/ transgenics indicated a significant contribution by cone photoreceptors to this assay of photic-entrainment under UV light. Generation of an Opn1sw knockout lacking the UVS opsin gene confirmed a critical role of UVS cones in the non-image forming system of the mouse, differing from that established for the middle-wave sensitive (MWS) cone opsin, and confirmed that UV light could be used for visual tasks in a visual adaptation of the novel-object recognition assay. Finally, examination of retinal c-fos induction found evidence of an inhibitory influence of the cone pathway linked to short-wavelength sensitivity. That the contribution of UVS opsin was significantly greater than similar experiments have found for MWS cones, despite widespread cone opsin co-expression, may indicate a distinct role for the UVS-only s-cones in the non-image forming visual system. Overall these data suggest that the role of ultraviolet light in the circadian system of the mouse may be central to its unique cone opsin characteristics and provides new insight concerning this critical research model relevant to its use in the investigation of human biology.

Keywords: EYE
OPHTHALMOLOGY
MOUSE
SHORT-WAVELENGTH
S-CONES
CIRCADIAN
VISION
OPN1SW
ULTRAVIOLET
LIGHT
NON-IMAGE FORMING VISUAL SYSTEM
PHOTORECEPTORS
UVS CONES
CONE
Advisor: Foster, R
Sekaran, S
Anomaly detection in vessel track data

This thesis introduces novelty detection techniques that use a combination of Gaussian processes, extreme value theory and divergence measurement to identify anomalous behaviour in both streaming and batch marine data. The work is set in context by a review of current methodologies, identifying the limitations of current modelling processes within this domain.
Marine data modelling is first improved by endowing the Gaussian process with the capacity to model both first order and second order dynamics; enhancing maritime data modelling through exploration of appropriate Gaussian process kernels. Gaussian processes are then used to forecast probable future vessel positions. The concept of combining the predictive uncertainty from the Gaussian process with extreme value distributions is then introduced. This provides a means of detecting anomalous vessel dynamics given the previously learnt model. The process is made amenable to online operation through adaption of the Gaussian process to sequential updates. The latter allows the model to be updated in an efficient online manner, after confirming that received data lies within the probability bounds of the model forecast behaviour. Finally a means of measuring distance between functions is introduced, which is used to identify communities of similar vessel types based on the underlying vessel dynamics. This is used to address the issue of vessel class (i.e. fishing vessel, cargo vessel etc.) misrepresentation through detection of anomalies between the inferred vessel class and the class broadcast by the vessel.

Keywords: Maritime Traffic
Gaussian Process
Outlier Detection
Novelty Detection
Extreme Value
Advisor: Roberts, S
Dimension reduction of streaming data via random projections

A data stream is a transiently observed sequence of data elements that arrive unordered, with repetitions, and at very high rate of transmission. Examples include Internet traffic data, networks of banking and credit transactions, and radar derived meteorological data. Computer science and engineering communities have developed randomised, probabilistic algorithms to estimate statistics of interest over streaming data on the fly, with small computational complexity and storage requirements, by constructing low dimensional representations of the stream known as data sketches. This thesis combines techniques of statistical inference with algorithmic approaches, such as hashing and random projections, to derive efficient estimators for cardinality, l_{alpha} distance and quasi-distance, and entropy over streaming data. I demonstrate an unexpected connection between two approaches to cardinality estimation that involve indirect record keeping: the first using pseudo-random variates and storing selected order statistics, and the second using random projections. I show that l_{alpha} distances and quasi-distances between data streams, and entropy, can be recovered from random projections that exploit properties of alpha-stable distributions with full statistical efficiency. This is achieved by the method of L-estimation in a single-pass algorithm with modest computational requirements. The proposed estimators have good small sample performance, improved by the methods of trimming and winsorising; in other words, the value of these summary statistics can be approximated with high accuracy from data sketches of low dimension. Finally, I consider the problem of convergence assessment of Markov Chain Monte Carlo methods for simulating from complex, high dimensional, discrete distributions. I argue that online, fast, and efficient computation of summary statistics such as cardinality, entropy, and l_{alpha} distances may be a useful qualitative tool for detecting lack of convergence, and illustrate this with simulations of the posterior distribution of a decomposable Gaussian graphical model via the Metropolis-Hastings algorithm.

Keywords: maximum likelihood estimation
cardinality
MCMC convergence diagnostics
random projections
data streaming
L-estimation
entropy
Advisor: Clifford, P
Structural and biophysical studies of HIV Rev and HBV e-antigen

