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The environment in which cells find themselves is a complex, three dimensional one which provides a variety of inputs and cues capable of controlling and guiding cell behaviour. These environmental signals take a fertilised egg through development to become an adult human being made up of trillions of cells. As such, the power of environmental cues to provide context and guidance to cell behaviour cannot be understated. Without attempting to directly mimic the in vivo environment, it has been shown that micro- and nanostructured surfaces can influence cell behaviour when we try and engineer biology in vitro. Identification and optimisation of powerful topographies is, however, tedious, and so this thesis provides techniques to expedite the discovery of new and potent surfaces to drive cell behaviour. A new fabrication technique has been developed which allows for the fabrication of gradients of feature height at both the micro- and nanoscale. This involves the use of plasma polymer gradients as novel etch masks alongside existing lithographic techniques. After fabrication and mass replication by injection moulding, use of these surfaces as platforms for the high-content screening of cell response is demonstrated. These can be considered high-content due to both the range of surface structures on a single sample, and also the microscopy techniques used to investigate cell response. Distinct cell types were found to respond differently to topographical cues, exhibiting varying degrees of alignment, proliferation, and organisation in both mono- and co-culture systems. A new cell culture device has also been developed and patented which ensures that screening experiments begin with an accurate and repeatable distribution of cells across the high content array. The impact of uneven cell seeding on studies involving stem cell differentiation was also investigated – showing the importance of improved control. Finally, the interaction of cells with such nanostructured surfaces is investigated using new super-resolution microscopy techniques. New methods are presented for the correlation of multiple nanoscale imaging techniques to view cell-nanostructure interactions with unprecedented resolution. This reveals insights into the way in which the cellular substructure is being modulated by underlying nanotopography. Indeed, it paints a picture which is remarkably different to the structure observed under a standard widefield microscope over the past 10 years.

This thesis comes in three main parts. In the first of these (comprising chapters 2 - 6), the basic theory of Riemannian and conformal submersions is described and the relevant geometric machinery explained. The necessary Clifford algebra is established and applied to understand the relationship between the spinor bundles of the base, the fibres and the total space of a submersion. O'Neill-type formulae relating the covariant derivatives of spinor fields on the base and fibres to the corresponding spinor field on the total space are derived. From these, formulae for the Dirac operators are obtained and applied to prove results on Dirac morphisms in cases so far unpublished. The second part (comprising chapters 7-9) contains the basic theory and known classifications of G2-structures and Spin+ 7 -structures in seven and eight dimensions. Formulae relating the covariant derivatives of the canonical forms and spinor fields are derived in each case. These are used to confirm the expected result that the form and spinorial classifications coincide. The mean curvature vector of associative and Cayley submanifolds of these spaces is calculated in terms of naturally-occurring tensor fields given by the structures. The final part of the thesis (comprising chapter 10) is an attempt to unify the first two parts. A certain `7-complex' quotient is described, which is analogous to the well-known hyper-Kahler quotient construction. This leads to insight into other possible interesting quotients which are correspondingly analogous to quaternionic-Kahler quotients, and these are speculated upon with a view to further research.

This thesis is about the role, nature and importance of marketing within small firms. The definition for small firms’ used here is organisations’ with up to 50 employees. This is the definition used by The Department for Business, Innovation and Skills (2012). There are over four million of such commercial organisations in the UK and they account for over half of the UK’s GDP and over half of the UK’s employment (The Department for Business Innovation and Skills November 2011 /12). Most firms’ in the UK are small and yet the marketing for small firms’ seems to be a neglected area in the standard text books and in the mainstream business school curriculum. Why is this and what can be done to make the subject of marketing more relevant and more appropriate to the smaller enterprise? This doctorial submission is based on published work. There are 24 individual pieces of work making up the submission. All of the works submitted are related to the subject of marketing for small business. Throughout the works’ submitted the author addresses a fundamental question which has occupied his mind for many years. This question is highly pertinent to the developing subject of marketing within small firms’ (Gilmore and Coviello, 1999). The question is ‘is conventional marketing theory and practice from the ‘classical school’ applicable to all types of organisations no matter what their size’? The fundamental question this work addresses is do smaller firms need a different sort of marketing, more suited to their particular needs (Nyman, Berck, and Worsdorfer, 2006; Reynolds and Day, 2011; Hills and Hultman, 2011; Shaw, 2002; Gilmore, 2011; McAuley, 2011; Hills and LaForge, 1992)? The author can find no real evidence of any need for a totally new paradigm although some areas of the standard business school ‘model’ of marketing management might need some important adaptation to make it more suitable for the majority of smaller firms’. The key approach would seem to be standardisation as far as possible then necessary adaptation. The collection of papers and related materials making up this thesis submission conclude that in many cases the central core hub of marketing that has become known as the ‘classicist philosophy of strategic marketing management’ is appropriate in many areas (Drucker, 1954). It can often be employed to the smaller enterprise with beneficial commercial effects (see Reynolds, 2007; Brennan, Baines, and Garneau, 2003). The author has attempted to demonstrate that a body of work has developed and evolved over time in a purposeful manner and with a common theme. The material submitted here, placed into three separate but related categories, has been structured to have an overall thematic shape. The ‘grand theme’ interwoven into this account is marketing for small business. The author does not claim to have investigated every vestige of the subject but does feel that over the years he has made a contribution to the knowledge in this area. Each of the three sub - themes used in this work are related and can be integrated into a ‘grand narrative’ or ‘story line’. This ‘grand narrative’ is encapsulated in the title of this thesis which is; ‘Marketing for small business: The development of a practical and conceptual contribution towards a new paradigm 1986 to 2011’.

