3,407 research outputs found

    Challenges for the implementation of the renewable heat incentive : an example from a school refurbishment geothermal scheme

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    The Government run UK Renewable Heat Incentive (RHI) scheme allows cash back payments to be made to producers of renewable heat. As a world first for renewable heat, it aims to tackle head on the issues surrounding emissions, energy use, and climate change targets. However, whilst the scheme goes a long way towards meeting these climate change targets, issues have been identified that may compromise its effectiveness. This paper aims to examine the progress of the RHI since its launch in November 2011, and avenues towards a more effective deploymen

    Unseen and unheard? Women managers and organizational learning

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    This paper aims to use (in)visibility as a lens to understand the lived experience of six women managers in the headquarters of a large multinational organization in the UK to identify how “gender” is expressed in the context of organizational learning. Design/methodology/approach: The researchers take a phenomenological approach via qualitative data collection with a purposeful sample – the six female managers in a group of 24. Data were collected through quarterly semi-structured interviews over 12 months with the themes – knowledge, interaction and gender. Findings: Organizations seek to build advantage to gain and retain competitive leadership. Their resilience in a changing task environment depends on their ability to recognize, gain and use knowledge likely to deliver these capabilities. Here, gender was a barrier to effective organizational learning with women’s knowledge and experience often unseen and unheard. Research limitations/implications: This is a piece of research limited to exploration of gender as other, but ethnicity, age, social class, disability and sexual preference, alone or in combination, may be equally subject to invisibility in knowledge terms; further research would be needed to test this however. Practical implications: Practical applications relate to the need for organizations to examine and address their operations for exclusion based on perceived “otherness”. Gendered organizations cause problems for their female members, but they also exclude the experience and knowledge of key individuals as seen here, where gender impacted on effective knowledge sharing and cocreation of knowledge. Social implications: The study offers further evidence of gendered organizations and their impacts on organizational effectiveness, but it also offers insights into the continues social acceptance of a masculinized normative model for socio-economic practice. Originality/value: This exploration of gender and organizational learning offers new insights to help explain the way in which organizational learning occurs – or fails to occur – with visibility/invisibility of one group shaped by gendered attitudes and processes. It shows that organizational learning is not gender neutral (as it appears in mainstream organizational learning research) and calls for researchers to include this as a factor in future research

    Perturbative behaviour of a vortex in a trapped Bose-Einstein condensate

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    We derive a set of equations that describe the shape and behaviour of a single perturbed vortex line in a Bose-Einstein condensate. Through the use of a matched asymptotic expansion and a unique coordinate transform a relation for a vortex's velocity, anywhere along the line, is found in terms of the trapping, rotation, and distortion of the line at that location. This relation is then used to find a set of differential equations that give the line's specific shape and motion. This work corrects a previous similar derivation by Anatoly A. Svidzinsky and Alexander L. Fetter [Phys. Rev. A \textbf{62}, 063617 (2000)], and enables a comparison with recent numerical results.Comment: 12 pages with 3 figure

    The role of SOXC transcription factors in B-cell development and lymphoid malignancies

