VictorJuiz/thesis huggingface dataset:
Towards an absolute chronology of early Mesopotamia: a radiocarbon perspective

The region of Southern Mesopotamia, modern-day southern Iraq, saw a number of important socio-cultural transformations during the 4th - 3rd millennia BC, which led to the emergence of the world’s first urban, literate civilisation. These crucial developments reverberated across the neighbouring regions and greatly contributed to the later Classical and Judaeo-Christian traditions. Despite the importance of this period, our understanding of its chronology is limited. The main aim of this thesis is to build a reliable absolute chronology for the Uruk, Early Dynastic, and Akkadian periods in Mesopotamia using radiocarbon (14C) dating. Radiocarbon dates published in the archaeological literature underwent a thorough evaluation in order to ensure that only reliable measurements were included in the analysis. New dates were produced for the periods and contexts most lacking in radiocarbon data. Archaeological and textual sources were used to create Bayesian models in order to produce even more precise time estimates. The resulting periodisation of Mesopotamia was compared to the contemporary cultural sequences of ancient Iran and the Syrian Jezirah. While corroborating the standard Middle Chronology model, the results highlighted a number of intricacies relevant to our understanding of the early history of the Mesopotamian civilisation. Most importantly, this thesis argues that the developmental process was one of long periods of cultural continuity punctuated by sudden changes and shorter phases of innovation and creativity.

Keywords: archaeology
Bayesian
Jezirah
Mesopotamia
radiocarbon
Iran
Advisor: Ramsey, B
Dee, M
Characterisation of the innate immune sensor MDA5

Melanoma Differentiation-Associated gene 5 (MDA5) is a cytosolic RNA receptor. Its activation triggers the production of the antiviral cytokines type I and III Interferons (IFN). It is believed that MDA5 detects viral and/or cellular RNAs. The latter case may be relevant in the context of cancer treatment with DNA demethylating agents, and in autoinflammatory and autoimmune diseases. In all these settings, physiological MDA5 agonists have not been identified. To identify MDA5-stimulatory RNAs, we generated mouse monoclonal antibodies against human MDA5. We showed that some of these antibodies are specific and detect MDA5 protein by Western Blot, in immunofluorescence, and work in immunoprecipitation (IP). To identify MDA5's RNA ligands in living cells, we employed the UV-crosslinking and IP (iCLIP) technique. Interestingly, we found that MDA5 associated with RNAs regardless of virus infection. Sequencing and characterisation of these RNA species will be performed in the future. MDA5 overexpression led to IFN-I induction, which could be explained by MDA5 binding to cellular RNAs. Indeed, two bioassays developed here suggest that MDA5 can sense RNAs from uninfected human cells and tissues. In a second project, we demonstrated that Zika Virus (ZIKV) replication generated MDA5 and, RIG-I immunostimulatory RNAs. RIG-I-dependent IFN-I induction was sensitive to alkaline phosphatase treatment, in line with the requirement for 5'-ppp groups for RIG-I activation. Furthermore, by using a mini-screen of ZIKV proteins, we identified the non-structural protein 5 (NS5) as a potent inhibitor of the type I IFN signalling pathway. We show that this inhibitory mechanism is unrelated to: i) NS5's nuclear localisation, ii) mutations found in strains of the current outbreak, and iii) a conserved residue in the methyltransferase domain. In sum, we provide novel insights into the biology of MDA5, new reagents for the studies of MDA5, as well as data on the role of RNA sensors in detecting ZIKV infection and evasion of innate immunity by ZIKV.

Advisor: Rehwinkel, J
Eggeling, C
Intervention methods against mosquito-borne diseases

Mosquito-borne diseases account for hundreds of thousands of deaths each year, highlighting the need for successful intervention methods, which can be targeted at either the pathogen, mosquito vector, or human host. This thesis aims to contribute to better intervention methods focused against malaria and dengue by either (i) improving available research tools, (ii) enhancing the understanding of a promising intervention method or (iii) designing new intervention candidates. Firstly, a superior method for studying in vitro malaria infection of the liver is shown, with implications for vaccine and drug interventions. Secondly, the biology of Wolbachia infection in Anopheles gambiae mosquitoes in the context of the target of rapamycin signalling cascade is investigated in an attempt to improve our understanding of its malaria inhibitory phenotype and inability to stably infect An. gambiae mosquitoes. Finally, an algorithm is developed for the design of a hypothesis driven conservation-based vaccine against viral mosquito diseases with a particular focus on dengue.