Roman civilisation had penetrated South Eastern Gaul more than any region in Western Europe. It is where Christianity gained its first converts and the first episcopal sees were established. For these reasons alone Gallo-Roman traditions might be expected to linger longer than elsewhere, but there is a marked transition: inscriptions set up during the Gallo-Roman period are predominantly votive or honorific as well as funerary, after c.300 AD they are almost exclusively funerary, suggesting a change in emphasis of purpose. Sentiments expressed on an inscription exposed to public view were expressly designed to be read by the passer-by, thereby recording something of the mores of the society that inscribed them, the spread of literacy and fashions in orthography and palaeography. Moreover, such a corpus may be expected to reflect demographic changes during a period encompassing Germanic invasion and subsequent settlement; did such changes affect the numbers of inscriptions set up and even their textual content over time? This corpus offers an invaluable mirror to the evolving society of South Eastern Gaul during the transition from the Gallo-Roman to early medieval period.;Chapter One describes briefly the sites where inscriptions have been discovered. Chapter Two discusses the dating methods employed, Chapter Three describes the most common funerary formulae employed. Chapter Four proposes and employs statistical methods for the reconstruction and dating of those epitaphs where some or most of the data discussed in Chapter Three are no longer extant. Chapter Five discusses the social background of the recipients of the epitaphs and the themes and eulogies inscribed. Chapter Six provides a conclusion explaining the reasons for such a concentration of epitaphs within their cultural and historical contexts.

There is a current trend towards ever more slender concrete floor structures, which is resulting in more frequent problems with their vibration serviceability. Predictive methods for vibration serviceability must consider not only the structures themselves, but also the non-structural elements which are attached to them, as these may have a significant effect on the dynamic characteristics of the floor structural system. As there has been very little past research in this area, this thesis describes an investigation into the effects of raised access floors on the vibration serviceability of long-span concrete floors. The development of a new modal testing facility based on electrodynamic shaker excitation, which was capable of producing high quality estimates of the modal properties of full-scale floor structures, is described. This was subsequently utilised to determine the modal properties of three full-scale floor structures, before and after the installation of various configurations of raised access floors. The response of these structures to controlled pedestrian excitation was also measured. Realistic finite element models of all structures were developed and updated using the results from the experimental work. These were subsequently utilised for investigation of the experimentally measured effects of the raised access floors. It was found that raised access floors had only minor effects on the modal properties of the long-span concrete floors. Reductions in natural frequencies due to the increased mass were, to some extent, offset by the slight increases in stiffness following the installation of the access floors. Modal damping ratios increased for some modes of vibration, but these changes were rather unpredictable and hence they were too unreliable to be used in design. The response of the structures under controlled pedestrian excitation reduced following the installation of various configurations of raised access floors. The reduction appeared to be greater for relatively deep access floors (500 - 600 mm) than for relatively shallow access floors (150 - 200 mm). Therefore, it is recommended that the effects of access floors may be included in vibration serviceability analyses by applying a reduction factor to predicted responses calculated by assuming a bare floor. The proposed reduction factors are 0.9 for access floors where the finished floor height is less than 500 mm and 0.8 for access floors where the finished floor height is 500 mm or greater.

