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oai:www.repository.cam.ac.uk:1810/2436502025-12-19T17:56:35Zcom_1810_721com_1810_256064col_1810_218856

A computational analysis of the vibrational absorption of molecular solids in the teraherz range 10.17863/CAM.16291 Tomerini, Daniele In this thesis, we deal with the application of transmission terahertz spectroscopy as an analysis tool for the study of molecular solids, in particular organic crystals of pharmaceutical interest. Most of the work has been performed using two computational packages aimed at the interpretation of the spectra, one based on molecular forcefields (DMACRYS), the other on solid state density functional theory (CASTEP). We compare low temperature determinations of several molecular organic crystals to calculated spectra, and attempt to assign calculated modes of vibrations to absorption peaks, based on the similarity in frequency between the measured and calculated peaks. One of the main aims of this work is to establish the limits of our forcefield approach, which is based on the approximation that the intramolecular degrees of freedom can be neglected. We analyse the normal modes of vibration calculated with CASTEP, evaluating the amount of rigid molecule rotational and translational contribution to each eigenvector as a function of frequency, in order to validate our forcefield approach. We also compare the two sets of eigenvectors from the DMACRYS and CASTEP calculations to assess the similarity between the two approaches. We perform the same eigenvectors analysis on several hydrate systems in order to understand the role of water in the lattice dynamics of crystalline hydrates. We attempt a classification of the eigenvectors based on the strength of the forces involved in the molecular vibrations and based on the amount of the water contribution to each normal mode. A set of isostructural crystals is analysed in order to understand the effect that small variations (in the molecular formula and in the unit cell arrangement) have on the measured and calculated absorption spectra of a crystal. Finally, we discuss the use and development of computational methods that allow us to have a more realistic description of the molecular electrostatic in DMACRYS. University of Cambridge 2012-07-03 Thesis Doctoral Doctor of Philosophy (PhD) eng This work was supported by Astra Zeneca http://www.dspace.cam.ac.uk/handle/1810/243650 https://www.repository.cam.ac.uk/handle/1810/243650 https://www.repository.cam.ac.uk/bitstreams/60151c98-8b8c-46bf-8df6-6663c3375a6f/download 14b29f8e9c7b2859e3efd67308545c8c https://www.repository.cam.ac.uk/bitstreams/c002279d-948e-4ce3-8f14-5fc665b8c855/download 48dcdf38f646da27e5e4bc6c1893d4fc https://www.rioxx.net/licenses/all-rights-reserved/ Terahertz Spectroscopy Organic Materials Simulation DFT DMACRYS CASTEP

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Essays in International and Monetary Economics https://doi.org/10.17863/CAM.111924 Domenech Palacios, Maria Del Mar Faraglia, Elisa The forthcoming chapters delve into monetary and international economics, with a particular focus on the role of uncertainty and risk in driving the strategies of economic agents. They explore the interplay between individual behaviors and macroeconomic trends by leveraging micro data to answer macroeconomic questions. The first chapter explores the drivers of inflation inequality across households. In particular, it examines how households use heterogeneously the quality margin of the varieties they purchase to insure themselves against shocks. Using household scanner data of supermarket consumption for Germany, I analyse the extent to which households trade down in the quality of goods in the aftermath of a recession. First, I document that, on average, lower income households tend to purchase lower quality goods. Furthermore, lower income households exhibit a low propensity to trade down, presumably due to a limited capacity to do so. This is in contrast with the rest of households, who appear to trade further down in the quality of goods. This is suggestive evidence of a lower bound in the quality margin available for certain households. Next, I analyse the aggregate effects of this phenomenon on product-level inflation, namely, the effect of an aggregate demand shift towards lower quality varieties in the beginning of a recession. For it, I employ a shift-share research design based on population growth of narrowly defined groups of households to predict the amount of trading down when the recession hits, therefore identifying a reasonably exogenous demand shifter. The intuition is that in the regions where the household groups that are more likely to trade down in the quality of goods grow faster, the amount of trading down once the recession starts will be larger. I find that a generalised demand shift toward lower quality goods during recessions leads to an increased price of low quality varieties compared to the price of higher quality varieties. In particular, on average, a 1% increase in the demand for lower quality varieties due to households trading down in the quality of the varieties they purchase translates into a 0.33% increase in the relative price of low compared higher quality varieties. The second chapter, co-authored with Giancarlo Corsetti and Luca Dedola, investigates whether and how heterogeneity in consumption risk and inflation across households affect consumption demand and growth under the lens of an incomplete markets framework. Our model of household-level risk sharing imposes minimal restrictions on the financial market structure, allowing for both aggregate and idiosyncratic tradeable risks to be at least partially diversified, and for precautionary saving motives. We bring the model to bear on empirical evidence, using household-level scanner data from Euro area regions and United Kingdom, together with a matching model for financial market participation. Our contribution is twofold: first, we develop a theoretical framework mapping consumption (rather than income) risk and inflation differentials onto consumption growth at regional level; second, we assess theoretical conditions empirically, exploiting heterogeneity in risk and risk sharing, by preference, income, residence and participation in financial markets. Our empirical analysis provides evidence that tradeable risk is insured primarily among financial market participants, and across regions of the euro area than regions across the border (provided that differences in inflation are accounted for). Consumption risk, proxied using variability of consumption growth within regions and income groups, weigh on consumption demand. The third chapter, co-authored with Meredith Crowley, Elisa Faraglia and Chryssi Giannitsarou, explores how British firms adapted to the uncertain commercial environment through establishing new EU subsidiaries and operations. In particular, we first study the intertemporal variation in the number of newly-established subsidiaries of British firms in the EU from 2016 to 2021. We find that, in the post-referendum period, more subsidiaries were established by British parents in months and sectors in which the uncertainty over the future commercial relationship between the UK and EU was higher. This evidence suggests that subsidiaries were established to help firms hedge the risk of losing their access to the EU market. Finally, we use annual balance sheet data to examine the characteristics of British parent firms establishing their first subsidiary in the EU before and after the Brexit referendum. We conduct a difference-in-differences analysis in which we compare the characteristics of British parent firms establishing a first subsidiary in the EU to those of EU parent firms establishing a first subsidiary in another EU country before and after the referendum. We find that, in the year in which British parent firms established a first subsidiary in the EU and the year before that, the growth of turnover, profits, assets and cash flow was substantially lower for those firms establishing their first subsidiary between 2016 and 2022 relative to between 2012 and 2015 and relative to the change in growth for EU parent firms between these two periods. University of Cambridge 2024-03-25 Thesis Doctoral Doctor of Philosophy (PhD) eng Cambridge Trust Advanced Education Trust Cambridge Keynes Fund https://www.repository.cam.ac.uk/handle/1810/373563 https://www.repository.cam.ac.uk/bitstreams/540d82e3-eeb8-4054-bf74-d9d08b0c79ff/download 6016cd637f09dfadcde373d81036bc44 https://www.repository.cam.ac.uk/bitstreams/78f57df6-71dd-4ae1-90c0-c5fe4873c164/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ consumption inequality Heterogeneity inequality inflation inequality instrumental variables micro data policy uncertainty risk sharing scanner data shift-share research design trading down uncertainty

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Fabrication and Characterization of Three-Dimensional Magnetic Nanostructures 10.17863/CAM.41404 Sanz Hernández, Dédalo 0000000255528836 Fernández-Pacheco, Amalio 0000000238628472 Today, two-dimensional nanoscale magnetic systems are well understood, being used in applications from spintronic circuits to automotive sensing. Despite the great progress achieved in the field during the last decades, the development of three-dimensional devices is still hindered by phenomenal patterning and characterization challenges. Most lithographic and probing techniques have historically targeted planar samples and are not suitable for three dimensional geometries. This thesis achieves three key points to overcome these fabrication and characterization challenges: improving the understanding and control of 3D nano-printing of cobalt nanostructures using Focused Electron Beam Induced Deposition (FEBID), improving the performance of synchrotron-based magnetic X-ray microscopy in 3D geometries and adapting existing magneto-optical techniques to rapidly probe 3D nanostructures in the lab. As a result of this work, new tools and skills are available in the field of 3D nano-magnetism, unlocking a path for the development of sophisticated 3D nanomagnetic devices with increased functionality and performance. University of Cambridge 2019-04-09 Thesis Doctoral Doctor of Philosophy (PhD) en Girton College Pfeiffer Graduate Scholarship Winton Fund for the Physics of Sustainability https://www.repository.cam.ac.uk/handle/1810/294306 https://www.repository.cam.ac.uk/bitstreams/6e235828-b3f6-4933-9b5e-cf3cff492822/download eb4cf804f29a5ee27ec038e8f3959bfa https://www.repository.cam.ac.uk/bitstreams/b3fe8c51-184e-4a00-b5b1-771a08713230/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ 3D Three-Dimensional Magnetic MOKE Magneto Optical Kerr Effect Dark-Field Spintronics Micromagnetism Focused Electron Beam Induced Deposition FEBID Dicobalt Octacarbonyl Co2(CO)8 nanoprinting nanofabrication XMCD X-ray microscopy Hexapole Domain wall Racetrack memory Double Helix

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Femtosecond time-resolved intersubband relaxation measurements in GaAs/AlGaAs quantum wells. 10.17863/CAM.17313 Schumacher, Kimberly University of Cambridge 1995-06-13 Thesis Doctoral Doctor of Philosophy (PhD) eng Digitisation of this thesis was sponsored by Arcadia Fund, a charitable fund of Lisbet Rausing and Peter Baldwin. https://www.repository.cam.ac.uk/handle/1810/270439 https://www.repository.cam.ac.uk/bitstreams/b17d7f66-c138-440f-8605-53db6989461f/download 87eda9de84448d1f82354d60eee3eb5f https://www.repository.cam.ac.uk/bitstreams/d8c8941b-3ac3-4eda-829d-da5253dedb9c/download 187720372585cbb8c67e537c653de457 https://www.repository.cam.ac.uk/bitstreams/019442cb-84bc-467a-aa55-f4fbe4ac5035/download 269435cd7936e89e72cb4f2249580681 https://www.rioxx.net/licenses/all-rights-reserved/

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Machine learning methods for detecting positive selection https://doi.org/10.17863/CAM.128461 West, Charlotte Goldman, Nick Molecular evolutionary biology seeks to explain the diversity of life by uncovering the processes that shape genomes over time. A central aim within this field is to identify the genetic basis of adaptation, often manifesting as signatures of positive selection acting on protein-coding genes. Detecting such signals sheds light on evolutionary processes such as functional divergence, coevolutionary dynamics and phenotypic innovation. However, whilst the study of natural selection has been foundational in evolutionary theory, reliably identifying its genomic footprints remains a persistent challenge. Traditional methods for detecting interspecific positive selection are grounded in statistical, likelihood-based methods, typically employing codon substitution models. These approaches infer rates of nonsynonymous to synonymous substitutions (dN/dS) from nucleotide multiple sequence alignments (MSAs) of homologous, protein-coding genes, interpreted as a proxy for positive selection. These approaches have been instrumental in advancing our understanding of adaptive evolution, but they are not without their limitations. Statistical approaches are often computationally demanding, vulnerable to model misspecification, and underpowered when applied to realistic evolutionary scenarios. Models are forced to make simplifying assumptions to make the analysis tractable in the likelihood framework, which can contribute to both type I and type II error. Misalignments tend to further inflate false positive inference. As genomic datasets have grown in both scale and complexity, the shortcomings of classical inference methods have become increasingly apparent. This creates a pressing need for approaches that can harness large genomic datasets more flexibly, while capturing the complex dependencies inherent in sequence evolution. In parallel with these challenges, recent advances in machine learning have transformed diverse areas of biology, including molecular evolution. In particular, deep neural network architectures such as convolutional neural networks (CNNs) and transformer models have demonstrated an ability to extract meaningful patterns from raw biological data, without heavy reliance on human-curated features. Nevertheless, applying machine learning to molecular evolution presents its own challenges: the task requires large amounts of biologically realistic training data, architectures and resources equipped to handle such data, and rigorous evaluation frameworks that connect machine learning predictions to established evolutionary theory. There is very little or no evolutionary data for which we know the ground truth regarding how it has evolved; therefore, I rely on simulated data for training and evaluation. This thesis addresses these challenges by developing and evaluating machine learning methods for detecting positive selection in protein-coding genes. I first establish simulation frameworks that can be used to generate training data, and design benchmarking experiments to compare machine learning models against widely used statistical methods. I then develop CNNs trained to classify MSAs as evolving under positive selection or not, which were simulated from constrained phylogenies as a proof-of-principle. These models perform well when tested on data that resemble the training data, but struggle to generalise outside of the target domain. Nonetheless, these CNNs were successful in providing a faster, efficient and more accurate solution for positive selection detection compared to likelihood methods when trained for a specific phylogenetic scenario. This is useful for analyses such as genome-wide selection scans, where many MSAs are associated with the same phylogeny. To address the limitations of CNNs I then switch my focus to developing transformer models, which generalise more effectively across varied phylogenetic scenarios due to their global receptive field (ability to capture long-range dependencies across sequences) and permutation-invariant (insensitivity to the order of input elements) attention mechanism. I compare transformers directly with CNNs, showing comparable performance before extending to generalised models, capable of handling a wide range of phylogenetic scenarios. In addition to binary classification --- where whole genes are inferred to have evolved under positive selection or not --- I develop transformer models that predict sitewise dN/dS values for codon-specific inference of positive selection. To develop these models I evaluate a range of architectures and training strategies. These analyses demonstrate that machine learning approaches can achieve comparable or superior sensitivity to established likelihood-based methods. At the same time, I explore strategies to biologically interpret what these models learn. Exploiting the flexibility of the machine learning framework, I increase the realism of simulations by incorporating more realistic evolutionary processes that cannot typically be used in likelihood-based approaches. Finally, I apply generalised transformer models to empirical datasets. These analyses highlight their utility in cases where statistical methods lack power, while also revealing limitations that point to directions for future development. The contributions of this thesis are threefold. First, I provide an assessment of the limitations of current statistical methods, clarifying where they fall short in practice. Second, I develop new methodological tools that adapt machine learning architectures for evolutionary inference, with particular emphasis on CNNs and transformer models applied to MSAs. Third, I present an evaluation framework that bridges machine learning predictions with evolutionary theory, working towards methodological advances that are robust and biologically meaningful. Together, these contributions demonstrate how machine learning can extend the methodological toolkit of molecular evolution in ways that are difficult to achieve with traditional likelihood-based approaches. Machine learning models learn complex, non-linear patterns directly from data, capture signals of selection that are inaccessible to predefined parametric models, exploit the flexibility of simulation, and scale efficiently to large datasets. This work shows both the promise and the limitations of deep learning for detecting selection, and it points toward a future in which data-driven and theory-driven approaches are integrated to achieve faster, more flexible, and more accurate evolutionary inference. University of Cambridge 2025-10-04 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/400206 https://www.repository.cam.ac.uk/bitstreams/37398577-a0d4-4081-913f-8d24013984c3/download c7e829ad6a13c69de4d98c10228c5c97 https://www.repository.cam.ac.uk/bitstreams/ebc89992-3a94-4635-a704-883a06b959e6/download 87eda9de84448d1f82354d60eee3eb5f https://creativecommons.org/licenses/by/4.0/ machine learning evolution positive selection

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Photodetection and Spectrometry at the Nanoscale 10.17863/CAM.62628 Albrow-Owen, Thomas 000000030443014X Hasan, Tawfique Over the past fifteen years, one- and two-dimensional nanostructures have drawn intense attention across a range of scientific fields. For optoelectronic device applications these nanomaterials are particularly attractive due to their fundamental physical properties, such as dramatic environmental or photo-sensitivity, and effects arising from their sub-wavelength dimensions. Furthermore, their physical size alone presents an opportunity for their use as nanoscale components within miniaturised or flexible systems. In this thesis, optoelectronic device platforms based around two such nanomaterial systems – compositionally-engineered nanowires and layered black phosphorus – are developed and studied. An ultra-miniaturised microspectrometer device platform is demonstrated, based on individual compositionally-engineered nanowires. Representing the most compact microspectrometer design to date, by over two orders of magnitude, this strategy is independent of the complex optical components, cavities or CCDs that constrain further miniaturisation of current systems. It is demonstrated that incident spectra can be computationally reconstructed from the different spectral response functions and measured photocurrents along these nanowires. This platform is highly versatile; operation can straightforwardly be expanded across the infrared to ultraviolet range. Despite their simplicity, these devices are capable of accurate monochromatic and broadband light reconstruction, as well as spectral imaging from centimetre-scale image planes down to lensless, single-cell-scale in-situ mapping. This could open new opportunities for almost any miniaturised spectroscopic application, including lab-on-a-chip systems, smartphones, drones, implants, and wearable devices. Further to this, the first scalable strategy for depositing solution-processed black phosphorus films with viable device performance and stability is demonstrated. High concentration black phosphorus dispersions are produced by liquid-phase-exfoliation. Optimisation of a solvent-exchange method facilitates conversion of these dispersions into inks, which can be reliably inkjet printed to produce highly uniform black phosphorus films without significant flake degradation. Parylene-C encapsulation of these films ensures their long-term stability (>30 days) when incorporated into photodetectors and lasers, operating under intense irradiation without any observed drop in performance over time. University of Cambridge 2019-09-05 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/315521 https://www.repository.cam.ac.uk/bitstreams/acb18da4-fb87-4e5a-9e7c-89743c7ca44c/download 84e57f0525611dad677de03b802e7ba5 https://www.repository.cam.ac.uk/bitstreams/d88fdf6a-88ab-47d3-b3a6-e9178bf767b3/download 353adac0d1ebdfd65ab16480263c3c87 https://www.rioxx.net/licenses/all-rights-reserved/ Nanotechnology Nanowires 2d Materials Semiconductor Engineering Applied Physics Optoelectronics Spectrometers

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Aggregation of alpha-synuclein using single-molecule spectroscopy 10.17863/CAM.8525 Iljina, Marija Klenerman, David The aggregation of alpha-synuclein (αS) protein from soluble monomer into solid amyloid fibrils in the brain is associated with a range of devastating neurodegenerative disorders such as Parkinson’s disease. Soluble oligomers formed during the aggregation process are highly neurotoxic and are thought to play a key role in the onset and spreading of disease. Despite their importance, these species are difficult to study by conventional experimental approaches owing to their transient nature, heterogeneity, low abundance and a remarkable sensitivity of the oligomerisation process to the chosen experimental conditions. In this thesis, well-established single-molecule techniques have been utilised to study the aggregation and oligomerisation of αS in solution. University of Cambridge 2017-03-23 Thesis Doctoral Doctor of Philosophy (PhD) en Dr Tayyeb Hussain Studentship, Christs College Cambridge https://www.repository.cam.ac.uk/handle/1810/263216 https://www.repository.cam.ac.uk/bitstreams/e70a814c-bb9d-4137-adf4-bb0af4ac63fb/download 87eda9de84448d1f82354d60eee3eb5f https://www.repository.cam.ac.uk/bitstreams/d0a198a3-bec6-468d-8aa4-96a4af28c77e/download 90146a56aab51b8810cf36d9f28556d1 https://www.rioxx.net/licenses/all-rights-reserved/ alpha-synuclein single-molecule FRET protein aggregation neurodegeneration

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Reassessing New Labour's Political Economy: A study of housing and regional economic policy 10.17863/CAM.95211 O'Shea, Jerry Sloman, Peter Kelly, Duncan This thesis is a study of housing policy and regional economic policy under Tony Blair and Gordon Brown, which uses interviews, archives, and public documents to explore the spatial dimension within New Labour’s wider political economy. It focusses particularly on the work of John Prescott’s Department of the Environment, Transport and the Regions (DETR)—which became the Department for Transport, Local Government and the Regions (2001-2) and the Office of the Deputy Prime Minister (2002-6)—and represents the first serious attempt to assess Prescott’s substantive impact on policymaking. The thesis argues that key New Labour figures thought about their political economic project as being more statist, interventionist, and Keynesian than political scientists or political economy ‘Anglo-liberal growth model’ scholars have contested. Support is lent to Jim Tomlinson and Ben Clift’s ‘New Keynesian’ description of New Labour’s broad political economic project. However, I push back against Tomlinson’s argument that delivering economic support for struggling regional economies was not deliberate or even articulated by New Labour. Rather, I demonstrate that John Prescott (1999) considered his super-departments, the Department for the Environment, Transport and the Regions and the Office of the Deputy Prime Minister, “very important economic department[s] […] massive deliverer[s], particularly when we have decided public expenditure is there to uphold the economy in the traditional Keynesian way”. Prescott used these departments to run a regionally selective economic strategy that enacted policies and realised institutions that Prescott had designed in 1982 as part of Labour’s ‘Alternative Economic Strategy’. Specifically, analysis of case studies such as the Regional Development Agencies and the Housing Market Renewal Pathfinders shows that these institutions were designed to provide swift intervention in both the supply and demand side of regional economies, while bypassing the complex and electorally sensitive issue of local government governance and spending. In addition, the findings demonstrate that for Brown and Balls, this regional economic policy part formed an important theoretical part of their ‘constrained discretion’ macroeconomic policy. Interviews, archival analysis, and lesser studied command papers and grey literature analysis reveal that Brown and Balls endorsed Prescott’s regional economic project as the regional component of the state’s arsenal in operating a discretionary monetary, fiscal, and interventionist policy. This policy, I argue, was explicitly intended to reduce rising regional inequalities and shelter the UK economy from the dangers of the vicissitudes of global financial markets and the “straitjacket” of the European Monetary Union and the EU’s regional policy. University of Cambridge 2022-08-01 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/347794 https://www.repository.cam.ac.uk/bitstreams/9492cbc9-bbd4-4962-8d31-8998f8e74d4e/download aa3b52de16c35d3ea0cd1b2a61418cdf https://www.rioxx.net/licenses/all-rights-reserved/ Ed Balls Gordon Brown housing policy John Prescott Labour Party regional policy

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Investigating anharmonic effects in condensed matter systems 10.17863/CAM.22695 Prentice, Joseph Charles Alfred 0000000196414643 Needs, Richard This thesis presents work done on the calculation of the effects of anharmonic nuclear motion on the properties of solid materials from first principles. Such anharmonic effects can be significant in many cases. A vibrational self-consistent field (VSCF) method is used as the basis for these calculations, which is then improved and applied to a variety of solid state systems. Firstly, work done to improve the efficiency of the VSCF method is presented. The standard VSCF method involves using density functional theory (DFT) to map the Born-Oppenheimer (BO) energy surface that the nuclei move in, a computationally expensive process. It is shown that the accurate forces available in plane-wave basis DFT can be used to help map the BO surface more accurately and reduce the computational cost. This improved VSCF+f method is tested on molecular and solid hydrogen, as well as lithium and zirconium, and is found to give a speed-up of up to 40%. The VSCF method is then applied to two different systems of physical interest. It is first applied to the case of the neutral vacancy in diamond, in order to resolve a known discrepancy between harmonic ab initio calculations and experiment -- the former predict a static Jahn-Teller distortion, whilst the latter leads to a dynamic Jahn-Teller effect. By including anharmonic corrections to the energy and nuclear wavefunction, we show that the inclusion of these effects results in agreement between first-principles calculations and experiment for the first time. Lastly, the VSCF method is applied to barium titanate, a prototypical ferroelectric material which undergoes a series of phase transitions from around 400 K downwards. The nature of these phase transitions is still unclear, and understanding them is an active area of research. We describe the physics of the phase transitions of barium titanate, including both anharmonicity and the effect of polarisation caused by long wavelength vibrations, to help understand the important physics from first principles. University of Cambridge 2018-05-19 Thesis Doctoral Doctor of Philosophy (PhD) en https://www.repository.cam.ac.uk/handle/1810/275467 https://www.repository.cam.ac.uk/bitstreams/b485776d-4b10-4f24-b336-5866b1342069/download 87eda9de84448d1f82354d60eee3eb5f https://www.repository.cam.ac.uk/bitstreams/855dea8a-411b-429a-81b9-141483612a5b/download d53b34e8b0af76500cc88aaff5bf69e6 https://www.rioxx.net/licenses/all-rights-reserved/ Computational physics Phonons Anharmonicity Vibrational self-consistent field method Barium titanate Defects in diamond Density functional theory

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The molecular, hormonal and symptomatic responses to hypoglycaemia in mice 10.17863/CAM.89461 Staricoff, Emily Evans, Mark I hypothesised that mouse models could be used to investigate the molecular, hormonal and symptomatic responses to acute and recurrent hypoglycaemia. To test this hypothesis, I used hyperinsulinaemic clamps to create carefully controlled experimental manipulations of blood glucose. It is well established that the hypothalamus plays a fundamental role in glucose sensing and coordination of the concerted effort to maintain blood glucose within a tight homeostatic range. However, little is known about the molecular changes that take place in the hypothalamus under conditions of hypoglycaemia or hyperglycaemia. Therefore, I aimed to use single-nucleus RNA sequencing (snRNAseq) to reveal the hypothalamic molecular signatures and gene expression profiles of different blood glucose levels. Hyperinsulinaemic clamps were used to create carefully controlled hypoglycaemic, euglycaemic and hyperglycaemic experimental interventions. Upon sequencing of the hypothalami, two thirds of nuclei were identified as neuronal. Across the dataset, there was relatively low expression of immediate early genes (IEGs), which could evidence support for the successful minimisation of experimentally induced stress during the hyperinsulinaemic clamp technique. Numerous genes that were differentially expressed under hypoglycaemic or hyperglycaemic conditions were identified. Increased understanding of the glucose responsive transcriptome in health will provide the basis for subsequent investigations into changes that take place in pathophysiological states, such as impaired awareness of hypoglycaemia (IAH). IAH resulting from recurrent exposure to hypoglycaemia (RH) remains a major obstacle when intensive insulin therapy is used to treat diabetes. RH can cause attenuation of the usual protective physiological (hormonal and behavioural) responses, termed hypoglycaemia associated autonomic failure (HAAF). HAAF has been reproduced experimentally in both humans and rats, however a mouse model of HAAF has not yet been comprehensively validated. In this thesis I found that four consecutive days of hypoglycaemia in mice was sufficient to significantly reduce hormonal responses to a subsequent hypoglycaemic episode, and therefore create a murine model of HAAF. Using this 4-day HAAF model I examined glucoprivic feeding to assess hunger, as an important symptom of hypoglycaemia awareness, and found a non-significant trend towards attenuation of the feeding response following HAAF induction. I also began to probe the neurocircuitry of IAH through designing and piloting an experimental paradigm to investigate restoration of HAAF. Validation of a murine HAAF model is essential to ensure future basic research is reproducible and accurately reflects the clinical condition. This will allow application of powerful modern molecular techniques to investigate neurocircuitry implicated in HAAF development. Improved mechanistic understanding of HAAF will facilitate the identification of potential therapeutic targets to either prevent the loss of, or restore, awareness to hypoglycaemia in the clinic. University of Cambridge 2022-07-21 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/342045 https://www.repository.cam.ac.uk/bitstreams/d2cdb8db-1094-433e-b8e2-6d9b4fee48d9/download f6c7128bc5ff057e1c08e8695a0ad20f https://www.repository.cam.ac.uk/bitstreams/143a0631-f0b8-494f-a668-73b21d85c698/download 830b620c40fe243145a0a4ddb72ee1a3 https://www.rioxx.net/licenses/all-rights-reserved/ Hypoglycaemia

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Science And Social Policy: Underpinning of Soviet Industrial Paradigms 10.17863/CAM.45820 Laumulin, Chokan 0000000173150104 Nolan, Peter Soviet policy-makers, in order to aid and abet industrialisation, seem to have chosen science as an agent for development. Soviet science, mainly through the Academy of Sciences of the USSR, was driving the Soviet industrial development and a key element of the preparation of human capital through social programmes and politechnisation of the society. This provided a broad set of the skills, including management and governance, multidisciplinary synthesis, and analytical ability which were required to ensure sustainable technical and industrial development. This process of human capital development in the USSR could not take place without a particular Soviet social policy which was designed by the Party and Government and included the development of science, education, healthcare in synchronisation. The success was achieved due to the implementation of the large programme for human capital development in whose preparation both basic research and education played the critical role. Science was regarded in the USSR as an indispensable tool for modernising the country, and, for the first time in world history, was recognised as a natural resource beyond the doctrine of Marxism which helped cope with the challenges, including industrialisation, WWII and the import substitution programme. The investments in the development of fundamental science eventually paid off both nationally and later - at the global level. Many of the Soviet scientific discoveries started to appear as products in global households only decades after the Soviet collapse. Without many Soviet discoveries and developments, the current digital and industrial development would be hardly possible as they are integral parts of the global technology chains which constitute the modern hi-tech industry, economy, and most various markets. University of Cambridge 2019-11-30 Thesis Doctoral Doctor of Philosophy (PhD) en https://www.repository.cam.ac.uk/handle/1810/298764 https://www.repository.cam.ac.uk/bitstreams/0d112e1e-b12b-481b-a29a-fe9c67767c79/download 127e34d48b605bb67b400f26711a7c5b https://www.repository.cam.ac.uk/bitstreams/8fafadc4-65ad-45ce-b39b-f4466aaa3b14/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ The Soviet Union Industrialisation Science Policy Social Policy Industrial Policy Polytechnic Education Innovation Chain Science and Development Polytechnisation Pyotr Kapitsa Abram Ioffe Physics and Industry School of Soviet Physics Industrial Kazakhstan Technology Transfer Soviet Space Programme The Academy of Sciences of the USSR Curiosity in Science Fundamental Science and Engineering Basic Research Technology and Innovation Superconductivity Laser Nikolay Basov Soviet Health Care The Alma-Ata Declaration Human Capital and Industrial Development Mstislav Keldysh

