Protein structural change at the cytoplasmic surface as the cause of cooperativity in the bacteriorhodopsin photocycle

The effects of excitation light intensity on the kinetics of the bacteriorhodopsin photocycle were investigated. The earlier reported intensity-dependent changes at 410 and 570 nm are explained by parallel increases in two of the rate constants, for proton transfers to D96 from the Schiff base and from the cytoplasmic surface, without changes in the others, as the photoexcited fraction is increased. Thus, it appears that the pKa of D96 is raised by a cooperative effect within the purple membrane. This interpretation of the wild-type kinetics was confirmed by results with several mutant proteins, where the rates are well separated in time and a model-dependent analysis is unnecessary. Based on earlier results that demonstrated a structural change of the protein after deprotonation of the Schiff base that increases the area of the cytoplasmic surface, and the effects of high hydrostatic pressure and lowered water activity on the photocycle steps in question, we suggest that the pKa of D96 is raised by a lateral pressure that develops when other bacteriorhodopsin molecules are photoexcited within the two-dimensional lattice of the purple membrane. Expulsion of no more than a few water molecules bound near D96 by this pressure would account for the calculated increase of 0.6 units in the pKa

A Critical Evaluation of Cohesive Zone Models of Dynamic Fracture

Finite element calculations of dynamic fracture based on embedding cohesive surfaces in a continuum indicate that the predictions are sensitive to the cohesive law used. Simulations were performed on a square block in plane strain with an initial edge crack loaded at a constant rate of strain. Cohesive laws that have an initial elastic response were observed to produce spontaneous branching at high velocity, but to modify the linear elastic properties of the body. As a consequence the cohesive surface spacing cannot be refined arbitrarily and becomes an important length scale in the simulations. Cohesive laws that are initially rigid do not alter the linear elastic response of the body. However, crack branching behavior was not observed when such a cohesive relation was implemented using a regular finite element mesh.Earth and Planetary SciencesEngineering and Applied Science

“You can’t be a person and a doctor”. The work-life balance of doctors in training: a qualitative study

Objectives Investigate the work–life balance of doctors in training in the UK from the perspectives of trainers and trainees. Design Qualitative semistructured focus groups and interviews with trainees and trainers. Setting Postgraduate medical training in London, Yorkshire and Humber, Kent, Surrey and Sussex, and Wales during the junior doctor contract dispute at the end of 2015. Part of a larger General Medical Council study about the fairness of postgraduate medical training. Participants 96 trainees and 41 trainers. Trainees comprised UK graduates and International Medical Graduates, across all stages of training in 6 specialties (General Practice, Medicine, Obstetrics and Gynaecology, Psychiatry, Radiology, Surgery) and Foundation. Results Postgraduate training was characterised by work–life imbalance. Long hours at work were typically supplemented with revision and completion of the e-portfolio. Trainees regularly moved workplaces which could disrupt their personal lives and sometimes led to separation from friends and family. This made it challenging to cope with personal pressures, the stresses of which could then impinge on learning and training, while also leaving trainees with a lack of social support outside work to buffer against the considerable stresses of training. Low morale and harm to well-being resulted in some trainees feeling dehumanised. Work–life imbalance was particularly severe for those with children and especially women who faced a lack of less-than-full-time positions and discriminatory attitudes. Female trainees frequently talked about having to choose a specialty they felt was more conducive to a work–life balance such as General Practice. The proposed junior doctor contract was felt to exacerbate existing problems. Conclusions A lack of work–life balance in postgraduate medical training negatively impacted on trainees' learning and well-being. Women with children were particularly affected, suggesting this group would benefit the greatest from changes to improve the work–life balance of trainees

Self-Reported Outcome Measures of the Impact of Injury and Illness on Athlete Performance: A Systematic Review

BACKGROUND: Self-reported outcome measures of athlete health, wellbeing and performance add information to that obtained from clinical measures. However valid, universally accepted outcome measures are required. OBJECTIVE: To determine which athlete-reported outcome measures of performance have been used to measure the impact of injury and illness on performance in sport and assess evidence to support their validity. METHODS: The authors searched Ovid MEDLINE, Ovid EMBASE, CINAHL Plus, SPORTDiscus with Full Text and Cochrane library to January 2016. Predefined inclusion and exclusion criteria were applied and papers included if an outcome measure of performance, assessed in relation to illness, injury or a related intervention, was reported by an elite, adult, able-bodied athlete. A checklist was used to assess eligible outcome measures for aspects of validity. Reporting of this study was guided by PRISMA guidelines for systematic reviews. RESULTS: Twenty athlete-reported outcome measures in 21 papers were identified. Of these 20, only four cited validation. Of these four, three reported evidence to support validity in elite athlete groups as defined by the predetermined checklist. Fifteen patient-reported outcome measures were identified, of which four demonstrated validity in young athletic populations. CONCLUSIONS: Most athlete-reported outcome measures of performance have been designed for individual studies with no reported assessment of validity. Despite some limitations, the Oslo Sports Trauma Centre overuse injury questionnaire demonstrates validity and potential utility to investigate the self-reported impact of pre-defined conditions on athletic performance across different sports

