VictorJuiz/thesis huggingface dataset:
Functional analysis of the fat mass and obesity associated (Fto) gene and protein
Keywords: FTO
nuclear transport
mouse models
protein-protein interactions
gene knock-out
cellular localisation

Genome wide association studies have shown that common variants in the human fat mass and obesity-associated (FTO) gene predispose to obesity and increased fat mass. Mice globally lacking Fto are lean, while mice globally overexpressing Fto have increased body weight due to increased fat mass. FTO protein was shown to localise to the nucleus and demethylate ssDNA and ssRNA. However, the mechanisms by which FTO mediates its effects on body phenotype remain unknown.
In this thesis, I found that native FTO can be detected in both the nucleus and the cytoplasm during interphase, and that nuclear FTO was exported through the nuclear membrane during early prophase of the mitotic cell division. I developed co-immunoprecipitation (Co-IP) protocol to pull-down native FTO and identified a large number of new candidate binding partners (CBPs). Computational analysis predicted a role for FTO, and many CBPs, in RNA post-transcriptional modification and processing. I confirmed that the E3 ubiquitin-protein ligase TRIM21 interacts with FTO in multiple mouse tissues and binds FTO through its SPRY domain. Importantly, TRIM21 ubiquitinated FTO which did not lead to its degradation. FTO partially co-localised with TRIM21 and the decapping enzyme DCP2 in mRNA processing bodies (p-bodies). Overexpression of TRIM21 led to the accumulation of FTO outside the nucleus, but was reversed when both proteins were overexpressed. Additionally, I created a muscle specific Fto knock-out mouse model and found that lack of FTO in muscle did not result in the body composition phenotype reported in global Fto knock-out mice.
Taken together, FTO can function in both the cytoplasm and the nucleus, where it interacts with TRIM21 which ubiquitinates FTO and potentiates its cytoplasmic localisation. Moreover, function of FTO in muscle does not mediate the obesity phenotype in mice.
Tailored carbon-based nanomaterials for biological energy electrocatalysis
Keywords: Electrocatalysis
Biocatalysis
Carbon nanomaterials
Carbon nanotube columns
Hetero carbon nanotubes
Flow catalysis

Hydrogenases are energy relevant bio-electrocatalysts. Their study and applications require immobilisation on carbon scaffolds and benefit from carbon materials design. The present thesis first compares eleven carbon materials for the adsorption of hydrogenase-1 from E. coli. All of them accommodate the enzyme in an electroactive configuration. A high surface area and/or abundance of 'edge' carbon planes are identified as important features to improve studies and applications of hydrogenases. The nanomaterials screened facilitate the coupling of infrared spectroscopy and electrochemistry for study of adsorbed species. This is demonstrated for the first time with a flavin mononucleotide molecule and the hydrogenase and opens the way to unprecedented investigation of (bio)electrocatalysts.
In situ growth of multi-wall carbon nanotubes (MWCNTs) inside quartz columns by aerosol assisted chemical vapour deposition (AACVD) is investigated. Control over the column filling and the thickness of the MWCNT forest profile along the column is achieved. The flow rate of carrier gas is identified as a key parameter for this control. The final structures obtained are columns with their inner walls covered with a porous, interconnected and conductive carbon network. Through H2-driven biocatalysis, the conversion of acetophenone to 1-phenylethanol is achieved in a flow reactor configuration. The MWCNT columns are shown to be successful and simple, yet versatile, platforms for flow (bio/electro)catalysis.
Finally, large quantities of hetero-MWCNTs are obtained by an original combination of AACVD and chemical vapour deposition. The MWCNTs are extensively characterised and display continuous junctions between nitrogen-doped and un-doped sections along a single MWCNT. The controlled change of chemical properties but also graphitic structure obtained is exploited for the first time to perform spontaneous and selective (1) oxidation reactions and (2) immobilisation of platinum particles on different parts of a single MWCNT. This new approach could be relevant for localised immobilisation of enzymes along a nanomaterial.
This thesis achieves three different degree of carbon nanomaterials design to develop scaffolds suitable for bio-electrocatalyst immobilisation in targeted applications.
Oxidation of soot with modified silver catalysts
Keywords: Soot Combustion
Meta;-Support Interaction
Morphology Modification
Size Effect
Heterogeneous Catalyst

