VictorJuiz/thesis huggingface dataset:
Interactions of perihperal membrane proteins with phosphatidylinositol lipids: insights from molecular dynamics simulations
Keywords: Phosphatidylinositol phosphate lipids
Molecular dynamics
Peripheral membrane proteins

Interactions between proteins and membranes are central to many signalling pathways and other cellular processes. Phosphatidylinositol phosphates (PIPs) are a family of lipids often acting as second messengers and targeted by peripheral proteins in these processes. A pipeline was developed combining the molecular dynamics (MD) approaches of umbrella sampling and coarse-grain modelling, and used to quantify and compare the interactions with PIP-containing model membranes of 13 pleckstrin homology (PH) domains, a common lipid-binding domain found in many proteins showing varied affinities and specificities for PIPs. Lipid selectivity generally agreed with previous observations. Several membrane-binding modes were identified, revealing PIP interactions through a secondary site are more common than suggested experimentally and appear to be related to overall affinity. Results suggest that simultaneous binding of multiple PIP lipids is required to achieve the high affinities characteristic of PH domains. Multiscale MD, combining coarse-grain binding simulations and atomistic refinement, was used to investigate PTEN, a tumour suppressor catalysing interconversion of PIPs and associated with many cancers and other disorders. Regions often ignored in previous studies were revealed to favour productive binding, largely via electrostatics. PIP clustering by bound PTEN and membrane insertion in the productive mode were demonstrated. Existence of an N-terminal PIP-binding site was supported, with this region appearing disordered, rather than helical as previously suggested. Changes in interdomain orientation when bound and with the clinically-relevant R173C mutation further suggest the importance of the interdomain interface for productive binding. Together, this work demonstrates the important contributions MD can make towards understanding protein/membrane interactions, particularly in the context of managing the diseases caused by their disruption.
Security and privacy in app ecosystems
Keywords: app
privacy
security
smartphone
ecosystem

Smartphones are highly-capable mobile computing devices that have dramatically changed how people do business, interact with online services, and receive entertainment. Smartphone functionality is enhanced by an ecosystem of apps seemingly covering the entire gamut of functionality. While smartphone apps have undoubtedly provided immeasurable benefit to users, they also contribute their fair share of drawbacks, such as increases in security risks and the erosion of user privacy. In this thesis, I focus on the Android smartphone operating system, and pave the way for improving the security and privacy of its app ecosystem.
Chapter 3 starts by doing a comprehensive study on how Android apps have evolved over a three-year period, both in terms of their dangerous permission usage and the vulnerabilities they contain. It uncovers a trend whereby apps are using increasing numbers of dangerous permissions over time and at the same time becoming increasingly vulnerable to attack by adversaries.
By analysing the Google Play Store, Android's official app marketplace, Chapter 4 shows that many general-purpose apps can be replaced with functionallysimilar alternatives to the benefit of the user. This confirms that users still wield power to improve their own security and privacy. Chapter 5 combines this insight with real-world data from approximately 30,000 smartphones to understand the actual risk that the average user faces as a result of their use of apps, and takes an important first step in measuring the improvements that can be made.
Users, however, are not always aware of the risks they face and thus Chapter 6 demonstrates the feasibility of a classification system that can transparently and unobtrusively identify and alert users to the presence of apps of concern on their devices. This classification system identifies apps from features in the network traffic they generate, without itself analysing the payload of their traffic, thus maintaining a high threshold of privacy.
While the work presented in this thesis has uncovered undesirable trends in app evolution, and shows that a large fraction of users are exposed to non-trivial risk from the apps they use, in many cases there is suficient diversity in the offerings of general-purpose apps in the Google Play Store to empower users to mitigate the risks coming from the apps they use. This work takes us a step further in keeping users safe as they navigate and enjoy app ecosystems.
Dynamics of temporal anticipation in perception and action
Keywords: Parkinson's disease
Ageing
Temporal orienting
MEG
Neural oscillations
Attention