Keywords: Dengue
Malaria
Wolbachia
Advisor: Reyes-Sandoval, A
Sinkins, S
Jupiter's tropospheric composition and cloud structure from 5-μm spectroscopy

This thesis uses infrared observations from spacecraft and ground-based telescopes to investigate the composition and cloud structure of the jovian atmosphere. It focuses on a single spectral region, known as the 5-μm window, where Jupiter's upper atmosphere becomes optically thin. This allows us to probe down beneath the planet's thick cloud decks to the 4{8 bar region in the middle troposphere. Two different data sources are combined to build up a three-dimensional picture of Jupiter's troposphere. The first dataset is from the Cassini VIMS instrument, and was taken during the 2000-2001 Jupiter yby. These observations cover a wide spectral range, provide global coverage and include both the nightside and the dayside of the planet, making them well suited to studying clouds. The VIMS spectra can be modelled using a single tropospheric cloud deck, subject to the following constraints: (i) the cloud base is located at pressures of 1.2 bar or lower; (ii) the cloud particles are highly scattering; and (iii) the cloud is sufficiently spectrally at. The second dataset is from the CRIRES instrument at the Very Large Telescope in Chile. These observations have a very high spectral resolution, allowing the absorption lines of individual molecular species to be resolved. The CH3D line shape varies between belts and zones, which can be interpreted as variations in the opacity of a deep cloud, located at around 5 bar. There is also evidence for spatial variability in two disequilibrium species, AsH3 and PH3, both of which show an enhancement at high latitudes. This is in contrast to a third disequilibrium species, GeH4, which shows no evidence for spatial variability. The CRIRES dataset also includes several strong emission lines, which are identified as H3+, an auroral species in Jupiter's ionosphere. The strengths of these lines were measured in order to determine the ionospheric temperatures. The work in this thesis contributes to our understanding of the dynamical, chemical and cloud-forming processes shaping Jupiter's troposphere and provides a reference point for future work, including observations made by NASA's Juno mission.

Advisor: Irwin, P
Fletcher, L
Viral and host factors regulating influenza virus replication

Avian influenza A viruses typically do not replicate very efficiently when exposed to a mammalian host species. One of the reasons for this is the low activity of the viral RNA-dependent RNA polymerase of avian influenza viruses in mammalian cells. This host restrictive effect can be overcome by adaptive mutations in the avian polymerase, many of which are found in the 627-domain of the PB2 polymerase subunit. Deletion of the 627-domain revealed that this domain is not required for enzymatic functions of the polymerase in vitro, but that it essential for viral replication in a cellular environment in a nucleoprotein-independent manner. While the 627-domain is not necessary for viral RNA synthesis, it was demonstrated that it is involved in mediating encapsidation of nascent replication products.
Recently the host factor ANP32A was shown to be the main determinant of host range restriction of the viral polymerase. It was demonstrated that during viral infections ANP32A interacts with KPNA2, a host factor strongly linked to host range restriction of the viral polymerase. It was also revealed that avian polymerases specifically are restricted in vRNA synthesis, a defect that was reversed in the presence of avian ANP32A. ANP32A was shown to be an enhancer of vRNA synthesis in vitro.
Viral polymerase-polymerase interactions have been reported previously and presumably fulfil several essential functions during viral replication. Here the potential interaction interfaces of two different polymerase dimers were investigated and a role of polymerase dimers in replication and in trans-activation of cRNA-bound polymerases was found.
RNA-binding proteins are essential for RNA metabolism and therefore cell physiology. It has been reported that the RNA-binding proteome responds to biological stimuli. Here the response of the RNA-binding proteome to influenza virus infection was investigated using an in vivo UV crosslinking interactome capture technique. It was demonstrated that the RNA-binding proteome is significantly altered and that this effect is independent of protein abundance. Several host RNA-binding proteins were identified that change their RNA-binding behaviour and that could have pro- or antiviral functions during influenza virus infection.

Advisor: Fodor, E
Proteases and inhibitors in the interaction between Nicotiana benthamiana and Agrobacterium tumefaciens – systematic analysis and emerging solutions for molecular farming

