VictorJuiz/thesis huggingface dataset:
A self-inflating vp/mma hydrogel expander as a potential treatment for Crohn’s Disease problem

Crohn’s disease (CD) is associated with chronic inflammation in regions throughout the gastrointestinal (GI) tract but is most likely to develop at the end of the small intestine and the first part of the colon. A single massive resection or multiple repeated resections in CD leads to short bowel syndrome (SBS). Therefore, a novel treatment to cure SBS is needed. Poly (vinyl pyrrolidone-methyl methacrylate) hydrogel is chosen as a self-inflating expander device to address the issue of inadequate functional intestinal length in SBS. The hydrogel employs mechanotransduction, wherein mechanical force elongates the intestine and activates cellular mechanisms regulating growth. In this study, the VP/MMA hydrogel was designed by varying the composition ratio of each monomer and size. The ratios of VP to MMA were 95:5wt%, 90:10wt%, and 85:15wt%. The shape of hydrogel was cylindrical with the sizes of 12mmD & 3mmL (A), 6mmD & 3mmL (B), 6mmD & 6mmL (C), 6mmD & 9mmL (D), 3mmD & 3mmL (E). These variables influenced the pore size structure, swelling capacity, swelling force, and mechanical property. Finally, the hydrogel with a composition ratio of 85:15 wt% VP/MMA (VP85) was chosen for ex vivo and in vivo studies. The reason is due to the pressure generated during swelling (77.9 kPa) close to the required stress value to stretch the small intestine (78.9 kPa). Due to the small size of the rat intestine, the 2mmD & 2mmL hydrogel was chosen. A stretched segment of the intestine was found to lengthen 2.5-folds from the original length on days 1 and 7. Histological intestine sample after being stretched using hydrogel showed a significantly greater muscularis thickness, crypt depth and villous height.

Keywords: vinyl pyrrolidone
GI Tract
Short Bowel Syndrome
Hydrogel Tissue Expander
methyl methacrylate
Crohn's disease
Advisor: Czernuszka, J
Laser-accelerated ions and their applications

Since the first studies of target-normal sheath acceleration around the year 2000, production of energetic ion beams from intense laser-matter interactions has been investigated in great depth. New acceleration mechanisms such as radiation pressure acceleration, collisionless shock acceleration, the hybrid breakout afterburner mechanism, and special regimes such as light-sail radiation pressure acceleration have been discovered and demonstrated. Applications of ion beams produced by these mechanisms range from common diagnostic techniques for laser plasma interactions to industrial radiography and even—albeit needing significant improvements to predictability and reproducibility before this can be realised—their proposed use in medical treatments like hadron therapy, which if successful could significantly reduce the cost to hospitals of hosting such therapies. I present work on three topics around laser-accelerated ion beams and their applications: Firstly, I present an experiment which sought to demonstrate acceleration of ions from a laser-driven collisionless shock within a plasma produced from low-density plastic foam. This acceleration mechanism produces ions with a narrow energy spectrum, compared to the more well-established target-normal sheath acceleration. Despite limitations to the accessible experimental conditions, I present evidence that ions were accelerated with the narrow energy spectrum characteristic of this mechanism. Secondly, I introduce the reader to an important application of fast ion beams: the proton radiography diagnostic. This diagnostic is used to measure the electromagnetic fields present in a plasma through their influence on a beam of protons as it traverses the plasma. I explain the theory of proton radiography and describe a laser-plasma channelling experiment on which proton radiography was used to probe the magnetic fields associated with a laser-produced plasma channel. I demonstrate the analysis of some proton radiographs using an improved solver I have implemented in a community analysis package. Finally, I propose improving the information accessible to the proton radiography diagnostic by making observations of the plasma from several different directions, a procedure I term ‘proton tomgraphy’. I then derive methods of improving the quality of data recovered from proton tomography. Compared to standard tomographic algorithms I achieve an orders-of-magnitude improvement in reconstrution quality of synthetic data when very few lines of sight are available

Keywords: plasma physics
ion acceleration
Advisor: Norreys, P
Do women only have rights when it is economically profitable? Limits of the legislative rationality behind international women’s rights

The thesis studies how capitalist logic is ingrained in the fabric of women’s rights; and argues that it limits women’s rights’ ambitions and possibilities to emancipate women. The inquiry is based on two case-studies of adopting international women’s rights: the UN Convention on Marriage (UNCM) granting women a right to reject forced marriage; and CEDAW, granting women a right to family planning in its Art. 16 e). The thesis, in the context of the case-studies, shows that a combination of capitalist imaginaries of women’s needs, means of emancipation and the deference to ‘autonomous’ economic forces are imprinted in the legal form of women’s rights. These imaginaries come together in a core unemancipatory dynamic of the rights. This dynamic is such that the aim of the legal form signified under ‘rights’ is not women’s attainment of power or entitlements, but a creation of conditions for women to join the course of ‘autonomous’ economic forces which will then presumably lead to this attainment. This technology within the rights then functions to distribute emancipation and subordination according to the structures of patriarchal and racial capitalism. This perspective helps explains why poor and non-Western women are structurally subordinated by and within the merit of the mentioned rights, despite these rights being adopted to empower these exact women.