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The Social Life of Teen Attention: Navigating Citizenship, Schooling and the World Wide Web in Cochabamba, Bolivia and Warsaw, Poland https://doi.org/10.17863/CAM.113026 Buzanska, Katarzyna Lazar, Sian This thesis is an anthropological treatise on teenage attention based on ethnographic fieldwork at two urban schools in Cochabamba, Bolivia, and Warsaw, Poland. It proposes a socio-cognitive framework for an analysis of attention as a nexus comprised of ideological, bureaucratic, somatic, and affective elements as well as a form of practice that acts upon the world. I argue that youth are attentional agents capable of modifying their environment through attentional practice, which is, nevertheless structured by factors within the attentional nexus. I further argue that attentional practice has an intrinsically political character. The first section of this thesis considers the historical and institutional setting of my fieldsites and the import of combining psychological and anthropological perspectives on cognition towards an understanding of social phenomena at the collective level. In Chapter 1, I introduce the concept of the social attentionscape to speak of elements within a delineated society that come to the centre of collective attention and are likely to become part of political agendas, including educational policies. The social attentionscape is grounded in historically shaped value systems and world imaginaries endorsed by governments and civil society. In Bolivia, imaginaries of Western modernity and development have a strained coexistence with ideologies of decolonisation. In Poland, a nationalist and Catholic ideal of Polishness clashes with the urban ideal of liberal European citizenship. In Chapter 2, I consider how those imaginaries relate to quotidian practices at the school, guiding pedagogic orientations through the (re)production of teachers’ normative attention and interacting with on-the-stop attentional needs of exam bureaucracy in Warsaw and the local community in Cochabamba. The second section of the thesis examines three areas of alleged youth ‘disconnection’: political participation (Chapter 3), social media (Chapter 4), and the classroom (Chapter 5). Social media and digital marketing technologies are often considered root causes of bottomless distraction and youth disinterest. Without negating their attention-grabbing qualities, I flip the focus to the broader ecology of youth’s attention. I show how youth disenchantment in electoral politics is not tantamount to political disinterest. Political participation is contingent on attention-grabbing moral sentiments such as “the right to decide” (for Warsaw youth) or “the right to work” (for my interlocutors in Cochabamba). I analyse the sphere of teenage digital sociality in terms of the phatic attention mechanisms it engages but also recognise social media as an integral constituent of other spheres of attentional practice, influencing political decision-making and youth’s attention at school. Attention in the classroom is shaped by a nexus of institutional and social factors. Those affect the development of joint attention and mutual correspondence between students and teachers. The thesis contributes to long-established anthropological debates on the relationship between agency and structure and between global and local influences, considering their interaction in attentional management. It also speaks to the rather novel concern in anthropology of the politics of cognition by exploring how directions in collective and individual attention work to assemble, strengthen, and reshape local cultural landscapes and power relations, contributing to the reproduction and contestation of the discursive and institutional status quo. University of Cambridge 2024-05-17 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/375298 https://www.repository.cam.ac.uk/bitstreams/d728a5fa-111a-4140-bce1-b00a757dde97/download c7b10b144449d93ce1d8d77d16e9b83c https://www.repository.cam.ac.uk/bitstreams/871ec9a4-d5b5-42bc-9d27-23cb1cce889e/download 87eda9de84448d1f82354d60eee3eb5f https://creativecommons.org/licenses/by-nc/4.0/ Adolescence Attention Bolivia Poland Politics Schooling

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Public health approaches for identifying and responding to mental health difficulties amongst children and adolescents 10.17863/CAM.92625 Soneson, Emma 0000000316663012 Jones, Peter Fazel, Mina Howarth, Emma Summary Public health approaches for identifying and responding to mental health difficulties amongst children and adolescents Emma Soneson Mental health difficulties amongst children and adolescents are a significant societal concern requiring urgent attention and action, and public health approaches may be useful in reducing their incidence, prevalence, and impact. Schools are increasingly featured within UK policy as a key setting for addressing mental health difficulties, yet school staff often do not feel adequately prepared for this role. In this dissertation, I aimed to explore what role schools can play within the public health approach to child and adolescent mental health difficulties; determine whether schools can improve the identification of and response to mental health difficulties; and identify the ‘key ingredients’ of an effective, feasible, and acceptable school-based approach to student mental health. The introductory chapter provides an overview of the scope, aetiology, and impact of mental health difficulties amongst children and adolescents; describes the public health framework that supports the research in this dissertation; and highlights the role of schools within the public health approach to child and adolescent mental health difficulties. The first two empirical chapters present two studies that examined self-report data from the OxWell Student Survey to better understand English school students’ access to and perceptions of school-based and other mental health support. The first of these studies determined whether experience of adversity is related to access to and perceived need for mental health support amongst secondary school students. The second study explored whether various aspects of students’ school experience and their impressions of their wider school culture influence their perceptions of school-based mental health support. The next two chapters describe two studies aimed at improving UK primary schools’ response to pupil mental health difficulties. The first of these chapters describes a consensus study that contributed to the development of a new school-based identification programme. The second presents a feasibility study of an existing low-intensity teacher training programme that aimed to improve identification of and response to pupil mental health difficulties. In the first empirical chapter, I demonstrated that experience of adversity is significantly associated with both prior access to and perceived need for mental health support. This chapter illustrated how many children and adolescents who may benefit from mental health support, and particularly those with experience of adversity, are not accessing it. In the next chapter, I showed how schools may be able to address this care gap through school-based mental health provision, but that students’ perceptions of such support vary according to their school experience and impressions of their wider school culture. This suggested that the provision of mental health support is only one aspect of a broader school-based approach to mental health. In the next chapter, I described the development of the new identification programme guided by stakeholder consensus. The prototype programme features a ‘combined’ approach of staff training, mental health education for pupils, and (potentially) universal screening, and merits further development and evaluation. In the final empirical chapter, I demonstrated how an existing teacher training programme may be a potentially effective, feasible, and acceptable intervention for promoting more accurate identification and facilitating access to support for pupils with mental health difficulties. Taken together and as discussed in my final chapter, these findings provide valuable insight into the role of schools within the public health approach to child and adolescent mental health difficulties. First, the included studies illustrated several ways that schools can be involved in prevention and early intervention. Second, the studies demonstrated that schools do have significant potential to improve both identification of and response to mental health difficulties. Finally, the findings of this dissertation suggested five ‘key ingredients’ for school-based approaches to mental health, including (1) contextualisation of all mental health interventions within a wider school culture that values mental health; (2) identification and management of barriers to intervention implementation and sustainability; (3) support from wider systems; (4) attention to the needs of vulnerable children and adolescents; and (5) partnership working with key stakeholders. It is paramount that schools are supported and empowered to take an increased role in child and adolescent mental health. University of Cambridge 2022-08-09 Thesis Doctoral Doctor of Philosophy (PhD) eng Gates Cambridge Trust; UKRI Emerging Minds Network https://www.repository.cam.ac.uk/handle/1810/345205 https://www.repository.cam.ac.uk/bitstreams/3ece8ab0-2bb9-49c3-901c-409b3f450ae8/download 0eb294cc87a4ac54af646a16b9e887d4 https://www.rioxx.net/licenses/all-rights-reserved/ adolescents children mental health public health schools

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Characterising disease-related and developmental changes in correlation-derived structural and functional brain networks 10.17863/CAM.25157 Váša, František Bullmore, Edward T. 0000000289558283 Human structural and functional brain architecture is increasingly studied by applying the mathematical framework of complex networks to data from magnetic resonance imaging. Connections (edges) in such brain networks are commonly constructed using correlations of features between pairs of brain regions, such as regional morphology (across participants) or neurophysiological time series (within participants). Subsequent analyses frequently focus on summary network statistics calculated using the strongest correlations, but often neglect potential underlying shifts within the correlation distribution. This thesis presents methods for the construction and analysis of correlation-derived structural and functional brain networks, focusing on the implications of changes within the correlation distribution. First, schizophrenia is considered as an example disease which is known to present a reduction in mean correlation between regional neurophysiological time series. Previous studies reported increased network randomisation in schizophrenia, but these results may have been driven by inclusion of a greater number of noisy edges in patients’ networks, based on retention of a fixed proportion of the strongest edges during network thresholding. Here, a novel probabilistic thresholding procedure is applied, based on the realisation that the strongest edges are not necessarily most likely to be true following adjustment of edge probabilities for effects of participant in-scanner motion. Probabilistically thresholded functional networks show decreased randomness, and increased consistency across participants. Further, applying probabilistic thresholding eliminates increased network randomisation in schizophrenia, supporting the hypothesis that previously reported group differences originated in the application of standard thresholding approaches to patient networks with decreased functional correlations. Subsequently, healthy adolescent development is studied, to help understand the frequent emergence of psychiatric disorders in this period. Importantly, both structural and functional brain networks undergo maturational shifts in correlation distribution over adolescence. Due to reliance of structural correlation networks on a group of subjects, previous studies of adolescent structural network development divided groups into discrete age-bins. Here, a novel sliding-window method is used to describe adolescent development of structural correlation networks in a continuous manner. Moreover, networks are probabilistically thresholded by retaining edges that are most consistent across bootstrapped samples of participants, leading to clearer maturational trajectories. These structural networks show non-linear trajectories of adolescent development driven by changes in association cortical areas, compatible with a developmental process of pruning combined with consolidation of surviving connections. Robustness of the results is demonstrated using extensive sensitivity analyses. Finally, adolescent developmental changes in functional network architecture are described, focusing on the characterisation of unthresholded (fully weighted) networks. The distribution of functional correlations presents a non-uniform shift over adolescence. Initially strong cortical connections to primary sensorimotor areas further strengthen into adulthood, whereas association cortical and subcortical edges undergo a subtler reorganisation of functional connectivity. Furthermore, individual subcortical regions show distinct maturational profiles. Patterning of maturation according to known functional systems is affirmed by partitioning regions developing at similar rates into maturational modules. Taken together, this thesis comprises novel methods for the characterisation of disease-related and normative developmental changes in structural and functional correlation brain networks. These methods are generalizable to a wide range of scenarios, beyond the specific disease and developmental age-ranges presented herein. University of Cambridge 2018-07-21 Thesis Doctoral Doctor of Philosophy (PhD) en Gates Cambridge Trust https://www.repository.cam.ac.uk/handle/1810/277816 https://www.repository.cam.ac.uk/bitstreams/022c0998-5775-4ba3-9677-ac09f7e3651a/download 0c816cf00c42d5395f469ca0de854fa7 https://www.repository.cam.ac.uk/bitstreams/e7a81192-590a-45b2-9d0b-cc3c4b7eacc5/download 87eda9de84448d1f82354d60eee3eb5f https://creativecommons.org/licenses/by-nc-nd/4.0/ neuroimaging connectome brain network MRI adolescence development schizophrenia graph theory magnetic resonance imaging correlation

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Enantio- and diastereocontrol with silicon compounds in organic synthesis 10.17863/CAM.19586 Crump, Roger Adrian Neil Callow University of Cambridge 1993-01-01 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/272577 controlled.access https://www.repository.cam.ac.uk/bitstreams/d9dde802-b92e-40c2-ad96-0e9246e34927/download 5cb0c75cacbb70a149287d80c4ce7f68 https://www.repository.cam.ac.uk/bitstreams/c3b76f14-3c6f-4870-8c6e-8a7af4b868dd/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/

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Female Equestrian Culture in France, 1600-1715 10.17863/CAM.58333 Zanetti, Valerio Rublack, Ulinka This dissertation investigates female equestrianism in France between 1600 and the end of Louis XIV’s reign in 1715. The introduction situates the study of female horseback riding within the scholarship on early modern women’s sport, elite femininity and corporeal culture in seventeenth-century France. It also positions the analysis of equestrian garments within current trends in fashion and dress history. Chapter I examines definitions of female athleticism in medical and pedagogic literature. It highlights how traditional humoral models of the body and conservative views of women’s education gradually made space for new progressive conceptualisations of the female ‘Amazonian’ athletic body. Chapter II starts by reassessing the significance of equestrianism within French aristocratic culture, emphasising its role as an elite medical practice. It then traces the development of female horse-riding techniques in the seventeenth century. Chapter III explores the social and political significance of female horse riding in seventeenth-century France with reference to aristocratic women’s lives. The first part shows how, far from being exclusively associated with hunting, riding was connected with crucial economic and military functions. The second part focuses on the court of Louis XIV and highlights how female horse riding moved beyond hunting conventions and established itself as an independent athletic practice. Chapter IV explores the evolution of female riding attire, revealing how liberating forms of dress were created to suit new spaces of corporeal freedom. First, it examines the donning of riding breeches and the fashion for a particular ‘Amazonian’ feather headdress in the mid-seventeenth century. It then traces the emergence of a recognisable tailored outfit that represented the first sporting uniform for women. The conclusion outlines how, by the turn of the eighteenth century, the ‘Amazonian’ French horsewoman had been fashioned into a powerful and influential ideal of athletic femininity. University of Cambridge 2020-10-28 Thesis Doctoral Doctor of Philosophy (PhD) eng AHRC Cambridge Trust https://www.repository.cam.ac.uk/handle/1810/311239 https://www.repository.cam.ac.uk/bitstreams/54a3bfd4-5493-4456-8b25-c95f990e3150/download 31b87bff5e479eae2d6fc41ecfdeb58a https://www.repository.cam.ac.uk/bitstreams/4ac81a5b-c927-496c-a4df-4f1d56d824c7/download 353adac0d1ebdfd65ab16480263c3c87 https://www.rioxx.net/licenses/all-rights-reserved/ Sport History Court Studies Early Modern France Equestrianism Fashion History

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Functional Metal Oxide Coatings from Molecular Precursors for Energy Applications https://doi.org/10.17863/CAM.100062 Riesgo Gonzalez, Victor 0000000224338562 Wright, Dominic Grey, Clare The ability to create and optimise new interfaces is essential to develop and optimise materials for use in sustainable energy storage and conversion technologies. In this thesis, the solution-deposition of coatings from molecular precursors is explored as a promising approach towards this end. First, a facile method for the deposition of electrocatalytically active zirconium-based films for photoelectrochemical water oxidation is developed. The films were derived from three novel alkoxy cage compounds containing Zr and a first-row transition metal (Co, Fe or Cu). The deposition of a Co-doped ZrO₂ coating onto the BiVO₄ photoanode lowers its onset potential by 0.12 V to 0.21 V vs. the reversible hydrogen electrode (RHE) and increases the maximum photocurrent density by ∼50% to 2.41 mA cm^-2 compared to the uncoated BiVO₄. In the next chapter, a new solution deposition method to coat the Li-ion battery cathode LiNi_0.8Mn_0.1Co_0.1O₂ (NMC811) with Al₂O₃ using aluminium isopropoxide (AIP) is developed. High-field solid-state nuclear magnetic resonance spectroscopy (SSNMR) probes the formation of γ-LiAlO₂ at 600 °C and doping of aluminium into NMC811 starting at 500 – 600 °C. NMC811 coated with amorphous Al₂O₃ (200 – 400 °C) had a capacity retention comparable to pristine NMC811, while higher annealing temperatures led to more crystalline coatings and surface Al-doping which were found to increase the rate of degradation of NMC811 upon cycling. Finally, LiAlO₂ coatings are deposited onto NMC811 using heterobimetallic alkoxides: LiAl[(OCH₂Ph)₄], LiAl[(OⁱPr)₄] and LiAl[(O^tBu)₄]. The later showing the most promise as a coating precursor due to its high solubility in tetrahydrofuran (THF), low temperature decomposition (283 °C) and reaction with hydroxyl groups present on the surface of NMC811. This coating was tested on polycrystalline NMC811 (PC-NMC811) and Al₂O₃ coated single-crystal NMC811 (Al₂O₃/SC-NMC811). Significant improvements in capacity retention (17.2% more C/2 capacity retained after 107 cycles vs. Al₂O₃/SC-NMC811) were seen in the LiAlO₂/Al₂O₃/SC-NMC811 system. Furthermore, coating PC-NMC811 that was previously degraded by soaking in water improved the capacity retention (50.1% more capacity retention at C/2 after 215 cycles vs. uncoated PC-NMC811 soaked in water and annealed at 400 °C) suggesting that the combination of a LiAlO₂ coating and subsequent annealing step can recover NMC811 surfaces that have been previously degraded by soaking in water. University of Cambridge 2023-03-28 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/354053 https://www.repository.cam.ac.uk/bitstreams/aacaf5d0-b660-40ae-af64-336cf7766929/download fb11570e508df68bbcbb1c36b5542723 https://www.repository.cam.ac.uk/bitstreams/0954b7c9-ef66-472d-9f1d-82562a96b26f/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ Batteries Chemistry Coatings Deposition Electrocatalysis Electrochemistry Inorganic Materials Molecular Oxides Precursors Single-source Synthesis

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Natural Language Understanding and Generation for Task-Oriented Dialogue 10.17863/CAM.84040 Tseng, Bo-Hsiang Byrne, William The success of deep learning methods has stimulated the rapid development of many NLP research areas. Still, task-oriented dialogue modelling remains challenging due to both the inherent complexity of human language and task difficulty. Moreover, building such systems usually relies on large amounts of data with fine-grained annotations, and in many situations, it is difficult to obtain such data. It is thus important for dialogue systems to learn efficiently in low-resource scenarios so that the models can still effectively fulfill their tasks. This thesis aims to provide novel methods to tackle these difficulties in dialogue modelling. To communicate, most commonly, a dialogue system converts a semantic representation (e.g., a dialogue act) into natural language in a process known as Natural Language Generation (NLG). A tree-based NLG model is proposed and shown to be more easily adapted to unseen domains in comparison to other models. This desirable property arises due to the fact that modelling semantic structure facilitates knowledge sharing between source and target domains. We also show that the NLG task can be jointly learned with its dual task, the natural language understanding (NLU), which maps natural language utterances to semantic counterparts. Our approach consists of a stochastic generative model with a shared latent variable for two tasks, which can be trained with significantly less data than individual components. The focus then shifts to a more general setup of dialogue generation. In end-to-end dialogue modelling, systems consume user utterances and learn to directly generate responses, where intermediate dialogue acts are usually used as auxiliary learning signals for model optimisation. We show that semi-supervised methods that were proposed for computer vision tasks can be beneficial to dialogue modelling. We also address the problem of developing dialogue systems when little training data is available. To this end, we propose a learning framework where user and dialogue models are jointly optimised. We show that the data generated by their interaction can be used to further optimise the two models and leads to improved model performance. Yet again, this approach reduces the amount of data for end-to-end dialogue modelling on low-resource domains. Lastly, an understanding model is proposed to address the prevalent phenomena of coreference and ellipsis in dialogues. This model first performs coreference resolution and then rewrites the input user utterance into a complete sentence that resolves coreferent entities and omitted information. As a side contribution, the acquired data for model training is released to the research community. University of Cambridge 2021-09-01 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/336619 https://www.repository.cam.ac.uk/bitstreams/f95cd2d1-680b-4235-8ddd-44a627db5982/download b70225ef6a11226af440c014c39a07b8 https://www.rioxx.net/licenses/all-rights-reserved/ task-oriented dialogue machine learning natural language processing natural language understanding natural language generation

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Standard model physics from an algebra? 10.17863/CAM.37465 Furey, C This thesis constitutes a first attempt to derive aspects of standard model particle physics from little more than an algebra. Here, we argue that physical concepts such as particles, causality, and irreversible time may result from the algebra acting on itself. We then focus on a special case by considering the algebra $\mathbb{R}\otimes\mathbb{C}\otimes\mathbb{H}\otimes\mathbb{O}$. Using nothing more than $\mathbb{R}\otimes\mathbb{C}\otimes\mathbb{H}\otimes\mathbb{O}$ acting on itself, we set out to find standard model particle representations. From the complex quaternionic portion of the algebra, we find generalized ideals, and show that they describe concisely all of the Lorentz representations of the standard model. From the complex octonionic portion of the algebra, we find minimal left ideals, and show that they mirror the behaviour of a generation of quarks and leptons under $su(3)_c$ and $u(1)_{em}$. We then demonstrate a rudimentary electroweak model which yields a straightforward explanation as to why $SU(2)_L$ acts only on left-handed states. This holds in the case of leptons. Finally, we demonstrate how $\mathbb{C}\otimes\mathbb{O}$ can generate a 64-$\mathbb{C}$-dimensional algebra, wherein we find the $SU(3)_c$ irreducible representations corresponding to three generations of quarks and leptons. We then conclude by showing how to arrive at all 48 electric charges. Thesis eng https://www.repository.cam.ac.uk/handle/1810/292005 https://www.repository.cam.ac.uk/bitstreams/f5e4bbbd-bb43-47e1-9ede-09d59854e167/download c83c365b9d4030a8ed92c0034c3c9305 https://www.repository.cam.ac.uk/bitstreams/2197ef55-c717-4aff-93ea-2a989280e697/download dc15e953c5bb65731138629ef41004fc hep-th hep-th math-ph math.MP

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Hybrid Simulation Modelling to Support the Development of Recycling Infrastructures 10.17863/CAM.79201 Purnama, Aloisius Rabata Barlow, Claire 0000000151039851 An enormous amount of waste material arises internationally due to linear economic structures in which natural materials are converted into products which are discarded after use. This problem could be addressed by a shift towards a circular economy, whereby products are kept in use for longer and the material is recovered at end-of-life as a valuable resource. Recycling is therefore central to the development of a circular economy. However, recycling levels are low in many countries, often due to lack of recycling infrastructures. This research aims to support the development of waste management and recycling infrastructures by developing a model to experiment with new systems, particularly looking at the balance between centralised and delocalised systems for collection, sorting and recycling. The model utilises hybrid simulation modelling due to the accuracy and flexibility that the method provides. The model was developed using an agent-based architecture which includes three submodels to describe the process, logistics, and communication. With this architecture, the model has the capability to simulate a wide range of waste management systems. The frameworks developed in this research provide a new approach to using hybrid simulation modelling. Moreover, the frameworks can be used as guidelines for the development of future tools and models. The model was implemented into two case studies, in different geographic locations. The first case study investigated the waste management structures in Singapore and compared the performance of centralised and distributed systems. The results showed that the facility processes are more favourable in a centralised system due to economies of scale. On the other hand, the logistics perform better in a distributed system. The balance between centralised and distributed structures can be analysed using the model developed in this research, informing decision-making processes for future developments. The second case study applied the model to analyse the potential for introducing new waste management infrastructures in Indonesia, working with a company currently tasked with reducing waste mismanagement in small cities and rural areas. The results validated the model capability in experimenting with new systems and offered insights into the relative performance of centralised and distributed waste management systems. The work has provided a valuable additional dimension to the feasibility studies and contributes to the recommendations. Both case studies have demonstrated the viability and applicability of this hybrid simulation model as a tool that can be adapted to optimise waste management infrastructures in different environments. University of Cambridge 2021-08-20 Thesis Doctoral Doctor of Philosophy (PhD) eng Jardine Foundation https://www.repository.cam.ac.uk/handle/1810/331752 https://www.repository.cam.ac.uk/bitstreams/c2a1b292-6d10-41e5-8c31-ff0839b0ea88/download f80053bad7a3f82e799ed5373e830258 https://www.rioxx.net/licenses/all-rights-reserved/ Waste management Recycling Simulation modelling Circular economy

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Characterisation of polymers using laser microprobe mass spectrometry 10.17863/CAM.19255 Cunningham, Paul John University of Cambridge 1992-01-01 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/272246 controlled.access https://www.repository.cam.ac.uk/bitstreams/3e126135-ca07-4b84-90d9-1c9b9b0a20a2/download 858cac010af315624c3aced25aa10d76 https://www.repository.cam.ac.uk/bitstreams/274c1ef9-c18d-48a0-9d12-88dac347bb39/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/

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Absorption spectroscopy and atomistic modelling on nitride semiconductors 10.17863/CAM.31321 Zhang, Siyuan, University of Cambridge 2014-04-29 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/283955 controlled.access https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/4a6fd328-213f-43bb-a511-008bc411bb36/download 5fa56e6d222b2c76d5b5262961fe888e https://www.rioxx.net/licenses/all-rights-reserved/

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Data Flows & Menstruation: How Users of Period Trackers Navigate the Datafication & Commodification of their Menstrual Cycles https://doi.org/10.17863/CAM.110745 Felsberger, Stefanie Wilcox, lauren My PhD explores how users of cycle trackers access information about their menstrual cycles and how they understand and navigate data commodification in their everyday lives through a data justice approach. The commodification of user data is portrayed as an all-encompassing, totalising “version” of capitalism. By shifting the focus from the logic of data commodification to the ways in which people navigate this system, I contribute to a different understanding of how value is accrued from data in the digital economy. A focus on CTA users is especially useful because: first, the data these apps collect are more valuable than most user data; second, the bodies of people who menstruate have historically been controlled for in order to extract free reproductive labour. Guided by Participatory Action Research methodologies (PAR), I interviewed 30 app users in Vienna. Through a data justice lens, I introduce questions of power inequalities to discourses on privacy, moving beyond a focus on individual rights and ownership of data to address material aspects of and injustices built into data infrastructures. To do so, my PhD moves through three overarching and interconnected lines of inquiry. First, I ground my inquiry by analysing the context in which the datafication of menstrual cycles intervenes: how do people access knowledge and information about menstrual cycles. How is knowledge about menstruation shaped, controlled, and limited? I argue that menstrual knowledge is deeply shaped by ideas of normality, the imperative to conceal one’s menstrual status, and demands for menstrual management. I discuss how participants navigated these three factors to learn about their cycles. Second, I turn my attention to the use of CTAs. I investigate why and how participants find CTAs useful and essential, contributing a new understanding menstrual tracking through the lens of menstrual management. Simultaneously, I question what ways of knowing menstruation CTA data can provide users. I demonstrate that CTAs are designed for a cis-heterosexual user in monogamous relationships with a normative regular cycle and contribute a novel contextualisation of CTAs in the historical effort to make menstruation calculable and reproduction plan-able. I contribute insights into how the data- driven lens of menstruation and encoding of Norma’s cycle shape how participants track. Third, I pose two interconnected questions. How people encounter and navigate this system of data extraction in the context of their menstrual data? I argue that users strike a deliberate bargain whereby they exchange their data for a tool to manage menstruation. I argue that CTAs datafy and commodify users’ social reproductive work of managing menstruation. I contribute a different lens into how data capitalism is experienced and sustained through the lens of CTA users. Additionally, I ask how participants understand the value of the (menstrual) data they generate which are accumulated by CTAs? I argue that due to users’ experience of menstrual stigma and concealment, they assume data about menstruation to be of little to no interest in the context of data capitalism, contrary to how valuable menstrual data actually are. University of Cambridge 2024-12-20 Thesis Doctoral Doctor of Philosophy (PhD) eng Cambridge Trust ESRC https://www.repository.cam.ac.uk/handle/1810/371615 https://www.repository.cam.ac.uk/bitstreams/7b5b9072-dcee-488d-a05d-1665eb846a49/download 36ffe56e60c7c9a3d36ebdc1d4262954 https://www.repository.cam.ac.uk/bitstreams/3ffa7fc6-47d0-4027-b27b-a2a73bebf2bd/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ data justice datafication gender labour menstruation self-tracking technology

