Shuffling and Unshuffling

We consider various shuffling and unshuffling operations on languages and words, and examine their closure properties. Although the main goal is to provide some good and novel exercises and examples for undergraduate formal language theory classes, we also provide some new results and some open problems

Ambient temperature fracture strength of pure alumina

The fracture of alumina copper-vapor laser tubes has led to great interest in the mechanical properties of pure alumina ({alpha}-Al{sub 2}O{sub 3}) in the Copper Laser Program. In particular, knowledge of the fracture strength of the alumina used to make these tubes is required at temperatures ranging from ambient to 1500{degree}C. The purpose of the work reported here was to confirm that the fracture strength data reasonably well describe the behavior of the alumina used in the Copper Laser Program. The goal was to make this investigation with the minimum of effort and cost. To this end, only ambient temperature tests were planned

Challenges in valuing and paying for combination regimens in oncology: reporting the perspectives of a multi‐stakeholder, international workshop

Background It is increasingly common for two or more treatments for cancer to be combined as a single regimen. Determining value and appropriate payment for such regimens can be challenging. This study discusses these challenges, and possible solutions. Methods Stakeholders from around the world attended a 2-day workshop, supported by a background paper. This study captures key outcomes from the discussion, but is not a consensus statement. Results Workshop attendees agreed that combining on-patent treatments can result in affordability and value for money challenges that delay or deny patient access to clinically effective treatments in many health systems. Options for addressing these challenges include: (i) Increasing the value of combination therapies through improved clinical development; (ii) Willingness to pay more for combinations than for single drugs offering similar benefit, or; (iii) Aligning the cost of constituent therapies with their value within a regimen. Workshop attendees felt that (i) and (iii) merited further discussion, whereas (ii) was unlikely to be justifiable. Views differed on the feasibility of (i). Key to (iii) would be systems allowing different prices to apply to different uses of a drug. Conclusions Common ground was identified on immediate actions to improve access to combination regimens. These include an exploration of the legal challenges associated with price negotiations, and ensuring that pricing systems can support implementation of negotiated prices for specific uses. Improvements to clinical development and trial design should be pursued in the medium and longer term

Functional modelling of complex multi‑disciplinary systems using the enhanced sequence diagram

YesThis paper introduces an Enhanced Sequence Diagram (ESD) as the basis for a structured framework for the functional analysis of complex multidisciplinary systems. The ESD extends the conventional sequence diagrams (SD) by introducing a rigorous functional flow-based modelling schemata to provide an enhanced basis for model-based functional requirements and architecture analysis in the early systems design stages. The proposed ESD heuristics include the representation of transactional and transformative functions required to deliver the use case sequence, and fork and join nodes to facilitate analysis of combining and bifurcating operations on flows. A case study of a personal mobility device is used to illustrate the deployment of the ESD methodology in relation to three common product development scenarios: (i) reverse engineering, (ii) the introduction of a specific technology to an existent system; and (iii) the introduction of a new feature as user-centric innovation for an existing system, at a logical design level, without reference to any solution. The case study analysis provides further insights into the effectiveness of the ESD to support function modelling and functional requirements capture, and architecture development. The significance of this paper is that it establishes a rigorous ESD-based functional analysis methodology to guide the practitioner with its deployment, facilitating its impact to both the engineering design and systems engineering communities, as well as the design practice in the industry

Functional modelling of complex multi‑disciplinary systems using the enhanced sequence diagram

YesThis paper introduces an Enhanced Sequence Diagram (ESD) as the basis for a structured framework for the functional analysis of complex multidisciplinary systems. The ESD extends the conventional sequence diagrams (SD) by introducing a rigorous functional flow-based modelling schemata to provide an enhanced basis for model-based functional requirements and architecture analysis in the early systems design stages. The proposed ESD heuristics include the representation of transactional and transformative functions required to deliver the use case sequence, and fork and join nodes to facilitate analysis of combining and bifurcating operations on flows. A case study of a personal mobility device is used to illustrate the deployment of the ESD methodology in relation to three common product development scenarios: (i) reverse engineering, (ii) the introduction of a specific technology to an existent system; and (iii) the introduction of a new feature as user-centric innovation for an existing system, at a logical design level, without reference to any solution. The case study analysis provides further insights into the effectiveness of the ESD to support function modelling and functional requirements capture, and architecture development. The significance of this paper is that it establishes a rigorous ESD-based functional analysis methodology to guide the practitioner with its deployment, facilitating its impact to both the engineering design and systems engineering communities, as well as the design practice in the industry

It's all about the sex, or is it? Humans, horses and temperament

We propose that the anthropomorphic application of gender stereotypes to animals influences human-animal interactions and human expectations, often with negative consequences for female animals. An online survey was conducted to explore riders’ perceptions of horse temperament and suitability for ridden work, based on horse sex. The questionnaire asked respondents to allocate three hypothetical horses (a mare, gelding and stallion) to four riders compromising a woman, man, girl and boy. Riders were described as equally capable of riding each horse and each horse was described as suitable for all riders. Participants were also asked which horses (mares, geldings or stallions) were most suitable for the three equestrian disciplines of showjumping, dressage and trail-riding. Logistic regression analyses were conducted to investigate people’s perceptions about suitability of horse types for particular riders, to evaluate if age, strength or gender were important in rider choice and to investigate riders’allocation of various descriptors to a gelding, stallion or mare. There were 1,233 survey respondents, 94% of whom were female and 75% of whom were riders with at least eight years of experience. Binomial logistic regression revealed the girl had 2.5 times the odds of being allocated the gelding compared to the boy (p < 0.001). Respondents were significantly more likely to allocate the stallion to the man and nearly 50% of respondents did not allocate a horse to the boy, even though they ranked rider gender as least important to their choice (p < 0.001). In a forced choice selection of a positive or negative descriptor from a series of nine paired terms to describe horse temperament, a greater proportion of respondents assigned geldings positive ratings on terms such as calm, trainable, reliable and predictable. In terms of suitability for the three equestrian disciplines of show-jumping, dressage and trail-riding, participants overwhelmingly chose geldings for trail-riding, with mares being least preferred for both dressage and show-jumping. The results suggest that female riders are entering the horse-human dyad with gendered ideas about horse temperament and view horse-riding as an activity primarily for women and girls. This could have far-reaching implications for equine training and welfare

