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The field of systems biology has developed under the acknowledgement that quantitative approaches are necessary to fully understand the complexities that shape cells' structure and behaviour. The development of automated microscopy protocols has led to the accumulation of high-throughput data sets but the high resolution of modern imaging hardware compounded with time series generates an analysis bottleneck. I develop machine learning tools to track Saccharomyces cerevisiae cells in time lapses that are resilient experimental and technical noise. Then I coordinate cell segmentation and tracking software to develop software that automates analyses and makes them reproducible. I then study the protein aggregation dynamics of metabolic enzymes that form reversible aggregates via phase separation. Using single-cell information provides a deeper understanding of the impact of these proteins on yeast cells' growth and division. Heterogeneous responses, distinguishable by using mutant strains with varying aggregation phenotypes, provide several novel insights. This work shows that the development of computational tools can make the acquisition of biological insight faster and increases reproducibility while providing a toolset to tackle the challenge of dealing with high-content microscopy data - one without existing solutions able to scale computationally. it also furthers biological understanding of a conserved phenomenon such as reversible protein aggregation, in a way only possible by studying behaviour and physiology of thousands of cells at the same time. my thesis aims to pave the way for more comprehensive analyses using aggregated high-quality data.

In response to the financial crises of the 2000s, central banks implemented unconventional monetary policies (UMP) to restore liquidity and promote credit creation. This thesis investigates the effects of these policies, which involved using the composition and size of central bank balance sheets as instruments of policy. Specifically, this thesis examines the theoretical foundations and quantitative transmission mechanisms of UMP in scenarios where interest-rate-based monetary policy is constrained by the lower bound of the nominal policy rate. The first two papers of this thesis present theoretical models of a three-period economy, where households, firms, and a consolidated government interact. In the context of a liquidity trap scenario and the presence of nominal rigidities, the first paper shows that UMP in the form of outright purchases of illiquid assets by the central bank have no real effects in a perfect risk-sharing environment but can provide partial insurance against idiosyncratic unemployment risk under imperfect risk-sharing. The second paper examines the effects of UMP when an uncertainty shock generates the liquidity trap scenario and shows that, in this context, UMP can improve welfare. The third paper of the thesis provides a quantitative assessment of the effects of UMP. Using a dynamic model of a small open economy member of a monetary union, I show that UMP in the context of a negative shock to the price of sovereign bonds, has positive effects on output and unemployment. By combining theoretical and quantitative analyses, this thesis sheds light on the complex mechanisms through which central bank balance sheet policies affect the economy in different scenarios and provides insights for policymakers and researchers alike.

This thesis analyses the cycle of urban tenant struggles against corporate landlords in Barcelona following the 2008 Global Financial Crisis. It conceptualises this struggle as an emerging urban class conflict by weaving together the field of financialization studies and the literature on tenant movements. While these two fields have increasingly become intertwined, there is a lack of engaged research analysing how the political economy of housing, particularly the private rental sector (PRS), is being contested and shaped by the politics of tenant movements. This thesis contributes knowledge on this question by analysing the contentious politics that the Tenants' Union of Barcelona (TUB; Sindicat de Llogateres) has deployed against corporate landlords. Hence the analysis proceeds in two dialectical moments. On the one hand, this research analyses the shifting political economy of housing in Spain after the great mortgaging period that burst in 2008. In doing so, I trace the ascendancy of corporate landlords and the servicing industry in Spain, while I argue for a novel and significant rearrangements of the real estate/financial complex. Through a qualitative approach, this research explains the process through which corporate landlords have transformed non-performing loans into profitable rental yields in the housing system. Unlike previous research which has focused primarily on the role of the public 'bad bank' and the rise of investment funds, this thesis unveils the crucial role of private-funded asset management companies (AMCs), also known as servicers. On the other hand, this research this research builds upon several years of my engaged research in the TUB, and it aims to provide the tenant movement more tools to un-derstand the housing processes in tow, and to formulate appropriate collective strategies in response. While a well-established scholarship has analysed the Platform of Mortgage-Affected People's (PAH) repertoire of contention, far less research has focused on the expansion of tenant struggles in the private rental sector. I examine the emergence of the TUB in 2017 not only as the result of a new cycle of capital accumulation through housing financialization, but also as the result of the prevailing housing movement's repertoire of contention. Through participant observation and in-depth interviews conducted during a year of fieldwork in Barcelona, this thesis makes two core arguments. First, it claims that the existing repertoire of housing contention laid the groundwork for the rise of tenant struggles, which expanded urban housing struggles in Barcelona by unfurling new effective antagonisms against private landlordism. Second, it contends that the TUB's Stay Put campaign introduced tactical innovations to the PAH's repertoire of contention to gain bargaining leverage against landlords, to foster organisational growth, and to garner public support in order to change and improve legal protections for tenants.

The ability to create and optimise new interfaces is essential to develop and optimise materials for use in sustainable energy storage and conversion technologies. In this thesis, the solution-deposition of coatings from molecular precursors is explored as a promising approach towards this end. First, a facile method for the deposition of electrocatalytically active zirconium-based films for photoelectrochemical water oxidation is developed. The films were derived from three novel alkoxy cage compounds containing Zr and a first-row transition metal (Co, Fe or Cu). The deposition of a Co-doped ZrO₂ coating onto the BiVO₄ photoanode lowers its onset potential by 0.12 V to 0.21 V vs. the reversible hydrogen electrode (RHE) and increases the maximum photocurrent density by ∼50% to 2.41 mA cm⁻² compared to the uncoated BiVO₄. In the next chapter, a new solution deposition method to coat the Li-ion battery cathode LiNi₀.₈Mn₀.₁Co₀.₁O₂ (NMC811) with Al₂O₃ using aluminium isopropoxide (AIP) is developed. High-field solid-state nuclear magnetic resonance spectroscopy (SSNMR) probes the formation of γ-LiAlO₂ at 600 °C and doping of aluminium into NMC811 starting at 500-600 °C. NMC811 coated with amorphous Al₂O₃ (200-400 °C) had a capacity retention comparable to pristine NMC811, while higher annealing temperatures led to more crystalline coatings and surface Al-doping which were found to increase the rate of degradation of NMC811 upon cycling. Finally, LiAlO₂ coatings are deposited onto NMC811 using heterobimetallic alkoxides: LiAl[(OCH₂Ph)₄], LiAl[(OⁱPr)₄] and LiAl[(O^tBu)₄]. The later showing the most promise as a coating precursor due to its high solubility in tetrahydrofuran (THF), low temperature decomposition (283 °C) and reaction with hydroxyl groups present on the surface of NMC811. This coating was tested on polycrystalline NMC811 (PC-NMC811) and Al₂O₃ coated single-crystal NMC811 (Al₂O₃/SC-NMC811). Significant improvements in capacity retention (17.2% more C/2 capacity retained after 107 cycles vs. Al₂O₃/SC-NMC811) were seen in the LiAlO₂/Al₂O₃/SC-NMC811 system. Furthermore, coating PC-NMC811 that was previously degraded by soaking in water improved the capacity retention (50.1% more capacity retention at C/2 after 215 cycles vs. uncoated PC-NMC811 soaked in water and annealed at 400 °C) suggesting that the combination of a LiAlO₂ coating and subsequent annealing step can recover NMC811 surfaces that have been previously degraded by soaking in water.