Keywords: feminist theory
human rights
critical theory
international law
critique of political economy
Investigating and improving the electronic properties of perovskite single crystals

The aim of the work presented in this thesis is to advance the understanding of the physics underpinning metal halide perovskite single crystals, both in terms of the characterisation of its electronic properties and techniques to improve stability. This study goes on to present a unique mechanism, revealing a new A-site lead halide perovskite, that is also capable of delivering stable high-efficiency photovoltaic cells. Despite being a young technology, perovskites as material for photophysics and opto-electronic purposes has seen an unparalleled rise in the research community. Results indicate that perovskite-based solar cells provide a step change in performance, compared with older and more established techniques. Their high efficiency, in combination with the ability to process perovskites inexpensively, make perovskite-based cells a new hope in the fight against climate change. In recent works, electrical characterisation techniques are liberally being applied within the field of perovskite photovoltaics to extract ‘key figures of merits’ such as trap site density and mobility. However, conventional semiconductor physics do not apply to perovskite-based devices due to the mixed ionic nature of these materials. Therefore, the results from electrical characterisation of perovskites that exemplify the remarkable properties of these materials generate misleading results. For the development of perovskite-based electronic devices, accurate characterisation of the material’s fundamental properties - such as trap and ion density, charge carrier density and mobility value - is of great importance. Therefore, this work initially focuses on investigating the ‘space-charge limited current’ methodology - a technique that probes the extraction of current as a function of applied bias, through a combination of experimentation and modelling, notably with consideration of the mobile ions which are present in perovskites. Due to inevitable defects associated with grains, grain boundaries and surface interfaces in polycrystalline perovskites, this work focuses on macroscopic single crystal perovskites, to be able to distinguish the bulk surface properties, and focus on intrinsic key quantities of these materials. This work introduces a new property measurement methodology and analysis. With the proposed numerical modelling, the new method highlights the complexity of the charge transport in the material and provides detailed insights into the fundamental electronic characteristics of perovskite single crystals. Another grand challenge is the long-term stability of perovskite-based devices. Therefore, the final part of this thesis focuses on understanding the use of an additive to enhance the stability of perovskite single crystals from several hours to over a year. By conducting a comprehensive characterisation of both electronic and material properties, with and without the additive, this study shows a unique mechanism, and reveals the existence of a new mixed A-site perovskite that enables highly stable and efficient photovoltaic devices.
How bilingual language experience shapes the infant lexicon: implications for word learning and lexical access

In this thesis, I investigate how the words known by bilingual toddlers affect their learning of new words. I explore phonological and semantic connections both within and between languages. I analyse vocabulary questionnaire data collected via parent report for bilingual and monolingual toddlers growing up in the UK. Firstly, I show that while bilinguals’ English vocabulary size lags behind that of monolinguals, conceptual vocabulary size is similar across groups. Notably, when words across both languages are added together, bilinguals understand many more words compared to monolinguals. Bilinguals’ vocabularies include words with the same meaning across languages (translation equivalents). I found that if a word is known in one language (e.g., English "dog"), they have a high likelihood of also learning its translation equivalent (i.e., Spanish "perro"). Additionally, the acquisition of translation equivalents may be supported by systematicity between phonology and meaning. Even monolingual adults are able to make use of cross-linguistic similarity to guess the meaning of unfamiliar foreign words. I show that bilingual toddlers learn cognates (translation equivalents with phonological overlap) earlier than non-cognates, suggesting that toddlers can make use of cross-linguistic similarity to support word learning. Toddlers also display sensitivity to semantic connections in their language(s). Using semantic network analyses, I show that high frequency words and words that have a large number of associative connections to other words are learnt earlier by toddlers than words with low frequency and few connections to other words. The words within a toddlers’ lexicon also have dense connectivity with each other, much more than would be expected if associative patterns in the learning environment had no impact on word acquisition order. Findings from this thesis highlight how bilingual toddlers can capitalise on phonological and semantic connections between words to facilitate learning two languages in parallel.

