Population displacement has long been a controversial companion of development. The central tension has been between the position challenging the kind of development that removes people from their homes, livelihoods and communities, and a managerial position that the impoverishment risks of displacement can be mitigated through an effective intervention. Whereas recent research has been devoted to unpacking a rather unsuccessful performance of involuntary resettlement as a mitigation measure, this study aims to question the assumption of mitigation itself by expanding the concept of development impacts beyond the realm of displacement. Through an empirical study of a railway project in Metro Manila, the Philippines, I examine how urban residents are affected by a large-scale demolition and displacement that took place in their locality. Semi-structured interviews were conducted along the railway tracks after the land was cleared of informal settlements since the study placed particular focus on residents who were not physically displaced. They are identified in my research as non-displaced people. Few studies have addressed the possibility that other people might have been adversely affected in situ and this is particularly so in urban areas. Empirical findings reveal that the physical environment and socio-economic relationships in the locality were significantly transformed through the clearance; impacting the tenure status, livelihoods and social milieu of non-displaced people. Tenure security was important for avoiding displacement but was not a definitive factor as a number of people are still informal settlers who continue to be faced with other eviction threats. For the non-displaced, the physical change of the locality became relevant when their productive capital, notably, a second house or business space, was affected. The loss or erosion of physical capital had a secondary impact on livelihoods, which was compounded by the rupture in the local livelihood network following a mass population outflow. Whereas the income of locally-based businesses decreased substantially, livelihoods that operate beyond the locality remain relatively resilient. Differentiated experiences of a local change are also reflected in a range of evaluations that describe local social ambiance before and after the event. Diverse ways in which non-displaced people were affected underline that the current conceptualisation of impacts is limited to one dimension of displacement. This raises the need to adopt a more holistic and disaggregated approach to understanding the complexities of development impacts. A discussion on whether and how they can be mitigated would benefit further from such a comprehensive study.

Tomato is an important food crop and a model for fleshy fruit development. The process of fruit ripening involves changes in chemical composition and in particular the accumulation of sugars, organic, amino acids and carotenes. The research described in this thesis aimed to identify key regulatory aspects associated with the accumulation of the major acids in tomato fruit by analysis of introgression lines resulting from a cross between a cultivated variety, Solanum lycopersicum, and a wild progenitor species, Solanum pennellii. Line 2-5 showed increases in citrate, malate, aspartate and glutamate in fruit grown under greenhouse conditions. The genetic differences between line 2-5, its overlapping lines, sub-introgression lines and the recurrent parent were used to link the metabolite phenotypes to smaller chromosomal regions. This analysis suggested multiple epistatic loci control fruit metabolite accumulation. Investigation of the biochemical differences between line 2-5 and the recurrent parent revealed that organic and amino acid accumulation did not dependent upon increased TCA cycle capacity. Regulation at the metabolic level was identified for citrate accumulation with changes in cytosolic aconitase in line 2-5. As these metabolites accumulate in the vacuole, tonoplast transport was investigated. Correlation of ATPase-dependent malate influx with altered malate content suggested malate tonoplast transport plays a role in malate accumulation and highlights the importance of vacuolar storage and transport in the regulation of organic and amino acid accumulation.

This work concerns itself with understanding the organisation of cellular immune responses to three major human pathogens - HIV, CMV and Hepatitis C (HCV). Each was studied to form three projects, each undertaken with a different approach - arrived at independently - and largely owing their origins to opportunity and circumstance as much as design. Each project led to exploration of a particular aspect of T-cell phenotype (that is the expression of particular molecular markers on T-cells) and its’ broader biological significance. I found that T-cell phenotype was strongly linked to the magnitude of T-cell responses (CMV) and the ability of T-cells to control infection (HIV). Finally I explored the significance of expression of a molecule known as CD161 on the surface of HCV specific CD8+ T-cells, indicating a phenotype of T-cell that may not follow the ‘normal rules’ applicable to T-cells in general.

