VictorJuiz/thesis huggingface dataset:
Rumination and reward processing in anorexia nervosa
Keywords: anorexia nervosa
rumination
reward
eating disorders

Anorexia nervosa (AN) is an eating disorder characterised by severe emaciation due deliberate restriction of food intake and an intense fear of gaining weight. Theoretical accounts of AN have to date focused predominately on cognitive elements of the disorder, yet resulting treatments have been inadequate and outcome for AN remains poor. Understanding the processes that maintain the disorder is an important step in developing effective strategies to augment existing treatments. With this in mind, the question arises: what processes drive AN?
Novel frameworks for AN suggest that particular information processing configurations or “modes” may underpin many symptoms of AN, such as preoccupation with control of eating, weight and shape. More specifically, it is proposed that a ruminative mode of processing may function as an avoidance strategy in AN, enabling individuals to neglect salient and rewarding stimuli, such as food, and thus uphold restrictive eating practices. Whilst empirical studies have examined processes such as rumination, avoidance and reward in depression, they have seldom been studied in AN. The aim of this thesis is therefore to understand the role of rumination and reward processes in AN.
Chapter 1 reviews the literature on AN, rumination and reward processing. Chapter 2 presents data demonstrating to what extent the content of rumination in AN differs from rumination in depression and the effect that rumination may have on ED symptoms. The study conducted in Chapter 3 examines whether individuals with AN can be switched out of rumination around meal times and what effect this has on AN psychopathology. Chapter 4 presents neuroimaging data which elucidates the brain regions involved in processing rewarding and aversive food stimuli after recovery from AN. The study reported in Chapter 5 teases apart hedonic (liking) versus motivational (wanting) aspects of food reward in AN. The final study (Chapter 6) provides further evidence using neuroimaging that rumination may be an important process in AN which may override appetitive responses to rewarding stimuli, such as food. The studies reported support the notion that rumination and aberrant reward processing may be involved in the maintenance of AN.
The evolution of viral diversity
Keywords: virus
antigenic evolution

This thesis focuses on the population dynamics of three antigenically diverse RNA viruses: dengue, influenza and HIV-1. It comprises a set of studies highlighting the roles of structural constraints on critical antigenic determinants, interactions between immune responses to different antigenic types, host lifespan, and the degree of mixing between different host populations in determining the epidemiology and within-host dynamics of these pathogen systems.
Dengue exists in humans as a collection of four antigenically related serotypes. Although infection by one serotype appears to convey life-long protection to homologous infection, it is believed to be a risk factor for severe disease manifestations upon secondary, heterologous infection due to the phenomenon of Antibody-Dependent Enhancement (ADE). It is not clear if third or fourth infections are possible, and if so, how they contribute to dengue epidemiology. In this thesis, I investigate the effect of third and fourth infections on the transmission dynamics of dengue.
By contrast with dengue, human influenza viruses are known to be in rapid antigenic flux, manifesting in the sequential replacement of antigenic types. This pattern of evolution does not appear to be the same in shorter-lived hosts such as swine and birds. In this thesis, I have used a simple multi-locus model to explore the relationship between host lifespan and viral evolution, as well as to elucidate the effects of transmission between hosts of different lifespan in effort to capture the cross-species element of influenza transmission.
My final chapter concerns the within-host evolution of HIV-1. I propose a new model for the pathogenesis of HIV-1 where the transition to AIDS is primarily linked to the gradual loss of the ability to make new antibody responses as the CD4+ population declines.
Together these studies emphasise that it is the changing profile of immune responses – either at the population level or within the host – that is the principal determinant of the dynamics of the pathogen, rather than the mode and tempo of antigenic innovation.
Petrogenesis of the phonolitic rocks of the Velay oriental, France
Keywords: basalt
phonolite
Sr-isotope
fractionation
Daly Gap
France
cumulate
K-Ar
Velay oriental

The Velay oriental (Massif Central, France) is a basaltic plateau with abundant viscous phonolite extrusions. The plateau lavas grade from alkali basalt to mugearite, but intermediate compositions are volumetrically scarce. Pyroclastics are absent. The most complete plateau sections are in the south, while in the north intermediate lavas appear only as viscous, phenocryst-rich extrusions.
The plateau lavas were erupted between 11.7Ma and 7.6Ma, the southern phonolites 8.5Ma- 6.5Ma and new data show that the northern phonolites were erupted between 13.3Ma and 10.5Ma. Basement uplift occurred during the plateau-building stage, due to the emplacement of magma chambers. Intermediate lavas are scarce because they remained in the magma chambers due to their density, whereas phonolite was able to rise hydrostatically. The magma chambers were within 5km of the surface.
Phonolites are divided into miaskitic and agpaiitic types on the basis of their chemistry and petrography. They evolved from the basalt by crystal settling in the magma chambers, whereas the aphyric plateau lavas evolved by plating crystals onto their conduit walls as they flowed towards the surface.
Sr-isotopes show that the basalt-phonolite series is uncontaminated, whereas the northern intermediate lavas evolved by assimilation-fractional-crystallisation.
A suite of cumulate nodules was recovered from a pyroclastic unit, which is probably younger than the Velay Miocene lavas. They are related to the northern intermediate lavas, and belong to the "Group II" class of nodules.
Geothermobarometry suggests that both the cumulates and the northern intermediate lavas crystallised at a depth of 15-20km and probably became contaminated due to the smaller temperature difference between the geotherm and granite solidus at that depth.
The vast majority of the Velay lavas are identical to alkalic ocean-island lavas, geochemically unaffected by their passage through the lithosphere, but with their relative proportions at the surface controlled by the density contrast between the basalt and basement granite.
Analysing and modelling the impact of habitat fragmentation on species diversity: a macroecological perspective
Keywords: biogeography
ecology
habitat fragmentation
macroecology
habitat loss

