VictorJuiz/thesis huggingface dataset:
Functional investigation of microRNA pathways in human speech and language disorders
Keywords: FOXP2
exome sequencing
microarray
microRNAs

The forkhead-box protein P2 (FOXP2) is a transcription factor implicated in an inherited human speech and language disorder. A heterozygous R553H mutation in the gene is associated with a monogenic form of developmental verbal dyspraxia. Reduced functional dosage in mice brains causes altered synaptic plasticity in cortico-striatal circuits, and impairs motor learning. Genome-wide in vivo ChIP–chip screens for Foxp2 binding in the developing mouse brain have identified a set of microRNAs (miRNAs) whose promoter regions were occupied by Foxp2. Thus, I employed microarray expression profiling to identify microRNAs regulated by Foxp2 in the embryonic mouse brain. Interestingly, the microarray results were divergent from in vitro effects of Foxp2/FOXP2 on these microRNAs, suggesting that regulation of these microRNAs is context-specific. In light of the regulation of MIR137 by FOXP2, I went on to study a putative genetic network involving FOXP2, TCF4, CNTNAP2 and MIR137. While TCF4, CNTNAP2 and MIR137 each are regulated in vitro by FOXP2, the regions bound by FOXP2 were insufficient to generate the anticipated transcriptional regulation when cloned upstream of a reporter gene. To test if FOXP2-regulated microRNAs are risk factors for specific language impairment (SLI), I performed candidate association analyses on a large family-based cohort of SLI probands. I also identified 5 common variants and 3 rare variants in predicted microRNA binding sites in the 3' UTR from the exomes of 48 of these probands. I tested them for association with SLI in the larger cohort. rs72727021, lying in the miR-192/215 binding site of the C9ORF100 3' UTR, was significantly associated with nonword repetition in the SLI cohort (p-value = 2.75 X 10-4). Testing of rs72727021 and the 3 rare variants with a luciferase reporter assay revealed that 2 rare variants affected gene expression levels independently of the microRNA, suggesting that these 2 microRNA binding sites might be risk factors contributing to the SLI phenotype. FOXP2/Foxp2 is likely to act through microRNAs to generate and fine-tune neural gene expressionpatterns that underlie neuronal function and neural circuits important for vocal learning, and for human speech and language.
Anion and neutral molecule recognition by electron deficient boranes 
Keywords: inorganic chemistry
molecular chemistry
boranes

This thesis reports on the synthesis of a series of Lewis acidic boranes used as detectors for the cyanide or fluoride ion, and for the activation of molecular oxygen.
Chapter III focuses on the formation of monodentate boranes featuring a pendant ferrocenyl moiety. A systematic study of the fluoride and cyanide binding capabilities of isomeric ferrocenyl-functionalized phenyl boranes was conducted via spectroscopic, crystallographic and voltammetric techniques. The synthesis of receptors supported by an indenyl scaffold was also investigated and the binding properties of such systems studied in details. All receptors proved to be competent at binding both cyanide and fluoride in dry solvents; moreover one such indenyl receptor can selectively bind cyanide in aqueous media and signal the binding event by a green-to-red colour change.
Chapter IV constitutes an extension of the previous chapter targeting bidentate receptors with an (indenyl)(cyclopentadienyl)iron(II) back bone. A principle objective was the development of systems offering the chelation of fluoride, and hence a measure of selectivity over the more strongly basic cyanide ion. While bis(dimesitylborane) receptors proved to be synthetically inaccessible, a series of phosphine- and phosphonium-borane species was prepared and their comparative F-/CN- binding abilities determined. Thus, while cationic phosphonium boranes favour fluoride binding by employing a bifunctional binding motif, the neutral phosphine boranes exclusively bind cyanide.
Chapter V details the activation of molecular oxygen by pentafluorophenyl-boranes in presence of weak reductants featuring a ferrocene unit. The highly Lewis acidic ferrocenyl bis(pentafluorophenyl)borane was initially studied, and its reaction with dry dioxygen shown to generate a (fully characterized) ferrocenium peroxoborate. Similar reactivity was observed for simple metallocenes such as cobaltocene and ferrocene (or even organic reductants) in presence of a strong Lewis acid, with the trapping of the O22- ion by the borane thought to be a key thermodynamic driving force for the O2 reduction.
Wittgenstein and Sellars on intentionality
Keywords: Wilfrid Sellars
intentionality
Ludwig Wittgenstein