The purpose of this thesis is to develop a vertex model framework that can be used to perform computational experiments related to the dynamics of epithelial tissues in developmental systems. We focus on three example systems: the Drosophila wing imaginal disc, the Drosophila epidermis and the visceral endoderm of the mouse embryo. Within these systems, key questions pertaining to size-control mechanisms and coordination of cell migration remain unanswered and are amenable to computational testing. The vertex model presented here builds upon existing frameworks in three key ways. Firstly, we include novel force terms, representing, for example, the reaction of a cell to being compressed and its shape becoming distorted during a highly dynamic process such as cell migration. Secondly, we incorporate a model of diffusing morphogenetic growth factors within the vertex framework, using an arbitrary Lagrangian-Eulerian formulation of the diffusion equation and solving with the finite-element method (FEM). Finally, we implement the vertex model on the surface of an ellipsoid, in order to simulate cell migration in the mouse embryo. Throughout this thesis, we validate our model by running simple simulations. We demonstrate convergence properties of the FEM scheme and discuss how the time taken to solve the system scales with tissue size. The model is applied to biological systems and its utility demonstrated in several contexts. We show that when growth is dependent on morphogen concentration in the Drosophila wing disc, proliferation occurs preferentially in regions of high concentration. In the Drosophila epidermis, we show that a recently proposed mechanism of compartment size-control, in which a growth-factor is released in limited amounts, is viable. Finally, we examine the phenomenon of rosettes in the mouse embryo, which occur when five or more cells meet at a common vertex. We show, by running simulations both with and without rosettes, that they are crucial facilitators of ordered migration, and are thus critical in the patterning of the early embryo.

The high-throughput technologies developed in the last decade have revolutionized the speed of data accumulation in the life sciences. As a result we have very rich and complex data that holds great promise to solving many complex biological questions. One such technology that is very well established and widespread is DNA microarrays, which allows one to simultaneously measure the expression levels of tens of thousands of genes in a biological tissue. This thesis aims to contribute to the development of statistics that allow the end users to obtain robust and meaningful results from DNA microarrays for further investigation. The methodology, implementation and pragmatic issues of two important and related topics – sample size estimations for designing new studies and meta-analysis of existing studies – are presented here to achieve this aim. Real life case studies and guided steps are also given. Sample size estimation is important at the design stage to ensure a study has sufficient statistical power to address the stated objective given the financial constraints. The commonly used formula for estimating the number of biological samples, its short-comings and potential amelioration are discussed. The optimal number of biological samples and number of measurements per sample that minimizes the cost is also presented. Meta-analysis or the synthesis of information from existing studies is very attractive because it can increase the statistical power by making comprehensive and inexpensive use of available information. Furthermore, one can also easily test the generalizability of findings (i.e. the extent of results from a particular valid study can be applied to other circumstances). The key issues in conducting a meta-analysis for microarrays studies, a checklist and R codes are presented here. Finally, the poor availability of raw data in microarray studies is discussed here with recommendations for authors, journal editors and funding bodies. Good availability of data is important for meta-analysis in order to avoid biased results and for sample size estimation.

Human Artificial Chromosomes (HACs) have been confirmed as viable gene expression vectors and a potential tool for gene therapy. However, standard lipid-based delivery methods pose a developmental barrier. The work presented in this thesis includes the development of a novel and efficient HAC vector system for gene delivery into human cells using Herpes Simplex Virus-1 (HSV-1) amplicon technology. The development of HSV-1 amplicons for HAC delivery is a major step forward in the HAC field. In this study, utilising the technology allowed the generation of HACs at a high efficiency in a range of human cell types, which is a significant step in the development for HAC gene expression systems. Further work also showed a significant difference in HAC stability between cell lines. Real-time PCR analysis determined that Aurora B was over expressed in cell lines in which the HACs were unstable. This correlated with high levels of chromosomal instability and was confirmed by western blot analysis. Since Aurora B is a kinase involved in at least two cell cycle checkpoints, cellular phosphorylation levels were perturbed to mimic that observed in the unstable cells, using okadaic acid, which is both a protein phosphatase inhibitor and activates Aurora B. Treatment of cells showed an increase in both HAC and overall chromosomal instability and an increase in histone H3 Serine 10 and Serine 28 phosphorylation. The project also focussed on the development of a gene expression system using HSV-1 amplicons. Two different strategies were explored. Firstly, one approach involved engineering the HPRT genomic locus into an HSV-HAC vector, by Red mediated recombination for complementing the HPRT deficiency in HPRT- HT1080 cells. As an alternative approach, co-infection of two different HSV-1 HAC amplicons for generating a single HAC gene vector was investigated. Initial experiments utilising the latter approach were the most successful and show promise for generating HAC containing genes via this strategy.

