1,113 research outputs found

    From white elephant to Nobel Prize: Dennis Gabor’s wavefront reconstruction

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    Dennis Gabor devised a new concept for optical imaging in 1947 that went by a variety of names over the following decade: holoscopy, wavefront reconstruction, interference microscopy, diffraction microscopy and Gaboroscopy. A well-connected and creative research engineer, Gabor worked actively to publicize and exploit his concept, but the scheme failed to capture the interest of many researchers. Gabor’s theory was repeatedly deemed unintuitive and baffling; the technique was appraised by his contemporaries to be of dubious practicality and, at best, constrained to a narrow branch of science. By the late 1950s, Gabor’s subject had been assessed by its handful of practitioners to be a white elephant. Nevertheless, the concept was later rehabilitated by the research of Emmett Leith and Juris Upatnieks at the University of Michigan, and Yury Denisyuk at the Vavilov Institute in Leningrad. What had been judged a failure was recast as a success: evaluations of Gabor’s work were transformed during the 1960s, when it was represented as the foundation on which to construct the new and distinctly different subject of holography, a re-evaluation that gained the Nobel Prize for Physics for Gabor alone in 1971. This paper focuses on the difficulties experienced in constructing a meaningful subject, a practical application and a viable technical community from Gabor’s ideas during the decade 1947-1957

    Effects of 5-HT2C, 5-HT1A receptor challenges and modafinil on the initiation and persistence of gambling behaviours

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    Rationale Problematic patterns of gambling are characterised by loss of control and persistent gambling often to recover losses. However, little is known about the mechanisms that mediate initial choices to begin gambling and then continue to gamble in the face of losing outcomes. Objectives These experiments first assessed gambling and loss-chasing performance under different win/lose probabilities in C57Bl/6 mice, and then investigated the effects of antagonism of 5-HT2CR with SB242084, 5-HT1AR agonism with 8-OH-DPAT and modafinil, a putative cognitive enhancer. Results As seen in humans and other species, mice demonstrated the expected patterns of behaviour as the odds for winning were altered increasing gambling and loss-chasing when winning was more likely. SB242084 decreased the likelihood to initially gamble, but had no effects on subsequent gambling choices in the face of repeated losses. In contrast, 8-OH-DPAT had no effects on choosing to gamble in the first place, but once started 8-OH-DPAT increased gambling choices in a dose-sensitive manner. Modafinil effects were different to the serotonergic drugs in both decreasing the propensity to initiate gambling and chase losses. Conclusions We present evidence for dissociable effects of systemic drug administration on different aspects of gambling behaviour. These data extend and reinforce the importance of serotonergic mechanisms in mediating discrete components of gambling behaviour. They further demonstrate the ability of modafinil to reduce gambling behaviour. Our work using a novel mouse paradigm may be of utility in modelling the complex psychological and neurobiological underpinnings of gambling problems, including the analysis of genetic and environmental factors

    The medium-term sustainability of organisational innovations in the national health service

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    Background: There is a growing recognition of the importance of introducing new ways of working into the UK's National Health Service (NHS) and other health systems, in order to ensure that patient care is provided as effectively and efficiently as possible. Researchers have examined the challenges of introducing new ways of working-'organisational innovations'-into complex organisations such as the NHS, and this has given rise to a much better understanding of how this takes place-and why seemingly good ideas do not always result in changes in practice. However, there has been less research on the medium-and longer-term outcomes for organisational innovations and on the question of how new ways of working, introduced by frontline clinicians and managers, are sustained and become established in day-to-day practice. Clearly, this question of sustainability is crucial if the gains in patient care that derive from organisational innovations are to be maintained, rather than lost to what the NHS Institute has called the 'improvement-evaporation effect'. Methods: The study will involve research in four case-study sites around England, each of which was successful in sustaining its new model of service provision beyond an initial period of pilot funding for new genetics services provided by the Department of Health. Building on findings relating to the introduction and sustainability of these services already gained from an earlier study, the research will use qualitative methods-in-depth interviews, observation of key meetings, and analysis of relevant documents-to understand the longer-term challenges involved in each case and how these were surmounted. The research will provide lessons for those seeking to sustain their own organisational innovations in wide-ranging clinical areas and for those designing the systems and organisations that make up the NHS, to make them more receptive contexts for the sustainment of innovation. Discussion: Through comparison and contrast across four sites, each involving different organisational innovations, different forms of leadership, and different organisational contexts to contend with, the findings of the study will have wide relevance. The research will produce outputs that are useful for managers and clinicians responsible for organisational innovation, policy makers and senior managers, and academics