The aim of the thesis is to explore Ludwig Wittgenstein’s and Wilfrid Sellars’s views on intentionality. In the first chapter I discuss the account of intentionality and meaning the early Wittgenstein developed in his Tractatus logico-philosophicus. I present his idea that sentences are pictures of states of affairs with which they share a ‘logical form’ and to which they stand in an internal ‘pictorial relationship’. I argue that Wittgenstein thought of this relationship as established by acts of thought consisting in the operation of mental signs corresponding to the signs of public languages. In the second and third chapters I discuss the later Wittgenstein’s criticism of ideas at the heart of the Tractarian account of intentionality, as well as his explanations of the phenomena that motivated it. In the second chapter I examine his rejection of the idea that thinking consists in the operation of mental signs and his criticism of the idea that meaning and understanding are mental processes accompanying the use of language. In the third chapter I turn to Wittgenstein’s criticism of the idea that representations stand in an internal ‘pictorial relation’ to objects in the natural order that are their meaning. I illuminate his later views by discussing Sellars’s non-relational account of meaning, in particular his claim that specifications of meaning do not relate expressions to items that are their meaning, but rather specify their rule-governed role in language. I conclude with a discussion of the later Wittgenstein’s account of the relationship between intentional phenomena and the objects at which they are directed. In the final fourth chapter I provide a detailed discussion of Sellars’s account of thinking. I conclude with some criticisms of Sellars’s views.
The late Ming courtesan Ma Shouzhen (1548-1604): visual culture, gender and self-fashioning in the Nanjing pleasure quarter 
Keywords: visuality
courtesan
early modern courtesanship
Ma Shouzhen
gender
social networks
women's history
self-fashioning
Chinese visual culture
Nanjing
Chinese painting
Chinese women artists

Ma Shouzhen (1548-1604) was a cultured courtesan who lived in the famous pleasure quarter along the Qinhuai River in Nanjing, the southern capital of the Ming dynasty (1368-1644). She was talented in dance and music, painting and poetry, and surprisingly for her time, she was also a playwright. Although she was a celebrity of the prolific Nanjing cultural milieu and there is a good corpus of extant material by and about her, the particular contribution of Ma Shouzhen - her character and her work - have been marginalised, or even neglected, by the previous scholarship.
This thesis is a cross-disciplinary study of Ma Shouzhen and is the first in-depth scholarly investigation into the entirety of her activities. It employs material and methods traditionally pertaining to the disciplines of sinology, history, art history, literary and drama studies. The thesis has a dual aim: first, to provide a nuanced understanding of the courtesan, her cultural production and social practice; second, to reclaim the agency and legacy of her character within the cultural milieu of late Ming Nanjing and beyond. These aims will be achieved through two main research objectives: (1) recovering and re-evaluating visual and written sources by and about the courtesan; (2) investigating those sources in order to comprehend her modes of self-representation and strategies of self-fashioning, analysed especially through the lens of gender.
The main body of the thesis is composed of an introduction, five core chapters, and an epilogue; the chapters are structured so as to provide as complete a picture of Ma Shouzhen as possible. Chapter Two explores the space of the pleasure quarter, Ma’s biography and its entwinement within the complexities of the historical moment. Chapter Three focuses on her painting, Chapter Four considers her poetry, and Chapter Five explores her theatre practice; Chapter Six extends the investigation to focus on the construction of Ma’s historical character in later decades.
In its content and aims, this thesis contributes to women’s and gender history, as well as to studies in visual culture and literature.
The political economy of violence and post-conflict recovery in sub-Saharan Africa
Keywords: field experiment
reconciliation
conflict
development economics