Many telephone companies, especially in Eastern-Europe and the 'third world', are developing new telephone networks. In such situations the network design engineer needs computer based tools that not only supplement his own knowledge but also help him to cope with situations where not all the information necessary for the design is available. Often traditional network design tools are somewhat removed from the practical world for which they were developed. They often ignore the significant uncertain and statistical nature of the input data. They use data taken from a fixed point in time to solve a time variable problem, and the cost formulae tend to be on an average per line or port rather than the specific case. Indeed, data is often not available or just plainly unreliable. The engineer has to rely on rules of thumb honed over many years of experience in designing networks and be able to cope with missing data. The complexity of telecommunication networks and the rarity of specialists in this area often makes the network design process very difficult for a company. It is therefore an important area for the application of expert systems. Designs resulting from the use of expert systems will have a measure of uncertainty in their solution and adequate account must be made of the risk involved in implementing its design recommendations. The thesis reviews the status of expert systems as used for telecommunication network design. It further shows that such an expert system needs to reduce a large network problem into its component parts, use different modules to solve them and then combine these results to create a total solution. It shows how the various sub-division problems are integrated to solve the general network design problem. This thesis further presents details of such an expert system and the databases necessary for network design: three new algorithms are invented for traffic analysis, node locations and network design and these produce results that have close correlation with designs taken from BT Consultancy archives. It was initially supposed that an efficient combination of existing techniques for dealing with uncertainty within expert systems would suffice for the basis of the new system. It soon became apparent, however, that to allow for the differing attributes of facts, rules and data and the varying degrees of importance or rank within each area, a new and radically different method would be needed. Having investigated the existing uncertainty problem it is believed that a new more rational method has been found. The work has involved the invention of the 'Uncertainty Window' technique and its testing on various aspects of network design, including demand forecast, network dimensioning, node and link system sizing, etc. using a selection of networks that have been designed by BT Consultancy staff. From the results of the analysis, modifications to the technique have been incorporated with the aim of optimising the heuristics and procedures, so that the structure gives an accurate solution as early as possible. The essence of the process is one of associating the uncertainty windows with their relevant rules, data and facts, which results in providing the network designer with an insight into the uncertainties that have helped produce the overall system design: it indicates which sources of uncertainty and which assumptions are were critical for further investigation to improve upon the confidence of the overall design. The windowing technique works by virtue of its ability to retain the composition of the uncertainty and its associated values, assumption, etc. and allows for better solutions to be attained.

The road system from the late Republican to Arab period is outlined. Late Roman-Visigothic settlement in the Vinalopo Valley is then assessed. Particular attention is paid to the dating of sites. This is done with pottery from both survey and excavation and with a new typology of late Roman-Visigothic period pottery found in the region. Detailed observations on the source and distribution of pottery (local, regional and imported; fine wares, amphorae and coarse wares) in the Vinalop6 Valley are made, through time and by class and location of site. Special attention is paid to an analysis of the archaeological evidence for the Byzantine reconquest of south-eastern Spain and its effects on the supply of pottery to the Vinalopo Valley. The range and relative quantities of imported pottery found in the region are then compared with the distribution of imports on selected Western Mediterranean coastal sites. The work concentrates on the identification of distinct regional distribution patterns through time and the analysis of their significance. The relative roles of Tunisia and the Eastern Mediterranean, in particular, as exporters of foodstuffs and pottery to Western Mediterranean sites through the pre-Vandal, Vandal and Byzantine periods are outlined and discussed. Factors that may have dictated the regional distribution of potte.rj are suggested. Several major shipping routes and the independent distribution of Eastern Mediterranean and Tunisian goods are also suggested by this archaeological evidence. It is concluded that the supply of imports to Alicante through the 4th-7th centuries was dictated by changing political trends in "export policy", dependence to a lesser degree, and the region's location on or by major south-west Mediterranean shipping routes from the East and Tunisia. Contacts with Tunisia are particularly strong and somewhat exceptional from the 5th-mid 6th centuries. The Byzantine reconquest of south-east Spain maintained the strong links between Carthage and Cartagena, the capital of the Byzantine province, but not Alicante.

This thesis is concerned with the application of statistical techniques in the field of crystallography - a branch of science dealing with the structure, classification and properties of crystals - and an analysis of some of the associated statistical problems. We shall concentrate throughout on the estimation of atomic co-ordinates within the unit cells of crystals. The science of X-ray crystallography will be introduced and a review of some of the existing methodology given. We shall then consider how statistical ideas may be used to improve this methodology. We shall be particularly concerned with the area of sequential experimentation, in which the data collection process itself is modified as a result of analysing the data already collected. Sequential experimentation for improved efficiency in any particular crystallographic problem requires that decisions be made as to which additional data should be collected in order to achieve the desired objective. Ways of selecting suitable sampling strategies will be described, together with associated stopping rules. We will also describe methods for handling relevant prior information - e.g. structural information available in crystallographic data bases - and nuisance parameters, and procedures for dealing with the inherent non-linearity of the crystallographic model, matrix updating and the recursive addition of data. The central problem of X-ray crystallography - the 'phase problem' - will also be analysed from a statistical perspective. Practical application of some of our ideas will be given. Much emphasis is placed on non-linear parameter estimation problems such as those arising in crystallography. A review of relevant statistical work in this general field is undertaken, and geometry-based ideas of our own proposed. We concentrate on either seeking suitable re-parameterisations (in a sense which we define) or on seeking alternatives to the standard tangent plane approximation to the solution surface based on relevant curvature measures. The thesis ends with a few relevant concluding comments and some ideas for further related statistical work in the area of X-ray crystallography.

