VictorJuiz/thesis huggingface dataset:
Investigating enteric fever – application of controlled human infection models to understand enteric fever pathogenesis and immunity

The development of novel vaccines for typhoidal Salmonella is hampered, in part, by a limited understanding of protective host immune responses to infection, the absence of reliable immunological correlates of protection, and uncertainties relating to disease pathogenesis. Controlled human infection models (CHIM) for Salmonella Typhi and Paratyphi have recently been re-established. In this thesis, I describe the application of two controlled human infection studies (CHIM), designed to offer insights into enteric fever pathogenesis and immunity.
In the first study, I investigate a recently identified virulence factor encoded by S. Typhi and Paratyphi, termed the typhoid toxin. Following generation, manufacture and characterisation of challenge strains, I compared the response to challenge with either wild type S. Typhi or typhoid toxin-deficient isogenic mutant strain in 40 healthy volunteers using a novel challenge protocol. There was no significant difference in the rate of infection after challenge with wild type or typhoid toxin deficient strains, although there was a trend toward a more severe clinical syndrome in participants challenged with the typhoid toxin deficient strain. Collectively these data suggest that expression of the typhoid toxin is not an absolute requirement for the establishment of acute typhoid fever.
In a second study, I recruited naïve volunteers with no prior exposure to Salmonella Typhi or Paratyphi and compared the response to challenge with a cohort of previously-exposed volunteers. Homologous re-challenge with S. Typhi or Paratyphi A was associated with a 37% and 56% relative reduction in attack rates, respectively and a prolonged time to disease. These are the first data indicating prior Salmonella Paratyphi exposure confers protection against re-challenge. In contrast, heterologous re-challenge was not associated with significant reduction in attack rates. Protection from the disease on re-challenge was most pronounced in older participants and in individuals who did develop disease on primary exposure. Baseline serum antibody and memory B-cell measurements did not correlate with protection after re-challenge, and previous exposure was not associated with a demonstrable boosting of humoral immune responses. Further studies identified that previous exposure and Vi-vaccination were significantly associated with reduced shedding of S. Typhi after challenge.
Collectively, these studies demonstrate the expanding application and potential of controlled human infection models to understand of enteric fever pathogenesis and immunity. It is hoped that the data presented herein will ultimately aid efforts aimed at disease control, by identifying correlates of protection and to provide a platform for further vaccine studies.

Keywords: Controlled human infection study
Paratyphoid fever
Human challenge studies
Typhoid fever
Advisor: Pollard, A
Rollier, C
Voluntariness, consent, and justification

When we consent to something (e.g. a medical procedure, sex, a tattoo), we permit people to act in ways that would otherwise be legally or morally impermissible. However, in order for consent to be valid, certain conditions must be met. In this thesis, I discuss the condition that consent needs to be voluntary, I focus specifically on consent to medical procedures, and I argue that such consent is voluntary unless it is motivated by an influence that cannot be interpersonally justified. I call my view Interpersonal Consenter-Consentee Justification (ICCJ). ICCJ introduces the concept of interpersonal justification, known from the debate on contractualism, to the debate on consent and most clearly differs from other views in the literature by (i) focusing on the reasons or motivation for which a person consents, instead of mere causal links or counterfactuals, (ii) allowing the moral legitimacy and not just the strength of an influence to have a bearing on the voluntariness of consent, and (iii) making the behaviour of the person receiving consent (the consentee) central to its approach.

Keywords: consent
nudging
clinical trials
causation
organ donation
voluntariness
interpersonal justification
coercion
Advisor: Hyman, J
Wilkinson, D
What do we know about the effectiveness of group work in Japan’s secondary English education? A systematic review of an ‘active learning’ technique