We Built this City (WBTC) is a broker venture trading innovative London-themed goods in a pop-up shop in the emblematic Carnaby Street in central London. WBTC was born by founder Alice Mayor's vital purpose to support creative professionals, bringing together a team to fulfil her vision through a journey of five shops and a successful e- commerce website. Putting together a functional team can be challenging for emerging ventures and even more for sole founders leading small groups of workers, where organisational roles will develop overtime alongside limited resources. Organisational role literature has mainly studied roles from psychological and sociological perspectives that cannot comprehensively explain changing contexts where roles adapt. The previous exposes a gap in understanding how roles unfold, encompassing dynamic organisational development over time. This study attempts to fill this gap by asking how the WBTC team enact their role to successfully perform brokerage relations within the venture's networks. From here, this research aims to understand how roles shape, evolve and articulate within an emergent and fast-growing venture from the creative sector. To answer this question, I adopted a longitudinal approach gathering rich qualitative data through multiple methods, to observe how the WBTC team performed their roles over time. I took an interactionist perspective that considered roles as non- fixed positions collectively constructed from different elements in individuals' social systems. I observed team roles evolving through the organisation's emergence and throughout its organising, stabilising and growing consecutive phases. To start, I mapped team members' interactions with suppliers and consumers, where roles collaborated to alleviate workload and avoid role overload. The data led to identifying two organisational dimensions where the WBTC team roles operate in tandem: (1) an individual dimension, engaging in dyadic relations with suppliers and consumers; and (2) a collective dimension, re-distributing role responsibilities to tackle contingent ventures needs while protecting individuals from role burnout. The individual dimension showed specialised types of relations categorised as customised and commoditised, leading team members to enact their roles in distinctive ways. These findings suggest that although in the individual dimension, team members categorised their relations in specific ways, in the collective dimension, they did not discriminate any category and shared responsibilities and tasks with actors from a different relational type or motivation of their own. Therefore, in this study, roles appear as a malleable structure that despite being initially scripted, were flexible to effectively reconfigure, allowing the team to act as a firmly integrated block in the face of change. These findings deepen our understanding on how different roles operate within creative teams. From theory, this research extends contemporary organisational role theory from a dynamic process perspective, extending our understanding on how roles shape and articulate in small teams as ventures evolve, showing how flexibility is vital to protect team members from suffering from role overload and for small teams to navigate multilevel network relations, which are critical for organisational survival and growth.

The increase in temperature as a consequence of climate change is predicted to impact adversely on UK apple production by affecting the dormancy cycle. Warmer winters, and an increased risk of frost damage due to earlier bud break, are of major concern to UK growers. Although chilling and heat accumulation models are often used to predict time of bud break and anticipate cultivar suitability to new climes, existing models do not consider different cultivar responses or climate change scenarios and so are of limited use. The aim of this PhD research programme was to improve our understanding of the temperature effect on the dormancy cycle in a range of apple cultivars, and to develop cultivar-specific models to predict cultivar suitability in a climate change context. All experimental work was carried out in the UK between 2017 and 2021, using a combination of methodologies and plant materials including excised shoots, potted trees, floral buds, and xylem sap from orchard trees. Data were collected through experiments in controlled environment conditions, from UK apple orchards, and from analytical work in the laboratory. The depth of dormancy was highly variable between cultivars, as evidenced by the finding of different sensitivities to warm temperatures during ecodormancy. A lower optimum temperature for chilling accumulation was observed compared to previous models, indicating that future reductions in winter chill accumulation could be more severe than predicted. A new chilling model was created, the Malus model, which represents a better approximation of temperature contributions towards chilling accumulation. Results also indicated a partial overlap between chilling and heat accumulation, and a new modelling approach was developed that accounted for the correlation between both temperature-driven processes. Changes in carbohydrate concentrations in apple buds and xylem sap during winter occurred in parallel to chilling and heat accumulation, indicating a link between carbohydrate dynamics and the progression of dormancy. The outputs from this PhD research programme corroborate the industry's concern that warmer winters will pose significant challenges for UK apple production. Nevertheless, new fundamental knowledge needed to develop more accurate chilling and heat accumulation models was generated, and this will help to inform climate change adaptation strategies so that potential impacts on the UK apple sector can be managed and mitigated more effectively.

