VictorJuiz/thesis huggingface dataset:
Transcriptional regulation by non-coding RNAs in Saccharomyces cerevisiae

Genome-wide studies in Saccharomyces cerevisiae have revealed that the majority of the genome is transcribed on both strands, producing both coding and non-coding RNAs (ncRNAs). Initially, these ncRNAs were regarded as spurious transcripts but some have since been shown to have important roles as transcriptional regulators. Very little is understood about how ncRNAs are initiated, terminated and processed or how this influences their function. To address these questions, the expression, stability, and subcellular localization of the ncRNAs at the endogenous GAL locus was analysed. This revealed a complex interleaved transcript map, challenging the conventional view of a transcription unit (TU) flanked by 5’ sequences or promoters (P) that initiate transcription and 3’ regions, known as terminators (T), which control events such as transcript cleavage, polyadenylation, export and transcription termination. By creating conventional (PGAL-T) or unconventional (PGAL-P) hybrid TUs at the GAL locus, in which a promoter or terminator is positioned downstream of a galactose-inducible promoter, this work shows that both promoters and terminators are able to initiate antisense transcription to yield stable antisense transcripts. The data suggest that terminators contribute to efficient but variable expression from the promoter. An unconventional P-P TU, lacking a terminator, is transcribed on both strands but the sense transcript remains at low levels, through the repressive action of antisense transcription, and is retained in the nucleus. In contrast, the conventional P-T bi-directional TUs are plastic, with the Rrp6 component of the nuclear exosome and TATA-like sequences in the 3’ UTR determining whether the predominant transcript is antisense or sense. By relieving the repressive action of antisense transcription, this allows high levels of sense transcript to accumulate in the cytoplasm, contributing to gene expression, supporting a novel mode of gene regulation involving components of RNA quality control pathways acting through the 3’ region of genes.

Keywords: S. cerevisiae
non-coding RNAs
transcription
Advisor: Mellor, E
Investigating and developing beginner learners' decoding proficiency in second language French: an evaluation of two programmes of instruction

Second language (L2) decoding – the sub-lexical process of mapping the graphemes of an alphabetic writing system onto the phonemes they represent – is argued to underpin various aspects of L2 learning, particularly vocabulary acquisition. Recently, second language acquisition research has shown increased interest in decoding, consistently finding evidence for L1-to-L2 transfer effects on learners’ processing mechanisms and outcomes. Correspondingly, studies conducted in Modern Foreign Language (MFL) classrooms in English secondary schools – an under-researched context – have found that beginner learners of French tend to (a) pronounce L2 words according to English decoding conventions and (b) make poor progress in this aspect of L2 learning. Recent official guidance for MFL teachers has addressed this problem by advocating an explicit focus on decoding, but there is a lack of convincing evidence (both in the MFL context and more widely) that explicit L2 decoding instruction can be effective. The current study therefore trialled two programmes of French decoding instruction for beginner MFL learners, delivered in ten- to fifteen-minute segments over around thirty lessons. Three intact secondary school classes followed a phonics-based approach; three classes from another school followed a programme in which learners were encouraged to derive the pronunciations of French graphemes from ‘source words’ in a memorized poem; and six classes in two other schools received no explicit decoding instruction. Participants (N=186) completed pre- and post-tests of French decoding; a sub-sample (N=15) also completed task-based self-report interviews. The two intervention groups made significantly more progress than the comparison group in terms of the number of graphemes pronounced ‘acceptably’, although the magnitude of the difference between the groups was small. Compared to the comparison group, the two intervention groups also appeared to show different and more extensive patterns of change in their realizations of individual graphemes, even where their pronunciations were still not ‘acceptable’. Finally, self-report data generally revealed little change in participants’ strategic reasoning, either in the intervention or comparison group. Together, these findings suggest that explicit instruction can improve beginner learners’ proficiency in decoding L2 French, but that their progress may follow a longer and more complex trajectory than simply moving directly from ‘incorrect’ to ‘correct’ forms. Further research is required to assess the effects (if any) of a given improvement in decoding proficiency on other language-learning outcomes; and to design and evaluate alternative programmes of instruction.