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    Mantle cell lymphoma (MCL) accounts for 5-10% out of all Non-Hodgkin lymphomas (NHLs) and is one of the most aggressive forms of lymphomas with a median survival of less than 5 years. Currently, MCL is considered to be an incurable disease. MCL is characterized by the t(11;14)(q13;q32) CCND1/IGH translocation that results in high expression of cyclin D1. This translocation takes place at the pre-B cell stage and is generally recognized as the hallmark and primary oncogenic event in the evolution of MCL. Recently, the neural transcription factor SRY (sex-determining region Y) box 11 (SOX11) gene was found to be expressed in over 90% of all MCLs. The SOX11 protein is not detected in the vast majority of other lymphomas or mature B-cells and its expression is independent of cyclin D1 status. Moreover, SOX11 has been proposed to have a functional role in the pathogenesis of MCL and may not only serve as a diagnostic biomarker. In this thesis, the functional role of the SOXC genes (SOX4, SOX11 and SOX12) have been studied in several different ways, both in MCL primary samples/cell lines and in non-MCL related cells with focus on the SOX11 gene. The SOXC transcription factors are known to compete for the same target genes. For the first time in MCL, the SOXC genes were quantified by qPCR in a set of MCL patients and MCL cell lines. As previously reported, SOX11 expression was high in MCL, but also SOX12 mRNA levels were found to be higher compared to non-malignant B-cells, whereas the expression levels of SOX4 varied. Further, expression of the SOXC genes correlated in SOX11 positive MCL (determined by immunohistochemistry). How SOX11 gene expression in MCL is regulated was also addressed by studying its promotor region. The promotor region of SOX11 was found to be hypomethylated in MCL patients and cell lines, but also in non-malignant B-cells indicating regulation by other epigenetic mechanisms than promotor methylation. Fast and accurate differentiation between similar entities of lymphoma is important since MCL has a more aggressive clinical course. Although having certain distinctive phenotypical markers, MCL and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL) are both CD19+, CD20+ and usually CD5+, which could complicate diagnosis by flow cytometry. We developed a method to accurately implement SOX11 in the diagnostic flow panel that consistently detected SOX11 protein in ex vivo isolated MCL cells, but not in CLL/SLL. When conjugated SOX11-antibodies are available, this method could be implemented in the clinic for CLL/SLL with aberrant immune phenotypes or rare cyclin D1- MCLs. The expression levels of SOX11 were further studied in a relatively large group of MCL patients (n=102) by qPCR to determine a cut-off for SOX11-negative MCL and to investigate how quantitative expression related to positivity/negativity by IHC. A cut-off was defined, which resulted in misclassification of only 2/102 by qPCR and IHC. However, for the IHC SOX11+ cases, the qPCR analysis was not able to find a natural cut-off that would identify cases with low expression. When grouping the samples based on expression (10% lowest expression versus the remaining cases), nodal disease was less frequent (p=0.01) and lymphocytosis more frequent (p=0.005) in the qPCR SOX11low-cases. Leukemic non-nodal MCL often expresses low levels of SOX11. The quartile of patients with the lowest SOX11 expression had significantly shorter overall survival in the group of patients who did not receive autologous stem cell transplantation. Studies were conducted in primary murine B-cells and a murine pro-B cell line to study Sox11 oncogenic potential and role in differentiation in early B-cells. In the studied cell types, Sox11 did not per se act as an oncogene. Instead the rate of proliferation was reduced in the pro-B cell line and these cells changed morphology upon expressing the Sox11 gene. Gene expression analysis revealed upregulation of early cell cycle and cellular adhesion genes upon introduction of the Sox11 gene in the pro-B cells. Despite high similarity to Sox4 (important for B-cell survival and development), no obvious effect on selected B-cell differentiation stage associated genes were detected, which suggest that the effects of Sox11 are context dependent and might differ in murine pro-B cells compared to MCL and during embryogenesis

    Secretory vesicles are preferentially targeted to areas of low molecular SNARE density

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    Intercellular communication is commonly mediated by the regulated fusion, or exocytosis, of vesicles with the cell surface. SNARE (soluble N-ethymaleimide sensitive factor attachment protein receptor) proteins are the catalytic core of the secretory machinery, driving vesicle and plasma membrane merger. Plasma membrane SNAREs (tSNAREs) are proposed to reside in dense clusters containing many molecules, thus providing a concentrated reservoir to promote membrane fusion. However, biophysical experiments suggest that a small number of SNAREs are sufficient to drive a single fusion event. Here we show, using molecular imaging, that the majority of tSNARE molecules are spatially separated from secretory vesicles. Furthermore, the motilities of the individual tSNAREs are constrained in membrane micro-domains, maintaining a non-random molecular distribution and limiting the maximum number of molecules encountered by secretory vesicles. Together our results provide a new model for the molecular mechanism of regulated exocytosis and demonstrate the exquisite organization of the plasma membrane at the level of individual molecular machines

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    Unseen and unheard? women managers and organizational learning

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    Purpose This paper uses (in)visibility as a lens to understand the lived experience of 6 women managers in the U.K. HQ of a large multinational organization, in order to identify how ‘gender’ is expressed in the context of organizational learning Design/methodology/approach The researchers take a phenomenological approach via qualitative data collection with a purposeful sample –the six female managers in a group of 24. Data was collected through quarterly semi structured interviews over 12 months with the themes - knowledge, interaction and gender. Findings Organisations seek to build advantage in order to gain and retain competitive leadership. Their resilience in a changing task environment depends on their ability to recognize, gain and use knowledge likely to deliver these capabilities. Here gender was a barrier to effective organizational learning with women's knowledge and experience often unseen and unheard. Research limitations/implications This is a piece of research limited to exploration of gender as other but ethnicity, age, social class, disability and sexual preference, alone or in combination may be equally subject to invisibility in knowledge terms, further research would be needed to test this however. Practical implications Practical applications relate to the need for organizations to examine and address their operations for exclusion based on perceived ‘otherness’. Gendered organizations cause problems for their female members but they also exclude the experience and knowledge of key individuals as seen here, where gender impacted on effective knowledge sharing and cocreation of knowledge. Originality/value This exploration of gender and organisational learning offers new insights to help explain the way in which organisational learning occurs – or fails to occur - with visibility/invisibility of one group shaped by gendered attitudes and processes. It shows that organizational learning is not gender neutral (as it appears in mainstream organizational learning research) and calls for researchers to include this as a factor in future research

    RNA interference screening demystified

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    Genetic screens, where the effects of modifying gene function on cell behaviour are assessed in a systematic fashion, have for some time provided useful information to those interested in disease pathogenesis and treatment. Genetic screens exploiting the phenomenon of RNA interference (RNAi) are now becoming commonplace. This article explains the different RNAi screen formats and describes some of the applications of RNAi screening that may be pertinent to the research pathologist
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