An Investigation of Rural Welsh Cinemas:Their Histories, Memories and Communities

This thesis explores rural Welsh cinema history, in terms of both exhibition practice and audience experience, prior to 1970. In doing so it provides new contexts for the burgeoning, though still underrepresented, field of rural cinema studies. In considering rural regions of Wales, this thesis also seeks to overturn a dominance of urban studies within the limited amount of scholarship concerning Welsh cinema history. Utilising a combination of archival and ethnographic methodologies, this thesis then asks what were the unique factors of rural Welsh cinemagoing and exhibition history. Furthermore, this thesis rejects any view of rural Wales as a culturally homogeneous zone and considers if these experiences and practices vary across the differing social, political, economic and linguistic regions of the country

Interleukin-17A upregulates receptor activator of NF-kappaB on osteoclast precursors.

IntroductionThe interaction between the immune and skeletal systems is evidenced by the bone loss observed in autoimmune diseases such as rheumatoid arthritis. In this paper we describe a new mechanism by which the immune cytokine IL-17A directly affects osteoclastogenesis.MethodsHuman CD14+ cells were isolated from healthy donors, cultured on dentine slices and coverslips and stimulated with IL-17A and/or receptor activator of NF-kappaB ligand (RANKL). Osteoclast differentiation was evaluated by gene expression, flow cytometry, tartrate-resistant acid phosphatase staining, fluorescence and electron microscopy. Physiologic bone remodelling was studied in wild-type (Wt) and IL-17A-/- mice using micro-computer tomography and serum RANKL/osteoprotegerin concentration. Functional osteoclastogenesis assays were performed using bone marrow macrophages isolated from IL-17A-/- and Wt mice.ResultsIL-17A upregulates the receptor activator for NF-kappaB receptor on human osteoclast precursors in vitro, leading to increased sensitivity to RANKL signalling, osteoclast differentiation and bone loss. IL-17A-/- mice have physiological bone homeostasis indistinguishable from Wt mice, and bone marrow macrophages isolated from these mice develop fully functional normal osteoclasts.ConclusionsCollectively our data demonstrate anti-IL-17A treatment as a selective therapeutic target for bone loss associated with autoimmune diseases

Deprojecting and constraining the vertical thickness of exoKuiper belts

Constraining the vertical and radial structure of debris discs is crucial to understanding their formation, evolution and dynamics. To measure both the radial and vertical structure, a disc must be sufficiently inclined. However, if a disc is too close to edge-on, deprojecting its emission becomes non-trivial. In this paper we show how Frankenstein, a non-parametric tool to extract the radial brightness profile of circumstellar discs, can be used to deproject their emission at any inclination as long as they are optically thin and axisymmetric. Furthermore, we extend Frankenstein to account for the vertical thickness of an optically thin disc ($H(r)$) and show how it can be constrained by sampling its posterior probability distribution and assuming a functional form (e.g. constant $h=H/r$), while fitting the radial profile non-parametrically. We use this new method to determine the radial and vertical structure of 16 highly inclined debris discs observed by ALMA. We find a wide range of vertical aspect ratios, $h$, ranging from $0.020\pm0.002$ (AU Mic) to $0.20\pm0.03$ (HD 110058), which are consistent with parametric models. We find a tentative correlation between $h$ and the disc fractional width, as expected if wide discs were more stirred. Assuming discs are self-stirred, the thinnest discs would require the presence of at least 500 km-sized planetesimals. The thickest discs would likely require the presence of planets. We also recover previously inferred and new radial structures, including a potential gap in the radial distribution of HD 61005. Finally, our new extension of Frankenstein also allows constraining how $h$ varies as a function of radius, which we test on 49 Ceti, finding that $h$ is consistent with being constant.Comment: Accepted for publication in MNRAS. 17 pages. 16 figure

Interleukin-17A upregulates receptor activator of NF-κB on osteoclast precursors

IntroductionThe interaction between the immune and skeletal systems is evidenced by the bone loss observed in autoimmune diseases such as rheumatoid arthritis. In this paper we describe a new mechanism by which the immune cytokine IL-17A directly affects osteoclastogenesis.MethodsHuman CD14+ cells were isolated from healthy donors, cultured on dentine slices and coverslips and stimulated with IL-17A and/or receptor activator of NF-kappaB ligand (RANKL). Osteoclast differentiation was evaluated by gene expression, flow cytometry, tartrate-resistant acid phosphatase staining, fluorescence and electron microscopy. Physiologic bone remodelling was studied in wild-type (Wt) and IL-17A-/- mice using micro-computer tomography and serum RANKL/osteoprotegerin concentration. Functional osteoclastogenesis assays were performed using bone marrow macrophages isolated from IL-17A-/- and Wt mice.ResultsIL-17A upregulates the receptor activator for NF-kappaB receptor on human osteoclast precursors in vitro, leading to increased sensitivity to RANKL signalling, osteoclast differentiation and bone loss. IL-17A-/- mice have physiological bone homeostasis indistinguishable from Wt mice, and bone marrow macrophages isolated from these mice develop fully functional normal osteoclasts.ConclusionsCollectively our data demonstrate anti-IL-17A treatment as a selective therapeutic target for bone loss associated with autoimmune diseases

Reduction of fibrillar strain-rate sensitivity in steroid-induced osteoporosis linked to changes in mineralized fibrillar nanostructure

As bone is used in a dynamic mechanical environment, understanding the structural origins of its time-dependent mechanical behaviour – and the alterations in metabolic bone disease – is of interest. However, at the scale of the mineralized fibrillar matrix (nanometre-level), the nature of the strain-rate dependent mechanics is incompletely understood. Here, we investigate the fibrillar- and mineral-deformation behaviour in a murine model of Cushing’s syndrome, used to understand steroid induced osteoporosis, using synchrotron small- and wide-angle scattering/diffraction combined with in situ tensile testing at three strain rates ranging from 10-4 to 10-1 s-1. We find that the effective fibril- and mineral-modulus and fibrillar-reorientation show no significant increase with strain-rate in osteoporotic bone, but increase significantly in normal (wild-type) bone. By applying a fibril-lamellar two-level structural model of bone matrix deformation to fit the results, we obtain indications that altered collagen-mineral interactions at the nanoscale – along with altered fibrillar orientation distributions – may be the underlying reason for this altered strain-rate sensitivity. Our results suggest that an altered strain-rate sensitivity of the bone matrix in osteoporosis may be one of the contributing factors to reduced mechanical competence in such metabolic bone disorders, and that increasing this sensitivity may improve biomechanical performance