VictorJuiz/thesis huggingface dataset:
Quantitative analysis of incorporation dynamics of conserved Centriole proteins in Drosophila early embryos
Keywords: Incoroporation
Centrioles
Centriolar
Centriole
Assembly
Dynamics
Drosophila
Centrosome

To divide efficiently, cells of animals and many other higher eukaryotes, rely upon centrosomes to help nucleate the bipolar mitotic spindle. At each division, two centrosomes are required, such that one centrosome is ultimately inherited by each daughter cell. Consequently, centrosomes must duplicate precisely once during each cycle of cell division. At the core of each centrosome is a mother centriole that can duplicate by growing a new daughter centriole off its side, which will later mature into a mother and nucleate its own centrosome. The core components of the centriole are highly conserved across higher eukaryotes, despite this there is still a lack of detail regarding their function and their hierarchy of assembly.
In this thesis, I perform a comparative analysis of the incorporation dynamics of several conserved centriole proteins, using both standard and super-resolution microscopy, and the Drosophila early embryo as a model. I show that the daughter centrioles in the Drosophila early embryo appear to begin assembling earlier than previously reported. Further, I provide evidence that several core centriole proteins may be recruited into a transient centrosomal primordial “soup” in addition to the centriole proper. In addition, I refine the order of assembly of the centriole - allowing incorporation of Sas-6, Ana2, Ana3, CEP135, Ana1 and Asl to be placed on a continuous timeline alongside the cell cycle. Finally, through the use of CEP135 mutants, I show that, CEP135 does not appear to be necessary to recruit Ana1 into centrioles, in contrast to previous findings.
In summary, my work redefines the initial incorporation dynamics of centriole assembly, challenging several previous assumptions and providing new avenues for interrogation of the specific functions of the core centriole proteins.
Writing in creole contexts: a study of Jamaican primary school students and teachers
Keywords: literacy
writing
EAL
creole
English language learners

The poor writing outcomes of Jamaican students across all levels of education have been a subject of lament for educators and policymakers for several years. Despite such concerns, very little research has explored the challenges experienced by learners with Jamaican Creole as a home language when writing in English. While Jamaican Creole is the first language of most speakers, only Standard Jamaican English (English) is afforded official status and therefore is the language of instruction. Within this context, many children are educated through the medium of English while their first language is often disregarded and denigrated in the classroom. Given the differences between the languages, particularly in the areas of morphosyntax and phonology, as well as the importance of these skills in writing — it is worth exploring the nature of writing among learners in the Jamaican context. The present study therefore explores the characteristics of writing among learners with Jamaican Creole as their home language relative to their English dominant peers and investigates whether there are specific writing challenges experienced by these learners. The wider ecology of the writing classroom (instruction, curriculum, and language education policy) is also taken into consideration to gain a fuller understanding of student writing outcomes. A sequential mixed methods design consisting of three phases of gradually increasing focus was employed. In the first phase, a systematic review of the research on writing development among learners more typically identified as EAL was conducted to provide some insight on the nature of writing among learners whose home language differs from English –– the language of schooling. This was followed by the content analyses of the Jamaican curriculum and policy documents guiding writing instruction. In the final stages, semi-structured interviews were carried out with classroom teachers and language and literacy measures were administered to 90 Jamaican primary school students in Grade Six. Statistically significant differences were found in the overall writing outcomes of learners with Jamaican Creole as a home language and their peers with English as a home language (p < .001), with the former group performing more poorly on all writing subskills. In terms of the ecology of the writing classroom –– instructional approaches more in line with English immersion were dominant in both the classroom and the policy and curriculum documents, with teachers reporting feeling ill-equipped to teach writing in the Jamaican creole context. Findings from each phase of the study are integrated and discussed with reference to the simple view of writing and wider research to create a fuller account of the writing outcomes of learners with Jamaican Creole as a home language. Implications for second language writing theory as well as for writing pedagogy and policy in creole-speaking contexts are also discussed.
Investigating the inhibition of endoplasmic reticulum α-Glucosidase II for the development of broad-spectrum antivirals
Keywords: endoplasmic reticulum quality control
enzymology
glycobiology
protein-protein interfaces
iminosugars
antivirals
computational biochemistry