Keywords: French
Phonics
Second language writing systems
Instructed foreign language learning
Foreign language phonics
Decoding
Phonological decoding
Advisor: Macaro, E
Towards the total synthesis of calyciphylline A-type Daphniphyllum alkaloids

This thesis details the studies towards the total synthesis of the calyciphylline A-type Daphniphyllum alkaloids, with a particular focus on daphniyunnine D (23).
Chapter 1 introduces these biologically and synthetically interesting polycyclic natural products and describes our designed approach towards their synthesis. Separate studies targeting the construction of two tricyclic ring systems have been developed. These provide rapid entry to synthetically versatile intermediates, allowing for the potential synthesis of numerous members of the alkaloid family.
Chapter 2 describes the first study which focuses on the construction of the main tricyclic [6‒5‒7] ACD core 172 via a proton transfer/IMDAF reaction cascade as the main step. Large scale synthesis of the precursor to this cascade 164 has allowed for the successful investigation of an asymmetric variant giving rise to an enantioenriched adduct 104.
Chapter 3 describes a novel design for the construction of the [7‒5‒5] DEF tricycle common to 100+ Daphniphyllum alkaloids. An IMPKR, double-bond migration, allylic oxygenation protocol was first validated on a model system and later applied in combination with the synthetic route developed in chapter 2 to achieve the construction of the [6‒5‒7‒5‒5] ACDEF pentacycle 249.
Chapter 4 focuses on the construction of the piperidine ring B via an intramolecular gold-catalysed 6-exo-trig hydroalkylation. During the development of the route to daphniyunnine D, various intermediates were afforded which were further elaborated to provide appropriate cyclisation substrates for this study. Their synthesis combined with proof of principle experiments for the desired cyclisation conclude this dissertation work.

Keywords: organic chemistry
organocatalysis
alkaloids
total synthesis
Advisor: Dixon, D
Aristotle on the matter of the elements

This thesis is an investigation into the simplest material entities recognised by Aristotle's theory of nature. In general, the position I defend is that the four 'so-called elements' fire, air, water, and earth are, for Aristotle, genuine elements, i.e., the simplest material constituents, of bodies. In particular, I deal with two problems, the first concerning the relationship between the four 'so-called elements' and the primary contraries, hot-cold, dry-wet; and the second concerning the nature of the matter from which the latter come to be. Responses to these problems in the secondary literature tend to conclude that the contraries (usually together with 'prime matter'), are constitutive of the so-called elements. I reject this conclusion. In the first part of this thesis I consider, and dismiss, the alleged evidence that Aristotle denies to fire, air, water, and earth the status of genuine elements, and I argue that the status of the contraries as the differentiae of the elements effectively rules out the possibility that they could be the constituents of the latter. In the second part of this thesis I attempt to unpack Aristotle's assertion at De Gen. et Cor. II. 1 that the matter of the perceptible bodies is that from which the so-called elements come to be. I argue that the matter of the perceptible bodies, although it is that from which the elements come to be, is not the 'matter of the elements', in the sense of a matter that composes the elements. On the contrary, the 'matter of the perceptible bodies', i.e., the constitutive matter of composite bodies, is itself composed of the elements: it is a mixture of the four elements. Thus the latter can be said to come to be 'from' the 'matter of the perceptible bodies', but this must be understood in a non-constitutive sense of 'from'.

