VictorJuiz/thesis huggingface dataset:
The evolution and functional morphology of hemipteran vibrational organs

Acoustic and vibrational signals are among the prevalent modes of arthropod communication, exploited by at least 230,000 species (Cocroft and Rodríguez, 2005). Vibroacoustic signals dominate hemipteran communication, being generated by stridulation, wing buzzing, percussion, membrane buckling and shaking of the body relative to the legs (tremulation). The last two mechanisms are produced by basi-abdominal organs known as tymbals in Cicadomorpha and tergal plates in Heteroptera, respectively, whose systematic distribution and homologies are poorly understood. Other groups, such as the planthoppers (Fulgoromorpha) and moss bugs (Coleorrhyncha), are more enigmatic, as they generate vibrations with mechanisms which have so far remained unexplored. In spite of limited available morphological evidence, it has been suggested that all hemipteran basi-abdominal organs are homologous and evolved once (Tymbalia hypothesis) (Wessel et al, 2014). The aim of this dissertation is to elucidate the evolution of hemipteran vibroacoustic organs by describing their biomechanics, morphology and systematic distribution, and to use the resulting data to test the claims of the Tymbalia hypothesis.
I used a combination of state-of-the-art methods such as X-ray synchrotron microtomography and confocal laser scanning microscopy with more traditional techniques 10 (e.g. scanning electron microscopy), in order to describe the morphology of vibroacoustic organs from taxa selected from across hemipteran phylogeny. For experiments with living specimens, I used laser Doppler vibrometers to record their vibrational signals and high speed cameras to film the motion of the organs responsible for their production.
I find that Fulgoromorpha produce vibrational signals with a novel mechanism I term the “snapping organ”, which is biomechanically and morphologically distinct from tymbals. Furthermore, re-examination of supposed stridulatory organs in derbid planthoppers reveals that they are instead more likely to be used in chemical signalling. I show that tymbals are ubiquitous in Cicadomorpha, and that their segmental affinities were misinterpreted by most previous studies. Finally, I document the tergal plate in a systematically important group of Heteroptera, and I challenge the evidence used to support the Tymbalia hypothesis. Overall, this dissertation documents the morphology and systematic distribution of hemipteran vibroacoustic organs in unprecedented detail, and provides a significant step towards resolving their evolutionary origins.

Advisor: Taylor, G
Mortimer, B
Measurement of localized oxygen extraction fraction in brain using magnetic resonance imaging

Magnetic resonance imaging (MRI) is a non-invasive medical imaging technique which, thanks to the variety of both structural and functional information it provides, is increasingly used throughout the world for clinical diagnosis. Due to the different magnetic properties of haemoglobin when it is bound to oxygen, MRI is sensitive to the oxygen saturation levels of the blood, however, accurate measurement of this property remains challenging in the brain. Specifically, there does not yet exist a robust MR method for quantifying regional differences in brain tissue oxygenation, which can provide important diagnostic information in cases where oxygen delivery to a specific region of the brain may be impaired, e.g. in stroke. In this thesis a new method for measuring the oxygen extraction fraction of tissue in the brain on a regional level is presented. The technique is called Selective Localized T2-Relaxation-Under-Spin- Tagging, or SL-TRUST and measures the oxygen saturation of outflowing venous blood in the superior sagittal sinus.
Using SL-TRUST venous oxygen saturation measurements are achieved in individual brain hemispheres and in a smaller tissue region, approximately 70x70x80 mm3, above the middle cerebral artery. Comparison of two contralateral regions can be achieved in a scan time of less than 5 minutes. The robustness of SL-TRUST is assessed in healthy volunteers in a reproducibility study and the coefficients of variation for regional measurements found to be comparable to those of global measurements.
SL-TRUST is developed further as a method of mapping the oxygenation of venous blood from across the whole brain using phase encoding methods. Low resolution T2 maps in healthy volunteers are obtained as proof-of-concept of this method.