High resolution spatial modelling of greenhouse gas emissions from land use change to energy crops in the UK

We implemented a spatial application of a previously evaluated model of soil GHG emissions, ECOSSE, in the United Kingdom to examine the impacts to 2050 of land-use transitions from existing land use, rotational cropland, permanent grassland or woodland, to six bioenergy crops; three ‘first-generation’ energy crops: oilseed rape, wheat and sugar beet, and three ‘second-generation’ energy crops: Miscanthus, short rotation coppice willow (SRC) and short rotation forestry poplar (SRF). Conversion of rotational crops to Miscanthus, SRC and SRF and conversion of permanent grass to SRF show beneficial changes in soil GHG balance over a significant area. Conversion of permanent grass to Miscanthus, permanent grass to SRF and forest to SRF shows detrimental changes in soil GHG balance over a significant area. Conversion of permanent grass to wheat, oilseed rape, sugar beet and SRC and all conversions from forest show large detrimental changes in soil GHG balance over most of the United Kingdom, largely due to moving from uncultivated soil to regular cultivation. Differences in net GHG emissions between climate scenarios to 2050 were not significant. Overall, SRF offers the greatest beneficial impact on soil GHG balance. These results provide one criterion for selection of bioenergy crops and do not consider GHG emission increases/decreases resulting from displaced food production, bio-physical factors (e.g. the energy density of the crop) and socio-economic factors (e.g. expenditure on harvesting equipment). Given that the soil GHG balance is dominated by change in soil organic carbon (SOC) with the difference among Miscanthus, SRC and SRF largely determined by yield, a target for management of perennial energy crops is to achieve the best possible yield using the most appropriate energy crop and cultivar for the local situation

The utilisation of health research in policy-making: Concepts, examples and methods of assessment

The importance of health research utilisation in policy-making, and of understanding the mechanisms involved, is increasingly recognised. Recent reports calling for more resources to improve health in developing countries, and global pressures for accountability, draw greater attention to research-informed policy-making. Key utilisation issues have been described for at least twenty years, but the growing focus on health research systems creates additional dimensions. The utilisation of health research in policy-making should contribute to policies that may eventually lead to desired outcomes, including health gains. In this article, exploration of these issues is combined with a review of various forms of policy-making. When this is linked to analysis of different types of health research, it assists in building a comprehensive account of the diverse meanings of research utilisation. Previous studies report methods and conceptual frameworks that have been applied, if with varying degrees of success, to record utilisation in policy-making. These studies reveal various examples of research impact within a general picture of underutilisation. Factors potentially enhancing utilisation can be identified by exploration of: priority setting; activities of the health research system at the interface between research and policy-making; and the role of the recipients, or 'receptors', of health research. An interfaces and receptors model provides a framework for analysis. Recommendations about possible methods for assessing health research utilisation follow identification of the purposes of such assessments. Our conclusion is that research utilisation can be better understood, and enhanced, by developing assessment methods informed by conceptual analysis and review of previous studies

Estrogen regulation of TRPM8 expression in breast cancer cells

<p>Abstract</p> <p>Background</p> <p>The calcium-permeable cation channel TRPM8 (melastatin-related transient receptor potential member 8) is over-expressed in several cancers. The present study aimed at investigating the expression, function and potential regulation of TRPM8 channels by ER alpha (estrogen receptor alpha) in breast cancer.</p> <p>Methods</p> <p>RT-PCR, Western blot, immuno-histochemical, and siRNA techniques were used to investigate TRPM8 expression, its regulation by estrogen receptors, and its expression in breast tissue. To investigate the channel activity in MCF-7 cells, we used the whole cell patch clamp and the calcium imaging techniques.</p> <p>Results</p> <p>TRPM8 channels are expressed at both mRNA and protein levels in the breast cancer cell line MCF-7. Bath application of the potent TRPM8 agonist Icilin (20 μM) induced a strong outwardly rectifying current at depolarizing potentials, which is associated with an elevation of cytosolic calcium concentration, consistent with established TRPM8 channel properties. RT-PCR experiments revealed a decrease in TRPM8 mRNA expression following steroid deprivation for 48 and 72 hours. In steroid deprived medium, addition of 17-beta-estradiol (E₂, 10 nM) increased both TRPM8 mRNA expression and the number of cells which respond to Icilin, but failed to affect the Ca²⁺entry amplitude. Moreover, silencing ERα mRNA expression with small interfering RNA reduced the expression of TRPM8. Immuno-histochemical examination of the expression of TRPM8 channels in human breast tissues revealed an over-expression of TRPM8 in breast adenocarcinomas, which is correlated with estrogen receptor positive (ER⁺) status of the tumours.</p> <p>Conclusion</p> <p>Taken together, these results show that TRPM8 channels are expressed and functional in breast cancer and that their expression is regulated by ER alpha.</p