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Investigating the Molecular basis of Cole Carpenter Syndrome
Get PDFCole Carpenter syndrome (CCS) is a rare genetic syndrome affecting bone integrity and durability. It is believed to be related to osteogenesis imperfecta (OI), a group of genetic disorders commonly known as brittle bone disease. The molecular mechanism of the syndrome has yet to be discovered, however two distinct types have been identified: CCS1 and CCS2, linked to mutations in protein disulphide isomerase (PDI), and SEC24D (a component of the COPII vesicle export complex) respectively. This thesis will provide groundwork in investigating the molecular basis of CCS1. This variant is characterised by a single amino acid substitution mutation (Y393C) in PDI, an endoplasmic reticulum (ER) specific protein disulphide isomerase and molecular chaperone involved in collagen folding. Without this chaperone, collagen cannot fold into its triple helical tertiary structure, and this misfolded protein may accumulate in the ER, activating the unfolded protein response (UPR). It has been suggested that a failure to resolve this response may result in the brittle bone phenotype of Cole Carpenter syndrome. This thesis presents work in both primary cells and established cell lines to identify potential interacting partners of Y393C-PDI, hypothesising the potential downstream effects on collagen matrix production. Indirect immunofluorescent labelling of collagen I suggests that collagen production is impaired, and confocal microscopy revealed abnormal ER and lysosome organelle morphologies in Y393C-PDI expressing cells. Overall cell viability of affected cells appears significantly decreased, and they are less influenced by the action of small molecule inhibitors than wild-type cells. Altogether, these preliminary data shed light on the cause of the bone specific phenotype of Cole Carpenter Syndrome 1, and potentially help to understand other OI-related disorders
Satellite remote sensing of supraglacial lakes in East Antarctica
Get PDFDeveloping accurate projections of ice-sheet responses to climate change remains a key scientific challenge. Understanding the controls on the distribution and evolution of surface meltwater around the Antarctic Ice Sheet (AIS) and its impacts on ice dynamics is critical for improving model predictions of AIS contributions to global mean sea-level rise. This thesis aims to better quantify the current controls on the distribution and evolution of supraglacial lakes (SGLs) on the East Antarctic Ice Sheet (EAIS) and their potential impact on ice-sheet mass balance and dynamics. The thesis begins with a review of recent advances in our understanding of SGLs in Antarctica, aided by developments in satellite remote sensing. Seasonal SGL evolution is then examined on the Shackleton Ice Shelf, chosen for its potential vulnerability to future surface meltwater-induced disintegration. Seasonal lake variability on this ice shelf is sensitive to snowmelt intensity associated with katabatic wind-driven melting. The role of SGLs in the rapid disaggregation of the Voyeykov Ice Shelf is then determined. It is shown the weakening and removal of stabilising ice m\'elange and multiyear landfast sea ice triggered this event, rather than surface meltwater. This implies that lakes are not always a necessary precursor of ice-shelf collapse. The first pan-ice-sheet observations of SGLs around the entire EAIS periphery over seven consecutive melt seasons (2014-2020) reveal SGL area and volume are highly variable on interannual timescales and are asynchronous between ice shelves. Climatic and surface controls on this interannual variability are explored, revealing significant relationships with modelled summer surface melt and runoff on some ice shelves deemed vulnerable to hydrofracture. Together, these findings represent novel observations of SGL evolution and the controls on interannual SGL variability around the EAIS. Using these observations in future ice-shelf models will help improve representation of the complex relationships between local climate, ice/firn conditions, surface melt and runoff. This will help constrain ice-sheet model projections of how surface meltwater-induced dynamic losses from the AIS will contribute to sea-level rise in the 21st Century and beyond
Characterisation of the Early-Late Triassic Stratigraphy of the Solway Firth, UK: Potential for CO2 storage