Nicotiana benthamiana is now an established platform for molecular farming, the production of biopharmaceuticals in plants. Infiltration with Agrobacterium tumefaciens (agroinfiltration) is commonly used to transiently express one or multiple transgenes in N. benthamiana leaves. Agroinfiltrated N. benthamiana is a flexible and scalable recombinant protein (RP) production platform, but is impeded by low RP yields. Plant proteases can degrade RPs and thus limit RP accumulation.
To inform, design and implement strategies for enhancing RP accumulation, I present four papers about proteases and protease inhibitors in agroinfiltrated N. benthamiana. First, I investigated the transcriptome, extracellular proteome and active secretome to understand the plant response to agroinfiltration and investigate the expressed proteases. I show that an extracellular immune response is mounted at the expense of photosynthesis. Comprehensive annotation and monitoring uncover a large, diverse repertoire of proteases in agroinfiltrated leaves, indicating that broad-range depletion of protease activity may be required to enhance RP accumulation. Second, I reviewed the literature on multifunctional plant protease inhibitors (PIs) and grouped them into three types of multifunctional PIs that evolved independently. Third, I screened candidate PIs and discovered that three new, unrelated PIs enhance RP accumulation. I present universal elements of the RP degradation machinery, uncovering new questions on our understanding of the protease network that degrades RPs. Fourth, I identified targets of SlCYS8, a PI that enhances RP accumulation. The target proteases of SlCYS8 are implicated in RP degradation and the high specificity of SlCYS8 can be used to study their role in other processes.
By elucidating the immune response to agroinfiltration, by uncovering the N. benthamiana protease repertoire and by providing new tools to deplete the activity of specific proteases, this thesis makes a relevant contribution to both basic plant research and molecular farming.

Keywords: SlCYS8
proteomics
RNAseq
recombinant protein
Advisor: van der Hoorn, R
Kelly, S
Student Engagement and Empowerment in Higher Education

Student engagement, which emphasises students’ role in shaping their higher education experiences, has become embedded as a core aim of national policy and the everyday management of universities. It has provoked a reconceptualisation of traditional hierarchies within higher education and offers the potential to be empowering for students. However, it has also been criticised for diminishing student agency by reinforcing ideas of student-as-consumer. Drawing on focus groups with students across three universities in England, this study aims to explore students’ experiences and perspectives of empowerment in the context of student engagement policy. The research finds that students who do not have a representative role face significant barriers to shaping their academic experiences; they are excluded from decision-making processes and rarely get to experience any changes that result from their feedback. Although students’ consumer identities give them confidence to demand more of their institutions, consumer rationales for student engagement may limit students’ sphere of influence. A sense of community, enhanced by the quality and quantity of student-staff contact, can be truly empowering but the effects of massification and marketisation present significant challenges to promoting this. These findings lead to a number of policy recommendations, which can be used by those who wish to create empowering opportunities for students to influence their life at university.

Keywords: Thematic analysis
Student voice
Citizen participation
Power
Engagement
Capability approach
Focus group
Education
Empowerment
Consumer
Higher education
Amartya Sen
Marketisation
Students
Agency
Qualitative
Student repesentation
Advisor: Ertl, H
Fast and accurate hot-spot estimation in electrical machines

Temperature is one of the parameters that limits the output torque and reduces the lifespan of electrical machines. Models that can provide accurate estimation of the temperature field in the most critical components (e.g. windings) at lower computational effort can be useful to improve the design process and reduce the time to market. Depending on the application, engineers usually rely on hi-fidelity models, e.g. based on the finite elements method (FEM), or lower order models, e.g. thermal equivalent circuits (TECs). The aim of the present work is to provide new tools and methodologies to obtain the temperature distribution within the windings using reduced order hi-fidelity models or improved TEC that could account for any working condition, including AC effects.
A new methodology, based on the multiple scales method (MSM), is introduced which homogenises the complex windings domain and allows for the estimation of its effective thermal properties. The homogenisation through the MSM is performed solving a single elementary cell. The MSM also allows for the reconstruction of the actual thermal field. Extensive numerical and experimental validation is provided, in particular for the case of electrical windings encapsulated with epoxy.
The thermal homogenisation is then combined with an electromagnetic homogenisation technique to estimate winding losses including AC effects, such as proximity and skin effects. The coupled analysis is validated numerically on reference test problems, and experimentally, on a suitably built "motorette". The method is proven to correctly predict losses including thermal effects and to estimate magnitude and location of the temperature hotspot within the winding domain.
This work also introduces a new approach for building thermal equivalent circuits that represents the most commonly employed modelling technique for electrical machine thermal analysis. Here the TEC approaches are thoroughly analysed, highlighting limitations. The proposed new technique extends the range of numerical accuracy, accounting for high Biot numbers (up to Bi = 2) and internal heat generation. The result of this approach is higher spatial resolution about the temperature field within the winding domain and thus enables improved information on hotspot location and magnitude. The method is experimentally validated and also applied to model an electrical machine for full-electric in-wheel vehicle propulsion.

