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Eukaryotic translation elongation factor eEF1A2 is responsible for delivering aminoacylated tRNAs to the ribosome during protein synthesis. Heterozygous de novo missense mutations in EEF1A2 have been identified in individuals with epilepsy, autism and intellectual disability. The primary aim of this thesis was to assess whether these mutations operated through a loss of function, gain of function or dominant negative mechanism. To investigate this, I analysed eEF1A2 protein interactions, how these interactions varied between mutations and the functional consequences of changes in the interactome. I used affinity purification mass spectrometry to identify the interactome of eEF1A2 and compared the changes resulting from mutations in eEF1A2. Co-immunoprecipitation experiments determined that mutations could be grouped by changes in their interaction with the cognate guanine exchange factor eEF1B. One group showed complete or partial loss of binding to all four subunits of the eEF1B complex, whilst another cluster showed no change in binding compared to wildtype eEF1A2. No specific patterns of clinical features or phenotypic severity could be attributed to these groupings. My results suggested that protein synthesis would be impaired by this disrupted interaction. In vivo and in vitro protein synthesis experiments failed to detect any differences that could be attributed to the presence or absence of the D252H mutation. As no apparent differences in protein synthesis could be detected between muscle tissue from Eef1a2⁻/⁻ and Eef1a2⁺/⁺ mice or between eEF1A2⁻/⁻ and wild-type cells, it is likely that in both cases the protein synthesis assay employed was not performing adequately. Comparative analysis of Eef1a2ᴰ²⁵²ᴴ/ᴰ²⁵²ᴴ and Eef1a2⁻/⁻ mouse phenotypes determined that there is a gain of function or dominant negative element to the eEF1A2ᴰ²⁵²ᴴ mutation, highlighting that this mutation does not operate simply through a loss of function mechanism. Interactome was unable to successfully identify what this might be. In conclusion eEF1A2 mutations may operate via both a loss and gain of function mechanism. Depending on the precise mutation, eEF1A2 may be compromised in its ability to operate in protein synthesis, but at least some mutations may also result in a degree of toxicity.

Although for the Chinese authorities, colour, and in particular architectural colour, has always been a crucial way to exercise influence, classify hierarchies, and maintain national and international order, the significant relationship between Chinese architectural colour and political power has long been being neglected by theorists and historians. This thesis addresses this omission. The power-oriented use of colour was continually exercised from the Shang Dynasty (ca.1600-1046 BC) to the Qing Dynasty (1636-1912), although the meanings of specific and related colours changed and evolved as they were continuously renewed in response to changes in the social context and the appearance of new knowledge. This thesis focuses on the Summer Palace in Beijing(1750-1912), which witnessed how the Qing Empire went from its apogee to its collapse. The Palace is a microcosm of the Qing Empire constituted by over 3,000 buildings, which were purpose-built for the imperial court, including religious temples, royal residences, and the naval academy. All these buildings were constructed to perpetuate the supremacy and legitimacy of successive sovereigns. Accordingly, the thesis investigates how the colour of these buildings demonstrated and implemented imperial power, laying particular emphasis on four integral perspectives: politics, religion, the imperial family, and the military. The aim of the thesis is to answer three questions: why were specific colours chosen by the Qing Monarchs for the Palace; how did these colours express and exercise power; and what kind of social-political results were produced by successive colour schemes? The thesis offers a new way of understanding architectural colour in the Chinese context and particularly during the Qing Dynasty, when architectural colour was employed in the service of authority. It was a practical technique for the expression of monarchical power that functioned in many dimensions, ultimately as a web of power relations. In exploring the importance of architectural colour in the historical context, the thesis will also shed light on both the use and interpretation of colour in contemporary architectural practice in China.

