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Solid-state nuclear magnetic resonance (ssNMR) has proved to be a useful tool in the analysis of structural and dynamic properties of proteins. However, the inherent low sensitivity of NMR hinders further advancements of the field. This thesis focuses on improving the sensitivity of ssNMR, be this through an improvement in signal to noise or an effective improvement in sensitivity by enhancing the information content. The mixed rotational and rotary resonance (MIRROR) sequence1 was employed to facilitate protein backbone assignment under moderate spinning speeds. Through the band selective nature of MIRROR, bidirectional transfer of magnetisation from the CCO site to the adjacent Cα and to the Cα of the next amino acid is possible. When applied to a 3D-NCOCA experiment this may be used to double the information content, providing correlations from CCO(i-1) to both Cα(i-1) and Cα(i). The MIRROR recoupling of CCO to Cα, is inherently low-power, allowing MIRROR to be utilised in a low-power experiment. Through this, greater enhancements in sensitivity per unit time can be realised. The longitudinal relaxation time (T1) limits the sensitivity per unit time at both room and cryogenic temperatures. To develop the use of relaxation agents for cryogenic NMR experiments, the room temperature relaxation properties and dynamics of the model protein, GB3, were explored. Site-specific relaxation measurements were used to understand the relaxation of residues in the protein and gain understanding into how this relates to the dynamics of the protein. In addition, low-temperature NMR measurements were used to investigate the effect temperature has on relaxation. The ongoing development of polarisation enhancement methods and machinery have made great progress in recent years particularly on the application towards biomolecules. However, arguably the most promising polarisation enhancement technique, dynamic nuclear polarisation (DNP) suffers from a variety of problems. Namely, line broadening effects as a result of the low-temperatures required and through doping with paramagnetic agents. Furthermore, the current method of sample preparation for DNP via the use of doping with exogenous radicals is not viable for all samples. Endogenous radicals for the DNP of large biomolecules may offer several advantages to their exogenous counterparts, including but not limited to, a greater understanding of quenching effects and polarisation transfer. This thesis explores the possibility of creating pseudo-biradicals bound covalently to a protein surface to elicit enhancements through the cross effect DNP mechanism. In summary, we have developed a range of methods that enhance the information content and sensitivity, which will provide new approaches for researchers investigating proteins using ssNMR.

3'-Thiopurine 2'-deoxynucleosides have been incorporated into model oligodeoxynucleotides (DONs) thus giving rise to ODNs that consist of the 3- S-phosporothiolate (3'-sp) linkage. Due to the complex chemical manipulations implicated, the preparation of such analogues has been scarcely explored to date. The 3'-thiopurine nucleosides were prepared prior to incorporation into the desired DON sequences by traditional automated 3'---+5' solid-phase phosporamidite chemistry. Two different strategies, one involving neighbouring group participation and the other an in situ oxidation-reduction, were successfully applied for the key C3' epimerisation in deoxyadenosine and deoxyguanosine, respectively. Subsequent UV denaturation studies revealed that the destabilisation effect recorded in DNA/DNA duplexes consisting of a single 3'-sp modified residue on one strand was diminished when more 3'-sp modified residues were incorporated. The destabilisation is expected on the basis that the sugars on the 3'-sp modified and neighbouring residues predominantly adopt the RNA-like North conformation. A surprising stabilisation effect was, moreover, observed for DNA/RNA hybrids containing 3'-sp modifications in the RNA strand. Additionally, when 3'-sp modifications were incorporated into both strands of the homo- or hetero-duplexes, an additive effect was generally exhibited. UV denaturation studies revealed a significant position specific 3'-sp substitution effect when incorporated into G-quadruplexes; the thermal stability of the tetramolecular complex was significantly increased when either of the two central guanines in the G-tract of the sequence was modified. A clear position-dependent substitution effect on the rate of association of the quadruplex was also observed, however, no correlation between the kinetics of association and the recorded thermal stability was realised.

This thesis consists of three parts. In the first part, we review the literature and some of the key issues in UK transport. We identify a need to discourage car use and the role that public transport plays in this. We discuss the various options available to policymakers to reduce problems of congestion and pollution. We note how the emphasis on deregulation and competition to promote public transport, and discourage car use, have had perverse side effects. In some cases, public transport services have become disintegrated; resulting in reductions in flexibility and increasing the generalised cost of travelling – making public transport less attractive. This raises an important question: how do we encourage a greater degree of service integration without undoing the gains from competition? The second part of the thesis, explores this issue using a theoretical transport network model. We find that various regimes involving private firms are likely to lead to the provision of an integrated ticketing system, but that not all such regimes are socially desirable. We consider how the configuration of regulatory policy may steer the private firms to produce more socially desirable outcomes. The deregulation of elements of the UK public transport network has often led to situations approaching local monopoly. The third part of this thesis investigates the private (monopoly) incentive to offer joined-up services relative to the social incentive. The more complete the service provision, the closer the match with consumer’s preferences, and the lower the generalised cost of travel. We find the monopolist does not always choose the socially desirable level of service, even when economically viable, but it may be possible to induce this provision through entry or threats of entry on a sub-set of the network. The thesis ends with a summary of the main results and suggestions for further work.

Environmental degradation from problems of the 'Brown Agenda' is an everyday reality in Kenya's rapidly growing urban centres; and it is the low-income majority who are most affected. Deficient water supply and sanitation, inadequate solid waste disposal, and poor drainage are among the foremost problems that characterize informal settlements in which indigent urbanites are compelled to live. Analysis of environmental problems at settlement and household level can provide vital information about the appraisive environmental perceptions and cognitions of inhabitants of informal settlements, as well as their satisfaction with the infrastructural services to which they have access and their housing conditions, in general. Such information is essential to the formulation of apposite strategies for sustainable improvement of environmental conditions in informal settlements. Based largely on a comprehensive review of theoretical perspectives on the urban housing question in the South, international policy responses and experiences with settlement upgrading, this thesis seeks a better understanding of the socioeconomic and physio-environmental dynamics of urban low-income informal settlements and the formulation and implementation of upgrading policies. A comparative analysis of two majengos in Kenya-one of which has been upgraded while the other has not-serves to contextualize the study. The central thesis in the present study is that settlement upgrading is the most rational approach to improving the residential circumstances of the urban poor majority in Kenya. Applying a fundamentally liberal approach, the development of pragmatic opportunities is discussed, and pursuable policies and programmes, which are realistic and implementable, for effective environmental planning and management of urban low-income informal settlements in Kenya are proposed.