This thesis presents theoretical work on armed group activity and empirical work on post-conflict recovery.
In chapter two, I develop a general equilibrium model of violence to explain observed variation in coercive practices in conflict zones. Armed groups own land in the resource sector and allocate military resources between conflict and coercion, which assign de facto ownership over land and labour respectively. I find that coercion is higher if labour is scare relative to land, production is labour-intensive, or if one group is dominant relative to others. Furthermore, contrary to other studies, I find that coercion could decreases with price if military power is sufficiently decentralised, since conflict draws resources away from coercion.
In chapter three, I evaluate a reconciliation program in post-conflict Sierra Leone. The program provides a forum for villagers to air war-time grievances, and also forges institutions designed to improve conflict resolution and build social capital. I find that respondents who received the intervention are more forgiving and are more charitable in their views of ex-combatants. Furthermore, conflict resolution improved and involvement in village groups and activities increased. However, psychological health---depression, post-traumatic stress disorder and anxiety---deteriorated. This study has direct implications for the design of transitional justice programs, as well as programs that aim to promote institutional change.
In chapter four, I experimentally vary foreigner presence across behavioural games conducted in 60 communities in Sierra Leone, and assess its effect on standard measures of generosity. I find that foreigner presence substantially increases player contributions in dictator games, by an average of 19 per cent. Furthermore, the treatment effect is smaller for players who hold positions of authority; and subjects from villages with greater exposure to development aid give substantially less and are more inclined to believe that the behavioural games were conducted to test them for future aid.
In chapter five, I use a model of repeated bargaining with one-sided asymmetric information to investigate the difficulties of reaching and sustaining power sharing agreements. I show that asymmetric information can explain the persistence of conflict, since learning slows down when there are future opportunities for bargaining.
The effect of obesity upon the lumbar spine
Keywords: obesity
epidemiology
intervertebral disc
spine surgery
orthopaedic surgery
IVDD
back pain

Back pain is a massive global public health problem with multiple contributing factors including obesity. Obesity is thought to be linked to back pain through mechanical factors. However, obesity also causes a systemic low-grade inflammatory milieu. This would suggest a possible biochemical link between obesity, intervertebral disc degeneration, and back pain. Furthermore, the relationship between obesity and the clinical presentation of spine patients is unclear. This thesis aims to examine the effect of and relationship between obesity, the intervertebral discs, and back pain from biochemical, clinical, and epidemiological perspectives
In this thesis, an in vitro study assessed the effect of leptin, a fat-specific cytokine, upon the intervertebral disc. The bovine intervertebral disc was used as a model in a cell culture system. An ex vivo study examined leptin and pro-inflammatory cytokines produced by paraspinal adipose tissue taken during routine surgical procedures from spinal patients. Plasma taken from patients presenting with low back pain was analysed by mass spectrometry and multiplex immunoassay to identify possible protein biomarkers. At an epidemiological level, statistical modelling of the Genodisc patient population was conducted. This was a pan-European study of 2636 patients presenting to tertiary spinal units. Analyses were performed to examine relationships between obesity, quantified by body mass index (BMI), and pain, clinical diagnosis, and spinal degeneration identified on magnetic resonance imaging (MRI).
Leptin was shown to increase the production of and expression of degradative and pain-generating molecules by disc cells. A pro-inflammatory environment, especially IL-6, potentiated this response. Leptin and pro-inflammatory cytokines produced by paraspinal fat were unrelated to clinical symptoms. However, levels of the pro-inflammatory cytokines, TNF-α and IL-6, were raised in the plasma of patients with greater pain or those with spinal stenosis. Furthermore, clusterin and complement were identified, by mass spectrometry, as potential biomarkers for spine patients. Epidemiological analyses revealed that obesity was associated with greater back pain, although the magnitude of this association was small. Similarly, obesity was associated with a diagnosis of spinal stenosis. Finally, increased BMI was found to be an independent predictor of disc degeneration, spinal stenosis, and disc herniation on MRI.
In summary, this thesis has furthered the clinical understanding of lumbar spine pathology and back pain. It will provide clinicians with a better framework to assess spine patients. These results show that obesity is associated with lumbar spine degeneration and pain. Leptin could be a factor mediating this relationship. Further studies should concentrate on clarifying the mechanism of action of leptin upon the intervertebral disc and assessing the longitudinal effect of obesity upon the lumbar spine.
Computer-aided detection and classification of microcalcifications in digital breast tomosynthesis
Keywords: CAD
Breast Cancer
Tomosynthesis
DBT
Classification
Computer-Aided Detection
Digital Breast Tomosynthesis
Mammography
Microcalcifications