Plasmodium knowlesi is a zoonotic malaria parasite of Southeastern macaque monkeys that causes zoonotic malaria in humans. P. knowlesi is also an experimental model for malaria, and information on P. knowlesi largely stem from experimental lines first isolated >four decades ago, rather than contemporary isolates causing human infections. The experimental lines are laboratory-restricted and have become relatively genetically stagnant and free from the selection pressure that would naturally occur in nature. Within the P. knowlesi genome exist the Schizont Infected Cell Agglutination variant antigen (SICAvar) and Plasmodium knowlesi interspersed repeat (kir) multigene families significant, which are of biological and scientific interest. To provide context using contemporary clinical isolates, this project aimed to generate high-quality genome sequences using long-sequencing from clinical 'wild-type' samples from infected patients. This includes generating new information on variant multigene families in P. knowlesi genomes generated from clinical patient whole blood. The work presented here details a method to deplete leucocytes in thawed P. knowlesi-infected patient whole blood samples to generate parasite-enriched DNA for whole-genome sequencing, resulting in >95% human DNA reduction. The extracted DNA was sequenced with long-read sequencing technology to create de novo whole-genome assemblies. From these, two isolate genomes representing the two dimorphic clusters of P. knowlesi in clinical samples were analysed. The generated genomes are highly syntenic to the published reference genome, sharing >4500 orthologous clusters with the PKNH reference genome. However, the number of SICAvar and kir genes present in the dataset deviated from the published reference genomes of P. knowlesi. The successful generation and construction of these patient genomes aid further interrogation of the contemporary P. knowlesi genome, with a focus on the constituent genes present in comparison to the experimental line.

Midkine (MK) is a 13 kDa heparin-binding growth and differentiation factor. Immunohistochemistry revealed that MK is expressed in a precise temporal-spatial pattern during lung morphogenesis, however, its role in pulmonary homeostasis is unknown. MK staining in the respiratory epithelial cells correlated with sites of expression of thyroid transcription factor 1 (TTF-1), a transcription factor regulating formation and gene expression in the lung. Increased MK staining and mRNA expression were observed in the lungs of hypoxia-susceptible CAST/eiJ mice during hypoxia and MK expression was induced by hypoxia in vitro. We tested whether the modulator of cellular responses to hypoxia, hypoxia inducible factor-1α (HIF-1α ), mediated the increase in MK expression. HIF-1α enhanced the transcription of MK, acting on HIF-1α response elements (HREs). Mutation of the 3´ HRE blocked the stimulatory effects of HIF-1α. In order to directly assess the role of MK on lung morphogenesis, transgenic mice were generated which express MK in the respiratory epithelium of the developing lung. MK increased muscularization of small pulmonary arteries, increasing α-smooth muscle actin (α-SMA) and caldesmon staining and the expression of myocardin. MK directly enhanced the expression of myocardin and smooth muscle specific genes in vascular smooth muscle precursor cells. These data provide a model wherein the respiratory epithelium responds to hypoxia via HIF-1α-dependent regulation of MK. Furthermore, MK acts as a paracrine factor that enhances myocardin expression in order to influence the activation of pulmonary vascular genes.