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Terrorism, Law, and Sovereignty in India and the League of Nations, 1897-1945 10.17863/CAM.13806 McQuade, Joseph Harper, Tim This research examines the emergence of terrorism as a legal and political category in late colonial India from 1897 to 1946. Chapter 1 traces debates surrounding laws of sedition from the 19th century and follows these laws into the early twentieth century, where they come to be viewed as increasingly inadequate in dealing with the unprecedented challenge presented to the colonial regime by secret societies using bomb assassinations against the government. Chapter 2 then examines how these discussions change in the context of the First World War, when a language of war and concerns regarding third party German involvement provide the opportunity for the imperial government to strengthen its emergency laws by legislating against 'conspiracy'. Chapter 3 demonstrates how, following the end of the war, conspiracy became itself viewed as an inadequate term and officials made a conscious decision to present revolutionaries under the label of 'terrorism' in subsequent speeches. This continued into the early 1930s, where laws in India began to target terrorism as a discrete category of crime, in legislation such as the Suppression of Terrorism Outrages Act of 1932. Chapter 4 situates this process within the context of the international system of the interwar period, first exploring India's under-studied relationship with the League of Nations and then indicating how this relationship became a point of critique for those labelled by the government as terrorists, particularly the Bengali revolutionary Rash Behari Bose. Chapter 5 shows how the discussions surrounding the Convention for the Prevention and Punishment of Terrorism in 1937, the world's first international law to target terrorism as a discrete category of crime, reflected many of the concerns that animated discussions in India. The chapter also examines India's role in the Convention, as the only member-state of the League to ultimately ratify the treaty. University of Cambridge 2017-10-01 Thesis Doctoral Doctor of Philosophy (PhD) en Gates Scholar, Gates Cambridge Trust https://www.repository.cam.ac.uk/handle/1810/267882 https://www.repository.cam.ac.uk/bitstreams/c976f2c6-d388-41c7-9a1a-bd4d8523178b/download 87eda9de84448d1f82354d60eee3eb5f https://www.repository.cam.ac.uk/bitstreams/8ca83933-487b-4ff0-b533-acc8193631be/download fe7c1aad2507614658f0fc48f967ce4e https://www.rioxx.net/licenses/all-rights-reserved/ India Terrorism League of Nations

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The History, Ideology, and Organisation of the Rashtriya Swayamsevak Sangh in the post-colonial India, 1948–1991 https://doi.org/10.17863/CAM.115579 Chaudhary, Neha Sen, Samita This thesis explores the postcolonial history of the Sangh that marked its ascendancy from a marginal paramilitary organisation in the late 1940s to the apex organisation of the Hindu Nationalist movement with a dense network of branches, cadres, and subsidiaries by the 1990s. This thesis gives precedence to the Sangh’s dynamic and malleable character to elucidate its survival and expansion in these five decades, which goes beyond the existing academic arguments that focus on factors external to the Sangh (the socio-political developments of the 1980s) and its ideological puritanism to explain the ‘rise’ of Hindu Nationalism in the late 1980s. Thus, this thesis argues that the Sangh’s dynamism, marked by its ability to act as an organisation that is cultural and political, Brahminical and caste-conciliatory and, violent and welfarist simultaneously, was the result of a distinct turn under the leadership of the Sangh’s third chief, M.D. Deoras. Deoras framed Hindu nationalist politics in the language of civic nationalism, allowing the Sangh to expand its narrow cultural Hindu nationalism to include civic ideas of constitutionalism, democracy, social welfare and caste emancipation. While the RSS showed a readiness for change even during the first two decades of its postcolonial history, Deoras’s ideological interventions amplified its tendencies to engage itself with contradictory political discourses and figures. By complicating the relationship between civic and ethnic nationalisms, this thesis not only enriches the expanding literature on Hindu Nationalism in India but also contributes significantly to the understanding of how organisations on the far right have been able to survive and thrive under democratic structures. University of Cambridge 2024-07-28 Thesis Doctoral Doctor of Philosophy (PhD) eng Cambridge Trust, Faculty of History and Newnham College https://www.repository.cam.ac.uk/handle/1810/379500 embargo 2030-03-11 https://www.repository.cam.ac.uk/bitstreams/dfa99158-8e2f-4493-b15a-85cf3a4ed89d/download f99ab7c28026e08ceb841b4201c93681 https://www.repository.cam.ac.uk/bitstreams/1e653482-d338-4600-8678-08bbbda316b8/download 87eda9de84448d1f82354d60eee3eb5f http://purl.org/NET/rdflicense/allrightsreserved Hindu Nationalism Post-colonial India Hindutva Ethnic nationalism

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The elaborate interplay of natural killer cells and vaccinia virus 10.17863/CAM.60487 Depierreux, Delphine Marie-France C Smith, Geoffrey L Ferguson, Brian 0000000268731032 Vaccinia virus (VACV) is a poxvirus and is the vaccine used to eradicate smallpox. It is also an expression vector for heterologous antigens and an oncolytic virus for cancer therapy. VACV encodes multiple proteins that aid evasion of the host immune response. There is, however, an incomplete understanding of how this immune suppression by VACV is consistent with such a strong immune response and subsequent memory. There is especially little known about the relationship between natural killer (NK) cells and VACV. Previous studies showed that during VACV infection, NK cells proliferate, are activated, limit viral replication, kill VACV-infected cells and display memory-like qualities. However, how NK cells recognise and interact with VACV-infected cells, which ligand(s) trigger NK cell activation, which NK receptors (NKR) are involved, and whether VACV uses strategies to interfere with the NK cell response remains elusive. This thesis aimed to address such questions using screening methods in parallel to candidate-based approach to tackle the challenges caused by the high diversity of NKRs and NK ligands. First, the responsiveness of murine NK cells to systemic VACV infection was studied ex vivo. Transcriptomic analysis, along with validation at the protein level, indicated NK cell activation and preparedness to mediate effector functions. Analysis of NK cell transcriptomic signature indicated that the stimuli triggering NK cell activation in the context of VACV infection correspond primarily with direct cell recognition but also cytokines such as Il-12 and -18, and IFNs. NKRs expression level in response to VACV was investigated, both at the transcript and protein level, and candidate NKRs involved specifically in the response to VACV were defined. Using a published dataset, the human and murine NK cell response to VACV was compared, revealing strong similarities. Second, the modulation of the plasma membrane (PM) proteome after VACV infection was studied using a proteomic screen that allowed to i) determine how VACV affects NK ligands expression; ii) give insights into VACV host surface protein modulation mechanism; iii) highlight previously unrecognised VACV strategies to evade NK cell response, iv) establish for the first time, a comprehensive analysis of VACV proteins expressed at the host PM and, v) suggest VACV surface proteins that potentially engage with NK cells. Third, the impact of the absence of VACV A56, an NK ligand candidate, and the murine natural cytotoxicity receptor (NCR) NKp46, were studied, in vitro and in vivo, in the context of VACV infection. This confirmed that VACV A56 prevents cell fusion, anchors VACV K2 and VCP (virus complement control protein) at the cell surface and enhances the binding of human and murine NCRs to VACV-infected cells. Further, it revealed that A56 deletion did not affect plaque size or EEV (extracellular enveloped virus) release, did not alter NK ligands surface expression, but led to decreased VACV-infected cells killing by murine NK cells. Lastly, the impact of VACV A56 and NKp46 deletion, on VACV infection outcome were assessed in vivo, in the acute and the memory stage and did not reveal substantial differences. Collectively, these data constitute a valuable resource concerning the interaction of VACV with NK cells and the factors influencing their interplay. These data can contribute to improve the development of VACV-based vaccines vectors and oncolytic viruses, and further our understanding of host-pathogen interactions. University of Cambridge 2020-04-01 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/313379 https://www.repository.cam.ac.uk/bitstreams/f0008685-0c76-4d9d-adea-a0a68ac15a11/download b012d162555176eceb3d8600d5cdc074 https://www.repository.cam.ac.uk/bitstreams/a2dd7f3c-f4f5-4e3c-b875-627f8a2727c0/download 353adac0d1ebdfd65ab16480263c3c87 https://www.rioxx.net/licenses/all-rights-reserved/ vaccinia virus natural killer cell host-pathogen interactions

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Environmental change impacts on shell formation in the muricid Nucella lapillus 10.17863/CAM.89105 Mayk, Dennis 0000000250171495 Harper, Elizabeth Peck, Lloyd Environmental change is a significant threat to marine ecosystems worldwide. Ocean acidification, global warming and long-term emissions of anthropogenic effluents are all negatively impacting aquatic life. Marine calcifying organisms, in particular, are expected to be severely affected by decreasing seawater pH, resulting in shell dissolution and retardations during the formation and repair of shells. Understanding the underlying biological and environmental factors driving species vulnerabilities to habitat alterations is thus crucial to our ability to faithfully predict impacts on marine ecosystems under an array of environmental change scenarios. So far, existing knowledge about organism responses mainly stems from short to medium term laboratory experiments of single species or over- simplified communities. Although these studies have provided important insights, results may not translate to organism responses in a complex natural system requiring a more holistic experimental approach. In this thesis, I investigated shell formation mechanisms and shape and elemental composition responses in the shell of the important intertidal predatory muricid Nucella lapillus both in situ and across heterogeneous environmental gradients. The aim was to identify potential coping mechanisms of N. lapillus to environmental change and provide a more coherent picture of shell formation responses along large ecological gradients in the spatial and temporal domain. To investigate shell formation mechanisms, I tested for the possibility of shell recycling as a function to reduce calcification costs during times of exceptional demand using a multi-treatment shell labelling experiment. Reports on calcification costs vary largely in the literature. Still, recent discoveries showed that costs might increase as a function of decreasing calcification substrate abundance, suggesting that shell formation becomes increasingly more costly under future environmental change scenarios. However, despite the anticipated costs, no evidence was found that would indicate the use of functional dissolution as a means to recycle shell material for a more cost-efficient shell formation in N. lapillus. To investigate shell formation responses, I combined morphometric and shell thickness analyses with novel statistical methods to identify natural shape and thickness response of N. lapillus to large scale variability in temperature, salinity, wind speed and the carbonate system across a wide geographic range (from Portugal to Iceland) and through time (over 130 years). I found that along geographical gradients, the state of the carbonate system and, more specifically, the substrate inhibitor ratio ([HCO3−][H+]−1) (SIR) was the main predictor for shape variations in N. lapillus. Populations in regions with a lower SIR tend to form narrower shells with a higher spire to body whorl ratio. In contrast, populations in regions with a higher SIR form wider shells with a much lower spire to body whorl ratio. The results suggest a widespread phenotypic response of N. lapillus to continuing ocean acidification could be expected, affecting its phenotypic response patterns to predator or wave exposure regimes with profound implications for North Atlantic rocky shore communities. On the contrary, investigations of shell shape and thickness changes over the last 130 years from adjacent sampling regions on the Southern North Sea coast revealed that contrary to global predictions, N. lapillus built continuously thicker shells while maintaining a consistent shell shape throughout the last century. Systematic modelling efforts suggested that the observed shell thickening resulted from higher annual temperatures, longer yearly calcification windows, nearshore eutrophication, and enhanced prey abundance, which mitigated the impact of other climate change factors. An investigation into the trace elemental composition of common pollutant metals in the same archival N. lapillus specimens revealed that shell Cu/Ca and Zn/Ca concentration ratios remained remarkably constant throughout the last 130 years despite substantial shifts in the environmental concentration. However, Pb/Ca concentration ratios showed a definite trend closely aligned with leaded petrol emissions in Europe over the same period. Discussing physiological and environmental drivers for the observed shell bound heavy metal patterns, I argue that, unlike for Pb, constraints on environmental dissolved Cu species abundance and biologically mediated control on internal Zn levels were likely responsible for a decoupling of shell-bound to total ambient Cu and Zn concentrations. The results highlight the complexity of internal and external pathways that govern the uptake of heavy metals into the molluscan shell and suggest that the shell of N. lapillus could be a suitable archive for a targeted investigation of Pb pollution in the intertidal zone. University of Cambridge 2022-07-01 Thesis Doctoral Doctor of Philosophy (PhD) eng NE/L002507/1 https://www.repository.cam.ac.uk/handle/1810/341684 https://www.repository.cam.ac.uk/bitstreams/d565a02a-7d8d-449e-a1bb-bcc308377c14/download 037577844ac9e8589b9d6dd85245f7d2 https://www.rioxx.net/licenses/all-rights-reserved/ environmental change biomineralisation shell plasticity climate change intertidal

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A theory of Greek colonisation : EIA Thrace and initial Greek contacts. 10.17863/CAM.11622 Owen, Sara Susan The study of Greek colonisation is still dominated by Hellenocentric and Imperialist approaches. Furthermore, culture historical methodologies are still common. Studies often prioritise Imperialist readings of Greek literature, and even (as demonstrated here) restore fragments of Archilochos according to these assumptions. They also demonstrate a reified view of ethnicity, particularly in their adherence to the model of 'Hellenisation'. This thesis attacks the colonialist assumptions which pervade even the more theoretically sophisticated literature on the subject. Instead it attempts to provide a theoretically-informed account of the Greek settlement of Thrace, a region complicated by the presence of a divisive national frontier between Greece and Bulgaria. It rejects the Hellenocentric models and attempts to contextualise the first material evidence of Thracian contacts with Greeks. In so doing, thiss tudy demonstrates that first contacts with Greeks must be seen in the context of profound social (in which are embedded technological and economic) changes within Thrace which led to the active seeking out of exotic objects on the part of nascent elites. It does this through the media of studies on the adoption of iron, landscape, megaliths and burial in Early Iron Age Thrace, and a case study of burial, settlement and cult evidence from the island of Thasos. This thesistherefore has wider implications than just for the study of the Early Iron Age, or Greek 'colonisation' of this area. It demonstrates that the local social context is crucial to understanding the nature of the phenomenon of Greek colonisation. More than that, it demonstrates that the local context and local populations can no longer be seen as tabulae rasae for the imposition of Greek culture. University of Cambridge 1999-12-31 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/265444 controlled.access https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/428bead3-0b09-4bc0-90a2-50fb1971a988/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/

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Inkjet Printed Graphene-Based Smart Gas Sensors https://doi.org/10.17863/CAM.104468 Ogbeide, Osarenkhoe Hasan, Tawfique The current commercial landscape for gas sensing is dominated by metal oxide (MOx) based sensors due to their balance of performance and cost as well as the opportunity for simple device integration, potential for miniaturisation and incorporation into multi-analyte detection systems. However, MOx sensors have significant shortcomings which include poor stability and selectivity, high power consumption/operating temperatures, long recovery and response times. I investigated the limitations of industry leading gas sensors and addressed a number of issues plaguing traditional sensors, with a fully inkjet-printed metal oxide(MOx)/graphene-based intelligent sensor capable of predictive gas sensing in mixed environments. Through optimisation of new synthesis strategies of the active sensing material, exploitation of the synergistic advantages of a combined MOx/2D nanocomposite material, the use of inkjet printing as a scalable device manufacturing process and a combination of data analysis and machine learning (ML), I could successfully distinguish 5-different gas classes with 98.1% accuracy at very low concentrations whilst also compensating for humidity interference using a single sensor. My sensors allow detection at room temperature, offering opportunities for low power sensing networks enabled by Internet of Things (IoT) revolution. Beyond detection, my proposed strategy also represents the first ever demonstration of a predictive gas sensor that can successfully detect gases at untrained concentrations in a mixed gas environment, representing a revolutionary step towards robust, highly sensitive, scalable, low cost and low power sensors for indoor air quality monitoring. Building upon my previous work, I synthesize 5 rGO/MOx (rGO/Co₃O₄, rGO/Cu₂O, rGO/WO₃, rGO/CuOₓ/CoOₓ and rGO/CoOₓ/WOₓ) inks and present a fully inkjet printed 4th order Hilbert-Piano fractal sensor array for room temperature CH₂O detection. I demonstrate the highest room temperature gas sensing response for 1 ppm formaldehyde (CH₂O) in literature using my rGO/CuOₓ/CoOₓ material, overcoming the difficulty with its detection and providing evidence for increased sensitivity through the implementation of a heating platform to my fabricated sensors. My findings offer a cost effective, sensitive VOC sensing framework, capable of selective detection of formaldehyde at the concentrations where adverse health effects start to occur. University of Cambridge 2023-04-01 Thesis Doctoral Doctor of Philosophy (PhD) eng Alphasense Limited https://www.repository.cam.ac.uk/handle/1810/361990 https://www.repository.cam.ac.uk/bitstreams/d7ca0fec-a2e4-4e94-9282-c78da84fb79b/download d0b49c0e224b98d5567f6b83b02ba631 https://www.repository.cam.ac.uk/bitstreams/d70f77c5-8d68-449b-8e9e-face0531123b/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ Air Quality Monitoring Fractal Electrode Gas Prediction Gas Sensors Graphene Inkjet Printing Machine Learning Metal Oxide Principal Component Analysis Sensor Array

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Pseudomonas aeruginosa​ genetics and virulence in cystic fibrosis and bacteraemia 10.17863/CAM.53780 Kidman, Samuel Parkhill, Julian 0000000270695958 Welch, Martin 0000000336461733 Pseudomonas aeruginosa ​is an opportunistic pathogen that can invade and colonise the lungs of people with cystic fibrosis (CF), cause septic shock through bacteraemia infections, and lead to serious infection of burn injuries. It is one of the most critical multi-drug resistant bacteria, and is associated with high morbidity and mortality. A total of 4,094 ​P. aeruginosa isolates were sampled from nine patients with CF over a six-month time period. These isolates were collected from sputum samples during stable, acute, and recovery timepoints from periods of sudden and rapid lung function decline, called acute pulmonary exacerbations (APEs). These isolates were previously analysed for the presence and absence of ten virulence-related phenotypes. The ​P. aeruginosa isolates were whole-genome sequenced to investigate the inter- and intra-patient genotypic diversity, associations with phenotypic diversity, and adaptation within the CF lung. Each of the nine patients with CF were colonised with a distinct clone of ​P. aeruginosa​. Six patients were infected with well-characterised, highly-transmissible strains of either the Liverpool Epidemic Strain (LES) or the Manchester Epidemic Strain (MES). The remaining three patients were infected with novel sequence types (STs); ST3307 or ST3308. Putative transmission was identified between the two patients infected with ST3307. Two large deletions in genetic regions commonly associated with progression from acute to chronic infection were identified in ST3307. The acquisition of the LES by one of the patients was very recent, estimated to have occurred within the two years prior to the study. This recent acquisition provides an insight into the immediate adaptation of P. aeruginosa to the CF lung, with adaptation observed in genetic regions associated with progression from acute to chronic ​P. aeruginosa​ infection. The timepoints for each APE within the individual patients were not associated with variation in the diversity of the populations of isolates. This was confirmed by random distribution of phylogenetic clusters with respect to each APE timepoint for most patients, suggesting that APEs, and the treatment of APEs, do not substantially affect the diversity of the ​P. aeruginosa​ population within the patient lung. Genome-wide association studies (GWAS) were carried out on the CF isolates, to investigate any associations with the ten previously-tested virulence-related phenotypes. Population structure could be effectively controlled for in this highly structured dataset, using linear mixed models. Multiple GWAS approaches were required to capture the different classes of genetic variation, resulting in the identification of biologically relevant associations for complex phenotypes, most notably a premature stop-codon in the global transcriptional regulator r​hlR,​ as well as several novel, potentially significant associations. An additional 352 ​P. aeruginosa ​isolates from patients with bacteraemia were also whole-genome sequenced. These isolates were sourced from both a local collection and from a UK-wide surveillance collection, and broadly match the defined population structure of ​P. aeruginosa.​ Three STs were overrepresented in this dataset, which are associated with virulence and multi-drug resistance; ST175, ST253 and ST395. One of these overrepresented STs, ST175, was distributed across the UK, shows significant geographical clustering and temporal signal, and is predicted to have been introduced into the UK between the late 1980s and the early 1990s. Antimicrobial resistance profiles showed that current therapeutic options are still viable for most ​P. aeruginosa bacteraemia infections, and that colistin is still effective against the most multi-drug resistant isolates. University of Cambridge 2019-08-01 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/306693 https://www.repository.cam.ac.uk/bitstreams/2dd61c04-839d-4495-9c55-f87f933468c0/download e38383067d522bcf77112d7e4089b848 https://www.repository.cam.ac.uk/bitstreams/687b8729-019b-40f3-9e87-0f101a2a0ed9/download 353adac0d1ebdfd65ab16480263c3c87 http://purl.org/NET/rdflicense/allrightsreserved Bioinformatics Pseudomonas aeruginosa Cystic fibrosis DNA Sequencing Next Generation Sequencing Comparative genomics

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Double-stranded RNA uptake in Caenorhabditis elegans 10.17863/CAM.42831 Braukmann, Fabian 000000032660450X Miska, Eric 000000024450576X dsRNA uptake from the environment is a common phenomenon in many invertebrates and can be harnessed for acquiring pest control. In the nematode Caenorhabditis elegans, a transmembrane protein named systemic RNAi deficient-2 (sid-2) is required for dsRNA uptake from the environment through the intestine. Furthermore, the tyrosine-protein kinase sid-3 promotes import dsRNA. However, the molecular mechanism underlying environmental RNA uptake and its natural phenotypic roles are largely unknown. Here I characterized the intracellular properties of SID-2 and its role during the nematode development. I determined SID-2 localization at the intestinal apical membrane and the trans-Golgi-network (TGN). This localization is dependent on sid-3 and its potential substrate viro-2, hence demonstrating a molecular interplay between the different SID proteins. The spatial organisation of SID-2 is conserved across species, suggesting a role for the TGN in environmental RNA uptake. By combing small RNA and transcriptome profiling with developmental studies I identified a novel role for systemic RNAi in worm morphology. A detailed phenotypical analysis ruled out a nutritional role for dsRNA uptake, implying that environmental RNA uptake affects morphology through gene regulation. These results uncover the first phenotypic role for the Sid pathway and identifies the TGN as a central cellular compartment for environmental dsRNA uptake. University of Cambridge 2020-01-01 Thesis Doctoral Doctor of Philosophy (PhD) en https://www.repository.cam.ac.uk/handle/1810/295784 https://www.repository.cam.ac.uk/bitstreams/bc7e234b-3599-4da1-9ee9-4a80d1787d6d/download 9551240202549b32dd798458aa710c16 https://www.repository.cam.ac.uk/bitstreams/430bc4f9-51fc-4e6a-9283-e26b30a0ba71/download 87eda9de84448d1f82354d60eee3eb5f https://creativecommons.org/licenses/by-nc/4.0/ C. elegans dsRNA RNAi

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Effects of timing on users' perceived control when interacting with intelligent systems 10.17863/CAM.37907 Yu, Guo Blackwell, Alan F. Cross, Ian This research relates to the usability of mixed-initiative interaction systems, in which actions can be initiated either through a choice by the user or through intelligent decisions taken by the system. The key issue addressed here is how to preserve the user's perceived control ("sense of agency'') when the control of the interaction is being transferred between the system and the user in a back-and-forth manner. Previous research in social psychology and cognitive neuroscience suggests timing is a factor that can influence perceived control in such back-and-forth interactions. This dissertation explores the hypothesis that in mixed-initiative interaction, a predictable interaction rhythm can preserve the user's sense of control and enhance their experience during a task (e.g. higher confidence in task performance, stronger temporal alignment, lower perceived levels of stress and effort), whereas irregular interaction timing can have the opposite effect. Three controlled experiments compare alternative rhythmic strategies when users interact with simple visual stimuli, simple auditory stimuli, and a more realistic assisted text labelling task. The results of all three experiments support the hypothesis that a predictable interaction rhythm is beneficial in a range of interaction modalities and applications. This research contributes to the field of human-computer interaction (HCI) in four ways. Firstly, it builds novel connections between existing theories in cognitive neuroscience, social psychology and HCI, highlighting how rhythmic temporal structures can be beneficial to the user's experience: particularly, their sense of control. Secondly, it establishes timing as a crucial design resource for mixed-initiative interaction, and provides empirical evidence of how the user's perceived control and other task experiences (such as reported levels of confidence, stress and effort) can be influenced by the manipulation of timing. Thirdly, it provides quantitative measures for the user's entrainment behaviours that are applicable to a wide range of interaction timescales. Lastly, it contextualises the design of timing in a realistic application scenario and offers insights to the design of general end-user automation and decision support tools. University of Cambridge 2019-05-18 Thesis Doctoral Doctor of Philosophy (PhD) en Cambridge Commonwealth European and International Trust Scholarship Cambridge Philosophical Society research studentship Gonville & Caius College hardship grant China Scholarship Council (CSC) (The agreement with CSC has been officially cancelled on 28 December 2017.) https://www.repository.cam.ac.uk/handle/1810/290707 https://www.repository.cam.ac.uk/bitstreams/04d6ea73-899a-4c20-90e2-62a666254971/download 9db282f5efa9de738570607d48d7cfbf https://www.repository.cam.ac.uk/bitstreams/90bfa088-4c78-4303-b6c0-81e8c6e80d47/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ mixed initiative interaction human-computer interaction sense of control entrainment rhythmic agency temporal expectation

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Role of ASCL1 and Its Interactors in Neuroblastoma https://doi.org/10.17863/CAM.106756 Mykhaylechko, Lidiya Philpott, Anna Neuroblastoma (NB) arises due to incomplete differentiation of sympathoadrenal cells during development, and is maintained by either an adrenergic or mesenchymal core transcriptional regulatory circuitry (CRC). Differentiation therapies are an attractive therapeutic approach for NB. However, it is still not fully understood how to modulate NB cell behaviour to limit proliferation and potentiate differentiation. Achaete-scute complex-like 1 (ASCL1) is a transcription factor required for both progenitor maintenance and neuronal differentiation in normal sympathoadrenal development. In NB, ASCL1 also has a dual role - as a component of the adrenergic CRC, ASCL1 supports cell proliferation, while promoting differentiation and cell-cycle exit on ASCL1 over expression. The mechanism behind these two functions is not fully understood but is likely to involve ASCL1 interactors regulating its transcriptional activity on chromatin. In this dissertation, the mechanisms by which ASCL1 induces differentiation are explored by characterising its genome-wide transcriptional targets, chromatin binding, whole proteome and protein-protein interactor differences between two pairs of NB cell lines overexpressing exogenous ASCL1. Each cell line was chosen to represent different genetic and epigenetic backgrounds of neuroblastoma disease. It was found that ASCL1 overexpression inhibited proliferation and induced morphological and transcriptional features of neuronal differentiation to a differing extent in each cell line. In the cell lines more responsive to ASCL1-induced differentiation, ASCL1 was found to associate more with proteins known to positively impact neuronal differentiation during development, such as BCL11B, PBX1, PHOX2B, SOX11, and others. On the other hand, in the cell lines less responsive to ASCL1-induced differentiation, ASCL1 associated more with proteins involved in cell-cycle regulation, such as CDKs and cyclins, or showed weaker association with most of its interactors, including E-protein TCF4, compared to a more responsive cell line. This work suggests understanding ASCL1 interactors could help explain whether this key transcriptional regulator promotes cell proliferation or differentiation of NB, allowing modulation of ASCL1-mediated differentiation to improve therapeutic options for this devastating disease. University of Cambridge 2023-09-01 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/365449 https://www.repository.cam.ac.uk/bitstreams/7f058ad1-c7af-4930-8b6a-49b9f00f3484/download 17a151a49fc8d6b065335a955084f06f https://www.repository.cam.ac.uk/bitstreams/ee0a2b16-8c81-45dd-afa4-7ae4c16ff816/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ ASCL1 cell cycle differentiation neuroblastoma neuronal protein-protein interactions

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Multisource Evaporation of Perovskite Solar Cells 10.17863/CAM.93950 Chiang, Yu-Hsien Stranks, Samuel 0000000283037292 Anaya Martin, Miguel This thesis focuses on the emerging semiconductor family of metal-halide perovskites for their application in solar cells. Halide perovskite materials have shown several promising properties, such as high absorption coefficient, low exciton binding energy, high charge mobility, long diffusion length and low annealing temperature. Moreover, their tunable bandgaps, with emission from the blue to near-infrared spectrum region possible, demonstrates their potential for different optoelectronic applications, such as solar cells, light-emitting diodes and transistors. The device performance of perovskite solar cells has increased rapidly to 25.7% in 12 years. This incredible improvement is based on a myriad of research works, mostly on solution- processed perovskites, as solution processing allows rapid screening of experiment protocols in the lab. However, scaling up perovskite solar cells for real-world impact is critical to solving energy demand crisis and climate change by using renewable energy with low-carbon emissions. Vacuum deposition, an industrially compatible deposition method, can provide smooth, uniform and solvent-free thin films for solar cell fabrication. In this thesis, the deposition and characterisation of multisource evaporated perovskite films with MA-free composition for solar cells has been studied. Chapter 4 shows that the underlying substrate can affect the perovskite quality, form different grain sizes and preferred structure orientations. Excess PbI2 during the evaporation can improve the film moisture stability and photoluminescence quantum efficiency. The importance of deposition rate is also highlighted here, showing the issue with halide uniformity. Furthermore, non-radiative losses in p-i-n architecture has been identified. After optimising the amount of excess PbI2, solar cell device performance of 18.1% can be achieved, which was the highest MA-free perovskite solar cell from multisource evaporation system at the time of the work. In chapter 5, the loss between perovskite and hole-transporting layer is minimised, leading to an even further improved device performance of 20.7% from a bandgap of 1.62 eV perovskite. A tandem solar cell is a promising route to exceed the single-junction Shockley–Queisser limit. A wide bandgap perovskite with bandgap from 1.62 eV to 1.8 eV, fabricated by multisource evaporation, is explored by controlling the PbBr2 evaporation rate. The photoluminescence, time-resolved photoluminescence and phase segregation have been studied and these results indicate the most optimised material under these conditions for tandem solar cells has a 1.77 eV bandgap. Perovskite solar cells with these bandgap absorbers have been fabricated and tested. Their device open-circuit voltage (VOC) increases monotonically to 1.24 V for a bandgap of 1.77 eV perovskite, compared to a VOC of 1.1 V from a bandgap of 1.62 eV. To understand the non-radiative loss, PLQE measurements have been performed, and the surface passivation treatment by Ethane-1,2-diammonium iodide (EDAI) leads to an improvement in VOC and fill factor. The narrow bandgap perovskite with Pb/Sn composition is prepared and the film morphology, crystal structure, and photoluminescence has been characterised and optimised to make all-perovskite tandem solar cell. The same EDAI passivation is also useful for the Pb/Sn perovskite as surface passivation by further improving the device VOC and FF. The interconnect layer by atomic layer deposition for SnOX layer is developed to connect the wide and narrow bandgap perovskite. A 2-terminal all-perovskite tandem solar cell with a PCE of 24.1% is shown, where at least one subcell is prepared by multisource evaporation. Chapter 6 presents the versatility of evaporated perovskite in different applications. We have demonstrated a proof of concept of evaporated perovskite for perovskite/Si tandem solar cells, solar fuel device and large-scale deposition. Finally, chapter 7 provides a conclusion and outlook. To sum up, this thesis provides a deep understanding of the multisource evaporation process, non-radiative loss in the device, solar cells optimisation and all-perovskite tandem solar cells. University of Cambridge 2022-09-30 Thesis Doctoral Doctor of Philosophy (PhD) eng The author acknowledges the support from the Taiwan Cambridge trust scholarship and Rank prize funding. https://www.repository.cam.ac.uk/handle/1810/346534 https://www.repository.cam.ac.uk/bitstreams/95d60df4-2520-447d-ad45-5b6ac1e3e926/download afab1a72a22ffc5ae7e9eb0f6429a84c https://www.rioxx.net/licenses/all-rights-reserved/ Evaporation perovskite solar cells