Currently, mammography is the most common imaging technology used in breast screening. Low dose X-rays are passed through the breast to generate images called mammograms. One type of breast abnormality is a cluster of microcalcifications. Usually, in benign cases, microcalcifications result from the death of fat cells or are due to secretion by the lobules. However, in some cases, clusters of microcalcifications are indicative of early breast cancer, partly because of the secretions by cancer cells or the death of such cells. Due to the different attenuation characteristics of normal breast tissue and microcalcifications, the latter ideally appear as bright white spots and this allows detection and analysis for breast cancer classification. Microcalcification detection is one of the primary foci of screening and has led to the development of computer-aided detection (CAD) systems.
However, a fundamental limitation of mammography is that it gives a 2D view of the tightly compressed 3D breast. The depths of entities within the breast are lost after this imaging process, even though the breast tissue is spread out as a result of the compression force applied to the breast. The superimposition of tissues can occlude cancers and this has led to the development of digital breast tomosynthesis (DBT). DBT is a three-dimensional imaging involving an X-ray tube moving in an arc around the breast, over a limited angular range, producing multiple images, which further undergo a reconstruction step to form a three-dimensional volume of breast. However, reconstruction remains the subject of research and small microcalcifications are "smeared" in depth by current algorithms, preventing detailed analysis of the geometry of a cluster. By using the geometry of the DBT acquisition system, we derive the "epipolar" trajectory of a microcalcification. As a first application of the epipolars, we develop a clustering algorithm after using the Hough transform to find corresponding points generated from a microcalcification. Noise points can also be isolated. In addition, we show how microcalcification projections can be detected adaptively.
Epipolar analysis has also led to a novel detection algorithm for DBT using a Bayesian method, which estimates a maximum a posterior (MAP) labelling in each individual image and subsequently for all projections iteratively. Not only does this algorithm output the binary decision of whether a pixel is a microcalcification, it can predict the approximate depth of the microcalcification in the breast if it is.
Based on the epipolar analysis, reconstruction of just a region of interest (ROI) e.g. microcalcification clusters is possible and it is more straightforward than any existing method using reconstruction slices. This potentially enables future classification of breast cancer when more clinical data becomes available.
For Christ and Germany: German Catholicism and the Second World War
Keywords: History of the Third Reich

This dissertation examines the roles played by Catholicism on the German Home Front during the Second World War. It analyses to what extent German Catholics supported their nation’s war effort, and how they sought to reconcile their religious convictions with Nazism and its conduct of the conflict. The thesis examines the oscillations of morale within the Catholic ‘milieu’ during the war years, and analyses its responses to German defeats from 1943 onwards. In addition to these overtly political themes, this dissertation analyses the social history of religion during this period. In order to focus its analysis on a manageable scale, this thesis focuses on the experiences and activities of Catholics from the Rhineland and Westphalia. Its concluding chapter uses its findings concerning Catholicism during the war years to revise current understandings of the formation of a conservative ‘restoration’ in West Germany after May 1945.
Many existing works concerning German Catholicism during this period provide a monolithic portrayal of the confession’s internal coherence, and domination of its adherents’ political beliefs. This thesis, by contrast, argues that profound divides existed amongst German Catholics during the Second World War. Younger clergymen were frequently more sympathetic to völkisch nationalism than their older colleagues, and desired a more pro-Nazi stance from the German episcopate. The Catholic laity, moreover, was similarly often frustrated by the conservatism of episcopal Neo-Scholastic theology, and wanted sermons and pastoral letters that would endorse the German war effort in more unambiguous terms. The war years witnessed a complex negotiation of religious, political and national loyalties amongst Catholic communities, ensuring the thesis provides a nuanced picture of the confession’s place in German society during this period.
Conceptual investigation and the ontology of law
Keywords: philosophy of law
law
jurisprudence

