201 research outputs found

    [Chapter 1 from] The Power of Invisible Leadership: How a Compelling Common Purpose Inspires Exceptional Leadership

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    A powerful force draws people to leadership in countless businesses, nonprofits, government agencies, and social movements—we call it invisible leadership. Invisible leadership embodies situations in which dedication to a compelling and deeply held common purpose is the motivating force for leadership. Common purpose is more than a mission statement. It is a profound sense of common destiny, a life course or calling, aligned with a mission that resonates profoundly with our values and our sense of ourselves and others. This readable, research-based book shows readers how invisible leadership exists in the space between leaders and followers, artists and subjects, and purposes and people. Rather than reinforcing the idea that leadership is embodied in celebrity leaders or in gifted and charismatic individuals, the well known and highly admired authors of this insightful new book identify “charisma of purpose” as the motivating force for invisible leadership. A brief discussion of how invisible leadership impacts businesses, nonprofits, government agencies, and social movements guides the reader toward an understanding of the antecedents and possibilities of this way of thinking.https://scholarship.richmond.edu/bookshelf/1012/thumbnail.jp

    Identification of Class I HLA T Cell Control Epitopes for West Nile Virus

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    The recent West Nile virus (WNV) outbreak in the United States underscores the importance of understanding human immune responses to this pathogen. Via the presentation of viral peptide ligands at the cell surface, class I HLA mediate the T cell recognition and killing of WNV infected cells. At this time, there are two key unknowns in regards to understanding protective T cell immunity: 1) the number of viral ligands presented by the HLA of infected cells, and 2) the distribution of T cell responses to these available HLA/viral complexes. Here, comparative mass spectroscopy was applied to determine the number of WNV peptides presented by the HLA-A*11:01 of infected cells after which T cell responses to these HLA/WNV complexes were assessed. Six viral peptides derived from capsid, NS3, NS4b, and NS5 were presented. When T cells from infected individuals were tested for reactivity to these six viral ligands, polyfunctional T cells were focused on the GTL9 WNV capsid peptide, ligands from NS3, NS4b, and NS5 were less immunogenic, and two ligands were largely inert, demonstrating that class I HLA reduce the WNV polyprotein to a handful of immune targets and that polyfunctional T cells recognize infections by zeroing in on particular HLA/WNV epitopes. Such dominant HLA/peptide epitopes are poised to drive the development of WNV vaccines that elicit protective T cells as well as providing key antigens for immunoassays that establish correlates of viral immunity. © 2013 Kaabinejadian et al

    Community resilience : a policy tool for local government?

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    In many countries, local government has been a prime target of austerity measures. In response, local authorities are exploring a new repertoire of policy approaches in a bid to provide more with less. In England, local authorities have been drawn to community resilience as a pragmatic response to the challenge of deploying shrinking resources to support communities exposed to social and economic disruption. This application of resilience thinking is not without its challenges. It demands a working definition of community resilience that recognises the potential for communities to prove resilient to shocks and disruptions, but avoids blaming them for their predicament. There is also the practical challenge of developing and targeting interventions to promote and protect resilience. This paper sets out to explore these issues and establish the potential utility of community resilience as a policy tool through case study analysis in the city of Sheffield

    Seasonal changes in plankton respiration and bacterial metabolism in a temperate shelf sea

