VictorJuiz/thesis huggingface dataset:
Toward functional imaging of the placenta

In obstetrics, the application of computer-based image analysis to provide deeper insight into pathology in early pregnancy is highly desirable but underdeveloped. One such pathology, fetal growth restriction (FGR) is a leading cause of mortality and morbidity in pregnancy. FGR affects approximately 3-10% of pregnancies in the western world leading to increased risk of stillbirth and health problems in later life. Morphometric or functional measurement of the placenta in pregnancy in utero may aid diagnosis of this pathology as the interface between placenta and mother is the site where the pathology manifests itself. Detection of growth restriction is yet to be resolved as poor, unreliable biochemical and image-based biomarkers have made it hard to detect and manage these pregnancies effectively.
By the provision and development of tools for quantification of the placenta by three dimensional (3D) ultrasound (US) using image segmentation and mesh processing, this thesis aims to better facilitate clinical investigation of this major problem in obstetric healthcare.
In a first contribution, 3D placental volume measurement using 3D US is used to classify the difference between normal and FGR pregnancies. Volume was estimated using the semi-automated random walker (RW) algorithm. The repeatability and reliability of the method was tested between three observers and showed the new method to be equivalent to manual segmentation. In a study of 143 women performed by our clinical partners, significantly smaller placental volume was found in pregnancies defined as small-for-gestational age (SGA).
Expanding on volumetry, the utero-placental interface (UPI) is the location where the pathology that leads to FGR occurs. Manual manipulation of the volume is requiredtovisualisetheinterface, soweinvestigatedapplyinga“meshflattening” process to convert the contorted UPI into a disc to provide a standardised way to view the interface between acquistions and subjects.
Finally, an existing, two dimensional (2D) Doppler standardisation technique was extended into 3D to provide standardisation of values of Doppler vascularity. This technique was then applied to measure the vascularity of volumes of interest relative to the interface between placenta and mother. This test was then applied clinically in 143 women and found that the vascularity of the small-for-gestational age (SGA) pregnancies was significantly smaller than that of the population who produced appropriately sized babies. These three tools each provide augmentation of our understanding of placental health and function in pregnancy. From measuring the gross volume to estimating the blood flow we show the potential clinical application for image analysis performed on 3D power Doppler (PD) ultrasound volumes.

Keywords: volumetric
3D
obstetrics
ultrasound
Doppler
analysis
placenta
Advisor: Noble, J
The molecular biology of chemotactic signal transduction in rhodobacter sphaeroides

This study has succeeded in identifying, cloning and sequencing three genes previously unknown in R. sphaeroides, che W, che R and che Y2. These genes are homologous to genes recently discovered in Rhizobium meliloti and also show a lesser homology to genes in other organisms including the well characterised enteric chemotaxis genes.
A comparative analysis of the deduced proteins has been made to determine structural and functional similarities between the R. sphaeroides genes and their homologues in R. meliloti and in E. coli. Considerable conservation of functionally important amino acid residues was revealed.
In vivo complementation was done using the R. sphaeroides Che W protein to complement Che W- strain of E. coli. The R. sphaeroides protein complemented the E. coli strain empirically proving similarity of function of the protein between these widely divergent genera.
Homologous recombination using transposon-interrupted genes and internal gene fragments was attempted and met with limited success because R. sphaeroides proved permissive to the suicide vectors used.
The most significant result of this study has been not in the similarities revealed between the chemotaxis systems of R. sphaeroides and the enterics, but in the differences discovered. It is now known that R. sphaeroides possesses two Che Y proteins, Che Y and Che Y2, and that whereas the R. sphaeroides Che Y2 protein is closely related to the E. coli Che Y protein, the R. sphaeroides Che Y protein shows considerable evolutionary divergence from it's enteric homologue. The significance of a second copy of Che Y protein suggests that these two response regulators act independently at the motor/switch complex and that they represent the final elements of two functionally distinct chemotactic sensory transduction pathways. This dual pathway system is not present in the enteric bacteria (a member of the γ-group of proteobacteria) but, we propose, may be present in a large group of environmentally important bacteria, the α-group of proteobacteria. Caulobacter, Agrobacterium, Rhizobium and Azospirillum species (α-group proteobacteria) all show behavioural similarities, and there are genetic clues to suggest that these organisms possess a dual chemotactic sensory transduction similar to the one we have found in R. sphaeroides.
Apart from being fundamentally important, the dual sensory pathway hypothesis explains the wild-type behaviour of R. sphaeroides, as well as the difficulty in obtaining behavioural mutant phenotypes using methods developed during the investigation of E. coli.

