VictorJuiz/thesis huggingface dataset:
Mood instability: its cognitive and neural correlates and the effects of L-type calcium channel antagonism
Keywords: Mood instability
Transdiagnostic
Remote monitoring
Calcium channel antagonism
Cognitive function
Randomised control trial
Magnetoencephalography

Mood instability is commonly experienced in the general population. It is associated with risk for subsequent diagnosis of bipolar disorder (BD) and is a prominent feature of several other psychiatric disorders. Despite the significance of mood instability in psychopathology, there is little research examining its potential underlying mechanisms. In a study measuring mood, cognitive function and resting-state magnetoencephalography (MEG) over 10-weeks, the first part of this thesis aimed to characterise mood instability and explore its cognitive and neural correlates in healthy individuals at low and high risk of BD as indicated on the Mood Disorder Questionnaire (MDQ). Findings demonstrated that instability in negative mood was significantly different between individuals scoring low and high on the MDQ. Individuals with high MDQ scores demonstrated deficits in learning context-based regularities across days, and higher levels of negative mood instability in this group were also associated with changes in neural activity such as reduced switching between brain states, and reduced time spent in a fronto-limbic state thought to be necessary for mood regulation.
The second part of this thesis aimed to explore the candidacy of L-type calcium channel (LTCC) antagonism as a potential treatment for mood instability. Healthy individuals with high MDQ scores participated in a double-blind, placebo-controlled, experimental medicine study. For two weeks in the absence of any intervention, measures of mood and neural activity were assessed. This was followed by a 2-week randomisation phase to either nicardipine SR or placebo, during which all measures were repeated. Compared to placebo, LTCC antagonism was not found to reduce mood instability or significantly affect resting-state MEG measures of spectral power, alpha peak frequency, or characteristics of fast transient brain states.
Overall, these findings provide insights into the potential mechanisms that might underlie mood instability, highlighting areas for future investigation. While the candidacy of LTCC antagonism in mood instability was not confirmed, this work demonstrates the feasibility of multimodal, high-intensity studies to investigate transdiagnostic constructs and the potential of new treatments.
Adequacy of damages
Keywords: private law theory
commercial remedies
private law
judicial discretion
injunctions
equity
specific remedies
specific performance

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease whose molecular pathogenesis serves as a useful model for understanding other chronic inflammatory conditions. Activated macrophages are critical for RA pathogenesis, since they promote the inflammation that causes cartilage damage, bone remodelling, pain and irreversible disability. Macrophages are activated by stimuli in their environment, and responses to these stimuli are fine-tuned by their interactions with highly sulfated heparan sulfate (HS) glycosaminoglycans. HS is sulfated in complex patterns, but 6-O-sulfation of HS glucosamine subunits is known to be particularly important for regulating activity of many cytokines, chemokines and growth factors. 6-O-sulfation is hence tightly regulated, and it is the only HS sulfation motif that can be post-synthetically removed by the extracellular sulfatases SULF1 and SULF2. Although extensively studied in cancer and development, the effect of 6-O-sulfation on inflammation and macrophage function is unknown.
In this thesis I showed that Sulf2 is mainly expressed by macrophages, monocytes and dendritic cells. Sulf2 is particularly highly expressed by protective resident alveolar macrophages in the lung and resident synovial macrophages in the joint, indicating that Sulf2 is likely to be important for maintaining homeostasis and suppressing inflammation. Moreover, Sulf2 is downregulated by many inflammatory stimuli, suggesting that downregulation of Sulf2 may enable macrophages to convert from a protective phenotype to an activated inflammatory phenotype. Phagocytosis was increased in Sulf2-deficient macrophages, while macrophage polarisation was inhibited.
Sulf2-deficient bone marrow chimeras were generated to investigate the role of Sulf2 in immune function during antigen-induced arthritis (AIA) as an example of a chronic inflammatory disease. These Sulf2-deficient mice developed increased knee swelling, which was associated with an increase in pro-arthritic Th17 cells.
In conclusion, SULF2 is important for maintaining homeostasis by suppressing macrophage activation, indicating that therapies reducing 6-O sulfation of HS might be effective for the treatment of RA and other chronic inflammatory diseases.
A Bayesian account of learning and generalising representations in the brain
Keywords: entorhinal cortex
representation learning
hippocampus
biological backprop
non-spatial reasoning
generative models
Bayesian
artificial neural networks
predictive coding

