VictorJuiz/thesis huggingface dataset:
A double-acting hydraulic ram pump for deep-well water pumping

Many existing deep-well water pumping technologies that are affordable to developing world smallholders suffer from reliability issues, low efficiency and/or expensive running costs. The Double-Acting Hydraulic Ram Pump (DAHR) has the potential to address these problems. An evolution of the classic hydraulic ram pump that converts kinetic energy from free-flowing water sources into a reduced flow at a much higher head, the DAHR contains virtually no moving parts or dynamic seals. The result is a deep-lift technology that can be both highly efficient and extremely reliable. This thesis investigates the potential of the DAHR, taking an initial proof-of-concept rig to a design that is ready for outdoor field trials.
The beta prototype design process has been aided considerably by the development of a suite of numerical models. Like the conventional hydraulic ram, the DAHR has clearly defined acceleration and delivery phases either side of an impact event. The fluid motion during acceleration is modelled using a 1D lumped element approach whereas the delivery phase modelling is based on the shock equations for both compression and rarefaction waves. Unlike the conventional hydraulic ram, the DAHR makes full use of the kinetic energy downstream of the impact. The numerical results facilitate the selection of drive pipe diameter, inlet/delivery valves and the choice of pipe material via the resulting sound speed.
A 15 m tall test facility housed within a three storey public stairwell was set up to help simulate pumping from deep underground. The DAHR sitting in a tank at the bottom would lift water to the top of the stairwell before it was returned under gravity to complete the circuit. The driving power input to create the low pressure, high volume oscillatory flow within the DAHR U-tube is provided by two custom-made pneumatic fluidynes. The data acquired over several weeks of testing with three different plastic drive pipe materials required an automated post-processing routine capable of analysing DAHR performance impact-by-impact. Computed efficiencies of up to 75 percent were achieved while pumping 350 L/h at 32 m head. Experimental observations also showed good agreement with numerical modelling.
A single-acting design, capable of fitting down a smaller borehole, was considered as an alternative way forward. A further prototype, with the second drive pipe replaced by a gas spring, was designed, built and tested in the same facility. The prototype proved substantially more difficult to control and estimated efficiency was approximately half that of the DAHR validating the original double-acting approach.

Advisor: Stone, R
Role and regulation of TBX2 and TBX3

The T-box family of transcription factors plays a crucial role during embryonic development, especially in heart and limb formation. In the adult organism, two members of the family, TBX2 and TBX3, have been found to be overexpressed in several types of cancer associating them with tumour biology. However, little is known about their regulatory targets and subsequent function aside from their well-described role during development, that would give indications of their overall contribution to tumourigenesis. Here, an agnostic, genome-wide approach is chosen to reveal novel TBX2 and TBX3 regulated target genes in a human melanoma cell line, shedding further light on their regulatory activity. Furthermore, the regulation of the two T-box factors themselves by growth regulating pathways, dysregulated in cancer, is assessed. Both T-box factors are proposed to be involved in cancer homoeostasis, a process balancing nutrient supply and demand within the cancer cell to facilitate long-term proliferation without depletion of nutrients. Moreover, TBX2 and TBX3 are demonstrated to be regulated by the PI3K pathway mediated by PAX3, and that this regulation is implicated in the bypass of oncogene induced senescence.

Keywords: cancer
Advisor: Goding, C
Artemisinin resistant falciparum malaria in Myanmar