With its 2017/18 revised curriculum guidelines for junior high school and high school (Courses of Study; to be implemented in 2020), Japan’s education ministry (MEXT) requires that teachers adopt ‘active learning’ techniques; such as ‘discov-ery learning’ and group work. MEXT (2012, p. 37) promotes group work as an “effective” method for teaching English to Japan’s junior high school and high school students; in preference to what the ministry terms “unidirectional lecture-style” teaching (i.e. Japan’s version of grammar-translation and other teacher-centred approaches).
This systematic review is an assessment of the empirical basis for using group work over alternatives in Japan’s secondary English education. It reviews experimental studies of group work in junior high school and high school English lessons in Japan, that measured linguistic proficiency or academic attainment between 2009 and 2019. A systematic search of 8 bibliographic databases plus web searches, conducted in May 2019, revealed only 8 studies that met inclusion criteria. Of these, 4 favoured group work, 3 found no difference between group work and alternatives such as individual work, and 1 was not interpretable. Findings of a narrative, best-evidence synthesis concerning the effects of group work in this context were equivocal. The evidence base was small and lacked robust designs. On measures of linguistic proficiency and academic attainment, it was not clear if group work differs meaningfully from alternatives such as individual work. For English teachers at junior high schools and high schools in Japan to have an evidence-based understanding of the effects of group work in their context, more intervention research is needed.
【要約】 平成29･30年改訂（令和2年実施予定）中･高等学校学習指導要領により、文部科学省は教師が「発見学習」やグループワークなどの「アクティブラーニング」（主体的･対話的で深い学び）技法の採用を義務付けています。文部科学省は、「一方向的な講義形式」の指導（つまり、文法訳読法などの教師中心のアプローチ）よりも、日本の中学生や高校生に英語を教えるのに「有効な」方法としてグループワークを推進しています。このシステマティックレビューは、日本の中等英語教育における他の方法よりもグループワークを使用するための根拠を検討します。
2009年から2019年の間の、言語能力や学力を測定した日本の中学校および高等学校の英語授業でのグループワークの実験的研究をレビューしました。 2019年5月に行われた8つの書誌データベースとウェブ検索の系統的な検索では、基準を満たした研究は8つだけであった。これらのうち、4つの研究はグループワークの有効性を支持し、３つはグループワークと個人ワークのような他の方法との間に違いが見つからず、1つは解釈不能でした。定性的ベスト・エビデンス統合（best-evidence synthesis）における日本の中等英語教育でのグループワークの効果に関して、知見はあいまいであった。証拠基盤が小さく、堅牢なリサーチ･デザインが欠けていました。言語能力と学力の尺度に関しては、グループワークが個人ワークのような他の方法と有意に異なるかどうかは明らかではなかった。日本の中学校および高等学校の英語教師がグループワークの効果についてのエビデンスに基づいた理解を持つためには、さらなる介入研究が必要です。

Keywords: MEXT
グループワーク
systematic review
システマティックレビュー
Japan
narrative synthesis
主体的･対話的で深い学び
EFL
active learning
policy
English as a foreign language
中等英語教育
group work
secondary education
Advisor: Chalmers, H
The recognition, generation and detection of 5-hydroxymethylcytosine

5-hydroxymethylcytosine (5hmC) is a DNA modification generated from the oxidation of 5-methylcytosine (5mC) by ten-eleven translocation (TET) enzymes. 5hmC is enriched at promoters, gene bodies and enhancers. The enrichment of 5hmC at the gene body is positively correlated with gene expression. Low levels of 5hmC are observed in various solid tumours and haematological malignancies. The distribution of 5hmC in the genome is strand asymmetric at CG sequences. There are high levels of adjacent and opposing hydroxymethylated and methylated CpG (H/M) sites in the genome. 5hmC in H/M sites account for around 60% of all 5hmC. In this thesis, proteins that specifically recognise H/M sites were identified using DNA pull down followed by LC-MS/MS. However, the binding specificity requires more biochemical validations. The enzymatic pathway that generates H/M site was studied and preliminarily results showed that TET2 have strand selective activity on double strand DNA, which might be a possible way to generate H/M sites. To better understand the distribution of 5hmC in the genome, a 5hmC selective oxidation reaction was applied to map 5hmC on DNA and RNA. The method can be further expended to 5mC mapping in RNA in combination with TET oxidation of 5mC to 5hmC.