Human immunodeficiency virus (HIV) Rev and Hepatitis B virus (HBV) e-antigen are both viral proteins that have key functions in their respective viral replication cycles. Both have evaded crystallization for decades due to their tendency to aggregate and/or form higher-order species. In this thesis the structure determination of HIV Rev and HBV e-antigen is presented—achieved via complexing with monoclonal antibody Fab fragments—and their structures are analysed.
HIV Rev is a small regulatory protein that mediates the nuclear export of viral mRNAs, an essential step in the HIV replication cycle. In this process, Rev cooperatively oligomerises onto a highly structured RNA motif, the Rev response element. The structure of Rev (complexed with Fab), determined to 2.3 Å resolution, reveals a molecular dimer where the ordered portion of each subunit (N-terminal domain; NTD; residues 9-65) contains two coplanar a-helices arranged in hairpin fashion. Rev subunits dimerise via interaction of identical hydrophobic patches that overlap to form a V-shaped assembly. Mating of hydrophobic patches on the outer surface of the dimer promotes higher order interactions. Cryo-electron microscopy and helical image reconstruction of in vitro assembled Rev filaments were performed to better understand higher-order Rev oligomerisation. Reconstructions of Rev filaments were determined to ~13 Å resolution, permitting docking of the Rev NTD structure. Conformational variability of the Rev dimer subunits and use of a third ligomerisation interface engender filaments that can expand and contract. Both characteristics were also observed in the crystal structures of Rev. Surface features of the Rev filaments are altered in different expansion states, which may have implications for the assembled forms that Rev adopts during nuclear export of RNA and subsequent re-import into the nucleus. Various models for Rev oligomerisation onto the viral RNA are proposed.
Chronic Hepatitis B virus (HBV) infection afflicts millions worldwide with cirrhosis and liver cancer. HBV e-antigen (HBeAg), a clinical marker for disease severity, is a soluble variant of the protein (core antigen, HBcAg) that forms the building-blocks of capsids. HBeAg is not required for virion production, but is implicated in establishing immune tolerance and chronic infection. The crystal structure of HBeAg clarifies how the short N-terminal propeptide of HBeAg induces a radically altered mode of dimerisation relative to HBcAg (~140 rotation), which is locked into place through formation of intramolecular disulfide bridges. This structural switch precludes capsid assembly and engenders a distinct antigenic repertoire, explaining why the two antigens are cross-reactive at the T-cell level (through sequence identity) but not at the B-cell level (through conformation). The structure offers insight into how HBeAg may establish immune tolerance for HBcAg while evading its robust immunogenicity.

Keywords: X-ray crystallography
cryo-electron microscopy
structural biology
Advisor: Grimes, J
Stuart, D
How fast can we see? The latency development in human infants to pattern, orientation, and direction-reversal visual evoked potentials

The goal of this thesis is to track latency changes in three visual evoked potentials (VEP) stimuli as an indication of overall brain development, in order to provide a normative baseline to differentiate visual and neurological development from pathological processes.
VEP- neural electrical activity recorded from the scalp surface and synchronized with visual stimulus transitions- is one of the common techniques in understanding infant vision development. Past work has concentrated on responses to pattern reversal and to the latency of the initial positive peak. Here we compare the timing of responses to pattern, orientation, and direction-reversal VEPs, and transient peak latencies to those calculated from the gradient of steady-state phase against reversal rate. The three stimuli were tested in 81 adults at 1- 16 r/s and 137 infants (3.6- 79.0 weeks) at 2- 8 r/s. Initial responses to orientation and direction were as fast as for contrast- around 100 ms, consistent with other findings that V1 is orientation selective. Cortical processing for both OR and DR yielded longer latencies (200 ms) by the calculated method, perhaps reflecting more involvement of higher visual processing in comparison to PR. Orientation and direction latencies also had a delayed onset and longer developmental period to reach maturity. Infants reached adult transient PR latency values by 15 weeks, for OR by 50 weeks, and for DR by 10 weeks. For the calculated latency, infants reached both adult PR and DR latencies by 30 weeks while OR showed little change across age.
We successfully confirmed that (1) phase-based calculation of latency is effective, easy to use, and taps into a different cortical pathway; (2) motion processing has an additional, faster, subcortical pathway; (3) a parallel processing of initial contrast and orientation; and (4) later visual processing is not only developmentally delayed for all three stimuli but also more vulnerable to perinatal brain damage. These latency differences provided a baseline for clinical evaluations where identification of delayed latencies should aid early diagnosis and guide therapies for adults and infants.

Keywords: visual evoked potentials
motion
direction
pattern reversal
ERP
orientation
VEP
Advisor: Braddick, O
A dynamic logistic model for combining classifier outputs

Many classification algorithms are designed on the assumption that the population of interest is stationary, i.e. it does not change over time. However, there are many real-world problems where this assumption is not appropriate. In this thesis, we develop a classifier for non-stationary populations which is based on a multiple logistic model for the conditional class probabilities and incorporates a linear combination of the outputs of a number of pre-determined component classifiers. The final classifier is able to adjust to changes in the population by sequential updating of the coefficients of the linear combination, which are the parameters of the model. The model we use is motivated by the relatively good classification performance which has been achieved by classification rules based on combining classifier outputs. However, in some cases such classifiers can also perform relatively poorly, and in general the mechanisms behind such results are little understood. For the model we propose, which is a generalisation of several existing models for stationary classification problems, we show there exists a simple relationship between the component classifiers which are used, the sign of the parameters and the decision boundaries of the final classifier. This relationship can be used to guide the choice of component classifiers, and helps with understanding the conditions necessary for the classifier to perform well. We compare several "on-line" algorithms for implementing the classification model, where the classifier is updated as new labelled observations become available. The predictive approach to classification is adopted, so each algorithm is based on updating the posterior distribution of the parameters as new information is received. Specifically, we compare a method which assumes the posterior distribution is Gaussian, a more general method developed for the class of Dynamic Generalised Linear Models, and a method based on a sequential Monte Carlo approximation of the posterior. The relationship between the model used for parameter evolution, the bias of the parameter estimates and the error of the classifier is explored.

Keywords: dynamic classification
online learning
multiple classifier systems
Advisor: Ripley, B