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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An in-core grid index for transferring finite element data across dissimilar meshesThe simulation of a manufacturing process chain with the finite element method requires the selection of an appropriate finite element solver, element type and mesh density for each process of the chain. When the simulation results of one step are needed in a subsequent one, they have to be interpolated and transferred to another model. This paper presents an in-core grid index that can be created on a mesh represented by a list of nodes/elements. Finite element data can thus be transferred across different models in a process chain by mapping nodes or elements in indexed meshes. For each nodal or integration point of the target mesh, the index on the source mesh is searched for a specific node or element satisfying certain conditions, based on the mapping method. The underlying space of an indexed mesh is decomposed into a grid of variable-sized cells. The index allows local searches to be performed in a small subset of the cells, instead of linear searches in the entire mesh which are computationally expensive. This work focuses on the implementation and computational efficiency of indexing, searching and mapping. An experimental evaluation on medium-sized meshes suggests that the combination of index creation and mapping using the index is much faster than mapping through sequential searches.
Coronin7 regulates WASP and SCAR through CRIB mediated interaction with Rac proteinsCoronin7 (CRN7) stabilizes F-actin and is a regulator of processes associated with the actin cytoskeleton. Its loss leads to defects in phagocytosis, motility and development. It harbors a CRIB (Cdc42- and Rac-interactive binding) domain in each of its WD repeat domains which bind to Rac GTPases preferably in their GDP-loaded forms. Expression of wild type CRN7 in CRN7 deficient cells rescued these defects, whereas proteins with mutations in the CRIB motifs which were associated with altered Rac binding were effective to varying degrees. The presence of one functional CRIB was sufficient to reestablish phagocytosis, cell motility and development. Furthermore, by molecular modeling and mutational analysis we identified the contact regions between CRN7 and the GTPases. We also identified WASP, SCAR and PAKa as downstream effectors in phagocytosis, development and cell surface adhesion, respectively, since ectopic expression rescued these functions.
Tumor matrix stiffness promotes metastatic cancer cell interaction with the endotheliumTumor progression alters the composition and physical properties of the extracellular matrix. Particularly, increased matrix stiffness has profound effects on tumor growth and metastasis. While endothelial cells are key players in cancer progression, the influence of tumor stiffness on the endothelium and the impact on metastasis is unknown. Through quantitative mass spectrometry, we find that the matricellular protein CCN1/CYR61 is highly regulated by stiffness in endothelial cells. We show that stiffness-induced CCN1 activates β-catenin nuclear translocation and signaling and that this contributes to upregulate N-cadherin levels on the surface of the endothelium, in vitro This facilitates N-cadherin-dependent cancer cell-endothelium interaction. Using intravital imaging, we show that knockout of Ccn1 in endothelial cells inhibits melanoma cancer cell binding to the blood vessels, a critical step in cancer cell transit through the vasculature to metastasize. Targeting stiffness-induced changes in the vasculature, such as CCN1, is therefore a potential yet unappreciated mechanism to impair metastasis.
The role of the SWI/SNF ATP dependent chromatin remodelling complex in the regulation of the human hair follicle cell proliferation and control of the human cutaneous wound healingEpigenetic regulation of gene expression occurs at a number of levels including covalent DNA and histone modifications, nucleosome positioning and ATP-dependent chromatin remodelling as well as higher order chromatin folding and 3D genome organisation. ATP-dependent chromatin remodelling complexes modulate nucleosome structure, positioning and chromatin de-compaction and are involved in gene activation and repression. SWI/SNF ATP-dependent chromatin remodelling complexes contain either BRG1 or BRM as the core ATPase together with other common and variable subunits. BRG1 is required for terminal epidermal differentiation in mice and humans and for hair follicle stem cell activation during mouse hair follicle regeneration and cutaneous wound healing. However, the role of SWI/SNF complexes in human hair growth and wound healing remain unknown. Here it is demonstrated that genes encoding SWI/SNF complex subunits are expressed in human hair follicles. It also highlights that siRNA mediated suppression of SWI/SNF complexes in hair follicle culture has no effect on hair growth, or anagen-catagen transition in the short term, but a significant increase in proliferation of the outer root sheath keratinocytes was seen. The data also documents the expression of several SWI/SNF subunits in human epidermis and that siRNA mediated SMARCA4 gene suppression in primary human keratinocyte monolayers defined the requirements of BRG1 for wound closure through control of cell migration, but not proliferation. In summary, this data revealed a diverse SWI/SNF complex subunit composition in human epidermis and hair follicle, and an essential role of the core complex ATPase BRG1 in keratinocyte migration during wound closure and re-epithelisation.
Addressing inequalities in eye health with subsidies and increased fees for General Ophthalmic Services in socio-economically deprived communities: A sensitivity analysisObjectives: Poor knowledge of eye health, concerns about the cost of spectacles, mistrust of optometrists and limited geographical access in socio-economically deprived areas are barriers to accessing regular eye examinations and result in low uptake and subsequent late presentation to ophthalmology clinics. Personal Medical Services (PMS) were introduced in the late 1990s to provide locally negotiated solutions to problems associated with inequalities in access to primary care. An equivalent approach to delivery of optometric services could address inequalities in the uptake of eye examinations. Study design: One-way and multiway sensitivity analyses. Methods: Variations in assumptions were included in the models for equipment and accommodation costs, uptake and length of appointments. The sensitivity analyses thresholds were cost-per-person tested below the GOS1 fee paid by the NHS and achieving break-even between income and expenditure, assuming no cross-subsidy from profits from sales of optical appliances. Results: Cost per test ranged from £24.01 to £64.80 and subsidy required varied from £14,490 to £108,046. Unused capacity utilised for local enhanced service schemes such as glaucoma referral refinement reduced the subsidy needed. Conclusions: In order to support the financial viability of primary eye care in socio-economically deprived communities, income is required from additional subsidies or from sources other than eye examinations, such as ophthalmic or other optometric community services. This would require a significant shift of activity from secondary to primary care locations. The subsidy required could also be justified by the utility gain from earlier detection of preventable sight loss.