Keywords: DNA modifications
5-methylcytosine
5-hydroxymethylcytosine
Advisor: Song, C
Kriaucionis, S
Single cell analysis of the fibrotic landscape in Dupuytren's disease

Fibrotic disorders represent some of the most devastating and poorly treated conditions in the Western World. Despite this, effective therapeutic interventions have yet to be identified for many of these conditions. A major barrier to identification of novel targets and successful clinical translation is a poor understanding of the myofibroblast-rich human fibrotic microenvironment, compounded by the dynamic nature of this ecosystem. Here, I use Dupuytren’s disease (DD), a localized fibrotic condition of the hand, as a model to construct a stromal cell atlas in human fibrosis at single cell resolution. I identify three fibroblast subsets in DD, including a novel ICAM1+ chemokine-enriched fibroblast. After this, I demonstrate heterogeneity in myofibroblasts and report discrete proliferative and CD82+ populations. Using a newly optimized functional assay, I show phenotypic diversity along modelled signature of myofibroblast activation and validate a novel cell surface marker of this cell type, CD82, Finally, I show CD82 functions to regulate cell cycle progression in DD myofibroblasts.

Advisor: Nanchahal, J
Furniss, D
Subjects of self-reliance: a critical history of refugees and development

In four empirical chapters spanning three regions of the world in the 20th and 21st centuries, I examine continuities and changes in institutional assistance to foster refugee self-reliance. I employ archival and ethnographic methods to document assistance practices and forms of implementation. I draw upon programme and evaluation reports of the League of Nations and UNHCR as key primary texts due to these institutions’ historical influence and prominence in refugee assistance, as well as private collections by individual assistance actors. I find that efforts to foster refugee self-reliance have largely occurred through development projects targeting both refugees and locals, and even entire regions; in so doing, this assistance has largely treated refugees as workers in need of employment. This ‘refugee self-reliance assistance’, as I term it, has been a main feature of refugee assistance yet has been hitherto neglected in academic scholarship in Refugee Studies as well as International Development.
Through a Marxian reading of history I link refugee self-reliance assistance to material interests, outcomes, and changes. Drawing on critical welfare studies, I develop a theoretical framework of ‘international welfare’ and employ the theoretical concepts of instrumentalisation and reserve army of labour to explain how refugee self-reliance has become an instrument that alternately serves and exemplifies changes in social, political, and economic structures.
The rhetoric surrounding refugee self-reliance belies shifting interests and their underlying values – whether self-reliance is espoused as an economic imperative, a protection instrument, or a human right, for example. The identification of these linkages has implications for understanding the conditions under which refugee self-reliance is ‘fostered’, for analysing the means through which it is intended to be attained, and its explicit and implicit outcomes. Through this examination, my thesis reveals that refugee self-reliance is not an end in itself but instead a malleable instrument to achieve economic gain, political exploits, and social control.

Keywords: Afghan Refugees in Pakistan
Development Assistance
Urban refugees in Uganda
Greek refugees
Marx
Refugees in Tanzania
Refugee Self-Reliance
Historical refugee assistance
Advisor: Betts, A
Real-time synchrotron X-ray radiography of nucleation, growth and phase selection of FE-rich intermetallic compounds in Al alloy solidification

In-situ synchrotron X-ray radiography has been used to study the dynamics of nucleation, growth and other temperature related phe- nomena of Fe-rich and analogous faceted IMCs. Measurements from radiographs have been combined with post-solidification microscopy.
A method was developed to estimate the temperature at any time and any position in the radiography field of view and applied to obtain tip temperatures of 203 secondary Fe-rich IMCs growing in an Al- Cu-Fe alloy. The cooling rate and grain refiner additions affected the IMC tip temperature, phase selection and the final population, primarily by affecting the inter-dendritic liquid channel tortuosity. Adding grain refiners and using a higher cooling rate delayed the growth of secondary IMCs to lower temperatures.
The formation dynamics of Fe-rich IMCs were investigated at different cooling rates, thermal gradients and inoculation conditions (no inoc- ulation, TiB2 and TiC) in a hypereutectic Al-Fe alloy that formed Al13Fe4 as a primary phase. Without inoculation, IMCs formed on the oxide of sample surface; with inoculants, IMC formation in the melt was increased. When a thermal gradient was imposed/increased, the IMC number density and average formation rate decreased, and it was inferred that their formation temperature also decreased. A conceptual model for IMC nucleation was proposed.
Last, faceted growth of primary and secondary IMCs was studied in three model alloys: Al-Cu-Fe, Al-Fe and Al-Pt-Er that formed primary Pt-rich IMCs related to the Fe-rich IMCs while providing stronger X-ray absorption imaging contrast. Time-resolved radiogra- phy measurements suggested that growth of both secondary IMCs in constrained liquid and primary IMCs in non-constrained liquid, were governed by solute diffusion effects in the liquid. Repeated forma- tion of twin plane re-entrant (TPRE) corners facilitated preferential anisotropic growth and resulted in IMC platelets with a high aspect ratio of up to 10. In contrast, the formation of layered twins perpen- dicular to the preferential growth direction, promoted crystals with a much lower aspect ratio. The findings suggest that if "modifying" ele- ments could be added to poison the TPRE mechanism of IMC growth, layered twins might be promoted to obtain IMCs with a lower, more uniform aspect ratio. In this scenario, the usual embrittling effects of high-aspect ratio, platelet IMCs may be reduced.

