Active learning of the thermodynamics-dynamics tradeoff in protein condensates

Phase-separated biomolecular condensates exhibit a wide range of dynamical properties, which depend on the sequences of the constituent proteins and RNAs. However, it is unclear to what extent condensate dynamics can be tuned without also changing the thermodynamic properties that govern phase separation. Using coarse-grained simulations of intrinsically disordered proteins, we show that the dynamics and thermodynamics of homopolymer condensates are strongly correlated, with increased condensate stability being coincident with low mobilities and high viscosities. We then apply an "active learning" strategy to identify heteropolymer sequences that break this correlation. This data-driven approach and accompanying analysis reveal how heterogeneous amino-acid compositions and non-uniform sequence patterning map to a range of independently tunable dynamical and thermodynamic properties of biomolecular condensates

On fixed point sets and Lefschetz modules for sporadic simple groups

We consider 2-local geometries and other subgroup complexes for sporadic simple groups. For six groups, the fixed point set of a noncentral involution is shown to be equivariantly homotopy equivalent to a standard geometry for the component of the centralizer. For odd primes, fixed point sets are computed for sporadic groups having an extraspecial Sylow p-subgroup of order p^3, acting on the complex of those p-radical subgroups containing a p-central element in their centers. Vertices for summands of the associated reduced Lefschetz modules are described.Comment: 22 page

'Just open your eyes a bit more': The methodological challenges of researching black and minority ethnic students' experiences of physical education teacher education

In this paper we discuss some of the challenges of centralising 'race' and ethnicity in Physical Education (PE) research, through reflecting on the design and implementation of a study exploring Black and minority ethnic students' experiences of their teacher education. Our aim in the paper is to contribute to ongoing theoretical and methodological debates about intersectionality, and specifically about difference and power in the research process. As McCorkel and Myers notes, the 'researchers' backstage'-the assumptions, motivations, narratives and relations-that underpin any research are not always made visible and yet are highly significant in judging the quality and substance of the resulting project. As feminists, we argue that the invisibility of 'race' and ethnicity within Physical Education Teacher Education (PETE), and PE research more widely, is untenable; however, we also show how centralising 'race' and ethnicity raised significant methodological and epistemological questions, particularly given our position as White researchers and lecturers. In this paper, we reflect on a number of aspects of our research 'journey': the theoretical and methodological challenges of operationalising concepts of 'race' and ethnicity, the practical issues and dilemmas involved in recruiting participants for the study, the difficulties of 'talking race' personally and professionally and challenges of representing the experiences of 'others'. © 2012 Copyright Taylor and Francis Group, LLC

Tales from the playing field: black and minority ethnic students' experiences of physical education teacher education

This article presents findings from recent research exploring black and minority ethnic (BME) students’ experiences of Physical Education teacher education (PETE) in England (Flintoff, 2008). Despite policy initiatives to increase the ethnic diversity of teacher education cohorts, BME students are under-represented in PETE, making up just 2.94% of the 2007/8 national cohort, the year in which this research was conducted. Drawing on in-depth interviews and questionnaires with 25 BME students in PETE, the study sought to contribute to our limited knowledge and understanding of racial and ethnic difference in PE, and to show how ‘race,’ ethnicity and gender are interwoven in individuals’ embodied, everyday experiences of learning how to teach. In the article, two narratives in the form of fictional stories are used to present the findings. I suggest that narratives can be useful for engaging with the experiences of those previously silenced or ignored within Physical Education (PE); they are also designed to provoke an emotional as well as an intellectual response in the reader. Given that teacher education is a place where we should be engaging students, emotionally and politically, to think deeply about teaching, education and social justice and their place within these, I suggest that such stories of difference might have a useful place within a critical PETE pedagogy

3D Visualisation of Additive Occlusion and Tunable Full-Spectrum Fluorescence in Calcite

From biomineralization to synthesis, organic additives provide an effective means of controlling crystallisation processes. There is growing evidence that these additives are often occluded within the crystal lattice, where this promises an elegant means of creating nanocomposites and tuning physical properties. Here, we use the incorporation of sulfonated fluorescent dyes to gain new understanding of additive occlusion in calcite (CaCO3), and to link morphological changes to occlusion mechanisms. We demonstrate that these additives are incorporated within specific zones, as defined by the growth conditions, and show how occlusion can govern changes in crystal shape. Fluorescence spectroscopy and lifetime imaging microscopy also show that the dyes experience unique local environments within different zones. Our strategy was then extended to simultaneously incorporate mixtures of dyes, whose fluorescence cascade creates calcite nanoparticles that fluoresce white. This offers a simple strategy for generating biocompatible and stable fluorescent nanoparticles whose output can be tuned as required

