2,109 research outputs found
Primary physical education, coaches and continuing professional development
This is an Author's Accepted Manuscript of an article published in Sport, Education and Society, 16(4), 485 - 505, 2011, copyright @ Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/13573322.2011.589645.Physical education (PE) in primary schools has traditionally been taught by qualified primary teachers. More recently, some teaching of PE in primary schools has been undertaken by coaches (mostly football coaches). These coaches hold national governing body awards but do not hold teaching qualifications. Thus, coaches may not be adequately prepared to teach PE in curriculum time. The purpose of this study was to evaluate the perceptions of a group of community-based football coaches working in primary schools for the impact of a Continuing Professional Development (CPD) programme on their ability to undertake ‘specified work’ to cover PE in primary schools. The programme focused on four areas identified as important to enable coaches to cover specified work: short- and medium-term planning, pedagogy, knowledge of the curriculum and reflection. Results showed that for the majority of coaches the CPD programme had made them more aware of the importance of these four areas and had helped to develop their knowledge and ability to put this into practice in covering planning, preparation and assessment time. However, further input is still required to develop coaches’ knowledge and understanding in all four areas, but especially their curriculum knowledge, as well as their ability to put these into practice consistently. These findings are discussed in relation to the implications of employing coaches to cover the teaching of PE in primary schools and, if employed, what CPD coaches need to develop the necessary knowledge, skill and understanding for covering specified work in schools
Emotional Support and Mental Health Among Somali Men in a Rural Midwestern Town
Perceived social support has been correlated with refugees’ positive mental health outcomes; yet, little is known about the perceived sources of support after secondary migration to new-destination rural towns. Somali refugee men (n _ 49) residing in a rural Midwest United States community were recruited using respondent-driven sampling to complete a self-administered structured survey in English or Somali using audio computer-assisted self-interview software. Questions assessed perceived sources of support, psychological distress, and happiness. Somali participants reported low utilization of both informal (30.4%) and formal (24.4%) supports when sad, stressed, or worried. Two thirds of participants reported low levels of distress and 98% reported being happy or very happy. This exploratory research contributes to understandings of Somali men’s perceived support in a postsecondary migration setting. We discuss implications for social support interventions and culturally tailored assessment, diagnoses, and treatment to enhance Somalis’ support and psychological well-being
A novel role for p120 catenin in E-cadherin function
Îndirect evidence suggests that p120-catenin (p120) can both positively and negatively affect cadherin adhesiveness. Here we show that the p120 gene is mutated in SW48 cells, and that the cadherin adhesion system is impaired as a direct consequence of p120 insufficiency. Restoring normal levels of p120 caused a striking reversion from poorly differentiated to cobblestone-like epithelial morphology, indicating a crucial role for p120 in reactivation of E-cadherin function. The rescue efficiency was enhanced by increased levels of p120, and reduced by the presence of the phosphorylation domain, a region previously postulated to confer negative regulation. Surprisingly, the rescue was associated with substantially increased levels of E-cadherin. E-cadherin mRNA levels were unaffected by p120 expression, but E-cadherin half-life was more than doubled. Direct p120–E-cadherin interaction was crucial, as p120 deletion analysis revealed a perfect correlation between E-cadherin binding and rescue of epithelial morphology. Interestingly, the epithelial morphology could also be rescued by forced expression of either WT E-cadherin or a p120-uncoupled mutant. Thus, the effects of uncoupling p120 from E-cadherin can be at least partially overcome by artificially maintaining high levels of cadherin expression. These data reveal a cooperative interaction between p120 and E-cadherin and a novel role for p120 that is likely indispensable in normal cells
Emergent dynamic chirality in a thermally driven artificial spin ratchet
Modern nanofabrication techniques have opened the possibility to create novel functional materials, whose properties transcend those of their constituent elements. In particular, tuning the magnetostatic interactions in geometrically frustrated arrangements of nanoelements called artificial spin ice1, 2 can lead to specific collective behaviour3, including emergent magnetic monopoles4, 5, charge screening6, 7 and transport8, 9, as well as magnonic response10, 11, 12. Here, we demonstrate a spin-ice-based active material in which energy is converted into unidirectional dynamics. Using X-ray photoemission electron microscopy we show that the collective rotation of the average magnetization proceeds in a unique sense during thermal relaxation. Our simulations demonstrate that this emergent chiral behaviour is driven by the topology of the magnetostatic field at the edges of the nanomagnet array, resulting in an asymmetric energy landscape. In addition, a bias field can be used to modify the sense of rotation of the average magnetization. This opens the possibility of implementing a magnetic Brownian ratchet13, 14, which may find applications in novel nanoscale devices, such as magnetic nanomotors, actuators, sensors or memory cells
Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial
© Cuzick et al. Open Access article distributed under the terms of CC BY.http://dx.doi.org/10.1016/S1470-2045(14)71171-
Mathematical and Statistical Techniques for Systems Medicine: The Wnt Signaling Pathway as a Case Study
The last decade has seen an explosion in models that describe phenomena in
systems medicine. Such models are especially useful for studying signaling
pathways, such as the Wnt pathway. In this chapter we use the Wnt pathway to
showcase current mathematical and statistical techniques that enable modelers
to gain insight into (models of) gene regulation, and generate testable
predictions. We introduce a range of modeling frameworks, but focus on ordinary
differential equation (ODE) models since they remain the most widely used
approach in systems biology and medicine and continue to offer great potential.