As the demand for motor vehicles has soared dramatically with the emergence of rapidly developing countries, the need for regulating vehicle emissions and pollutants is increasingly more important. With the newest regulations for diesel particulate emissions soon to be enforced, there is a great need to catalytically convert soot particles from the exhaust into relatively less polluting carbon dioxide.
Here a supported silver catalyst is reported for the soot oxidation reaction. The silver catalyst is protected and supported using various capping agents and metal oxides, and modified using various synthetic methods. The catalysts are then tested with soot using thermogravimetric analysis (TGA) at a reaction temperature up to 700oC.
In order for a better design and modification of the silver catalyst, an improved understanding of the interaction between silver nanoclusters and the metal oxide support must be established.
XPS and UV/VIS spectroscopy are amongst the techniques used to probe the metal/metal oxide interaction. It is shown that the surface plasmon resonance of silver can be perturbed by the metal oxide support, modifying its band structure. It is also extremely important for the catalyst to be thermally stable up to 600°C for it to be employable in an exhaust system. In-situ XRD can be used to investigate the thermal stability of both the silver and metal oxide species in an oxidising environment. The phase changes, if any, of either species under heating can also provide a better understanding of the metal/metal oxide interaction and ultimately the soot combustion mechanism.
It has been demonstrated that different catalyst surfaces can have different catalytic performances. By altering the morphology of the support, preferential growth of one surface can be achieved, thereby modifying the catalytic performance for soot combustion.
The political economy of NPOs promoting  "active ageing" programs for the elderly in Taiwan
Keywords: Non-Profit Organizations
Taiwan
Active Ageing
Political Economy

From the 1990s, welfare state and civil society in Taiwan were confronted with challenges and opportunities brought by population ageing. The author chooses NPOs with "Active Ageing" programs for the elderly, a group thriving as a consequence of Taiwan's unique transitional democratization and privatization under Neoliberalism, as a case to systematically investigate the governance structure. Four core NPOs of various scales and capacities are sampled while their stakeholders are also interviewed. Findings reveal that after the pension reform made possible by social movement and electoral politics, these institutionalized social forces secure their position in the welfare delivery system. However, problems remain unresolved because of structural inertia while NPOs operate under the changing field frame and conflicting institutional logics between the welfare state and civil society. Though partially impeded, NPOs develop an East-Asian way of solution with various counterplots. Contrasting rationales of networking explain NPOs' diverse achievements while quasi-subordination and structural loop consolidate respective constituency. Four patterns of perceived relational social capital relate to NPOs' networking practices and institutional settings. The connection among institutions, networking configurations, and relations further crystalizes the tripartite governance structure composed of the institutional, technical, and social environment. Legitimation of means functions mainly within the institutional environment while legitimation of ends through technical and social environment also justifies NPOs' social appropriateness. Various types of legitimacy are conferred to NPOs at different development stages while both formal and informal norms guide NPOs' behavior in the two-dimensional governing kinetics. Through this case study, the author also demonstrates how a meso-level approach of organizational study, integrating Sociological Institutionalism and Organizational Social Capital Theory, possibly sheds lights on the different areas of Sociology, especially those of social movement, NPOs, and ageing society.
Beyond number sense: Contributions of domain-general processes to the development of numeracy in early childhood
Keywords: cognitive development
executive functions
numerical cognition
preschool

A large proportion of recent research on the development of numerical cognition has focused on the foundational role of approximate number sense, yet number sense alone cannot fully explain how young children acquire numeracy skills. This thesis aims to investigate how other domain-specific processes and domain-general cognitive processes relate to numeracy in early childhood and whether they play a role in learning about mathematics. The experiments presented in Chapter 2 explored how domain-general processes relate to young children’s attention to discrete number in non-symbolic representations through a correlational approach. Results supported the role for inhibitory control in selecting numerosity as the relevant stimulus dimension. In order to investigate causal relationships in emerging maths performance, Chapter 3 reports a cognitive training study aimed at contrasting transfer effects of domain-general and domain-specific training in pre- schoolers. Findings suggested caution in interpreting published transfer effects without the highest level of control. The latter chapters targeted learning mechanisms by tackling a specific process in mathematical cognition: acquiring the meaning of numerical symbols. Specifically, the experiments presented in Chapter 4 employed an artificial learning paradigm to test factors influencing adults' and children’s formation of novel symbolic numerical representations. Congruency between discrete and continuous non-symbolic quantity influenced novel representations and numerical order information facilitated learning, especially in children. In order to explore symbolic representations of real numbers, Chapter 5 focuses on associations between different representational formats of real numbers in young children and how this relates to both domain-specific and domain-general factors. Children had stronger mappings between symbols and precise non-symbolic representations for numbers smaller than four, than between larger numbers and approximate non-symbolic representations. Taken together, results from the experiments presented in this thesis highlight the need to incorporate factors beyond number sense in theories of numeracy development.
The Visio Baronti in its early medieval context
Keywords: medieval literature
future life
visions
visio baronti