Advisor: Grant, P
Liotti, E
Climbing ladders: children and monastic formation in England, c.950-1200

This thesis seeks to understand the lives of oblates, children given by their parents to Benedictine monasteries in England between c.950 and 1200. Scholars have long recognised that children were important to monastic recruitment and drawn attention to the significance of the ritual by which they entered religious houses, but few have explored their experiences afterward. This thesis addresses that gap. It seeks to demonstrate the capacity of surviving sources to establish conditions of boyhood and girlhood after oblation, and it argues that these give us access to and allow us to understand changes in their development between infancy and adolescence.
It also argues that a child-centric approach, focussed on examining evidence for child experience, allows us to represent children’s development in a more realistic way, showing how their world-views were informed by encounters with religious knowledge in disciplinary, liturgical, and literary spheres. Chapter one asks whether children’s experience of discipline relied upon the preferences of teachers in Anglo-Saxon England, but were shaped by processes of institutionalisation at Canterbury after the Norman Conquest. Chapter two assumes that boys and girls were probably formed by similar experiences of liturgical performance, but it also examines evidence for competition, and suggests that processions became more significant to boys’ experiences after the Conquest and that girls may have encountered a different emphasis in their needlework. Chapter three, on literary instruction, explores how experiences of learning Latin grammar played a role in shaping children’s religious knowledge, behaviour, and monastic identities. Chapter four, on adolescence, argues that adulthood was signposted by the emergence of a new ritual of confirmation as well as by children’s training in activities explored previously, and it confirms the significance of some of these experiences through an examination of children’s own surviving compositions.

Keywords: Childhood
Anglo-Saxon
Adolescence
Benedictine Reform
Latin Learning
Career trajectories
Twelfth Century Renaissance
Norman Conquest
School books
Anglo-Norman
Advisor: Foot, S
XUV lensless imaging with spatially shaped high-harmonic beams

This thesis presents two novel advances in the field of high harmonic generation along with a demonstration of application to the lensless imaging technique known as Fourier Transform Holography. Also presented are images obtained with the technique of coherent diffractive imaging.
The first advance is that of an increase in harmonic brightness through the manipulation of the spatial phase of the driver laser. The transverse driver intensity in the focal plane of a fixed lens was shaped from Gaussian to supergaussian whilst the spot size was concomitantly increased. Within the range of experimental values, the increasing supergaussian order enabled the harmonic source size to increase at a faster rate than the driver spot size. This changed the scaling relationship between the detected harmonic flux and driver spot size from quadratic to a power of 2.3±1.72. Without changing the focussing optic, the brightness of the harmonic beam was increased by a factor of 5±0.65.
The second advance is that of the generation of multiple harmonic sources through the manipulation of the spatial phase of the driver laser. The intensity distribution of the driver beam was spatially shaped to form a user defined distribution of foci with programmable positions and relative energies. For two foci, experimental results are presented showing the generation of two independent but mutually coherent harmonic beams. Using these two harmonic beams, a Fourier Transform Holography target comprising two distinct features was illuminated. It is shown that under comparable conditions, distributing the illumination to match the shape of the target yielded an image with a superior signal to noise ratio.