Keywords: hot-spot
Thermal analysis
homogenisation
Electrical machines
Multiple scales
Advisor: Howey, D
Bruna, M
Rigid origami of thick panels and deployable membranes

Rigid origami is about folding flat inextensional facets which are connected by creases. It is gaining popularity and being used in an increasing number of engineering applications. Since this is a relatively new field, a number of challenges exist, e.g., folding facets with a finite thickness and achieving folding compactness. This dissertation summarises two attempts to address these two issues. Specific attention has been drawn to the offset crease technique and the wrapping membrane patterns.
In the first part of this dissertation, I have established a kinematic model describing the offset crease models, which leads to a proof that the motion of the thick panel folding is kinematically equivalent to that of its parent pattern with zero thickness. A detailed design approach for adapting this technique has been proposed and proven to be effective by various physical implementations. In order to achieve a higher compactness, an anisotropic tessellation has been derived from the traditional Miura-ori pattern. Its compatibility with pre-existing thickness accommodation approaches has been demonstrated via thick-panel models.
The second part of the dissertation examines a number of deployable membrane patterns. Firstly, the hexagonal winding membrane has been validated with a strict mathematical proof that a rigid transition is non-existent. Therefore, a number of newly proposed wrapping patterns have been designed and their motions have been studied via numerical simulation to discover the adequate rigid-foldable patterns. The algorithm of the simulation has been synthesised to create visualisation software for simulating general origami patterns. Furthermore, we have proposed a comprehensive scheme to allow arbitrary material thickness to be accommodated for the wrapping patterns. Finally, a sequential square twist pattern with a high deployed-to-stowed ratio has been created.

Keywords: deployable membrane
offset crease
Advisor: You, Z
The experiment of eight million people: an investigation into the process of designing social policies in China

This project problematizes the general understanding of China's birth planning regime. By providing an analytical history of a two-child policy experiment, it moves beyond previous work to generate granular accounts of key policymaking decisions.
A 'critical junctures' approach centred around what has been called the 'Experiment of Eight Million People' was leveraged to unlock this alternative chronology within China’s national fertility policy. The Experiment was a two-child pilot that governed select rural counties for more than thirty years, but it has not yet been systematically examined in the English-language literature. Tools from critical junctures theory, or the idea that explicating possible inflection points builds understanding of policy mechanisms, provide a framework to identify the times when the two-child design appeared most likely to be on the cusp of national expansion. Data from Chinese media, declassified internal government documents, secondary literature, and interviews with elite Chinese academics and policymakers are then leveraged to provide detailed descriptions of the events that predicated the policy outcomes at these points. This process yielded the first English account of the mechanisms that triggered China's change to a national two-child policy in 2015. Finally, results from this analysis were used to hypothesize about which political factors were most central in facilitating or obstructing changes in a Chinese social policy. Beyond Chinese birth planning specifically, the project has implications for the study of political factors enabling or constraining social policy change, welfare policy in East Asian and authoritarian states, and the degree to which population policies serve a social function.

Advisor: Gietel-Basten, S
Clouds on the horizon: identifying global priorities for conservation marketing and planning the conservation of the Sunda clouded leopard on Borneo

Conservation effort and action is limited by resources. In response previous authors have sought to identify priorities for conservation and it has become clear that making decisions about conservation priorities necessitates encompassing the fields of human behaviour and psychology, politics, economics and fundamental ecology. In this thesis I bring together two novel strands of research in this arena, 'conservation marketing' and the identification of priority locations for conservation.
In the first part of this thesis I present an analysis of how a representative subset of mammalian species might be prioritised in the context of conservation marketing. I develop a novel collaboration with a market research firm to assess quantitatively which species a large sample of English-speaking people value for conservation, and analyse their choices to reveal the attributes that drive these preferences. Developing this idea, I extend this analysis to all terrestrial mammals to identify potential Ambassadors for conservation marketing campaigns. Felids perform well on metrics of charisma, and for many species of big cat their large biogeographical ranges encompassing many other threatened mammalian species make them good potential Ambassadors.
Despite its relative unfamiliarity to the public, the Sunda clouded leopard (Neofelis diardi) is among the species identified as a potentially good ambassador for conservation marketing and it is also one that faces severe threats from land use change across its range.
The second part of this thesis therefore provides insight into the threats faced by clouded leopards, how these threats impact them, and how they might be mitigated. I develop the first map of predicted deforestation across Borneo and use this to map the historic and future impacts of land-use change on clouded leopard populations (their demography and genetics), taking account of their favoured habitats and its fragmentation. Finally, I compare a number of contrasting policy scenarios to highlight how the existing network of protected areas provides poor coverage for clouded leopards and how new protected areas might improve this. These techniques demonstrate a toolset that can be usefully applied to a wide range of species and habitats in the future.

Advisor: Malhi, Y