Enhancing Practice and Achievement in Introductory Programming With a Robot Olympics

© 2015 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission. See http://www.ieee.org/publications_standards/publications/rights/index.html for more information

Mechanically activated Piezo1 channels of cardiac fibroblasts stimulate p38 mitogen-activated protein kinase activity and interleukin-6 secretion

Piezo1 is a mechanosensitive cation channel with widespread physiological importance; however, its role in the heart is poorly understood. Cardiac fibroblasts help preserve myocardial integrity and play a key role in regulating its repair and remodeling following stress or injury. Here we investigated Piezo1 expression and function in cultured human and mouse cardiac fibroblasts. RT-PCR experiments confirmed that Piezo1 mRNA in cardiac fibroblasts is expressed at levels similar to those in endothelial cells. The results of a Fura-2 intracellular Ca2+ assay validated Piezo1 as a functional ion channel that is activated by its agonist, Yoda1. Yoda1-induced Ca2+ entry was inhibited by Piezo1 blockers (gadolinium and ruthenium red) and was reduced proportionally by siRNA-mediated Piezo1 knockdown or in murine Piezo1+/− cells. Results from cell-attached patch clamp recordings on human cardiac fibroblasts established that they contain mechanically activated ion channels and that their pressure responses are reduced by Piezo1 knockdown. Investigation of Yoda1 effects on selected remodeling genes indicated that Piezo1 activation increases both mRNA levels and protein secretion of IL-6, a pro-hypertrophic and profibrotic cytokine, in a Piezo1-dependent manner. Moreover, Piezo1 knockdown reduced basal IL-6 expression from cells cultured on softer collagen-coated substrates. Multiplex kinase activity profiling combined with kinase inhibitor experiments and phosphospecific immunoblotting established that Piezo1 activation stimulates IL-6 secretion via the p38 mitogen-activated protein kinase downstream of Ca2+ entry. In summary, cardiac fibroblasts express mechanically activated Piezo1 channels coupled to secretion of the paracrine signaling molecule IL-6. Piezo1 may therefore be important in regulating cardiac remodeling

Foot pain and foot health in an educated population of adults: results from the Glasgow Caledonian University Alumni Foot Health Survey

Abstract Background Foot pain is common amongst the general population and impacts negatively on physical function and quality of life. Associations between personal health characteristics, lifestyle/behaviour factors and foot pain have been studied; however, the role of wider determinants of health on foot pain have received relatively little attention. Objectives of this study are i) to describe foot pain and foot health characteristics in an educated population of adults; ii) to explore associations between moderate-to-severe foot pain and a variety of factors including gender, age, medical conditions/co-morbidity/multi-morbidity, key indicators of general health, foot pathologies, and social determinants of health; and iii) to evaluate associations between moderate-to-severe foot pain and foot function, foot health and health-related quality-of-life. Methods Between February and March 2018, Glasgow Caledonian University Alumni with a working email address were invited to participate in the cross-sectional electronic survey (anonymously) by email via the Glasgow Caledonian University Alumni Office. The survey was constructed using the REDCap secure web online survey application and sought information on presence/absence of moderate-to-severe foot pain, patient characteristics (age, body mass index, socioeconomic status, occupation class, comorbidities, and foot pathologies). Prevalence data were expressed as absolute frequencies and percentages. Multivariate logistic and linear regressions were undertaken to identify associations 1) between independent variables and moderate-to-severe foot pain, and 2) between moderate-to-severe foot pain and foot function, foot health and health-related quality of life. Results Of 50,228 invitations distributed, there were 7707 unique views and 593 valid completions (median age [inter-quartile range] 42 [31–52], 67.3% female) of the survey (7.7% response rate). The sample was comprised predominantly of white Scottish/British (89.4%) working age adults (95%), the majority of whom were overweight or obese (57.9%), and in either full-time or part-time employment (82.5%) as professionals (72.5%). Over two-thirds (68.5%) of the sample were classified in the highest 6 deciles (most affluent) of social deprivation. Moderate-to-severe foot pain affected 236/593 respondents (39.8%). High body mass index, presence of bunions, back pain, rheumatoid arthritis, hip pain and lower occupation class were included in the final multivariate model and all were significantly and independently associated with moderate-to-severe foot pain (p < 0.05), except for rheumatoid arthritis (p = 0.057). Moderate-to-severe foot pain was significantly and independently associated lower foot function, foot health and health-related quality of life scores following adjustment for age, gender and body mass index (p < 0.05). Conclusions Moderate-to-severe foot pain was highly prevalent in a university-educated population and was independently associated with female gender, high body mass index, bunions, back pain, hip pain and lower occupational class. Presence of moderate-to-severe foot pain was associated with worse scores for foot function, foot health and health-related quality-of-life. Education attainment does not appear to be protective against moderate-to-severe foot pain

Barry Unsworth's Morality Play: Narrative, detection, history

© 2016 Macmillan Publishers Ltd. Morality Play is a historical detective novel set in the late fourteenth century and published in 1995, at a time of flourishing for historical fiction in Britain. This article argues that the novel shares some of the features of contemporary British historical fiction (notably, a degree of self-referentiality and a concern with the relationship between reality and representation), but also retains more traditional historical novels' desire to show the fate of individuals caught at moments of historical change. Using White's reflections on forms of historical writing and an understanding of the history of detective fiction, the article brings this currently under-examined text to critical attention and, in so doing, contributes to current scholarly understanding of the so-called 'historical turn' in late-twentieth century British fiction