Lung cancer is the leading cause of cancer-related deaths in our society due to the inefficiency of early detection strategies and the high rate of treatment failure. Therefore, a better understanding of the mechanisms underlying its origin and the response to current treatment paradigms are crucial to improve lung cancer survival. Cellular senescence is a powerful tumour-suppressive mechanism whereby cells stably enter a cell-cycle arrest in response to oncogenic stress. However, the accumulation of senescent cells can alter the tumour microenvironment through a strong paracrine secretion of factors that can lead to detrimental and tumour-promoting effects. Intriguingly, senescence has been reported to be a defining feature of early lesions in Non-Small Cell Lung Cancer (NSCLC), a subtype that accounts for over 80% cases of lung cancer. In addition, senescence has also been reported to occur in response to the standard of treatment for this disease. It is thus conceivable that senescence may play a role in the origin and progression of this disease, despite a causal connection remains to be deciphered. Pharmacologic therapeutics that preferentially target senescent cells, known as senolytics, have been successful in preventing and even reversing senescence-driven detrimental effects in multiple pathological processes. However, their suboptimal specificity and toxicities hamper their clinical translation. Therefore, the targeting of senescent cells through the development of second-generation senolytics that can overcome these obstacles has the potential to revolutionise cancer treatment. The aim of this work is to define the role of cellular senescence at the origin and progression of lung cancer and in response to chemotherapy, and to develop safer and more effective therapeutic approaches to eliminate senescent cells in the context of lung malignancies. In this thesis, we studied the accumulation of senescent cells during the development of lung adenocarcinoma using a KrasG12V-driven lung cancer mouse model. We demonstrate that senolytic treatment of early lesions results in a significant reduction in lung tumour burden and increased survival, providing evidence of the tumour-promoting effect of senescence in early stages of NSCLC. Our research also reveals that platinum-based chemotherapy of human and murine lung adenocarcinoma cells induces senescence, which in turn promotes malignant phenotypes on untreated cancer cells in a paracrine manner in vitro, in xenografts and in orthotopic models of lung adenocarcinoma. Through high throughput unbiased transcriptomic and proteomic approaches, we show that secreted TGF-β ligands activate the Akt/mTOR pathway in untreated cells resulting in enhanced tumour growth. We further demonstrate that senolytic treatment and pharmacologic inhibition of TGFβR1 in tumours can prevent increased proliferation and enhance survival of lung tumour-bearing mice. In order to develop a novel approach for improved senolytic treatment, we show that the galacto-conjugation of senolytic ABT-263 (navitoclax) in the form of an activatable pro-drug significantly enhances cytotoxicity in combination with cisplatin, resulting in reduced lung cancer tumour growth. Importantly, our approach demonstrates decreased navitoclax-associated toxicities, including platelet apoptosis in human and murine blood treated ex vivo and decreased thrombocytopenia in mouse lung cancer models. In summary, this PhD thesis provides evidence of the incidence and role that cellular senescence plays in promoting the progression of early and advanced NSCLC and demonstrates that cisplatin chemotherapy drives pro-tumorigenic phenotypes in a paracrine fashion, which can be prevented with senolytic and TGFβR1 inhibitory treatments. Lastly, it proposes a novel second-generation therapeutic approach to mitigate senolytic toxicities and enhance the efficiency of targeting senescence in the context of lung cancer.

Through this study, I investigate the making of temporary spatial practices in the city of Santiago, Chile. I approach those as experimental actions driven by a multiplicity of actors: citizens, civic organizations, and government bodies, conceived to last for some time and determined by a will to produce transformative changes in the city. The wide variety of practices reverberating across different geographies, spaces and scales are bringing fresh prominence to the contemporary debate on public space. However, the topic, widely explored in European and North American cities has been less studied in the Latin American context, and specifically, in Chile, where this research focuses. I reflect critically on the ambiguous character of such temporal operations and their discourses: such practices could defy dominant forms of power in the production of space and could align, through their values and relations, to the structures of power by becoming complicit with forms of capital accumulation. Inquiring about how such practices challenge the making of contemporary public space, I assume that these practices could challenge the production and meaning of 'the public' in the city. Therefore, I draw attention to how their making makes the 'public', by emphasising the differentiating character of these practices and their political dimension. I interpret such temporary operations through a political lens, for exploring their contradictions and their possibilities to confront the presumed stability and predicted desirability of the contemporary city project. This research is theoretically and methodologically positioned at the crossover between urban design and social science. For framing the theoretical and analytical limits of the research question, I propose to use the locution 'temporary urban' which brings together the interrelated dimensions of time, use, and the public. Using an interpretive paradigm of qualitative research, I explore the controversial relationships between temporary spatial practices and the neoliberal urban project of the city of Santiago. Empirically, such examination is driven by an analysis that focuses on the meanings and values that different actors bring to the urban discourse and on the relationships established among them, exploring the contested and changeable power interplay among agents of city-making.

This thesis examines the production of Chilean science schoolteachers' and teacher educators' subjectivities in and around a continuous professional development (CPD) programme focused on big ideas of science education. The framework of big ideas is now part of the Chilean school science curriculum. Drawing on the sociopolitical turn in science education and on my practice as a teacher educator working in a team providing CPD, I designed an intervention to explore the gap between how the curriculum is designed and how both schoolteachers and teacher educators understand it, teach it, and ultimately bring it to life. I worked with 11 colleagues to design and deliver CPD focussed on big ideas with 21 schoolteachers. I also conducted classroom observations and interviews with two schoolteachers to further explore their conceptualisations and practice in teaching big ideas. Using dialogue as an analytical tool, I explored the different types of discourse that emerged: i) during a design meeting before the CPD; ii) during the implementation of the CPD; and iii) around two of the schoolteachers' experiences of teaching big ideas in the classroom. Dialogical analysis of key events afforded the opportunity to depict different subjective positionings of those participating in the CPD. My analysis articulates two main ideas. First, I describe changes in subjectivities: teacher educators produce different positioning in relation to their institution, and their different identities combine and differentiate at different moments; and schoolteachers shifted their pedagogical and epistemological positionality because of the work around activities they undertook. Secondly, the conceptualisation of the big ideas framework and its role in the curriculum is contested between the levels of policy, the CPD, and teachers' school-based practice. By problematising the contested understanding of big ideas between these levels, I argue that there is a chain of exclusions for these conceptualisations to exist.

In this thesis we will establish the stick-breaking representation of the convex minorant and the extrema of an arbitrary Levy process. Our self-contained elementary proof is based on the analysis of piecewise linear convex functions and requires only very basic properties of Levy processes. We then use the stick-breaking representation to create geometrically convergent simulation algorithm for the extrema of a Levy process whose increments can be sampled. For processes whose increments cannot be sampled we develop a multilevel Monte Carlo algorithm using the stick-breaking representation. In all cases, the algorithms present in this thesis outperform the existing algorithms in the literature.

