737 research outputs found

    Stereodivergent Synthesis of Enantioenriched 4-Hydroxy-2- cyclopentenones

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    Protected 4-hydroxycyclopentenones (4-HCPs) constitute an important class of intermediates in chemical synthesis. A route to this class of compound has been developed. Key steps include Noyori reduction (which establishes the stereochemistry of the product), ring-closing metathesis, and simple functional group conversions to provide a set of substituted 4-HCPs in either enantiomeric form

    Analysis of the shearing instability in nonlinear convection and magnetoconvection

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    Numerical experiments on two-dimensional convection with or without a vertical magnetic field reveal a bewildering variety of periodic and aperiodic oscillations. Steady rolls can develop a shearing instability, in which rolls turning over in one direction grow at the expense of rolls turning over in the other, resulting in a net shear across the layer. As the temperature difference across the fluid is increased, two-dimensional pulsating waves occur, in which the direction of shear alternates. We analyse the nonlinear dynamics of this behaviour by first constructing appropriate low-order sets of ordinary differential equations, which show the same behaviour, and then analysing the global bifurcations that lead to these oscillations by constructing one-dimensional return maps. We compare the behaviour of the partial differential equations, the models and the maps in systematic two-parameter studies of both the magnetic and the non-magnetic cases, emphasising how the symmetries of periodic solutions change as a result of global bifurcations. Much of the interesting behaviour is associated with a discontinuous change in the leading direction of a fixed point at a global bifurcation; this change occurs when the magnetic field is introduced

    Modelling production-consumption flows of goods in Europe: the trade model within Transtools3

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    The paper presents a new model for trade flows in Europe that is integrated with a logistics model for transport chain choice through Logsum variables. Logsums measures accessibility across an entire multi-modal logistical chain, and are calculated from a logistics model that has been estimated on disaggregated micro data and then used as an input variable in the trade model. Using Logsums in a trade model is new in applied large-scale freight models, where previous models have simply relied on the distance (e.g. crow-fly) between zones. This linkage of accessibility to the trade model makes it possible to evaluate how changes in policies on transport costs and changes in multi-modal networks will influence trade patterns. As an example the paper presents outcomes for a European-wide truck tolling scenario, which showcases to which extent trade is influenced by such a policy. The paper discusses how such a complex model can be estimated and considers the choice of mathematical formulation and the link between the trade model and logistics model. In the outcomes for the tolling scenario we decompose the total effects into effects from the trade model and effects from the logistics model

    'Why Should I Study English If I'm Never Going To Leave This Town?' Developing Alternative Orientations To Culture in the EFL Classroom Through CAR

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    This article describes the progress and findings of a collaborative action research project on the cultural dimension in primary levels of EFL education in Valencia (Spain). Its aim was to explore whether the EFL subject tended to ignore the students¿ native cultural background, and if so, whether this omission brought negative pedagogical consequences. It involved ten student-teachers who were carrying out their practicum placements at schools in the region, ten EFL school teachers, and a university researcher. Collective meetings were held to critically analyze the school experiences, and design experimental interventions to give a different orientation to culture in the EFL class. By the end of the CAR, the STs had become better teachers and researchers: they were more aware of the need for the learners¿ cultural background to become integrated into the communicative aims of the EFL subject, and more prepared to improve their theoretical and practical understanding of this dimension through research on their own teaching

    Framing interculturality: a corpus-based analysis of on-line promotional discourse of higher education intercultural communication courses

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    This paper examines how intercultural communication (ICC) and the notion of culture are framed in on-line promotional discourse of higher education intercultural communication courses. It analyses a specialised corpus comprised of 14,842 words from 43 course websites of master’s programmes in intercultural communication in the UK and the US—internationally, the two largest providers of such programmes. Through combining corpus tools with a ‘situated meaning’ approach, the analysis reveals that while a small number of courses acknowledge cultural ‘complexity’, culture is still very often reduced to an essentialised and static notion, despite growing criticism against such an approach in ICC literature. Intercultural communication is valorised as a combination of desirable skills and knowledge conducive to effective communication of different cultural groups and for those working in international arenas. Significant differences between the UK and US courses are identified with regard to the extent of associations with diversity-related social categories. The lack of interpretive, critical and constructivist positions on culture in promotional discourse is discussed in the context of neoliberal discourse and the current thinking towards professional competences dominant in Britain, North America, and other parts of the world

    Another tool in the genome-wide association study arsenal: population-based detection of somatic gene conversion

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    The hunt for the genetic contributors to complex disease has used a number of strategies, resulting in the identification of variants associated with many of the common diseases affecting society. However most of the genetic variants detected to date are single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) and fall far short of explaining the full genetic component of any given disease. An as yet untapped genomic mechanism is somatic gene conversion and deletion, which could be complicit in disease risk but has been challenging to detect in genome-wide datasets. In a recent publication in BMC Medicine by Kenneth Ross, the author uses existing datasets to look at somatic gene conversion and deletion in human disease. Here, we describe how Ross's recent efforts to detect such occurrences could impact the field going forward

    Dosage Effects of Cohesin Regulatory Factor PDS5 on Mammalian Development: Implications for Cohesinopathies

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    Cornelia de Lange syndrome (CdLS), a disorder caused by mutations in cohesion proteins, is characterized by multisystem developmental abnormalities. PDS5, a cohesion protein, is important for proper chromosome segregation in lower organisms and has two homologues in vertebrates (PDS5A and PDS5B). Pds5B mutant mice have developmental abnormalities resembling CdLS; however the role of Pds5A in mammals and the association of PDS5 proteins with CdLS are unknown. To delineate genetic interactions between Pds5A and Pds5B and explore mechanisms underlying phenotypic variability, we generated Pds5A-deficient mice. Curiously, these mice exhibit multiple abnormalities that were previously observed in Pds5B-deficient mice, including cleft palate, skeletal patterning defects, growth retardation, congenital heart defects and delayed migration of enteric neuron precursors. They also frequently display renal agenesis, an abnormality not observed in Pds5B−/− mice. While Pds5A−/− and Pds5B−/− mice die at birth, embryos harboring 3 mutant Pds5 alleles die between E11.5 and E12.5 most likely of heart failure, indicating that total Pds5 gene dosage is critical for normal development. In addition, characterization of these compound homozygous-heterozygous mice revealed a severe abnormality in lens formation that does not occur in either Pds5A−/− or Pds5B−/− mice. We further identified a functional missense mutation (R1292Q) in the PDS5B DNA-binding domain in a familial case of CdLS, in which affected individuals also develop megacolon. This study shows that PDS5A and PDS5B functions other than those involving chromosomal dynamics are important for normal development, highlights the sensitivity of key developmental processes on PDS5 signaling, and provides mechanistic insights into how PDS5 mutations may lead to CdLS
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