Perceived causes of differential attainment in UK postgraduate medical training: a national qualitative study

Objectives: Explore trainee doctors’ experiences of postgraduate training and perceptions of fairness in relation to ethnicity and country of primary medical qualification. Design: Qualitative semistructured focus group and interview study. Setting: Postgraduate training in England (London, Yorkshire and Humber, Kent Surrey and Sussex) and Wales. Participants: 137 participants (96 trainees, 41 trainers) were purposively sampled from a framework comprising: doctors from all stages of training in general practice, medicine, obstetrics and gynaecology, psychiatry, radiology, surgery or foundation, in 4 geographical areas, from white and black and minority ethnic (BME) backgrounds, who qualified in the UK and abroad. Results: Most trainees described difficult experiences, but BME UK graduates (UKGs) and international medical graduates (IMGs) could face additional difficulties that affected their learning and performance. Relationships with senior doctors were crucial to learning but bias was perceived to make these relationships more problematic for BME UKGs and IMGs. IMGs also had to deal with cultural differences and lack of trust from seniors, often looking to IMG peers for support instead. Workplace-based assessment and recruitment were considered vulnerable to bias whereas examinations were typically considered more rigorous. In a system where success in recruitment and assessments determines where in the country you can get a job, and where work–life balance is often poor, UK BME and international graduates in our sample were more likely to face separation from family and support outside of work, and reported more stress, anxiety or burnout that hindered their learning and performance. A culture in which difficulties are a sign of weakness made seeking support and additional training stigmatising. Conclusions: BME UKGs and IMGs can face additional difficulties in training which may impede learning and performance. Non-stigmatising interventions should focus on trainee–trainer relationships at work and organisational changes to improve trainees’ ability to seek social support outside work

Effect of stress-triaxiality on void growth in dynamic fracture of metals: a molecular dynamics study

The effect of stress-triaxiality on growth of a void in a three dimensional single-crystal face-centered-cubic (FCC) lattice has been studied. Molecular dynamics (MD) simulations using an embedded-atom (EAM) potential for copper have been performed at room temperature and using strain controlling with high strain rates ranging from 10^7/sec to 10^10/sec. Strain-rates of these magnitudes can be studied experimentally, e.g. using shock waves induced by laser ablation. Void growth has been simulated in three different conditions, namely uniaxial, biaxial, and triaxial expansion. The response of the system in the three cases have been compared in terms of the void growth rate, the detailed void shape evolution, and the stress-strain behavior including the development of plastic strain. Also macroscopic observables as plastic work and porosity have been computed from the atomistic level. The stress thresholds for void growth are found to be comparable with spall strength values determined by dynamic fracture experiments. The conventional macroscopic assumption that the mean plastic strain results from the growth of the void is validated. The evolution of the system in the uniaxial case is found to exhibit four different regimes: elastic expansion; plastic yielding, when the mean stress is nearly constant, but the stress-triaxiality increases rapidly together with exponential growth of the void; saturation of the stress-triaxiality; and finally the failure.Comment: 35 figures, which are small (and blurry) due to the space limitations; submitted (with original figures) to Physical Review B. Final versio

Improved Algorithms for Approximate String Matching (Extended Abstract)

The problem of approximate string matching is important in many different areas such as computational biology, text processing and pattern recognition. A great effort has been made to design efficient algorithms addressing several variants of the problem, including comparison of two strings, approximate pattern identification in a string or calculation of the longest common subsequence that two strings share. We designed an output sensitive algorithm solving the edit distance problem between two strings of lengths n and m respectively in time O((s-|n-m|)min(m,n,s)+m+n) and linear space, where s is the edit distance between the two strings. This worst-case time bound sets the quadratic factor of the algorithm independent of the longest string length and improves existing theoretical bounds for this problem. The implementation of our algorithm excels also in practice, especially in cases where the two strings compared differ significantly in length. Source code of our algorithm is available at http://www.cs.miami.edu/\~dimitris/edit_distanceComment: 10 page

Poor oral health including active caries in 187 UK professional male football players: clinical dental examination performed by dentists

The few studies that have assessed oral health in professional/elite football suggest poor oral health with minimal data on impact on performance. The aim of this research was to determine oral health in a representative sample of professional footballers in the UK and investigate possible determinants of oral health and self-reported impact on well-being, training and performance