Keywords: TRUST
Oxygen extraction fraction
Regional Oxygenation
Advisor: Jezzard, P
Okell, T
Colour constancy for glossy objects under complex lighting environments

Colour constancy refers to our visual ability to identify the colour of objects under different illuminations. As a result of research over decades, our understanding of the mechanisms underlying this ability has advanced considerably.
However, a significant limitation of past studies has been that they have mostly employed oversimplified experimental stimuli that only partially reflect the properties of surfaces and illuminations in the natural environment. Stimuli were mostly matte, two-dimensional, and uniformly illuminated by single illumination. In the real world, in contrast, we know that objects sometimes include gloss (perceptual attribute of specular reflection), and their shape is usually three-dimensional rather than flat. Moreover, an object placed in the natural environment receives illumination from every direction as light is reflected from other objects in the scene, and the spectra of those lights might vary from one direction to another.
In this thesis, I report five research projects. The first three are all experiment based, and they were designed to find mechanisms that underpin human colour constancy for three-dimensional glossy objects that are placed under complex lighting environments. We conducted first an experiment where observers were asked to judge surface and illuminant colour changes for glossy objects under point light sources. The second and third experiments explored our ability to identify surface colours of glossy objects under environmental illumination that introduces a complex spatial pattern of specular highlights on the surfaces. All experiments used computer-rendered objects that take account of the complex interaction between material and illumination in the real world. Collectively these experiments suggest that observers are able to extract surface colour, even with complex stimuli in which simple heuristics are unlikely to be reliable. Instead, the results suggest that observers may build up complex internal models from which they can segregate colours of surface and illumination.
The fourth chapter is based on field work that was conducted in collaboration with Prof. Sergio Nascimento at University of Minho, Portugal. We report newly collected hyperspectral environmental illuminations recorded in eight outdoor scenes and four indoor scenes. The aim was to characterise the directional spectral variation that occurs in natural environments and its application to more precise simulation of objects using computer graphics. Subsequent fifth chapter was motivated by the striking variation of illuminant spectra in natural environments. We revisited a classical problem in human colour vision, called illuminant metamerism where two distinct surfaces appear the same under a specific illumination. We showed theoretically that this metamerism is less of an issue than previously thought thanks to the presence of directional variation of illumination.

Keywords: Illuminant Metamerism
Colour Constancy
Environmental Illumination
Specular Reflection
Advisor: Smithson, H
Synthesis without syntactic templates

Program synthesis is the mechanised construction of software. One of the main difficulties is the efficient exploration of the very large solution space, and tools often require a user-provided syntactic restriction of the search space. Writing such templates is often challenging, particularly since any constants required in the solution must be given in the template. In this dissertation we explore the research hypothesis that synthesis of programs without provision of such syntactic templates is computationally feasible using methods based on CounterExample Guided Inductive Synthesis (CEGIS).
The key contribution of this dissertation is a new approach to program synthesis that combines the strengths of a counterexample-guided inductive synthesizer with those of a theory solver, exploring the solution space more efficiently without relying on user guidance. We call this approach CEGIS(T ), where T is a first-order theory. Notably, since the publication of CEGIS(T ), a variant of the algorithm has been implemented inside leading synthesis solver CVC4. CEGIS(T) is as complete (or incomplete) as CEGIS, and it does not affect worst-case run-time complexity considerations.
In combination with the development of CEGIS(T ), we introduced several algorith- mic improvements that enhance both the performance of CEGIS(T ) and the baseline CEGIS algorithm. The first of these improvements is a significant change to the way we encode the synthesis problem for the SAT-based synthesis component of CEGIS in order to produce smaller formulae that can be more efficiently solved by SAT and SMT solvers. The second of these improvements is the use of incremental satisfiability solving in the synthesis component of CEGIS. Incremental satisfiability solving allows the SAT solver to re-use clauses learnt in previous CEGIS iterations, thus reducing the time per synthesis iteration.
We evaluate our contributions on a set of benchmarks taken from the Syntax Guided Synthesis Competition, and note that CEGIS(T ) is able to solve benchmarks which elude a standard implementation of CEGIS, specifically benchmarks that contain non-trivial constants. We find that the novel proposed encoding provides a substantial speed-up on all the benchmarks that require synthesising a program of length greater than one instruction. The use of incremental first-order solving in CEGIS decreases the solving time in some cases but not all, and we hypothesise that these are the benchmarks on which SAT-solver pre-processing is less important.