Artemisinin-based combination therapy (ACT) is first-line treatment for Plasmodium falciparum malaria globally but artemisinin resistance is now prevalent across Southeast Asia. Myanmar has the highest malaria burden in the region, and determining the prevalence of artemisinin resistance and current therapeutic efficacy of first-line antimalarial drugs is critical for both clinicians and policy makers planning malaria control and elimination programmes. The aim of this research was to study the geographical extent, prevalence, degree and optimum treatment of artemisinin-resistant falciparum malaria in Myanmar through a countrywide molecular survey and two multicentre clinical trials supported by parasitological and pharmacological investigations.
In a molecular survey of clinical falciparum malaria cases carried out in 55 sites across 10 administrative regions and border sites in neighbouring countries 39% of cases (371/940) were associated with parasites carrying a kelch13 propeller mutation. Kelch13 mutation prevalence exceeded 10% in much of the east and north of the country and was 47% in an area 25 km from the border with India.
In a trial conducted in central and northern Myanmar treatment efficacy of dihydroartemisinin-piperaquine (DP) was 100% but there was delayed parasite clearance associated with the kelch13 mutation F446I (median clearance half-life 4.7 hours, IQR, 3.7 to 6.2).
In a randomised controlled trial of 3-days versus 5-days artemether-lumefantrine (AL) treatment efficacy was 100% (95%CI, 94.9-100) and 97% (95%CI, 90-99.7) respectively and the two arms showed equal clearance rates (measured by an ultrasensitive quantitative polymerase chain reaction assay, uqPCR)..There was no association between the presence of kelch13 propeller mutations and residual parasite density at day 21, measured using uqPCR. Gametocyte carriage rates were high reinforcing the need to implement single low-dose primaquine (0.25 mg/kg) with ACTs to kill gametocytes in this area of artemisinin resistance.
In conclusion, artemisinin resistant falciparum malaria is widespread in Myanmar. While DP and AL remain efficacious, the partner drugs are vulnerable and if resistance develops treatment efficacy is likely to decline rapidly. Greater efforts are urgently needed to monitor treatment efficacy of first-line antimalarial drugs and develop alternative treatment regimens.

Advisor: Day, N
Smithuis, F
Horby, P
Who else takes part? Admitting the more-than-human into participatory art.

This practice-led research concerns how participatory and dialogic art practice can come to terms with conditions after the Anthropocene (Crutzen & Stoermer 2000), the epoch when humans were recognized as 'an earth-changing force' (Lorimer 2015). These forms of art practice draw heavily on a social-constructivism that emphasizes human cultural endeavour above all else. But if we are to live in an epoch when humans can no longer presume to have mastery over nature (Plumwood 1993), then how can such a anthropocentric practice remain tenable? Indeed, it now seems impossible, inappropriate even, to make such a clear distinction between humans and others things. This is not to claim the end of the human. Rather, it is an invitation to think the 'more-than-human' (Whatmore 2002; 2006), and to ask, who else takes part with us in the social forms enacted through participatory and dialogic art practice after the Anthropocene?
In doing so, this research turns towards aspects of new materialism (Dolphijn & van der Tuin 2015), and despite the associated risks – most obviously an accusation of "vulgarity" in insisting on the materiality of relations which subtend cultural and social ones – concludes that the benefits abound as the rest of the universe suddenly becomes our kin (Haraway 2015), our collaborators in research (Barad 2007), participants in art, and interlocutors in dialogue.
This research is conducted through art (Frayling 1993), and is presented as a series of artworks and accompanying printed publications. Together, they attempt to admit the more-than-human into art practice – both as things and as a concept.

Advisor: Gardner, A
Martin, D
Establishing rhythm as a theological category: experience, metaphysics, salvation

Rhythm is an important dimension of Christian liturgical practice as well as life in the world more generally. Given its significance, this study asks how theology ought to think about the nature and role of rhythm. It puts forward the argument that rhythm is a category of significance for Christian doctrine, particularly the doctrine of salvation, rather than one that pertains only to Christian religious expression (in liturgy for example) or aesthetics. This argument is made on the basis of three factors: (1) the pervasiveness of rhythm in dimensions of human experience that are salient to Christian soteriology, such as relationship and communication, make rhythm a dimension of experience worth theological consideration, (2) the fact that different conceptions of rhythm in various metaphysical accounts have different theological consequences requires theological discussion regarding the nature of rhythm, and (3) the capacity of rhythm to illuminate certain dimensions of the Christian doctrine of salvation such as the nature of participation, the relation between immanent and transcendent, and the relationship between interruption and continuity in Christian soteriology, make it a category that adds to theological understanding.
The thesis proposes a definition of rhythm as an oscillation between synchronic form and diachronic experience based in theories of poetic rhythm and supported by theological analysis. The project finds that particular philosophical or theological approaches to metaphysics incorporate either a synchronic or diachronic perspective on rhythm but that both of these perspectives are theologically problematic on their own, the former tending to an illusory perspective on the whole from a God's-eye-view and the latter tending towards a strict division between creature and creator such that the relationship between them is one of rupture and confrontation only and not salvific. The thesis therefore proposes an oscillation on the part of the theologian between these two perspectives after the metaphysics of Erich Przywara and demonstrates this approach to be appropriate to the Christian doctrine of salvation.