Advisor: Frede, M
Morison, B
The construction of colonial identity in the Canadas, 1815-1867

This thesis examines the construction and contestation of Anglo-Canadian identity from the end of the War of 1812 until Confederation in 1867. It argues that the conflict between English- and French-speakers in the Canadas was by no means inevitable but a function of the institutional and political circumstances of the time. It seeks to complicate the picture of the British in Canada by demonstrating that they were a diverse community of different groups, institutions and religions that only through struggle and the incentives of party politics were able to unify themselves into a single culture. The development of party politics not just coincided with the creation of Anglo-Canadian identity but played a fundamental role in creating it. Through the burgeoning newspaper industry, the Reform and Tory parties spread their ideas of what it meant to be British, loyal and Canadian to a widespread English-speaking audience. Canadian history in this period is better understood not in the traditional dualist framework of British against French but as the complex interactions of many different groups, including the English, the Scots, the Irish Protestants, the Irish Catholics, the Americans and the French-Canadians. The thesis seeks to deconstruct the terms ‘British’ and ‘loyal’. Both terms were appropriated by various individuals and groups seeking to gain benefits by defining themselves as such. Until the early 1830s, attempts were made to include certain classes of French-Canadians within the broader British polity and identity. The 1837 rebellions marked the ‘othering’ of French-Canadians. Meanwhile the Upper Canada rebellions presented an enemy in the United States and a new strain of anti-Americanism, separate to that of the loyalists, was developed. By 1849, the moment of the rebellion losses crisis, the fundamental tenets of the Anglo-Canadian identity had been established: anti-Americanism, a concern about French political influence and a sense of kinship with English speakers across the province of United Canada. These three periods are shown to have played a crucial role in the development of an anglophone identity that encompassed the whole of United Canada.

Keywords: nationalism
history
Canada
Advisor: Darwin, J
The development and applications of the Lewis acid-mediated osmium-catalysed oxidative cyclisation

The acid-mediated osmium-catalysed oxidative cyclisation of 1,2-diols bearing a pendent alkene has been shown to be a powerful method for the formation of cis-2,5-disubstituted tetrahydrofurans. This thesis describes the development of this methodology to broaden the scope of the general reaction, followed by applying the oxidative cyclisation to the synthesis of tetrahydrofuran containing natural products.
Introduction: This section reports a range of ractions that osmium oxo-species will facilitate, namely the formation of carbon-oxygen and carbon-nitrogen bonds in a selective manner. In addition to this a variety of similar metal-mediated oxidative cyclisations are discussed.
Results and Discussion: The process for optimising the oxidative cyclisation is documented, along with examples which directly compare newly developed methodology with existing methodology. The incorporation of a catalytic amount of a Lewis acid is shown to be more effective than using an excess of a Brønsted acid, with osmium catalyst loading being reduced to 0.2 mol%. Subsequently, this methodology is shown to facilitate the successful oxidative cyclisation of vinyl silanes to form silyl-substituted tetrahydrofurans, along with methodology to “unmask” the silane, as a potential route to lactols. Finally, the application of this methodology to synthesis is demonstrated, with the successful synthesis of neodysiherbaine A being achieved in 7 steps and the C21-30 fragment of pectenotoxin-4 in 12 steps.

Keywords: oxidative cyclisation
Pectenotoxin-4
osmium cyclisation
Neodysiherbaine A
Tetrahydrofuran synthesis
Advisor: Donohoe, TJ
The biographies of Ras-chung-pa

This thesis examines accounts of the life of Ras-chung-pa, also known as rDo- rje Grags-pa (1084-1161), written from the thirteenth to the eighteenth centuries. It identifies what sources are presently available and discusses their inter-relationship.
The thesis will present a development of narrative traditions that fuse and eventually climax in the sixteenth century Ras-chung-pa'i rNam-thar by rGod-tshang Ras-pa, which is the standard biography for present-day Tibetan Buddhism. This thesis will reveal how rGod-tshang Ras-pa's version of the first half of Ras-chung- pa's life is a late composite of various conflicting narratives.
As the primary source materials have been little studied or even identified, a major part of the thesis will be an exploration and identification of the sources. The thesis will both show how narratives about Ras-chung-pa evolved and suggest their possible historical sources.
[continued in text ...]
Charge transport dynamics in electrochemistry