    Toward a Theory of Innovation

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    The purpose of this article is to eliminate further conceptual obstacles to the develop ment of a workable theory of innovation and to move toward a better theoretic statement. The approach to overcoming the conceptual problems centers primarily around four ideas: (1) building a theory around the "innovation decision" as the unit of analysis, rather than either innovations or adopters: (2) lifting the level of general ity of independent variables so that a great deal of statistical interaction is avoided; (3) splitting the act of innovation into two stages, diffusion and adoption, to eliminate the confounding effects of time of awareness in studies of innovation; (4) introducing the idea of a "fair-trial point" into the conceptualization of innovation, solving sev eral additional problems at once.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68286/2/10.1177_009539977901000401.pd

    Conditional Deletion of Dnaic1 in a Murine Model of Primary Ciliary Dyskinesia Causes Chronic Rhinosinusitis

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    Studies of primary ciliary dyskinesia (PCD) have been hampered by the lack of a suitable animal model because disruption of essential ciliary genes in mice results in a high incidence of lethal hydrocephalus. To develop a viable mouse model for long-term studies of PCD, we have generated a transgenic mouse line in which two conserved exons of the mouse intermediate dynein chain gene, Dnaic1, are flanked by loxP sites (Dnaic1flox/flox). Dnaic1 is the murine homolog of human DNAI1, which is mutated in approximately 10% of human PCD cases. These mice have been crossed with mice expressing a tamoxifen-inducible Cre recombinase (CreER). Treatment of adult Dnaic1flox/flox/CreER+/− mice with tamoxifen results in an almost complete deletion of Dnaic1 with no evidence of hydrocephalus. Treated animals have reduced levels of full-length Dnaic1 mRNA, and electron micrographs of cilia demonstrate a loss of outer dynein arm structures. In treated Dnaic1flox/flox/CreER+/− animals, mucociliary clearance (MCC) was reduced over time. After approximately 3 months, no MCC was observed in the nasopharynx, whereas in the trachea, MCC was observed for up to 6 months, likely reflecting a difference in the turnover of ciliated cells in these tissues. All treated animals developed severe rhinosinusitis, demonstrating the importance of MCC to the health of the upper airways. However, no evidence of lung disease was observed up to 11 months after Dnaic1 deletion, suggesting that other mechanisms are able to compensate for the lack of MCC in the lower airways of mice. This model will be useful for the study of the pathogenesis and treatment of PCD

    Simultaneous chronic rupture of quadriceps tendon and contra-lateral patellar tendon in a patient affected by tertiary hyperparatiroidism

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    Spontaneous ruptures of the extensor mechanism of the knee are very rare. They tend to increase considerably in patients with metabolic diseases such as chronic renal failure, hyperparathyroidism, diabetes, gout, and systemic lupus erythematosus. The reported case regards a 48-year-old man with chronic, spontaneous and simultaneous quadriceps, and contra-lateral patellar tendon rupture. The patient suffered from chronic renal failure and for the past year from tertiary hyperparathyroidism. Ruptured tendons were repaired and both knee were evaluated monthly for the next 12 months. Good functional recovery was achieved on both knees without relapse. This case emphasizes the importance of long-term high parathyroid hormone level in the etiology of tendons ruptures

    Choosing a genome browser for a Model Organism Database: surveying the Maize community