High Throughput Imaging (HTI) has an important role in the High Throughput/Content Screening process (HTS/HCS). It is widely used in the drug discovery process and in a wide range of other applications including studies focused on cell cycle, cell proliferation, cell migration, apoptosis, protein expression, protein localization, signalling pathways or stem cell development and differentiation. Nowadays, most of the HCS experiments are performed on two-dimensional (2D) monolayer of cells cultured on planar plastic substrates which do not reflect the complex 3D architecture of a living tissues where the cells interact between each other and with the ExtraCellular Matrix (ECM). Currently, the state-of-the-art HCS systems that can be used for high throughput imaging of 3D cell culture models are based on confocal microscopy. Even though very efficient, these machines can reach the million-dollar price and thus might be affordable to big industry and phenotypic screening centres but not to most of smaller realities such as academic laboratories. This thesis project proposes a solution to link light sheet microscopy, one of the best techniques for the imaging of 3D cell culture models, with the currently available HTS/HCS platforms: the development of the affordable and user-friendly HT-LISH microscope first prototype have the potential to offer automated light sheet microscopy-based HTI capabilities for the study of 3D samples to industries, screening centres and also to smaller laboratories, where a lower throughput level is eventually required. Another important part of this PhD thesis is focused on CRISPR-based genome editing which during the recent decades has become an invaluable tool in cell and tissue biology. CRISPR interference (CRISPRi) and activation (CRISPRa) systems have been developed to allow the users to up-or down-regulate any gene of interest in a relative simple manner. Even though emerged as powerful techniques to regulate the gene expression levels, these tools lack in spatiotemporal resolution. In order to study and understand genetic patterns specific to a certain type of tissue it is important to achieve a precise control over the CRISPRi/a systems so that they can be selectively targeted to small populations of cells (spatial resolution) or be activated and de-activated at will (temporal resolution). This work, describes the development and the characterization of the Red Light CRISPR system, a novel CRISPR-based tool for precise gene regulation experiments that relies on the interaction of the Phytochrome B (PhyB) and Phytochrome-Interacting Factor 6 (PIF6), two light sensitive protein from the plant Arabidopsis Thaliana that dimerize under red light at 660 nm and separate when illuminated with infrared light at 740 nm. The Red Light CRISPR system fuses together the non-invasive and highly spatiotemporal resolved technique of optogenetics with the "easy to use" and efficient CRISPR approach. This system is thus joining the already available range of optogenetics tools that enable a precise spatiotemporal control of the CRISPR system and, in particular, it introduces for the first time a red/infrared lightbased CRISPR inducible system.

This thesis investigates the footfall excitation of higher modes of vibration in low-frequency floor structures. This is motivated by the increased number of floors reportedly failing to meet the required occupants comfort level although being designed in accordance with the current state-of-the-art design guidelines. In particular modern, lightweight, and slender floor structures. The contribution to knowledge of this thesis can be summarised as: quantifying the signal energy of measured walking forces within and above the natural frequency cut-off proposed by the current state-of-the-art design guidelines; quantifying the contribution of higher modes of vibration to the overall response of low-frequency floors to human walking; propose measures to judge the response nature of low-frequency floors, these are the relevant change of the point stiffness and the shape of frequency response functions; proposing a frequency-domain approach that enables designers to include higher modes of vibration in the design against human-induced vibration. It was found that the signal energy of walking forces is distributed well beyond the natural frequency cut-off proposed by the current state-of-the-art design guidelines. Also, the contribution of localised, higher, modes of vibration to the overall response of ultra-lightweight floors was significant. Moreover, it was found that higher modes affect the response of floors of various construction types in one way or another. Hence, it was recommended to consider their contribution in the design of floors against human-induced vibration. Also, it was found that the higher the relative change of the point stiffness the more higher modes contribute to the overall response of floors. Finally, the frequency-domain analysis was found less expensive than time-domain analysis and could result in similarly useful information.

The effect of single-step and two-step aging treatments on the tensile properties of an Al-6 wt. % Ag alloy and an Al-14 wt. % Ag alloy has been investigated. Results show that the tensile properties of these alloys were approximately the same whether they were given single or two-step aging treatments. Reversion treatments applied to the fully age-hardened Al-14 % Ag alloy after 15 minutes at various temperatures between 200 and 350 °C showed two maxima in the ultimate tensile strength and the yield strength. It is believed that this result was caused by two transformation processes occurring simultaneously: i.e., (1) the coarsening and dissolution of G.P. zones and (2) the growth of the intermediate precipitate, γ'.

This thesis investigates an alternative solution to deal with the civil structure vibration. Non-contact electromagnetic or Eddy current damping is selected as a score of vibration suppression. Electromagnetic damping relies on the interaction between a permanent magnet and conductor. An electromagnetic damper (EMD) is applied both to a laboratory footbridge structure and 6-storey model-scale aluminium moment resisting frame (AMRF). In this first study the EMD is connected in series with an electronic shunt circuit to construct an electromagnetic shunt damper (EMSD). A robust optimisation method is applied to develop the corresponding optimal design formula of the EMSD. The principle of an EMSD is to convert mechanical energy to electrical energy. Hence, the induced electromotive force (emf) is generated by electromagnetic induction. This emf induces an amount of shunt damping, which is fedback to the structure to achieve vibration suppression. It was found that when the impedance was applied, the shunt damping feature was of a similar nature to viscous dampers. In contrast, when an RLC (resistance-inductance-capacitance) circuit is connected, the shunt damping is analogous to a tuned mass damper. A second form of EMD is Eddy current damper (ECD), which relies on a geometrical arrangement of permanent magnets and conductors to produce damping forces. The vertical and horizontal orientation of the magnet, unidirectional and alternative pole projection and moving different direction of the conductor are investigated. A theoretical study involving the infinite boundary and finite boundary (the method of images current) is carried out to obtain an analytical calculation of the damping force. On the basis of this analysis, one type of ECD prototype was physically built. A performance test was carried out to determine the damping characteristics of the ECD, which agreed with the results of the numerical analysis. In addition, the ECD was applied to control the dynamics of the 6-storey AMRF. It was found that, the ECD can effectively increase system damping and have a satisfactory control effect.