The launch of the Curriculum for Excellence in Scotland has resulted in an extensive school building programme to rebuild or refurbish local authority schools nationwide. The Scottish Government has vowed to improve all of the school estate remaining in poor or bad 'condition' and 'suitability', in addition to constructing new school buildings that reflect 21st-century learning. The encouraging investment however raises questions on the learning experience for children and young people in remaining school buildings with more than a quarter per cent that predate World War II. This study, therefore, focuses on what pre-war schools offer for the pupils by scrutinising the factors that qualify the affordance of pre-war schools in the provision of 21st-century learning. Similar interests have been evident within the context of architecture, but little attention was given concerning educational spaces particularly schools. Prior to investigating what pre-war schools afford, this research gathers evidence on how pupils learn; where learning takes place; and what features support learning. This study incorporates three different methods of qualitative data collection: observation of the pupils' learning; interview of the classroom teacher; and focus group 'design charrette', which is an alternative mean of communication with the Primary 6 pupils through a series of collaborative activities. Three case studies were selected within the City of Edinburgh, constituting two Victorian, and one 1930's pre-war school. Generally, an analysis of the data showed that pupils learn both actively and passively in pre-war schools. Learning takes place mainly in the individual classroom area and elsewhere within the school building, but rarely in the outdoor area. The pupils highlighted 'leisure' as an elementary feature that supports learning in addition to 'resources' and 'furnishing'. The study suggests that for pre-war schools to offer exceptional quality of learning experience as in the new-build schools, three interdependent factors need to be addressed: social, spatial, and physical factors.

The Passivhaus standard is a building methodology that was established in Germany in the 1990s. It uses a passive design strategy to achieve built environment comfort with minimum energy consumption. However, research shows that not every Passivhaus project has been successful in terms of its comfort and energy performance. Passivhaus is a representation of a high-performance, low-energy prototype of sustainable buildings, which, as a new building typology, embraces new ideas of comfort and accommodates a range of occupants who have different attitudes and expectations. Thus, the social grounding of such a new typology needs to be reconsidered. Understanding the phenomenon of Passivhaus living in the UK context forms the starting point of my research. In reflection of existing Passivhaus post-occupancy evaluation (POE) research in the UK, the majority of this research is focused on performance and frequently adopts an approach using prediction and computer simulation. Only a few studies have examined the Passivhaus system from an architectural design point of view. Research into its energy performance lacks a deeper connection with the occupants' perception of comfort and the architectural design of the Passivhaus. This research focuses on the coherence of Passivhaus living and builds up a theoretical framework to understand the Passivhaus system in relation to occupants' daily lives. It argues that by providing more possibilities and opportunities within the design of the built environment for adaptive behaviours and norms of sustainable living, as opposed to stressing energy efficiency and technological advances, the sustainability embodied in the Passivhaus standard can be further actualised. Previous research into the POE field of Passivhaus has employed a predominantly quantitative method. However, the small amount of research conducted using a qualitative approach demonstrates the potential benefits of gaining a better understanding of sustainability in people's perceptions of comfort, their everyday practices and the nature of their energy use. The methodological approach for the proposed research will be qualitative in nature due to the need to understand highly context-bound experiential data. A mixed approach of quantitative and qualitative methods will be explored to collect and analyse data from various aspects related to the subject matter in order to draw valid conclusions. The research uses a combined framework of grounded theory methodology and a multiple case study approach as a way of taking a step back from empirical research and building up an inductive theory-building process. The combination of these two frameworks is tailored for this research, which enables them to complement each other. The research provides an exploration of Passivhaus living and an insight into the delicate relationship between the occupants and their domestic space. The study explores the shifting perception of comfort, the delicate relationship between habitat and inhabitant and the process of adaptation in the Passivhaus to understand the shaping of household behaviour in relation to different contexts and scenarios unique to the Passivhaus industry. The substantive theory that describes this relationship is summarised at the end of the thesis, with the aim of informing potential Passivhaus clients of the system's holistic sustainable design features and to make recommendations for better Passivhaus design to building professionals.