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The P-Rex1 Regulator Norbin Suppressess Neutrophil-Dependent Antibacterial Immunity 10.17863/CAM.46536 Pantarelli, Chiara 0000000258372056 Welch, Heidi C. 0000000178657000 P-Rex1 is a guanine-nucleotide exchange factor (GEF) that activates the small G protein Rac, thus regulating a wide range of physiological and pathophysiological responses. Neutrophils are leukocytes of the innate immune system in which P-Rex1 regulates several Rac-dependent responses, especially those elicited by GPCR signalling. The aim of my project was to assess the functional importance of a new interactor of P-Rex1, the GPCR adaptor protein Norbin, in neutrophils. Norbin is an essential neuronal protein that binds directly to GPCRs, regulating GPCR signalling and trafficking, through unknown mechanisms. Our laboratory recently identified that Norbin stimulates P-Rex1 Rac-GEF activity and promotes P-Rex1 membrane localisation. Furthermore, we showed that Norbin is expressed in myeloid cells. To investigate, we generated mouse strains with conditional deletion of Norbin in myeloid cells and with combined Norbin/Prex1 deficiency. Unexpectedly, I found increased adhesion, spreading, ROS production and degranulation responses in isolated Norbin-deficient neutrophils. Moreover, Norbin-deficient neutrophils had an increased ROS-dependent capacity to kill Staphylococcus aureus. In vivo, Norbin deficiency provided increased immunity against pulmonary infection with Streptococcus pneumoniae, even in immune-deficient Prex‒/‒ mice. Neutrophil depletion showed that Norbin deficiency renders neutrophils important for combatting this infection. Mostly, Norbin deficiency overrode the functional impairments caused by Prex1 deficiency, although some neutrophil responses remained P-Rex1-dependent. Mechanistically, the Norbin deficiency caused constitutive upregulation of some GPCRs onto the neutrophil surface and promoted the GPCR-dependent activities of Rac and Erk, whereas several other signalling pathways and the surface levels of adhesion molecules were not obviously affected. Together, my data indicate that the GPCR adaptor and P-Rex1 regulator Norbin plays an important role in suppressing the host defence functions of neutrophils. A subset of Norbin functions are P-Rex1 dependent, whereas others are likely mediated through other regulators of Rac and of Erk, as well as through the control of GPCR trafficking. University of Cambridge 2020-06-18 Thesis Doctoral Doctor of Philosophy (PhD) en BBRSC DTP https://www.repository.cam.ac.uk/handle/1810/299465 https://www.repository.cam.ac.uk/bitstreams/b7b7e543-214b-4ee7-a156-4bf3de08cca7/download d5f76188694a2288da25da6c69490655 https://www.repository.cam.ac.uk/bitstreams/210b0408-e1ed-40af-be5e-f3a826cfd00b/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ PREX1 Phosphatidylinositol-345-trisphosphate-Dependent Rac Exchange Factor 1 PREX2 Phosphatidylinositol-345-trisphosphate-Dependent Rac Exchange Factor 2 Rac Ras-related C3 botulinum toxin substrate ROS reactive oxygen species C5a Complement component 5a fMLP N-Formyl Methionyl-Leucyl-Phenylalanine

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Exploring the role of molecular imaging in the diagnosis and management of primary adrenocortical disease https://doi.org/10.17863/CAM.107621 Senanayake, Russell Gurnell, Mark With the advent and evolution of modern imaging techniques, there has been an increase in the detection of adrenal lesions, most often incidentally (4–7% of all abdominal CT scans in patients >40 y). Computed tomography (CT) is generally preferred for the evaluation of adrenal masses, and often informs treatment decisions (e.g., surgical resection) by establishing lesion size, density and homogeneity. However, anatomical imaging provides limited or no information regarding the functional status of an adrenal mass, which is a key element in the decision-making process, particularly with respect to recommending surgery, and in guiding pre-, peri- and postoperative endocrine management. These challenges are exemplified by primary aldosteronism (PA), a condition caused by autonomous aldosterone secretion from one or both adrenal glands, and which accounts for between 5–14% of all hypertension. Distinguishing between unilateral and bilateral disease is a key step in the management pathway as it identifies those patients who might benefit from unilateral adrenalectomy to effect cure of biochemical hyperaldosteronism with reversal or amelioration of hypertension (± hypokalaemia). Adrenal vein sampling (AVS) remains the current gold standard for lateralisation (i.e. determining whether one or both adrenal glands are implicated). However, it is limited by its invasive nature and the requirement for an experienced interventional radiologist, given the challenges associated with successfully cannulating the right adrenal vein. Accordingly, alternative techniques for distinguishing unilateral and bilateral causes of PA have been proposed, including adrenal molecular imaging with the positron emission tomography radiotracer [¹¹C]Metomidate (MTO PET). MTO has previously been shown to have high affinity for adrenocortical tissue (targeting the key enzymes CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase). This thesis examines the potential roles for molecular adrenal imaging with MTO PET in the management of (i) adrenal incidentalomas which are deemed indeterminate on conventional anatomical imaging, and (ii) in patients with PA. However, an important limitation of MTO is the requirement for an on-site cyclotron due to the short half-life (t½=20mins) of Carbon-11, which potentially limits the application of this imaging modality to a relatively small number of NHS sites across the UK. Therefore, this thesis also describes first-in-human studies with a related novel radiotracer [¹⁸F]CETO, which has a longer half-life (t½=110mins), to determine whether it has the potential to facilitate more widespread access to molecular adrenocortical imaging. The first chapter summarises the current knowledge base, including providing an overview of the current literature pertaining to adrenal adenomas and available imaging modalities, with a particular focus on molecular imaging modalities. Chapter two describes the methods that are common among the research studies presented in the subsequent chapters. Chapter three highlights the role of MTO PET in enhancing decision-making and improving outcomes for a proportion of cases where conventional imaging may fail to accurately characterise adrenal incidentalomas (AIs). This chapter highlights how MTO can be used to distinguish the origin of the indeterminate AI, and how a combination of imaging modalities [e.g., FDG PET, ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG)] can be used to characterise (a) the origin of the lesion i.e., adrenocortical or non-adrenocortical, and (b) determine the malignant potential of the lesion. This will increase the accuracy in detection of the underlying adrenal pathology associated with the AI, and in turn better guide the diagnostic pathway and proposed management of AIs, along with determining the prospective scanning frequency. In certain instances, I demonstrate how a combination of two imaging modalities may avert the need for unnecessary adrenal biopsy, which is commonly associated with low yield and often non-diagnostic, and unnecessary surgical resection. I then focus specifically on PA, with chapter four outlining the ability of MTO PET/CT to accurately distinguish between unilateral and bilateral disease, using either MTO alone, or in combination with AVS findings, to guide surgical management in PA patients through a retrospective series. The findings of the study permitted the creation of a decision matrix, so that clinicians can adopt a more systematic approach in using MTO PET/CT to guiding the decision to proceed to surgery. The positive findings from the retrospective study described in chapter four required validation in a prospective study design, which is addressed in the subsequent chapter. Chapter five describes a prospective multicentre study, MATCH, which evaluates the role of MTO PET/CT for lateralisation in PA by comparing findings with the current gold standard, AVS. Following on from both retrospective and prospective studies, a limitation that has been identified with reference to MTO is the short half-life, restricting synthesis to clinical sites with an on-site cyclotron which amounts to <10 NHS clinical sites. To overcome this limitation, a fluorinated radiotracer will possess a significant advantage, permitting distribution of the tracer to neighbouring clinical sites as far as 100-150miles away, and increasing accessibility to molecular imaging in a wider geographical area. Chapter six focuses on a first-in-human phase I clinical trial evaluating the efficacy and safety of a novel molecular tracer, [¹⁸F]CETO, comprising of five healthy volunteers and six PA patients (three unilateral and three bilateral disease). We assess the safety, tolerability, and efficacy of the tracer, and adopt dexamethasone administration in the protocol to determine how this impacts on the signal-to-noise ratio. Additionally, dosimetry calculations were undertaken to determine how tracer uptake compares in different organs. Throughout the studies described, adrenal specimens were taken and analysed to confirm aldosterone-producing adenoma(s), and whether the type of lesion correlates with the pattern of tracer uptake of the radiotracer. However, only a small number of studies in the current literature have outlined how certain histopathological characteristics may also correlate with other factors in PA, including pre- and postoperative outcomes. I conclude with chapter 7, which describes how specific histopathological findings in PA may correlate with pre- and postoperative outcomes. I take advantage of our retrospective patient cohort, of which a significant proportion would have proceeded to MTO to determine the appropriateness of surgical intervention. Therefore, I was able to assess the relationship between histopathological features on resected adrenal specimens, and the pattern of MTO tracer uptake on PET imaging. University of Cambridge 2023-10-31 Thesis Doctoral Doctor of Philosophy (PhD) eng The MATCH study was funded by the British Heart Foundation (BHF). The CETO study was funded by the MRC DPFS grant. https://www.repository.cam.ac.uk/handle/1810/366881 https://www.repository.cam.ac.uk/bitstreams/323e42ff-a4dc-4e37-b88f-a1affbf48f3c/download f33487457d58675857732253e025bcba https://www.repository.cam.ac.uk/bitstreams/9acec285-b54f-4555-a1ba-e4081b4d3e11/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ Adrenal Molecular imaging Primary aldosteronism

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Missions, mythologies and the search for non-European allies in the anti-Islamic holy war, 1291-c. 1540 10.17863/CAM.20411 Knobler, Adam University of Cambridge 1989-01-01 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/273382 controlled.access https://www.repository.cam.ac.uk/bitstreams/a70f4a6b-1cf1-4f76-8ad8-b550dbf36e22/download c4e356726301f74f08c11beb6cba805c https://www.repository.cam.ac.uk/bitstreams/e3ed4501-db77-431e-b3d8-9b02cf8b633f/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/

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Consequences of Plk4 overexpression in mouse pancreatic organoids 10.17863/CAM.65612 Ridings Figueroa, Rebeca Segal, Marisa 0000000318489388 Glover, David Overexpression of the polo-like kinase 4 (Plk4), the master regulator of centrosome duplication, leads to centrosome amplification, a common feature of cancer, including pancreatic cancer. Previous studies have shown that overexpression of Plk4 in mice carrying a doxycycline-inducible Plk4 transgene (Plk4OE) causes centrosome amplification, a reduction in primary cilia number, and increased proliferation of pancreatic endocrine α-cells and β-cells. This project aimed to investigate the consequences of Plk4 overexpression on pancreas cell biology using mouse pancreatic ductal organoids. In accord with previous observations, immunofluorescence experiments confirmed that Plk4 overexpression leads to centrosome amplification and reduction in primary cilia number. I also investigated the consequences of long-term Plk4 overexpression on the differentiation status of pancreatic organoids. Immunofluorescence and RT-qPCR analyses revealed ductal-to-endocrine transdifferentiation, with insulin secretion and expression of β-cell markers in Plk4OE +dox organoids. I then used whole-transcriptome sequencing to investigate the consequences of Plk4 overexpression on gene expression. Results revealed differential gene expression between control and +dox Plk4OE organoids, with enrichment for genes with centrosome, cilia, cell cycle, cell death, cancer and endocrine function. Finally, I optimised and tested a protocol for the in vitro differentiation of pancreatic organoids, with induced insulin production in pancreatic organoids, irrespective of Plk4 overexpression. In summary, the findings of this thesis confirm the reported effects of Plk4 overexpression on centrosomes and primary cilia. They also reveal a previously unknown effect of Plk4 overexpression on the identity of pancreatic ductal cells. However, whether this effect is a direct consequence of Plk4 overexpression itself or a secondary consequence of some Plk4-mediated event, such as the downregulation of primary cilia formation, remains unclear. Finally, I present an in vitro differentiation protocol capable of driving ductal organoids into insulin-producing organoids without the need for genetic modification. University of Cambridge 2020-12-18 Thesis Doctoral Doctor of Philosophy (PhD) eng Cancer Research UK studentship https://www.repository.cam.ac.uk/handle/1810/318498 https://www.repository.cam.ac.uk/bitstreams/c703a756-6a88-4446-b822-3029489f3674/download c3a0fc473c2f511fe9684f38b10203c1 https://www.repository.cam.ac.uk/bitstreams/3130f314-fb3e-403b-aa6a-d035c9b8e591/download 353adac0d1ebdfd65ab16480263c3c87 https://www.rioxx.net/licenses/all-rights-reserved/ pancreas organoids centrosome insulin

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Trusts : practice and doctrine, 1536-1660 10.17863/CAM.19770 Jones, Neil Gareth University of Cambridge 1994-01-01 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/272761 controlled.access https://www.repository.cam.ac.uk/bitstreams/012314cd-6376-4b32-b1bb-82196b4096bf/download b00e1f39eb3d9c04f3727a5be952fcf0 https://www.repository.cam.ac.uk/bitstreams/b087b32f-aa69-43bd-a7ce-eb4e0587da24/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/

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Characterisation of Novel Secreted Antiviral Factors to Human Cytomegalovirus 10.17863/CAM.94454 Potts, Martin Wills, Mark Weekes, Michael Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that infects a majority of the human population. Like other herpesviruses, HCMV readily establishes a latent infection that persists for the lifetime of the host and undergoes periodic lytic reactivation events. In healthy individuals, HCMV infection is typically asymptomatic, while in immunocompromised individuals, such as immunosuppressed transplant recipients, HCMV infection or reactivation of latent infection results in substantial end-organ disease and mortality. HCMV is also the most common congenital viral infection and can lead to neurological sequelae such as hearing loss and developmental delay. HCMV infection induces a multi-faceted immune response that controls but never clears the virus, due to a multitude of virally-encoded immune evasion factors. The broad immune response raised against the virus includes the action of intrinsic antiviral restriction factors, NK cells, neutralising antibodies and polyfunctional CD4+ and CD8+ T-cells. Although critical roles have been established for the antiviral cytokines IFNγ and TNFα during HCMV infection, the contribution of soluble factors to viral control remains poorly understood. In this thesis I demonstrate that the complement of secreted factors (secretomes) produced by immune cells co-cultured with HCMV-infected fibroblasts are capable of restricting HCMV in an in vitro viral dissemination assay. This activity was only partially mediated by IFNγ and TNFα and did not result from type I or type III interferon action. To determine the composition of immune cell antiviral secretomes using an unbiased quantitative approach, I developed a multiplexed proteomic method using a combination of SILAC and tandem mass tag (TMT) labelling. Application of this technology enabled detailed analysis of the secretomes produced by peripheral blood mononuclear cells (PBMC) derived from four HCMV-seropositive donors when co-cultured with HCMV-infected fibroblasts, including determination of the cellular origin of each secreted protein. This analysis identified critical components of the PBMC secretory response to HCMV, including secretion of the cytokines and chemokines IFNγ, IL-6, CXCL10 and CCL8 alongside potentially novel antiviral factors. Identification of the factors responsible for direct restriction of HCMV from this dataset proved challenging, however. Subsequent proteomic characterisation of the cellular pathways stimulated by the unidentified secreted antiviral factors implicated signalling via the NFκB pathway, providing avenues of investigation that may enable identification of these factors. Application of the novel secretomics methodology described here to isolated immune cell populations will facilitate further dissection of secreted antiviral immunity to HCMV in the future. University of Cambridge 2022-11-15 Thesis Doctoral Doctor of Philosophy (PhD) eng Wellcome Trust (203747/Z/16/Z) https://www.repository.cam.ac.uk/handle/1810/347039 https://www.repository.cam.ac.uk/bitstreams/4b4e1b48-ff68-475c-85ae-b4105e218235/download e91dfcea2e1ef0879a0b3b1a8d9fb977 https://www.rioxx.net/licenses/all-rights-reserved/ HCMV Human cytomegalovirus Secretome Immunology Virology

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Language and the politics of Roman identity 10.17863/CAM.37649 Elder, Olivia Laura 0000000337121693 Wallace-Hadrill, Andrew Clackson, James This thesis examines the relationship between language and Roman identity, defined in the broadest sense as the political and cultural practices involved in being Roman. It focuses on evidence of multilingualism: Roman identity was defined through opposition and interaction, and it is at points of contact that these debates are cast into relief. It looks predominantly at evidence of Greek-Latin bilingualism, but also considers evidence of other languages to consider how their relationship to Roman identity differs. It combines historical and sociolinguistic approaches to multilingualism. Understanding bilingual language practices requires close sociolinguistic reading of evidence to understand how languages interrelate and analysis of the historical factors and contexts that determine language choices and their social, cultural and political implications. The thesis responds especially to the use of bilingualism as a model for Roman cultural relations, arguing that a closer engagement with sociolinguistic terminology and with linguistic evidence is necessary if we are to use language and bilingualism as a way into broader issues of politics and identity. Language is simultaneously a model for identity that works across ancient and modern thought and a central part of this identity. It frequently plays into other markers of Roman identity and a range of themes and concerns surrounding it including integration, migration and citizenship. The thesis examines three case studies in detail: the different layers of bilingualism in Suetonius’ biographies; Greek in the graffiti of Pompeii; epigraphic and literary evidence for different languages in the city of Rome. These case studies demonstrate the politics of language in different types of practice and at different levels of society: the thesis argues that the overlaps between them are greater than has sometimes been appreciated. The case studies also show that the boundaries of Roman identity did not develop in a progressive or linear fashion but were continually defined and redefined through ongoing processes of absorption and rejection. University of Cambridge 2019-03-23 Thesis Doctoral Doctor of Philosophy (PhD) en Primary funding from a Peterhouse Research Studentship 2014–17. Additional funding from Peterhouse Gunn Studentship 2017–18 and a Classics Faculty Sandys Studentship 2016. https://www.repository.cam.ac.uk/handle/1810/290422 https://www.repository.cam.ac.uk/bitstreams/38b701ce-62a8-4bc0-969f-1fc6b29562dc/download 8d085e16074f031566098ff568c76e96 https://www.repository.cam.ac.uk/bitstreams/38e653de-759a-4892-8f52-19e3331a679a/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ Bilingualism Multilingualism Sociolinguistics Roman History Language Identity Roman Identity Roman Empire Migration Urban Multilingualism Suetonius Pompeii Rome City of Rome Graffiti Epigraphy

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The Memory of a Forgotten Landscape: A socio-topographical inquiry into the remains of Later Prehistoric Norfolk 10.17863/CAM.56773 Aines, Ethan Stoddart, Simon Joy, Jody Four decades of meticulous collection of metal detected finds data in Norfolk by the Norfolk Historic Environmental Record (NHER) and the Portable Antiquities Scheme (PAS) have given rise to one of the largest regional datasets in English archaeology. It is estimated that this dataset contains approximately 1.5 million data points on artefacts spanning prehistory to the modern era. It provides a remarkably dense spatial and temporal distribution of past activity and a compelling opportunity to intensively analyse the circulation, deposition, and social significance of metals and metalwork in the prehistoric landscape. More than 70% of these finds come from arable land and not from traditional archaeological contexts, so the dataset covers enormous areas and indicates the presence of thousands of archaeological sites, many of which have never been examined in any detail. This information, coupled with the data compiled by cropmark surveys, like the National Mapping Programme (NNM) in Norfolk, provides vast potential for inferences about past landscapes. Yet questions remain as to the best ways to make use of these types of large datasets, a problem that collections of grey literature equally face. However, the conscientious manipulation of the NHER/PAS datasets using a range of the latest techniques in GIS and statistics, including summed probability distributions for dating and geographically weighted regression to view the connections between disparate sites, coupled with the careful analysis and critique of biases in the underlying data structure, allows for a broad perspective on past patterns of life across much of later prehistoric Norfolk. It is possible to see trends occurring in both the circulation and deposition of metals in the longue-durée. This may shed light on the practice of votive deposition as a trend emerging from earlier prehistory but one that is largely dependent upon the social pressures of the current moment. This illuminates the ways in which certain features of social landscape recur again and again. The clustering and recurrence of hoards and other types of sites in certain localities across great time-spans is of particularly interest, and allows for commentary on place-making, social memory, and ritual during later prehistory. As Cyril Fox’s famous regional study of archaeology showed, however, there is no substitute for being there, and a critique often levelled against GIS projects is that they are overly reliant on technical wizardry to see things that might not actually exist outside a computer. Therefore, a significant part of this research has involved many trips crossing the landscape on foot or by rail or by car, visiting sites much like Fox did in Cambridgeshire a century ago. In such a way, it is possible to integrate the latest digital methods with more traditional landscape archaeology to present persuasive and novel models of the social, ecological, and geographical significance of Norfolk’s landscapes in the period leading up to the Roman conquest of Britain. Thus, this research clearly illustrates an array of methodological procedures for connecting the observations of metal detectorists to higher level discussions about the linkages between knowledge of place and knowledge of self, or identity, in the past. It also shows how large datasets can be used in thoughtful, contextual ways to learn about the past and to inform and shape future research agendas throughout the county. University of Cambridge 2019-10-30 Thesis Doctoral Doctor of Philosophy (PhD) eng Cambridge Trust https://www.repository.cam.ac.uk/handle/1810/309678 https://www.repository.cam.ac.uk/bitstreams/ed303c43-5762-418f-a20c-dbad44b28a1a/download cc4849b8e7b6445726756b9794b78638 https://www.repository.cam.ac.uk/bitstreams/c366f833-c28e-4db0-85a7-f7723cc0c3a8/download 353adac0d1ebdfd65ab16480263c3c87 https://www.rioxx.net/licenses/all-rights-reserved/ archaeology prehistory Iron Age landscape archaeology Norfolk archaeology of memory memory

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A New Travel Demand Model for Outdoor Recreation Trips 10.17863/CAM.32377 JIAO, XIHE Jin, Ying Travel to outdoor recreational spaces belongs to a general class of research questions for understanding destination and travel mode choices. In travel demand modelling, discrete choice models (DCMs) have been applied to understand and predict a wide range of choices, such as how people choose among alternative destinations for jobs, homes, shopping, personal services etc. Surprisingly, DCMs have rarely been used to understand and model travel to outdoor recreational spaces. In the current literature for modelling travel to outdoor recreational spaces, the established models are Negative Binomial Regression (NBR) models, such as what was used in the UK NEA studies. However, these NBR models were developed to assess the effects of travel to outdoor recreational spaces at a national level, and they are not intended for assessing choices of individual sites. One reason for this is, as identified by previous studies, is that compared with the DCMs, the NBR models have certain limits on estimating people’s choice behaviours. There is, therefore, no existing model that can represent and predict how people choose to travel to outdoor recreational spaces. Given the importance of outdoor recreational activities to urban land use planning and public health, this is a clear gap in the field. The aim of this study is to develop a new travel demand model capable of representing and predicting travel to individual outdoor recreational sites. This is achieved by answering four main research questions: First, how to build the new model for outdoor recreational travel? Secondly, is the estimation accurate enough? Thirdly, to what extent can the new model be transferred to destinations outside the case study area? And, finally, how can city planners and designers use this new method? The new model draws upon ideas from random utility theory that underlies the conventional travel demand models to represent trip generation, trip distribution and mode choice. This research follows the standard modelling procedure: data collection and preliminary analysis, model calibration, model validation and model application. The data are collated from a wide range of sources that, importantly for model transferability, cover all areas in England. The new model has been calibrated for a case study area which spanned 14 selected districts in the North-West region. Validation of the new model is based on estimating the numbers of trips to two outdoor recreational sites (Wigg Island and Wigan Flashes) and to nine English National Parks where data on visitor trips exist. In the final stage of the research, the new model is applied to estimate the changes that would arise from planning and design interventions in existing (Wigg Island and Moore Nature Reserve) and proposed (Arpley Country Park) sites. At the end of this process, it is possible to show that the new model can predict the number of trips to individual destinations and that the model can be transferred to other outdoor recreation sites. Furthermore, the new model presented here is capable of predicting the changes in the volume and catchment of visits to an existing green space after land use planning or urban ecological interventions. This is a completely new theoretical model that is focused on understanding and quantifying the travel choices to outdoor recreation sites, which can inform decision makers by forecasting changes in outdoor recreational travel demand, according to different planning scenarios. University of Cambridge 2018-11-24 Thesis Doctoral Doctor of Philosophy (PhD) en https://www.repository.cam.ac.uk/handle/1810/285006 https://www.repository.cam.ac.uk/bitstreams/cb80ae1c-6fde-4427-9473-014e0eb974cd/download b7801bb5906a787e07adde201c99a8b2 https://www.repository.cam.ac.uk/bitstreams/1186a6df-5d08-48ff-a253-2b82da8f5d1f/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ Travel Demand Modelling Discrete Choice Models Outdoor recreational trips Greenspace Urban Planning

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Komi reindeer herding: mobility and land use in a changing natural and social environment 10.17863/CAM.91013 Dwyer, Mark James Vitebsky, Piers Rees, Gareth Nomadic pastoralism is a form of animal husbandry characterised by movement. Herders and their animals move across the tundra and taiga displaying a curious dichotomous relationship of control by and response to each other. This field based research - carried out among Komi nomadic reindeer herders of the Russian far north - examines how Komi pastoral nomads choose a particular time, route and length of migration. This was explored by using anthropological as well as ecological methods to (i) identify how social and political change and environmental variability influence the reindeers’ and herders’ movements alike and (ii) examine how nomadic movements occur in relation to nonecological and ecological factors. It was found that there were essentially two types of human / animal movements; individual movements (made by the duty herder and his herd) and collective movements (made by the brigade). Both types of movement, in time and space, were fundamentally dependent upon herding skill and knowledge, and herd control: (a) the duty herder’s ability to maintain herd cohesion and (b) the general aim of preventing harm befalling the herd (by avoiding dangerous terrain). The duty herder’s selection of pastures was, therefore, made mainly according to where reindeer were the easiest to control. It was also found that individual movements could best be understood as emanating from the interplay between reindeer behaviour and the duty herder’s actions. This interplay is best described as being the duty herder’s skilful perception of and response to ethological changes, as advocated by Tim Ingold. Its main principle is based on the duty herder’s maintenance of herd cohesion, within a restricted territory, which has minimal impact upon reindeer behaviour, and which is achieved through skilful manoeuvring. Collective movements could best be described as a means of providing duty herders with the necessary space in which to manoeuvre their herds with the minimum recourse to herding techniques (such as grouping and re-grouping, stopping and turning the herd), and the avoidance of undesirable pasturing areas. Consequently, it is not by analysing the impact that individual factors have upon the nomadic collective (i.e., nomads and animals) as a whole, that nomadic pastoralist movement will be understood. A new model for analysing nomadic pastoralist movement - focusing on the interrelations between nomads and their animals and the impacts that individual factors have upon it - is proposed. University of Cambridge 2006-05 Thesis Doctoral Doctor of Philosophy (PhD) en https://www.repository.cam.ac.uk/handle/1810/343587 https://www.repository.cam.ac.uk/bitstreams/ef5e0784-2b3d-46a9-9348-f4bfc9cb6beb/download eb258a0d7ddbd2498a736e97b3bda7ca https://www.repository.cam.ac.uk/bitstreams/45b076da-18f5-4976-8195-d23cef6f33f1/download 6871b84e9d1ac5871ba57c554a2320ad https://www.repository.cam.ac.uk/bitstreams/5a269b2f-304c-473e-9e77-44edc261c5dd/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ Reindeer herding Nomadic pastoralism Komi