Advisor: Armitage, J
Measurement of CP violation in B -> DK* Decays with the LHCb Experiment

This thesis reports an analysis of 3.0fb-1 of pp collision data collected by the LHCb experiment in 2011 and 2012. Decays of neutral B mesons to neutral D mesons and excited neutral kaons are reconstructed, because of their sensitivity to the CP-violating phase of the CKM matrix, γ. The neutral D meson is reconstructed in four separate final states. These are K-π+, K
+π-, K+K- and π+π-.
Several observables are defined, in terms of the partial widths of B&rightarrow;DK* decays, that are sensitive to gamma and other, CP-conserving, parameters of the decays of the B and D mesons. The measured results include the CP asymmetry between the partial widths of B̅0&rightarrow;D(K+K-)K̅*0 and B0&rightarrow;D(K+K-)K*0 decays, which is found to be
A K K
d
= −0.198 +0.144 +0.019
−0.145 −0.020.
In addition, the Cabibbo-suppressed B0&rightarrow;D(K-π+)K*0 and B̅0&rightarrow;D(K+π-)K̅*0 decays are analysed for the first time with data collected by LHCb. The ratio of the partial widths of the Cabibbo-suppressed B0&rightarrow;D(K-π+)K*0 decay to the Cabibbo-favoured B0&rightarrow;D(K+π-)K*0 decay is measured, as well as the analogous quantity corresponding to B0bar decays. These are found to be
R +
d
= -0.057 +0.029 +0.009
−0.027 −0.012
    and     R −
d
= -0.056 +0.032 +0.009
−0.030 −0.012,
respectively.
Finally, the ratio of the magnitudes of the amplitudes corresponding to B0&rightarrow;D0K*0 and B0&rightarrow;D̅0K*0 decays is found to be
rB = -0.230 +0.063
−0.045
at a confidence level of 68.3% and the first constraints on γ from Bd&rightarrow;DK* decays are made.

Keywords: LHCb
CP violation
flavour physics
experimental particle physics
quantum mechanics
physics
LHC
particle physics
CERN
Advisor: Wilkinson, G
Ricciardi, S
Trauma and the peri-traumatic cognitive mechanisms involved in flashback formation

Post-traumatic stress disorder (PTSD) is classified as an anxiety disorder in the Diagnostic and Statistical Manual IV of the American Psychiatric Association. It is characterised by three main symptom clusters: re-experiencing (of which flashbacks are the hallmark symptom); hyperarousal; and avoidance. Diagnosis requires not only the occurrence of a traumatic event but also an intense emotional (fear, horror, or helplessness) reaction to it. Epidemiological data suggest that 80% of people will experience at least one qualifying event in their lifetime. However, prevalence rates of PTSD are much lower. Additionally, individuals with PTSD tend to experience flashbacks of only two or three particular ‘hot-spots’ of the entire trauma. Therefore, the question arises: why do some moments of trauma flash back and not others?
Clinical-cognitive theories of PTSD suggest that shifts in information processing at the time of the trauma (i.e. peri-traumatically) are the mechanism whereby flashbacks are created. However, for ethical and practical reasons peri-traumatic processes in real trauma are seldom studied. An analogue traumatic event has been developed to help study peri-traumatic processes – the trauma film paradigm. This paradigm is used through-out this thesis with the goal of investigating peri-traumatic cognitive mechanisms in flashback formation. Studies 1 and 2 extend previous work using dual tasks to manipulate intrusions in-line with clinical-cognitive theories. Studies 3 and 4 use neuroimaging techniques to investigate brain regions involved in real-time peri-traumatic encoding of analogue flashbacks. Chapter 9 presents heart rate data relating to peri-traumatic physiological response to flashback encoding. All of these studies support the notion that peri-traumatic shifts in processing are involved in flashback formation. In particular, Study 3 suggests that there may be a particular neural signature associated with the formation of flashbacks. Investigation of these brain areas may help solve the questions of why some individuals are more vulnerable to PTSD and why only a few specific moments of a trauma subsequently flashback. Furthermore, an improved understanding of the cognitive mechanisms involved in flashback formation may allow theory and evidence led improvements in PTSD treatments.

