Bradford Scholars

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.

Contact the repository team via openaccess@bradford.ac.uk with any queries about Open Access or how to deposit your research papers.

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  • PublicationMetadata only
    Parametric design of aircraft geometry using partial differential equations
    (Elsevier, 2009) Athanasopoulos, Michael; Ugail, Hassan; Gonzalez Castro, Gabriela
    This paper presents a surface generation tool designed for the construction of aircraft geometry. The software generates complex geometries which can be crafted or modified by the user in real time. The surface generation is based on partial differential equations (PDEs). The PDE method can produce different configurations of aircraft shapes interactively. Each surface is generated by a number of curves representing the character lines of a given part of the aircraft shape that can be manipulated in real time. Different surfaces then blend to create the full shape of the airplane. An important function of the proposed tool is its ability to change the aircraft shape through the adjustments of parameters associated with the initial curves. The user can apply linear transformations to the curves generating the airplane through simple input from the computer keyboard and the mouse. The updated curves can then be used to generate the surface leading to different configurations of a given airplane shape. The work presents detailed descriptions on the PDE method, parametric design and manipulation of aircrafts along with graphical demonstrations of its abilities and a series of examples to illustrate the capacity of the methodology implemented.
  • PublicationOpen Access
    Hypoxia modulates CCR7 expression in head and neck cancers
    (2018-05) Basheer, Haneen A.; Pakanavicius, E.; Cooper, Patricia; Shnyder, Steven; Martin, L.; Hunter, K.D.; Vinader, Victoria; Afarinkia, Kamyar
    The chemokine receptor CCR7 is expressed on lymphocytes and dendritic cells and is responsible for trafficking of these cells in and out of secondary lymphoid organs. It has recently been shown that CCR7 expression is elevated in a number of cancers, including head and neck cancers, and that its expression correlates to lymph node (LN) metastasis. However, little is known about the factors that can induce CCR7 expression in head and neck cancers. We compared the protein expression and functional responses of CCR7 under normoxia and hypoxia in head and neck cancer cell lines OSC-19, FaDu, SCC-4, A-253 and Detroit-562 cultured as monolayers, spheroids, and grown in vivo as xenografts in balb/c mice. In addition, we analysed the correlation between hypoxia marker HIF-1α and CCR7 expression in a tissue microarray comprising 80 clinical samples with various stages and grades of malignant tumour and normal tissue. Under hypoxia, the expression of CCR7 is elevated in both in vitro and in vivo models. Furthermore, in malignant tissue, a correlation is observed between hypoxia marker HIF-1α and CCR7 across all clinical stages. This correlation is also strong in early histological grade of tumours. Hypoxia plays a role in the regulation of the expression of CCR7 and it may contribute to the development of a metastatic phenotype in head and neck cancers through this axis.
  • PublicationOpen Access
    Sidechain structure-activity relationships of cyclobutane-based small molecule αvβ3 antagonists
    (2024-09) Throup, Adam E.; Zraikat, Manar Saleh Ali; Gordon, Andrew; Soumehsaraei, Shohreh J.; Haase, K.D.; Patterson, Laurence H.; Cooper, Patricia; Hanlon, K.; Loadman, Paul; Sutherland, Mark; Shnyder, Steven; Sheldrake, Helen
    The integrin family of cell surface extracellular matrix binding proteins are key to several physiological processes involved in tissue development, as well as cancer proliferation and dissemination. They are therefore attractive targets for drug discovery with cancer and non-cancer applications. We have developed a new integrin antagonist chemotype incorporating a functionalised cyclobutane ring as the central scaffold in an arginine–glycine–aspartic acid mimetic structure. Here, we report the synthesis of cyclobutanecarboxylic acids and cyclobutylamines with tetrahydronaphthyridine and aminopyridine arginine mimetic sidechains and masked carboxylic acid aspartic acid mimetic sidechains of varying length. Effective αvβ3 antagonists and new aspartic acid mimetics were identified in cell-based adhesion and invasion assays. A lead compound selected based on in vitro activity (IC50 < 1 μM), stability (t1/2 > 80 minutes) and synthetic tractability was well-tolerated in vivo. These results show the promise of this synthetic approach for developing αvβ3 antagonists and provide a firm foundation to progress into advanced preclinical evaluation prior to progression towards the clinic. Additionally, they highlight the use of functionalised cyclobutanes as metabolically stable core structures and a straightforward and robust method for their synthesis. This important contribution to the medicinal chemists' toolbox paves the way for increased use of cyclobutanes in drug discovery.
  • PublicationOpen Access
    Preclinical anti-cancer activity and multiple mechanisms of action of a cationic silver complex bearing N-heterocyclic carbene ligands
    (2017-09) Allison, Simon J.; Sadiq, Maria; Baronou, Efstathia; Cooper, Patricia; Dunnill, C.; Georgopoulos, N.T.; Latif, A.; Shepherd, S.L.; Shnyder, Steven; Stratford, I.J.; Wheelhouse, Richard; Willans, C.; Phillips, Roger M.
    Organometallic complexes offer the prospect of targeting multiple pathways that are important in cancer biology. Here, the preclinical activity and mechanism(s) of action of a silver-bis(N-heterocyclic carbine) complex (Ag8) were evaluated. Ag8 induced DNA damage via several mechanisms including topoisomerase I/II and thioredoxin reductase inhibition and induction of reactive oxygen species. DNA damage induction was consistent with cytotoxicity observed against proliferating cells and Ag8 induced cell death by apoptosis. Ag8 also inhibited DNA repair enzyme PARP1, showed preferential activity against cisplatin resistant A2780 cells and potentiated the activity of temozolomide. Ag8 was substantially less active against non-proliferating non-cancer cells and selectively inhibited glycolysis in cancer cells. Ag8 also induced significant anti-tumour effects against cells implanted intraperitoneally in hollow fibres but lacked activity against hollow fibres implanted subcutaneously. Thus, Ag8 targets multiple pathways of importance in cancer biology, is less active against non-cancer cells and shows activity in vivo in a loco-regional setting.
  • PublicationOpen Access
    Parametric Representations of Facial Expressions on PDE-Based Surfaces
    (2008) Gonzalez Castro, Gabriela; Ugail, Hassan; Willis, P.; Sheng, Y.
    Parameterisation of facial expressions on PDE surface representations of human faces are presented in this work. Taking advantage of the boundary-value approach inherent to Bloor-Wilson PDE method, facial expressions are achieved by manipulating the original boundary curves. Such curves are responsible for generating a surface representation of a human face in its neutral configuration, so that regions on these curves represent a given facial expression in a fast and realistic manner. Additionally, the parameterisation proposed here is carried out by applying different mathematical transformations to the affected curves according to the corresponding facial expression. Full analytic expressions parameterising some of the most common facial expressions such as smiling and eyebrow raising are in this work. Some graphical examples of these facial expressions are used to illustrate the results obtained using Bloor-Wilson PDE method as the foundations of the parameterisation scheme proposed here. Thus, it is shown that an efficient, intuitive and realistic parameterisation of facial expressions is attainable using Bloor-Wilson PDE method in along with a suitable mathematical expression.
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