Keywords: infant research
cognates
bilingualism
vocabulary questionnaire
language development
Advisor: Plunkett, K
Multi-level proteomics profiling of virus-restrictive and -permissive cellular environments to discover novel regulators of virus infection

Viruses rely on host cell resources to replicate and propagate. To mitigate, human cells can express a diverse set of antiviral proteins to combat virus infection. Understanding the host proteins that aid or repress virus infection can be instrumental for the development of novel antiviral strategies. This recent decade has witnessed rapid developments in discovering host proteins that regulate virus infection. However, our current knowledge of the landscape of host proteins that drive or restrict virus infection remains largely incomplete. Here I employed a multi-level proteomics analysis to identify novel regulators of virus infection in a model system that comprises cells highly permissive to viruses (HEK293T), cells at steady-state (HEK293), and cells restrictive to viruses (HEK293 stimulated with interferon alpha (IFN-α)). This analysis examines changes in protein and RNA abundance, phosphorylation, and RNA binding across different cellular states. Whole-cell proteomic analysis revealed that HEK293T cells are depleted of well-established antiviral factors and enriched in proteins that interact with viral protein and RNA, which could explain its high permissiveness to virus infection. Proteome-wide comparative analysis also highlights that a number of proteins exhibit distinct expression patterns across permissive, steady-state, and restrictive cellular states, including genes that have not been previously associated with IFN-α response. Further analysis comparing cellular proteome and transcriptome discloses substantial discordances between protein- and RNA-level responses after IFN-α stimulation. The analysis of RNA-bound proteome (RBPome) shows, for the first time, that IFN-a stimulation alters the protein-RNA interaction landscape in human cells. An in-depth phosphoproteomic analysis of IFN-α stimulated cells provides evidences that IFN-α could regulate the cellular RBPome through phosphorylation of RNA binding proteins. By integrating evidences from multiple levels, I have selected and generated stable expression cell lines for 19 candidate genes to test their potential regulatory roles in viral fitness. Collectively, this study provides an information-rich dataset that examines host determinants of virus-permissive or restrictive cellular states from multiple levels. This could be a valuable source for further analysis and validation studies to discover regulators of virus infection.

Keywords: proteome
interferon alpha
RNA bound proteome
transcriptome
phosphoproteome
HEK293
mass spectrometry
permissive
HEK293T
restrictive
virus infection
Advisor: Castello Palomares, A
Mohammed, S
Analysis of the extracellular battlefield of potato blight disease

Antagonistic interactions between plant and pathogens trigger plant immune responses that rely on complex signalling networks in which molecules and proteins of diverse nature interact to avoid pathogen colonisation. On their side, plant pathogens have developed mechanisms to suppress plant immunity. Secreted hydrolases play a key role in early plant immunity as they can release pathogen molecules in the apoplast that can be sensed by plant receptors and pathogens secrete inhibitors to supress their activity. This suppression of hydrolase activities can help the pathogen to overcome plant defences and establish a compatible interaction causing disease. In this thesis we investigated apoplastic hydrolytic activities during infection by the causal agent of potato blight disease: the oomycete Phytophthora infestans. In chapter 2, we monitored the impact of leaf detachment in infection assays in the model organism Nicotiana benthamiana. We addressed the hydrolytic activity changes on the apoplast upon detachment and we used proteomics to examine protein changes in apoplast and total extract. We then assessed the impact of detachment in specific immune responses triggered by pathogen-associated molecular patterns and effectors. In chapter 3, we used ABPP coupled with mass spectrometry to study the active proteome of the tomato apoplast during early infection of P. infestans. We compared abundance and activity data to identify putative post translational regulation of apoplastic hydrolases activity. Additionally, we performed convolution ABPP coupled with mass spectrometry to discover novel suppressed tomato hydrolases upon P. infestans infection. Finally in chapter 4, we characterised a novel secreted cysteine protease from P. infestans using transient expression in planta. We confirmed the activity of the novel P. infestans protease and its inhibition by protease secreted inhibitors from P. infestans using ABPP and substrate-specific activity assays. Furthermore, we compared the expression patterns of the P. infestans protease and inhibitors throughout the time course of infection. Altogether, the present thesis provides an overview of how plant immunity is affected in detached leaves infection assays. It also provides evidence for novel apoplastic hydrolytic activity in the context the potato blight disease and dwells into the impact of apoplastic proteases in immunity.