Regulation of cell size is controlled by multiple biochemical pathways, such as the mammalian target of rapamycin (mTOR) signalling pathway and the transcription factor Myc. The loss of tightly regulated control of cell size is known to be associated with multiple diseases such as cancer. Understanding how key molecular components in such pathways is necessary to elucidate the mechanisms behind cell size control. Since pathways consist of large networks of interacting molecules, changes in the expression of such molecules may have a large impact on the signalling cascade output, therefore investigating the impact of how the growth-regulating signalling cascade is affected by hampering expression of effectors involved in the pathway is of great interest. This thesis shows that chemical and siRNA downregulation of central pathway effectors of the mTOR pathway reduces cell size and volume, which also change the cell cycle distribution. Furthermore, RNAseq analysis from a dataset similar to our experiments showed that differentially expressed genes from cells exposed to rapamycin seem to be involved in ribosomal biogenesis and metabolism. We observed that over-expression of Myc lead to notable increases in cell size and volume which were linked to higher levels of protein and rRNA content. RNAseq analysis of this cells showed that differentially expressed genes seemed to be involved in different cellular mechanisms related to cell size. Remarkably, Myc over expressing cells that were exposed to the mTOR inhibitor Rapamycin had a size like non-treated cells but with higher content of protein and rRNA. Sequencing analysis from these cells revealed many down-regulated genes involved in cell metabolism, translation, and other cellular process. A combination of Rapamycin and the rRNA synthesis inhibitor, Actinomycin D reduced the size and rRNA content of the Myc overexpressing cells, suggesting that ribosome biogenesis could be the mechanism behind the size control. To identify an alternative effector involved in cell size and ribosome biogenesis, we show that incubation of cells with a p38 MAPK inhibitor further reduces cell size and rRNA content, suggesting a possible interaction between the PI3K/AKT/mTOR pathway, with the p38 MAPK pathway and Myc.

This thesis addresses the role of film festivals in Chile in creating, promoting, and consolidating film culture in Chile since its first initiatives emerged in the 1950s to the end of the 2010s. This thesis focuses on the development of film festivals as exhibition spaces for Chilean and international cinema, providing a specific vision of film festival studies, exposing the topics covered in this thesis as cinephilia, film culture, film communities, festival networks, and the conformation of Chilean film studies. The thesis explores the different definitions of film festivals; however, I will propose understanding the festivals as meeting places for a national cinephilia, gathered around their love for cinema. In this way, the thesis is inscribed within an expanding area of studies from a Latin American perspective. The central aim of this thesis is to explore how a large number of film festivals in Chile have established themselves as an exhibition circuit that keeps the cinephilia and film culture of a film community active. In this way, the thesis discusses the concept of an international "film festival network" (Stringer 2001, Elsaesser 2005, de Valck 2007) to find similarities and specific differences between this global network of festivals and the incipient Chilean film festival circuit. Using the concept of film festivals as an "Open System" (Fischer 2009) as a reference, I propose a circuit model based on the analogy with the water cycle. Thus, the thesis proposes that film festivals in Chile are organised in a virtuous cycle, where a group of festivals act as condensers of resources (films, guests, funds, press), use them and return them to the environment in three main processes: sublimation and deposition as the relationship between film festivals and film historiography; runoff as the circulation of films through the rest of the film festivals in the circuit; and infiltration and subsurface flow as the formative role played by cineclubs and film schools. A cinephile interest mediates all these processes. As a result, resources are transformed into new resources, understood as new films, and new filmmakers and a new generation of cinephiles, which are returned to the environment condensed again by this group of festivals, nourishing this "virtuous" circuit. Furthermore, this thesis explores the water cycle model through two case studies FICValdivia and SANFIC. These film festivals have consolidated themselves as the main condensers within the Chilean circuit, achieving international connections and prestige. Moreover, the thesis put in tension the model's operation with the circuit analysis during the Chilean social outburst of October 2019 and the COVID 19 pandemic in 2020. Finally, the thesis also dialogues with the expansion of Chilean film production since the mid-2000s, analysing its links to global trends in auteur cinema and observing its circulation in international film festivals.

This thesis presents a series of studies investigating laterality in chimpanzees and its links with personality examined as behavioural style and social networks. The studies presented in this work were conducted by observing a group of 19 chimpanzees in captivity and present new findings in this species. However, this thesis has a broad evolutionary perspective, addressing important questions regarding personality and laterality that could prove helpful to the understanding of the evolution of laterality in vertebrates. Chapter 1 offers a general review of the three main areas of knowledge investigated: laterality, animal personality and primate social networks. Then, the first study of this project, presented in Chapter 2, began by exploring hand preference in the chimpanzee group, investigating spontaneous actions and unimanual tasks and expanding previous research by studying posture, between-task consistency and temporal stability. Chapter 3 investigated additional measures of motor laterality and proposed a novel way of measuring laterality in primates. Together, Chapters 2 and 3 directly examine laterality in chimpanzees and serve as the base from which to explore the links between laterality, personality and social networks in the subsequent studies. If lateralization is rooted in emotional processing and hemispheric lateralization, then individual differences in behaviour (particularly those that reflect emotional expression) would show a relationship with individual laterality. In order to address this question, Chapter 4 studies behavioural style in chimpanzees and its possible link with laterality. Simultaneously, if intraspecific coordination plays a role in the development of population level laterality, similarly lateralised individuals would likely have strong bonds to coordinate with each other. Chapter 5 introduces the approach and techniques of social network analysis and uses them to explore and describe the social structure of the group while describing the integration of a new adult chimpanzee. Chapter 6 applies social network analysis to explore if laterality plays a role in the way the group is structured. Lastly, Chapter 7 integrates all empirical chapters and presents the final discussion and conclusions of the thesis.