We present methods for the analysis of a single model, comprising applications
of standard dynamical systems approaches such as nondimensionalization, steady
state, asymptotic and sensitivity analysis, and more recent statistical and
algebraic approaches to compare models with data. We present parameter
estimation and model comparison techniques, focusing on Bayesian analysis and
coplanarity via algebraic geometry. Our intention is that this (non exhaustive)
review may serve as a useful starting point for the analysis of models in
systems medicine.Comment: Submitted to 'Systems Medicine' as a book chapte
MATRIX DESIGN FOR STRATEGICALLY TUNED ABSOLUTELY RESILIENT STRUCTURES (STARS)
ABSTRACT This paper discusses Strategically Tuned Absolutely Resilient Structures (STARS) and steps taken to improve their performance by developing lightweight, high-performance cementitious composites that rely on the interfacial bonding between the aggregate [Poly(vinyl butyral) (PVB)] and reinforcement [Poly(vinyl alcohol) (PVA) fiber]. PVB is selected because it is light weight, adheres well to a variety of surfaces, and has good energy-absorbing characteristics. PVA fiber is used because it has a high tensile strength and bonds well with the cementitious matrix. We show that standard mortar techniques and components can produce relatively high strength flexible mortars without any hard aggregate at all. These mortars are not related to macro defect free cements which are usually prepared with very low w/c ratios and soluble polymers that do not act as aggregates; nor, are these mortars polymer concretes which use a cross linking polymer replacement for Portland cement. A comprehensive trial and error mix design process was followed to arrive at a fiber-free baseline mix having a low density of 1548 kg/m 3 (96.6 lb/ft 3 ) and an average compressive strength of 40 MPa (5800 psi). Mechanical properties such as the compressive strength, flexural strength, ductility, fracture toughness, and impact resistance are evaluated as fibers are added. Results show that the compressive strength decreases slightly with increasing fiber volume fraction whereas flexural strength, ductility, fracture toughness, and impact resistance increase
Alzheimer\u27s Therapeutics Targeting Amyloid Beta 1–42 Oligomers II: Sigma-2/PGRMC1 Receptors Mediate Abeta 42 Oligomer Binding and Synaptotoxicity
Amyloid beta (Abeta) 1-42 oligomers accumulate in brains of patients with Mild Cognitive Impairment (MCI) and disrupt synaptic plasticity processes that underlie memory formation. Synaptic binding of Abeta oligomers to several putative receptor proteins is reported to inhibit long-term potentiation, affect membrane trafficking and induce reversible spine loss in neurons, leading to impaired cognitive performance and ultimately to anterograde amnesia in the early stages of Alzheimer\u27s disease (AD). We have identified a receptor not previously associated with AD that mediates the binding of Abeta oligomers to neurons, and describe novel therapeutic antagonists of this receptor capable of blocking Abeta toxic effects on synapses in vitro and cognitive deficits in vivo. Knockdown of sigma-2/PGRMC1 (progesterone receptor membrane component 1) protein expression in vitro using siRNA results in a highly correlated reduction in binding of exogenous Abeta oligomers to neurons of more than 90%. Expression of sigma-2/PGRMC1 is upregulated in vitro by treatment with Abeta oligomers, and is dysregulated in Alzheimer\u27s disease patients\u27 brain compared to age-matched, normal individuals. Specific, high affinity small molecule receptor antagonists and antibodies raised against specific regions on this receptor can displace synthetic Abeta oligomer binding to synaptic puncta in vitro and displace endogenous human AD patient oligomers from brain tissue sections in a dose-dependent manner. These receptor antagonists prevent and reverse the effects of Abeta oligomers on membrane trafficking and synapse loss in vitro and cognitive deficits in AD mouse models. These findings suggest sigma-2/PGRMC1 receptors mediate saturable oligomer binding to synaptic puncta on neurons and that brain penetrant, small molecules can displace endogenous and synthetic oligomers and improve cognitive deficits in AD models. We propose that sigma-2/PGRMC1 is a key mediator of the pathological effects of Abeta oligomers in AD and is a tractable target for small molecule disease-modifying therapeutics
Biochemical and Structural Characterization of Selective Allosteric Inhibitors of the Plasmodium falciparum Drug Target, Prolyl-tRNA-synthetase
Plasmodium falciparum (<i>Pf</i>) prolyl-tRNA
synthetase (ProRS) is one of the few chemical-genetically validated
drug targets for malaria, yet highly selective inhibitors have not
been described. In this paper, approximately 40,000 compounds were
screened to identify compounds that selectively inhibit <i>Pf</i>ProRS enzyme activity versus Homo sapiens (<i>Hs</i>) ProRS. X-ray crystallography structures were
solved for apo, as well as substrate- and inhibitor-bound forms of <i>Pf</i>ProRS. We identified two new inhibitors of <i>Pf</i>ProRS that bind outside the active site. These two allosteric inhibitors
showed >100 times specificity for <i>Pf</i>ProRS compared
to <i>Hs</i>ProRS, demonstrating this class of compounds
could overcome the toxicity related to <i>Hs</i>ProRS inhibition
by halofuginone and its analogues. Initial medicinal chemistry was
performed on one of the two compounds, guided by the cocrystallography
of the compound with <i>Pf</i>ProRS, and the results can
instruct future medicinal chemistry work to optimize these promising
new leads for drug development against malaria
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