Keywords: CEGIS
Syntax-guided synthesis
Formal Verification
Formal synthesis
Programming languages
Advisor: Abate, A
Homeric hymn to Apollo: introduction and commentary on lines 1-178

Chapter 1: Unity. This chapter surveys the various arguments (formal, religious, geographical, etc.) that have been adduced to prove that DAp and PAp did not always form a single unified hymn. It is argued that these are all insufficient and that the hymn should be considered an original unity.
Chapter 2: Structure. This chapter analyses the hymn’s double structure, noting the numerous close correspondences between its two parts and some of the major devices (priamel, apostrophe, journeys) that are used to signal divisions.
Chapter 3: Date and Context. This chapter discusses the evidence for the dating of the hymn and for its context. Most of the supposed historical allusions are discounted as highly dubious. The hymn’s description of the Delian festival (147-76) suggests it had some original link to Delos, but this would not exclude later performances elsewhere. It is tentatively suggested that the hymn’s particular blend of Delian and Pythian themes would suit a Delian performance in the second half of the sixth century, perhaps in connection with the activities of the tyrants Peisistratus or Polycrates.
Chapter 4: Authorship. This chapter discusses the poet’s description of himself as the ‘blind Chian’ (172-3). It is argued that this reflects, and seeks to promote, an already existing legend about Homer, that this legend was at least partly fostered by the guild of Chian rhapsodes called Homeridae, and that therefore the ancient attribution of the hymn to the Homerid Cynaethus, which would not be incompatible with its likely date, may be tentatively accepted.
Chapter 5: Language. This chapter discusses the hymn’s language relative to the rest of early Greek hexameter poetry. Some signs of post-Homeric diction are noted. The difficulties of using language to construct a relative chronology of early epos are discussed. Doubt is cast upon the linguistic evidence for the hymn’s division. Non-Homeric and non-Hesiodic forms are assembled and briefly examined. The large number of parallels with the Homeric poems are assessed and it is suggested that, while much of this material is probably traditional, a close relationship between HAp and these poems is possible at certain points.
Chapter 6: Metre and Prosody. This chapter analyses the hymn’s inner and outer metric, and certain prosodic features. In most cases its practice does not diverge significantly from that of Homer and the other Hymns.
Chapter 7: Text and Transmission. This chapter summarises the hymn’s textual transmission. Places where the commentary diverges from Càssola’s text are noted.
Chapter 8. Commentary on lines 1-178.

Keywords: Homer
Homeric Hymns
Apollo
Advisor: Kelly, A
Phenotypic models of perfect adaptation by CD8+ T cells

T cells receive continuous antigenic stimulation in peripheral tolerance, cancer, and chronic infection. Persistent antigen exposure induces an initial cellular response. However, over time, T cells become unresponsive to the stimulus and cease activity, a behaviour known as adaptation. Although it is generally known that T cells adapt to persistent stimuli, the properties of this adaptation remain understudied. This thesis aims to characterize phenotypes of T cell adaptation and to suggest the possibility of relating these phenotypes to basic network models that produce adaptation.
To better understand T cell adaptive behaviour, a plate-based T cell receptor system was used to expose cells to step changes in antigen dose. In response to persistent antigen exposure, T cells can display perfect adaptation in cytokine production with incomplete TCR downregulation. Increasing the antigen dose leads to further tuning of the surface TCR level, independent of previous antigen exposure, with limited additional cytokine production. Thus, partial TCR downregulation tunes to antigen dose and perfect adaptation is observed even with partial downregulation. If T cells are exposed to gradual, incremental increases in antigen dose rather than a single dose, the cells are similarly silenced.
The experimental data was subsequently examined in the context of seven basic, preliminary models of adaptation. A model based on partial TCR downregulation with a second downstream mechanism aligns with experimental observations, suggesting the potential relevance of TCR downregulation. Clinically, T cell-modulating therapies often cause potent early cytokine production. As a proof-of-concept, I demonstrate that otelixizumab induces T cell adaptation as a non-pMHC stimulus. Further study of T cell adaptation is thus invaluable both to understanding T cell behaviour as well as therapeutic design.