Globalization has provided opportunities for Small and Medium-Sized Enterprises (SMEs) operating in high-cost regions. However, globalization also presents a risk to SME sustainability due to increased, worldwide competition. In an effort to reduce cost and grow their businesses, Multi-National Companies (MNCs) may decide to move their supply base to low-cost regions. SMEs in high-cost regions are therefore presented with a competitiveness challenge and how they address this challenge may define their sustainability. The aims of this study are to learn how SMEs select business sustainability approaches that successfully make it difficult for MNCs to transfer work from them and, also, identify why SMEs select specific approaches over other approaches, and how these approaches impact their ability to be financially sustainable. During the preparation of the thesis proposal, a preliminary literature review revealed that knowledge, resources, and innovation are relevant factors to SMEs' business sustainability. A conceptual model was created at the outset of the thesis work, presenting the relationships these factors and manufacturing business practices have on driving business sustainability. These factors then inspired the formulation of the research questions. This model was modified to include the seven factors (strategy, flexibility, cost reduction, knowledge, innovation, communication, and Supply Chain integration) identified through the systematic literature review, and then modified again to include the three essential practices (continuous improvement, lock-in, diversification) identified and influenced by the case studies field work. The methodology used during the study was the generation of a literature review, followed by a case study research approach. The literature review helped identify key factors that affect SMEs' business sustainability, and was used to craft the questionnaire used as a guideline during the case study interviews. The study was conducted in California, a high-cost region in the USA, and included visiting four companies, gaining consent for their participation in the research, interviewing four employees from the management team, including the highest-ranking person, and participating in a plant tour. Each company represents a case study. A questionnaire was designed and used to help guide the researcher during the interview process using a semi-structured approach, providing the participants with the freedom to share their operations and business sustainability experiences while also ensuring a consistent approach with each participant and case. After the visit to each company, a case study was written to document the participants' perspectives and responses to the posted questions, followed by an analysis of how they approach business sustainability. Each case revealed similarities and differences between participants. Furthermore, when a cross-case analysis was performed, various common themes were observed, including tactics the SMEs used to remain competitive and approaches to business sustainability. SMEs' tactics to remain competitive concerned the use of Lean Manufacturing techniques and material cost reduction through bidding processes. From a business sustainability standpoint, the main approaches related to locking-in business were ensuring SMEs' active participation in customers' new designs, customizing products, and gaining design co-ownership. In addition, diversification into other markets and industries was a common theme discussed as a long-term approach to business sustainability. Another key point from the research was that supply chain integration and collaboration initiatives, such as product customization and engaging in supply chain programs like Vendor Management Inventory (VMI), provided the SMEs with a lock-in mechanism to ensure business sustainability in the long-term. The new trend of reshoring or back shoring shows that the same factors identified during the literature review, particularly cost reduction, flexibility, knowledge and supply chain integration, continue to be important when companies decide on a location. In addition, continuous improvement practices and customization capabilities were important to MNCs when they decided with whom to partner during the reshoring or back shoring process.

This thesis aims to answer why Mexico has an atypical foreign policy for a country that can be considered a middle power and tackles this empirical puzzle through the analytical tools of role theory. In this work, I argue that conflicting expectations from several actors - domestic and external - have led to a foreign policy that is contradictory to what is expected for a country with Mexico's material capabilities and for its foreign policy objectives. The time frame of the thesis ranges from 1986 to 2018, when Mexico faced various transformations. These transformations occurred in the international system and domestically with democratization and an economic opening that drove the confrontation between its two foreign policy orientations. The different interpretations of these orientations on how to implement Mexico's foreign policy led to disputes that affected the country's diplomatic performance as a middle power. Through case studies, the thesis examines three specific settings where Mexico could have displayed middle-power behaviour. The first case study analyses Mexico's controversial membership and performance in the Iraq crisis within the Security Council of the United Nations from 2002-2003. The second case study examines Mexico's ambition to display a regional leadership role in regional multilateral bodies such as the Community of Latin American and Caribbean States and the Pacific Alliance. Finally, the third case study focuses on Mexico's engagement in the niche issue of respect for human rights and democracy promotion. These three case studies show how role conflict has operated in Mexico's foreign policy. In summary, this work contributes to scholarship on Mexican foreign policy and role theory, and it is the first comprehensive application of role theory to the study of Mexican foreign policy.

In this thesis, I analyse how young audiences engage with nostalgic media texts. In recent years, from remakes or reboots to media texts set in previous decades, nostalgia has become a key ingredient of recent media production. Hence, I address two specific research questions: 1) how do young audiences interpret the past represented in nostalgic media texts; and 2) how do the national context and social identities of young audiences mediate their engagement with nostalgic media texts? For this, I conducted a media consumption habits survey, 13 focus group discussions, and 35 paired interviews in one private and one public secondary education school in Costa Rica. My intention is to explore the reception of nostalgic media texts in a nation of the Global South in which the past has recently generated political and social tensions. Thus, I first argue that these young audiences interpret the past represented in nostalgic media texts through an aestheticisation of the past and by employing a particular nostalgic social imaginary. Following textual cues and national discourses, these young people idealise the styles of the past but exhibit a critical awareness in terms of some social tensions of previous decades. Then, I argue that nostalgia is a structure of feeling which emerges from an unsatisfying present. By exploring the social identities of the participants, I discuss how nostalgia is differently articulated depending on the social position of these young people. I identify how the students from the private school experience an aesthetic nostalgia, based on the romanticisation of the styles of the past but characterised by an optimistic appraisal of the future, and how the students from the public school experience a material nostalgia, an idealisation of the past derived from daily experiences of economic deprivation and the expectation of a precarious future.

This research focuses on the improvement of the bachelor of industrial design program offered by the University of Monterrey and the generation of knowledge through the use of several methods and methodologies relevant to the field of business administration and research. As a former employee in the industry, the researcher is aware of the importance for students and graduates to develop technical and interpersonal skills in order to efficiently attend their working demands. These skills however, are sometimes not in accordance to what the industry (identified in this research as the demand side in the stakeholder theory) might require, and the university (the supply side) offers as potential professionals as the result of years of training and education in the field of industrial design. This mismatch was identified as the managerial problem in this Thesis. For this study, the methodology of Action Research was selected. Different from traditional research methodologies, AR not only pretends to obtain and analyze data to obtain conclusions regarding a managerial problem, but also seeks to provide improvement in the organization. With the use of Action Research in this Thesis, the researcher was not only able to obtain valuable data from the stakeholders but to conduct analysis through various different cycles of learning, discuss the results with the organization, identify opportunity areas to mitigate and improve the situation of the problem. It was precisely thanks to the involvement and discussion of results that is expected to occur with the methodology that the researcher was able to obtain solid conclusions and identify areas of improvement that wouldn't be possible to achieve with other methodologies. To better understand how to attend the managerial problem, it was necessary to obtain data from every stakeholder regarding their perceptions and expectations towards different topics of industrial design such as skills and abilities they believed designers should have, as well as their perception towards this profession within the industry. Using Template Analysis as the data analysis method, the researcher was able to acquire seven overarching themes that gave a broad perspective of the different topics regarding the design profession. These were then discussed with the organization, and their analysis derived in four major opportunity areas that require their attention to mitigate the problem. Finally, the researcher was able to propose improvements to the program and offer methodological and practical contributions for knowledge, as well as for the organization, which the reader can find in the final chapter of this study.