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    The seasonal variability of plankton metabolism indicates how much carbon is cycling within a system, as well as its capacity to store carbon or export organic matter and CO2 to the deep ocean. Seasonal variability between November 2014, April 2015 and July 2015 in plankton respiration and bacterial (Bacteria+Archaea) metabolism is reported for the upper and bottom mixing layers at two stations in the Celtic Sea, UK. Upper mixing layer (UML, >75 m in November, 41 - 70 m in April and ~50 m in July) depth-integrated plankton metabolism showed strong seasonal changes with a maximum in April for plankton respiration (1.2- to 2-fold greater compared to November and July, respectively) and in July for bacterial production (2-fold greater compared to November and April). However UML depth-integrated bacterial respiration was similar in November and April and 2-fold lower in July. The greater variability in bacterial production compared to bacterial respiration drove seasonal changes in bacterial growth efficiencies, which had maximum values of 89 % in July and minimum values of 5 % in November. Rates of respiration and gross primary production (14C-PP) also showed different seasonal patterns, resulting in seasonal changes in 14C-PP:CRO2 ratios. In April, the system was net autotrophic (14C-PP:CRO2 > 1), with a surplus of organic matter available for higher trophic levels and export, while in July balanced metabolism occurred (14C-PP:CRO2 = 1) due to an increase in plankton respiration and a decrease in gross primary production. Comparison of the UML and bottom mixing layer indicated that plankton respiration and bacterial production were higher (between 4 and 8-fold and 4 and 7-fold, respectively) in the UML than below. However, the rates of bacterial respiration were not statistically different (p > 0.05) between the two mixing layers in any of the three sampled seasons. These results highlight that, contrary to previous data from shelf seas, the production of CO2 by the plankton community in the UML, which is then available to degas to the atmosphere, is greater than the respiratory production of dissolved inorganic carbon in deeper waters, which may contribute to offshore export

    A shared MHC supertype motif emerges by convergent evolution in macaques and mice, but is totally absent in human MHC molecules

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    The SIV-infected rhesus macaque (Macaca mulatta) is the most established model of AIDS disease systems, providing insight into pathogenesis and a model system for testing novel vaccines. The understanding of cellular immune responses based on the identification and study of Major Histocompatibility Complex (MHC) molecules, including their MHC:peptide-binding motif, provides valuable information to decipher outcomes of infection and vaccine efficacy. Detailed characterization of Mamu-B*039:01, a common allele expressed in Chinese rhesus macaques, revealed a unique MHC:peptide-binding preference consisting of glycine at the second position. Peptides containing a glycine at the second position were shown to be antigenic from animals positive for Mamu-B*039:01. A similar motif was previously described for the Dd mouse MHC allele, but for none of the human HLA molecules for which a motif is known. Further investigation showed that one additional macaque allele, present in Indian rhesus macaques, Mamu-B*052:01, shares this same motif. These “G2” alleles were associated with the presence of specific residues in their B pocket. This pocket structure was found in 6% of macaque sequences but none of 950 human HLA class I alleles. Evolutionary studies using the “G2” alleles points to common ancestry for the macaque sequences, while convergent evolution is suggested when murine and macaque sequences are considered. This is the first detailed characterization of the pocket residues yielding this specific motif in nonhuman primates and mice, revealing a new supertype motif not present in humans

    Rhesus macaque MHC class I molecules show differential subcellular localizations

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    The MHC class I gene family of rhesus macaques is characterised by considerable gene duplications. While a HLA-C-orthologous gene is absent, the Mamu-A and in particular the Mamu-B genes have expanded, giving rise to plastic haplotypes with differential gene content. Although some of the rhesus macaque MHC class I genes are known to be associated with susceptibility/resistance to infectious diseases, the functional significance of duplicated Mamu-A and Mamu-B genes and the expression pattern of their encoded proteins are largely unknown. Here, we present data of the subcellular localization of AcGFP-tagged Mamu-A and Mamu-B molecules. We found strong cell surface and low intracellular expression for Mamu-A1, Mamu-A2 and Mamu-A3-encoded molecules as well as for Mamu-B*01704, Mamu-B*02101, Mamu-B*04801, Mamu-B*06002 and Mamu-B*13401. In contrast, weak cell surface and strong intracellular expression was seen for Mamu-A4*1403, Mamu-B*01202, Mamu-B*02804, Mamu-B*03002, Mamu-B*05704, Mamu-I*010201 and Mamu-I*0121. The different expression patterns were assigned to the antigen-binding α1 and α2 domains, suggesting failure of peptide binding is responsible for retaining ‘intracellular’ Mamu class I molecules in the endoplasmic reticulum. These findings indicate a diverse functional role of the duplicated rhesus macaque MHC class I genes