Advisor: Dushek, O
Theory of killing and regeneration in continuous-time Monte Carlo sampling

We consider the theory of killing and regeneration for continuous-time Monte Carlo samplers. After a brief introduction in Chapter 1, we begin in Chapter 2 by reviewing some background material relevant to this thesis, including quasi-stationary Monte Carlo methods. These methods are designed to sample from the quasi-stationary distribution of a killed Markov process, and were recently developed to perform scalable Bayesian inference.
In Chapter 3 we prove natural sufficient conditions for the quasi-limiting distribution of a killed diffusion to coincide with a target density of interest. We also quantify the rate of convergence to quasi-stationarity by relating the killed diffusion to an appropriate Langevin diffusion. As an example, we consider a killed Ornstein-Uhlenbeck process with Gaussian quasi-stationary distribution.
In Chapter 4 we prove convergence of a specific quasi-stationary Monte Carlo method known as `ReScaLE'. We consider the asymptotic behavior of the normalized weighted empirical occupation measures of a diffusion process on a compact manifold which is also killed at a given rate and regenerated at a random location, distributed according to the weighted empirical occupation measure. We show that the weighted occupation measures almost surely comprise an asymptotic pseudo-trajectory for a certain deterministic measure-valued semiflow, after suitably rescaling the time, and that with probability one they converge to the quasi-stationary distribution of the killed diffusion.
In Chapter 5 we introduce the Restore sampler. This is a continuous-time sampler, which combines general local dynamics with rebirths from a fixed global rebirth distribution, which occur at a state-dependent rate. In certain settings this rate can be chosen to enforce stationarity of a given target density. The resulting sampler has several desirable properties: simplicity, lack of rejections, regenerations and a potential coupling from the past implementation. The Restore sampler can also be used as a recipe for introducing rejection-free moves into existing MCMC samplers in continuous time. Some simple examples are given to illustrate the potential of Restore.
We conclude the thesis in Chapter 6 with some concluding comments and open questions for future work.

Keywords: Monte Carlo inference
Markov chain Markov chain
Quasi-stationary distribution
Diffusion
Advisor: Steinsaltz, D
Roberts, G
Artificial oocyte activation (AOA) and phospholipase C zeta (PLCζ) in assisted reproductive technology (ART)