The selective deployment of attention over time optimises our perception and action at the moments when relevant events are expected to happen. Such "temporal orienting" to moments when something is going to happen is especially useful when this information can be combined with predictions about where and what events are likely to occur. A large body of research has already established how temporal predictions dynamically influence our perception and action, but questions remain regarding the neural bases of these attentional mechanisms. In this thesis I present three magnetoencephalography (MEG) studies that I conducted to investigate anticipatory neural dynamics associated with spatial-temporal orienting of attention for perception and action. I also investigate and discuss how such anticipatory dynamics change with ageing and neurodegeneration in Parkinson's disease (PD), and how these anticipatory neural dynamics behave in situations where a complex, hidden spatial-temporal structure is present. In Chapter 1, I introduce the topic of this thesis by reviewing the literature on temporal orienting of attention and by introducing my specific research questions. In Chapter 2, I present an MEG study on anticipatory neural dynamics of joint spatial-temporal orienting of attention in the visual domain, in younger and older adults. This study shows that neural dynamics with spatial, temporal and spatial-temporal orienting are all differentially affected by ageing. In Chapter 3, I describe an MEG experiment that investigates anticipatory neural dynamics during spatial-temporal motor preparation and compares PD participants to healthy control participants. This study reveals that both behavioural and neural dynamics with temporal orienting are affected in PD. In Chapter 4, I describe an experiment that explores how an implicit spatial-temporal structure is utilised to predict and prepare for upcoming actions. This study shows that motor cortical excitability is dynamically modulated in anticipation of the location and timing of events, even when such expectations are hidden in complex visual-motor sequences that remain largely implicit. In Chapter 5, the General discussion, I place these results in their wider context and discuss limitations and future directions.
Identification of novel Runx1 targets involved in HSC development
Keywords: Hematopoiesis
Runx1

Haematopoietic stem and progenitor cells (HSPCs) are de novo generated within in the ventral aspects of the embryonic dorsal aorta (DA). Cells of this haemogenic endothelium (HE) will eventually undergo an endothelial to haematopoietic transition (EHT) that involves cell budding out of the aortic wall. Despite the detailed description of the cellular events, the exact haemogenic lineage path and the underlying molecular mechanism that establish full haematopoietic competence are still not entirely understood.
The transcription factor Runx1 is critical for the emergence of HSPCs and shows expression in the zebrafish HE as early as 24 hpf. To facilitate a detailed analysis of the transient HE population I generated a TgBAC(runx1P2:Citrine) reporter line under the control of the endogenous runx1 promoter on a bacterial artificial chromosome (BAC). Double-transgenic reporter lines for runx1 and the endothelial marker kdrl allowed us to isolate specifically cells of the DA away from the whole endothelial population, which could be further sub-divided into HE and non-haemogenic cells. Genomewide expression analysis within the respective tissues and upon Runx1 loss of function enabled the identification of HE-specific Runx1-regulated genes. Hereby, the gfi1ab gene appeared as the functional homologue of the murine Gfi1. I show that in zebrafish, EHT is orchestrated through a conserved Runx1-Gfi1-Lsd1 axis. The cellular functions of the remaining Runx1 targets imply that maturation into fully functional HSCs depends on epigenetic regulation due to the up-regulation of de novo DNAmethyltransferases, as well as on factors that allow the developing HSCs to respond to extrinsic cues from haematopoietic niches.
Lastly, it became evident that the early HE expresses dll4 at similar levels to the rest of the aortic endothelium, indicating a common lineage path. In the absence of RUNX1 the HE remains essentially arterial and persists as an integrated part of the DA.
Homogeneous catalysts for the synthesis of oxygenated polymers
Keywords: Stereoselectivity
Polyester
Zinc
CO2
Homogeneous catalysis
Salen
Ring Opening Copolymerization
Dinuclear
Polycarbonate
Lactide
Indium
Isoselectivity
Epoxide
Mononuclear
Ring Opening Polymerization
Phosphasalen
Mechanistic studies