The thesis explores the experience of pain for people who live with chronic pain and engage in BDSM1 (or ‘kinky’) pain play. It is situated within disability studies, taking the position that chronic pain is a disability, and in the use of crip theory to explore narratives of experience. The narratives, told through multiple, detailed interviews were explored in the contexts of crip theory, disability, and medical and social understandings of pain. The thesis addresses three core aims; firstly, to hear narratives of experiences of chronic pain and BDSM play. Secondly, to explore those narratives to reveal experiences and understandings of pain sought by those who live with chronic pain and also engage in BDSM. Finally, to challenge normative conceptions of pain through a critical crip reading of the narratives. The narratives revealed a range of complex experiences. I drew out these narratives in three broad themes: the role of crip time in living with chronic pain; the multiple uses of BDSM – including pleasure and control of the self – and the role of stigma and abjection. The thesis has made a number of original contributions to knowledge. Firstly, it revealed how pain is discursively constructed as needing control and containment, but how non-normative methods of control and bodily engagement are not necessarily understood as such. Secondly, the thesis exposes how pain is assumed to be wholly destructive to the self, but instead ways to integrate pain into the self are sought. Thirdly, it adds to crip theory by expanding the notion of crip time to reflect the experience of living with chronic pain. Finally, by demonstrating how the narratives challenge understandings of the ‘normal,’ as reflected in discourses of chronic pain. The thesis thus exposes how normative constructions of pain are a part of the performance and construction of able-bodyminded heterosexuality.

This thesis is an investigation of Roman pottery from the Maltese islands from the 1st century BC to the mid-4th century AD, and how pottery can help assess Malta's economic role in the wider central Mediterranean region. The archipelago's locally produced vessels, its range of ceramic exports, and the quantification of the types of amphorae, fine, and cooking wares the islands imported, were studied and the data were used to compare with the pottery available from the small islands of Pantelleria, Lampedusa and the Kerkennah isles. The aim is to revisit the theme of the economic role of the Maltese islands and other similar-sized islands in the region by moving away from the tradition of unilateral and monographic narratives, which more often than not, omit the wealth of information that can be garnered from pottery. In the first instance, a detailed study of three complete and new ceramic assemblages, including amphorae, fine, cooking and coarse wares, was undertaken. The opportunity to quantify identifiable imports and compare them with local products - the first of its kind for fine, cooking and coarse wares - provided valuable proxy data for comparing Malta with neighbouring islands and centres, and demonstrated what proportion of ceramic vessels were locally supplied, and how these changed over time. These data were also fed into a series of network analyses, which plotted the common pottery links shared between small-island and mainland sites in the region. The analyses were interpreted in conjunction with a critique of existing pottery quantification methods, and the potential acceptance for utilising all known pottery data irrespective of the quality and quantity of the published data available. Most importantly, the import trends obtained from this study were incorporated into the existing narrative of how small islands and their local industries featured in the central Mediterranean's regional economy, highlighting the types of archaeologically visible industries that existed; how these developed symbiotically alongside other larger supply networks; and what effect this might have had on the integration of small islands in the Roman Mediterranean.

This thesis is concerned with two major areas: marketing communication via social media and small to medium size enterprise marketing for Kuwaiti SMEs. The researcher has been looking carefully at major social media sites such as Facebook, Twitter, Instagram and others by opening accounts and being involved in daily interactions in them. They have been observing and witnessing the great potential of social media and that led to five questions concerning social media marketing and its usefulness to SMEs in Kuwait. (i) Can SMEs market their products and services better through using social media rather than traditional media? (ii) Can SMEs reach their target customers through social media more easily than through traditional media? (iii) What are the benefits of marketing communication in social media? (iv) Can marketing communication be more effective by using social media rather than using traditional media? (v) Can Kuwait benefit from SMEs’ empowerment to improve its economy by reducing dependency on oil production? It was from these questions, the topic of this thesis was born, which is investigating the effectiveness of marketing communication through social media for SMEs in Kuwait. Primary data were collected through depth interviews from the owners/managers of Kuwaiti SMEs. Grounded theory as Strauss and Corbin was used. Five models are developed and recommendations made to improve the effectiveness of social media marketing communications for SMEs in Kuwait.