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Contesting the Word: Emily Dickinson and the higher critics. Stuart, Maria Perpetua. University of Cambridge 1998-07-10 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/251651 controlled.access https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/42c16acc-67a6-4f63-9e6e-f2843956a229/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/

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'Powellsnakes', a fast Bayesian approach to discrete object detection in multi-frequency astronomical data sets 10.17863/CAM.11747 Carvalho, Fernando Pedro Marinho Neto Pires de In this work we introduce a fast Bayesian algorithm designed for detecting compact objects immersed in a diffuse background. A general methodology is presented in terms of formal correctness and optimal use of all the available information in a consistent unified framework, where no distinction is made between point sources (unresolved objects), SZ clusters, single or multi-channel detection. An emphasis is placed on the necessity of a multi-frequency, multi-model detection algorithm in order to achieve optimality. We have chosen to use the Bayes/Laplace probability theory as it grants a fully consistent extension of formal deductive logic to a more general inferential system with optimal inclusion of all ancillary information [Jaynes, 2004]. Nonetheless, probability theory only informs us about the plausibility, a 'degree-of-belief', of a proposition given the data, the model that describes it and all ancillary (prior) information. However, detection or classification is mostly about making educated choices and a wrong decision always carries a cost/loss. Only resorting to 'Decision Theory', supported by probability theory, one can take the best decisions in terms of maximum yield at minimal cost. Despite the rigorous and formal approach employed, practical efficiency and applicability have always been kept as primary design goals. We have attempted to select and employ the relevant tools to explore a likelihood form and its manifold symmetries to achieve the very high computational performance required not only by our 'decision machine' but mostly to tackle large realistic contemporary cosmological data sets. University of Cambridge 2014-01-07 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/265569 controlled.access https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/42fb26e2-9d38-477d-997c-b3f518339c2b/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/

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The mechanisms underlying convergent evolution in the plumage patterns of birds 10.17863/CAM.16412 Gluckman, Thanh-Lan Convergent evolution is a central theme in biology. Birds are an ideal system to examine the mechanisms underlying convergent evolution. Although bird patterning is diverse, within-feather patterns have repeatedly converged on the same four types: mottled patterns, scales, bars and spots. Other avian patterns occur, e.g. stripes, but are rare. In my thesis I examine the four main mechanisms underlying convergent evolution in plumage patterns: evolutionary genetics, evolutionary development, natural selection for signaling and camouflage. Japanese quail (Coturnix japonica) is a model system in developmental biology. Examining the developmental basis of pattern formation using molecular techniques, the dorsal patterning of embryonic quail is likely due to activation of the melanocortin-1 receptor, which is a highly conserved pathway in vertebrates. I examined whether a reaction-diffusion based theoretical model of pattern formation may predict developmental constraint in two groups that have different lifestyles and spectacular patterns: waterfowl (Anseriformes) and gamebirds (Galliformes). Tracing the evolutionary trajectory of pattern evolution with Bayesian comparative modeling there was evidence for developmental constraint in pattern evolution. Adaptive explanations may also result in convergence. Cuckoo-hawk mimicry has been demonstrated in the common cuckoo (Cuculus canorus) and the Eurasian sparrowhawk (Accipiter nisus), but may be prevalent in Old World cuckoos. Randomly selecting a parasitic cuckoo from each genera of Old World cuckoos and <8 sympatric raptors, I quantified their barred patterns using digital image analysis and found that parasitism can explain convergent evolution in the patterns of parasitic cuckoos and raptors. Patterns may have evolved due to ecological selection. Examining the patterns of 80% of all avian species worldwide, I found that habitat does not predict patterning, and that all four patterns are found in all habitats. These results demonstrate that the mechanisms of convergent evolution are diverse, and that development and natural selection have contributed to pattern evolution. University of Cambridge 2015-03-03 Thesis Doctoral Doctor of Philosophy (PhD) en The Cambridge Commonwealth, European and International Trust, the John Stanley Gardiner Fund, and the Pembroke college graduate research fund. https://www.repository.cam.ac.uk/handle/1810/247220 https://www.repository.cam.ac.uk/bitstreams/ed85c172-b145-4a77-aab1-8c353c37c459/download fa00b21225a1931f3c06369e33aad6eb https://www.repository.cam.ac.uk/bitstreams/413a7ba8-8b79-41c7-83be-386cb488c51d/download 835269bda140c10400fe0606a14c3d21 https://www.rioxx.net/licenses/all-rights-reserved/ Evolutionary biology Convergent evolution evo-devo Behavioural ecology Camouflage Sexual selection Mimicry Molecular biology Developmental biology Comparative modeling Ecological selection Aves

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The consequences of early- and adult-life nutrition for the colour and conservation of hihi Notiomystis cincta 10.17863/CAM.16411 Walker, Leila Nutrition is profoundly important for practically all aspects of life. Getting enough of the right kind of food affects cellular function and energy acquisition, disease avoidance, mate attraction, trophic interactions and hence ecosystem structure. When nutritional needs are inadequately met, fecundity and survival can be adversely affected. However, the severity of these effects, and the importance of the particular life history stage when they were experienced, is incompletely understood. Understanding how and when nutritional conditions affect fitness is particularly important for the conservation of endangered species, especially when food supplementation is a key part of managing the few populations that remain. In this thesis, I explore the importance of nutrition during early- and adult-life for the hihi (Notiomystis cincta), a colourful, sexually dichromatic endangered New Zealand passerine. I begin by investigating the importance of nestling nutritional environment for the expression of colourful plumage in adulthood. By experimentally supplementing nestlings with alternative dietary treatments, I demonstrate that early life nutritional conditions have long-term consequences for the expression of both carotenoid-based and structurally produced plumage features. Next I investigate whether these colourful plumage traits are sexually selected. I show that different components of a male’s colourful plumage, including yellow carotenoid-based, black melanin-based and white structurally-based colour, are relevant for different aspects of reproductive success. Using the dietary supplementation experiment, I also consider the impact of alternative supplementary foods on the growth and subsequent survival of hihi. I show that directly supplementing nestlings with protein has a negligible long-term survival benefit over supplementing carbohydrates, and present evidence that males and females have divergent nutritional needs during development – an important consideration for any supplementary feeding program. Finally, I consider whether moulting male hihi selectively forage for carotenoid-rich foods in the wild, as would be expected in a species that requires these pigments for sexual display. I present evidence that adult male hihi do indeed target carotenoid-rich foods during moult, which is consistent with the suggestion that dietary carotenoid access maintains signal honesty. In short, by addressing evolutionary questions from a nutritional perspective, I discover how and when investment in key life history traits is prioritised, how this differs between the sexes and show how this knowledge might be used in supplementary feeding programs to the benefit of endangered species. University of Cambridge 2014-01-07 Thesis Doctoral Doctor of Philosophy (PhD) en https://www.repository.cam.ac.uk/handle/1810/246937 https://www.repository.cam.ac.uk/bitstreams/365281b4-1190-44d5-85cb-aa2ebe8b0db1/download a7fbd110fa2d88b0ade1bee9f1c1cabb https://www.repository.cam.ac.uk/bitstreams/29ff2d2a-cb21-4611-ac5e-b2a9b9a4121c/download 835269bda140c10400fe0606a14c3d21 https://www.rioxx.net/licenses/all-rights-reserved/

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Rekindling histories : families and British polar exploration 10.17863/CAM.44992 Warrior, Claire This thesis examines the roles that families played, and continue to play, in sustaining British polar exploration. It uses polar exploration as a case-study to investigate the ways in which people maintain or revive particular histories in public and in private, and probes the intersection between memory and history, family and nation. What people do is not necessarily unusual, but using a case-study allows for an appreciation of the extent to which their practices may be effective over extended periods of time . While words are important here (in the form of manuscripts and books), material culture, commemorative events and travel also play their part. My hypothesis is that history-making in a British context is closely connected to kinship and that the importance of familial relations has been naturalised, rather than questioned. It notes the continuity that is perceived to be generated by kinship ties, and demonstrates how families in the present attempt to reinforce it. This is connected to a notion of responsibility towards ancestors, an acknowledgement that a person may be both individual and dividual, balancing their own sense of self with wider familial concerns. In the case of polar exploration, the focus on particular heroic figures creates certain perceptions of the regions and also subdues the presence of other participants on specific expeditions. This thesis pays particular attention to the ways in which their family members in the present work to ensure that ancestors are publicly remembered. Institutions associated with making histories, such as museums, are similarly imbued with familial relations, yet this has rarely been acknowledged. A focus on the National Maritime Museum demonstrates how family memory becomes national history, and what this move means. It illustrates the ways in which families are pulled into commemorative activities by external parties, how this is perceived by them and what it entails. Finally, analysing the Museum's displays through time demonstrates how shifts in historical understanding are reflected in public spaces and the agency of families within them. University of Cambridge 2017-03-07 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/297938 https://www.repository.cam.ac.uk/bitstreams/8ac8a8c5-52ea-48cd-b0e5-522ecf47e677/download 587ece17d67ac6ab66d3925cd7005ef8 https://www.repository.cam.ac.uk/bitstreams/cbb75e34-2643-450d-a05d-7bdf8437e842/download 5fa56e6d222b2c76d5b5262961fe888e https://www.rioxx.net/licenses/all-rights-reserved/

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Glioblastoma: an electric symphony. Understanding the Electrotherapy and Electrophysiology of Glioblastoma https://doi.org/10.17863/CAM.102057 Jenkins, Elise Malliaras, George [Restricted] University of Cambridge 2023-02-21 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/358362 restricted https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/0ad18e40-534f-491c-8b49-4377451937b7/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ bioelectronics cancer neuroscience electrotherapy

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Goldsmithing technologies, metallurgical traditions and funerary rituals in the Saka societies of the Eurasian Steppe during the Iron Age (c. 900 - 500 BCE) https://doi.org/10.17863/CAM.118677 Amirova, Saltanat Martinon-Torres, Marcos This dissertation focuses on the goldsmithing technologies of the Early Iron Age (900–500 BCE) Saka population, who inhabited the territories of Central Asia, Kazakhstan, and Western and South Siberia from around 900 BCE. They were a semi-nomadic, horse-riding population that was part of the pan-Scythian world, renowned for manufacturing complex gold objects in the famous “Animal Style” for the elite strata of society. These included costume plaques, microbeads, torcs, and gold-decorated armour. Over 300 gold objects, along with several dozen bronze and iron artefacts, originating from two large Early Iron Age necropolises in East Kazakhstan, were analysed using techniques including pXRF, SEM-EDS, 3D microscopy, micro-CT, and experimental archaeology. The collection studied consists of archaeological assemblages from six Saka burials and three Saka hoards. Two of the burials are unique: one is a double burial from Kurgan 4 Eleke Sazy II, which was found intact—a rarity; the other is Kurgan 16 Shilikty 1, which was recently dated to the end of the 8th century BCE, making it the earliest gold-containing Saka burial. The other burials and hoards date from the 6th to the 4th centuries BCE. The researched collection combines gold objects and jewellery from both the earliest and later periods, providing an excellent opportunity to investigate the development and evolution of Saka goldsmithing traditions over a span of 600 years. Some traditions and technologies were abandoned, while others survived and successfully spread to other regions. The research revealed two types of gold objects as core elements of Saka elite festive costumes: plaques and microbeads. These elements were produced serially, in large quantities, and in great variety, with their production technologies being standardised. Their fixing mechanisms, known as "flipped" loops, were universal and implied threading rather than individual sewing. Various embossing, casting, and cutting techniques were employed in the production of the plaques. A unique joining technique employing tin was used by Saka goldsmiths for the production of gold microbeads. Tin-gold intermetallic compounds (tin-gold IMC) were detected in approximately 80% of all the researched gold objects, indicating probable local alluvial/placer gold sources in East Kazakhstan. A unique hollow cone granulation technique, known exclusively in the Eurasian steppe regions, was also revealed, alongside traditional gold granulation. Within 100–150 years (8th–6th centuries BCE), Saka goldsmiths created and developed unique steppe goldsmithing traditions that perfectly adapted to societal needs. These traditions were produced exclusively by local Saka goldsmiths during a period of experimentation and fine-tuning of techniques, meeting both broader societal expectations and, more specifically, the requirements of the Saka elite. The research revealed that the Saka elite controlled highly skilled goldsmiths, enabling them to specialise in goldsmithing and produce exquisite, prestige, and luxurious gold objects that were intensive in terms of time and labour. It is likely that this control was not confined to the territories of East Kazakhstan but also extended to Central and South-East Kazakhstan, as many exquisitely made gold objects found outside East Kazakhstan, show visible tin-gold IMCs on their surfaces. As a result, these traditions flourished and spread to the territories of the Sarmatian, Scythian, and Tagar cultures in the Eurasian Steppe over the subsequent millennia. Moreover, Saka goldsmithing influenced neighbouring agricultural societies, including China and Persia, both technologically and aesthetically. The situation changed around the 6th century BCE with the collapse of the Saka hierarchical system. This was probably caused by several external factors, such as the Saka-Achaemenid wars. These changes led to significant shifts in Saka goldsmithing. Gold from different sources, which were more argentiferous, and the use of artificial gold alloys with elevated copper levels, began to appear in the 6th century BCE. Specialised goldsmithing most likely ceased to exist, and local goldsmiths shifted to multi-crafting, producing gold objects of expedient quality, with an increase in the variety of produced objects. However, it is likely that they continued to produce high-quality gold objects as a means of forming and maintaining ties within and between communities. University of Cambridge 2025-01-02 Thesis Doctoral Doctor of Philosophy (PhD) David and Claudia Harding Foundatio; Magdalene College https://www.repository.cam.ac.uk/handle/1810/384796 embargo 2026-06-02 https://www.repository.cam.ac.uk/bitstreams/6365539c-2e5b-460a-abbf-ce5b688087ec/download 34ce8acfe2736e27c4226dc216220144 https://www.repository.cam.ac.uk/bitstreams/c7a032db-892c-42a1-9bce-e2e67ac0cf49/download 87eda9de84448d1f82354d60eee3eb5f http://purl.org/NET/rdflicense/allrightsreserved Animal style gold plaque Early Iron Age Eurasian steppe pastoralism Gold microbead Gold plaque Goldsmithing Nomadic craftsmanship Saka Theory of nomadism Tin-containing joint Tin-gold intermetallic compound (tin-gold IMC)

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High level indole signalling in Escherichia coli 10.17863/CAM.16332 Gaimster, Hannah Dorne Indole is a small signalling molecule, produced by many species of bacteria, including Escherichia coli. It is made by the enzyme tryptophanase, which converts tryptophan into indole, pyruvate and ammonia. Indole has diverse roles in E. coli, including regulation of biofilm formation, acid resistance and pathogenicity. In these cases, E. coli responds to a low, persistent level of indole (0.5-1 mM), similar to the concentration found in an E. coli culture supernatant in stationary phase (typically 0.3-0.8 mM). Recently, it has been shown that much higher concentrations of indole (3-5 mM) inhibit cell division by acting as an ionophore to dissipate the membrane potential. However the biological relevance of such high concentrations, and therefore these aspects of indole signalling, has been questioned. This work has investigated the role of indole signalling during entry into stationary phase, when indole production is quickly upregulated. The viability of non indole producing mutants was compared to wild-type indole producing cells. In the short term indole producers suffered a growth disadvantage, but in the long term they were significantly more viable than their indole non-producing counterparts. The addition of 1 mM indole to the indole non-producing culture failed to complement the phenotype. A hypothesis was developed that a high rate of indole production during stationary phase entry leads to a transient, high concentration of indole inside the cell. This regulates cell growth and division via the ionophore mechanism. The validity of this indole pulse signalling hypothesis was tested by measuring cellassociated indole. For a brief time during stationary phase entry cell-associated concentrations reached 60 mM. Cell-associated indole represents an average of indole in the cytoplasm and the cell membrane. It was shown that indole has an approximately 100-fold greater affinity for the cell membrane. 60 mM cell associated indole is equivalent to approximately 4 mM in the culture supernatant, suggesting that the indole ‘pulse’ is sufficient to inhibit growth and cell division on entry into stationary phase. The indole pulse was dependent on the stationary phase sigma factor, SigmaS, which increases tryptophanase expression on entry into stationary phase. This increased tryptophanase expression occurs immediately prior to increased indole production. The end of the pulse seems to correlate with the exhaustion of tryptophan in the growth medium. University of Cambridge 2014-06-10 Thesis Doctoral Doctor of Philosophy (PhD) en https://www.repository.cam.ac.uk/handle/1810/245706 https://www.repository.cam.ac.uk/bitstreams/f41490e8-e362-4d91-98e5-e3c357b8c95b/download 7de460bdc211e58186d8892b4c7427ec https://www.repository.cam.ac.uk/bitstreams/9898ba1b-0280-4d26-a0f0-1963510bec0a/download 835269bda140c10400fe0606a14c3d21

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The systematic build up and modification of high nuclearity osmium and osmium-mercury clusters and their role as model systems for small metal particles 10.17863/CAM.18922 Gade, Lutz Hans University of Cambridge 1991-01-01 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/271913 controlled.access https://www.repository.cam.ac.uk/bitstreams/71b587e7-be69-41ce-8467-3ab95873bc47/download bdce396b61fb5c4633195b4d305b5e4c https://www.repository.cam.ac.uk/bitstreams/41813369-f0f7-41a6-87c7-ef954a1ec461/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/

oai:www.repository.cam.ac.uk:1810/3822822025-12-20T01:41:36Zcom_1810_245310com_1810_256062col_1810_245312

Evidence for dissociable learning processes from the SRT task https://doi.org/10.17863/CAM.117170 Jones, Fergal Current evidence suggests that it may be fruitful to model learning using dissociable rule-based and associative processes. Such an account would predict that people should be able to learn the same sequences qualitatively differently under hypothesis-testing and incidental conditions. The aim of this research was to test this prediction in a two choice, serial reaction time (SRT) task setting. All the SRT experiments conformed to the following general design. An Experimental Group was trained on sequences constructed by concatenating the subsequences XXX, XYY, YYX and YXY, in a random order (where X and Y were the two trial types in the two-choice task). In addition, a Control Group was trained on a pseudo-random ordering for the same number of trials. Both groups were subsequently tested on a pseudo-random ordering, to ensure that any group differences could be attributed to sequence learning, as opposed to 'sequential effects'. The extent to which the Experimental Group's responding on the third trials differed from Control was used as an index of sequence learning. When the SRT task was carried out in incidental conditions and with an RSI of 500ms, the Experimental Group showed evidence of having learnt those subsequences that ended in an alternation (XXY and YXY) but not those that ended in a repetition (XXX and XYY). In contrast, under hypothesis-testing conditions subjects performed relatively better on those subsequences that began in a repetition, probably because they were expressing knowledge related to longer strings of Xs than Ys. Furthermore, when the contingencies were made less noisy by marking out the triplets in a second hypothesis-testing condition, the pattern of subsequence learning again qualitatively differed from that in the incidental condition, with subjects now learning XXX earliest. These dissociations are consistent with the operation of separable learning processes; with the hypothesis-testing patterns being attributable to a rule-based process that finds runs of repetitions especially salient, and the incidental pattern being explicable in associative terms, by the APECS SRN (but not by other contemporary associative models). According to this account, sequential effects and sequence learning had largely additive effects on the Experimental Groups' performance. This assumption was tested by replicating two of the previous conditions at a new RSI of 50ms, and so with a changed pattern of sequential effects; the idea being that an unaltered pattern of sequence learning would suggest additivity. However, the results were ambiguous; though they were not inconsistent with the above account. In conclusion, in the absence of an adequate single-process alternative, the experiments reported in this thesis support the rule-based/associative distinction. University of Cambridge 2001 Thesis Doctoral Doctor of Philosophy (PhD) https://www.repository.cam.ac.uk/handle/1810/382282 https://www.repository.cam.ac.uk/bitstreams/b6f85d35-67bb-4e3b-b29e-4b0d26c380a1/download dd33a30b45aa0643e74db1ca25c94845 https://www.repository.cam.ac.uk/bitstreams/10187ac5-1b2e-4eca-a8d2-83a5a902822a/download 051125998a5dd4455b9e6e291284dae4 https://www.repository.cam.ac.uk/bitstreams/05222a9a-8efd-42d4-8fbf-b1c940ce5425/download eb9d2d75cbfff5683a827dd2229be5c0 http://purl.org/NET/rdflicense/allrightsreserved/

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Designer nature : the papier-ma?che? botanical teaching models of Dr Auzoux in nineteenth-century France, Great Britain and America Olszewski, Margaret University of Cambridge 2010-10-12 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/252215 controlled.access https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/b7118f0b-f10e-491e-bce6-7abd253b2970/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/

oai:www.repository.cam.ac.uk:1810/3827582025-12-19T18:08:19Zcom_1810_224463com_1810_34581col_1810_224464

Investigating the Mental-Physical Health Interface Using National Register-based Data https://doi.org/10.17863/CAM.117409 Formánek, Tomáš Jones, Peter While existing research has convincingly demonstrated that many mental and physical health conditions do oftentimes co-occur together, the causality between distinct pairs of mental and physical health conditions as well as the outcomes resulting from the co-occurrence of these, remain incompletely described and understood. In the present thesis, I have set out to answer a set of questions connected to both the aetiology and consequences of co-occurring mental and physical health conditions, particularly using national register-based health data. Concerning the aetiology, I present novel evidence that the extensive psychiatric morbidity in childhood-onset type 1 diabetes is unlikely to be fully explicable by common underlying biological mechanisms, but at least part of the associations between rheumatoid arthritis and depression, schizophrenia, and Alzheimer’s disease might be a consequence of such mechanisms and/or disease related factors such as medication effects. Concerning the consequences of co-occurring mental and physical health conditions, I have demonstrated higher risks of mortality and larger losses of life-years in both people with substance use disorders and severe mental illnesses following the onset of a wide range of physical health conditions compared with counterparts who only had the respective physical health condition. In people with severe mental illness, I have showed that this excess mortality exceeds what could be attributed to having more physical comorbidity in this patient group. Further related to consequences of co-occurring mental and physical health conditions, I have showed that the elevated risk of post-SARS-CoV-2 infection mortality in people with substance use and psychotic disorders, demonstrated in a number of previous studies, persisted even after control for clinically-recorded physical illness, including at the later phases of the pandemic. Taken together, the findings of this thesis align with the notion that the old-fashioned silos between mental and physical healthcare are not reflective of empirical reality and are leading to unnecessary losses of human lives. Identifying ways of providing holistic care for mental and physical health conditions that is feasible, acceptable, affordable, effective, and, crucially, sustainable, thus constitutes probably one of the greatest challenges for medicine. University of Cambridge 2024-05-31 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/382758 https://www.repository.cam.ac.uk/bitstreams/3e3f1d1c-9ed3-42c7-8ec3-3399849811a7/download 02c4ada0498528aa9766aa6847b9b05c https://www.repository.cam.ac.uk/bitstreams/4838a64a-acbe-4c75-ba7b-e78d82fbeb11/download 87eda9de84448d1f82354d60eee3eb5f https://creativecommons.org/licenses/by/4.0/ Causal inference Evidence triangulation Life-years lost Mental disorders Mortality Observational data Somatic comorbidity

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Machine learning methods for detecting structure in metabolic flow networks 10.17863/CAM.48344 Jay, Maxwell 0000000189130909 Lio, Pietro Metabolic flow networks are large scale, mechanistic biological models with good predictive power. However, even when they provide good predictions, interpreting the meaning of their structure can be very difficult, especially for large networks which model entire organisms. This is an underaddressed problem in general, and the analytic techniques that exist currently are difficult to combine with experimental data. The central hypothesis of this thesis is that statistical analysis of large datasets of simulated metabolic fluxes is an effective way to gain insight into the structure of metabolic networks. These datasets can be either simulated or experimental, allowing insight on real world data while retaining the large sample sizes only easily possible via simulation. This work demonstrates that this approach can yield results in detecting structure in both a population of solutions and in the network itself. This work begins with a taxonomy of sampling methods over metabolic networks, before introducing three case studies, of different sampling strategies. Two of these case studies represent, to my knowledge, the largest datasets of their kind, at around half a million points each. This required the creation of custom software to achieve this in a reasonable time frame, and is necessary due to the high dimensionality of the sample space. Next, a number of techniques are described which operate on smaller datasets. These techniques, focused on pairwise comparison, show what can be achieved with these smaller datasets, and how in these cases, visualisation techniques are applicable which do not have simple analogues with larger datasets. In the next chapter, Similarity Network Fusion is used for the first time to cluster organisms across several levels of biological organisation, resulting in the detection of discrete, quantised biological states in the underlying datasets. This quantisation effect was maintained across both real biological data and Monte-Carlo simulated data, with related underlying biological correlates, implying that this behaviour stems from the network structure itself, rather than from the genetic or regulatory mechanisms that would normally be assumed. Finally, Hierarchical Block Matrices are used as a model of multi-level network structure, by clustering reactions using a variety of distance metrics: first standard network distance measures, then by Local Network Learning, a novel approach of measuring connection strength via the gain in predictive power of each node on its neighbourhood. The clusters uncovered using this approach are validated against pre-existing subsystem labels and found to outperform alternative techniques. Overall this thesis represents a significant new approach to metabolic network structure detection, as both a theoretical framework and as technological tools, which can readily be expanded to cover other classes of multilayer network, an under explored datatype across a wide variety of contexts. In addition to the new techniques for metabolic network structure detection introduced, this research has proved fruitful both in its use in applied biological research and in terms of the software developed, which is experiencing substantial usage. University of Cambridge 2018-08-07 Thesis Doctoral Doctor of Philosophy (PhD) en EPSRC https://www.repository.cam.ac.uk/handle/1810/301261 https://www.repository.cam.ac.uk/bitstreams/114e3e33-2dae-45ea-98f4-48acd38695e8/download 1843d568e4ca72f0ec0f55e80daea189 https://www.repository.cam.ac.uk/bitstreams/c8bde831-3895-42a8-be42-6d584c61df2b/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ Linear programming optimisation machine learning decision trees metabolic networks network structure flow networks network clustering

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Senses of the Future in 19th Century France and America, with Reference to the Philosophies of Victor Cousin, Henri Bergson, Ralph Waldo Emerson, and William James https://doi.org/10.17863/CAM.112787 Kretowicz, Michael Bell, Duncan This thesis examines a group of philosophers in Victor Cousin, Henri Bergson, Ralph Waldo Emerson, and William James, each of whom sought to resolve past, present, and future in a true vision of the world. I argue that these visions should be characterised as sets of practical accomplishments. That is to say, if they could be glimpsed in theories of perception or knowledge, they were only realised when lived out and held forth as models of human cultivation. Cousin, Bergson, Emerson, and James devoted considerable effort to combining in themselves the exemplary figures of the scientific knower and the spiritual guide concerned with the care and direction of the soul. They did so concretely, as teachers who worked within or against educational institutions that were completely transformed over the course of the nineteenth century. This thesis brings out how these philosophers sought to teach their respective audiences to look at the world differently so that they would know how to act purposefully in it. Each of my four chapters will show that the philosophy of its subject was a complex practice made up of several parts. The most important of these parts were habits of attention with respect to inner and outer phenomena, disciplines of self-correction and emotional regulation, and methods for the presentation and organisation of knowledge as well as the interpretation of past texts. These practices varied significantly between the four philosophers. Moreover, as complexes they were held together by different scholarly offices and exemplars of mental conduct. From an intellectual-historical perspective, the significance of such practical variation is that it registers the essential contingency of philosophical efforts to impose some degree of temporal unity on the world. Throughout this thesis I return to four sets of contingencies: the past thinkers or doctrines which each philosopher recognised as authoritative; the scholarly or scientific ethos that guided his thinking; the religious setting and atmosphere of belief in which he moved; and, finally, his institutional environment and its dominant mode of intellectual cultivation. Altogether, these contingencies help to characterise my subjects as philosophers and explain why the imposition of certain unities of perception and purpose was for them an activity centrally about the future of humankind. University of Cambridge 2024-07-31 Thesis Doctoral Doctor of Philosophy (PhD) eng Cambridge International & King's College Scholarship (Cambridge Trust) Prince Consort Studentship (Faculty of History) https://www.repository.cam.ac.uk/handle/1810/374903 https://www.repository.cam.ac.uk/bitstreams/236db7f6-8e25-4486-928a-34dd9d9d47c3/download 87eda9de84448d1f82354d60eee3eb5f https://www.repository.cam.ac.uk/bitstreams/e1f4d3b2-0551-4bda-9f9f-5101077cd34c/download c5579ea290c6ab0f6f5a257903cf054d https://www.rioxx.net/licenses/all-rights-reserved/ Henri Bergson History of Philosophy Intellectual History Ralph Waldo Emerson Victor Cousin William James