Africa's miombo woodlands constitute one of the most important dry tropical forests on earth, yet the hydraulic function of these woodlands remains poorly researched. Given the current predictions of increased aridity by the end of this century in the miombo ecoregion, understanding the likely response of miombo woodlands tree species to water stress is crucial in planning adaptation strategies. Predicting the response of miombo woodlands to future climate trends is hampered by a lack of knowledge on the physiology of the common miombo woodlands tree species. In particular, plant-water relations for this woodlands type are not well understood. An understanding of plant-water relations for this woodlands type will provide insights into how water limits tree species distribution in this ecosystem. This will also improve our prediction model on the likely response of this ecosystem to predicted climate change. For this reason, the overall objective of this research was to evaluate the hydraulic architecture and xylem vulnerability to cavitation for nine principal miombo woodlands tree species differing in drought tolerance ability and habitat preference. This was achieved by; examining the hydraulic properties and evaluating the extent to which each hydraulic design was vulnerable to water stress-induced xylem cavitation; investigating how seasonal changes in plant-water relations influences seasonal patterns of leaf display and; analyzing the relationship between stem hydraulic supply and leaf functional traits related to drought tolerance ability. This research has found that drought-intolerant tree species with mesic specialization have more efficient stem hydraulic systems than co-occurring habitat broad ranging species. Broad ranging tree species attain wider habitat distribution by adjusting their hydraulic supply in response to changing ecosystem water availability. The finding that hydraulic properties differ significantly between tree species with contrasting habitat preference suggests that tree hydraulic design may have some adaptive ecological role in influencing species habitat preferences in miombo woodlands. The evaluation of xylem vulnerability to cavitation revealed that mesic specialized tree species were more vulnerable to water stress-induced cavitation than habitat broad ranging tree species. Vulnerability to cavitation in individuals from the same broad-ranging species growing in contrasting habitats showed only marginal and statistically insignificant (P > 0.05) differences between wet and dry sites. In the investigation of the influence of seasonal changes in stem water relations on seasonal leaf display, seasonal rhythms in stem water status were found to exert significant controls on leaf phenology. Mesic specialists had strong stem water controls throughout the year in comparison to broad ranging tree species. An analysis of the relationship between stem hydraulic supply and leaf functional traits suggests that stem hydraulic supply constrains leaf biomass allocation patterns among miombo tree species. Mesic specialists tend to invest more in leaf longevity than broad ranging tree species. This thesis has uncovered some interesting relationships between plant-water-relations and the distribution of miombo woodlands tree species. These results lead to the conclusion that in an event of increased ecosystem drying under future climate trends, tree species with mesic specialisation are at a greater risk of experiencing cavitation related species mortality than broad ranging ones.

Among the most compelling and least well-understood tree species growing in the temperate forests of southern South America is Fitzroya cupressoides, a high biomass species and the second longest-lived tree species in the world. This thesis quantified the main components of the carbon cycle in Fitzroya forests (i.e. net primary productivity (NPP) and soil respiration) and evaluated the environmental variables that are most related to them. The study was focused on medium-age and old-growth forests growing in the Coastal Range (Alerce Costero National Park, AC) and the Andean Cordillera (Alerce Andino National Park, AA) of southern Chile, respectively. The specific objectives of this thesis were to: 1) assess the forest structure, species composition and characterise the environmental conditions of these forests; 2) assess biomass, aboveground NPP, carbon allocation and mean wood residence time in these forests; 3) assess soil respiration and relate it to soil environmental conditions. Additionally, to use a mass balance approach to estimate fine root productivity; 4) estimate total NPP using biometric and indirect estimates of productivity; 5) evaluate the climatic factors mainly related to Fitzroya stem radial change on an intra-annual basis; and 6) evaluate changes in Fitzroya's tree growth and carbon isotopes during recent decades, and determine which environmental factors are more related to them. The last two objectives focus on Fitzroya as the dominant species and the subject of this study. Two 0.6 ha plots were installed within each national park; NPP was estimated for a year and soil respiration and high resolution stem growth measurements were monitored over almost two years. Aboveground biomass estimates for the Andean site are among the most massive reported in the world and carbon fluxes in Fitzroya forests are among the lowest reported for temperate wet forests worldwide. The longevity as well as the particularly rainy and nutrient poor soil conditions where these ecosystems grow may influence their exceptionally slow carbon dynamics. Differences in carbon fluxes between sites seem most probably driven by different environmental conditions rather than by developmental stage. Moreover, carbon fluxes were more sensitive to interannual climate variability in AC than AA. Warmer and drier summer conditions, likely to become more common under future climate change, more significantly affected stem growth and soil respiration in the Coastal Range than in the Andes. Regarding long-term changes, tree growth has been decreasing in the coastal site in the last 40 years and increasing in the Andes since the 1900s. These trends have been accompanied by an increase in intrinsic water use efficiency which is likely caused by rises in CO₂ and changes in climate conditions in both sites. Although Fitzroya grows in particularly wet and cool areas, projected drier and warmer conditions may have a negative effect on Fitzroya stem growth and carbon sequestration in both study sites. This effect would be more critical in the Coastal Range though, because of its more Mediterranean climate influence and more restrictive soil conditions in this area. Adequate resources are needed for the monitoring and conservation of these slow growth and massive forests especially in the Coastal Range, in order to avoid ongoing illegal cuttings and threatening forest fires.

