Training young people through a school/enterprise partnership: a longitudinal study

This paper reports a longitudinal study of 58 students who undertook an engineering traineeship concurrent with their final two years of secondary school. The student experience was planned as a partnership arrangement between a manufacturing enterprise, a secondary school, and a post-secondary technical education institution. Results are discussed in terms of completion of studies, employment and career pathways, employment outcomes, and post-traineeship employment destinations. Both the quantitative and qualitative data indicate that participants have benefited significantly in each area investigated. The significance of the program in developing propositional, procedural, and dispositional workplace knowledge is also discussed.<br /

Changes in Creep Behaviour and Microstructure of Model Mozzarella Cheese During Working

The effect of shear work input on the microstructure, fat particle size and creep behavior of model Mozzarella type cheeses was studied. Cheese samples were prepared in a twin screw cooker at 70 °C by mixing protein and fat phases together with different amounts of shear work input. Major changes in cheese structure were observed while working at 150 rpm and 250 rpm screw speeds. Confocal microstructures plus macroscopic observations showed systematic changes in structure with increased shear work inputs with unmixed buttery liquid observed at kg−1, typical Mozzarella type microstructures (elongated fat-serum channels) at 6–15 kJ kg−1 and homogeneously distributed, small size fat droplets at \u3e58 kJ kg−1. At very high shear work inputs, \u3e 75 kJ kg−1, striations or anisotropy in the microstructures had disappeared and small micro-cracks were evident. A 4-element Burger\u27s model was found adequate for fitting the creep data of model cheese at 70 °C but a 6-element model was required at 20 °C. As shear work input increased retarded compliance decreased and zero shear viscosity increased indicating the more elastic behavior of the cheeses with higher shear work input. Changes in the protein matrix appear to be the main reason for increased elastic behavior

Measurement Techniques for Steady Shear Viscosity of Mozzarella-Type Cheeses at High Shear Rates and High Temperature

While measuring steady shear viscosity of Mozzarella-type cheeses in a rotational rheometer at 70 °C, three main difficulties were encountered; wall slip, structural failure during measurement and viscoelastic time dependent effects. Serrated plates were the most successful surface modification at eliminating wall slip. However, even with serrated plates shear banding occurred at higher shear rates. Because of the viscoelastic nature of the cheeses, a time dependent viscous response occurred at shear rates \u3c1 \u3es−1, requiring longer times to attain steady shear conditions. Prolonged continuous shearing altered the structure of the molten cheeses. The effects of structural change were greatly reduced by minimising the total accumulated strain exerted on the sample during flow curve determination. These techniques enabled successful measurement of steady shear viscosity of molten Mozzarella-type cheeses at 70 °C at shear rates up to 250 s−1

Moving from ‘what we know works’ to ‘what we do in practice’::An evidence overview of implementation and diffusion of innovation in transition to adulthood for care experienced young people

Global research has shown that most young people who are care experienced are not prepared to transition to independent living at 18 years of age and require support into early adulthood. We used rigorous systematic methods to identify English‐based peer reviewed and grey literature describing innovations relevant to care experienced young people as they transition into adulthood, with a focus upon lessons for their implementation and diffusion. We synthesised the evidence narratively and organise data linked to seven key areas important to the transition to adulthood: (1) Health and well‐being; (2) relationships; (3) education and training; (4) employment; (5) participation in society; (6) accommodation; (7) other. Twenty‐five papers met our inclusion criteria. This review has found that, whilst there are a broad spectrum of innovations taking place within the social care environment for care experienced young people to support their transition into adulthood, there exists limited insight into how best to support implementation and diffusion of evidence‐based innovation. We drew upon the ‘Consolidated Framework for Implementation Research’, developed in the setting of clinical service delivery, to highlight challenges in implementing and diffusing evidence‐based innovation for care experienced young people transitioning into adulthood

RNA exosome mutations in pontocerebellar hypoplasia alter ribosome biogenesis and p53 levels.

The RNA exosome is a ubiquitously expressed complex of nine core proteins (EXOSC1-9) and associated nucleases responsible for RNA processing and degradation. Mutations in EXOSC3, EXOSC8, EXOSC9, and the exosome cofactor RBM7 cause pontocerebellar hypoplasia and motor neuronopathy. We investigated the consequences of exosome mutations on RNA metabolism and cellular survival in zebrafish and human cell models. We observed that levels of mRNAs encoding p53 and ribosome biogenesis factors are increased in zebrafish lines with homozygous mutations of exosc8 or exosc9, respectively. Consistent with higher p53 levels, mutant zebrafish have a reduced head size, smaller brain, and cerebellum caused by an increased number of apoptotic cells during development. Down-regulation of EXOSC8 and EXOSC9 in human cells leads to p53 protein stabilisation and G2/M cell cycle arrest. Increased p53 transcript levels were also observed in muscle samples from patients with EXOSC9 mutations. Our work provides explanation for the pathogenesis of exosome-related disorders and highlights the link between exosome function, ribosome biogenesis, and p53-dependent signalling. We suggest that exosome-related disorders could be classified as ribosomopathies