Diabetes is a disease caused by a breakdown in the glucose metabolism resulting in abnormal blood glucose fluctuations. Traditional therapies involve external insulin injection in response to elevated blood glucose, which faces limitations such as delays in insulin action and the non-physiological absorption of insulin into the systemic circulation. Recently, bioelectronic medicine has emerged as a powerful strategy for treating chronic diseases, such as diabetes, by electrically interfacing with peripheral nerves and organs. The research conducted in this thesis combines different strategies to investigate the development of novel neuromodulation-pharmaceutical therapeutic technology for people with diabetes. Following a scientific-based approach, the thesis presents studies that allowed increasing our understanding of the physiological mechanisms underlying the neural glycemic regulation. In vivo experiments in rodents provided new insights into the impact of vagus nerve stimulation (VNS) frequency on blood glucose, insulin and glucagon concentrations. To further characterize this neuro-metabolic interaction, the first mathematical model describing the physiological metabolic events after cervicalVNSwas developed and validated. Using an application-based strategy, the thesis investigates the opportunities for incorporating bioelectronic medicine to traditional diabetes technology in clinical scenarios. In particular, one study presents the proof of concept of a novel closed-loop glucose controller that regulates the insulin and glucagon dose delivery, and drive the insulin sensitivity (SI) of virtual patients using neuromodulation. In silico experiments demonstrated improved safety and efficacy compared to traditional controllers. An additional study introduces an original data-driven approach to predict the quality of overnight glycaemia based on the application of binary classifiers on metabolic data. To fully exploit bioelectronic medicine as an alternative or complementary therapy for diabetes, advances in minimally invasive technology and promotion of our knowledge of the field are needed. The work presented in this thesis opens the door to further research that promises to transform the current healthcare scenario in diabetes.

Microsilica particles arise as a byproduct of silicon furnace operation, created inside high temperature flames due to the combustion reaction of silicon monoxide with oxygen. These nanoparticles, which grow as silicon dioxide vapour condenses on the surface of existing particles, are used in a variety of composite materials. The size and quality of the particles affect the performance of the material used for such applications, and hence control of these quantities is of importance to manufacturers. Motivated by this, we derive a mathematical model that connects local fluid flow, thermal and chemical conditions of the furnace to the formation and growth of microsilica particles. Since the regions where microsilica particles form are local to a very thin reaction zone, we focus on the dynamics within the flame front. We first study two distinct reductions of the model: the case of initially well-mixed or spatially homogeneous chemical species, and the case of initially separated chemical species. In the latter case, the one-dimensional domain is given by a cross section of the reaction zone and diffusion plays a dominant role in providing material to a combustion front. In order to incorporate fluid flow, we extend the previous work to 2-D by considering a mixing layer approach, that is, by assuming two parallel flows entering the domain with distinct velocities, temperatures, and concentrations. We study how the mixing layer evolves as both streams interact, and how mixing affects the formation and growth of particles. In all cases, we provide asymptotic approximations under various limits and neglecting the effect of the particles on the chemicals and temperature, and numerical solutions of the full model. Our results suggest that oxygen availability and a sufficiently high temperature are essential for the combustion reactions to occur, strongly influencing the width of the reaction zone and the particle size distribution. Furthermore, when the flow is almost uniform, fewer particles form and more of the total mass corresponds to large particles, in contrast with the non-uniform case.

In order to gain further understanding about the onset mechanisms of flash sintering, the electrical properties of cubic calcia-stabilised zirconia, CSZ (CaxZr1-xO2-x: 0.12≤x≤0.18) and Mg-doped alumina (0.05wt%MgO-Al2O3 and 0.5wt%(MgO/SiO2)- Al2O3) ceramics were investigated using impedance spectroscopy as a function of temperature, oxygen partial pressure and applied dc bias. Equivalent circuit analysis was carried out to identify the electrical microstructure of the materials. As part of this process, the relative importance of individual elements to the overall impedance response was highlighted by a new approach by the deconvolution of the impedance spectra. The bulk, grain boundary and electrode contact impedances of CSZ ceramics were characterised over the temperature range 200-930°C. The most appropriate equivalent circuit to characterise the bulk response required inclusion of a dielectric component, represented by a series RC element, in parallel with the oxide ion conductivity represented by a parallel combination of a resistance, capacitance and constant phase element. The dielectric component may be attributed to defect complexes involving CaZr''-VO •• pairs whereas long range conduction involves single oxygen vacancies. The activation energy for the dielectric component increased with increasing x. This was attributed to an increase in the number of pairs or to their coalescence into larger aggregates, causing greater difficulty in reorientation of the dipoles. The sample-electrode interface response was deconvoluted into two components, the charge transfer (Rct) and diffusion resistance (Rdiff), where Rct << Rdiff. Impedance analysis of CSZ ceramics under different atmospheres showed that the limits of the electrolytic domain vary with temperature and composition. Around 400°C, the bulk conductivity of all compositions remained independent of pO2 and the samples were pure oxide ion conductors, but near 930°C, x=0.12 showed introduction of n-type conduction and x=0.18 showed p-type whereas the intermediate composition x=0.15 did not show any pO2 dependence. The total resistance of CSZ ceramics decreased with application of a dc bias. This was attributed to the introduction of p-type conductivity. Electron holes might be located on under-bonded oxygen ions, associated either with the Ca dopant ions, or those near the ceramic surface, resulting in a mixed ionic-electronic conduction pathway. A flash sintering set-up was built. Flash sintering experiments on CSZ x=0.15 showed increased conductivity and emission of light, but no sample densification. It was concluded that the sintering process can be separated from the emission of light and increase in conductivity and therefore, that the origin of these phenomena, ie flash and sintering, might be different. Impedance measurements on two Mg-doped alumina ceramics, over the temperature range 400-910°C, showed a combination of low-level oxide ion conductivity and p-type electronic conductivity, depending on temperature, oxygen partial pressure and dopant content. The oxide ion conductivity was attributed to oxygen vacancies, introduced as charge compensation for the Mg dopant. The p-type conductivity was attributed to hole location on under-bonded oxide ions and was identified as the dominant conduction pathway for measurements in air at high temperatures. The sample resistance increased on application of a dc bias. This was attributed to electron-hole recombination and the loss of p-type conductivity associated with oxygen loss.