Enveloped viruses hijack the protein production machinery of their host in order to proliferate and their replication/infectivity relies on the correct folding of their surface glycoproteins. This dependence on glycoprotein quality control for viral proliferation makes the host endoplasmic reticulum quality control (ERQC) mechanisms an attractive target for the development of host-targeting antiviral agents, which may show broad-spectrum activity and a high genetic barrier to resistance. A key ERQC protein is α-glucosidase II (GluII), a heterodimeric enzyme bearing a catalytic α-subunit of the GH31 family and an accessory β-subunit that is necessary for full catalytic activity and for the localisation of the heterodimer in the ER. GluII mediates quality control of the folding of nascent glycoproteins by trimming glucose residues from its substrate glycan Glc1-2Man9GlcNAc2. Inhibition of GluII can be achieved using iminosugars which mimic the glucose residue of the native substrate, causing the build-up of misfolded protein in the ER and prevents the secretion of correctly folded glycoproteins. In the case of enveloped virus infection, this inhibits virion secretion or reduces infectivity of secreted virions and has been shown to elicit antiviral effect against a range of enveloped viruses in vitro and in vivo. Iminosugar inhibitors of GluII are effective, but have been associated with significant drug-related adverse effects.
In this thesis, I present a novel approach to the inhibition of GluII that involves disruption of the heterodimeric protein-protein interface within the enzyme. Removal of the accessory β subunit from the catalytic α-subunit has been shown to decrease catalytic activity and may induce the export of the catalytic domain out of the ER. Thiopyridones were discovered as small molecules that interfere with the α/β interface and I investigate this protein ligand interaction using techniques such as mass photometry, mass spectrometry and high performance liquid chromatography among others to confirm the capability of these molecules to disrupt the α/β interface and potentially inhibit GluII. Additionally, I outline the design and synthesis of novel iminosugar compounds with the aim of improving the selectivity for GluII relative to existing best-in-class iminosugars. I also use molecular dynamics for in silico examination of the full extent of the GluII α/β interface and the roles of peripheral domains of the β-subunit that are not fully understood based on existing structural data.
Indian industry 1950-1990: growth, demand and productivity
Keywords: Indian industry
productivity
demand
industries
India
economic conditions
growth

Industry in India has grown at different rates in different periods since 1950. Policy liberalization and increased deficit financing provides the context for an explanation of the acceleration in industrial growth in the 1980s.
In this thesis I develop a model of demand for industrial products using time series macro-econometric methods after first establishing that industrial prices in India are largely determined by costs. Using the Johansen Maximum Likelihood method, I formulate an overall consumption function and develop an error correction model of the demand for industrial output arising from consumption. I demonstrate that public equipment investment crowds out private investment in machinery and equipment and model demand for the purpose of equipment investment. With the help of recursive techniques, the models of consumption and investment are shown to be well specified and stable over the entire period considered, including the eighties. I contend that domestic factors were more important in increasing growth than the expansion of manufactured exports.
Stagnant levels of employment provide the backdrop for an examination of productivity growth in industry. I demonstrate that a limited improvement in total factor productivity was achieved subsequent to the acceleration in output growth in the 1980s. I question the assertion that productivity growth was responsible for the acceleration in output growth and refute the related contention that liberalization engendered the improvement in productivity. I establish that capital and labour inputs are able to account for the movements in industrial output only to a limited extent and demonstrate that consideration of raw material inputs is essential to an adequate explanation of supply side dynamics.
My analysis contends that changes in demand were accommodated by supply responses, which may have been aided by the relaxation of regulatory controls.
Changing patterns of marriage and cohabitation in post-reform China
Keywords: marriage
cohabitation
post-reform China

Premarital cohabitation has gained increasing popularity in China in the post-reform era (after the economic reform started in 1978). The central theme of this thesis is to examine this phenomenon, in particular, the socio-economic characteristics of cohabitors, and how cohabitation is associated with assortative mating outcomes and marital dissolutions. Drawing data from China Family Panel Studies (2010-2016), this thesis investigates three types of associations in heterosexual marriages: (i) between cohabitation and educational attainment; (ii) between cohabitation and educational assortative mating, and (iii) between cohabitation and subsequent divorce. Moreover, gender differences in each association and how these associations change across marriage cohorts (early-reform, mid-reform, and late-reform) were examined in detail. Chapter 1 explores the association between educational attainment and premarital cohabitation among married individuals. The results show that the positive association between education and premarital cohabitation has not decreased but instead strengthened over time. This trend is more consistent for women than men. Chapter 2 examines the association between premarital cohabitation and educational assortative mating outcomes. The results show that the differences in homogamy patterns between married couples with and without cohabitation experience vary across educational levels. Moreover, marriages preceded by cohabitation are more likely to cross educational barriers. Chapter 3 examines the association between cohabitation and divorce. The significant positive effect of premarital cohabitation on the risk of divorce is only found among males, and this effect persists across marriage cohort. The results from this thesis indicate a significant difference between China and both Western countries and other East Asian countries. The findings suggest that China is developing different patterns and trends of demographic changes because of its unique institutional and cultural context.
Compositional lexical networks: a case study of the English spatial adjectives
Keywords: spatial adjectives
degree semantics
lexical networks
compositionality
Dependent Type Theory