Keywords: post-traumatic stress disorder
cognitive psychology
clincal psychology
psychiatry
Advisor: Holmes, E
Mackay, C
Identification and characterisation of alternative forms of SETD2/HYPB (SET domain-containing protein 2 / Huntingtin yeast partner B)

SETD2/HYPB (SET domain−containing protein 2 / Huntingtin yeast partner B) is the predominant lysine methyltransferase in mammals that mediates histone H3 lysine-36 (H3K36) trimethylation, which is associated with transcription elongation and RNA splicing. SETD2 is further implicated in p53 function, vascular development, cancer progression and, through Huntingtin-interaction, Huntington's disease. Although different transcripts and putative protein isoforms have been detected previously, their identity, function and signiﬁcance have not been rigorously investigated.
This thesis aims to identify and characterise endogenous transcripts and protein isoforms of SETD2 in mouse ﬁbroblasts. Affnity-puriﬁed N- and C-terminal antibodies speciﬁcally detected the &TildeTilde; 290 kDa methyltransferase (p290SETD2), veriﬁed by RNAi, in addition to N terminal-speciﬁc &TildeTilde; 120 kDa protein, and C terminal-speciﬁc forms at &TildeTilde; 140 and &TildeTilde; 66 kDa (p66), which all appeared too stable to deplete by transient siRNA transfection. Conserved in human and mouse cells, immunodetection of p66 exhibited unusual requirement for denaturation with urea at 95°C. Subcellular fractionation revealed distinct extraction properties of putative isoforms and facilitated partial puriﬁcation of p66 for proteomic analysis. Co-fractionation and co migration by two-dimensional gel electrophoresis of p66 detected by two independent C terminal antibodies suggested it represents a novel C terminal-speciﬁc isoform. Reverse transcription−PCR and DNA-sequencing demonstrated the existence of multiple, alternatively-spliced Setd2 transcripts that plausibly generate truncated proteins. A transcript variant containing a novel complete open-reading-frame, consistent for p66 generation, was identiﬁed. Its ectopic expression in mouse ﬁbroblasts produced a distinct SETD2 isoform, whose physical and extraction characteristics were studied in comparison with endogenous immunoforms.
In summary, this thesis demonstrates that multiple alternatively-spliced transcripts arise from the Setd2 gene, consistent with immunodetection of several C- and N-terminal-speciﬁc putative SETD2 isoforms, additional to the H3K36 methyltransferase. Veriﬁcation of these isoforms by independent methods would have implications for proposed interactions and function of SETD2 in transcription, epigenetics, cancer development and Huntington’s disease.

Keywords: methyltransferase
denaturation
nucleosome
H3K36
chromatin
methylation
KMT3a
H3K36me3
urea
histone
SET2
isoform
Advisor: Mahadevan, LC
Mancini, EJ
Some problems in algebraic topology

In this thesis, we establish a pair of systems of higher order cohomology operations that act on the Ζp-ordinary cohomology of spaces that are free of p-torsion. These "pyramids" of operations are generated by the p-divisibility of certain sums of "pseudo" primary cohomology operations that operate on the p-local cohomology of p-torsion-free spaces.
The properties of these higher order operations allow us to prove theorems that either generalise or improve (in the sense of decreasing indeterminacy) several results in the literature.

Advisor: Hubbuck, J
Design, synthesis and application of novel light-activated molecular probes

Caged compounds are biologically active molecules that are rendered inert by masking an important functionality with a photolabile protecting, ‘caging’, group. The caging group can be removed by irradiation with light to reveal the active compound with restored pharmacological activity with high spatial and temporal control. This technology provides an ideal tool for the study of many chemical, physiological and biological systems.
This DPhil dissertation highlights several projects in which caging technology has been employed to address biological problems and questions. The first example of spatially controlled mitochondrial inactivation is reported - a tool for the study of the role of mitochondria in Ca2+ signalling. Caged TRPV1 agonists and antagonists have been developed to probe TRPV1, specifically the location of the agonist-binding site. T cell activation has been controlled with light as a tool to gain insight into the adaptive immune response. Caged sodium channel blockers have been investigated. Wavelength-orthogonal photolysis in a neuronal system has been demonstrated using the neurotransmitters glutamate and GABA - this represents a significant advancement in caging technology. This dissertation also includes investigations into the development of novel caging groups.