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2D Electron Systems in Undoped GaAs and InGaAs and Progress Towards Undoped GaAs Nano-Structures 10.17863/CAM.56208 Ramsay, Benjamin Ritchie, David The MBE growth of high-quality GaAs/AlGaAs epilayer structures has enabled the study of novel physical phenomena, such as the Quantum Hall and Fractional Quantum Hall in a 2D electron system (2DES), 1D transport, and single-electron transport in 0D systems. The wide range of systems that can be studied all start with a 2DES from which 1D and 0D systems are formed by further confining the carrier gas. Undoped devices, which use an externally applied electric field to form a potential well for carriers, replicating the effect of dopants in a doped device, can have higher carrier mobilities and a lower charge impurity background than doped devices. This gives them advantages in specific applications such as nano-structures where charge impurities can prevent the device functioning and examining the condition of the MBE system used to grow the material. Be- cause dopants are not needed in undoped devices, material systems were dopants are difficult to work with due to contamination of growth system or causing significant disorder resulting in low carrier mobility can be studying using undoped devices, side stepping these difficulties. In this thesis, undoped AlGaAs/GaAs wafers allow the fabrication of 2D electron system (2DES) for n-type, p-type and ambipolar devices for studying the Quantum Hall effect in the Al0.33Ga0.67As and In0.1Ga0.9As material systems. The Quantum Hall effect for electrons and holes in a In0.1Ga0.9As quantum well showed remarkable different behaviour to GaAs quantum wells despite the low indium content. Undoped devices have their own fabrication challenges and needed optimisation to produce n-type, p-type, and ambipolar, heterostructures and quantum wells with high enough yields of 2DES that 1D and 0D systems can be fabricated with a reasonable success rate. Functioning 1D p-type channels demonstrate the successful fabrication of undoped nano-structures. The carrier mobility in undoped devices is limited by unintentional dopants included in the structure during growth. This means that the carrier mobility is a measure of the ‘cleanliness’ of the MBE growth system. From the carrier mobility-density curve shapes the dopant source of disorder in the structure can be determined allowing for feedback on the condition of MBE system, not possible with other device and techniques. University of Cambridge 2020-02-01 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/309114 https://www.repository.cam.ac.uk/bitstreams/ab3d755d-c115-4e46-a93b-5ab17be9b70c/download 0d3cfef88bbebed5d7b48df9ae4591b1 https://www.repository.cam.ac.uk/bitstreams/a5f9d473-4036-4946-bd73-dc3e6925aafe/download 353adac0d1ebdfd65ab16480263c3c87 https://www.rioxx.net/licenses/all-rights-reserved/ GaAs InGaAs Electron Systems 2D Electron Gas

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An Experimental and Theoretical Investigation into Mg-ion Battery Electrodes using Nuclear Magnetic Resonance Spectroscopy 10.17863/CAM.39377 Lee, Jeongjae 0000000342944993 Grey, Clare Dutton, Sian This thesis presents a combined experimental and theoretical approach on studying Mg-ion battery electrode materials, where Nuclear Magnetic Resonance (NMR) spectroscopy plays a central role in identifying the local structure and dynamics of the magnesium ions. Density Functional Theory (DFT) techniques are used extensively to (i) calculate and rationalise the observed NMR shifts, (ii) provide insights into the dynamics involved in such electrode materials, and (iii) guide the synthesis of candidate electrode materials. This work begins by a systematic study of 25Mg solid-state NMR in paramagnetic oxides, where the presence of transition metals makes them suitable for applications in high-voltage cathode materials. DFT methods for predicting and rationalising the paramagnetic NMR shifts are developed, with experimental verifications on synthesised samples. Feasibility of using advanced NMR pulse sequences such as Rotor-Assisted Population Transfer and Magic Angle Turning is demonstrated on such systems to afford enhanced resolution and sensitivity. This approach of combined NMR and DFT techniques is then applied to two of magnesium vanadates for high-voltage cathode applications. In particular, DFT-based thermodynamic energies are used to rationally design the synthetic steps leading to the said vanadate materials, followed by DFT prediction of the migration barriers. The prepared material was subject to experimental characterisation using NMR and diffraction techniques, with an initial cycling data in an electrochemical cell. In the final part, a combined experimental and ab initio investigation on Mg3Bi2, a promising Mg-ion battery anode material, is presented. Previous reports on variable-temperature 25Mg NMR spectroscopy is validated by DFT calculations on the migration barrier and defect energetics. Mechanistic insights on the migration mechanism are presented using the hybrid eigenvector-following transition state searching method, where the relativistic effects of heavy bismuth is shown to influence the migration barrier. We show that the defect formation energy of a Mg vacancy is critical in the apparent Mg diffusion barrier, which is heavily influenced by sample preparation conditions. University of Cambridge 2019-05-18 Thesis Doctoral Doctor of Philosophy (PhD) en https://www.repository.cam.ac.uk/handle/1810/292227 https://www.repository.cam.ac.uk/bitstreams/a56c88de-5805-4d12-ac2e-c0bd49690e66/download e85ce7e6135f6da99bb894838e03235b https://www.repository.cam.ac.uk/bitstreams/0d27f38e-4693-47e8-b6a5-06e53e20ffbf/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ Density Functional Theory Mg-ion Battery Solid-state NMR

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Descriptive complexity of constraint problems 10.17863/CAM.23470 Wang, Pengming Dawar, Anuj 0000000340148248 Constraint problems are a powerful framework in which many common combinatorial problems can be expressed. Examples include graph colouring problems, Boolean satisfaction, graph cut problems, systems of equations, and many more. One typically distinguishes between constraint satisfaction problems (CSPs), which model strictly decision problems, and so-called valued constraint satisfaction problems (VCSPs), which also include optimisation problems. A key open problem in this field is the long-standing dichotomy conjecture by Feder and Vardi. It claims that CSPs only fall into two categories: Those that are NP-complete, and those that are solvable in polynomial time. This stands in contrast to Ladner's theorem, which, assuming P$\neq$NP, guarantees the existence of problems that are neither NP-complete, nor in P, making CSPs an exceptional class of problems. While the Feder-Vardi conjecture is proven to be true in a number of special cases, it is still open in the general setting. (Recent claims affirming the conjecture are not considered here, as they have not been peer-reviewed yet.) In this thesis, we approach the complexity of constraint problems from a descriptive complexity perspective. Namely, instead of studying the computational resources necessary to solve certain constraint problems, we consider the expressive power necessary to define these problems in a logic. We obtain several results in this direction. For instance, we show that Schaefer's dichotomy result for the case of CSPs over the Boolean domain can be framed as a definability result: Either a CSP is definable in fixed-point logic with rank (FPR), or it is NP-hard. Furthermore, we show that a dichotomy exists also in the general case. For VCSPs over arbitrary domains, we show that a VCSP is either definable in fixed-point logic with counting (FPC), or it is not definable in infinitary logic with counting. We show that these definability dichotomies also have algorithmic implications. In particular, using our results on the definability of VCSPs, we prove a dichotomy on the number of levels in the Lasserre hierarchy necessary to obtain an exact solution: For a finite-valued VCSP, either it is solved by the first level of the hierarchy, or one needs $\Omega(n)$ levels. Finally, we explore how other methods from finite model theory can be useful in the context of constraint problems. We consider pebble games for finite variable logics in this context, and expose new connections between CSPs, pebble games, and homomorphism preservation results. University of Cambridge 2018-10-13 Thesis Doctoral Doctor of Philosophy (PhD) en https://www.repository.cam.ac.uk/handle/1810/276188 https://www.repository.cam.ac.uk/bitstreams/74dfacf4-8208-4d96-a318-54d7471b1aed/download 12823e96c3e4bf1f921596ff9f7ee12b https://www.repository.cam.ac.uk/bitstreams/a242f641-cd3b-4da5-8b0f-2987262b8f9f/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ Complexity theory Constraint satisfaction Logic Computer science Optimisation

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To say nothing of the existence of God : the question of Martin Heidegger's later work for contemporary theology. 10.17863/CAM.11769 Hemming, Laurence Paul There has been a persistent suggestion that Heidegger's work has major implications for theology, and in particular for 'fundamental theology' or that area of theological thought which is concerned with the nature of God, of creation and of being human. Heidegger has had an astonishing influence on not just one, but several movements in 20th century theology, having influenced Catholic and Protestant theologians alike. Despite having been taken up so widely, his place in Christian theology has rarely been analysed as a problem within itself, and where it has, the verdict so far has been largely negative. By analysing carefully Heidegger's critique of his own work I have been able to show that there are flaws in the conventional view of a fracture separating his earlier and later work. This is a provocative approach in existing scholarship because it challenges the basis on which Heidegger is being read in English and French, and to some extent in German, as well as the way in which his connection with theology has been either posited or repudiated. By indicating what Heidegger believed himself to be doing in his own work it has been possible to relocate him in ' relation to theology. This has important implications for some recent re-evaluations of medireval theology, and in particular the work of St. Thomas Aquinas. Reading Heidegger in this way would appear to place his work as far more centrally concerned with the western theological tradition than is more usually allowed. I have undertaken a survey of all the major works published in his lifetime, and also many of his lecture courses now available in the eighty-one volume Gesamtausgabe of his collected works. The conclusions I have drawn include an evaluation of the relevant English-speaking secondary literature. I have coupled this with reference to the attempts by French theologians, and Jean-Luc Marion in particular, to respond to Heid egger's work. � In consequence my thesis seeks to indicate (1) the particular problems concerning the 'tum' described earlier; (2) the points of unity between Heidegger's early and later work; (3) that Heidegger' s relationship and indebtedness to Nietzsche and his conception of Nihilism and the "death of God" have been ill-understood. In the light of these three issues, I have suggested (4) that Heidegger' s work can be understood as representing a critique of Christian appropriations of and engagements with philosophical ideas central to Western metaphysics, and (5) his later work in particular is philosophically rigorous and represents a considerable challenge to future theological endeavour. University of Cambridge 1999-01-01 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/265591 controlled.access https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/a6e09bb5-c1b5-49cb-8d4a-1821bf36d7ea/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/

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Economy and society in rural Russia: the serf estate of Voshchazhnikovo, 1750-1860. 10.17863/CAM.11782 Dennison, Tracy Kristine The central idea of this dissertation is to compare the dominant view of Russian rural society, as classically formulated by Aleksandr Chayanov in the early twentieth century, with local evidence from a particular serf community. Chayanov's view has been widely accepted not only as portraying a general type (the archetypal peasant), but as a substantially accurate representation oflate nineteenth and early twentieth-century peasant communities across the whole of European Russia, and much of Eastern Europe as well. In this picture, peasants are a paradigm of 'traditional society', with little sense of private property, an aversion to market transactions, social and geographical immobility, early and universal marriage, large multiple-family households, and strong communal ties. These features are often regarded as part of an underlying 'peasant culture' on which external constraints, such as serfdom, had little effect. In this dissertation, archival evidence for the Sheremetyev estate of Voshchazhnikovo in Y aroslavl' province is used to test this widely-held view. Household listings, soul revisions, parish registers, serf petitions, landlords' instructions, account books, communal meeting minutes, land transactions contracts, credit contracts, passport lists, inventories, and wills are used to construct a detailed picture of the workings of a serf society, and to examine the role of institutions such as serfdom and the peasant commune in a local context. The main finding of the dissertation, based on this evidence, is that the Chayanovian view is largely false, not only on the particular estate ofVoshchazhnikovo, but at least regionally in the province of Yaroslavl', and possibly beyond. The social and economic behavior of peasants here was not dissimilar to what has been found in many parts of pre-industrial western Europe. Serfs at Voshchazhnikovo were active participants in land, labour, and credit markets at the local and regional level. They were free to sell, let, mortgage, or bequeath their substantial private landholdings. They were geographically mobile; labourers came to work on the Voshchazhnikovo estate from other parts of Russia, and many estate serfs lived in Moscow and St Peters burg as migTant labourers. There was agTeat deal of intra-communal conflict on the estate. Not all serfs at Voshchazhnikovo lived in large, multi-generational households; mean household size ranged from 4.6 in 1816 to 5.2 in 1850, and roughly half of all households were the simple-family type. Wealth was not distributed equally; in fact, there was a high degree of socio-economic stratification, and inter-:-generational transfers of wealth were common. Finally, contrary to the traditional view, the external institutional framework - serfdom, in particular - did have a significant effect on social structure ancl peasant behaviour. University of Cambridge 2004-01-01 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/265604 controlled.access https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/4365c16f-5f2a-40d8-9ec8-77f33ee40929/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/

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Essays on Global Imbalances and the Financial Crisis 10.17863/CAM.57318 Lu, Saite Coutts, Ken This thesis investigates the linkages and the underlying causes of the current episode of global imbalances and of the 2007-09 Global Financial Crisis (GFC). It consists of three independent yet interconnected essays. The first essay is a theoretical paper. It sets the scene for the theoretical debates by first describing how the GFC unfolded, its economic consequences, the causes that are identified. It is followed by a critical assessment of three competing theories to explain the linkages between the global imbalances and the GFC: the global savings glut (GSG) hypothesis, the endogenous money (EM) and the global financing glut (GFG) hypotheses. The second essay is an empirical paper, which seeks evidence for each underlying logic chain behind the three theories. It has a particular focus on how credit creation and international capital flows impact on the US housing boom, credit boom, and consequently the consumption boom, before the GFC. A partial equilibrium model is built to simulate the propagation mechanisms based on the empirical findings. The third essay is a modelling chapter. It begins with a discussion of the development of macroeconomic models in general. Following Wynne Godley’s stock-flow consistent (SFC) modelling approach, the focus of this essay is to build a fully estimated empirical SFC model for the UK. The model features detailed financial balance sheets for the banking sector, which can be used to simulate the endogenous credit creation process and the interactions between the real and the financial sector within an economy. The simulations focus on the role of housing finance in generating the economic expansions and contractions as discussed in the second paper. University of Cambridge 2019-12-01 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/310230 https://www.repository.cam.ac.uk/bitstreams/b8efbb67-8634-45ff-936e-169af6cb867b/download 36b0315a6761fc503289d858d6f71690 https://www.repository.cam.ac.uk/bitstreams/14aa1c79-f0ce-494c-8f3d-a6282d469f76/download 353adac0d1ebdfd65ab16480263c3c87 https://www.rioxx.net/licenses/all-rights-reserved/ Financial crisis Global imbalances Stock-flow consistent modelling

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Tryptophanase Regulatory Mechanisms in Escherichia coli https://doi.org/10.17863/CAM.112440 Kelly, Ellis Summers, David Indole is a heterocyclic signaling molecule, synthesized by a wide array of bacterial species, but most studied in *Escherichia coli*. Indole is formed by the degradation of L-tryptophan through the action of the enzyme tryptophanase (TnaA). The *tnaA* gene is part of the tryptophanase (*tna*) operon, which is regulated by catabolite repression and tryptophan-induced transcription antitermination. Recent studies have unveiled two distinct kinetic modes of indole signalling in *E. coli*: a long-lasting but low-level (persistent) signal, and a transient, high-level (pulse) signal. The underlying mechanisms that regulate the indole pulse phenotype have not been fully characterised. Pulse signalling is thought to be linked to the increased expression of tryptophanase during the transition from exponential to stationary phase. Nonetheless, empirical data from the literature indicates the presence of tryptophanase during early to mid-exponential phase when indole synthesis is low or non-existent. This contradictory evidence indicates the existence of additional regulatory mechanisms controlling tryptophanase activity, and the indole pulse. This work has combined conventional shake-flask culture approaches with single-cell analysis to investigate tryptophanase expression and activity across all *E. coli* growth phases. From these studies a hypothesis has emerged that the indole pulse is triggered, at least in part, by post-translational activation of tryptophanase that results in the surge of indole production. Initial experiments focused on characterising the indole pulse. Significant variability was observed in the timing of the indole pulse in shake-flask culture, its timing varying within a window of about 40 min and its duration ranging from 30 to 45 minutes. The inability experimentally to regulate the timing of the pulse by mutation of the *tna* operon or by plasmid-based tryptophanase expression indicated a post-translational regulatory mechanism might be acting on tryptophanase. Tryptophanase expression measured throughout growth showed tryptophanase protein levels *per* cell are similar in exponential and early stationary phase. This suggests the pulse is triggered by both *de novo* synthesis and activation of pre-existing tryptophanase enzyme. Tryptophanase activity assays on enzyme harvested at different growth phases were consistent with this idea. An indication of the mechanism of post-translational regulation came from the use of single-cell microfluidic studies. Within individual cells, tryptophanase was either concentrated at a polar focus or dispersed throughout the cell. The dispersal of polar foci appears to be critical for the triggering of the indole pulse. As a result of the COVID-pandemic, laboratory access was restricted for a substantial portion of this study, prompting the use of alternative research methods. Consequently, an exploration of tryptophanase distribution and potential evolutionary history was undertaken in *E. coli* and other gut microbial species. The results indicate TnaA is maintained in *E. coli*, and there is evidence that it is a component of the core genome. TnaA extends beyond *E. coli*, being identified in 10% of the bacterial species sequenced in the microbiome. It is present across various phyla of the gut microbiome, including Proteobacteria, Firmicutes, and Bacteroidota. University of Cambridge 2024-01-31 Thesis Doctoral Doctor of Philosophy (PhD) eng Cambridge Trust Gonville and Caius College https://www.repository.cam.ac.uk/handle/1810/374345 https://www.repository.cam.ac.uk/bitstreams/7ffb1be4-3a0d-4609-9806-723c82f584ba/download 1a4d746f492781090424f3c22efef0fd https://www.repository.cam.ac.uk/bitstreams/43eb10d9-b834-42c7-ae38-56c2d7e02153/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ Indole Tryptophanase

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Due process and international law: and the applicability of international standards for national courts to the international criminal courts. Viles, Thomas Charles. University of Cambridge 2000-03-14 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/251710 controlled.access https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/807dff13-8098-4c0e-8608-57a9deafa609/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/

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Quasinormal Modes of Nearly Extremal Black Holes https://doi.org/10.17863/CAM.106739 Joykutty, Jason 0000000347429480 Warnick, Claude Quasinormal modes are the gravitational wave analogue to the overtones heard after striking a bell; like many physical systems, black holes emit radiation as a response to perturbations. After a dynamical event, for example a black hole merger, the system is expected to relax to a stationary black hole solution. After sufficient time, the system can be treated as a perturbation to this stationary solution in what is called the ringdown phase. The observed gravitational wave signal is dominated by the ringing associated with these solutions to the linear perturbation equations in this period of the evolution. Each quasinormal mode is characterised by a complex frequency which encodes its behaviour in time: the imaginary part determines its oscillation and the real part its exponential decay. In light of the observation of gravitational wave signals in the past few years, quasinormal modes are important from an astronomical perspective. By comparing the observed gravitational wave signal from some dynamical event with the predictions provided by computing quasinormal frequencies, one can compare the fit given by general relativity against some modified theory of gravity and test which is a better model for these phenomena. This black hole spectroscopy could also be used to deduce the parameters of an astrophysical object from the gravitational wave signal. As horizons become extremal, various computations (from a range of authors including Detweiler, Hod and Zimmerman) have shown that in many cases, there exists a sequence of frequencies which become purely oscillatory in the limit and which cluster on a line in the complex plane. These zero-damped modes are typically the most slowly decaying resonances of the equation and hence are key to understanding stability. In the case of a positive cosmological constant, they are closely tied to the Strong Cosmic Censorship Conjecture: if the spectral gap is too large, the modes don't decay slowly enough to destabilise the Cauchy horizon. From the large variety of examples in the literature of nearly extremal black holes with zero-damped modes, it is natural to conjecture that this phenomenon is generic. This thesis explores mathematically rigorous results that can be obtained toward resolving this question. In particular, we shall review the literature on quasinormal modes (focussing on zero-damped modes), discuss the mathematical definition of these objects and the idea of co-modes or dual resonant states: solutions to the adjoint problem which can make identifying the frequencies easier. Finally, we shall use this framework and Gohberg-Sigal theory to prove existence results for zero-damped modes: firstly in the case of wave equations with potentials which decay sufficiently rapidly, then for a large class of static, spherically symmetric black hole spacetimes. There are also partial results toward resolving the question for the Kerr-de Sitter spacetime. University of Cambridge 2023-10-31 Thesis Doctoral Doctor of Philosophy (PhD) eng Department of Applied Mathematics and Theoretical Physics, Cambridge. Gonville & Caius College, Cambridge. https://www.repository.cam.ac.uk/handle/1810/365433 https://www.repository.cam.ac.uk/bitstreams/8a455878-c500-4f7f-9b98-4f3568238443/download fa4b3ea479c3f531ac3845b67289d525 https://www.repository.cam.ac.uk/bitstreams/143fe3b6-7110-42fc-9109-f47bff5b7468/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ Black holes General relativity Quasinormal modes

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The New Halal: Islamic Ethical Consumerism in the UK, Germany, and Egypt. A Social Movement Framing Approach 10.17863/CAM.51881 Shash, Maha Hany Kandil, Hazem This dissertation examines political consumerism using a social movement theory approach. It investigates the origins of Islamic consumer campaigns aimed at changing Muslim consumer behaviour, and integrating them into European societies. It draws upon the ‘framing perspective’ within social movement theory to analyse how Islamic campaigners promote the values of environmentalism, animal welfare, and fair trade in the UK, Germany, and Egypt. This dissertation argues that Muslim minorities in Europe frame a conventionally secular moral concern as a religious duty in order to connect Islam to contemporary consumption values. In the Muslim majority country of Egypt, these same consumption values are promoted based on secular ethics rather than religion. Based on the analysis of in-depth semi-structured interviews and campaign documents, posters, websites, events, and conferences, this dissertation demonstrates how the overall goal of these framing processes is to align Muslim consumer behaviour with ethical consumer campaigns in order to assimilate Muslims in Europe without undermining the guiding role of religion. It also aims at integrating Muslims into European culture by highlighting Islam’s potential as a catalyst for positive behaviour. University of Cambridge 2019-05-02 Thesis Doctoral Doctor of Philosophy (PhD) en https://www.repository.cam.ac.uk/handle/1810/304799 controlled.access https://www.repository.cam.ac.uk/bitstreams/60a3a6e4-98cb-4a2f-8d84-7486ca611b29/download c08583c38946fcab134fa91e09d3a558 https://www.repository.cam.ac.uk/bitstreams/26fcf239-72db-4fa1-bf1f-55ebfdc091d7/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ Islamic Ethical Consumerism Framing Islamic Environmentalism Islamic Vegetarianism Islamic Fair Trade Political Consumerism Ethical Consumerism Social Movement Theory Framing Analysis Collective Action Frames Islam in Europe Muslim Minorities Environmentalism Muslim Vegetarians Environmentalism in Egypt Muslim Consumer Behavior Animal Welfare Vegetarianism Fair Trade Muslims in Britain Muslims in Germany Halal and Tayyib Framing and Identity Consumer Campaigns Sociology of Consumption Diagnostic Framing Pro-environmental behaviour (PEB) cultural revitalization

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It's Not a SKZCAM! Accurate Surface Chemistry at Low Cost https://doi.org/10.17863/CAM.116944 Shi, Benjamin Xu Michaelides, Angelos Designing next-generation materials for e.g., heterogeneous catalysis or gas storage requires a deep understanding of their surface chemistry. Simulations provide the needed atomic-scale insights, allowing for fundamental quantities like the adsorption energy and oxygen vacancy formation energy to be calculated. Consistently achieving accurate predictions will require going beyond the standard density functional theory (DFT) to methods like coupled cluster theory with single, double, and perturbative triple excitations [CCSD(T)]. However, the high computational cost of CCSD(T) typically necessitates the use of embedded cluster models, where the surface is modelled as a finite cluster [treated with CCSD(T)] that is coupled to the environment. Unfortunately, designing converged yet computationally tractable clusters is challenging, which has limited the routine application of CCSD(T) to surface chemistry. This thesis introduces the SKZCAM (pronounced "scam") protocol to overcome the limitations of embedded cluster models for metal-oxide surfaces. It provides a general, automated framework applicable to a wide range of ionic crystal structures, surface terminations, and adsorption/defect sites. In particular, it leads to small cluster sizes that are amenable for CCSD(T), enabling us to resolve long-standing debates across surface chemistry. For example, we reach consensus with experiments on the adsorption energy for the notorious CO on MgO(001) and 18 other molecule-surface systems, including molecules on the TiO₂ rutile(110) and anatase(101) surfaces. At the same time, we have uncovered new insights into complex surface systems, such as the structure of Au₂₀ and the binding behaviour of H₂O and CH₃OH on MgO(001). In addition, this set of adsorption energy and vacancy formation energy CCSD(T) references -- the largest in surface chemistry -- has also offered new insights into the performance of common density functional approximations and dispersion corrections in DFT. By integrating the SKZCAM protocol into an open-source workflow, we have now set the stage for accurate, low-cost predictions of surface reactions for reliable catalyst design. University of Cambridge 2024-09-29 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/381924 https://www.repository.cam.ac.uk/bitstreams/ac56bafe-6923-40a0-8e24-5080ed86477f/download 1120e4f3647cb953b5c982f5686a9c40 https://www.repository.cam.ac.uk/bitstreams/05602345-d19e-443a-a598-62d870cd1dc8/download 87eda9de84448d1f82354d60eee3eb5f http://purl.org/NET/rdflicense/allrightsreserved density functional theory ionic crystals materials metal-oxides quantum chemistry surfaces wave function theory

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Novel Phenotyping of the Myocardium by Diffusion Tensor Cardiovascular Magnetic Resonance 10.17863/CAM.30595 Khalique, Zohya Pennell, Dudley Andrew, Scott Novel Phenotyping of the Myocardium by Diffusion Tensor Cardiovascular Magnetic Resonance Dr Zohya Khalique Introduction The heart has a complex microarchitecture facilitating its function. The helical cardiomyocyte arrangement (left-handed in the epicardium through to right-handed in the endocardium) drives torsion. Sheetlets are aggregated cardiomyocytes that realign from wall-parallel in diastole, to wall-perpendicular in systole. This sheetlet mobility is integral to wall thickening. Diffusion tensor cardiovascular magnetic resonance (DT-CMR) is a novel, non-invasive technique informing about myocardial microstructure, including cardiomyocytes and sheetlets. Few in-vivo human studies exist. This research aims to investigate microstructural changes in disease and assess the utility of DT-CMR as a novel phenotyping tool. Methods Biphasic DT-CMR was performed in controls and in patients with dilated cardiomyopathy (DCM), including recovered dilated cardiomyopathy (R-DCM) and congenital disease, as exemplified by situs inversus totalis (SIT). Two main DT-CMR sequences, stimulated echo acquisition mode (STEAM) and second-order motion-compensated spin echo (M2-SE) were compared in a hypertrophic cardiomyopathy cohort. Volumetric analysis, strain assessment and late gadolinium imaging was performed. Results In DCM sheetlet mobility was reduced, with a more diastolic orientation at both cardiac phases. In R-DCM, despite normalisation of left ventricular size and ejection fraction, microstructural abnormalities persisted, with impaired sheetlet mobility. In SIT, there was gross cardiomyocyte derangement, with an overall pattern of inversion of the helical arrangement basally, transitioning to a more normal pattern apically. This microstructural derangement led to reduced torsion and strain. Finally, STEAM and M2-SE results differ due to intrinsic differences in the two sequence types. Overall STEAM was more reliable than M2-SE in biphasic DT-CMR. Conclusion DT-CMR identified novel cardiomyocyte and sheetlet abnormalities in-vivo. DT-CMR offers unique insight into microstructural changes in disease, and this work supports its potential as a powerful clinical tool assessing course and prognosis in cardiac conditions. University of Cambridge 2018-10-02 Thesis Doctoral Doctor of Medicine (MD) en https://www.repository.cam.ac.uk/handle/1810/283229 controlled.access https://www.repository.cam.ac.uk/bitstreams/c0d79b5d-e7dc-4727-b123-7a7ce4350a25/download 8961379ec8c5d3dc78186bf28d2489d8 https://www.repository.cam.ac.uk/bitstreams/7ff4cc2f-8a77-48b5-9f0b-84ce9249ad86/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ Diffusion Tensor Cardiovascular Magnetic Resonance Cardiac Microstructure Dilated Cardiomyopathy Situs Inversus Totalis