Electrolytic solutions contain mobile ions that can pass current, and are essential components of any solution-phase electrochemical system. The Nernst–Planck–Poisson equations describe the electrodynamics and transport dynamics of electrolytic solutions.
This thesis applies modern numerical and mathematical techniques in order to solve these equations, and hence determine the behaviour of electrochemical systems involving charge transport. The following systems are studied: a liquid junction where a concentration gradient causes charge transport; an ideally polarisable electrode where an applied potential difference causes charge transport; and an electrochemical cell where electrolysis causes charge transport.
The nanometre Debye length and nanosecond Debye time scales are shown to control charge separation in electrolytic solutions. At equilibrium, charge separation is confined to within a Debye length scale of a charged electrode surface. Non-equilibrium charge separation is compensated in solution on a Debye time scale following a perturbation, whereafter electroneutrality dictates charge transport. The mechanism for the recovery of electroneutrality involves both migration and diffusion, and is non-linear for larger electrical potentials.
Charge separation is an extremely important consideration on length scales comparable to the Debye length. The predicted features of capacitive charging and electrolysis at nanoelectrodes are shown to differ qualitatively from the behaviour of larger electrodes. Nanoscale charge separation can influence the behaviour of a larger system if it limits the overall rate of mass transport or electron transfer.
This thesis advocates the use of numerical methods to solve the Nernst–Planck–Poisson equations, in order to avoid the simplifying approximations required by traditional analytical methods. As this thesis demonstrates, this methodology can reveal the behaviour of increasingly elaborate electrochemical systems, while illustrating the self-consistency and generality of fundamental theories concerning charge transport.

Keywords: electrochemistry
charge transport
double layer
Nernst-Planck-Poisson equations
migration
computational chemistry
electroneutrality
diffusion
charge separation
mass transport
Advisor: Compton, R
The role of Notch and GATA3 in postnatal and adult haematopoiesis

The role of Notch in cell fate determination and lineage restriction in the bone marrow (BM) is controversial in the field. Recent studies have convincingly shown that Notch is dispensable for haematopoietic stem cell (HSC) regulation in adult haematopoiesis (Maillard et al., 2008). In contrast, Notch signaling has been proposed to be of importance in the regulation of BM megakaryocyte progenitor differentiation, based on dominant negative genetic approaches, identifying a potentially distinct role for Notch in adult BM haematopoiesis (Mercher et al., 2008). Here, I found that by selectively ablating the gene coding the transcription factor recombination signal-binding protein J kappa (RBP-Jk), to which all canonical Notch signaling converges, canonical Notch signaling does not mediate HSC maintenance, neither in steady state nor in conditions of stress. Furthermore, I propose, in contrast with previous studies (Mercher et al., 2008), that canonical Notch signaling plays no role in myeloerythropoiesis cell lineage commitment in the BM. My data also show that key Notch target genes are suppressed by RBP-Jk, as their expression is unaffected in Notch1-deficient BM progenitors, while target genes are upregulated in Rbp-Jk-deleted megakaryocyte and erythroid progenitors. This establishes for the first time in mammalian cells in vivo, that Notch target genes are kept in a suppressed state by RBP-Jk, potentially restricting T cell commitment to the thymus and not to the BM, at the expense of myeloerythropoiesis.
Notch signaling and GATA3 are two master regulators in T cell commitment (Han et al., 2002; Ho et al., 2009; Pui et al., 1999; Radtke et al., 1999; Zhu et al., 2004). However, although very well established as being involved in the thymic stages of T cell restriction, there is little evidence of Notch and GATA3 being involved in the migration of a thymus settling progenitor (TSP) from the BM to the thymus or in the establishment of the earliest thymic progenitor (ETP) in the thymus. From this thesis work, I conclude that Notch signaling is essential for the emergence of ETPs in the thymus in a NOTCH1-independent manner. Moreover, I demonstrate, as supported by a very recent published study (Hosoya et al., 2009), that GATA3 is important for the development of the earliest T cell progenitor.
GATA1 and GATA2 mediate haematopoietic stem cell maintenance in the BM. GATA1 is required for erythropoiesis, megakaryocytes and eosinophils while GATA2 is important for the proliferation and survival of HSCs. In contrast, a role for GATA3 in the BM has never been established. By using a Gata3-conditional knockout mouse model, I demonstrate that GATA3 is dispensable for HSC maintenance in steady state and following active haematopoietic regeneration as well as for HSC self-renewal in the BM.