Keywords: molecular probes
light-activated
caged
caging
Advisor: Conway, S
The effects of neuroinflammation on the subventricular zone neurogenic compartment following Theiler's Murine Encephalomyelitis virus infection and its regulation by Galectin-3

The subventricular zone (SVZ) is an adult neurogenic niche that contains multipotent stem/progenitor cells that may be a viable target for remyelination in Multiple Sclerosis. In response to demyelination, SVZ progenitors are recruited into myelin lesions. Currently, the effect of inflammation on the endogenous brain stem cell compartment remains poorly characterised. Theiler's murine encephalomyelitis virus (TMEV) induces a demyelinating disease in susceptible SJL/J mice, due to persistence of the virus, which models the chronic progressive form of multiple sclerosis. In contrast, virus is rapidly cleared in TMEV resistant C57BL/6 mice. This viral clearance is critically dependent on infiltration of CD4+ and CD8+ T cells during the first 3-14 days after infection, through the blood vessels and meninges. This project aimed to characterise the impact of TMEV induced inflammation on SVZ homeostasis.
In both strains of mice the most pronounced and consistent inflammation in the CNS was observed in periventricular regions and in particular, the SVZ, which showed targeted infection by the TMEV virus. However, the time course and kinetics for infiltration at 3,7 and 14 days post infection have very different profiles between resistant C57BL/6 and susceptible SJL mice. Using RT-PCR arrays and ELISA I have shown that these differences in T cell infiltration to the SVZ may be due to much higher chemokine and cytokine expression levels in B6 mice. TMEV infection decreases SVZ cell proliferation and results in a loss of neuroblast numbers.
Galectin-3 (Gal-3) is a β-galactoside binding protein that is constitutively expressed specifically in the SVZ. Following TMEV infection Gal-3 levels are significantly upregulated in the SVZ, with higher expression in B6 mice compared to SJL mice. Primary SVZ astrocytes secrete extracellular Galectin-3 at much higher levels than cortical astrocytes. Galectin-3 is a pro-inflammatory mediator which upon secretion is able to activate immune and inflammatory signaling events and amplify pro-inflammatory cytokine production. Both SJL and B6 Gal-3-/- KO mice have decreased expression of CCL2, CCL5 CXCL10 and CCL8 chemokines in the SVZ after TMEV infection. Deletion of Gal-3 prevents the loss of SVZ proliferation and in B6 mice decreases hematopoietic cell infiltration and enhances ectopic neuroblast emigration. These data implicate Galectin- 3 as a novel regulator of the SVZ inflammatory response and may provide a new target for regulating T cell CNS immigration in autoimmune disease.

Keywords: Galectin-3
Theiler's
neuroinflammation
multiple sclerosis
Advisor: Szele, F
The sedimentation, tectonics and stratigraphy of the cretaceous/tertiary sequence of northwest Santander, northern Spain

The facies evolution of the Cretaceous/Tertiary sequence of NW Santander is considered in relation to the Cretaceous rifting and drifting, and Tertiary partial closure of the Bay of Biscay. Overlying the Palaeozoic basement are the fluvial Lower Triassic Buntersandstone and Upper Triassic Keuper evaporitic mudstone, deposited in a failed rift, extensional basin. Overlying Lower Jurassic carbonates are the syn-rift, continental elastics of the Vealden deposited in halfgrabens cut by transfer faults. The Vealden consists of two formations:- the lower, arenaceous-rich Barcena Mayor Fm. (braided stream environment) and the upper, argillaceous-rich Vega de Pas Fm. (meandering river). Overlying it is the Aptian Umbrera Fm. (calcarenite sheet), the Patrocinio Fm. (shoaling-up ward sandstone/marl alternation), the San Esteban Fm. (requienid/foraminiferal biomicrite of the internal platform) and the marls of the Rodezas Fm.. The Upper Aptian Reocin Fm. is a requienid/foraminiferal biomicrite with thinned calcarenites deposited over active, diapiric palaeohighs. After initial marine and then equant calcite (meteoric phreatic) cementation, invasion of meteoric-derived groundwater over palaeohighs generated lenses of sucrosic dolomite in the Reocin Fm.. Local mixing of further groundwater and Keuper-derived, sulphate-rich waters in karstic caverns precipitated sparry, baroque dolomite and Pb/Zn sulphides (by bacterial sulphate reduction). The clastic Lower Albian is a transgressive fluvial/estuarine/inner shelf sequence with tidal estuarine channels and sandwaves. The Middle/Upper Albian (syn-drift) has basal calcarenitic tidal sandwaves and is followed by storm/wave-reworked carbonates deposited on a homoclinal ramp. The clastic Lower Cenomanian is an estuarine/inner shelf deposit with tidal sandwaves and sandbars. The Middle/Upper Cenomanian is a storm/tide-dominated calcarenite. Outer shelf marls occur in the Turonian to Middle Campanian and the Upper Campanian to Middle Eocene is a sandy, foraminiferal inner shelf limestone. The Upper Eocene/Oligocene (syn-compression) is a carbonate slope-apron-reefal flysch deposit. It includes hemipelagic marl, neritic-derived calcarenitic turbidites and rudaceous mass flow deposits with highly polymict conglomerates. These were deposited coevally with Keuper piercement and thrust reactivation and date the Pyrenean compressional deformation here.