The focus of this thesis is the Visio Baronti (VB), an account of a seventh-century monk's journey to the other world. This text serves as a metaphoric fulcrum to support a more extensive study of early medieval conceptions of the other world and the historical context in which visionary accounts were produced. Chapter 1 contains an introduction to ideas of the other world, a survey of types of visionary experiences, their uses, imitations and historiographical responses to them. Chapter 2 focuses on medieval and modern responses to visions. This chapter includes a survey of the terminology for dreams and visions found in theoretical writings, compares dream theory with otherworld visions and identifies medieval methods of determining the validity of a visionary experience. Chapter 3 investigates the manuscript tradition of the VB, in order to illuminate medieval receptions and treatments of this text. Because the text appears unusual for the seventh century, chapter 4 provides an analysis of the grounds for dating the VB to the seventh century, while chapter 5 treats the VB in its seventh-century monastic context and assesses what influences shaped this text. Chapter 6 compares Barontus's vision with ninth-century visions and other Carolingian writings to consider Carolingian interest in the VB in light of their contributions to the genre. Chapter 7 examines the artistic response to this text through an examination of the illustrations which accompany the text in the ninth-century St Petersburg manuscript. A brief conclusion to this study follows.
National security, risk, and accountability
Keywords: closed material procedure
judicial review
public law
counterterrorism
administrative law
national security
procedural fairness

This thesis explores issues of procedural fairness across the major statutory counterterrorism powers which require the Closed Material Procedure (CMP) in judicial review. It also considers the Justice and Security Act 2013 which applies to civil proceedings of any nature engaging national security concerns on a discretionary basis. The analysis construes procedural fairness broadly by considering its application both in the curial context and inside the relevant administrative organisations. It argues that procedural fairness in the CMP should be understood as part of the routine risk-management responsibilities of administration and administrative law, as opposed to an initiative which is 'exceptional' by virtue of its national security subject matter. Procedural fairness in the CMP could be invigorated by taking seriously the presence of risk and risk assessment in the application of the statutory powers by the executive and in the operation of the CMP itself. This thesis also argues that the extension of the CMP to damages actions under the Justice and Security Act 2013 raises greater normative problems than actions in the existing province of the CMP. This is because such claims, whilst not the sole province of the Act, concern executive accountability for tortious actions, as opposed to judicial review of executive riskmanagement of terrorism. The analysis concludes with two critical recommendations for improving procedural fairness in law and administration in the relevant subject matters; but ultimately recognises that these are but a first step in a broader project which requires the development of an interdisciplinary substantive theory of necessary secrecy.
As Micronarrativas em Portugal: de Almada Negreiros a Ana Hatherly
Keywords: Microcontos
Micronarrativas portugal
Micronarrativas
Flash fiction Portugal
Short short fiction

Literary works and other manifestations that demonstrate, disseminate or stimulate the practice of extremely brief narrative texts have increasingly been gaining ground in the 21st-century. This phenomenon, which varies in intensity depending on the country – seemingly more substantial in the American continent and more timid in European countries –, has ramifications more or less on a global scale. Naturally, there has been, over the last few decades, a greater awareness of the dissemination of this type of productions, thanks to the visibility that new information technology, above all the Internet, has afforded. This tendency, however, just like any other human activity, is bound to have antecedents. To analyse its roots may help us to understand its relevance today. The research carried out here has as its object of study extremely brief narrative texts produced in Portugal. It focuses on a period of time which, it will be argued, is of utmost importance for the presence of micro-narratives in the Portuguese literary landscape: the period situated between the dawn of modernism at the beginning of the 1910s and the post-revolutionary moment when Ana Hatherly publishes the third volume of her overarching project entitled Tisanas, in 1980.
Mathematical modelling of drug-ion channel interactions for cardiac safety assessment
Keywords: Ion channel kinetics
Model selection
Mathematical modelling
Experimental design
Cardiac safety assessment
Model validation
human Ether-a-go-go Related Gene
Patch clamp
Parameter inference
Cardiac electrophysiology

