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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Investigation of cytochrome p450 isoforms 1A1, 1B1 and 2W1 as targets for therapeutic intervention in head and neck cancer. Probing CYP1A1, 1B1 and 2W1 activity with duocarmycin bioprecursorsCytochrome P450 enzymes such as CYP1A1 and CYP2W1 have been shown to be overexpressed in tumour tissue compared to surrounding normal tissue, providing an opportunity to develop targeted therapies. Recent studies have shown that re-engineered duocarmycins can be activated selectively by cancer cells expressing CYP1A1 and/or CYP2W1 to potent cytotoxins that damage DNA. This study aimed to explore CYP expression in HNC tissue, and link CYP1A1, 1B1 and 2W1 expression with capacity to bioactivate duocarmycin bioprecursors. A panel of HNC cell lines was investigated for CYP gene expression using Real Time PCR (RT-PCR), and protein expression by Western blot and/or immunofluorescence. The cell lines were also evaluated for anti proliferative activity using lead duocarmycin bioprecursor compounds (ICT2700, ICT2706 and ICT2726) and novel analogues. Various levels of mRNA expression were observed for CYP1A1 and 1B1, but not for CYP2W1, which was only detected at very low levels, contrasting with the moderate-to high CYP2W1 expression found in clinical tissues and xenografts. FaDu and Detroit-562 were identified as sensitive cell lines to several duocarmycins, and hence useful for assessing compound activity. Two novel compounds, ICT2700S and ICT11003, were shown to be the most potent duocarmycins evaluated in FaDu and Detroit-562, which primarily expressed CYP1A1. Using the comet assay and γH2AX, ICT2700S cytotoxic activity was correlated with DNA single-strand breaks (SSBs) and double-strand breaks (DSBs), while one benzofuran-based duocarmycin (ICT2724) was shown to cause more inter stand crosslinks (ICLs). The significance of target CYP expression and compound activity warrants further investigations in preclinical models to ascertain the clinical potential of duocarmycin-based bioprecursors.
Emerging markets from a multidisciplinary perspective: challenges, opportunities and research agendaThis book examines prominent issues in the Emerging Markets (EM) from a variety of disciplines in order to make useful societal contributions through knowledge exchange. EMs offer enormous opportunities, but realizing them is both challenging and risky due to inherent uncertainties of such markets. EM’s also have unique characteristics that makes them different from developed countries. This causes implications for both theory and practice. These markets necessitate substantial adaptations of developed theories and approaches employed in the Western world. This book investigates problems specific to emerging markets, and identifies new theoretical constructs, hypotheses (re)development, and emphasizes institutional contexts. The chapters in this book establish new conceptual and theoretical paradigms from multidisciplinary perspectives concentrated in the areas of information systems, electronic government, and digital and social media matters. The book focuses on topics in these areas such as digital enterprises, sustainability, telemedicine, and Information Communication Technology (ICT) and surveys the potential challenges and opportunities that may arise. These concepts and topics covered in this book are vital for making the global economy more equitable and sustainable.
Glycosyl disulfides: importance, synthesis and application to chemical and biological systemsThe disulfide bond plays an important role in the formation and stabilisation of higher order structures of peptides and proteins, while in recent years interest in this functional group has been extended to carbohydrate chemistry. Rarely found in nature, glycosyl disulfides have attracted significant attention as glycomimetics, with wide biological applications including lectin binding, as key components of dynamic libraries to study carbohydrate structures, the study of metabolic and enzymatic studies, and even as potential drug molecules. This interest has been accompanied and fuelled by the continuous development of new methods to construct the disulfide bond at the anomeric centre. Glycosyl disulfides have also been exploited as versatile intermediates in carbohydrate synthesis, particularly as glycosyl donors. This review focuses on the importance of the disulfide bond in glycobiology and in chemistry, evaluating the different methods available to synthesise glycosyl disulfides. Furthermore, we review the role of glycosyl disulfides as intermediates and/or glycosyl donors for the synthesis of neoglycoproteins and oligosaccharides, before finally considering examples of how this important class of carbohydrates have made an impact in biological and therapeutic contexts.
From ‘touch’ to a ‘multisensory’ experience: The impact of technology interface and product type on consumer responsesOnline retailers are increasingly using augmented reality (AR) and virtual reality (VR) technologies to solve mental and physical intangibility issues in a product evaluation. Moreover, the technologies are easily available and accessible to consumers via their smartphones. The authors conducted three experiments to examine consumer responses to technology interfaces (AR/VR and mobile apps) for hedonic and utilitarian products. The results show that AR is easier to use (vs. app), and users find AR more responsive when buying a hedonic (vs. utilitarian) product. Touch interface users are likely to have a more satisfying experience and greater recommendation intentions, as compared to AR, for buying utilitarian products. In contrast, a multisensory environment (AR) results in a better user experience for purchasing a hedonic product. Moreover, multisensory technologies lead to higher visual appeal, emotional appeal, and purchase intentions. The research contributes to the literature on computer-mediated interactions in a multisensory environment and proposes actionable recommendations to online marketers.
Technological innovation, organizational innovation and international performance of SMEs: The moderating role of domestic institutional environmentDespite the growing research on the performance implications of technological and organizational innovation, our understanding of how they impact SMEs’ international performance is limited. Drawing from the dynamic capability and the institutional theories, this study argues that technological and organizational innovation has a synergistic effect on international performance and that this effect is contingent on unique domestic institutional factors. We test this model using structural equation modeling on a sample of 204 internationalized SMEs operating in Ghana. The findings from the analysis show that high levels of organizational and technological innovation jointly improve SMEs’ international performance. In addition, the results show that institutional environment specificity and institutional environment enforceability enhance the complementary effect of organizational and technological innovation on the international performance of SMEs. The theoretical and managerial implications of the findings are discussed.