An important question for general jurisprudence concerns method: what is the right way to form a philosophical understanding of law? Exploration of this question has, in one form or another, featured as a constant part of the work of those within the discipline, and many different answers have been given. The aim of this thesis is to argue that a controversial conception of philosophical method – as an investigation into our rule-bound conceptual practices and uses of language – is the appropriate means of understanding the nature of law. The first three chapters establish the initial connection between conceptual or linguistic analysis and the ability to gain insight into the social reality of law. I argue, in chapter one, that institutional concepts have a linguistic basis and, in chapters two and three, that legal systems are borne out of the shared use of certain basic concepts on the part of those who make up their law applying institutions, i.e. the courts. To understand the rules according to which such concepts are deployed, I suggest, is to understand the essential structure of legal practice. An assumption of that argument is tested in chapter four by considering Ronald Dworkin’s famous claim that certain forms of disagreement between lawyers and judges are incompatible with a picture of law dependent upon their agreement in the use of basic legal concepts. Chapter five takes up the question of whether the account of social ontology contained in the thesis is compatible with the fact of philosophical disagreement about the nature of law. Finally, chapters six and seven discuss alternate models of theoretical success in general jurisprudence, the first inspired by externalist views of linguistic and mental contents, and the second dependent upon a naturalistic conception of philosophy.
The social drama of a learning experience: how is drama appropriated as a pedagogical toolkit in secondary classrooms?
Keywords: pedagogy
drama
social
learning
secondary

The thesis presents a qualitative study which examines teachers’ and pupils’ experiences of drama tasks in secondary school subject lessons other than Drama, where the tasks are incorporated in pursuit of curriculum-defined teaching and learning goals. I take a cultural-historical perspective in my analysis, interrogating the possibilities for meaningful appropriations of drama as a pedagogical toolkit by examining social interaction and communication within the cultural context of the classroom and how these practices may have developed over time.
Set in four secondary school classrooms in the UK, the study focused on the experiences of teachers, (who are not trained drama specialists), and their pupils as they undertook drama tasks as part of curriculum lessons. I carried out a series of lesson observations, supplemented by interviews with participants. Using Cultural Historical Activity Theory (Cole 1996, Engeström 1987, Engeström 1999) as a heuristic tool, I created an analytical framework that explored the tensions between communicative tools, rules of the classroom space, and teacher-pupil and peer relations. This theoretical stance appreciates both the dynamic nature of classrooms and the possibilities for pedagogies of choice. The emphasis on tool-mediated action offers a fresh perspective in that it creates a structured and detailed framework for exploring the subtle and complex process of empathetic thought.
This study reveals some of the ways in which tensions occur and existing and historically-embedded cultural practices are brought to the surface, and reinforced or challenged. I provide extracts from the data to illustrate a concern for an assessment-driven acquisition of curriculum content is a particular constraint, along with varying opportunities for both teacher and pupils to construct a framework for spontaneous in-role action within the dramatic form. The appropriation of communicative tools, although influential in achieving goals, does not always preclude emotional investment in the tasks. Although there are shifts from teacher authority to increased pupil decision-making, the way in which the teacher and pupils operate in these drama tasks reveals as much about the established and reinforced learning and social practices of the classroom, as the way these practices are changed.
The research considers how drama as a pedagogical toolkit has developed historically, and it reveals implications for future study and practice relating to the understanding of drama-as-toolkit within formal educational settings.