Generating synthetic fjord bathymetry for coastal Greenland

Bed topography is a critical boundary for the numerical modelling of ice sheets and ice-ocean interactions. A persistent issue with existing topography products for the bed of the Greenland Ice Sheet and surrounding sea floor is the poor representation of coastal bathymetry, especially in regions of floating ice and near the grounding line. Sparse data coverage, and the resultant coarse resolution at the ice-ocean boundary, poses issues in our ability to model ice flow advance and retreat from the present position. In addition, as fjord bathymetry is known to exert strong control on ocean circulation and ice-ocean forcing, the lack of bed data leads to an inability to model these processes adequately. Since the release of the last complete Greenland bed topography-bathymetry product, new observational bathymetry data have become available. These data can be used to constrain bathymetry, but many fjords remain completely unsampled and therefore poorly resolved. Here, as part of the development of the next generation of Greenland bed topography products, we present a new method for constraining the bathymetry of fjord systems in regions where data coverage is sparse. For these cases, we generate synthetic fjord geometries using a method conditioned by surveys of terrestrial glacial valleys as well as existing sinuous feature interpolation schemes. Our approach enables the capture of the general bathymetry profile of a fjord in north-west Greenland close to Cape York, when compared to observational data. We validate our synthetic approach by demonstrating reduced overestimation of depths compared to past attempts to constrain fjord bathymetry. We also present an analysis of the spectral characteristics of fjord centrelines using recently acquired bathymetric observations, demonstrating how a stochastic model of fjord bathymetry could be parameterised and used to create different realisations.This study was supported by UK NERC grant NE/M000869/1

The effects of symmetry on the dynamics of antigenic variation

In the studies of dynamics of pathogens and their interactions with a host immune system, an important role is played by the structure of antigenic variants associated with a pathogen. Using the example of a model of antigenic variation in malaria, we show how many of the observed dynamical regimes can be explained in terms of the symmetry of interactions between different antigenic variants. The results of this analysis are quite generic, and have wider implications for understanding the dynamics of immune escape of other parasites, as well as for the dynamics of multi-strain diseases.Comment: 21 pages, 4 figures; J. Math. Biol. (2012), Online Firs

Fanconi anemia manifesting as a squamous cell carcinoma of the hard palate: a case report

Fanconi Anemia is a rare autosomal recessive disorder characterized by various congenital malformations, progressive bone marrow failure at a very young age and of solid tumors development. The authors present a rare case of a squamous cell carcinoma of the hard palate in a Fanconi Anaemia patient. The atypical clinical manifestation rendered the diagnosis more difficult. This case, for age of appearance, sex and localization, is unique in international literature. We recommend a quarterly follow up of the oral-rhino-pharynx complex in FA patients and to consider as carcinomas, all oral lesions that last more than two weeks

Retinoic Acid Mediates Regulation of Network Formation by COUP-TFII and VE-Cadherin Expression by TGFβ Receptor Kinase in Breast Cancer Cells

Tumor development, growth, and metastasis depend on the provision of an adequate vascular supply. This can be due to regulated angiogenesis, recruitment of circulating endothelial progenitors, and/or vascular transdifferentiation. Our previous studies showed that retinoic acid (RA) treatment converts a subset of breast cancer cells into cells with significant endothelial genotypic and phenotypic elements including marked induction of VE-cadherin, which was responsible for some but not all morphological changes. The present study demonstrates that of the endothelial-related genes induced by RA treatment, only a few were affected by knockdown of VE-cadherin, ruling it out as a regulator of the RA-induced endothelial genotypic switch. In contrast, knockdown of the RA-induced gene COUP-TFII prevented the formation of networks in Matrigel but had no effect on VE-cadherin induction or cell fusion. Two pan-kinase inhibitors markedly blocked RA-induced VE-cadherin expression and cell fusion. However, RA treatment resulted in a marked and broad reduction in tyrosine kinase activity. Several genes in the TGFβ signaling pathway were induced by RA, and specific inhibition of the TGFβ type I receptor blocked both RA-induced VE-cadherin expression and cell fusion. Together these data indicate a role for the TGFβ pathway and COUP-TFII in mediating the endothelial transdifferentiating properties of RA

Modeling the pharmacodynamics of passive membrane permeability

Small molecule permeability through cellular membranes is critical to a better understanding of pharmacodynamics and the drug discovery endeavor. Such permeability may be estimated as a function of the free energy change of barrier crossing by invoking the barrier domain model, which posits that permeation is limited by passage through a single “barrier domain” and assumes diffusivity differences among compounds of similar structure are negligible. Inspired by the work of Rezai and co-workers (JACS 128:14073–14080, 2006), we estimate this free energy change as the difference in implicit solvation free energies in chloroform and water, but extend their model to include solute conformational affects. Using a set of eleven structurally diverse FDA approved compounds and a set of thirteen congeneric molecules, we show that the solvation free energies are dominated by the global minima, which allows solute conformational distributions to be effectively neglected. For the set of tested compounds, the best correlation with experiment is obtained when the implicit chloroform global minimum is used to evaluate the solvation free energy difference