14,342 research outputs found

    News fromthe Director General History: Sources on D-Day and the Normandy Campaign

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    News from the Directorate of History

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    News from the Director General History: Searching for Information about Individuals

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    Retransmission of Hydrometric Data in Canada

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    There are no author-identified significant results in this report

    Theorizing the relationship between UK schools and migrant parents of Eastern European origin: the parentsā€™ perspective

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    Schools may be particularly challenged in the building of relationships with immigrant families because of a potentially heightened mutual lack of knowledge or understanding about the other partyā€™s cultural norms (e.g. Crozier & Davis, 2007). In the context of increased immigration from Eastern and Central European states, this study seeks to initiate the development of model of multi-cultural family-school interaction drawing on existing frameworks drawn from the fields of education, psychology and sociology. With the intention of establishing the nature of migrant parentsā€™ constructions of their relationships with their childrenā€™s schools, we carried out in-depth, semi-structured interviews with 10 parents of school age children who had migrated to the UK from Eastern and Central Europe within the past 10 years. The key themes from the interviews indicated that the parentsā€™ expectations of their childrenā€™s schooling appear to clash with those of the UK school system and that this is amplified by perceptions of poor communication, inadequate school-parent cooperation & marginalisation. Through the use of existing theoretical frameworks it was established that there is potential for improved practice though development of a model though this must take account of the full contextual complexity of the relationships

    Intended or unintended strategy? The activities of middle managers in strategy implementation

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    When top managers task middle managers with implementing strategies, those strategies are often executed in a deviated form, which leads to the creation of unintended strategies. Despite much research on middle managers and their role and behaviors in strategy implementation, there is still only a limited understanding of the implementation activities that result in intended and unintended strategies. Using a strategy-as-practice perspective and interviews with 40 middle managers about 122 strategy implementations, we investigate strategy implementation activities and develop a model of middle manager activities in strategy implementation. We find that seven of the ten activities differ in frequency between intended and unintended strategies. This study extends the strategy implementation literature by conceptualizing a critical link in how different strategy implementation outcomes come about. We also broaden the middle management perspective in strategy by extending the range of activities that explain middle managersā€™ engagement with strategy and differentiating them across two strategy implementation outcomes

    Hypocretin-1 receptors regulate the reinforcing and reward-enhancing effects of cocaine: pharmacological and behavioral genetics evidence.

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    Considerable evidence suggests that transmission at hypocretin-1 (orexin-1) receptors (Hcrt-R1) plays an important role in the reinstatement of extinguished cocaine-seeking behaviors in rodents. However, far less is known about the role for hypocretin transmission in regulating ongoing cocaine-taking behavior. Here, we investigated the effects of the selective Hcrt-R1 antagonist SB-334867 on cocaine intake, as measured by intravenous (IV) cocaine self-administration in rats. The stimulatory effects of cocaine on brain reward systems contribute to the establishment and maintenance of cocaine-taking behaviors. Therefore, we also assessed the effects of SB-334867 on the reward-enhancing properties of cocaine, as measured by cocaine-induced lowering of intracranial self-stimulation (ICSS) thresholds. Finally, to definitively establish a role for Hcrt-R1 in regulating cocaine intake, we assessed IV cocaine self-administration in Hcrt-R1 knockout mice. We found that SB-334867 (1-4 mg/kg) dose-dependently decreased cocaine (0.5 mg/kg/infusion) self-administration in rats but did not alter responding for food rewards under the same schedule of reinforcement. This suggests that SB-334867 decreased cocaine reinforcement without negatively impacting operant performance. SB-334867 (1-4 mg/kg) also dose-dependently attenuated the stimulatory effects of cocaine (10 mg/kg) on brain reward systems, as measured by reversal of cocaine-induced lowering of ICSS thresholds in rats. Finally, we found that Hcrt-R1 knockout mice self-administered far less cocaine than wildtype mice across the entire dose-response function. These data demonstrate that Hcrt-R1 play an important role in regulating the reinforcing and reward-enhancing properties of cocaine and suggest that hypocretin transmission is likely essential for establishing and maintaining the cocaine habit in human addicts

    Structural modeling and functional analysis of the essential ribosomal processing protease Prp from Staphylococcus aureus

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    In Firmicutes and related bacteria, ribosomal large subunit protein L27 is encoded with a conserved N-terminal extension that is removed to expose residues critical for ribosome function. Bacteria encoding L27 with this N-terminal extension also encode a sequence-specific cysteine protease, Prp, which carries out this cleavage. In this work, we demonstrate that L27 variants with an un-cleavable N-terminal extension, or lacking the extension (pre-cleaved), are unable to complement an L27 deletion in Staphylococcus aureus. This indicates that N-terminal processing of L27 is not only essential but possibly has a regulatory role. Prp represents a new clade of previously uncharacterized cysteine proteases, and the dependence of S. aureus on L27 cleavage by Prp validates the enzyme as a target for potential antibiotic development. To better understand the mechanism of Prp activity, we analyzed Prp enzyme kinetics and substrate preference using a fluorogenic peptide cleavage assay. Molecular modeling and site-directed mutagenesis implicate several residues around the active site in catalysis and substrate binding, and support a structural model in which rearrangement of a flexible loop upon binding of the correct peptide substrate is required for the active site to assume the proper conformation. These findings lay the foundation for the development of antimicrobials that target this novel, essential pathway
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