Beta-Lactamase Repressor BlaI Modulates Staphylococcus aureus Cathelicidin Antimicrobial Peptide Resistance and Virulence.

BlaI is a repressor of BlaZ, the beta-lactamase responsible for penicillin resistance in Staphylococcus aureus. Through screening a transposon library in S. aureus Newman for susceptibility to cathelicidin antimicrobial peptide, we discovered BlaI as a novel cathelicidin resistance factor. Additionally, through integrational mutagenesis in S. aureus Newman and MRSA Sanger 252 strains, we confirmed the role of BlaI in resistance to human and murine cathelidicin and showed that it contributes to virulence in human whole blood and murine infection models. We further demonstrated that BlaI could be a target for innate immune-based antimicrobial therapies; by removing BlaI through subinhibitory concentrations of 6-aminopenicillanic acid, we were able to sensitize S. aureus to LL-37 killing

Barriers and enablers to engagement with a type 2 diabetes remission project in the North East of England: Qualitative perspectives of patients

\ua9 The Author(s), 2024.This qualitative research sought to identify factors influencing patient choice of, and patient-related internal and external enablers and barriers to engagement with, type 2 diabetes (T2D) remission strategies offered by the Remission in diabetes (REMI.D) project. Patients had a choice of three diets: Total Diet Replacement (TDR)-Formula Food Products, TDR-Food, and Healthy lifestyle approach; and three activity pathways: Everyday life, General Practitioner referral, and Social hub. Semi-structured interviews were recorded and transcribed. Thematic analysis used the Framework Method and NVivo 12 to assist with generation and organisation of codes, inductive and deductive (Theoretical Domains Framework). The REMI.D project was a place-based approach (place in this case being defined as two local authorities with significant rates of deprivation) situated in the North East of England. Twenty patients out of a possible 65 patients took part. Areas of interest included: patient choice, patient intention, patient adherence, patient non-Adherence, and patient stigma. Addition of a more moderate dietary strategy (not dissimilar to the diet in the Healthier You NHS Diabetes Prevention Programme) to the existing NHS England T2D Path to Remission programme may enable more patients to achieve remission or delayed progression with deprescribing of diabetes medications. Embedding a tailored physical activity path within or as a bolt-on to the NHS programme requires consideration. Limited resources should be targeted towards patients who identify with more barriers or fewer opportunities for health behaviour modification. Further research on use of virtual programmes in deprived areas is warranted

Barrel swirl breakdown in spark-ignition engines: insights from particle image velocimetry measurements

Particle image velocimetry (PIV) has been used here to study the formation and breakdown of barrel swirl ('tumble') in a production geometry, four-stroke, four-valve, motored, spark-ignition, optically accessed internal combustion (IC) engine. The barrel swirl ratio (BSR) of the cylinder head could be enhanced by means of a port face inducer gasket so that the flow processes taking place at low and high swirl ratios could be investigated conveniently. Double-exposed images from planes both parallel and perpendicular to the cylinder axis were recorded at selected crank angles through the induction and compression strokes at a motored engine speed of 1000 r/min, with a wide open throttle, for both high and low BSR cases. The recorded images were interrogated by digital autocorrelation to give two-dimensional maps of instantaneous velocity. In both high and low BSR cases, a barrel or tumbling vortex motion is generated during induction, which is shown to persist throughout the majority of the compression stroke. The details of barrel swirl formation during induction and its subsequent modification during compression, however, differ strongly between the two cases. These differences can be explained qualitatively in terms of two main events; the first being competition during induction between vortices of unequal strength and the second being competition between the large-scale swirl motion and the local flow field generated by piston motion during compression. In the low barrel swirl case, significant dissipation occurs owing to these interactions and consequently the large-scale motion exhibits lower mean velocities and undergoes significant distortion. In the case of high BSR, the competition effects are minimized and a single ordered vertical vortex exhibiting high velocity magnitudes is observed to avoid piston induced distortion. It then moves into the apex of the pent roof combustion chamber where it survives as a single ordered vortex until at least 40° crank angle (CA) before top dead centre (TDC). Limitations and developments of the PIV technique are discussed

A particle model of rolling grain ripples under waves

A simple model is presented for the formation of rolling grain ripples on a flat sand bed by the oscillatory flow generated by a surface wave. An equation of motion is derived for the individual ripples, seen as "particles", on the otherwise flat bed. The model account for the initial apperance of the ripples, the subsequent coarsening of the ripples and the final equilibrium state. The model is related to physical parameters of the problem, and an analytical approximation for the equilibrium spacing of the ripples is developed. It is found that the spacing between the ripples scale with the square-root of the non-dimensional shear stress (the Shields parameter) on a flat bed. The results of the model are compared with measurements, and reasonable agreement between the model and the measurements is demonstrated.Comment: 9 pages incl. figures. Revised versio

Dynamical models for sand ripples beneath surface waves

We introduce order parameter models for describing the dynamics of sand ripple patterns under oscillatory flow. A crucial ingredient of these models is the mass transport between adjacent ripples, which we obtain from detailed numerical simulations for a range of ripple sizes. Using this mass transport function, our models predict the existence of a stable band of wavenumbers limited by secondary instabilities. Small ripples coarsen in our models and this process leads to a sharply selected final wavenumber, in agreement with experimental observations.Comment: 9 pages. Shortened version of previous submissio