This work is an investigation into philosophical method and rational argument in moral philosophy. It makes an original contribution to human understanding, by taking some of the tools and techniques that Gordon Baker identifies in the later work of Wittgenstein, and using them as a way of fending for oneself in an area of philosophy that neither Baker, nor Wittgenstein, wrote on. More specifically, a discussion of some different aspects of the contemporary literature on Dancy’s (2004) moral particularism is used as a vehicle for illustrating how Baker’s therapeutic conception of philosophy offers alternative possibilities for how we can do philosophy, and what counts as rational argument in moral philosophy. I maintain that, by considering some indicative ways in which Baker’s therapeutic approach to philosophy can dissolve, rather than solve, the kinds of perplexities found in the existing literature on Dancy’s (2004) moral particularism, we can liberate ourselves from the traditional/theoretical view of how we ought to do philosophy, and an understanding of rational argument in moral philosophy, to which we need not be committed.

A key objective in the design of any sports stadium is to include the maximum number of spectators with minimum obstruction in the visual cone. This functional requirement often results in employing one or more cantilevered tiers, which in turn culminates in more slender grandstands often with relatively low natural frequencies and modal damping ratios. These natural frequencies may sometimes fall in the range of frequencies of human movement, which can possibly excite the structure in resonance resulting in vibration serviceability issues. One of the available techniques to reduce excessive responses is to use passive vibration control techniques such as Tuned Mass Dampers (TMD). However, the off-tuning problem is a potential drawback of this technique, whereby changes in natural frequencies caused by crowd-structure interaction may detune the TMDs. This thesis presents a study into the possibility of using Hybrid Tuned Mass Dampers (HTMDs) to augment the vibration serviceability of structures. An appropriate control algorithm is developed. It shows a comparative analysis of vibration mitigation performances that are likely to be attained by utilising the proposed HTMD. Also, an appropriate control scheme is utilised with the proposed HTMD to deal with the off-tuning issues in TMDs caused by crowd loading, and is shown to be effective. In addition, it shows a comparative experimental investigation of a passive TMD and a prototype HTMD applied on a slab strip structure. The most effective control algorithm to enhance the performance of the HTMD and also deal with the off-tuning problem is investigated. The experimental results verify the developed simulation studies and also demonstrate the effectiveness of employing a HTMD considering both structural response and cost (actuator effort).

The mechanism of body and organ size control is an unsolved puzzle. Initially characterized in Drosophila melanogaster, the Salvador/Warts/Hippo (Hippo) signalling pathway, highly conserved throughout evolution, defines a novel signalling cascade regulating cell contact inhibition, organ size control, cell growth, proliferation, apoptosis, and cancer development in mammals. The upstream regulation of this pathway has been less well defined than the core kinase cassette. Previously Willin/FRMD6 has been proposed as the human orthologue of Expanded and, to date, little is known about the functional role of Willin in mammalian cells. My study elucidated the mechanism by which Willin antagonizes the transcriptional co-activator YAP. In MCF10A cells, Willin ectopic expression antagonizes YAP-induced epithelial-mesenchymal phenotypes via YAP Ser127 phosphorylation site. Loss of Willin expression attenuates MST1/2, LATS1, and YAP phosphorylation promoting YAP's oncogenic transformation activity in vitro, as analysed by its ability to display epithelial-to-mesenchymal transition (EMT) features. These biological outputs are YAP dependent. These data support the involvement of Willin in the regulation of the mammalian Hippo signalling activity by activating the core Hippo pathway kinase cassette. KIBRA has been shown to function as an upstream member of the Hippo pathway by influencing the phosphorylation of LATS and YAP, but the functional consequences of these biochemical changes have not been previously addressed. I showed that in MCF10A cells, loss of KIBRA expression displays EMT features, which are concomitant with decreased LATS and YAP phosphorylation, but not MST1/2. In addition, ectopic KIBRA expression antagonizes YAP via the Ser 127 phosphorylation site and I showed that KIBRA, Willin and Merlin differentially regulate genes controlled by YAP. Willin/FRMD6 was first identified in rat sciatic nerve, which is composed of Schwann cells and fibroblasts. To elucidate the function of Willin in the mammalian sciatic nerve, I showed that Willin is predominantly expressed in fibroblasts and that its expression activates the Hippo signalling cascade and induces YAP translocation from the nucleus to the cytoplasm. In addition within these cells, although it inhibits cellular proliferation, Willin expression induces a quicker directional migration towards scratch closure and an increased expression of factors linked to nerve regeneration. These evidence show that Willin modulates sciatic nerve fibroblast activity, indicating that Willin may have a potential role in the regeneration of the peripheral nervous system.