Unintended drug interactions with ion channels in cardiac cells can alter normal electrical activity in the heart. This can lead to the onset of cardiac arrhythmias which can be potentially fatal. Such arrhythmias are a leading cause of market withdrawal of pharmaceutical compounds. It is therefore important for pharmaceutical companies to identify drugs which may cause adverse changes to cardiac electrical activity as early as possible in the drug development process.
Computational approaches provide great potential for assessing cardiac safety at low cost and high-throughput. Regulatory guidelines for the assessment of cardiac safety are being revised and computational approaches are envisaged to form an integral part of future guidelines. It is therefore important that computational methods proposed for use are both accurate and well validated.
This thesis is focused around the use of mathematical models for cardiac safety assessment. We evaluate an approach which uses information on the extent of drug block of cardiac ion channels to predict changes in cardiac electrical activity in a rabbit-based safety test. A possible limitation of this approach is the representation of drug-ion channel interactions within the mathematical model. We go on to explore the representation of the kinetics of the cardiac potassium channel encoded by hERG (human-Ether-a-go-go Related Gene) within mathematical cardiac electrophysiology models.
We demonstrate how existing mathematical models of hERG channel kinetics can behave very differently when used to simulate the same voltage protocol. We also show the impact that the choice of hERG channel representation used within an action potential model can have on the prediction of drug effects on cardiac activity. We design and perform novel experiments to allow us to construct and validate mathematical models describing hERG channel kinetics.
We demonstrate the potential for the use of computational approaches in cardiac safety assessment. However, at the same time we indicate that models used for this purpose must be carefully constructed and thoroughly validated, as well as illustrating ways this may be achieved. Such considerations are a prerequisite for more predictive computational assessment of cardiac safety.
New transformations of azacycles
Keywords: organic chemistry
azetidine
azacycles
asymmetric synthesis
heterocycles
organolithium

The work presented in this thesis involves new transformations of azacycles, focusing on the introduction of functionality α-to N. α-C-H functionalisation on an azetidine has been a long-standing challenge, with N-protecting/activating groups that work well in the higher and lower azacyclic systems not viable. A recent breakthrough in the Hodgson group showed the rarely used N-thiopivaloyl group was effective for α-deprotonation– electrophile trapping on azetidines, but was not without limitations concerning harsh removal conditions and scope for further substitutions. This thesis describes efforts to overcome these issues by development of a new protecting/activating group for N, t-butoxythiocarbonyl (Botc).
Electrophysiological responses to noxious stimuli in the anaesthetised child
Keywords: Nociception
Preterm
Anaesthesia
EEG
Paediatrics
Children

In the UK, more than 235,000 children admitted to hospital each year receive an operation or investigation under general anaesthesia. It is not known whether nociceptive stimulation evokes a change in cortical brain activity in the anaesthetised child. The aim of this thesis is to determine whether noxious stimulation administered to anaesthetised children results in a measurable change in brain activity and whether this evoked activity is altered in children who have been born prematurely and experienced a high level of pain in early life.
Changing patterns of neuronal activity evoked by noxious and non-noxious stimuli were 'time locked' to electrophysiological recordings by means of a novel high-speed camera and an event detection interface developed during this thesis. Changes in band power were examined pre- and post-stimuli and across the different stimulus modalities.
In all children, background EEG activity was dominated by delta (&LT;3 Hz) and alpha (8-12 Hz) band frequencies, consistent with previously reported anaesthetic literature. Clinical and experimental noxious stimulation, and tactile stimulation evoked a significant increase in delta activity (p&LT;0.05) with no changes in average heart rate or ipsilateral EMG activity observed between pre- and post-stimulus. The application of local anaesthetic to the stimulation site diminished the evoked increase in delta activity. The response to noxious stimulation in the children born prematurely was not significantly different from the age-matched control group (p&GT;0.05) but they had striking differences in their background EEG activity. Prematurely born children had significantly lower alpha and beta band activity.
The electrophysiological recordings we have obtained show that it is possible to measure evoked brain activity following a variety of noxious and non-noxious stimuli to investigate how the paediatric human brain processes sensory information under anaesthesia. The EEG measures were more sensitive to nociception than changes in autonomic activity and reflex withdrawal activity. Noxious stimulation caused a significant increase in delta activity, representing an increase in cortical synchronisation. While the children who were born prematurely did not respond differently to the noxious stimulation they had dramatically different background activity, which could have clinical relevance when using brain-derived patterns of EEG activity to help establish anaesthetic depth.