Without learning we would be limited to a set of preprogrammed behaviours. While that may be acceptable for flies, it does not provide the basis for adaptive or intelligent behaviours familiar to humans. Learning, then, is one of the crucial components of brain operation. Learning, however, takes time. Thus, the key to adaptive behaviour is learning to systematically generalise; that is, have learned knowledge that can be flexibly recombined to understand any world in front of you. This thesis attempts to make inroads on two questions - how can brain networks learn, and what are the principles behind representations of knowledge that allow generalisation. Though bound by a common framework of Bayesian thinking, this thesis considers the questions in two separate parts.
In the first part of the thesis, we investigate algorithms the brain may use to update connection strengths. While learning attempts to optimise a global function of the brain state, each connection only has access to local information. This is in contrast to artificial networks, where global information is easily conveyed to each synapse via the back-propagation algorithm. We show that, contrary to decades old beliefs, an analogous algorithm to back-propagation could be implemented in the local dynamics and learning rules of brain networks. We show an exact equivalence between the two algorithms and demonstrate that they perform identically on a standard machine learning benchmark. These results are the first to show that an algorithm as efficient as those used in machine learning could be implemented in the brain.
In the second part of the thesis, we investigate frameworks for learning and generalising neural representations. It is proposed that a cognitive map encoding the relationships between entities in the world supports flexible behaviour. This map is traditionally associated with the hippocampal formation, due to its beautiful representations mapping space. This cognitive map, though, seems at odds with the other well-characterised aspect of the hippocampus: relational memory. Here we unify spatial cognition and relational memory within the framework of generalising relational knowledge. Using this framework, we build a machine that learns and generalises knowledge in both spatial and non-spatial tasks, while also displaying representations that mirror those in the brain. Finally, we confirm model predictions in neural data. Together, these results provide a computational framework for a systematic organisation of knowledge spanning all domains of behaviour.
The role of extracellular sulfatase-2 in inflammation
Keywords: heparan sulfate
sulfatase
inflammation
rheumatoid arthritis
macrophage

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease whose molecular pathogenesis serves as a useful model for understanding other chronic inflammatory conditions. Activated macrophages are critical for RA pathogenesis, since they promote the inflammation that causes cartilage damage, bone remodelling, pain and irreversible disability. Macrophages are activated by stimuli in their environment, and responses to these stimuli are fine-tuned by their interactions with highly sulfated heparan sulfate (HS) glycosaminoglycans. HS is sulfated in complex patterns, but 6-O-sulfation of HS glucosamine subunits is known to be particularly important for regulating activity of many cytokines, chemokines and growth factors. 6-O-sulfation is hence tightly regulated, and it is the only HS sulfation motif that can be post-synthetically removed by the extracellular sulfatases SULF1 and SULF2. Although extensively studied in cancer and development, the effect of 6-O-sulfation on inflammation and macrophage function is unknown.
In this thesis I showed that Sulf2 is mainly expressed by macrophages, monocytes and dendritic cells. Sulf2 is particularly highly expressed by protective resident alveolar macrophages in the lung and resident synovial macrophages in the joint, indicating that Sulf2 is likely to be important for maintaining homeostasis and suppressing inflammation. Moreover, Sulf2 is downregulated by many inflammatory stimuli, suggesting that downregulation of Sulf2 may enable macrophages to convert from a protective phenotype to an activated inflammatory phenotype. Phagocytosis was increased in Sulf2-deficient macrophages, while macrophage polarisation was inhibited.
Sulf2-deficient bone marrow chimeras were generated to investigate the role of Sulf2 in immune function during antigen-induced arthritis (AIA) as an example of a chronic inflammatory disease. These Sulf2-deficient mice developed increased knee swelling, which was associated with an increase in pro-arthritic Th17 cells.
In conclusion, SULF2 is important for maintaining homeostasis by suppressing macrophage activation, indicating that therapies reducing 6-O sulfation of HS might be effective for the treatment of RA and other chronic inflammatory diseases.
The journey of young souls in early medieval England (c. 850 - c. 1050)
Keywords: original sin
origin of the soul
souls outside living bodies
ensoulment
Old English
medieval childhood
Anglo-Latin
Anglo-Saxon
souls
life journey of the soul

