Bradford Scholars is the University of Bradford online research archive. Access is free to anyone interested in research being conducted at Bradford. In the repository you will find a range of materials from journal articles and conference papers to research reports and theses.
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Pathways to public life for professional women in Afghanistan: Negotiating shifting patriarchal political regimes and gender regimesThis thesis examines how Afghan women from the professional social class have negotiated the patriarchy in that country and claimed their agency and public life during different political regimes. Resisting the Western representation of Afghan women as passive victims, it uses the life story method, based on interviews with a wide range of women in public life during the period of US-sponsored democracy and intervention, to analyse the complex factors involved in enabling women to access public life. From a historical sociological viewpoint it examines the shifts in the forms of patriarchy and their sustaining gender regimes from 19th century to the present, and draws on Walby’s six structures of patriarchy in order to understand how those shift affected the ability of women to access public life and employment. Those structures – culture, religion, education, employment, family – are explored through the experiences and life histories of my interviewees. The thesis also pays attention to the involvement of external, foreign actors in the affairs of Afghanistan and the impact of those interventions on the possibility for women’s agency and participation in professional and public life through different political regimes. It thus challenges a simplistic view 9/11 was a water-shed moment for women’s empowerment, and notes that the economic is-sues, an aid-dependent economy and political regimes, security and safety, poverty and psychological trauma, corruption and power struggles among different forces (local and foreign) in many ways undermined women’s prospects in public life. The finding of the research shows that the rights and position of women in Afghanistan have fluctuated over the last 100 years depending on the patriarchal cultural, political and religious ideology and practice of the political regimes, and in no small part due to the influence and interference of external actors in the country.
Microscopic Sampling of Dentine and Bone Collagen: Development of Sampling Methods for Carbon and Nitrogen Isotope AnalysisSampling methods for dentine and bone collagen have been evolving for several decades. Incremental dentine collagen sampling and bone collagen sampling have been limited by the available technology throughout that time. As the technology for isotope ratio mass spectrometry analysis improves, the sampling methods should improve as well. This research focused on developing a new incremental dentine collagen sampling method and bone collagen microsampling method for stable isotope analysis. This research aimed to increase the temporal resolution of incremental dentine collagen sampling and provided sequential collagen sampling from bone collagen for stable carbon and nitrogen isotope analysis while limiting the destructive nature of bioarchaeological analysis. It was determined that the temporal resolution for incremental analysis could be reduced to approximate three months, opposed to the nine months found in other sampling methods. It was also determined that detailed isotopic data could be obtained from bone collagen when sampling the microstructures. The increased amount of isotopic data from the bone collagen was an improvement on the commonly used bulk collagen sampling. This research can be utilised to answer several of the questions that archaeologists have been asking about past populations. Isotopic analysis using the methods developed in the research can provide a more detailed observation of the diet and health of past populations. In addition, the developed methods for bone and dentine collagen reduced the amount of tissue subjected to destructive analysis.
Role of N-terminal residues of CCL19 and CCL21 in binding and activation of CCR7Chemokines are chemotactic cytokines, which mediate cell trafficking and play a key role in mobilisation of leukocytes. More recently, chemokines and their cognate receptors have been described as key players in different aspects of cancer biology contributing to proliferation, angiogenesis and metastasis. In particular, chemokines CCL19 and CCL21 acting on their associated receptor CCR7 are postulated to be key drivers of lymph node metastasis in a number of malignancies including breast, colon, gastric, & thyroid cancers. It has been reported that the cleavage of the pre-cysteine bridge N-terminal residues of CCL21 (SDGGAQD) and of CCL19 (GTNDAED) renders both peptides incapable of fully activating CCR7. However, little is known about the nature of the interactions that occur between the N-terminal residues of CCL19 or CCL21 and the CCR7 receptor, or the role they have in activation of CCR7. The aim of this study is to investigate the role of the residues in the N-terminus of CCL19 and in particular CCL21 in the context of CCR7 activation and to use this information in the discovery of novel CCR7 antagonists or agonists. To achieve this, we synthesised a number of short (three to seven amino acids) peptides and peptidomimetics inspired by the seven N-terminal amino acid residues of CCL19 and CCL21 and pharmacologically characterised their ability to activate CCR7 or block the activation of CCR7 using a number of in vitro assays such as calcium flux, trans-well (Boyden chamber), and Western blotting. We also carried out computational studies to better understand and predict the activity of these peptides. Our results demonstrate that some of these peptides are indeed capable of acting as agonists or antagonists of CCR7.