This thesis describes the synthesis and characterisation of novel mono and dinuclear homogenous [Zn(II)] and [In(III)] metal complexes. Their applications as catalysts for CO2/epoxide or epoxide/anhydride ring opening copolymerisation and lactide ring opening polymerisation to generate polycarbonates and polyesters, respectively, are also reported.
Chapter 3 reports the first indium phosphasalen catalysts for CO2/cyclohexene oxide ring opening copolymerization. The catalysts are active at 1 bar pressure of CO2 and are most effective without any co-catalyst. It is also possible to use the complexes to isolate and characterise the key intermediates in the catalytic cycle. Kinetic and spectroscopic analyses show that polymerisation proceeds via a rare cis-mononuclear coordination- insertion mechanism.
Chapter 4 describes a series of mono and dinuclear zinc macrocycle catalysts with very high activities for the racemic lactide ring opening polymerisation. In most cases, the dinuclear zinc catalysts significantly out-perform the mono-zinc homologue. In addition, kinetic and spectroscopic investigations suggest a role for the ligand conformation in mediating rate. The catalysts perform very well under immortal conditions and operate at low catalyst loading, whilst conserving high activities.
Chapter 5 presents four dinuclear zinc acetate salen catalysts for the ring opening copolymerisation of CO2/cyclohexene oxide and phthalic anhydride/cyclohexene oxide. The catalysts show moderate activities for CO2/epoxide copolymerisation but are highly active for epoxide/anhydride copolymerisation. Structure/activity relationship studies reveal that the more flexible and electron donating ligand displays the highest activity. Poly(ester-b-carbonate)s are also afforded using the most active catalyst in terpolymerisations of anhydride/epoxide/CO2.
An investigation into the structural role of the CCR4-NOT complex in mRNA stability
Keywords: Expression of protein complexes
Deadenylation
Inflammatory gene expression
Protein expression

The CCR4-NOT complex is a global regulator of gene expression which controls mRNA levels by removing the poly-(A) tail, a step known as deadenylation and one that constitutes the rate-limiting step in mRNA decay. The human complex is comprised of eight stably associated CNOT subunits where CNOT1 forms the scaffold onto which CNOT2-11 bind. Although much has been learnt about the CCR4-NOT complex, questions still remain. Thus, this study focused on a number of sub-complexes of CNOT subunits and associated proteins to determine the mode of interaction with a hope to explore the mechanism of deadenylation by the CCR4-NOT complex. Firstly, the complex of CNOT10:CNOT11, found only in higher eukaryotes, was reconstituted for the first time using recombinant proteins. Crystallisation trials, limited proteolysis and mass spectrometry were used to isolate novel interaction regions between CNOT10 and CNOT11 which may provide direction for future structural and functional studies. Secondly, the interaction between CNOT9 and TTP was characterised. TTP is a RNA-binding protein which targets inflammatory mRNAs for deadenylation by recruiting the CCR4-NOT complex. This study highlights novel interactions between TTP and both CNOT2 and CNOT9. Moreover, BioLayer interferometry (BLI), peptide arrays and site-directed mutagenesis identified that TTP interacts with CNOT9 in a tryptophan-mediated manner. These findings change the known interface between TTP and the CCR4-NOT complex. Lastly, the MultiBac system was used to reconstitute a number of human CNOT sub-complexes, one of which was shown to effectively degrade a poly-(A) substrate, demonstrating it is enzymatically active. This achievement provides a tool for the future study of the CCR4-NOT complex. In summary, this study highlights novel interactions and characterises previously unknown binding mechanisms between CCR4-NOT subunits which expands our current understanding of the complex.
Explaining the trends in breastfeeding behaviours in Great Britain: Findings from the Infant Feeding Surveys, 1985 to 2010
Keywords: health inequalities
breastfeeding
health trends