This thesis explores the complex theological beliefs about young souls expressed during the late Anglo-Saxon period. Scholars have paid surprisingly little attention to the theology of the soul between the ninth and eleventh centuries except in relation to its fate after death. Yet, the living soul appears prominently in Latin and Old English prose and verse demonstrating the extent to which beliefs about the whole of the soul’s life journey were still evolving. So great an interest did contemporary writers show in questions relating to the origins of the soul and its early experiences that it proved impossible to address the whole life journey of the soul from creation to judgment within the space of a single doctoral thesis. This thesis therefore focuses on the life journey of the young soul up to the cusp of adulthood, following pivotal moments from the birth of the soul to its adolescence.
The first substantive chapter analyses the transfer of beliefs about the soul’s origin across this period from a Neoplatonic stance arguing for the soul’s pre-existence to a Creationist outlook. The second chapter questions the point at which the soul was first believed to enter the body and addresses the inconsistencies surrounding ensoulment during the period. The next chapter addresses ideas about the state of a child’s soul at the start of corporeal existence and the degree to which we can tell that the Anglo-Saxons believed in an inherited condition of original sin. The fourth chapter asks how long the soul received immediate entrance into heaven after baptism and where Anglo-Saxon writers drew the spiritual boundary between childhood and adulthood.
A conclusion addresses the necessity of looking further into Anglo-Saxon beliefs about the life journey of the soul. The following epilogue studies souls outside living bodies to demonstrate the diverse and dynamic beliefs which continually appear in later Anglo-Saxon sources.
Search for new physics through Higgs-boson-pair production at the LHC and beyond
Keywords: LHC
graviton
di-higgs
b quark
higgs pair
higgs boson
large hadron collider
heavy higgs
particle physics

This thesis presents a search for resonant production of highly energetic Higgs boson pairs, with each Higgs boson decaying to a b-quark pair, with the ATLAS detector. This analysis uses the complete ATLAS run 2 dataset of 139.0 fb−1 of proton-proton collisions at a centre-of-mass energy of sqrt(s) = 13 TeV. The expanded dataset, new flavour-tagging techniques, and novel subjet reconstruction algorithms provide better sensitivity than previous studies of the process. Two beyond-the-Standard-Model resonances are chosen as benchmarks for the result: a two-Higgs-doublet model scalar S and Kaluza-Klein (KK) gravitons G_kk predicted in the bulk Randall-Sundrum (RS) model. No significant deviations from Standard Model predictions are found, and upper limits are set on the production cross section of these resonances. A phenomenology study on the analysis strategy of this search in conditions of the future High Luminosity Large Hadron Collider is presented as well. This study shows proof-of-concept improvements in sensitivity by using a deep- learning approach to separate the hh → 4b signal, and discusses the optimization of the search to constrain the Higgs boson self-coupling parameter λ_hhh .
The development and applications of STEM ptychography using direct electron detectors
Keywords: Electron Microscopy
Ptychography
Contrast transfer functions
STEM

Since the introduction of direct electron detectors to scanning transmission electron microscopy (STEM), electron ptychography - a technique which utilises the interference in diffraction patterns to reconstruct the sample-induced phase changes of a transmitted electron wave - has significantly extended the capabilities of electron microscopy. However, a number of limitations to electron ptychography exist, namely the poor contrast transfer for low and high spatial frequencies to the phase reconstruction, and the relatively slow detector speeds used to acquire the ptychographic data (~ 1,000 fps). In this thesis, a number of strategies are introduced to further improve the robustness and dose-efficiency of focused-probe electron ptychography (FPP), after which several applications of FPP techniques are demonstrated.
Firstly, the contrast transfer properties of single side-band (SSB) ptychography are experimentally measured from an amorphous carbon sample in order to determine the optimal experimental parameters for ptychography. It is demonstrated that the probe convergence semi-angle can be used to tune the phase-contrast transfer function (PCTF) for each experiment, such that the relevant sample information is transferred with high contrast. Furthermore, careful consideration of the noise in the ptychographic data can provide an enhanced PCTF which broadens the transfer window in the image plane. These strategies are combined with a 1-bit fast (12,500 fps) acquisition scheme to enable the atomic-resolution phase reconstruction of a beam-sensitive zeolite sample using a low electron dose of 1.0 x 10^(5) e nm^(-2). By implementing these experimental and analytical strategies, the efficiency of FPP techniques can be signifificantly improved.
At the end of this thesis, several experimental challenges common to STEM are overcome using electron ptychography. Firstly, the precision of phase reconstructions are improved considerably by increasing the electron dose via multi-frame image acquisition, hence avoiding the slow-scan instabilities inherent to long STEM acquisition times. Furthermore, three-dimensional analysis of an unknown graphene defect is performed using a single ptychographic data set. Finally, electron ptychography is used to visualise oxygen vacancies in uranium dioxide for the first time.
Discourses of same-sex sexuality in British monolingual English dictionaries, 1604–1933
Keywords: lexicography
language and sexuality
dictionaries
history of sexuality