The destruction and fragmentation of natural habitat is the leading driver of the current extinction crisis. As a result, a research area has emerged focused on studying ecology in islands of natural habitat surrounded by a sea of anthropogenic land uses, so called ‘habitat islands’. However, this research has largely been undertaken on small-medium scales, generally in single systems. Furthermore, many habitat island studies have used previous results and theory derived in the context of oceanic island research. Thus, this thesis aims to examine a variety of macroecological and biogeographical patterns using a large number of purely habitat datasets sourced from both the literature and my own sampling, with the objective of teasing out any general statistical patterns. The various macroecological and biogeographical patterns can be grouped under four broad headings: 1) species–area relationships (SAR), 2) nestedness, 3) species abundance distributions (SADs), and 4) species incidence functions (function of area). Overall, it was found that there were few hard macroecological generalities that hold in all cases across habitat island systems. This is because most habitat island systems are highly disturbed environments, with a variety of confounding variables and undesirable species (e.g. species associated with human land uses) acting to modulate the patterns of interest. Nonetheless, some clear patterns did emerge. In particular, it was found that the power model was by the far the best general SAR model for habitat islands. The slope of the island species–area relationship (ISAR) was related to the matrix type surrounding archipelagos, such that habitat island ISARs were shallower than true island ISARs. Significant compositional and functional nestedness was rare in habitat island datasets, although island area was seemingly responsible for what nestedness was observed. Species abundance distribution models were found to provide useful information for conservation in fragmented landscape, but the presence of undesirable species substantially affected the shape of the SAD. Species incidence function curves were found to vary across space for a given species, but not in any systematic manner. In conclusion, this thesis finds that the application of standard island biogeography theory to habitat islands is too simplistic. It is hoped that the results of this thesis will act as a catalyst for a more macroecological approach to habitat island research, and a starting point for the development of an integrated theory of habitat islands.
Balance beyond work life: an empirical study of older people's time use in the UK
Keywords: life course
wellbeing
time use
time use of older people
later life
work-life balance

This thesis examines how patterns of time use change in later life and how the way in which older people use their time is related to well-being. Arguing that maintaining balance in time use concerns not only people of working age but matters for people of all ages, we propose an alternative theoretical framework of life balance. This consists of two conceptual models: The Life Balance Triangle and Multidimensional Life Balance (MLB). Using UK time use data, the thesis demonstrates the empirical applicability of these two models in enhancing our understanding of older people's daily lives.
The life balance model, which we built by modifying the theoretical categorisation of time use by Ås (1978) and the work-leisure triangle of Gershuny (2003), identifies and presents alteration in time use across the life course as changes in balance between constraints (committed time) and freedom of choice (discretionary time), controlling for time spent on biological/physiological maintenance (regenerative time). We find the balance shifts towards greater discretionary, and less committed, time in later life, with a significant gender gap. Life stage, which reflects social structure and expectations, rather than biological ageing, was found to be the most influential factor for life balance dynamics. Findings suggest that men may find it more difficult to adjust to life beyond work because of abrupt and greater changes in life balance, which may disrupt their daily time structure.
The multidimensional life balance model challenges the assumption of a linear relationship between the level of activity and well-being of older people. Adapting the Alkire-Foster method (Alkire and Foster, 2011), we propose a threshold-based approach that takes the heterogeneity of older people and multidimensionality of daily life into account, and emphasises overall balance in the level of activities across various activity domains. Results show MLB is associated positively with better self-assessed health, suggesting a threshold effect. We also identify the demographic/socio-economic groups more likely to lack MLB, as well as domains in which most people are deficient. The thesis contributes to work-life balance research by moving beyond paid-work centrality, and to ageing research by providing a multidimensional approach to activities and well-being in later life.
Measurement of the inclusive jet cross section with the ATLAS detector at the Large Hadron Collider
Keywords: jets
parton distribution functions
QCD
JES
inclusive jet cross section
PDF

This thesis presents the measurement of the inclusive jet cross section using data collected in 2010 by the ATLAS detector, with a particular focus on the reconstruction and calibration techniques used for jets in this measurement and on the estimate of the systematic uncertainty on their energy scale. The inclusive jet cross section measurement is used as input to fits of parton distribution functions. Although the PDF analysis in this thesis is preliminary and its main purpose is to serve as a proof of principle for future studies, improvements in the knowledge of the gluon density are observed thanks to the inclusion of ATLAS data.
Toward functional imaging of the placenta
Keywords: volumetric
3D
obstetrics
ultrasound
Doppler
analysis
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.
Measurement of CP violation in B -> DK* Decays with the LHCb Experiment
Keywords: LHCb
CP violation
flavour physics
experimental particle physics
quantum mechanics
physics
LHC
particle physics
CERN

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.
Trauma and the peri-traumatic cognitive mechanisms involved in flashback formation
Keywords: post-traumatic stress disorder
cognitive psychology
clincal psychology
psychiatry

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.
Identification and characterisation of alternative forms of SETD2/HYPB (SET domain-containing protein 2 / Huntingtin yeast partner B)
Keywords: methyltransferase
denaturation
nucleosome
H3K36
chromatin
methylation
KMT3a
H3K36me3
urea
histone
SET2
isoform

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.
Design, synthesis and application of novel light-activated molecular probes
Keywords: molecular probes
light-activated
caged
caging

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.