Colour energy and wellbeing in the context of architecture and design are underestimated in terms of the value they bring to design, branding and real estate development in all sectors, ranging from residential to corporate projects, including the hospitality and luxury industry. Colour, with a particular focus on its latent energy, has not yet been sufficiently explored, researched or discussed, and remains one of the great mysteries of perception. Colour is essential for life and survival, and reaches far beyond art and the decoration of space. The sensation of colour, as an expression of the sense of sight, influences wellbeing and is connected to deeply embedded themes and patterns on emotional, cultural, or personal levels, through which it impacts on wellbeing, health, and decision-making in essential ways, not least because vision has replaced odour as the most essential sense for survival. The majority of all conscious and unconscious decisions are affected by notions of colour, a discipline of constant debate in both art and science. Architecture is somewhere in between, and practising architects are expected to provide the client with individual solutions based on informed decisions. When they do this, however, basing their decisions on experience, unspecified knowledge and intuition, they are often perceived as arrogant. Architecture and the design of space are a constant concern for everyone. The desire to build a home, a temple or a public building in a three dimensional environment is a fundamental urge and as old as mankind itself. Yet perhaps because of these strong impulses, the complexity of creating space is often underestimated. Our body records millions of impressions per minute across all five senses. The five senses keep us alive; they warn, nurture, and alert us, and human perception is based on receiving the vibrations caused by energy fields. These sensory vibrations are directly linked with the human body and it is through them that experiences like I am feeling good in this space and even unconscious memories are triggered. Clients may expect the architect to know everything about the perception of space. Architecture, however, is a very complex matter, and in most academic programs little or no time is allowed for the in-depth study of perception, psychology, colour energy, or wellbeing. Even architecture and interior design are often conflated, and treated as one combined subject rather than two complementary disciplines. What is most striking is that colour is often ignored in Western architecture. Furthermore, there is a bias in the literature and education of the West when compared to the holistic approach in the East. In the Orient, holistic means body, spirit and soul. In the Occident, in contrast, it means body, mind and brain. Spirit and soul are missing. And although the sense of something missing becomes more evident in the West, research fights shy of spirit and soul, and leaves unaddressed questions like: 1. What is the relation of colour energy, wellbeing and space in the Occident and Orient? 2. Why is colour not used more often and more instrumentally to improve wellbeing and influence perception? 3. Where do the inhibitions and obstacles come from that prevent occidental architecture and design from reflecting and applying ancient oriental knowledge and belief to colour healing, health, and wellbeing? As a colour theorist, architect and designer I propose that colour energy offers effective principles that provide an invaluable source for informed architectural decisions, which are genuinely independent of subjective taste or contemporary fashion trends, and that enable a truly holistic approach. This research proposes that wellbeing is both timeless and priceless and that wellbeing, health and perception can be stimulated by colour energy.

The nature of this research is in advancing conventional structures and their methods of construction by exploring new technology. The formwork construction of the modern concrete structure involves the use of rigid materials such as steel and timber. This type of formwork often produces structures of forms with limited flexibility which would also hinder the even distribution of the induced stresses. To construct concrete structures with more organic forms; ones that responds to a more natural flow of the induced stresses, it is thought to be more logical to use flexible mould such as the fabric formwork. In such form-active shape the materials’ utilization can be maximized and the degree of material waste can be reduced. For example, when the form responds to the externally applied loads in the way that the internally incurred stresses at any point of the body closely match the capacity of the material, then the form is material-efficient and said to be in its optimal form. The use of fabric formwork, due to its permeability can also improve the quality of concrete by eliminating any air holes on the surface, and also there are reports showing the increase in concrete’s compression strength due to the reduction in water-cement ratio when cast in a fabric mould. This research concentrates on finding such material-efficient form (thus more sustainable) for reinforced concrete beam of improved material quality, through the development of the more efficient construction system of flexible fabric formwork. For this research 11 different types of beams have been built and tested in total, and their construction methods are illustrated and discussed also (Chapter 7 and Chapter 4 respectively). The designs of the beams are developed through consecutive experiment, analysis, evaluation, and modification process (Chapter 6). For the structural analysis of the beams, the most widely accepted analysis methods are reviewed and adapted (Chapter 8). Based on the evaluations of the analytical results the following variables of the beams are modified through the development of the beam designs: The effect of Compression Steel Mesh in Flange Stress Distribution Around Anchorage; Vertical and Horizontal Web Geometry Varying Depth of Flange Steel Content Also it is a part of the current research’s aim to look at the possible application of the current design methods for the design of the fabric formed beams that are discussed in this research. Thus the experimental results are compared with the results which are calculated from the standard design methods suggested by the British Standard Code of Practice (BS8110) (Chapter 9). Computational finite element (FE) analysis is carried out where more intensive analysis is required (Chapter 10). The results of the FE analysis are also compared with the theoretical and experimental results for the verification purpose. The material efficiency of the beam in its final form is assessed through the embodied energy analysis, which compares the total embodied energy consumed through the construction of the beam with a virtual beam that is designed in accordance with the BS8110 (Chapter 11). The analysis indicates that the total embodied energy of the fabric formed beam is about 20~40% less in comparison with the beam designed in accordance with the BS8110. This thesis has the purpose to illustrate and provide the practical information on the design and the construction process of the fabric formed beams, which can be used as a reference to the future research and construction.