Keywords: SLM
HHG
Femtosecond
Advisor: Hooker, S
Development of copper-catalysed addition reactions to alkynes

In this thesis, new copper-catalysed addition reactions to alkynes have been developed. The new methodologies exploit hydro-functionalisation to transform readily available starting materials into N-heterocycles and enol esters via addition of amides and acids to alkynes, respectively.
Chapter 1 is a literature review covering the transition metal-catalysed hydroamination and hydro-oxycarbonylation of alkynes, and some of the well-known copper-catalysed reactions.
Chapter 2 documents our new methodology on exploiting the copper-catalysed hydroamination of terminal alkynes to synthesis 5-ylidenepyrrol-2(5H)-ones and 5-hydroxypyrrol-2(5H)-ones, using readily available α-keto amides and terminal alkynes. A method towards the synthesis of asymmetric maleimides is also reported.

Advisor: Willis, M
Systematic design of reaction systems with prescribed behaviors: deterministic and stochastic methods

Synthetic biology is a growing interdisciplinary field, with far-reaching applications, which aims to design biochemical systems that behave in a desired manner. With the advancements in nucleic-acid-based technology in general, and strand-displacement DNA computing in particular, a large class of abstract biochemical networks may be physically realized using nucleic acids, which may be integrated into a variety of environments, ranging from test-tubes, cell-sized compartments, to living cells.Mathematical methods for a systematic design of the abstract systems with prescribed behaviors, used as blueprints for the nucleic-acid-based ones, have received less attention, and form the focus of this thesis.
At the (less-detailed) deterministic level, suitable when the abstract reaction networks involve only high-abundance species, and applicable when the nucleic-acid-based physical networks are integrated into test-tubes, the so-called kinetic transformations are developed.The transformations map ordinary differential equations with polynomial right-hand sides to reaction-rate equations, allowing one to design biochemical reaction networks with desired deterministic dynamics. At the (more-detailed) stochastic level, suitable when the abstract reaction networks involve some low-abundance species, and applicable when the nucleic-acid-based physical networks are integrated into vesicles or living cells, the so-called noise approximation algorithm is developed. The algorithm structurally modifies any given reaction network under mass-action kinetics, in such a way that (i) controllable state-dependent noise is introduced into the stochastic dynamics, while (ii) the deterministic dynamics are preserved.
Combining the developed deterministic and stochastic methods, together with the result that any reaction with more than two reactants may be stochastically approximated by up-to bi-molecular reactions, a deterministic-stochastic hybrid approach of designing reaction networks is put forward. In particular, the kinetic transformations may be used to construct networks with desired deterministic dynamics, and the noise approximation algorithm may then be used to favorably reprogram the intrinsic noise in the stochastic dynamics, while preserving the deterministic skeleton. The capabilities of this approach are demonstrated by designing reaction networks displaying biochemically relevant exotic dynamics, such as (noise-induced) multistability and oscillations, and specific bifurcation structures.

Advisor: Erban, R
On the protein-nucleic acid interplay in dsRNA viruses

Viruses harbouring double-stranded RNA (dsRNA) genomes are highly diverse and their host range spans from bacteria to fungi, plants and mammals. dsRNA viruses share a number of characteristics including the possession of icosahedrally symmetric capsids which shelter their genomes. As many other icosahedral capsids, those of dsRNA viruses have been extensively characterised by cryogenic electron microscopy (cryo-EM). In contrast, in situ structures of genomes and genome-associated proteins such as RNA-dependent RNA polymerases (RdRPs) are scarce due to their characteristic asymmetry and high degree of heterogeneity. This thesis sets to expand the arsenal of image processing algorithms aimed at overcoming such hurdles and to resolve the architectures of capsid interiors in quiescent and mRNA-producing i.e. transcribing φ6 nucleocapsids (QNCs and TNCs), as well as rotavirus QNCs.
The φ6 genome is organised in spooled fashion, bearing strong resemblance to the canonical arrangement of viral dsDNA genomes. In φ6 QNCs 12,000 base pairs accounting for over 90% of the entire genome are modelled. φ6 TNCs depict the concerted rearrangements required to activate transcription, namely the outer capsid disassembly, inner capsid expansion and RdRP reorganisation. Rotavirus QNCs paint an entirely different picture as the RdRP-dsRNA interplay displays such extraordinary flexibility that thousands of unique capsid interior arrangements are made possible. Taken together, these results further the understanding of virus capsid interiors and highlight important disparities among dsRNA viruses.

Keywords: cryogenic electron microscopy
structural biology
Advisor: Huiskonen, J