Roles of key active-site residues in flavocytochrome P450 BM3

Abbreviations used: P450, cytochrome P450 mono-oxygenase; ImC12, 12-(imidazolyl)dodecanoic acid; 1-PIM, 1-phenylimidazole.The effects of mutation of key active-site residues (Arg-47, Tyr-51, Phe-42 and Phe-87) in Bacillus megaterium flavocytochrome P450 BM3 were investigated. Kinetic studies on the oxidation of laurate and arachidonate showed that the side chain of Arg-47 contributes more significantly to stabilization of the fatty acid carboxylate than does that of Tyr-51 (kinetic parameters for oxidation of laurate: R47A mutant, Km 859 µM, kcat 3960 min-1; Y51F mutant, Km 432 µM, kcat 6140 min-1; wild-type, Km 288 µM, kcat 5140 min-1). A slightly increased kcat for the Y51F-catalysed oxidation of laurate is probably due to decreased activation energy (DG‡) resulting from a smaller DG of substrate binding. The side chain of Phe-42 acts as a phenyl 'cap' over the mouth of the substrate-binding channel. With mutant F42A, Km is massively increased and kcat is decreased for oxidation of both laurate (Km 2.08 mM, kcat 2450 min-1) and arachidonate (Km 34.9 µM, kcat 14620 min-1; compared with values of 4.7 µM and 17100 min-1 respectively for wild-type). Amino acid Phe-87 is critical for efficient catalysis. Mutants F87G and F87Y not only exhibit increased Km and decreased kcat values for fatty acid oxidation, but also undergo an irreversible conversion process from a 'fast' to a 'slow' rate of substrate turnover [for F87G (F87Y)-catalysed laurate oxidation: kcat 'fast', 760 (1620) min-1; kcat 'slow', 48.0 (44.6) min-1; kconv (rate of conversion from fast to slow form), 4.9 (23.8) min-1]. All mutants showed less than 10% uncoupling of NADPH oxidation from fatty acid oxidation. The rate of FMN-to-haem electron transfer was shown to become rate-limiting in all mutants analysed. For wild-type P450 BM3, the rate of FMN-to-haem electron transfer (8340 min-1) is twice the steady-state rate of oxidation (4100 min-1), indicating that other steps contribute to rate limitation. Active-site structures of the mutants were probed with the inhibitors 12-(imidazolyl)dodecanoic acid and 1-phenylimidazole. Mutant F87G binds 1-phenylimidazole > 10-fold more tightly than does the wild-type, whereas mutant Y51F binds the haem-co-ordinating fatty acid analogue 12-(imidazolyl)dodecanoic acid > 30-fold more tightly than wild-type

Reduced LIMK2 expression in colorectal cancer reflects its role in limiting stem cell proliferation

Objective: Colorectal cancer (CRC) is a major contributor to cancer mortality and morbidity. LIM kinase 2 (LIMK2) promotes tumour cell invasion and metastasis. The objectives of this study were to determine how LIMK2 expression is associated with CRC progression and patient outcome, and to use genetically modified Drosophila and mice to determine how LIMK2 deletion affects gastrointestinal stem cell regulation and tumour development.&lt;p&gt;&lt;/p&gt; Design: LIMK2 expression and activity were measured by immunostaining tumours from CRC-prone mice, human CRC cell lines and 650 human tumours. LIMK knockdown in Drosophila or Limk2 deletion in mice allowed for assessment of their contributions to gastrointestinal stem cell homeostasis and tumour development.&lt;p&gt;&lt;/p&gt; Results: LIMK2 expression was reduced in intestinal tumours of cancer-prone mice, as well as in human CRC cell lines and tumours. Reduced LIMK2 expression and substrate phosphorylation were associated with shorter patient survival. Genetic analysis in Drosophila midgut and intestinal epithelial cells isolated from genetically modified mice revealed a conserved role for LIMK2 in constraining gastrointestinal stem cell proliferation. Limk2 deletion increased colon tumour size in a colitis-associated colorectal mouse cancer model.&lt;p&gt;&lt;/p&gt; Conclusions: This study revealed that LIMK2 expression and activity progressively decrease with advancing stage, and supports the hypothesis that there is selective pressure for reduced LIMK2 expression in CRC to relieve negative constraints imposed upon gastrointestinal stem cells.&lt;p&gt;&lt;/p&gt

‘Mind the Gap’ : extending outcome measurement for accountability and meaningful innovation

We examine the outcome measurement landscape in care leaver innovation, where many innovations to support transitions of young people leaving care fail to sustain beyond a fixed-term pilot, and fewer impact wider transition policies. Our empirical qualitative study comprises interviews with 31 senior UK children’s social care policy and practice professionals, 103 interviews across five innovation-focused case studies within England with a range of public and private providers. We consider these data in relation to evaluations from a nationally diffused social care innovation. We identified three measurement landscape challenges. First, we highlight the limits of the economically oriented measurement and identify an overlooked outcome measurement demand. Second, we emphasise a need to stratify care leaver population outcomes to better reflect individuals transition through different domains of life and trajectory. Third, we identify areas of precarity around the intended use of care leaver experience. We conclude that tensions exist between the pull towards a unified approach to outcome measurement and the reality of decoupled outcome requirements and legitimacy-seeking priorities which differ according to stakeholder. These tensions entrench stagnant innovation. Recognition of roles and legitimacies that exist across the process of care leaver innovation is warranted. Opportunities for action are discussed