Get PDFThe Solway Basin and onshore Carlisle Basin (Solway Firth) contains the Early-Middle Triassic (Olenekian-Anisian) Sherwood Sandstone Group (SSG) reservoir and the Middle-Late Triassic (Anisian-Rhaetian) evaporitic mudstone seal of the Mercia Mudstone Group (MMG). This succession forms a ‘saline aquifer’ that is locally under-characterised. Imminent CO2 storage in analogous stratigraphy in the depleted hydrocarbon fields of the adjacent East Irish Sea Basin (EISB) raises the question whether the Solway Basin could have similar utility. Onshore outcrop analogues, legacy offshore hydrocarbon data and well cuttings are used to characterise this reservoir-seal system and determine its suitability for CO2 storage. An extensive petrographic, diagenetic, depositional and reservoir quality investigation of the SSG reservoir has been conducted, alongside burial history modelling and stable isotope analysis. The Solway Basin was likely connected to the EISB, forming a distal section of the vast (>400 km) overarching ‘Budleighensis’ river system. A detailed facies evolution study suggests the very fine-grained fluvial facies of the Annan Sandstone Formation, with stacked channels, flood plain fines and playa facies, represents the terminal site of this significant fluvial system. The aeolian dune facies and subordinate playa facies of the Kirklinton Sandstone Formation marks its abandonment and retraction from the Solway Basin. Facies have played a key role in reservoir quality distribution. The heterogenous nature of the Annan Sandstone Formation is reflected in its porosity (2-25%), where reservoir quality is moderate within the ribbon channel facies but has been severely impeded in finer grained facies by two phases of calcite cementation, quartz cementation and pore-filling matrix illite. The Kirklinton Sandstone Formation has preserved excellent reservoir quality (porosity 14-28%), similar to or better than benchmark EISB sandstones despite a finer grain-size, mainly due to clay grain-coats. This petrography is thought geochemically optimum for CO2 sequestration, with a significant storage potential (~500 Mt). The MMG was characterised mainly using XRD, SEM and wire-line data, revealing an excellent, thick (700-800 m) seal of pure halite beds, halite-mudstones and silty to sandy claystones. The illite-rich caprock will likely be stable during CO2 storage geochemically. The greatest risks to caprock integrity are chlorite and dolomite dissolution and heterogenous silt and sand presence. The Solway Basin is seen as an excellent CO2 storage target that is not hindered by the issues of previous hydrocarbon extraction but where characterisation has been aided by regional hydrocarbon reservoir analogues. The facies development and reservoir qualities identified suggest that Triassic targets that were distal or marginal to fluvial systems can form prime CO2 storage sites
Synthesis and Material Properties of Aromatic Cation-Centred Compounds
Get PDFAromatic cations, such as cyclopropenium and tropylium, have access to delocalised electrons that spread the charge across their rings, enabling them to form stable ionic molecules.1 They are readily accessible species which makes them of interest for integration as part of functional materials.
In the field of ionic liquid crystals, while aromatic species such as imidazoliums have been widely investigated as part of molecular design of mesogens,2 the investigation of cyclopropeniums as part of liquid crystals has only just been undertaken.3 However, their molecular structure lends themselves to being the symmetrical core part of a discotic liquid crystal, while integrating a charged character to the material to give them potential as functional materials for electronic devices.
This thesis will discuss the synthesis of a range of cyclopropenium centred liquid crystals, which possess columnar liquid crystal phases and show a conductive character. The electron study revealed the preservation of a liquid-like conductivity of these materials into the liquid crystal and solid phases, and no conductive anisotropy in the liquid crystal phase. The initial synthesis and characterisation of a new series of aminocyclopropenium liquid crystals with greater thermal stability was also undertaken. In addition, attempts to adapt the procedures used for the tropylium species are discussed, including the challenges of applying this chemistry to the larger cation
On Semantic Segmentation for Vehicle Sensing in Adverse Conditions
Get PDFAutomotive scene understanding and segmentation has become increasingly popular in recent years as it meets the high demand for automotive computer vision to support future vehicle autonomy. Understanding and analysing the entire scene for tasks such as image classification and segmentation for automotive applications is extremely challenging and is made significantly more challenging by variable illumination and weather changes in outdoor environments. While most contemporary scene understanding approaches are applied under ideal weather conditions, there is a lack of research on automotive scene understanding under extreme weather conditions. Indeed, these existing approaches are unlikely to provide optimal performance compared to using established \textit{a priori} insights into extreme-weather understanding.