A large number of cell surface proteins contain an SH3 type 5 domain (SH3_5) responsible for the cell wall binding of these proteins to peptidoglycan. SH3_5 domains are involved in the recognition of peptidoglycan in different pathogenic bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE). This work sought to elucidate the mechanisms underpinning the recognition of peptidoglycan by SH3_5 proteins. As a model system, we focused on the C-terminal SH3_5 domain from the lysostaphin enzyme. Lysostaphin is a bacteriolytic enzyme produced by S. simulans that cleaves the pentaglycine crossbridge in S. aureus peptidoglycan. This potent enzyme can efficiently lyse MRSA strains and disrupt biofilms. The lysostaphin enzyme contains an N-terminal catalytic domain with glycylglycil endopeptidase activity and a C-terminal SH3_5 cell wall targeting domain. Nuclear Magnetic Resonance (NMR) titrations, X ray crystallography, and mutational analyses, revealed how this SH3_5 domain efficiently recognises S. aureus peptidoglycan. Our NMR titrations showed that the pentaglycine crossbridge and the peptide stem are recognized by two independent binding sites located on opposite sides of the SH3_5 domain. The 1.4 Å crystal structure of the SH3_5 domain, in complex with a synthetic peptidoglycan fragment, revealed a dual SH3_5 binding mechanism whereby the G5 ligand from a monomeric fragment was recognized by one SH3_5 domain and the P4 peptide was bound to another SH3_5 protein. We propose that this binding mechanism leads to a synergistic and structurally dynamic binding, which induces clustering of the SH3_5 domains and increases the local concentration of the enzyme resulting in its potent bacteriolytic activity. We propose that this research will serve as a framework for understanding how bacteria control the enzymatic activity of PG hydrolases and will contribute to the development of antimicrobial approaches.

This dissertation studies the history of women’s activism and feminism through the lens of the Chile solidarity movement. It seeks to shed light on the transnational nature of feminism and women’s movements by exploring the organisations, networks, practices and ideas that became involved in—or emerged from—Chile solidarity politics. On the one hand, it looks at the involvement of women’s international organisations in Chilean solidarity, which built on practices of international solidarity and human rights activism developed well before the 1973 military coup. On the other hand, it delves into the case study of the British solidarity movement, exploring connections with the women’s movement (both in Chile and the UK) and the influence of feminist ideas and practices. As a result, the thesis shows the mutually reinforcing nature of Chilean solidarity politics and women’s activism in the 1970s and 1980s. Women’s activism fuelled the solidarity movement by introducing new concerns and participants to the campaigns involving Chile. The plight of Chilean women, the gendered dimension of human rights, women’s experiences of exile in the UK and elsewhere, and the gender dynamics of political organisations became key issues as female activists and feminists became increasingly involved in Chile solidarity. Furthermore, the study contends that the history and accounts of international solidarity and exile played a major role in the development of both women’s international activism and feminism in Britain. It shows how solidarity politics and the phenomenon of exile expanded women’s and feminist organising by including new actors and perspectives. All in all, the solidarity networks established by women’s international organisations, solidarity and human rights committees, women’s groups, and feminist activists show the complex interactions between the multiple layers of women’s transnational activism.

Many client organisations act as project sponsors, owners, and users in project settings. Thus, they organise themselves across the project to configure, design and deliver valuable outcomes for the long-term. However, research in projects has shown that many projects fail to meet mandatory objectives and ultimately to accomplish the project vision in the longterm (Morris 2013). Some projects, rather than creating value, they destroy it, directly affecting organisational business models and other societal aspects (Fuentes et al. 2019). One of the key problems behind this lack of focus on the value for long-term has been that, historically, projects have focused upon engineering value through manufacturing and production. While these aspects are relevant, a complementary perspective is necessary to design and deliver valuable outcomes for the long-term. Thus, the purpose of this research is to offer an alternative perspective on how to co-create valuable outcomes for the client organisation. From a theoretical approach, the Service-Dominant Logic (SDL), from marketing, is to date the most relevant and modern framework to explore how value outcomes can be co-created for the long-term (Vargo and Lusch 2016; Grönroos 2017). Thus, SDL is taken as a starting point, yet this study critically analyses SDL to understand what aspects can be used in the business of the project. To this end, this research used six qualitative empirical project case studies of two public sector client organisations in England. The results originally offer a process by which value outcomes are co-created. The process shows: (a) eight key-value interactions to co-create value; (b) four key-generative mechanisms to facilitate an organisational structure to co-create valuable outcomes; and, (c) a set of five types of integrated value outcomes, which emerge on the long-term. This research, therefore, may provide a set of principles for project practitioners on how to cocreate value outcomes across the project lifecycle.

In Multiple Sclerosis (MS), the insulating membrane that ensheaths axons termed myelin, is lost by a process known as demyelination. Initial regeneration of myelin, termed remyelination, restores neuronal function. However, remyelination failure with disease leads to a loss of cognitive, sensory and motor functions. There are no currently approved therapies aimed at inducing remyelination, highlighting the need to investigate new targets that can promote this process. Astrocytes are the most abundant glial cell type in the central nervous system (CNS). They are known to support myelin formation in development and its maintenance during adulthood, yet their roles during remyelination are controversial and remain poorly understood. The work from this thesis explores the changes in astrocytes at the cellular and molecular level during remyelination. Using two different in vivo models of toxin induced demyelination, I have found that astrocytes during remyelination undergo a series of changes in numbers, reactivity (assessed by GFAP, vimentin, nestin and NFIA), and morphology, which indicate a temporal regulation of reactivity. Interestingly, I observed that astrocytes increase in reactivity at the time at which the myelin-forming cells, termed oligodendrocytes, differentiate to remyelinate axons. These findings suggest that astrocytes are important for regulating remyelination. To explore this, unbiased RNA-sequencing of astrocyte translating mRNA, isolated using translational ribosome affinity purification (TRAP), was used to identify changes in their gene expression. I found that astrocytes upregulate genes indicative of neuroprotective functions early after demyelination, characterised by the upregulation of the Nrf2 pathway. Subsequently, at the time of oligodendrocyte differentiation, astrocytes downregulate Nrf2 signalling and activate cholesterol biosynthesis, which is essential during myelination. Here, I hypothesised whether Nrf2 is an critical regulator of astrocyte functions that are important for remyelination. Hence, I used a transgenic mouse model in which Nrf2 is overexpressed in reactive astrocytes. The results suggested that upon sustained Nrf2 overexpression, cholesterol biosynthesis in astrocytes is impaired and consequently remyelination is poor. This study identifies a mechanism by which astrocytes regulate their functions after demyelination to control the timing of remyelination. These findings are of translation relevance, given that some MS therapies are thought to act via Nrf2 activation.