Keywords: Rbp-Jk
Notch
haematopoietic stem cell
GATA3
T cell progenitor
myeloid
Advisor: Jacobsen, S
Methods and models for acute hypotensive episode prediction

Hypotension is both a dangerous condition and a critical marker for the progression of certain conditions and diseases.Additional research has shown that the more quickly a hypotensive state is predicted, the better the probability of survival.
This thesis explores the creation of models to predict an acute hypotensive episode at a minimum of one hour before occurrence. Models were based on data acquired from MIMIC II, a large-scale ICU database. A variety of techniques including Parzen models of normality, logistic regression, and neural networks are used to analyse the relationship between vital signs and the occurrence of hypotension in the general ICU population.
Both univariate and multivariate models were evaluated, and multi-variate neural network models were found to be the best predictors of hypotension in our dataset. The best model was a multi-layer perceptron constructed using values and first-order statistical functions of a patient's mean arterial blood pressure, respiration rate, blood oxygenation level, and heart rate. Best performance occurred at a time of 60 minutes prior to the onset of a patient's first recorded hypotensive episode, and yielded an AUC of 0.84. This corresponded to a classification accuracy of 82% in a balanced dataset and 84% in an unbalanced dataset which more closely rejects the prevalence of hypotensive data in an ICU. These results indicate that there are early patterns underlying general hypotension detectable in patient physiology.

Keywords: prediction
hypotensive episode
hypotension
biomedical engineering
modeling
Advisor: Tarassenko, L
Perceptions of public opinion. British foreign policy decisions about Nazi Germany, 1933-1938

This thesis examines the historical problem of determining the relationship between a government's perception of public opinion and the decisions it takes. We introduce evidence for the social habits of the Cabinet in order to suggest new formulations of 'élite' and 'mass' public opinion. We argue that parliamentary opinion was generally more important in decision-making for the Cabinet, except at moments of extreme crisis when a conception of 'mass' opinion became equally significant. These characterization of mass opinion were drawn from a set of stereotypes about public opinion which academic and political theorization had produced. It is argued that this theorization was stimulated by ongoing debates about mass communication, the importance of the ordinary man in democracy and the outbreak of the first world war during the inter-war period.
The thesis begins with an introduction to the methodological problems involved, followed by one chapter on theorization about public opinion in the inter-war period. Three diplomatic crises are considered in the case study chapters: the withdrawal of Germany from the Disarmament Conference in 1933, the German reoccuption of the Rhineland in 1936 and the threat of invasion of the Sudetenland in 1938. Two further chapters examine the role of public opinion in protests to Germany about the treatment of the Jews in 1933 and in 1938. It is argued that perceptions of public opinion played a much more important role in decision-making than has hiterto been thought. The most significant argument posits that perceptions of public opinion were equally as important as military considerations in the decision to refuse the Godesberg terms in 1938. More generally, the way in which politicians used public opinion rhetorically is described and the limits of the usefulness of the term for historians are suggested.

Keywords: Jews
Nazi Germany
interwar-period
mass opinion
Cabinet
foreign policy
diplomatic crises
decision-making
public opinion
Advisor: Stevenson, J