This thesis provides a significant contribution to a contemporary automotive semantic scene understanding by proposing a model capable of performing semantic segmentation from a monocular image input taken in adverse illumination and weather conditions. Firstly, we investigate the use of illumination-invariant image pre-transformations to reduce illumination variations of scenes when shadows are present; we do this by assessing their impact as an initial pre-process before using an existing fully deep Convolutional Neural Network (CNN). Within this context, we propose a novel approach based on illumination-invariant image representation that is combined with the chromatic component of a perceptual colour-space to improve contemporary automotive scene understanding and segmentation. Our subsequent proposed approach takes advantage of a multi-modal architecture that leverages both recent advances in adversarial training and domain adaptation as a method to correct for the
degraded visibility present under foggy weather conditions. As an end-to-end pipeline, our framework includes a competitive encoder-decoder architecture for semantic segmentation, with low computational complexity, thus enabling real-time performance. We employ distinct encoders with dense connectivity and features fusion to effectively exploit information from different inputs such as RGB colour, depth and luminance images, which contributes to more comprehensive feature extraction to better facilitate the representation of different key features. To avoid information loss and share high-resolution features in the latter reconstruction stages of CNN upsampling, we leverage skip connections. We expand this approach to perform multi-task learning as well as utilise depth as a complementary information source for the semantic segmentation task. Furthermore, we outline the process of training two domains (\textit{normal} and \textit{foggy}) simultaneously with shared weights, where each model is trained on each weather condition. Experimental evaluation of our proposed approach is performed on the challenging benchmark datasets including synthetic and real-world examples illustrating competitive quantitative and qualitative performance when compared to contemporary state-of-the-art approaches
The Design & Verification of an Automatic Occlusion Speech Valve for Voice Rehabilitation
Get PDFThis work investigates the restoration of the lost functions of the upper airway in patients who have
undergone total laryngectomy surgery. The primary airway functions were defined as ventilation and
patency, heating and humidification of air, filtration of air, coughing, swallowing, speech, olfaction,
gustation and chemo sensitisation and air resistance.
Through a review of the literature, the performance of the airway functions was compared pre and
post laryngectomy. It was found that all of the aforementioned functions were negatively affected
by total laryngectomy which led to lower quality of life and increased risk of harm or disease
compared to healthy individuals of the same age groups.
There are medical devices described in the literature used for the restoration of upper airway
function. For most identified functions there was a medical device and or therapeutic solution to
restore them partially or fully. Research found no evidence that existing medical devices had the
level of filtration they provided verified. Many devices in the literature restored one function,
requiring patients to use a combination of devices, this has benefits and disbenefits, mostly relating
to in use life. This work aimed to restore as many functions as possible within a singular device.
A singular device was designed to restore the upper airway functions. The variability of the
difference in resistance of the larynx to inhalation and exhalation identified in the literature was
incorporated into the device, the phenomenon was approximately matched by employing fluid
structure interaction within the device. The design featured a novel bistable diaphragm that the
patient can close hands free when they want to redirect air through a speech device. This had the
benefit of remaining closed during pauses in speech.
Different functions of the candidate device were evaluated through a combination of tests, including
tests following established methodologies and new tests and test apparatus developed as part of
this work. Pneumatic test apparatus was built to produce outputs that matched laryngectomy
patient spirometry data found in the literature.
The first iteration of the design was tested in vitro. The design was translated into FEA, validated
with the lab results and optimised. Heat and moisture exchange and filtration were fully restored.