Advisor: Ward, G
Loss- and gain-of-function analyses of the role of MAP kinase signalling in testis determination

Sexual differentiation is the process by which an organism develops as either male or female. In mammals, this process is governed chromosomally, principally by the presence or absence of the Y chromosome. In the mouse, sex determination occurs at 11.5 days post coitum (dpc), when expression of Sry in the XY gonad kick-starts testis determination. SRY drives the subsequent expression of genes that both promote testis differentiation and inhibit ovarian differentiation, leading to specification of the testis. In cases where sex determination is disrupted, disorders of sexual development (DSD) can occur. Many genes have been described that are required for testis determination. However, we still know relatively little about how Sry itself is regulated.
MAP kinase (MAPK) signalling is involved in testis determination in mice and humans. MAP3K4 is required for testis determination in the mouse: loss of MAP3K4 is associated with male-to-female sex reversal in embryos and insufficient expression of Sry at 11.5 dpc. Likewise, loss of function of a protein known to interact with MAP3K4, GADD45γ, also leads to sex reversal. In humans, mutations in the gene encoding the related kinase, MAP3K1, have been identified as a key cause of DSD. Thus, MAPK signalling appears to play a key role in testis determination both in humans and mice.
This thesis describes experiments designed to further elucidate the role of MAPK-related signalling in testis determination. Firstly, an attempt was made to generate mice bearing a human sex-reversing mutation in Map3k1, however this was not successful. Additionally, RNA-seq was employed to investigate transcriptional targets of GADD45γ. Finally, the role of MAP3K4 as a dose-dependent modifier of sensitivity to sex reversal in mice is described, utilising a Map3k4 transgene to rescue sex reversal in B6 mice harbouring a Y chromosome from the Mus poschiavinus strain. These mice undergo sex reversal in the absence of the Map3k4 transgene, and also exhibit delayed Sry expression. By utilising this genetic tool, this thesis investigates the mechanism of sex reversal in these mice, with particular focus on the role pf Map3k4 in Sry expression.

Keywords: GADD45
Genetics
sex determination
MAPK
testis
Advisor: Greenfield, A
Christian, H
The impact of antigen processing on CD8+ t cell memory inflation

T cell "memory inflation" is the sustained induction of effector memory cells that home to peripheral tissues and retain their functionality. Defining the mechanisms that drive these non-classical memory responses may contribute towards the development of novel prophylactic or therapeutic vaccines. A model of memory inflation based on responses to β-galactosidase delivered by a non-replicating adenoviral vector provides a robust tool for investigating the underlying mechanisms. This work has shown that these responses are not dependent upon the human cytomegalovirus (HCMV) promoter within the model, this being the only part of the model that is CMV-derived. This model has been used to test the hypothesis that bypassing antigen processing would result in inflationary memory responses to CD8+ T cell epitopes that are not normally the targets of such responses. When the β-gal497-504 restricted epitope (ICPMYARV) was expressed as a minigene in a recombinant adenovirus vector, inflationary CD8+ T cell responses were induced, instead of the classical responses obtained with full-length β-galactosidase. Similar results were obtained with the M45985-993 (HGIRNASFI) epitope from the mouse cytomegalovirus M45 protein. These data demonstrate that the polypeptide context of a CD8+ T cell epitope may determine whether classical or inflating memory responses are induced. This could be relevant to the design of recombinant antigens in adenoviral vectors, which have emerging therapeutic and prophylactic applications.