This thesis examines the role of international organizations (IOs) at the domestic level. While International Relations (IR) offers an extensive literature on IOs, with understandings of IOs ranging from instruments of states to autonomous actors, it tends to ignore the role of IOs working at the domestic level, with an 'on-the-ground' presence of their own, and what this means for the IO's relationship with the state. The thesis develops a heuristic framework for understanding what is called IO 'domestication', which outlines a range of ways an IO can work domestically. It then focuses on one type domestication in particular: surrogate statehood, or cases where an IO substitutes for the state by providing services, executing functions of governance, and assuming authority in a given locale. The framework identifies indicators of surrogacy, the conditions for IO surrogacy, and reasons why it is sustained. It also considers the various types of relationship that can emerge from IO surrogacy between the IO and the state, ranging from states that willingly choose to abdicate responsibility to the IO, to states that partner with the IO. Empirically, the thesis examines these relationships through the case studies of the United Nations High Commissioner for Refugees (UNHCR) in Kenya, Tanzania and Uganda, which present a spectrum of UNHCR’s surrogacy over time. Ultimately, the thesis puts forth a counterintuitive claim: IOs that take on surrogate state properties actually have less influence on the states in which they are working. The analysis draws on two mechanisms to help explain this outcome: marginalisation of the state, and responsibility shifting.

Precise regulation of cell cycle events by the Cdk-control network is essential for cell proliferation and the perpetuation of life. The unidirectionality of cell cycle progression is governed by several critical irreversible transitions: the G1-to-S transition, the G2-to-M transition, and the M-to-G1 transition. Recent experimental and theoretical evidence has pulled into question the consensus view that irreversible protein degradation causes the irreversibility of those transitions. A new view has started to emerge, which explains the irreversibility of cell cycle transitions as a consequence of systems-level feedback rather than of proteolysis. This thesis applies mathematical modelling approaches to test this proposal for the Mto- G1 transition, which consists of two consecutive irreversible substeps: the metaphase-to-anaphase transition, and mitotic exit. The main objectives of the present work were: (i) to develop deterministic models to identify the essential molecular feedback loops and to examine their roles in the irreversibility of the M-to-G1 transition; (ii) to present a straightforward and reliable workflow to translate deterministic models of reaction networks into stochastic models; (iii) to explore the effects of noise on the cell cycle transitions using stochastic models, and to compare the deterministic and the stochastic approaches. In the first part of this thesis, I constructed a simplified deterministic model of the metaphase-to-anaphase transition, which is mainly regulated by the spindle assembly checkpoint (the SAC). Based on the essential feedback loops causing the bistability of the transition, this deterministic model provides explanations for three open questions regarding the SAC: Why is the SAC not reactivated when the kinetochore tension decreases to zero at anaphase onset? How can a single unattached kinetochore keep the SAC active? How is the synchronized and abrupt destruction of cohesin triggered? This deterministic model was then translated into a stochastic model of the SAC by treating the kinetochore microtubule attachment at prometaphase as a noisy process. The stochastic model was analyzed and simulation results were compared to the experimental data, with the aim of explaining the mitotic timing regulation by the SAC. Our model works remarkably well in qualitatively explaining experimental key findings and also makes testable predictions for different cell lines with very different number of chromosomes. The noise generated from the chemical interactions was found to only perturb the transit timing of the mitotic events, but not their ultimate outcomes: all cells eventually undergo anaphase, however, the time required to satisfy the SAC differs between cells due to stochastic effects. In the second part of the thesis, stochastic models of mitotic exit were created for two model organisms, budding yeast and mammalian cells. I analyzed the role of noise in mitotic exit at both the single-cell and the population level. Stochastic time series simulations of the models are able to explain the phenomenon of reversible mitotic exit, which is observed under specific experimental conditions in both model organisms. In spite of the fact that the detailed molecular networks of mitotic exit are very different in budding yeast and mammalian cells, their dynamic properties are similar. Importantly, bistability of the transitions is successfully captured also in the stochastic models. This work strongly supports the hypothesis that uni-directional cell cycle progression is a consequence of systems-level feedback in the cell cycle control system. Systems-level feedback creates alternative steady states, which allows cells to accomplish irreversible transitions, such as the M-to-G1 transition studied here. We demonstrate that stochastic models can serve as powerful tools to capture and study the heterogeneity of dynamical features among individual cells. In this way, stochastic simulations not only complement the deterministic approach, but also help to obtain a better understanding of mechanistic aspects. We argue that the effects of noise and the potential needs for stochastic simulations should not be overlooked in studying dynamic features of biological systems.