The momentum spectrum of cosmic ray muons above 300 GeV/c in the vertical direction

The sea-level vertical rauon momentum spectrum Has been measured in the momentum range 100 GeV/c to 3000 GeV/c, using the MARS spectrograph in Durham, The various instrumental effects which affect either the shape or the absolute intensity of the measured spectrum have been studied in detail. The analysis procedure has been discussed in detail including the accuracy of the analysis technique and the criteria for rejection of certain events. A simple muon production and propagation model has been used to predict the plon and kaon production spectra using the rauon spectrum derived from the results of this experiment. It has not been found possible to predict the ratio of the number of kaons to the number of pions produced at production and an estimate of this ratio (0.106) has been used to fit a constant exponent power law spectrum. The present results have been compared with those of other workers and are found to yield a smaller value of the exponent for the fitted power law production spectra. This result suggests that the pion and kaon production spectra are somewhat flatter than previously measured for momenta above 100 GeV/c by previous HAliS experiments(Ayre et al., 1975). The present results on the muon spectrum, however, ogree, within the limits of the statistical accuracy, with other spectrograph data. Comparison with surveys of indirect measurements of the aiuon momentum spectrum suggest that the present results give a higher absolute intensity for the muon momentum spectrum above 1000 3aV/c

Integrating Research Data Management into Geographical Information Systems

Ocean modelling requires the production of high-fidelity computational meshes upon which to solve the equations of motion. The production of such meshes by hand is often infeasible, considering the complexity of the bathymetry and coastlines. The use of Geographical Information Systems (GIS) is therefore a key component to discretising the region of interest and producing a mesh appropriate to resolve the dynamics. However, all data associated with the production of a mesh must be provided in order to contribute to the overall recomputability of the subsequent simulation. This work presents the integration of research data management in QMesh, a tool for generating meshes using GIS. The tool uses the PyRDM library to provide a quick and easy way for scientists to publish meshes, and all data required to regenerate them, to persistent online repositories. These repositories are assigned unique identifiers to enable proper citation of the meshes in journal articles.Comment: Accepted, camera-ready version. To appear in the Proceedings of the 5th International Workshop on Semantic Digital Archives (http://sda2015.dke-research.de/), held in Pozna\'n, Poland on 18 September 2015 as part of the 19th International Conference on Theory and Practice of Digital Libraries (http://tpdl2015.info/

Dasatinib as a treatment for Duchenne muscular dystrophy

Identification of a systemically acting and universal small molecule therapy for Duchenne muscular dystrophy would be an enormous advance for this condition. Based on evidence gained from studies on mouse genetic models, we have identified tyrosine phosphorylation and degradation of β-dystroglycan as a key event in the aetiology of Duchenne muscular dystrophy. Thus, preventing tyrosine phosphorylation and degradation of β-dystroglycan presents itself as a potential therapeutic strategy. Using the dystrophic sapje zebrafish, we have investigated the use of tyrosine kinase and other inhibitors to treat the dystrophic symptoms in this model of Duchenne muscular dystrophy. Dasatinib, a potent and specific Src tyrosine kinase inhibitor, was found to decrease the levels of β-dystroglycan phosphorylation on tyrosine and to increase the relative levels of non-phosphorylated β-dystroglycan in sapje zebrafish. Furthermore, dasatinib treatment resulted in the improved physical appearance of the sapje zebrafish musculature and increased swimming ability as measured by both duration and distance of swimming of dasatinib-treated fish compared with control animals. These data suggest great promise for pharmacological agents that prevent the phosphorylation of β-dystroglycan on tyrosine and subsequent steps in the degradation pathway as therapeutic targets for the treatment of Duchenne muscular dystrophy

An inductive exploration into the flow experiences of European Tour golfers

© 2014 Taylor & Francis. This study explored perceptions regarding the experience of flow in elite golf; a sport which is different to those studied previously due to its self-paced, stop-start nature. In-depth, semi-structured interviews were conducted with 10 European Tour golfers. Whereas the majority of previous studies have deductively coded data into Csikszentmihalyi’s dimensions, the data in this study were analysed inductively. Thirteen categories were generated which described the flow experiences of these golfers, and these were compared with the original flow dimensions after analysis. In contrast to previous understanding, these golfers reported being aware that they were in flow as it occurred, and seemingly were able to manage their flow experiences. A category describing altered cognitive and kinaesthetic perceptions was also generated which was not accounted for in the existing flow framework, while the participants also suggested that flow was observable (e.g. through changes in behaviour). Findings are discussed in relation to the existing literature, and recommendations made for future research including possible revisions to the flow framework to better describe this experience within golf and other sporting contexts

Suppression of the NF-κB cofactor Bcl3 inhibits mammary epithelial cell apoptosis and, in breast tumours, correlates with poor prognosis