Keywords: CD8+ T cell memory inflation
Advisor: Klenerman, P
Gilbert, S
Conservation and innovation - the evolution of the metazoan microRNA landscape and its contribution to reproduction and development

There are major gaps in our understanding of the evolution of microRNA (miRNA) genes and how this relates to evolutionary changes in metazoan development. miRNAs function as trans-acting post-transcriptional modulators of gene expression. They are implicated in the canalization of development and the consequent provision of evolvability. Here I present data and analyses on miRNA evolution in insects and mammals, both on a phylogenetic scale as well as at the level of individual miRNA genes. I also perform case studies cross-comparing the expression and functions of intronic miRNAs to those of their host genes, and compare tissue-specific enrichment of miRNAs in a specific tissue (butterfly ovary) relative to the whole body.
A broad overview of miRNA evolution across a clade is presented for the Lepidoptera using a combination of small RNA sequencing in two lepidopteran species coupled with bioinformatic analysis of available genomic and miRNA data across the clade. This analysis reveals a burst of rapid miRNA gain on the stem lineage of the Lepidoptera prior to the radiation of the diverse butterfly and moth lineages. I also propose that the uneven distribution of miRNA gain across the lepidopteran phylogeny, coupled with observations of high numbers of newly-emergent miRNAs on terminal branches, is evidence for a model of miRNA evolution comprising high rates of turnover for newly-acquired miRNAs with variable rates of stable miRNA retention. In depth examination is carried out on two miRNA genes, both of which occur within homeobox gene introns - eutherian-specific mir-615 and lepidopteran-specific mir-2768. Phylogenetic distribution and theories for the acquisition of mir-615 in Eutheria are considered. A combination of publicly available expression data and epigenetic modification data is used to demonstrate the existence of transcriptional regulation for mir-615 independent from that of its host gene. The study of mir-2768 reveals the first experimental evidence for an intronic miRNA performing a complementary function to that of its host gene. I also present the first miRNA transcriptome from a butterfly ovary and compare this to whole-body miRNA expression in the same species. This provides insights into the roles performed by miRNAs in the butterfly ovary, including conserved functions, and enables comparison of ovarian miRNA tissue specificity relative to time of origin.
Overall, this work provides a multi-faceted analysis of miRNA evolution in animals and presents an integrated approach to our understanding of the roles of miRNAs in evo-devo.

Advisor: Holland, P
Non-equilibrium dynamics of interacting many-body quantum systems in one dimension

In this thesis we study three examples of interacting many-body systems undergoing a non equilibrium time evolution.
Firstly we consider the time evolution in an integrable system: the sine-Gordon field theory in the repulsive regime. We will focus on the one point function of the semi-local vertex operator eiβφ(x)/2 on a specific class of initial states. By analytical means we show that the expectation value considered decays exponentially to zero at late times and we determine the decay time. The method employed is based on a form-factor expansion and uses the "Representative Eigenstate Approach" of Ref. [73] (a.k.a. "Quench Action").
In a second example we study the time evolution in models close to "special" integrable points characterised by hidden symmetries generating infinitely many local conservation laws that do not commute with one another, in addition to the infinite commuting family implied by integrability. We observe that both in the case where the perturbation breaks the integrability and when it breaks only the additional symmetries maintaining integrability, the local observables show a crossover behaviour from an initial to a final quasi stationary plateau. We investigate a weak coupling limit, identify a time window in which the effects of the perturbations become significant and solve the time evolution through a mean-field mapping. As an explicit example we study the XYZ spin-1/2 chain with additional perturbations that break integrability.
Finally, we study the effects of integrability breaking perturbations on the non-equilibrium evolution of more general many-particle quantum systems, where the unperturbed integrable model is generic. We focus on a class of spinless fermion models with weak interactions. We employ equation of motion techniques that can be viewed as generalisations of quantum Boltzmann equations. We benchmark our method against time dependent density matrix renormalisation group computations and find it to be very accurate as long as interactions are weak. For small integrability breaking, we observe robust prethermalisation plateaux for local observables on all accessible time scales. Increasing the strength of the integrability breaking term induces a "drift" away from the prethermalisation plateaux towards thermal behaviour. We identify a time scale characterising this crossover.