Most words cannot be given a single precise definition, but instead consist of multiple senses related to each other like members of a family. In cognitive approaches to semantics, this kind of category is described by a lexical, a diagram in which nodes represent senses and arrows represent sense connections. However, lexical network theory is not compositional: it does not explain how lexical networks are combined together to yield the meanings of phrases and sentences. The aim of this thesis is to develop lexical network theory in a formal, compositional setting. I argue that a traditional approach to formal semantics based on the simply-typed lambda calculus is not rich enough to implement lexical networks because it is unable to type the arrows which link word senses together. Instead, I propose replacing simple type theory with Martin-Löf Dependent Type Theory, and show how this allows for a fully compositional implementation of lexical networks. The resulting theory is applied to the description of the English spatial adjectives - high, low, tall, long, short, deep, shallow, thick and thin. These adjectives are an ideal starting point for studying the interaction between lexical and compositional semantics, since they have been studied extensively from both points of view. I illustrate how a compositional theory of lexical networks can provide an interface by which the insights of cognitive semantics can be imported into formal semantics, and vice versa.
A decision support system for integrated semi-centralised urban wastewater treatment systems
Keywords: sanitation
decision making
geographic information systems
sustainability
sustainability management
wastewater
cities
water reclamation
genetic algorithms
scenario planning
water supply
probabilistic design
decision support system
water security
infrastructure
water management

The importance of adequate water supply and sanitation infrastructure as cornerstones for the development of civilizations is undeniable. Although a strategy based on centralised infrastructure has proven to be successful in the past, in some circumstances such conventional systems are inappropriate for future needs. A Semi-centralised Urban Wastewater Treatment System (SUWWTS) may be considered a viable sustainable urban water management solution to promote water security. A SUWWTS merges regulations of traditional centralised systems with the concepts of close-loop and resource recovery of decentralised systems. However, research on the design and feasibility of implementing semi-centralised systems is in its infancy.
This Thesis is a first attempt to articulate the complexity, to systematize and to automatize the design of a SUWWTS. Here we show a novel method, referred to as framework, for the development of SUWWTS with allowance for the socio-economic and geographic context of any urban area. To demonstrate the proposed framework a Decision Support System (DSS) was developed; its output is a recommended design comprised of several wastewater treatment plants, their respective technology, and their associated sewerage and reclaimed water distribution networks. The results demonstrate the capabilities and the usefulness of the DSS; it applies the design engineers’ subjective preferences, such as regional technological inclinations and implementation strategies.
The results from a feasibility study on the city of Rio de Janeiro validated and demonstrated how the DSS can be used to assist decision-makers. This Thesis discusses the framework, the DSS and the demonstration case. Overall, it will hopefully help both other researchers and practitioners by contributing to the discussion on how to promote urban water security, to decrease urban areas’ dependency on ecosystem services whilst delivering better social welfare.
Development of a SQUID magnetometry system for cryogenic neutron electric dipole moment experiment

Keywords: cryogenics
precision particle physics
neutron electric dipole moment
SQUIDs
magnetostatics

A measurement of the neutron electric dipole moment (nEDM) could hold the key to understanding why the visible universe is the way it is: why matter should predominate over antimatter. As a charge-parity violating (CPV) quantity, an nEDM could provide an insight into new mechanisms that address this baryon asymmetry. The motivation for an improved sensitivity to an nEDM is to find it to be non-zero at a level consistent with certain beyond the Standard Model theories that predict new sources of CPV, or to establish a new limit that constrains them.

CryoEDM is an experiment that sought to better the current limit of |dn|<2.9×10−26e
cm by an order of magnitude. It is designed to measure the nEDM via the Ramsey Method of Separated Oscillatory Fields, in which it is critical that the magnetic field remains stable throughout. A way of accurately tracking the magnetic fields, moreover at a temperature ∼0.5
K, is crucial for CryoEDM, and for future cryogenic projects.

This thesis presents work focussing on the development of a 12-SQUID magnetometry system for CryoEDM, that enables the magnetic field to be monitored to a precision of 0.1
pT. A major component of its infrastructure is the superconducting capillary shields, which screen the input lines of the SQUIDs from the pick up of spurious magnetic fields that will perturb a SQUID's measurement. These are shown to have a transverse shielding factor of >1×107
, which is a few orders of magnitude greater than the calculated requirement.

Efforts to characterise the shielding of the SQUID chips themselves are also discussed. The use of Cryoperm for shields reveals a tension between improved SQUID noise and worse neutron statistics. Investigations show that without it, SQUIDs have an elevated noise when cooled in a substantial magnetic field; with it, magnetostatic simulations suggest that it is detrimental to the polarisation of neutrons in transport. The findings suggest that with proper consideration, it is possible to reach a compromise between the two behaviours.