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Synthesis of neuromorphic circuits with neuromodulatory properties 10.17863/CAM.53750 Ribar, Luka 0000000270506387 Sepulchre, Rodolphe The field of neuromorphic engineering shows great promise in delivering novel devices inspired by biological principles that would undertake sensory and processing tasks with an unprecedented level of efficiency. In order to achieve that, engineers are required to understand and implement the many complex biological regulatory mechanisms that allow the nervous system to robustly operate and adapt over scales covering many orders of magnitude, while at the same time using unreliable and noisy components. As a step towards that, this thesis aims at discussing and implementing the principles of neuromodulation in neuromorphic hardware, mechanisms which allow neurons to change and regulate their behaviour through the continuous control of their internal currents. We discuss how neural dynamics and its modulation can be broken down into four essential feedback loops, and we introduce a simplified model of the neural membrane respecting this fundamental structure. We present a novel methodology for controlling the neuron's behaviour through the shaping of its I-V curves in distinct timescales, thus characterising the behaviour of the neural circuit through its input-output properties. We show how modulation of the feedback loops affects the behaviour, and importantly, captures the transition between spiking and bursting oscillatory regimes, two major signalling modes of neurons. We then show how the architecture can be easily implemented using well-known neuromorphic building blocks based on subthreshold MOSFET circuits. Finally, we discuss how the excitability switch captured by the model can be exploited in simple network settings, thus opening up the possibility for future research into novel architectures where the control of cellular properties is utilised to shape the global behaviour of the network. University of Cambridge 2019-10-31 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/306663 https://www.repository.cam.ac.uk/bitstreams/4dd6e037-ebce-456a-bcae-b30b606b8764/download c7925bab872ab7bbba190b8fbc814f72 https://www.repository.cam.ac.uk/bitstreams/f3bc2fce-b45b-40a9-bf13-417da365b0a7/download 353adac0d1ebdfd65ab16480263c3c87 https://www.rioxx.net/licenses/all-rights-reserved/ Neuromorphic engineering Neuronal behaviors Neuromodulation Neuronal bursting I-V curve shaping Subthreshold electronics

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Pastoralists, Peasants, and Politics in Roman North Africa https://doi.org/10.17863/CAM.101614 Shaw, Brent Donald Reynolds, Joyce Pastoralists, Peasants, and Politics is an investigation of the interaction between nomads and sedentarists in North Africa during the period of Roman rule, with concentration on the aspects of the relationship that pertain directly to the extension of Roman political authority over the Maghrib. Following a brief discussion of the place of the subject in modern historiography, the introductory chapters turn to a consideration of the prehistoric origins of pastoral nomadism in the Saharan neolithic, and trace its gradual infiltration into the Maghrib and its relationship to incipient agricultural sedentarism. The last of the introductory chapters reviews the literature of the Mediterranean elites and reveals their attitudes towards the pastoral nomad as a type. The analysis seeks to establish the precise nature of sedentarist prejudices as a necessary precursor to the rational interpretation of the Classical literary sources. In the central chapters of the dissertation the political history of the relations between the Roman state and nomadic groups (viz. the Gaetuli) who inhabited the regions beyond the Roman province is analyzed. The history of the violent encounters between the two is combined with a synchronic typology of the various types of violence in Gaetulia. The narrative culminates with an investigation of the 'rebellion of Tacfarinas', its possible causes, and the supposed responses of the Roman administration to nomad problems (e.g. the myth of tribal reserves). The latter part of the dissertation concludes with a synoptic view of two aspects of the nomad-sedentarist interaction during the period of the full establishment of Rome's African empire. The first aspect is one which has not received due attention in modern scholarship, namely, the degree of symbiosis between nomads and sedentarists based on various types of exchange -- social, economic, and political. The final chapter concentrates on the problem of frontier relations, specifically the place of pastoral nomadism within the framework of the different types of limes systems constructed for the protection of sedentarist communities along the southern frontier of the Roman provinces. University of Cambridge 1978-08 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/357339 https://www.repository.cam.ac.uk/bitstreams/8bf5f8e8-7e15-4b37-84ea-551f19ed0e3f/download eb9d2d75cbfff5683a827dd2229be5c0 https://www.repository.cam.ac.uk/bitstreams/617d7c09-e4b2-40b2-ad84-ab9bc0440d16/download f4d08039cd8f7b66b8d0a5bf826a68c9 https://www.repository.cam.ac.uk/bitstreams/2a204aff-e67e-4f05-bf9d-5050aaacbe44/download c4b08e534ca4b0d60b57f7f06ec099a9 https://www.rioxx.net/licenses/all-rights-reserved/ Nomads Sedentarists North Africa Roman rule Pastoralists

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A study of ultra-high field strength structural and spectroscopic MR imaging in dementia with Lewy bodies and Alzheimer’s disease https://doi.org/10.17863/CAM.122651 McKiernan, Elizabeth O'Brien, John Su, Li Despite its position as the second commonest form of neurodegenerative dementia, dementia with Lewy Bodies (DLB) is relatively poorly understood, with little research focusing on its pathophysiology or symptomatology in comparison with Alzheimer’s disease (AD) or Parkinson’s disease (PD), to which it is closely related. In contrast to AD, which typically presents with amnesic cognitive deficits, DLB more commonly presents with complex neuropsychiatric symptoms, including complex visual hallucinations, cognitive fluctuations, rapid eye movement (REM) sleep behaviour disorder (RBD), and parkinsonism. In this PhD thesis I present a detailed investigation of neuroimaging changes found in DLB compared to in AD, in comparison to cognitively healthy older adults, using ultra-high field, 7 tesla (7T), brain magnetic resonance imaging (MRI) and single voxel proton magnetic resonance spectroscopy (MRS). First, I conducted systematic reviews of the AD and DLB, MRI and MRS literature, demonstrating that DLB is under-represented in high (3T) and ultra-high (7T) field strength MR research. Next, I gathered neuropsychological and neuropsychiatric data, alongside 7T structural, susceptibility and spectroscopy imaging data, in a cohort of 65 participants with DLB, AD, and normal cognition. I collected this data as part of a study I conducted known as 7T-DLB. The aim of 7T-DLB is to utilise the benefits of 7T MR to gain a deeper understanding of the changes in brain structure, tissue susceptibility, and neurochemistry underlying DLB, and in association with its key symptoms. I analysed 7T-DLB structural data, concentrating on the measurement of subfield volumes in the hippocampus, amygdala, and thalamus, showing that, in mild to moderate DLB, pronounced amygdala subfield atrophy is present (compared to controls), is almost as marked as in AD, and is associated with measures of cognition and visual hallucinations. I also show that widespread hippocampal subfield atrophy is present in DLB (compared to controls), and though it is less pronounced than in AD, it is more extensive than has previously been described at lower MR field strengths. Finally, I analysed 7T-DLB spectroscopy data, from voxels placed in the left occipital lobe and left thalamic region showing that myoInositol (a putative marker of neuroinflammation) is higher in patients compared to controls. I also suggest that changes in concentrations of gamma-aminobutyric acid (GABA) and glutamate (the primary inhibitory and excitatory neurotransmitters in the brain) may be related to visual hallucinations and cognitive fluctuations, though these analyses were exploratory and findings tentative. In summary, 7T-DLB is a novel study as it uses a relatively new technology to investigate an under-researched disease and focuses on key non-cognitive symptoms. Together the findings presented in this thesis demonstrate the utility of ultra-high field imaging for the investigation of DLB. University of Cambridge 2025-04-23 Thesis Doctoral Doctor of Philosophy (PhD) eng The pilot section of the study was funded via a £5K pump-priming grant from the East Network Centre of Alzheimer’s Research UK (ARUK). The main study was funded via an Alzheimer’s Society Clinical Research Fellowship grant of £232.5K (AS-CTF-17b-003). An additional £2.5K of funding for consumables was granted by ARUK. Around £10K of scanning was provided by Cambridge Centre for Parkinson’s Plus, an anonymous philanthropic donation https://www.repository.cam.ac.uk/handle/1810/391558 embargo 2026-10-30 https://www.repository.cam.ac.uk/bitstreams/4a21b301-29e6-49cf-8948-512a2c61a375/download f7725ecd509bc89fab60b9262b542ce9 https://www.repository.cam.ac.uk/bitstreams/ad6ae52a-66ca-44ff-8d1b-1971f905494a/download 87eda9de84448d1f82354d60eee3eb5f http://purl.org/NET/rdflicense/allrightsreserved Alzheimer's disease dementia with Lewy bodies magnetic resonance imaging magnetic resonance spectroscopy seven tesla MRI

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The governance of England : law, reform and the common weal, c. 1460 - c. 1560 10.17863/CAM.19529 Lockwood, Shelley University of Cambridge 1991-01-01 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/272520 controlled.access https://www.repository.cam.ac.uk/bitstreams/209ea7dd-e4ab-4cfe-b115-d653727d9c9b/download 414e4fee864fd6cd81dbca6f7c74a444 https://www.repository.cam.ac.uk/bitstreams/b9962d9d-5079-4c9e-b6ee-97aee57d3633/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/

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Understanding and designing complex architectures of biomolecular condensates https://doi.org/10.17863/CAM.111884 Erkamp, Nadia Knowles, Tuomas Biomolecular condensates emerge when a homogeneous liquid phase separates into the condensate and a dilute phase. Condensates in cells function as membrane-less organelles and perform a variety of (temporary) functions. They may also be involved with pathological processes, like the progression of neurodegenerative diseases. Additionally, they are of interest for various bioengineering applications such as drug delivery and synthetic biology research. The mesoscale architecture of condensates, how different phases are organized compared to each other, is intimately connected to their function. However, very little tools are available to control the structure. In my thesis, I establish methods for understanding and controlling different mesoscale architectures of condensates. Firstly, I have worked on the development of microfluidic methods to measure phase diagrams. These allowed us to measure protein solubility and tie lines, as well as understand when and how condensates form. Then, I studied the nucleation of droplets in liquid-like condensates, including the nucleation of the dilute phase and dense phase droplets. Lastly, I've applied the developed techniques to work on a biological problem: the use of phase separating antimicrobial peptides. Overall, my findings and developments provide understanding and control over condensate architecture in a range of condensate systems with direct implications of therapeutic interventions. University of Cambridge 2024-04-12 Thesis Doctoral Doctor of Philosophy (PhD) eng Royall Scholarship https://www.repository.cam.ac.uk/handle/1810/373498 https://www.repository.cam.ac.uk/bitstreams/0fe611fe-509f-4782-a368-57b2fec4882f/download 00d1bf7970a5f0c93d0ba9c7080b9dff https://www.repository.cam.ac.uk/bitstreams/90978f09-fed2-477b-82af-a84a1af2f12e/download 87eda9de84448d1f82354d60eee3eb5f https://creativecommons.org/licenses/by/4.0/ biomolecular condensates Dynamics Microfluidics Phase diagram

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The Acoustics of Cerebral Aneurysms 10.17863/CAM.87800 Lamarquette, Amélie Agarwal, Anurag Stroke is not only the second leading cause of death worldwide, accounting for several million deaths per year, but also a leading factor of disability. Ruptured aneurysms are the most common cause of spontaneous subarachnoid haemorrhage, a devastating type of stroke. Aneurysms are localised expansions of blood vessels. Brain aneurysms most often form a bulge at a blood vessel bifurcation. The possible outcomes of ruptured aneurysms are disastrous, with a high death rate. The rupture of aneurysms is a complex phenomenon resulting from damage to walls of the blood vessel. Heamodynamics and vibrations are thought to be involved in the degradation of blood vessel structure. A sound, called bruit, is sometimes produced by unruptured brain aneurysms, which is a sign that these cerebral lesions are subject to wall vibrations. The aim of this thesis is to provide a better understanding of aneurysm sounds as they could be a crucial source of information to understand the reasons behind aneurysm rupture. Here we present an acoustic experiment investigating the source of aneurysm sound. In our simplified geometry, we identify that self-excited flow oscillations can generate sound at a distinct frequency. Periodic flow fluctuations have been observed in aneurysms by various studies. However, the potential of flow oscillations to cause aneurysm wall vibrations (hence sound) had not yet been proven. In our acoustic experiment we observe that, at critical flow rates, the frequency of the self-excited flow structures matches the structural natural frequency of the aneurysm model, leading to a resonance. We propose a theoretical model to predict the structural natural frequencies of our simplified model. Previously, the hypothesis that aneurysms vibrate at their preferred frequencies had been subject to debate as some researchers suggested that aneurysms are in fact stable (i.e. aneurysms do not vibrate at their natural frequency). This thesis constitutes an experimental proof that aneurysm are subject to resonance under certain conditions. More research is needed to link the mechanisms observed in this thesis and the rupture of aneurysms but, knowing if a cerebral lesion is subject to self-excited vibrations or resonance could be a valuable information in the estimation of the rupture risk, which in turn could help surgeons make more informed decisions. University of Cambridge 2021-09-30 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/340362 https://www.repository.cam.ac.uk/bitstreams/eefb303b-c8c3-4612-a3a5-ba095c54ef40/download 9ff39b78ac5b89fdb8b51b6859b32340 https://www.repository.cam.ac.uk/bitstreams/76970057-ec90-47e5-b860-0ff3ab499198/download a0d5feb2f73df664ad914ac779a77f35 https://www.repository.cam.ac.uk/bitstreams/b55bf502-f8e3-4e98-8ba3-7ba5136bcf00/download 038a7e66cf832cd067fac3f6544aed9f https://www.repository.cam.ac.uk/bitstreams/d3d6e07a-d259-4ae1-a843-8f8abddc9e0e/download 547eec5edca49e71cd986f5b3da8ac87 https://www.rioxx.net/licenses/all-rights-reserved/ aneurysm cerebral saccular instability self-excited acoustics flow oscillations vibrations fluid mechanics

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Bayesian Methods and Machine Learning in Astrophysics 10.17863/CAM.36974 Higson, Edward John 0000000183834614 Lasenby, Anthony Hobson, Mike Handley, Will This thesis is concerned with methods for Bayesian inference and their applications in astrophysics. We principally discuss two related themes: advances in nested sampling (Chapters 3 to 5), and Bayesian sparse reconstruction of signals from noisy data (Chapters 6 and 7). Nested sampling is a popular method for Bayesian computation which is widely used in astrophysics. Following the introduction and background material in Chapters 1 and 2, Chapter 3 analyses the sampling errors in nested sampling parameter estimation and presents a method for estimating them numerically for a single nested sampling calculation. Chapter 4 introduces diagnostic tests for detecting when software has not performed the nested sampling algorithm accurately, for example due to missing a mode in a multimodal posterior. The uncertainty estimates and diagnostics in Chapters 3 and 4 are implemented in the $\texttt{nestcheck}$ software package, and both chapters describe an astronomical application of the techniques introduced. Chapter 5 describes dynamic nested sampling: a generalisation of the nested sampling algorithm which can produce large improvements in computational efficiency compared to standard nested sampling. We have implemented dynamic nested sampling in the $\texttt{dyPolyChord}$ and $\texttt{perfectns}$ software packages. Chapter 6 presents a principled Bayesian framework for signal reconstruction, in which the signal is modelled by basis functions whose number (and form, if required) is determined by the data themselves. This approach is based on a Bayesian interpretation of conventional sparse reconstruction and regularisation techniques, in which sparsity is imposed through priors via Bayesian model selection. We demonstrate our method for noisy 1- and 2-dimensional signals, including examples of processing astronomical images. The numerical implementation uses dynamic nested sampling, and uncertainties are calculated using the methods introduced in Chapters 3 and 4. Chapter 7 applies our Bayesian sparse reconstruction framework to artificial neural networks, where it allows the optimum network architecture to be determined by treating the number of nodes and hidden layers as parameters. We conclude by suggesting possible areas of future research in Chapter 8. University of Cambridge 2018-10-01 Thesis Doctoral Doctor of Philosophy (PhD) en https://www.repository.cam.ac.uk/handle/1810/289728 https://www.repository.cam.ac.uk/bitstreams/58a2b8a9-4626-4f6e-82df-f86012ba7d14/download 183fbba033a77437ef07afc68fce63e5 https://www.repository.cam.ac.uk/bitstreams/e1138ca9-a93d-42cf-b4a4-c82b3a5a18ac/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ Machine Learning Bayesian Inference Nested sampling Cosmology Black Holes Gravitational Waves Neural Networks Regression Astrophysics Sparsity Parameter Estimation Bayesian Evidence Bayesian Statistics Bayesian Sparse Reconstruction Computational Methods Error Analysis Dynamic Nested Sampling nestcheck perfectns dyPolyChord dynesty Image Processing Sparse Reconstruction Planck diagnostic tests error analysis PolyChord MultiNest Hubble Space Telescope Fitting Nonparametric statistics

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Mixed Lead-Tin Halide Perovskites for Optoelectronic Applications https://doi.org/10.17863/CAM.97120 Dey, Krishanu 0000000334696184 Stranks, Sam Mixed lead-tin (Pb-Sn) perovskites are unique materials in the family of halide perovskites. Unlike Pb perovskites, these mixed-metal systems can demonstrate bandgaps below 1.3 eV and are therefore essential constituents for low bandgap bottom subcell in all-perovskite tandem solar cells as well as for near-infrared light emitting diodes (LEDs), lasers and photodetectors. Although the air stability of these Sn-containing perovskites are relatively poor due to the facile oxidation of Sn2+ to Sn4+, these materials do possess certain bright aspects in their optoelectronic properties which have received less attention in the community and this forms the foundation of this thesis. Chapter 1 provides a bigger picture of the need to explore sustainable alternatives to energy generation and consumption and the role of emerging semiconductor materials, especially metal halide perovskites, in that pursuit. Chapter 2 provides a general background to semiconductors and outlines the operating principles of solar cells and FETs. It also presents the current understanding of the optoelectronic properties and degradation mechanisms of mixed Pb-Sn halide perovskites. All the experimental techniques used in the thesis are introduced in Chapter 3. Chapter 4 summarises the optimization strategies of mixed Pb-Sn halide perovskite systems for demonstrating reliable and hysteresis-free p-type perovskite FETs with high hole mobility reaching 5.4 cm2/Vs and ON/OFF ratio approaching 106, which are among the best metrics in the field of perovskite FETs. We also rationalize these findings of long-range lateral transport with the support of theoretical calculations, film morphology studies and chemical analysis of defects in these materials. We then extend the above work to probe the lateral charge transport mechanism in mixed Pb-Sn perovskite FETs in Chapter 5. Through temperature-dependent field-effect mobility measurements, aided further with photoluminescence microscopy under bias, we show that ionic screening effects are greatly suppressed in mixed Pb-Sn devices when compared to their Pb-based analogues. We also demonstrate that dipolar disorder (associated with methylammonium, MA+ cation) induced lowering of FET mobility near room temperature can also be seen for mixed Pb-Sn perovskites and hence further efforts need to be invested in going MA-free in future. Next, we generalize the above findings of suppressed ion dynamics in mixed Pb-Sn systems by fabricating optoelectronic device stacks with vertical charge transport in Chapter 6, which are relevant for solar cells and LEDs. We reconcile these findings through first principles calculations, which reveal the key role played by Sn vacancies (with low formation energy) in increasing the migration barrier for iodides due to severe local structural distortion in the lattice. In Chapter 7, we show that the partial or complete incorporation of Sn in the metal (B) site of mixed halide perovskites offer very promising intrinsic stability to halide segregation under a host of processing and operational conditions. We further study the optoelectronic properties of these mixed halide Pb-Sn perovskites to understand the impact of light soaking on the charge carrier recombination and transport in these materials. We also assess the device performance of these mixed halide perovskite materials by fabricating single single junction solar cells. Chapter 8 summarises the key findings of this thesis and proposes several potential directions of research involving these mixed Pb-Sn perovskites. All the work presented herein provides an important advance to the fundamental understanding and applied device integration of mixed lead-tin perovskite materials and can be leveraged for demonstrating a ‘perovskite optoelectronic universe’ with high performance and stability. University of Cambridge 2022-11-01 Thesis Doctoral Doctor of Philosophy (PhD) eng Cambridge Trusts, Cambridge Philosophical Society, Churchill College, European Research Council, Institution of Engineering & Technology (IET), The Armourers and Brasiers' Gauntlet Trust, SuperGen SuperSolar https://www.repository.cam.ac.uk/handle/1810/350831 embargo 2026-06-12 https://www.repository.cam.ac.uk/bitstreams/9d83c65a-a5e3-4951-9578-4682eba45e25/download 035b079255f707604362640ea2e04136 https://www.repository.cam.ac.uk/bitstreams/2763acef-106c-429f-8bc2-e1d7877ad93d/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ Halide perovskites Lead-tin perovskites perovskite optoelectronics Perovskite solar cells Perovskite field effect transistors

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William Lord Hastings and the governance of Edward IV, with special reference to the second reign (1471-83) 10.17863/CAM.19121 Westervelt, Theron University of Cambridge 2001-01-01 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/272111 controlled.access https://www.repository.cam.ac.uk/bitstreams/1be5a0ac-6b3b-436b-85bc-bc6645e40dc5/download 48dabae4b8acfe892469615a68f525fb https://www.repository.cam.ac.uk/bitstreams/c1c26f75-53b7-455a-90ff-5167b6a66c99/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/

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Genomic insights into the host range and interspecies transmission dynamics of Staphylococcus aureus 10.17863/CAM.80382 Matuszewska, Marta 0000000226537725 Weinert, Lucy 0000000292796012 Holmes, Mark 0000000254541625 Staphylococcus aureus is an important human bacterial pathogen with a wide host range, including livestock, companion, and wild animal species. Genomic and epidemiological studies show that S. aureus can freely transmit between different species, with some of these transmissions resulting in successful adaptation and ongoing transmission in a new species. Given an ever-increasing risk of zoonotic disease emergence due to changes in the humananimal interface, it is increasingly important that we understand the capacity for human pathogens such as S. aureus to move between and adapt to different host species. In this thesis, I apply comparative genomic analyses to investigate the host range, transmission dynamics and host adaptation of S. aureus in livestock, companion animal, and wild animal populations. Chapters 2 and 3 consider the role of horizontal gene transfer in the adaptation of S. aureus clonal-complex (CC) 398 to livestock. CC398 is the dominant S. aureus lineage in European livestock and is implicated in increasing numbers of human infections. I found that the emergence of livestock-associated CC398 coincided with acquiring a Tn916 transposon carrying a tetracycline resistance gene, which has now been stably maintained for 57 years. This was followed by the acquisition of a SCCmec type V that carries methicillin, tetracycline, and heavy-metal resistance genes, which some lineages have maintained for 35 years. In contrast, a phage containing human immune evasion genes is dynamically gained and lost. These contrasting dynamics result in no loss of antimicrobial resistance but the rapid acquisition of the human adaptive element when methicillin-resistant S. aureus (MRSA) jumps from livestock into humans. In later chapters, I address a gap in our understanding of host specificity of S. aureus through using unbiased sampling of both methicillin-sensitive S. aureus (MSSA), and MRSA isolates from both an unsampled wild animal population and an undersampled companion animal species. Chapter 4 investigates the prevalence and risk factors associated with S. aureus carriage in cats in south-eastern Poland. Results suggest that older cats, sick cats, and cats with an S. aureus colonised owner increase the risk of carriage. I then used whole-genome sequences to investigate population structure, showing that S. aureus in cats is diverse and has no dominating lineage. Chapter 5 demonstrates that transmission between cats and their owners can occur within households, and I characterise potential catassociated lineages. In chapter 6, I found no S. aureus isolates in wild populations of brown trout in the Scottish Highlands. This population is phylogenetically divergent from the host species S. aureus is most associated with and is geographically and ecologically isolated. Together these results highlight the considerable transmissibility of S. aureus between host species. Most transmission events that I identify reflect spillover events that are self-limiting in their new populations. Nevertheless, I demonstrate that some level of persistence is common, enough that intermediary hosts can transmit to new species. This highlights the connectedness of S. aureus among different host species and that antimicrobial use in other hosts may impact human health. University of Cambridge 2022-01-18 Thesis Doctoral Doctor of Philosophy (PhD) eng MRC-Sackler PhD fellowships https://www.repository.cam.ac.uk/handle/1810/332957 https://www.repository.cam.ac.uk/bitstreams/9dc6c36c-7381-4988-ac2c-636b92db876a/download c45f25afa4cf69a001f9f1ac77bb4997 https://www.rioxx.net/licenses/all-rights-reserved/ Staphylococcus aureus host range host adaptation MRSA Mobile Genetic Elements Zoonotic transmission Antimicrobial resistance

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Palladium-Catalysed Carbonylation of Aliphatic Amines and its Application in the Total Synthesis of Cylindricine C 10.17863/CAM.25145 Hogg, Kirsten Fiona Gaunt, Matthew James This thesis comprises three projects on the theme of catalytic C(sp3)–H carbonylation of secondary aliphatic amines. Chapter 2 describes the development of a general methyl C–H carbonylation of secondary aliphatic amines to form synthetically useful β-lactam building blocks. Amines exhibiting a range of substitution patterns around the nitrogen functionality, and bearing a wide variety of functional groups, could be tolerated in the reaction. The desired β-lactam products were delivered in high yields, with excellent selectivity observed for the β-C–H position. Computational studies suggested that the reaction proceeds through a novel carbamoyl cyclopalladation pathway, which is distinct from classical cyclopalladation. The subsequent discovery of a selective methylene C–H carbonylation of α-tertiary amines (ATAs) is discussed in chapter 3. By employing the ATA motif, remarkable levels of selectivity for β-methlyene C–H bonds were achieved, even in the presence of traditionally more reactive methyl C–H and C(sp2)–H bonds. Once more, the reaction was found to exhibit excellent functional group tolerance, delivering highly functionalised β-lactam building blocks in high yields and selectivity. Chapter 4 presents work towards the total synthesis of the marine natural product (±)cylindricine C. The key step of this synthesis was demonstrated to proceed in good yield and excellent selectivity. University of Cambridge 2018-07-21 Thesis Doctoral Doctor of Philosophy (PhD) en https://www.repository.cam.ac.uk/handle/1810/277806 controlled.access https://www.repository.cam.ac.uk/bitstreams/d4d43822-35ba-4f23-b7b4-aad4f42481ca/download f632d2b0f99977ad7f2b1cba3deb7816 https://www.repository.cam.ac.uk/bitstreams/a1060289-1997-4696-ae09-fe471fdc065f/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ C-H activation carbonylation palladium catalysis Aliphatic amines

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Thermophoresis in Colloidal Suspensions 10.17863/CAM.21479 Burelbach, Jérôme Eiser, Erika This dissertation examines the motion of colloids in a temperature gradient, a non-equilibrium phenomenon also known as thermophoresis. Chapter 1 gives an introduction to the existing applications and basic concepts of thermophoresis and outlines some of the experimental and theoretical challenges that serve as a motivation for this PhD project. In Chapter 2, a general theoretical description for thermophoresis is formulated using the theory of non-equilibrium thermodynamics. The colloidal flux is split up into an interfacial single-colloid contribution and a bulk contribution, followed by a determination of transport coefficients based on Onsager’s reciprocal relations. It is further shown how the phenomenological expression of the thermophoretic flux can be recovered when the fluid is at steady-state. The results issuing from this description are then discussed and compared to other existing approaches, some of which are shown to neglect the hydrodynamic character of colloidal thermophoresis. Chapter 3 is dedicated to the validation of the introduced theoretical framework by means of computer simulations, using a simulation technique known as multi-particle collision dynamics. More specifically, the dependence of the thermophoretic force on different system parameters is examined and deviations from the theoretical prediction are explained by an advective distortion of interfacial fluid properties at the colloidal surface. Chapter 4 presents steady-state measurements of functionalised colloids in a temperature gradient, showing how the addition of molecular surface groups increases the experimental complexity of thermophoretic motion. The relaxation process behind this steady-state is also studied, to determine how the relaxation speed depends on the applied temperature gradient. In chapter 5, a general conclusion is drawn from the presented work and its implications are briefly discussed in relation to the current state of knowledge. Finally, the discussion is closed with an outlook on remaining challenges in understanding colloidal motion that could be the subject of future research. University of Cambridge 2018-06-01 Thesis Doctoral Doctor of Philosophy (PhD) en https://www.repository.cam.ac.uk/handle/1810/274357 https://www.repository.cam.ac.uk/bitstreams/652ff0b1-25cc-4d9e-80d6-45989ba6c59f/download 87eda9de84448d1f82354d60eee3eb5f https://www.repository.cam.ac.uk/bitstreams/d350ef62-2ff1-478c-a2bf-58ba68a3b9f3/download a643fec441acaf56c873ae55aca4ce1d https://www.rioxx.net/licenses/all-rights-reserved/ non-equilibrium thermodynamics phoretic motion thermophoresis interfacial phenomena Onsager reciprocal relations multi-particle collision dynamics colloidal suspension