Cough, breathing resistance and speech were partially restored. It was concluded that a singular
device can restore most of the upper airway functions to a level closely resembling prelaryngectomy. Additionally, it was concluded that a device must be used in conjunction with other
restorative medical devices to effectively restore all lost functions to pre-laryngectomy upper airway
performance
The Origins of Visual Culture? Psychological Foundations of Upper Palaeolithic Figurative Cave Art in Northern Spain
Get PDFUpper Palaeolithic cave art is enthralling; the depiction of animals by our most ancient ancestors captures the imagination. It is no surprise that this art has been subject to extensive academic attention, with a breadth of perspectives that attempt to understand why people drew animals in caves. Fundamentally, this previous research focused on the aesthetic form of the art and attempted to explain it with singular explanations: from art for art’s sake through to the shamanic. This thesis argues that these “grand narrative” approaches are unsatisfying, and instead shifts focus to explore the meaning within the making of Upper Palaeolithic figurative cave art. A biographical framework that integrated novel digital techniques and insights from visual psychology was developed, to evaluate the making of depictions within three cave art sites situated around Monte Castillo (Cantabria, Spain). This revealed the fundamental role of visual psychological responses, triggered in the immersive and low-light conditions of caves, as influencing this making. When understood through the biographical framework, it was revealed that these responses may have facilitated a dialogue between the artist, the cave wall, light, pigment, and the depicted animals. The material engagement involved in completing the animal depictions, evaluated through high resolution images and digital tracings, further supported this. The application of pigment appeared to directly relate to visual phenomena experienced in caves, tracing natural topographic features of cave walls to capture the intangible visual images that the artist may have perceived. When taken together, this thesis emphasises the role of the visual system as central to the making of Upper Palaeolithic figurative cave art. It reveals intimate moments of human interaction embedded within the art, from visceral perceptual experiences in caves through to the playful manipulation of light to add dynamism to animal forms
The Digital Transformation of Marketer Identities in Figured Worlds
Get PDFThe digital transformation of marketing has been ongoing for more than three decades but the
breadth and depth of change in the last five years has been unprecedented. We know from
extensive research on identities in organisations that change in work practices can prompt
identity work, yet there has been relatively little prior research about marketer identities.
Moreover, there has been even less research about marketer identities relating to digital
transformation. This thesis addresses these gaps; however, it does so by looking at the
intersection of marketer identities and digital transformation via a Pragmatist reading of Holland
et al.’s (1998) concept of Figured Worlds, a social practice theory of identity with roots in
Vygotsky, Bakhtin, Mead, and Bourdieu. This approach enabled the study of processes of
transformation in relation to the various artefacts which make up figured worlds, such as
vocabularies, practices, and materialities which come together to construct understandings about
‘how things work’ or what is considered ‘normal’ by the people who inhabit them. The main
body of the thesis centres on an ethnographically-oriented case study of the marketing
department of a large Canadian NGO (Canango) in the process of shifting from a traditional
‘NGO helper’ culture to a so-called ‘Agile marketing’ culture based on project management
practices originating in software development that have been growing in popularity among
practitioners. The thesis identifies a number of ‘classes’ of marketer identities: managerially
supplied ; technologically afforded ; socially afforded ; emergent ; and, performed along with what
each type enables one to do. Using ideas from Figured Worlds theory and multimodal discourse
analysis, a heuristic framework is then developed made of the elements ‘ matter ’ (phenomena),
‘ meaning ’, mediators , ‘ me ’ (identity) and ‘ motion ’ (action) to study how these identities are
used to accomplish contextual goals. This framework is then applied to study the way that three people variously appropriated or resisted a particular supplied identity: the ‘Agile organiser’.
Finally the ideas developed through the first three phases of the thesis are applied in a final phase
in which Canango begins using a new digital collaborative work platform. The study looks at the
identity implications of this move, evidencing the ways in which the work platform serves as a
‘bridge’ between worlds and how such bridges may be used to change worlds and make new
ones
The Individual and the Collective in Institutional Translation: A Case Study of Political News in Kuwait
Get PDFThe translation phenomenon is one that is affected by many factors. In an institutional setting these factors can vary. Institutions are collective in nature with translators being individuals in these institutions. This research has three aims. First, to explore the influence of the individual and the collective on the translation process and product in an institutional translation setting. Second, the research aims to examine the agency of the translator in an institutional setting dealing with political news. Third, to examine the effects of personal social attributes (nationality, religion, and political views) of translators in an institutional setting.