Advisor: Reading, HG
Precipitation behaviour of calcium phosphate

Various aspects of the precipitation behaviour of calcium phosphate in aqueous media have been investigated using seeded growth in conjuction with constant-volume and constant-composition techniques under different physical and chemical conditions. In each case, precipitation was allowed to proceed for up to seven days. The solid precipitates thus obtained were characterised by means of scanning electron microscopy, powder X-ray diffractometry and wavelength dispersive spectroscopy.
During these precipitation experiments, the formation of the thermodynamically most stable and most supersaturated phase was invariably preceded by the appearance of less supersaturated precursor phase(s). These precursors subsequently underwent step-wise phase transformation into more stable phases. The preferred precursor and the rates of precipitation and phase transformation were dependent on the physical conditions and the chemical composition of the calcifying medium.
Under physiological conditions, precipitation experiments were also carried out with the addition of certain non-collagenous bone-specific bio-chemicals. Phosphoserine dramatically accelerated the precipitation of a large quantity of small plate-like crystals, while osteonectin and phosphatidylserine induced the formation of quasi-cubic crystals at a slow rate. Bone protein extract displayed the strongest inhibitory effect on calcification. Bovine serum albumin showed signs of being irreversibly adsorbed to the crystal surface, thereupon inducing a high degree of calcium deficiency in the precipitate stoichiometry.
Using a number of phosphorylated amino acids of different molecular masses, it was found that the processes of precipitation and phase transformation were facilitated by organic molecules whose phosphoryl functional groups were sterically accessible and highly electronegative. However, the acceleration brought about by the presence of a phosphorylated amino acid was maximised at an optimum concentration. The existence of such an optimum was very likely to be consequent of the competition for free calcium ions by the ongoing complexation and precipitation reactions.
A model has also been developed to describe and predict the precipitation behaviour of calcium phosphate. The model is based on the Avrami-Johnson-Mehl expression for threedimensional nucleation and growth processes. Appropriate modifications to the original equation have been made, in order to adapt to this multi-ionic aqueous system. The resulting model has been found to describe the actual precipitation process accurately. It has also been applied to systems in which organic additives were present, and has again furnished predictions closely resembling the behaviour as observed experimentally.

Advisor: Czernuszka, J
Play, risk and children's sociality in urban Vancouver

This thesis demonstrates how children challenge the boundaries adults place on them, out of concern for their safety, through child-specific cultural practises. The thesis argues that these boundaries emerge from contemporary changes in the perception of risk to children and have driven the systematic limitation of spaces that children are allowed to experience on their own. Based on data collected among elementary school-age children during twelve months of fieldwork (2008-2009), across multiple sites in the city of Vancouver, Canada, I argue that children creatively adapt to spatial and social limits imposed on them through play, consumption and exchange. Moreover, the research demonstrates that through gathering social knowledge and experimenting with self-presentation and systems of social order, children create a sophisticated peer culture. This incorporates social differentiations and hierarchies that differ from those of adult society however, are interdependent with it. My work thus challenges the position of children as objects and ‘anecdotes’ in anthropology: considered ‘works in progress’ and lacking full status as persons in society. Rather, I argue that they should be treated as competent social actors in their own right with their own social meanings and cultural practises.

Keywords: friendship
risk
games
childhood
toys
play
Advisor: Daniels, I