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High-Energy Aspects of Inflationary Cosmology 10.17863/CAM.20391 Lee, Hayden 0000000275770806 Baumann, Daniel Since the discovery of the cosmic microwave background (CMB), our understanding of the cosmos has been rapidly evolving. Detailed measurements of the CMB temperature fluctuations have led to a standard cosmological model, which traces the origin of the large-scale structure of the universe to quantum fluctuations during inflation. Although the basic framework of inflationary cosmology is now well-established, the microphysical mechanism responsible for the accelerated expansion remains a mystery. In this thesis, we describe how the physics underlying inflation can be probed using two cosmological observables: higher-order correlations of primordial density perturbations (non-Gaussianity) and primordial gravitational waves (tensor modes). In the first part of the thesis, we explore novel signatures of high-energy physics in higher- order correlation functions of inflationary perturbations. First, we use causality and unitarity to make connections between cosmological observations and the underlying short-distance dynamics of single-field inflation. We obtain a constraint on the size and the sign of the four-point function in terms of the amplitude of the three-point function. We then study the imprints of extra massive particles of arbitrary spin on the three-point function. We classify the couplings of these particles to inflationary scalar and tensor perturbations and derive explicit shape functions for their three- point functions that can serve as templates for future observational searches. Establishing the particle content during inflation would provide important hints for the microscopic theory of inflation. In the second part, we study ways of testing the nature of inflation using inflationary tensor modes. We consider effects of gravitational corrections to Einstein gravity in models of high-scale inflation. We show that these scenarios can lead to a violation of the tensor consistency condition (i.e. the relation between the amplitude and the scale-dependence of the tensor two-point function) that is satisfied by canonical single-field inflationary models. Finally, we consider the prospects for measuring the inflationary superhorizon signature in future observations. We define an estimator that captures superhorizon correlations and present forecasts for the detectability of the signal with future CMB polarization experiments. University of Cambridge 2017-07-21 Thesis Doctoral Doctor of Philosophy (PhD) en The author was supported by scholarships from the EPSRC and the Cambridge Overseas Trust. https://www.repository.cam.ac.uk/handle/1810/273359 https://www.repository.cam.ac.uk/bitstreams/15a786e1-b0f5-4541-acf9-6b6900ff94c4/download 87eda9de84448d1f82354d60eee3eb5f https://www.repository.cam.ac.uk/bitstreams/8251fd77-1e5a-43d6-bbd9-47dbe5e677a4/download ee303dc813f3be36d837603427db8f33 https://www.rioxx.net/licenses/all-rights-reserved/ theoretical physics cosmology inflation cosmic microwave background effective field theory

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Regulating and Quenching Star Formation in Galaxies across the Cosmic Epochs https://doi.org/10.17863/CAM.122562 Looser, Tobias Maiolino, Roberto D'Eugenio, Francesco This PhD thesis uncovers the mechanisms regulating and quenching star formation in galaxies from cosmic dawn to the present. Based on optical spectroscopy of 10,000 local galaxies from the MaNGA survey, I report the discovery of a stellar Fundamental Metallicity Relation, a smooth relation between stellar mass, star-formation rate and stellar metallicity, analogous to the well-established gas-phase FMR. The existence of the stellar FMR suggests that the metal-poor gas accreted from the intergalactic/circumgalactic medium – or the lack thereof – is continuously imprinted onto the stars over cosmic times. This discovery points to “starvation”, i.e. the cut-off of gas supply, as the main path through which galaxies stop forming stars, i.e., “quench”, at low redshift. Additionally, I provide evidence that this starvation is likely caused by time-integrated feedback from Active Galactic Nuclei (AGN). In contrast, quenching mechanisms in the young, high-redshift universe may differ significantly. Using groundbreaking data from the James Webb Space Telescope (JWST), I identify an extremely rapidly “(mini-)quenched” galaxy at redshift z=7.3, when the universe was only 700 million years old. Its star-formation history (SFH) consists of a short and intense burst terminating only 10-40 million years before the epoch of observation. Its stellar mass is very low, only 400–600 million solar masses. This suggests that this galaxy was quenched by different physical mechanisms than local galaxies. The most compelling scenarios are ejective feedback from a supermassive black hole or efficient feedback from star formation. Both of these mechanisms may have driven powerful outflows, expelling the gas and depleting the galaxy of its fuel for star formation – perhaps only temporarily, until the gas returns. This finding supports theoretical models, which predict that SFHs were stochastic or 'bursty' during the universe's first billion years. I further test this theoretical hypothesis, based on the analysis of deep JWST NIRSpec prism spectra of ~200 galaxies at redshifts 0.6<z<11. Inferring key physical quantities, such as star-formation rates, stellar masses, stellar ages, or burstiness parameters, I confirm that SFHs were indeed strongly stochastic during these epochs. I conclude by presenting observational strategies to optimize high-redshift galaxy surveys for environmental information, with a particular emphasis on constraining environmental quenching at cosmic noon, when most massive galaxies quench. Overall, this thesis improves our understanding of galaxy evolution, particularly the mechanisms of galaxy quenching from the local universe to the highest redshifts. University of Cambridge 2024-11-15 Thesis Doctoral Doctor of Philosophy (PhD) eng Cambridge CDT for Data Intensive Science. https://www.repository.cam.ac.uk/handle/1810/391425 https://www.repository.cam.ac.uk/bitstreams/6b5ac5bb-f4bf-46c5-acbf-1a83ce317490/download 0dd2c5208549417dfc1e1c857d29cfa6 https://www.repository.cam.ac.uk/bitstreams/916ada8f-40d8-488d-9d69-3266bf39041b/download 87eda9de84448d1f82354d60eee3eb5f http://purl.org/NET/rdflicense/allrightsreserved Galaxies Galaxy feedback Galaxy formation and evolution Galaxy quenching Regulation of star formation

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Canterbury jurisdiction and influence during the Episcopate of William Warham, 1503-1532 10.17863/CAM.31113 Kelly, M. J University of Cambridge 1963-10-29 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/283744 controlled.access https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/94b3a7d2-7094-4af2-97ee-f8725c4da9b7/download 5fa56e6d222b2c76d5b5262961fe888e https://www.rioxx.net/licenses/all-rights-reserved/

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Girl Incorporated. Corporate Empowerment Programmes for Women Workers: What Drives them and Who Benefits? 10.17863/CAM.95258 Hengeveld, Maria Abdel Rahman, Maha The past two decades have seen a surge in partnerships between multinational corporations and women’s rights organizations professing to empower women and girls in the Global South. This trend – dubbed ‘Transnational Business Feminism’ (TBF) by feminist political economist Adrienne Roberts (2012) – has generated a lively debate amongst feminist social scientists around the ideological characteristics, limitations, benefits and effects of these alliances, and the extent to which they signal the ‘co-optation’ of certain feminist strands. This dissertation identifies and addresses three gaps in the TBF literature, namely: the perspectives of influential feminist groups participating in TBF projects; the effects of these initiatives on their beneficiaries in the Global South; and the rise of supply chain focused TBF projects targeting women workers. A contribution to this debate, this dissertation examines the logics, functions, and effects of worker-focused TBF projects from the perspectives of those who design these projects in the Global North, and explores the effects of such projects on two groups of women workers in the Global South. What lies behind the rise in supply-chain focused TBF partnerships? How do feminist professionals who design and promote these projects make sense of the impact, limits, and ideological implications of their work? How might the experiences of some small groups of beneficiaries illuminate the broader politics of TBF? These are the main questions animating this dissertation. A qualitative case study methodology is used to answer these questions. The selected case studies are the New York based United Nations agency UN Women, the International Center for Research on Women (ICRW) in Washington DC, and the partnerships of these organizations with fashion corporation The Gap (Gap) and the household goods company Unilever. Data has been gathered through: in-person and online interviews with feminist professionals in the United States, India, and the United Kingdom; group interviews with Gap workers in India, and phone interviews with former Unilever tea workers in Kenya. Additional interviews were held with feminist professionals at CARE International, Women Deliver, Business for Social Responsibility (BSR) and the UN Global Compact. Textual data has been obtained through the websites, social media pages, promotional literature, and annual reports of the organizations under study, Freedom of Information requests at the European Commission and court records capturing workers testimonies. I have gathered additional data by attending multiple TBF-related webinars and conferences. University of Cambridge 2022-06-30 Thesis Doctoral Doctor of Philosophy (PhD) eng Gates Cambridge Trust https://www.repository.cam.ac.uk/handle/1810/347840 https://www.repository.cam.ac.uk/bitstreams/c0c73ad8-41a3-4fa9-a63f-18cfaa122b1e/download d6836fec5797bfe11d62feccc0345791 https://www.rioxx.net/licenses/all-rights-reserved/ corporate social responsibility ethical capitalism feminist capitalist realism transnational business feminism women's empowerment

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Space use and site structure : an ethnoarchaeological study of Shona settlement patterning 10.17863/CAM.19983 Mahachi, Godfrey University of Cambridge 1991-01-01 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/272974 controlled.access https://www.repository.cam.ac.uk/bitstreams/ee63d980-7dee-4b58-acb7-098838993e44/download fa7d6dff577a16b7d1a8cbfb94d7b0d1 https://www.repository.cam.ac.uk/bitstreams/579d82bc-c70a-4f8d-bb28-f2c3952c6983/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/

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Serving the Patris in the Roman Empire: Civic Patriotism in Basil of Caesarea, the Emperor Julian, and Gregory Nazianzus 10.17863/CAM.87206 Langley, Thomas 0000000195725300 Kelly, Christopher Lunn-Rockliffe, Sophie This thesis is a study of civic patriotism in the fourth-century Roman Empire in the East. Civic patriotism is often viewed as dead or irrelevant in late Antiquity. This thesis argues that civic patriotic language remained a powerful force, being endorsed, adapted and contested by a variety of elite thinkers, three of whom this thesis studies in detail. The thesis employs the methodology of a ‘language of politics’ to model this process of adaption, redefinition and contestation. In particular, this thesis demonstrates that Julian and his Christian contemporaries addressed similar theological and political concerns and were part of the same debates – though providing different answers. At times, Julian’s position on civic issues was closer to either Basil or Gregory than either of the two Christians were to each other. Religious allegiance thus did not entirely determine the intellectual positions even of committed late-antique religious reformers. Structurally, this thesis examines civic patriotism from three angles: a secular political language, a foil for religious reformers, and a way of linking local belonging and religious allegiance. Firstly, elites adapted the language of civic patriotism to the new political circumstances of the expanded late Roman state. They refashioned service to the patris as participating in elite networks and promoting local men to government office, advertised in literary culture through letters, poems and panegyrics. This effort was cross-confessional. Julian’s enthusiasm for civic patriotic language, rather than an anachronism that, reflected mainstream fourth-century political culture. Secondly, however, ascetic and universalist ideas springing from contemporary philosophy offered significant challenges to the place of civic patriotic language in elite political thought. Basil and Gregory adapted civic terminology to describe heavenly, ecclesiastical, and monastic belonging. As a result, earthly patris had to be rejected entirely. By contrast, while Julian shared some of their theological assumptions due to his theology he did not reject the patris outright. Thirdly, Basil, Julian, and Gregory attempted to combine these attitudes by elaborating a ‘spiritualised’ vision of civic patriotism. They claimed civic patriotism either for Christianity or for Neoplatonic paganism, redefining civic identity and rewrite elite obligations to encourage citizens to view their patriotic and religious duties as identical. This spiritualised form of patriotism had substantial later influence on the culture, politics and society of the medieval Christian world. Overall, this thesis showcases the continuing significance of civic patriotic language in late Antiquity, and the productive tensions it fostered in political thought, practical politics, and religious culture. University of Cambridge 2021-07-14 Thesis Doctoral Doctor of Philosophy (PhD) eng AHRC Doctoral Training Project AH/L503897/1; Grants and tenth-term funding from the Faculty of Classics; Grants from Peterhouse https://www.repository.cam.ac.uk/handle/1810/339787 https://www.repository.cam.ac.uk/bitstreams/ba1c38cb-5a0f-4998-9ac1-cb02680dd088/download 71cdc1b7a61299dd2040c83228ba923b https://www.rioxx.net/licenses/all-rights-reserved/ Polis Patris Paideia Basil of Caesarea Gregory Nazianzus Gregory of Nazianzus Emperor Julian Julian the Apostate Byzantine Early Christianity Cities Civic Patriotism Civic Ideas Political Thought Political Philosophy Neoplatism Classical Religion Classical Paganism Late Antiquity Late Roman Empire Late Roman Government Elite Networks Ancient Politics

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Neural parameter inference for large-scale multi-agent systems https://doi.org/10.17863/CAM.122122 Gaskin, Thomas 0000000256444431 Girolami, Mark Schoenlieb, Carola-Bibiane In this thesis, I present a computational framework for integrating deep learning into mechanistic models. A neural network is trained to learn unknown system components—such as constant or time-varying parameters—by differentiating through the full set of governing equations. I argue that a targeted incorporation of machine learning to augment, rather than replace, physics-informed models (e.g. partial differential equations) addresses several of the limitations typically associated with machine learning in scientific applications. First, the reliance on large quantities of training data is reduced, as the underlying system dynamics are explicitly modelled and can be leveraged for extrapolation. Second, the outputs of the neural network remain interpretable within the broader context of the mechanistic model. Third, the need for ad-hoc parametrisation—whether through hand-picked covariates or pre-specified basis functions—can be avoided. Instead, neural networks offer a more flexible and data-driven alternative, leveraging their universal function approximation capabilities to model unknown system components in a realistic and expressive way. This is particularly beneficial in the social and economic sciences, where human behaviour is often modelled using overly simplified parametric forms, calibrated via regression techniques. The thesis begins with a brief overview of modern deep learning methods and their emerging role in the applied sciences, followed by a presentation of the proposed computational framework. Its performance is first demonstrated on a synthetic model of infectious disease dynamics, where a neural network is trained to infer constant parameters from a single time series and later extended to learn time-dependent components using recurrent neural networks. The following two chapters of the thesis focus on real-world, multi-agent systems in the social sciences: the global trade of agricultural commodities and international human migration since 1990. Both exhibit complex spatio-temporal correlations that traditional models struggle to capture. In the trade study, a deep neural network is used to fit an optimal transport model to bilateral trade flows, significantly improving upon the accuracy and flexibility of classical gravity models. The optimal transport formulation captures spatial interactions, while the network learns to solve the inverse problem of estimating abstract cost structures from noisy flow data. In the migration case study, we train a recurrent neural network on a set of socio-economic, political, cultural, and geographic covariates to model international migration patterns. The recurrent architecture enables the learning of long-term temporal dependencies, resulting in a high-resolution dataset of annual bilateral migration flows and migrant stock estimates on a global scale. A key theme throughout this work is the quantification of uncertainty in neural network predictions, approached in a tractable and computationally efficient manner. We explore various strategies, including propagating input uncertainty through the network, ensemble training, and a novel method inspired by weighted importance sampling, where the training process itself is used to gather samples of the inferred parameters. These approaches are benchmarked against classical Markov Chain Monte Carlo (MCMC) methods both on synthetic datasets and two real-world systems: the spread of COVID-19 in Berlin, and urban retail dynamics in Greater London. In both cases, our framework yields more accurate parameter distributions at significantly reduced computational cost. In the final chapter, we extend the framework to the inference of network adjacency matrices from time series data. We analyse its scaling behaviour, demonstrating favourable performance compared to both MCMC and standard regression methods. This approach is then applied to a case study on the British electricity grid, where the framework is used to localise power line failures and quantify the uncertainty of these inferences, thereby enabling rigorous statistical hypothesis testing. Taken together, this thesis offers a practical and theoretically grounded approach to blending deep learning with classical numerical modelling. The framework is simple to implement, computationally efficient, and broadly applicable—opening the door to a new generation of data-driven yet interpretable models across the computational sciences. Future research may explore extensions to weakly differentiable systems; applications in forecasting, where long-term predictive accuracy and robust uncertainty quantification are essential; and connections to manifold learning, where the latent, lower-dimensional structure of the parameter space is inferred. University of Cambridge 2025-06 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/390569 https://www.repository.cam.ac.uk/bitstreams/0fc3d67a-c4d6-4816-bceb-69700feb8b3e/download 5da00ed4e5c241970d96292d42acc98a https://www.repository.cam.ac.uk/bitstreams/a0524eff-d510-4b9d-9e4b-2a614d330f0a/download 87eda9de84448d1f82354d60eee3eb5f https://creativecommons.org/licenses/by/4.0/ Neural Networks Parameter calibration Deep learning Complex systems

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The Limits of Screening 10.17863/CAM.53085 Wu, Joseph Lewens, Tim This thesis is about screening for cancer—about testing healthy individuals for disease. The traditional way to approach this subject is to begin by considering whether screening is effective. So, for example, there is a hearty debate about whether cancer screening reduces mortality to a meaningful degree. Some people claim that it does; others claim that it does not. But all seem to think that determining whether screening reduces mortality will resolve the controversy around screening. The motivating idea behind this thesis is that focusing on effectiveness obscures a deeper and different set of issues. The central claim is that understanding and justifying cancer screening requires attention to its moral dimensions. Ethical issues arise throughout the debate— not only in constructing a theory of effectiveness, but also in deciding evidentiary thresholds, in adjudicating which principles should guide screening policy, and in judging how to cope with risk and uncertainty. The subsequent chapters aim to show how significant progress and clarity can be achieved in the screening debate with some aid from ethics. Taken together, these chapters develop a framework for thinking about how cancer screening can and should be justified. University of Cambridge 2019-08 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/306007 https://www.repository.cam.ac.uk/bitstreams/f8505341-4873-430c-a391-674cf6098a65/download 075f579548f7ebd6ad8c39e9298ba11e https://www.repository.cam.ac.uk/bitstreams/ebcc8c99-e7c1-4a97-9dea-4b75f86e64ee/download 353adac0d1ebdfd65ab16480263c3c87 https://www.rioxx.net/licenses/all-rights-reserved/ public health ethics philosophy of medicine philosophy of science

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Magnetic charges and phase space renormalization of gravity https://doi.org/10.17863/CAM.107408 Tomova, Bilyana Perry, Malcolm In the first part of this thesis we perform a complete and systematic analysis of the solution space of six-dimensional Einstein gravity. We show that a particular subclass of solutions – those that are analytic near I+ – admit a non-trivial action of the generalised Bondi-Metzner-van der Burg- Sachs (GBMS) group which contains infinite-dimensional supertranslations and superrotations. The latter consists of all smooth volume-preserving Diff×Weyl transformations of the celestial S4. Using the covariant phase space formalism and a new technique which we present in this thesis (phase space renormalization), we are able to renormalize the symplectic potential using counterterms which are local and covariant. The Hamiltonian charges corresponding to GBMS diffeomorphisms are non-integrable. We show that the integrable part of these charges faithfully represent the GBMS algebra and in doing so, settle a long-standing open question regarding the existence of infinite-dimensional asymptotic symmetries in higher even dimensional non-linear gravity. In the second part of this thesis, we study the dual charges of N = 1 supergravity in asymptotically flat spacetime. The action considered is the usual supergravity action with a topological contribution. This is the Nieh-Yan term and the magnetic term of the free Rarita-Schwinger field. Through methods of the covariant phase space formalism we construct the charges conjugate to supersymmetry, diffeomorphism and Lorentz transformations. The additional term in the action will lead to new, non-vanishing contributions to these charges. The magnetic diffeomorphism charges are equivalent to the ones previously found for gravity, while the dual supersymmetric charges are new and do not appear for the free Rarita-Schwinger field. We find that the asymptotic symmetry group for supergravity can only include global conformal transformations on the celestial sphere. University of Cambridge 2023-10-01 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/366537 https://www.repository.cam.ac.uk/bitstreams/bc344a37-5694-48b6-9ab1-a8e5877dd860/download 82ecc8e8adc39f3a6cbae583dbdf399f https://www.repository.cam.ac.uk/bitstreams/d711aff3-848d-46bf-be68-f13d7b7f3471/download 87eda9de84448d1f82354d60eee3eb5f https://www.rioxx.net/licenses/all-rights-reserved/ asymptotic symmetries gravity

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Disruption of mitochondrial redox homeostasis as a cellular signal. 10.17863/CAM.81183 Cvetko, Filip Murphy, Michael Mitochondria are crucial components of eukaryotic cells and exchange signalling molecules, metabolites, proteins and lipids with the rest of the cell. The organelle is key for energy metabolism as they provide most of the cellular ATP through oxidative phosphorylation and regulate intermediate metabolism. Mitochondria are also a major source of reactive oxygen species (ROS), which are by-products of aerobic respiration and recently recognised as important signalling molecules that control various cellular functions. To avoid the potential damaging effects of ROS, mitochondria contain protein antioxidant systems to help maintain thiol homeostasis. Mitochondria are emerging as an important redox signalling node and are involved in a myriad of signalling pathways, which have a redox component, either through a response to a particular ROS or the shift of the redox state of a responsive group. It is not surprising that mitochondria are therefore heavily regulated by retrograde signalling of the master regulator of cellular antioxidant defence, nuclear factor erythroid-derived 2-related factor 2 (Nrf2). Until now it has not been possible to disentangle the overlapping effects of mitochondrial ROS signalling compared to a redox signal stemming from disruption of mitochondrial thiol homeostasis. Furthermore, it is important to distinguish between disturbing the cytosolic and mitochondrial protein antioxidant systems. I characterised the effects of mitochondrial thiol homeostasis disruption on mitochondrial physiology with MitoCDNB, showing mitochondrial fission. I found that selective disruption of the mitochondrial glutathione pool and inhibition of its thioredoxin system led to Nrf2 activation, while using MitoPQ to enhance production of mitochondrial superoxide and hydrogen peroxide alone did not. To further our understanding of how mitochondrial redox homeostasis is sensed in the cytoplasm and signalled to the nucleus I used an RNAseq approach to investigate the intricacies of early mitochondrial retrograde signalling. University of Cambridge 2021-06-28 Thesis Doctoral Doctor of Philosophy (PhD) eng https://www.repository.cam.ac.uk/handle/1810/333766 https://www.repository.cam.ac.uk/bitstreams/ef1639cb-bc6c-4dfa-bd2b-06691efe520b/download 9c97e0a9ab9f03fe7fccda610c8b58e9 https://www.rioxx.net/licenses/all-rights-reserved/ Mitochondrial biology Redox Biology ROS

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FRP-Based High-Performance Building Envelopes - An investigation on the environmental performance of GFRP sandwich panels 10.17863/CAM.85488 Paparo, Isabelle-Denise Overend, Mauro Geometrically complex building envelopes are typical in contemporary architecture. The conventional approach during their design is to provide a succession of layers and materials in their build-up, each one addressing a particular requirement (thermal, structural, water tightness etc.). This approach often becomes problematic and costly. Glass fibre reinforced polymer (GFRP) sandwich panels consisting of GFRP laminate face sheet and adhered to a polymer foam core can potentially provide an integrated, loadbearing and lightweight solution for geometrically complex building envelopes. One of the barriers to their uptake is the lack of data on their durability and long-term performance in service conditions. Facades are inevitably exposed to transient environmental conditions, involving several degrading weathering agents which in the field often exacerbate each other’s individual damage. A thorough understanding of the influence and synergistic effects of these agents is essential for an economic and safe design that accounts for the long service-life expected for façade panels. This thesis, firstly, provides a state-of-the-art review on FRP applications in the civil sector with focus on architectural projects. The literature review focusses on the long-term performance of FRP materials subjected to ageing parameters comparable to the natural weathering, which corresponds to the load regime the targeted application, a façade, will be subjected to under real life conditions. A comprehensive summary of the material degrading mechanisms resulting from the interaction of environmental and mechanical ageing factors is composed. Based on the outcome, an environmental ageing program is developed for the consecutive experimental investigation. The long-term durability of GFRP sandwich panels subjected to façade-like weathering are investigated under laboratory conditions. The GFRP specimens are subjected to a total of five weathering agents (1) abrasion, replicating debris and sand impact onto the outer skin of the building, (2) moisture only for the evaluation of rain/ high humidity impact, (3) moisture combined with temperature (freeze-thaw-cycles) as a realistic replication of temperature deltas specifically between day and night times, (4) sustained load mimicking the influence of adhesively attached cladding material or supporting structures, and, lastly, (5) fatigue load replicating the influence of wind load onto the building envelope causing component vibrations due to the nature of wind directionality and speed change. In the case of a façade system, UV radiation as a result of sun light exposure was deemed to have only a minor effect on the structural performance when system was to be protected by a UV prohibiting coating whilst being subjected to regular maintenance. Despite the initial hypothesis that material degradation would occur under the developed ageing regime, it was found that the investigated sandwich panel consisting of glass fibre reinforced laminates and a PU foam core were durable and more resistant towards the ageing parameters than anticipated. Degradation effects were within reason or negligible for most ageing conditions or ranged within the expected variation. Face sheet degradation that was measured in the laminates-only tests had no distinct effect on the overall performance of the sandwich panel when evaluating the sandwich panel configuration. This is attributed to the sandwich panels failure more which is not governed by the face sheet’s strength. The effects of thermal cycling were the only results that showed consistency, although the magnitude of degradation could be considered acceptable over the life span of a façade system. University of Cambridge 2021-07-05 Thesis Doctoral Doctor of Philosophy (PhD) eng EPSRC Friedrich Ebert Foundation https://www.repository.cam.ac.uk/handle/1810/338078 https://www.repository.cam.ac.uk/bitstreams/9a5e707f-ec30-4287-b598-af498987d2b8/download a8efb645777168be7ded4e91820df84e https://www.rioxx.net/licenses/all-rights-reserved/ GFRP Sandwich Panel Weathering Ageing Building Envelope Facade PU foam core GFRP Face sheets

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The Preparation and Properties of some Derivatives of Diimide 10.17863/CAM.17319 Tims, John University of Cambridge 1964-02-04 Thesis Doctoral Doctor of Philosophy (PhD) eng Digitisation of this thesis was sponsored by Arcadia Fund, a charitable fund of Lisbet Rausing and Peter Baldwin. https://www.repository.cam.ac.uk/handle/1810/270445 https://www.repository.cam.ac.uk/bitstreams/b8b1a718-8367-463f-9e6b-e5e66752909b/download 87eda9de84448d1f82354d60eee3eb5f https://www.repository.cam.ac.uk/bitstreams/6dce2062-3e7b-4d25-8de0-79e5391b32ac/download 3cc9f9f4c1fad5ab62994a3960be6cbc https://www.repository.cam.ac.uk/bitstreams/f3966577-61dc-4c04-8ae1-490d173f3c10/download 377507f4e0a176c14b9d5e8ce03ac7e5 https://www.repository.cam.ac.uk/bitstreams/9eb26cfd-3a61-45d9-a74e-288fc9057b95/download 84fd92b2f5d1e392f56ff05c5287d936 https://www.rioxx.net/licenses/all-rights-reserved/

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Merlin, the Brain, and the Market: Intelligent Machines and Global Order in Public Debates in Britain 1945-50 10.17863/CAM.86975 Rees, Peter Staley, Richard Schaffer, Simon During and immediately after World War Two (1939-1945), influential public debates in Britain concerned the postwar settlement. This was a global war and Britain was a global empire in its final epoch. A crucial aspect of several schemes for reconstruction and the establishment of global order concerned the place of science—an ostensibly global knowledge form—in the social order. Historians have tended to draw on a relatively narrow range of interlocutors to interpret this polemical landscape as a debate over freedom and planning. This thesis offers a new account of this set of influential polemical interactions by examining a richer cast of participants and by attending to the reflexive quality of the media technologies they used to articulate their arguments. I focus on the programmes forged by three major public intellectuals: J D Bernal, C S Lewis, and F A Hayek. These figures are rarely considered in direct relation to one another and are identified with very different intellectual contributions and political positions, but I show how they were each intensely concerned with the nature and role of science in the social order. All three articulated an image of science as a self-organising system of intelligence which would form the basis of global order. Setting these three figures in their social and intellectual milieux, I compare and contrast how Bernal, Lewis, and Hayek articulated their different notions of the global and images of the intelligent machinery which would secure global order. These images included Bernal's technoscientific world brain, Lewis’s fairy-tale protagonist Merlinus Ambrosius, and Hayek’s market or price mechanism. I show how, in each case, the media through which they articulated these images claimed to manifest and exercise the power of the intelligent machinery which they described. These figures’ work to articulate these images in mass media to educate their audiences was the work of forging the new global order. They each attempted to transform readers’ attitudes towards and tacit assumptions about science and the globe and to thereby transform the body politic and reconstitute the relationships between humans, nature, and technology. Often exciting and entertaining, their accounts invited and trained public audiences to participate as actors in a world and to see their enemies as occupying different consciousnesses, times, or worlds. I show how these works were cosmological interventions by examining the rhetorical and iconographical strategies they employed to project the techniques of their own cosmology onto the global history of science. An important output of the thesis is its provision of a historical explanation for why images of science matter in public culture. I argue that these figures deployed images of science to define the criteria for who counted as legitimate experts on human affairs. Finally, I use this analysis to reinterpret significant aspects of the genesis of British sociology of scientific knowledge. My first two chapters focus on Bernal, the third and fourth chapters on Lewis, and my fifth and sixth chapters on Hayek. University of Cambridge 2022-02-22 Thesis Doctoral Doctor of Philosophy (PhD) eng The Royal Society https://www.repository.cam.ac.uk/handle/1810/339557 embargo 2026-07-27 https://www.repository.cam.ac.uk/bitstreams/f10bf59b-b8cc-439f-8477-394eee47e5dc/download 9016438275119af652d7b87ee6cfa42f https://www.rioxx.net/licenses/all-rights-reserved/ C. S. Lewis F. A. Hayek J. D. Bernal uketd_dc////100