Influence of topography on tide propagation and amplification in semi-enclosed basins

An idealized model for tide propagation and amplification in semi-enclosed rectangular basins is presented, accounting for depth differences by a combination of longitudinal and lateral topographic steps. The basin geometry is formed by several adjacent compartments of identical width, each having either a uniform depth or two depths separated by a transverse topographic step. The problem is forced by an incoming Kelvin wave at the open end, while allowing waves to radiate outward. The solution in each compartment is written as the superposition of (semi)-analytical wave solutions in an infinite channel, individually satisfying the depth-averaged linear shallow water equations on the f plane, including bottom friction. A collocation technique is employed to satisfy continuity of elevation and flux across the longitudinal topographic steps between the compartments. The model results show that the tidal wave in shallow parts displays slower propagation, enhanced dissipation and amplified amplitudes. This reveals a resonance mechanism, occurring when\ud the length of the shallow end is roughly an odd multiple of the quarter Kelvin wavelength. Alternatively, for sufficiently wide basins, also Poincaré waves may become resonant. A transverse step implies different wavelengths of the incoming and reflected Kelvin wave, leading to increased amplitudes in shallow regions and a shift of amphidromic points in the direction of the deeper part. Including the shallow parts near the basin’s closed end (thus capturing the Kelvin resonance mechanism) is essential to reproduce semi-diurnal and diurnal\ud tide observations in the Gulf of California, the Adriatic Sea and the Persian Gulf

Clinical effectiveness and cost-effectiveness of pegvisomant for the treatment of acromegaly: a systematic review and economic evaluation

Background: Acromegaly, an orphan disease usually caused by a benign pituitary tumour, is characterised by hyper-secretion of growth hormone (GH) and insulin-like growth factor I (IGF-1). It is associated with reduced life expectancy, cardiovascular problems, a variety of insidiously progressing detrimental symptoms and metabolic malfunction. Treatments include surgery, radiotherapy and pharmacotherapy. Pegvisomant (PEG) is a genetically engineered GH analogue licensed as a third or fourth line option when other treatments have failed to normalise IGF-1 levels. Methods: Evidence about effectiveness and cost-effectiveness of PEG was systematically reviewed. Data were extracted from published studies and used for a narrative synthesis of evidence. A decision analytical economic model was identified and modified to assess the cost-effectiveness of PEG. Results: One RCT and 17 non-randomised studies were reviewed for effectiveness. PEG substantially reduced and rapidly normalised IGF-1 levels in the majority of patients, approximately doubled GH levels, and improved some of the signs and symptoms of the disease. Tumour size was unaffected at least in the short term. PEG had a generally safe adverse event profile but a few patients were withdrawn from treatment because of raised liver enzymes. An economic model was identified and adapted to estimate the lower limit for the cost-effectiveness of PEG treatment versus standard care. Over a 20 year time horizon the incremental cost-effectiveness ratio was pound81,000/QALY and pound212,000/LYG. To reduce this to pound30K/QALY would require a reduction in drug cost by about one third. Conclusion: PEG is highly effective for improving patients' IGF-1 level. Signs and symptoms of disease improve but evidence is lacking about long term effects on improved signs and symptoms of disease, quality of life, patient compliance and safety. Economic evaluation indicated that if current standards (UK) for determining cost-effectiveness of therapies were to be applied to PEG it would be considered not to represent good value for money

The underpotential deposition that should not be : Cu(1x1) on Au(111)

Peer reviewedPostprin

The challenges of intersectionality: Researching difference in physical education

Researching the intersection of class, race, gender, sexuality and disability raises many issues for educational research. Indeed, Maynard (2002, 33) has recently argued that ‘difference is one of the most significant, yet unresolved, issues for feminist and social thinking at the beginning of the twentieth century’. This paper reviews some of the key imperatives of working with ‘intersectional theory’ and explores the extent to these debates are informing research around difference in education and Physical Education (PE). The first part of the paper highlights some key issues in theorising and researching intersectionality before moving on to consider how difference has been addressed within PE. The paper then considers three ongoing challenges of intersectionality – bodies and embodiment, politics and practice and empirical research. The paper argues for a continued focus on the specific context of PE within education for its contribution to these questions