Background Several transcription factors have been shown to play important roles in the regulation of apoptosis at the onset of murine mammary involution. These include LIF-activated STAT3, c/ebpdelta, Ap-1 and IKK/NF-κB-mediated regulation of death receptor ligands. A study of STAT3 and STAT5 transcriptional targets in mammary epithelial cells in vitro showed that both c/ebpdelta and c-fos (a component of Ap-1) were upregulated by STAT3, suggesting a degree of interdependence between these transcription factor pathways in mediating their apoptotic effects. Interestingly, while no NF-κB or IKK genes were significantly regulated by STATs, the NF-κB cofactor gene, Bcl3, was found to be a principal transcriptional target of STAT3. This factor plays a role in altering the transcriptional capacity of specific NF-κB subunits and has previously been described as an oncogene in B-cell lymphomas. In this study we set out to establish whether Bcl3 had a role in regulating the cell fate of mammary epithelial cells either in the normal mammary gland or in mammary/breast cancer. Methods Archived material representing a range of tumour grades and types was collected from breast cancer patients immediately after surgery (tumour tissues = 122, normal tissues = 32). The median follow-up of the patients was 120 months (range 12 to 156 months). QRT-PCR for Bcl3 was performed and this information was used to determine statistically significant correlations with the clinical data on breast pathology. MCF7, T47D and MDA-MB231 human breast cancer cell lines were subjected to Bcl3-specific siRNA knockdown and subsequently assessed for cell motility characteristics using ECIS technology. Bcl3-knockout mice were assessed histologically for alterations in apoptosis rate during the adult pregnancy cycle. Western blots, quantitative PCR and DNA binding assays were used to determine the activity of molecular markers of apoptosis in these animals. Bcl3-deficient animals were crossed with mmtv-neu (c-erbB2) mice to establish the role of Bcl3 in primary (neu-dependent) mammary tumour growth, and magnetic resonance imaging was performed on tumour-bearing animals, to establish metastasis rates in the presence/absence of Bcl3. Results An analysis of 122 human breast cancer tissues showed that Bcl3 gene expression was suppressed in a significant proportion of invasive tumours, which correlated with poor prognosis. This also correlated with a significant decrease in Bcl3 gene expression in human breast cancer cell lines exhibiting increased motility characteristics. The effects of siRNA-mediated knockdown of Bcl3 are ongoing. In the mouse mammary gland, Bcl3 expression was restricted to epithelial cells during the first 24 hours of involution. Bcl3 deficiency resulted in a transient delay in the appearance of apoptotic bodies in the early involuting mammary gland in Bcl3-/- mice, while pSTAT3 levels were unchanged compared with equivalent timepoints in control animals. The activities of initiator/executor caspases of both intrinsic and extrinsic pathways were significantly decreased in Bcl3-/- tissues at this time, which correlated with decreases in the expression of key regulators of intrinsic/extrinsic apoptosis. Results from the ongoing magnetic resonance imaging study of tumour incidence/progression in mmtv-neu/Bcl3-/- mice will be presented. Conclusion These observations suggest that Bcl3 promotes apoptosis in the mammary gland and provides preliminary evidence of cross-talk between STAT3 and NF-κB pathways, both of which have been implicated in breast cancer. Our current data on Bcl3 in primary breast tumours and breast cancer cell lines contrasts with other studies, to suggest that Bcl3 suppresses the metastatic progression of primary breast cancer and has a neutral role in breast cancer incidence or primary tumour growth

Decolonising indigenous social impact research using community-based methods

© 2019 Association of Researchers in Construction Management, ARCOM 2019 - Proceedings of the 35th Annual Conference. All rights reserved. Indigenous procurement policies encourage the construction sector to provide new training, employment and business opportunities for Indigenous people suffering from economic and social disadvantage. However, the success of these policies is often distorted by the failure of policy evaluations to account for Indigenous perceptions of social value. Since these often differ markedly from non-Indigenous values, this can distort the allocation of funds to Indigenous communities and exacerbate the marginalisation of the communities these policies are meant to help. Drawing on theories of community-based research, this methodological paper seeks to reconceptualise approaches to measuring Indigenous social value in an Indigenous social procurement policy context. Working in partnership with a peak body for Aboriginal business in Australia, we have co-designed a novel approach to Indigenous social impact research that recognises the legitimacy of Indigenous perspectives when investigating the social value Indigenous procurement policies create. We argue that culturally appropriate focus groups (yarning discussion groups) are appropriate in Indigenous social impact research because they prioritise Indigenous people's experiences of Indigenous procurement policies, rather than focusing on simplistic policy targets. As a method that promotes community involvement in social impact research to define how social value is perceived, yarning discussion groups have significant implications for future research seeking to represent Indigeonus perspectives of social value. It is concluded the approach developed here can be operationalised in the field to better understand the nature of Indigenous social value and the impact created by Indigenous procurement policies in Australia and other countries with disadvantaged Indigenous populations

Inverse-designed diamond photonics

Diamond hosts optically active color centers with great promise in quantum computation, networking, and sensing. Realization of such applications is contingent upon the integration of color centers into photonic circuits. However, current diamond quantum optics experiments are restricted to single devices and few quantum emitters because fabrication constraints limit device functionalities, thus precluding color center integrated photonic circuits. In this work, we utilize inverse design methods to overcome constraints of cutting-edge diamond nanofabrication methods and fabricate compact and robust diamond devices with unique specifications. Our design method leverages advanced optimization techniques to search the full parameter space for fabricable device designs. We experimentally demonstrate inverse-designed photonic free-space interfaces as well as their scalable integration with two vastly different devices: classical photonic crystal cavities and inverse-designed waveguide-splitters. The multi-device integration capability and performance of our inverse-designed diamond platform represents a critical advancement toward integrated diamond quantum optical circuits