This research examined the institutional translation of political news in Kuwait as a case study to achieve these aims. This case study explores the previous phenomena by analysing three qualitative data sets and one quantitative data set. The qualitative data sets are critical discourse analysis (CDA) of political news texts in Kuwait (30 texts), translators’ interviews analysis (33 participants), and three open-ended questions analysis. the quantitative data set is from a multiple-choice questionnaire (33 participants). This corpus was collected from four Kuwaiti news translation institutions, two public institutions and two private ones. The public institutions are the Kuwaiti Ministry of Information and the Kuwait News Agency, the private ones are the Arab Times newspaper and the Kuwait Times newspaper.
The results show that, in the institutional translation of political news, collective (institutional) influence on the translation process and product exceeds that of the individual (translator) influence. This institutional influence was observed in the guidelines and protocols of each studied institution. This was more prominent in public institutions compared to the private ones. Mainly, this is due to public institutions having to be reflective of the state’s political views and policies. The translator’s agency in an institutional setting was found to be limited, due to the translator having to be in line with the institution’s guidelines and established translation process. The translator’s agency seems to also be affected by the general policy of the institution, which makes a translator working in an institutional setting likely to have limited agency.
The effects of the personal factors of political views, religion, and social background were limited as the translators and their translations were found to be more affected by institutional factors rather than personal ones. This was observed in two main instances. First, the majority of interviewed translators argued against the effects of personal factors. Second, the translations’ analysis showed that the translations were more affected by collective/institutional factors rather than personal ones. This made the translations more reflective of their respective institution.
A general overview of the state of institutional translation of political news in Kuwait was established. This was achieved by studying the recent translation processes and products of four prominent news translation institutions in Kuwait as a case study. Institutional translation of political news in Kuwait follows a defined translation process at the four institutions. This process is governed by strict procedures, guidelines, and protocols that the translators and their translations must abide by for the translations to be published. The translation process and product were found to be affected by external factors such as strict Kuwaiti publication laws, Kuwait’s foreign state policy, Kuwait’s diplomatic relationships, and the Amiri Diwan
Disability, Desire, and the Lyric in Seventeenth-Century France
Get PDFThis thesis asks whether seventeenth-century French lyric poets’ depiction of disability challenges entrenched ideals of beauty, gender, sexuality, and form. It contends that by interrogating the rich and varied imagery of disability found in lyric verse, we deepen our understanding of how French writers and readers of this century interpreted desire and the human body.
The primary corpus comprises unpublished manuscripts and printed sources, grouping lyrics thematically rather than by author. This approach treats the poems as a heterogenous collective, enabling a discussion of lesser-known, unpublished, and anonymous poets. Named poets in this corpus include Paul Scarron, Denis Sanguin de Saint-Pavin, Anne de Rohan-Soubise, Charles Vion d’Alibray, François Maynard, and Théophile de Viau. Some poets write about their personal experiences of disability, while others portray disabled protagonists or draw upon imagery of disability in their verse. This thesis puts their lyrics into dialogue with several theoretical approaches to disability through a Critical Disability Studies framework. The chapters deal with crip theory, metaphor theory, the grotesque and carnivalesque, spatial theory, queer theory, transhumanism, and posthumanism. The poets’ negotiation of bodily regimes holds much in common with their concurrent negotiation of the formal constraints of lyric verse, allowing this thesis to ask why poetry – and the seventeenth-century lyric in particular – is so replete with imagery of disability.
Due to its examination of the intersections between disability, gender, and sexuality, this thesis will be of interest to scholars of gender and sexuality as well as those studying disability and early modern French literature. Seventeenth-century authors working under a different set of bodily regimes were more likely to imagine disability in ways unfamiliar to twenty-first-century readers, so this research also questions current assumptions about what disability is and is not, while nuancing existing theoretical frameworks used to read disability in literature
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