Keywords: Prethermalization
Non-equilibrium time evolution
Quantum Quenches
Advisor: Essler, F
Essays on the marriage market

This thesis consists of a short introduction and three self-contained chapters.
Chapter 1 develops a model of intra-household specialization and human capital formation for couples, taking into account of assortative sorting on income potentials in the marriage market. I assume people are matching on potential wage growth rates which differ across individuals and are realized through actual work experiences. The model is estimated by a simulated minimum distance estimator with PSID data from 1968 to 2011. I find there is strong positive assortative matching on wage growth rates, which helps explain the correlated wage growth residuals of married couples. If matching is switched to random, there will be more variation in household specialization arrangements and higher observed wage growth rates. The estimated elasticity of substitution between market goods and home production is approximately 0.37. Husband's time and wife's time turn out to be complements in the home production function.
Chapter 2 studies a marriage market with two-sided information asymmetry in which the gains from marriage are stochastic. Contracts specify divisions of ex-post realized marital surplus. I first study a game in which one side of the matching market offers contracts, and then study a social planner's problem, finding necessary and sufficient conditions for a truthful direct revelation mechanism to achieve matching efficiency. These conditions become more stringent as the number of agents in the matching market increases.
Chapter 3 examines the relationship between women's preference towards marriage and her marital outcomes. I propose using the mother's marital status as a proxy for her daughter's ex-ante preference towards marriage. Using 1980 and 2008 U.S. Census data, I estimate the impact of women's preference towards marriage and their educational attainments on their probability of getting married, and with Heckman correction, the impact on their husbands' earnings conditional on being married.

Keywords: Family Economics
Women's Preference towards Marriage
Human Capital Formation
Two-Sided Information Asymmetry
Assortative Matching
Matching in Marriage Market
Intra-household Specialization
Advisor: Browning, M
Meyer, M
Investigation and characterisation of poly(ADP-ribose)-binding proteins in Dictyostelium discoideum

The genome is under continual assault from endogenous and exogenous sources of DNA damage. The cell has therefore evolved a number of pathways to identify, signal, and ultimately repair DNA lesions. Poly(ADP-ribosyl)ation, the addition of multiple ADP-ribose moieties to proteins to form poly(ADP-ribose) (PAR) chains, has been implicated in several DNA repair pathways. One function of these PAR chains is to act as a scaffold for the recruitment of downstream repair proteins, suggesting the existence of protein domains that specifically bind PAR. Several of these domains have been identified, the best characterised being the PBZ and macro domains.
We utilise in silico genome-wide searches to identify novel proteins containing PAR-binding domains in the simple eukaryotic model organism Dictyostelium discoideum. We identity three proteins with unannotated macro domains in Dictyostelium: DNA ligase III (Lig3), an aprataxin-like protein (APL), which also contains a PBZ domain, and Q54R54. The macro domain of APL was found to be circularly permuted compared to the other human and Dictyostelium macro domains; however, structure prediction by homology modelling indicated that it had retained the structure of a classical macro domain. We performed in vitro PAR-binding assays that indicated that the macro domains of both Lig3 and APL bind to PAR chains. Lig3 is enriched on DNA following the infliction of base damage, indicating its role in the SSBR pathway. However, the dependence of this pathway on PARylation has not been determined. In contrast, APL was found to be enriched on chromatin in response to DNA inter-strand cross-links and S-phase-associated double-strand breaks, which was reduced following mutation of both the PBZ and macro domains of APL. Furthermore, APL was found to be mono-ubiquitinated in response to DNA inter-strand cross-links, an event that is dependent on its macro domain region. These data indicate a role for APL in the repair of DNA inter-strand cross-links, or S-phase associated DNA damage, which would not be predicted from its homology to aprataxin, thereby suggesting a protein with novel characteristics in the DDR in Dictyostelium.

Advisor: Lakin, N