Crystal Engineering of Pharmaceuticals: Modulating Physicochemical Properties of Active Ingredients by the Formation of CocrystalsPharmaceuticals with suitable therapeutic properties often found to encounter challenges with dosage form development due to their poor physicochemical properties. Aim of thesis is to evaluate potential of crystal engineering directed cocrystallisation of active ingredients in modulating their physical attributes. The model compounds considered are isoniazid, caffeine, nifedipine, glyburide, chlorpropamide and riboflavin. Co-formers selected are based on the suitability of functional groups for hydrogen bond formation. Co-crystal screening and preparation methods used include neat grinding (NG), liquid assisted grinding (LAG) and solution crystallisation. Antituberculosis drug, isoniazid, upon cocrystallisation with melamine, solubility has reduced as per high performance liquid chromatography assay, however, antimicrobial properties determined using REMA assay confirms that cocrystal anti-mycobacterial activity is not compromised. Next, caffeine-glutaric acid cocrystal polymorphic forms (Forms I and II) subjected to mechanical property evaluations in multiple faces using nanoindentation and correlated relationship between crystal structure and mechanical property. The results suggest that metastable form, Form I, could display suitable tablet properties to that of thermodynamically stable form, Form II. Subsequently, photosensitive drug, nifedipine, cocrystallised with theophylline and caffeine. Notably, photochemical stability along with solubility and drug release of cocrystals is found to be superior to that of nifedipine. Lastly, crystal engineering principles utilised in preparation of multicomponent crystals of antidiabetic model drugs, glyburide and chlorpropamide with various coformers. Interestingly, during the preparation of chlorpropamide-2-nitrobenzyl alcohol, high Z prime crystal (Z’=3) of 2- nitrobenzyl alcohol is serendipitously identified. In conclusion, crystal engineering based cocrystallisation is a viable technology for modulating physicochemical properties of pharma and nutraceuticals.
En face OCT imaging for the assessment of glaucomaGlaucoma is a leading cause of irreversible vision loss globally, and demands early and accurate diagnosis. OCT has become a key investigative technique in glaucoma, and, although it provides invaluable clinical support, detection of early glaucoma remains imperfect. Recent OCT developments enabled direct assessment of retinal nerve fibre bundle (RNFB) reflectance in en face OCT images. The technique has considerable potential in the assessment of glaucoma, yet it has limited clinical usability due to an incomplete understanding of RNFB features in healthy and glaucoma eyes and the lack of accepted methods to identify reflectance defects. This thesis aimed to better understand characteristics of RNFB reflectance in en face OCT imaging and to develop objective methods to extract defects in this domain. Structural and functional measures of glaucoma changes were collected in eyes with established glaucoma and age-similar controls. Results showed that the healthy configuration of RNFB varies across the retina and between different eyes. We developed a method for automated and objective examination of reflectivity changes in en face images. This method considers individual anatomy and varying RNFB configuration, and found more abnormalities than previous approaches. Measures of en face reflectance and conventional retinal nerve fibre layer thickness were strongly related. The agreement between changes of reflectance and visual function was moderate-to-good, and both testing domains presented concordant abnormalities in all tested eyes. Following further minimisation of artefacts in en face images, direct use of reflectance analysis or its combination with perimetry appear viable and with significant potential for clinical examination of glaucoma.