This thesis is a diachronic analysis of the discourses through which monolingual English dictionaries compiled and published in Britain represented same-sex sexuality over the course of three centuries—from the 1604 appearance of Robert Cawdrey’s A Table Alphabeticall, generally regarded to be the first monolingual English dictionary, to the publication of the first Supplement to the Oxford English Dictionary (OED) in 1933. The thesis argues that dictionaries are a valuable site of data on historical articulations of same-sex acts, desires, and identities because they throw light not only on past linguistic ‘knowledges’ of sexuality, but on their complementary ‘ignorances’ (cf. Sedgwick 1990: 8). That is, dictionaries offer didactic models of what their users ought to know and not know about sex, which sexual practices are sanctioned or prohibited, and how users should act (or be acted upon) as proper sexual subjects (or objects). The backbone of the thesis is concerned with English lexicography aimed at non-specialist readers—namely, hard-word dictionaries in the seventeenth century and general dictionaries thereafter—but it also compares these genres to specialized dictionaries of law, classical myth, medicine, and criminal cant.
The thesis is equally situated in the research traditions of lexicography and queer linguistics. It elaborates a theoretical framework that draws on queer performativity theory to argue that dictionaries do not merely reflect ‘common’ or ‘correct’ linguistic usage, but construct permissible and impermissible forms of language in relation to sets of linguistic and cultural norms. The application of this framework to the data is bolstered by tools from critical discourse analysis. Finally, the thesis proposes that queer linguistics can and should extend its research agenda back before the coining of homosexuality in the late nineteenth century, to attend to the ways that sexual discourses in the present have been shaped by those in the past.
Royal administration in East Anglia, c. 917-1066
Keywords: administration
government
Anglo-Saxon England

This thesis examines the administrative development of East Anglia between 917 and 1066, the period which saw the region integrated into a growing English kingdom. It explains how this process operated at a regional and local level by considering what claims underpinned it, how new administrative structures were introduced, and what gave royal officers power in the localities. In answering these questions for East Anglia, the thesis reinterprets the basis of English government in the tenth and eleventh centuries. What is conventionally viewed as an advanced ‘Anglo-Saxon state’ drew its strength not so much from military and bureaucratic organisation as from the widespread and direct relationship between the king and his subjects.

The first two chapters take the king’s perspective to deal with royal claims. Territorial expansion by successive members of the West Saxon dynasty rested on sworn submissions and the resulting personal loyalties, rather than profound tenurial or ideological change. The privilege known as soke is reinterpreted as a device for manipulating the relationship between king and freemen for the king’s fiscal and military convenience, with implications for both administration and land tenure. Two further chapters consider the origins of East Anglian hundreds and burhs. These institutions emerge as generally irregular adaptations of earlier structures, although they were forced into a uniform pattern. Both served as frames for organising freemen often subject to no one but the king. The fifth chapter shows that royal office-holders in East Anglia frequently owed their appointment to the private resources which they could mobilise in the king’s interests, as the offices themselves long remained institutionally unstable.

This study brings evidence from a neglected region to bear on developments which were common to the whole realm. If tenth- and eleventh-century England was not as uniform and ordered a kingdom as has been imagined, unsuspected features in its governance ultimately make it appear scarcely less precocious.
Justifying limitations on the freedom to manifest religion or belief and the freedom of expression under the ICCPR
Keywords: Limitations
Treaty interpretation
Freedom of religion or belief
ICCPR
Freedom of expression
Human rights
Duties of justice

The freedom to manifest religion or belief, and the freedom of expression (‘the Two Freedoms’) are of paramount importance to the inner realm of the human person; yet they may be limited on certain grounds. Articles 18(3) and 19(3) of the International Covenant on Civil and Political Rights (ICCPR) accordingly set out the legal basis on which states may limit the Two Freedoms. This thesis seeks to answer the following question: to what extent can a conceptually coherent, normatively compelling, and politically appealing justificatory burden be placed on states when they limit the Two Freedoms under the ICCPR? The thesis contains seven chapters. The first evaluates the common approaches to justifying limitations on the Two Freedoms – both of which are recognised as basic liberties and claim rights in the liberal tradition. The second chapter presents a conceptual, normative and political case for an alternative approach to justifying limitations on the Two Freedoms. This alternative approach requires the state to demonstrate that the competing interests at play are sufficient reason to impose on the individual concerned a duty of justice to refrain from engaging in the impugned conduct. Chapters three, four and five deal with the historical discourse surrounding the drafting of articles 18(3) and 19(3), the orthodox interpretation of these two limitation clauses, and the jurisprudence of the United Nations Human Rights Committee respectively. These three chapters reveal that the two limitation clauses are particularly vulnerable to abuse. The final two chapters explain that a simple good faith approach to interpreting the ICCPR can offer a more conceptually coherent, normatively compelling, and politically appealing approach to justifying limitations on the Two Freedoms, i.e. a ‘duty-based’ approach. The thesis concludes that this approach can actually be accommodated within the object and purpose of the ICCPR, and can provide the Committee with a doctrinal framework to advance a justificatory approach based on duties of justice. Such an approach could add further impetus to our perennial struggle to defend two of our most cherished freedoms: the freedom to manifest religion or belief, and the freedom of expression.