Keywords: infestans
mass spectrometry
hydrolases
protease
proteomics
tomato
Advisor: van der Hoorn, R
Regulatory network analyses highlight transcription factor cooperation in haematopoiesis and leukaemogenesis

The regulation of gene expression is a complex process that confers cell identity and drives cell differentiation. Transcription factors (TFs) are an important modulator of gene expression and are critical to understanding the regulatory code characterising cell behaviour. However, TFs function in cooperation with one another, acting as a complex combinatorial code to enact gene regulation. Gene regulatory network (GRN) models are used to describe the regulation of genes and to account for this combinatorial code. When the regulatory code underpinning normal cell behaviour goes awry this can lead to abnormal GRNs and the development of disease. This poses two questions: how does TF cooperation drive cellular processes, and how are normal GRNs deregulated in disease?
Haematopoietic stem cells are first established in the developing embryo through a process known as the endothelial-to-haematopoietic transition (EHT). EHT involves dynamic gene regulation across well-defined populations, and is critically dependent on the master TF regulator, RUNX1. EHT is therefore a fascinating system to study TF regulation in driving a complex developmental process. When haematopoietic GRNs are misregulated this can lead to disease. A common childhood leukaemia involves chromosomal rearrangements resulting in novel Mixed Lineage Leukaemia (MLL) fusion proteins that aberrantly drive transcription. MLLrearranged leukaemias are considered a wholly transcriptional disease, and as such are uniquely suited for studying through GRN approaches.
In this thesis, the study of GRNs underpinning normal and malignant haematopoietic processes revealed insights into the role of TF cooperation. Notably, Runx1 cooperates with TFs to drive repression of a transiently activated network during EHT. In MLL-AF4 leukaemia, MLL-AF4 drives TF cooperation by altering the chromatin environment and encouraging local TF binding, and within this MLL-AF4 context RUNX1 activity is biased towards activation. RUNX1 was also found to cooperate with MYB to synergistically activate BCL2 and MYC, promoting leukaemogenesis.

Keywords: GRN
leukaemia
combinatorial logic
MLL-rearranged leukaemia
network
tanscription factor
haematopoiesis
endothelial-to-haematopoietic transition
gene regulatory network
Advisor: Milne, T
De bruijn, M
Morrissey, E
Cyclin F: roles in genome stability and oncogenic pathways

F-box proteins are a family of substrate recruitment factors that assemble into multi-subunit complexes known as SCFs to ubiquitylate their substrates and thereby alter their fate, ex. by directing them to the proteasome for degradation. Cyclin F is the founding member of this family, and it has been identified by our lab to be protecting cells against ionising radiation (IR). This discovery is the result of a CRISPR screen focused on the ubiquitin system in cells treated with IR. Data from my affinity purification and mass spectrometry studies revealed that EXO1 is the Cyclin F substrate responsible for this phenotype. EXO1 is an exonuclease whose upregulation has been shown to drive DNA hyper-resection which impedes DNA repair. I report that SCF-Cyclin F targets EXO1 for proteasomal degradation in the G2/M phases of the cell cycle and upon challenging the cells with IR, and that this is dependent on a phosphorylation event by the kinase CDK2. Using cell survival assays I prove that IR-sensitivity in cells lacking Cyclin F can be fully rescued by EXO1 depletion, underlining the IR-sensitising effects of EXO1 accumulation. I also demonstrate that Cyclin F is involved in a regulatory loop with the most frequently mutated oncoprotein, RAS. Using affinity purification to pull-down active RAS, I show that Cyclin F loss contributes to suppressing RAS activity. This effect is reflected in the cellular response to RTK inhibitor therapy, whereby the signature RTK inhibitor resistance of RAS mutant cells is attenuated in Cyclin F depleted settings. Results from a deep proteomic study of the Cyclin F-KRAS axis present valuable insights into the implicated pathways and demonstrate clinically-exploitable weaknesses of this axis. Together, results from both projects highlight novel roles for Cyclin F in genome stability maintenance and oncogenic pathways.

Keywords: KRAS
DIA vs DDA mass spectrometry
E3 ubiquitin ligases
Cyclin F
RTK inhibitors
F-box proteins
EXO1
DNA repair
ionising radiation
ubiquitin-proteasome system
A framework for the study of “Mercury Jars” and other stoneware from the Temasek Period of Singapore, alongside 12th to 14th-century stoneware from Kota Cina, Sumatra

This dissertation concerns the study of stoneware vessels, an often-overlooked corpus of material in Southeast Asian archaeology due to the relative ease with which peculiarities in earthenware clay can be studied and the intricate decorations and glazes of porcelains are more easily catalogued and correlated.
These so-called “functional” and “trade” wares are used as proxies to investigate trends of ceramic production, trade and exchange in Southeast Asia during the 12th-15th centuries, a period marked by the fragmentation of centralised political control and the emergence of “atomistic” trading-posts and city-states such as Kota Cina and Singapore, which are taken as the temporal ends of this period in this study.
It may be hoped that through the high-resolution scanning electron microscope study of these materials, that in addition to insights on these aforementioned trends, so as to demonstrate the further potential of this overlooked material in future studies of Southeast Asian history.

Keywords: mercury jar
southeast asia
scanning electron microscopy
glaze
stoneware
body paste
clay
sem-eds
ceramics
archaeology