    High-resolution net and gross biological production during a Celtic Sea spring bloom

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    Shelf seas represent only 10% of the ocean area, but support up to 30% of all oceanic primary production. There are few measurements of shelf-sea biological production at high spatial and temporal resolution in such heterogeneous and physically dynamic systems. Here, we use dissolved oxygen-to-argon (O2/Ar) ratios and oxygen triple isotopes (16O, 17O, 18O) to estimate net and gross biological production in the Celtic Sea during spring 2015. O2/Ar ratios were measured continuously using a shipboard membrane inlet mass spectrometer (MIMS). Additional discrete water samples from CTD hydrocasts were used to measure O2/Ar depth profiles and the δ(17O) and δ(18O) values of dissolved O2. These high-resolution data were combined with wind-speed based gas exchange parameterisations to calculate biologically driven air-sea oxygen fluxes. After correction for disequilibrium terms and diapycnal diffusion, these fluxes yielded estimates of net community (N(O2/Ar)) and gross O2 production (G(17O)). N(O2/Ar) was spatially heterogeneous and showed predominantly autotrophic conditions, with an average of (33±41) mmol m-2 d-1. G(17O) showed high variability between 0 and 424 mmol m-2 d-1. The ratio of N(O2/Ar) to G(17O), ƒ(O2), was (0.18±0.03) corresponding to 0.34±0.06 in carbon equivalents. We also observed rapid temporal changes in N(O2/Ar), e.g. an increase of 80 mmol m-2 d-1 in less than 6 hours during the spring bloom, highlighting the importance of high-resolution biological production measurements. Such measurements will help reconcile the differences between satellite and in situ productivity observations, and improve our understanding of the biological carbon pump

    Opportunities for improving animal welfare in rodent models of epilepsy and seizures

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    Animal models of epilepsy and seizures, mostly involving mice and rats, are used to understand the pathophysiology of the different forms of epilepsy and their comorbidities, to identify biomarkers, and to discover new antiepileptic drugs and treatments for comorbidities. Such models represent an important area for application of the 3Rs (replacement, reduction and refinement of animal use). This report provides background information and recommendations aimed at minimising pain, suffering and distress in rodent models of epilepsy and seizures in order to improve animal welfare and optimise the quality of studies in this area. The report includes practical guidance on principles of choosing a model, induction procedures, in vivo recordings, perioperative care, welfare assessment, humane endpoints, social housing, environmental enrichment, reporting of studies and data sharing. In addition, some model-specific welfare considerations are discussed, and data gaps and areas for further research are identified. The guidance is based upon a systematic review of the scientific literature, survey of the international epilepsy research community, consultation with veterinarians and animal care and welfare officers, and the expert opinion and practical experience of the members of a Working Group convened by the United Kingdom's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs)

    Problem drug use the public health imperative: what some of the literature says

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    <p>Abstract</p> <p>Background</p> <p>With more than 200,000 problem drug users is contact with structured treatment services in England the public health imperative behind drug treatment is great. Problem drug use for many is a chronic and relapsing condition, where "cure" is often neither a reasonable or appropriate expectation and it can further be argued that in these circumstances problem drug use is no different from any number of chronic and enduring health conditions that are managed in the health care system and therefore should be conceptualised as such.</p> <p>Discussion</p> <p>A public health approach to drug treatment emphasises the need for drug users in or accessing treatment, to reduce their harmful drug use, reduce drug use related risks such as sepsis and overdose and stay alive for longer. However a public health perspective in relation to problem drug use isn't always either apparent or readily understood and to that end there is still a significant need to continue the arguments and debate that treatment and interventions for problem and dependent drug users need to extend beyond an individualistic approach. For the purposes of discussion in this article public and population health will be used interchangeably.</p> <p>Summary</p> <p>A recognition and acceptance that a public and population health approach to the management of problem drug users is sound public health policy also then requires a long term commitment in terms of staffing and resources where service delivery mirrors that of chronic condition management.</p
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