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    As the B73 maize genome sequencing project neared completion, MaizeGDB began to integrate a graphical genome browser with its existing web interface and database. To ensure that maize researchers would optimally benefit from the potential addition of a genome browser to the existing MaizeGDB resource, personnel at MaizeGDB surveyed researchers’ needs. Collected data indicate that existing genome browsers for maize were inadequate and suggest implementation of a browser with quick interface and intuitive tools would meet most researchers’ needs. Here, we document the survey’s outcomes, review functionalities of available genome browser software platforms and offer our rationale for choosing the GBrowse software suite for MaizeGDB. Because the genome as represented within the MaizeGDB Genome Browser is tied to detailed phenotypic data, molecular marker information, available stocks, etc., the MaizeGDB Genome Browser represents a novel mechanism by which the researchers can leverage maize sequence information toward crop improvement directly

    The Treasured Hunt: Collecting Medieval and Renaissance Manuscripts, Past, Present, and Future

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    Welcome and Opening Remarks: E. Ann Matter, University of Pennsylvania, and Lynn Ransom, Free Library of Philadelphia Session 1. Beginnings: Collecting in the Middle Ages and Renaissance Session Chair: Emily Steiner, Department of English, University of Pennsylvania Claire Richter Sherman, Center for Advanced Study in the Visual Arts at the National Gallery of Art, The Manuscript Collection of King Charles V of France: The Personal and the Political David Rundle, History Faculty and Corpus Christi College, Oxford University, The Butcher of England and the Renaissance Arts of Book-Collecting Session 2: Civic Service: The Legacies of Philadelphia-Area Collectors Chair: Peter Stallybrass, Department of English, University of Pennsylvania James Tanis, Director of Libraries and Professor of History Emeritus, Bryn Mawr College, Migrating Manuscripts Derick Dreher, Director, The Rosenbach Museum & Library, Of Private Collectors and Public Libraries: Dr. A. S. W. Rosenbach and John Frederick Lewis Session 3: Keynote address Welcome: H. Carton Rogers, Vice Provost & Director of Libraries, University of Pennsylvania Chair: Robert Maxwell, Department of the History of Art, University of Pennsylvania Christopher de Hamel, Gaylord Donnelley Fellow Librarian, Corpus Christi College, Cambridge University, The Manuscript Collection of C. L. Ricketts (1859-1941) Session 4: The Hunters and the Hunted: A Roundtable Discussion with Private and Institutional Collectors Chair: David Wallace, Department of English, University of Pennsylvania Moderator: Richard Linenthal, Bernard Quaritch Ltd. Panelists: Lawrence J. Schoenberg, Private Collector Gifford Combs, Private Collector Toshiyuki Takamiya, Private Collector, Keio University Consuelo Dutschke, Curator of Medieval and Renaissance Manuscripts, Columbia University William Noel, Curator of Manuscripts and Rare Books, The Walters Art Museu

    Synthesis, Characterization and Magnetic Susceptibility of the Heavy Fermion Transition Metal Oxide LiV_{2}O_{4}

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    The preparative method, characterization and magnetic susceptibility \chi measurements versus temperature T of the heavy fermion transition metal oxide LiV_{2}O_{4} are reported in detail. The intrinsic \chi(T) shows a nearly T-independent behavior below ~ 30 K with a shallow broad maximum at about 16 K, whereas Curie-Weiss-like behavior is observed above 50-100 K. Field-cooled and zero-field-cooled magnetization M measurements in applied magnetic fields H = 10 to 100 G from 1.8 to 50 K showed no evidence for spin-glass ordering. Crystalline electric field theory for an assumed cubic V point group symmetry is found insufficient to describe the observed temperature variation of the effective magnetic moment. The Kondo and Coqblin-Schrieffer models do not describe the magnitude and T dependence of \chi with realistic parameters. In the high T range, fits of \chi(T) by the predictions of high temperature series expansion calculations provide estimates of the V-V antiferromagnetic exchange coupling constant J/k_{B} ~ 20 K, g-factor g ~ 2 and the T-independent susceptibility. Other possible models to describe the \chi(T) are discussed. The paramagnetic impurities in the samples were characterized using isothermal M(H) measurements with 0 < H <= 5.5 Tesla at 2 to 6 K. These impurities are inferred to have spin S_{imp} ~ 3/2 to 4, g_{imp} ~ 2 and molar concentrations of 0.01 to 0.8 %, depending on the sample.Comment: 19 typeset RevTeX pages, 16 eps figures included, uses epsf; to be published in Phys. Rev.
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