Available data from the quinquennial Infant Feeding Surveys (IFS) show that breastfeeding rates in Great Britain (GB) rose steadily between 1985 and 2010. However, the rates of breastfeeding continuation and exclusivity remain relatively low, and there is evidence that breastfeeding in public may still be considered unacceptable by many in GB. To date, no study has examined the reasons behind the increase in breastfeeding rates between 1985 and 2010, and the factors which influence women’s practice of breastfeeding in public in GB remain under-researched. Therefore, this DPhil research aimed to investigate whether the increase in breastfeeding rates in the first six weeks after childbirth in GB between 1985 and 2010 were driven by changes in the distribution of population characteristics, or changes in the differences in breastfeeding behaviours between subgroups of women. It also aimed to investigate the factors which influenced the practice of breastfeeding in public in GB in 1995 to 2010.
Data from the IFS surveys in 1985 to 2010 were analysed to, firstly, describe and summarise the distribution of selected explanatory factors among the childbearing population of GB from 1985 to 2010. This was followed by an estimation of the independent effects of these explanatory factors on breastfeeding initiation, breastfeeding continuation at one week and at six weeks, and breastfeeding in public, in each survey year. There was an assessment of the changes over time in the effects of each factor on breastfeeding initiation, and on breastfeeding continuation at one week and at six weeks. This was followed by an examination of the extent to which changes in the distribution of factors among the childbearing population contributed to the increase in breastfeeding rates in the first six weeks in GB between 1985 and 2010.
This DPhil research found no evidence of changes in the effects of factors on breastfeeding in the first six weeks between 1985 and 2010. This suggests that breastfeeding behaviours had not improved over time. At the same time, there were increases in the distribution of those factors which positively influence breastfeeding, suggesting that the increase in breastfeeding rates in the first six weeks between 1985 and 2010 were indeed attributable to population changes rather than improved breastfeeding behaviours. Additionally, breastfeeding in public was seemingly most influenced by women’s perceptions of the normality and acceptability of breastfeeding in GB. There is a clear need for more equitable interventions to target the needs and perceptions of those women in GB who remain characteristically less likely to breastfeed.
Regulating dissemination: a comparative digital ethnography of licensed and unlicensed spheres of music circulation
Keywords: Streaming
Digital Ethnography
File-sharing

This thesis examines the transformations of music circulation and consumption brought about by new media platforms. Specifically, it shows how the social and technical design of online music platforms link the consumption of music immanently to its circulation. The thesis makes contributions to ethnomusicology, media studies, and digital anthropology, as well as to the study of music's technical cultures. It is based on a comparative ethnographic study of music circulation and consumption within two field sites: the commercial streaming service Spotify and the extralegal, unlicensed peer to peer platform 'Jekyll'. Governance comes to the fore in both sites: the study shows how practices of music curation, collection and consumption are regulated by the technical design of these platforms. Surprisingly, music consumption and circulation on Jekyll generates a variety of social relations, including pronounced social hierarchies. This is far less apparent on Spotify, due to the platform's individuated mode of address. The subjectivities of online music consumers are mediated by both their personal histories and by the broader technical genealogies of the platforms they use. The thesis illuminates the mutual interdependencies of the licensed and extralegal spheres, two domains often portrayed as not only separate but antagonistic. It also provides insight into the hybrid modes of exchange that generate digital music platforms. Through examining the entailments of circulatory participation, the study offers new insights into digital polymedia and to labour, exchange and governmentality online, as well as providing nuanced understandings of the ownership and collection of music in digital environments. Moreover, it advances new concepts to identify core aspects of digital music cultures, namely 'circulatory maintenance' and 'circumvention technology'. The thesis shows overall how Spotify and Jekyll are not merely emblematic of emergent consumption practices engendered by new media, but are bound up in the mutual co-creation of culture, engendering novel musical subjectivities, practices, socialities and ideologies. The complex musical, technical and social assemblages formed around music circulation online point to the affective potentials of music itself, producing inalienable attachments to the objects through which music is formatted, experienced, and circulated.
New Songdo City, or, the potentiality of Asian urbanism(s)
Keywords: New Songdo City
City of Tomorrow
Asian Urbanism
Eco City
South Korea
International City
Urban Theory
Smart City