In 2014, the Chilean government promulgated the Law 20,571. This law gives to regulated clients, mainly residential electricity customers, the right to produce energy/electricity for self-consumption and sell any surplus to the grid. After five years of implementation, including an update in 2018, the installed capacity of these projects is still very low. In contrast, in Scotland it is possible to find a much higher citizen participation in energy production through more collective initiatives, specifically community energy projects. This situation begs important questions about the effectiveness of net billing schemes in promoting citizen participation in energy production. In this doctoral thesis, a variety of tools inspired by game theory, social science, and mathematical programming are used and adapted to answer these questions. This leads to the following findings. Firstly, the current Chilean net billing scheme may not be the best support mechanism for citizen-led energy production developments. Secondly, some residential electricity customers would be willing to participate in local energy initiatives by devoting money and/or time, even when their main concern is the lack of financial resources necessary to fund such projects, and project ownership can influence this willingness. Thirdly, community energy projects can be the best strategy to follow for residential electricity customers in Scotland and Chile, although cost subsidisation can further improve community energy incentives. Even when the incumbents do not know their share of the benefits at the time of choosing a particular energy production scheme or mechanism, community energy projects present more opportunities to be implemented in comparison with net billing schemes in both countries. Finally, under specific circumstances, community energy deployment can have positive effects on variables like social welfare, consumer surplus, nodal prices, and carbon dioxide emissions. Based on these findings, we then draw conclusions and recommendations, which can help further development in the community energy sector, particularly in Chile.

The field of functional biomaterials has seen huge progression with enormous efforts made to discover 3D scaffolds that support and promote tissue formation. Polymerbased 3D scaffolds are used extensively as a consequence of their remarkable tunability and biocompatibility. However, the scope of possible scaffolds, with respect to their physical and chemical properties, is vast encompassing chemical composition, wettability, 3D structure and mechanical properties to name but a few. In addition, the combined effects of these properties on cellular fate, in association with scaffold/protein binding, leads to highly complex systems with numerous processes occurring simultaneously at multiple levels, which hinders a full understanding of the cell–material interface. Therefore, despite huge efforts to understand how the physical and chemical cues of these 3D scaffolds trigger and control cellular behaviour, the effect of these properties on cells remains vague, yet continues to be a key element of tissue engineering. 2D polymer microarrays have been shown to be an efficient high-throughput technology to discover new functional polymers. However, these polymer features lack the necessary 3D structure and morphologies present within tissues. In this thesis, I present the development of a new strategy to fabricate arrays of 3D polymer scaffolds exploiting photo-polymerisation within a crystallisable solvent (dimethyl sulfoxide, DMSO), which serves as a template for the generation of pores. Initial studies involved the identification of suitable polyacrylates that were capable of binding and maintaining human bone osteosarcoma cells (SAOS-2 and MG-63). These were then used to optimise a polymerisation process that maximised the formation of pores in addition to analysing the effect of the solvent on the 3D structure of the scaffolds and their mechanical properties. An array of 24 different 3D polymer features was fabricated and screened with SAOS-2 cells as a proof of concept of the applicability of the array, showing that cell attachment, proliferation and morphology could be controlled by the composition of the scaffolds along with their 3D microstructures. A second project (a collaborative effort with the University of Southampton) used the developed screening platform to identify novel 3D scaffolds that promoted the formation of vascularised bone tissue with 45 different 3D polymer scaffolds (15 different polyacrylates with 3 levels of porosity) and foetal bone marrow stroma cells (FBMSCs). A highly biocompatible scaffold was discovered that promoted osteoblastic phenotype expression and vascularisation - the first time for such phenomena had been observed in polyacrylate scaffolds without externally supplied factors. This was validated ex vivo, with a chick chorioallantoic membrane (CAM), and in vivo, with a subcutaneous mouse model, confirming biocompatibility and the formation of new tissue/vasculature.

The coupling of flow chemistry with automated laboratory equipment has become increasingly common and used to support the efficient manufacturing of chemicals. A variety of reactors and analytical techniques have been used in such configurations for investigating and optimising the processing conditions of different reactions. However, the integrated reactors used thus far have been constrained to single phase mixing, greatly limiting the scope of reactions for such studies. This thesis presents the development and integration of a millilitre-scale CSTR, the fReactor, that is able to process multiphase flows, thus broadening the range of reactions susceptible of being investigated in this way. Following a thorough review of the literature covering the uses of flow chemistry and lab-scale reactor technology, insights on the design of a temperature-controlled version of the fReactor with an accuracy of ±0.3 oC capable of cutting waiting times 44% when compared to the previous reactor are given. A demonstration of its use is provided for which the product of a multiphasic reaction is analysed automatically under different reaction conditions according to a sampling plan. Metamodeling and cross-validation techniques are applied to these results, where single and multi-objective optimisations are carried out over the response surface models of different metrics to illustrate different trade-offs between them. The use of such techniques allowed reducing the error incurred by the common least squares polynomial fitting by over 12%. Additionally, a demonstration of the fReactor as a tool for synchrotron X-Ray Diffraction is also carried out by means of successfully assessing the change in polymorph caused by solvent switching, this being the first synchrotron experiment using this sort of device. The remainder of the thesis focuses on applying the same metamodeling and cross-validation techniques used previously, in the optimisation of the design of a miniaturised continuous oscillatory baffled reactor. However, rather than using these techniques with physical experimentation, they are used in conjunction with computational fluid dynamics. This reactor shows a better residence time distribution than its CSTR counterparts. Notably, the effect of the introduction of baffle offsetting in a plate design of the reactor is identified as a key parameter in giving a narrow residence time distribution and good mixing. Under this configuration it is possible to reduce the RTD variance by 45% and increase the mixing efficiency by 60% when compared to the best performing opposing baffles geometry.