Oocyte activation deficiency (OAD) is the main cause of total fertilisation failure/low fertilisation rate in assisted reproductive technology (ART). Phospholipase C zeta (PLCζ) is the dominant sperm-specific factor responsible for triggering oocyte activation in mammals. Abnormalities in PLCζ have been linked with OAD. Artificial oocyte activation (AOA) is currently the only option for OAD in clinic but lacks reliable diagnostic approach and may cause abnormal Ca2+ release in oocytes. Previous studies have attempted to synthesise recombinant human PLCζ (rhPLCζ) protein but struggled to purify the protein or maintain functionality and stability. This thesis aimed to address these shortfalls by investigating the mechanism(s) of OAD and improving the applicability of PLCζ as a diagnostic and therapeutic agent for male infertility. This thesis first compared the efficiency of two immunofluorescence methods to assess PLCζ expression in male sperm (n=26 males) and demonstrated that our in-house assay showed the best labelling results when compared with a recently-published antigen-unmasking (AUM) method. I further developed our in-house PLCζ assay into a clinical diagnostic assay, which targets on infertile candidates for the AOA treatment (i.e., Ca2+ ionophores). Four out of five couples received AOA and achieved healthy live-births (fertilisation rate from 18.6% to 56.8%, p<0.001). Cut-offs for the key PLCζ characteristics were also determined for the first time (mean PLCζ levels: 15.57 arbitrary units [a.u.], and the proportion of sperm exhibiting PLCζ: 71%). Globally, eleven mutations have been identified in the PLCζ gene; however, the XY-linker that connects the main X and Y domains has received for less research attention. In addition, CAPZA3 shares a bidirectional promoter with PLCζ and is responsible for sperm morphology and function. In this thesis, Sanger sequencing and next-generation sequencing (NGS) were used to screen PLCζ exons (n=61 males), and PLCζ promoter, XY-linker and CAPZA3 regions (n=33 males). Ten single polymorphisms (SNPs) in PLCζ introns and three mutations in CAPZA3 exon were identified, some of which may partially explain the causes for male infertility. In addition, this study attempted to synthesise a novel rhPLCζ with uses of a pHLsec vector feathered with secretion signal sequence and further examined the functionality of the protein. Surprisingly, simple incubation of the protein with mouse oocytes triggered activation (22/52 developed to the 2-cell stage, p<0.001), which not only suggests that the protein may be functional, but also indicates the possible existence of a novel plasma membrane-bound mechanism that may act alongside the sperm factor.

Keywords: phospholipase C zeta
artificial oocyte activation
oocyte activation deficiency
PLCζ deficiency
Advisor: Coward, K
Wells, D
Profiling Doublesex-DNA interactions with targeted DamID in Drosophila melanogaster

The transcriptional regulators doublesex (dsx) and fruitless (fru) function together to specify sexual physiology and behaviour in Drosophila melanogaster. Whilst fru has only been located in insect lineages, dsx is structurally and functionally conserved throughout the animal kingdom. The role of FRU proteins as transcriptional regulators has been studied extensively with DamID – a method that uses DNA adenine methylation to create ‘fingerprints’ in the genome that correspond to where Dam-tagged proteins have interacted with DNA. Comparatively little research has focused on DSX, and there are few direct dsx target genes in the CNS. In this study, we implement the novel targeted DamID (TaDa) approach for profiling DsxM and DsxF expressing neurons in the Drosophila adult CNS, marking the first time these neurons will be profiled in a cell-specific manner. TaDa harnesses the phenomenon of low frequency ribosome re-initiation, and the introduction of a primary open reading frame (ORF) encoded before the Dam-fusion, to enable low level expression of the Dam-fusion in a cell-type specific manner when driven using Gal4/UAS. We generate a rich list of putative dsx targets in the CNS. Comparisons with a published DSX-fat body DamID dataset, an organ in which dsx is known to be widely expressed, reveal a tendency towards tissue-specificity. Our Gene Ontology analyses reveal DSX targets are involved in nervous system development, confirming the known role attributed to dsx, and motif analyses identify novel putative GATA cofactors. Alongside independent protein-DNA interaction screens (ChIP-seq and yeast-one hybrid), we identify the neuropeptides Diuretic Hormone 31 (Dh31), Tachykinin 1 (Tk1) and Neuropeptide-like precursor 1 (Nplp1) for further analysis. dsx/ Nplp1 expression analyses reveal a single cluster of neurons in the female brain, likely pMN1, which we speculate is involved in post-mating behaviour. The wealth of putative dsx target genes generated here pave the way for further characterisation of the dsx machinery and thus a better understanding of its role in specifying sexual physiology and behaviour.

Keywords: doublesex
DamID
protein-DNA interactions
targeted DamID
CNS target genes
Drosophila melanogaster
Advisor: Goodwin, S