This thesis explores the nexus between 'urban expressionism' and the potentiality of 'Asian urbanism(s)' by exploring ways that different planning paradigms have been located/dislocated in the case of New Songdo City, South Korea. By investigating four expressions of New Songdo City - as an 'Eco-City', a 'Smart City', an 'International City', and as the 'City of the Future' - this thesis argues that urban expressionism can make important contributions to the aims of Asian urbanism(s). Ultimately, this research demonstrates the ways that urban expressionism can be used to destabilize hegemonic Western-centric urban knowledge and city-building practices, and further point to new geographies of theory from which important contributions to urban research can be made.
Urban expressions are made evident by various entwined urban rhetorics and worlding practices that operationalize multiple mediums of communication. Consequently, New Songdo City is, first and foremost, a city of simultaneity. To investigate this simultaneity, this research utilizes an exploratory case study approach and multiple qualitative methods that include semi-structured interviewing, focus groups, and surveys to gather insights from residents of Songdo, local experts, public and private sector actors, and other key stakeholder groups. Visual analysis is also used to explore mixed-mediums of data, including promotional videos, images, exhibition displays, magazines, and advertisements. The methods used to undertake this thesis provide a glimpse in to the development of New Songdo City and capture different urban expressions that are articulated by the city through various examples of urban rhetoric and worlding practices.
The urban expressions presented in the New Songdo City case are analysed through the lens of Asian urbanism(s) and investigate the ways that hegemonic Western and Euro-centric conceptualizations of ‘the urban’ and ‘the city’ have been deployed, articulated, experienced, challenged, and complicated. By extension, this thesis also contributes to a more nuanced conceptualization of Asian urbanism(s) as well as the relevance of New Songdo City for urban theory in South Korean, Asian, and more generalizable contexts.
Computer-aided analysis of fetal cardiac ultrasound videos
Keywords: Video Analysis
Rotation Invariance
Machine Learning
Algorithm
Fetal
Echocardiography
Tracking
Cardiac
Random Forests
Heart
Localization
Ultrasound

This thesis addresses the task of developing automatic algorithms for analysing the two-dimensional ultrasound video footage obtained from fetal heart screening scans. These scans are typically performed in the second trimester of pregnancy to check for congenital heart anomalies and require significant training and anatomical knowledge to perform.
The aim is to develop a tool that runs at high frame rates with no user initialisation and infers the visibility, position, orientation, view classification, and cardiac phase of the heart, and additionally the locations of cardiac structures of interest (such as valves and vessels) in a manner that is robust to the various sources of variation that occur in real-world ultrasound scanning. This is the first work to attempt such a detailed automated analysis of these videos.
The problem is posed as a Bayesian filtering problem, which provides a principled framework for aggregating uncertain measurements across a number of frames whilst exploiting the constraints imposed by anatomical feasibility. The resulting inference problem is solved approximately with a particle filter, whose state space is partitioned to reduce the problems associated with filtering in high-dimensional spaces.
Rotation-invariant features are captured from the videos in an efficient way in order to tackle the problem of unknown orientation. These are used within random forest learning models, including a novel formulation to predict circular-valued variables.
The algorithm is validated on an annotated clinical dataset, and the results are compared to estimates of inter- and intra-observer variation, which are significant in both cases due to the inherent ambiguity in the imagery. The results suggest that the algorithm’s output approaches these benchmarks in several respects, and fall slightly behind in others.
The work presented here is an important first step towards developing automated clinical tools for the detection of congenital heart disease.