Computational work to develop a simulation of SQUID data is detailed, which is based on the Laplace equation for the magnetic scalar potential. These data are ultimately used in the development of a linear regression technique to determine the volume-averaged magnetic field in the neutron cells. This proves highly effective in determining the fields within the 0.1
pT requirement under certain conditions.
Life and disease in Leopardi and Svevo
Keywords: prolongevity
energetics
Modernism
comparative literature
medical humanities
Giacomo Leopardi
literary influence
disease
nineteenth-century science
apocalypse
Brunonianism
ineptitude
the history of ideas
Dr Brown
evolution
medicine
Hufeland
Romanticism
Italo Svevo

This thesis looks at Giacomo Leopardi’s and Italo Svevo’s works from a comparative and interdisciplinary perspective. The elusive presence of Leopardi in Svevo is followed and justified via two sets of coordinates: both writers are connected via techniques of hybridization between medical and literary discourse, and via the goal of narrating a shared notion of vita as male or malattia. Through the four chapters of this thesis – focusing on ineptitude as physiological illness (Chapter I), experiments of prolongevity (II), revelations of life as disease (III), and stories of evolution and apocalypse (IV) – the notion of ‘disease’ is posited as a revelation of ‘life’ (physical and medical, metaphysical and cosmic) as a field of contradictory forces and energies, an impasse impossible to justify or cure through scientific or humanistic means.
A rationale is provided for the multifaceted Leopardian presence in Svevo. This thesis interweaves three methodologies: comparable physiological models narrativized into comparable discourses (‘comparability’), literary presences (‘literary’), and late-eighteenth and early-nineteenth century medical schools reformulated towards parallel conclusions (‘medical’). These elucidate and redirect to each other, proposing a comprehensive and hybrid perspective on narratives previously never systematically compared. This study expands on Svevo’s medical readings by detecting in his works ‘antiquated’ archetypes that Leopardi had, himself, integrated into comparable narratives.
It is in discourses where life appears as painful and arcane (physiological disease or metaphysical ill – or both) that Leopardi strategically emerges in Svevo’s works. This thesis concluded that Leopardi is – despite a lack of provable readings and clear philological traces as well as Svevo’s reticence in admitting this – a vital author for Svevo’s essays and narratives of malattia.
The methodology proposed in this thesis allows for studies beyond Leopardi and Svevo, hypothesising further interdisciplinary comparisons between Italian and European writers previously not attempted or, in fact, never considered possible.
Analysis of the roles of CDK1 and PP1 in the regulation of chromosome segregation
Keywords: Spindle Assembly Checkpoint
CDK1
Microscopy
Cell Biology
Phosphatases
Kinetochore
Mitosis
PP1
CRISPR
MPS1

Accurate chromosome segregation in mitosis is essential for the faithful inheritance of genetic material. The Spindle Assembly Checkpoint (SAC) ensures genomic stability is maintained by monitoring the attachment of chromosomes to the mitotic spindle and preventing erroneous chromosome segregation. Checkpoint regulation is coordinated by the opposing activities of kinases and phosphatases. CDK1 is the major mitotic kinase required for mitotic entry and activation of the SAC. In particular, CDK1 regulates recruitment of the principal checkpoint kinase MPS1 to kinetochores, a critical event for downstream checkpoint signalling. However, this thesis demonstrates that circumventing this particular requirement for CDK1 is insufficient for SAC signalling when CDK1 is inhibited, therefore revealing a crucial, unknown role of CDK1 in SAC signalling. Using high-resolution live and fixed cell imaging combined with biochemical assays, this study confirms that outer-kinetochore assembly is CDK1 dependent and that the disassembly of outer-kinetochore proteins is differentially regulated by the CDK1-opposing phosphatases PP1 and PP2A-B55. Critically, this work uncovers that the outer-kinetochore protein and checkpoint scaffold KNL1 is rapidly lost at the metaphase-to-anaphase transition, before other outer-kinetochore proteins. This occurs through a hitherto unrecognised CDK1-mediated interaction between the MIS12 complex and KNL1 that is critical for regulating checkpoint function. Therefore, specific phosphatase-mediated disassembly of the outer-kinetochore supports complete SAC shutdown through KNL1 loss while leaving microtubule-kinetochore attachments intact through maintenance of the NDC80 complex. This safeguards the integrity of the metaphase-to-anaphase transition and ensures accurate chromosome segregation. This study also highlights the key role of PP1 as a CDK1-opposing phosphatase at the metaphase-to-anaphase transition and sheds light on its previously poorly understood role in mammalian cells. CRISPR editing methodologies and high-resolution live cell imaging are used to develop novel tools for the investigation of the role of PP1 in human tissue culture cells. In particular, the generation of endogenously tagged PP1-GFP isoforms and constitutive PP1 isoform knock-outs now allows the observation of endogenous PP1 and the effect of isoform-specific loss respectively for the first time.