Foundations of character: methodological aspects of a study of character development in three- to six-year-old children with a focus on sharing behaviours

This article focuses on methodological issues arising in a study of character development, using illustrations of ‘sharing behaviours.’ Based primarily in six early years settings in southeast England the research records naturalistic observations of peer interactions for 55 children aged three to six years. Applying grounded theory to the processes of observing, analysing and interpreting evidence required a cautious and collectively reflective approach. The methodology sought to moderate the influence of the researchers' prior knowledge of ‘grand theories’ of moral development and assumptions about relevance to the observation records. The study's originality lay in the exploration of moral development without reference to any particular grand theory as an explanatory framework; and in the reluctance to be drawn to potentially simplistic rationalisations of the children's intentions on the basis of their observed behaviours. Exploring young children's subjective experiences, this research provides insights into the intricacy of this process, steering away from ‘neat’ findings and attempting to reflect the sophistication of the children's skilful and sometimes surprising negotiations of moral dilemmas. Implications for practice relate to the complexities involved in attempts to unravel the developing moral characters of young children and the practice through which this may be nurtured

Validity and worth in the science curriculum: learning school science outside the laboratory

It is widely acknowledged that there are problems with school science in many developed countries of the world. Such problems manifest themselves in a progressive decline in pupil enthusiasm for school science across the secondary age range and the fact that fewer students are choosing to study the physical sciences at higher levels and as careers. Responses to these developments have included proposals to reform the curriculum, pedagogy and the nature of pupil discussion in science lessons. We support such changes but argue from a consideration of the aims of science education that secondary school science is too rooted in the science laboratory; substantially greater use needs to be made of out-of-school sites for the teaching of science. Such usage should result in a school science education that is more valid and more motivating and is better at fulfilling defensible aims of school science education. Our contention is that laboratory-based school science teaching needs to be complemented by out-of-school science learning that draws on the actual world (e.g. through fieldtrips), the presented world (e.g. in science centres, botanic gardens, zoos and science museums) and the virtual worlds that are increasingly available through information and communications technologies (ICT)

Social representations and the politics of participation

Recent work has called for the integration of different perspectives into the field of political psychology (Haste, 2012). This chapter suggests that one possible direction that such efforts can take is studying the role that social representations theory (SRT) can play in understanding political participation and social change. Social representations are systems of common-sense knowledge and social practice; they provide the lens through which to view and create social and political realities, mediate people's relations with these sociopolitical worlds and defend cultural and political identities. Social representations are therefore key for conceptualising participation as the activity that locates individuals and social groups in their sociopolitical world. Political participation is generally seen as conditional to membership of sociopolitical groups and therefore is often linked to citizenship. To be a citizen of a society or a member of any social group one has to participate as such. Often political participation is defined as the ability to communicate one's views to the political elite or to the political establishment (Uhlaner, 2001), or simply explicit involvement in politics and electoral processes (Milbrath, 1965). However, following scholars on ideology (Eagleton, 1991; Thompson, 1990) and social knowledge (Jovchelovitch, 2007), we extend our understanding of political participation to all social relations and also develop a more agentic model where individuals and groups construct, develop and resist their own views, ideas and beliefs. We thus adopt a broader approach to participation in comparison to other political-psychological approaches, such as personality approaches (e.g. Mondak and Halperin, 2008) and cognitive approaches or, more recently, neuropsychological approaches (Hatemi and McDermott, 2012). We move away from a focus on the individual's political behaviour and its antecedents and outline an approach that focuses on the interaction between psychological and political phenomena (Deutsch and Kinnvall, 2002) through examining the politics of social knowledge

CoreSOAR Core Degradation State-of-the Art Report Update: Conclusions [in press]

In 1991 the CSNI published the first State-of-the-Art Report on In-Vessel Core Degradation, which was updated to 1995 under the EC 3rd Framework programme. These covered phenomena, experimental programmes, material data, main modelling codes, code assessments, identification of modelling needs, and conclusions including the needs for further research. This knowledge was fundamental to such safety issues as in-vessel melt retention of the core, recovery of the core by water reflood, hydrogen generation and fission product release. In the last 20 years, there has been much progress in understanding, with major experimental series finished, e.g. the integral in-reactor Phébus FP tests, while others have many tests completed, e.g. the electrically-heated QUENCH series on reflooding degraded rod bundles, and one test using a debris bed. The small-scale PRELUDE/PEARL experiments study debris bed quench, while LIVE examines melt pool behaviour in the lower head using simulant materials. The integral severe accident modelling codes, such as MELCOR and MAAP (USA) and ASTEC (Europe), encapsulate current knowledge in a quantitative way. After two EC-funded projects on the SARNET network of excellence, continued in NUGENIA, it is timely to take stock of the vast range of knowledge and technical improvements gained in the experimental and modelling areas. The CoreSOAR project, in NUGENIA/SARNET, drew together the experience of 11 European partners to update the state of the art in core degradation, finishing at the end of 2018. The review covered knowledge of phenomena, available integral experiments, separate-effects data, modelling codes and code validation, then drawing overall conclusions and identifying needs for further research. The final report serves as a reference for current and future research programmes concerning core degradation in NUGENIA, in other EC research projects such as in Horizon2020 and for projects under the auspices of OECD/NEA/CSNI