Method for the design of broad energy range focusing reflectrons

A novel method for the design of reflections capable of focusing large kinetic energy ranges is presented. The design method itself is a numerical approach that provides a geometrically flexible alternative to traditional analytical design solutions. This design method has been used to produce a reflectron that provides unit mass resolution for product spectra in a tandem reflectron time-of-flight (TOF) mass spectrometer despite a kinetic energy range of 1950–2700 eV. In this application, the systematic progression of reflectron design results in a practical, nonlinear field reflectron with the use of only two grids. Design improvements are proposed for more flexible systems, although geometric constraints in the current instrument limit their experimental evaluation

Exploring views on satisfaction with life in young children with chronic illness: an innovative approach to the collection of self-report data from children under 11

The objective of this study was to explore young children’s views on the impact of chronic illness on their life in order to inform future development of a patient-based self-report health outcome measure. We describe an approach to facilitating self-report views from young children with chronic illness. A board game was designed in order to obtain qualitative data from 39 children with a range of chronic illness conditions and 38 healthy controls ranging in age from 3 to 11 years. The format was effective in engaging young children in a self-report process of determining satisfaction with life and identified nine domains. The board game enabled children aged 5–11 years with chronic illness to describe the effects of living with illness on home, family, friends, school and life in general. It generated direct, non-interpreted material from children who, because of their age, may have been considered unable or limited their ability to discuss and describe how they feel. Obtaining this information for children aged 4 and under continues to be a challenge

Parametric design of non-axisymmetric separate-jet aero-engine exhaust systems

Future civil air vehicles are likely to feature propulsion systems which are more closely integrated with the airframe. For a podded underwing configuration, this close coupling is expected to require non-axisymmetric design capabilities for the aero-engine exhaust system. This work presents the development of a novel parametric representation of non-axisymmetric aero-engine exhaust system geometries based on Intuitive Class Shape Transformation (iCST) curves. An exhaust design method was established and aerodynamic analyses of a range of non-axisymmetric configurations was demonstrated. At typical flight conditions, the introduction of non-axisymmetric separate jet nozzles was shown to increase the engine net propulsive force by 0.12% relative to an axisymmetric nozzle

Shakespearean allusion and the detective fiction of Georgette Heyer

This essay argues that Shakespearean allusion is a recurrent and important factor in the detective novels of Georgette Heyer. Though the master text for Heyer is Hamlet, a variety of Shakespeare plays are referred to, and mention of them functions in multiple ways. Quotations from Shakespeare reveal truths about the characters and comment on their situations and personalities. They also afford points of entry for people previously unacquainted to talk to each other, and finally they have effects in terms of genre, since their presence can, with equal facility, tend towards comic relief (in line with a tradition in Golden Age crime fiction of using Macbeth in particular to comic effect) or work to add gravitas and resonance. The use of Shakespearean allusion is thus central to Heyer’s technique. This article is published as part of a collection to commemorate the 400th anniversary of William Shakespeare’s death

Genetic background influences tumour development in heterozygous Men1 knockout mice

Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder caused by MEN1 germline mutations, is characterised by parathyroid, pancreatic and pituitary tumours. MEN1 mutations also cause familial isolated primary hyperparathyroidism (FIHP), a milder condition causing hyperparathyroidism only. Identical mutations can cause either MEN1 or FIHP in different families, thereby implicating a role for genetic modifiers in altering phenotypic expression of tumours. We therefore investigated the effects of genetic background and potential for genetic modifiers on tumour development in adult Men1+/- mice, which develop tumours of the parathyroids, pancreatic islets, anterior pituitary, adrenal cortex and gonads, that had been backcrossed to generate C57BL/6 and 129S6/SvEv congenic strains. A total of 275 Men1+/- mice, aged 5–26 months were macroscopically studied, and this revealed that genetic background significantly influenced the development of pituitary, adrenal and ovarian tumours, which occurred in mice over 12 months of age and more frequently in C57BL/6 females, 129S6/SvEv males and 129S6/SvEv females, respectively. Moreover, pituitary and adrenal tumours developed earlier, in C57BL/6 males and 129S6/SvEv females, respectively, and pancreatic and testicular tumours developed earlier in 129S6/SvEv males. Furthermore, glucagon-positive staining pancreatic tumours occurred more frequently in 129S6/SvEv Men1+/- mice. Whole genome sequence analysis of 129S6/SvEv and C57BL/6 Men1+/- mice revealed >54,000 different variants in >300 genes. These included, Coq7, Dmpk, Ccne2, Kras, Wnt2b, Il3ra and Tnfrsf10a, and qRT-PCR analysis revealed that Kras was significantly higher in pituitaries of male 129S6/SvEv mice. Thus, our results demonstrate that Kras and other genes could represent possible genetic modifiers of Men1

The nucleotide and partial amino acid sequences of rat fetuin

Fetuins are among the major plasma proteins, yet their biological role has remained elusive. Here we report the molecular cloning of rat fetuin and the sequence analysis of a full-length clone, RF619 of 1456 bp with an open reading frame of 1056 bp encoding 352 amino acid residues. The coding part of RF619 was identical with the cDNA sequence of the natural inhibitor of the insulin receptor tyrosine kinase from rat (pp63) except for four substitutions and a single base insertion causing divergence of the predicted protein sequences. Partial amino acid sequences of rat plasma fetuin were in agreement with the predictions based on the RF619 cDNA. Purified rat fetuin inhibited the insulin receptor tyrosine kinase in vitro. Therefore, we conclude that RF619 and pp63 cDNA encode the same protein, i.e. authentic rat fetuin which is a functional tyrosine kinase inhibitor