Despite the improvements in mathematical forecasts and teh creation of new formulas in forecasting, the increase in the accuracy forecasts is not yet significant, thus, leading to an increase in the size of the gap between academia and practice. Furthermore, Applying mathematical forecasting techniques alone is not sufficient in light of the existing lack of knowledge about forecasting, which, thus, gives rise to the importance of judgements and the possible contributions they may add to the forecasting management process.

In the Western world, breast cancer is the most frequent malignancy in women and still the leading cause of cancer related deaths, therefore, a better understanding of the disease is needed. Adequate therapeutic targets for all breast cancer types have not been identified yet, and patients with the same type of cancer have often different outcomes. Polycomb proteins are emerging as important factors involved in breast cancer formation. Polycomb proteins play a crucial role in embryogenesis, early development, stem cell renewal and establishing and maintaining cell identity. Their alteration leads to mis-regulation of several important cellular factors including tumour suppressors, DNA repair factors, cell cycle regulation factors and cell-cell interaction factors. In this thesis the importance of several polycomb proteins in breast cancer has been investigated. The effect of EZH2 knockdown has been tested in breast cancer cell lines expressing different level of the protein and with different features. The results obtained are in line with other studies and suggest that the effect of EZH2 down-regulation in breast cancer cells is dependent on cellular context. In vitro experiments, using both established breast cell lines and primary epithelial cells have been used for investigating the importance of CBX8 in breast cancer. The results obtained showed that the polycomb proteins CBX8 does not play a central role in malignant transformation of the mammary epithelial cells tested.

This research is concerned with international Integrated Marketing Communications (IMC) by global banks targeting a Jordanian audience. The main research question addressed in this work is concerned with adaptation versus standardisation of international IMC by global banks. The aim of the research is to establish whether the standardised IMC approach is sufficiently effective when targeting Jordanian customers or whether adaptation of the IMC mix is necessary. A mixed methodological approach has been used consisting of qualitative in depth interviews and a more quantitatively based sample survey. Semistructured interviews were conducted with bank managers. Likewise, a survey instrument in the form of questionnaires were sent to the clients through bank management because of the confidentiality issues. The purpose of the research is to answer the standardisation versus adaptation question with the intention of deriving specific, operationally useful suggestions for IMC improvements for global banks operating in Jordan. The problems and weaknesses identified in current IMC policies used by global banks in Jordan are identified and suggestions for future marketing communications improvements made. These weaknesses and suggestions are integrated into a conceptual model. The managerial implications of adapting the suggestions made are examined and discussed. The weaknesses identified, suggestions made to overcome them and the managerial implications of implementation make an important and original contribution to the subject area from both a practical and conceptual point of view. The findings of the research strongly indicate that significant adaptation is required in order for the IMC approach by global banks to be effective. The findings should be specifically relevant to global banks operating in Jordan but may have relevance to other international companies from different sectors operating in or wishing to operate in Jordan.

This dissertation develops and tests the first theoretical model to understand and explain the differential impact of clusters and industrial agglomerations on both entrepreneurship and the relationship between entrepreneurship and development at the regional level. Clusters and entrepreneurship face high visibility among academics and policyrnakers, given that similar historical conditions explain their resurgence, and similar potential impacts on employment and innovation highlight their socio-economic importance. Yet conceptual, theoretical, and methodological constraints prevent the study of their relationship and joint impact on regional development. This dissertation aims to make theoretical and practical contributions addressing these constraints. Defining entrepreneurship as the creation of new organisations and a cluster as a geographically proximate group of interconnected firms and institutions in related industries, this study creates an intrinsic paradigm in which clusters, creation of organisations, and regional development are distinguished from industrial agglomerations, entry, and industry growth, respectively. Based on this intrinsic paradigm and a socio-economic approach, it elaborates a theoretical model that hypothesises a synergy between the liability of newness faced by new firms and the provision of external economies, established relationships, legitimisation processes, and complementary linkages by clusters. To empirically test the model, this study uses the 97 German Planning Regions as units of analysis, a multiple method and data approach to measure and identify clusters, and an OLS fixed-effect model to test the hypotheses. Clusters are measured using both quantitative secondary data and qualitative data from the existing literature on clusters and a survey of German regional experts in 31 regions. Entrepreneurship is measured using a four-year (2000-2003) pooled data taken from the German GEM dataset. The results show that clusters matter to entrepreneurship and to the relationship between entrepreneurship and regional development, but industrial agglomerations do not. Based on the theoretical elaboration and these results, this dissertation outlines theoretical contributions, practical implications for academics and policyrnakers, and directions for future research.