2,520 research outputs found

    Laments and serenades: relationship marketing and legitimation strategies for the cultural entrepreneur

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    This paper investigates how the marketing/entrepreneurship interface functions within the cultural sector. Specifically, the paper considers how cultural entrepreneurs in the music industry market not to customers, but to networks that control the resources necessary to support entrepreneurial ventures. Evidence is drawn from the qualitative research of a study on access to finance by owner-managers of independent music companies (“cultural entrepreneurs”). The findings support the notion that “legitimation” is a key factor in accessing such resources. Cultural entrepreneurs have difficulties in establishing either “pragmatic legitimation” (derived from the self-interest of organisations across marketing networks) or “cognitive legitimation” (derived from perceptions of normality and conformity within marketing networks). Marketing strategies at both individual and industry level are put forward to overcome these barriers. For individual businesses, a “selection strategy” using creative clusters or a “manipulation strategy” that manages the cultural environment are recommended. The implications for relationship marketing models are discussed

    Application of expert systems in project management decision aiding

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    The feasibility of developing an expert systems-based project management decision aid to enhance the performance of NASA project managers was assessed. The research effort included extensive literature reviews in the areas of project management, project management decision aiding, expert systems technology, and human-computer interface engineering. Literature reviews were augmented by focused interviews with NASA managers. Time estimation for project scheduling was identified as the target activity for decision augmentation, and a design was developed for an Integrated NASA System for Intelligent Time Estimation (INSITE). The proposed INSITE design was judged feasible with a low level of risk. A partial proof-of-concept experiment was performed and was successful. Specific conclusions drawn from the research and analyses are included. The INSITE concept is potentially applicable in any management sphere, commercial or government, where time estimation is required for project scheduling. As project scheduling is a nearly universal management activity, the range of possibilities is considerable. The INSITE concept also holds potential for enhancing other management tasks, especially in areas such as cost estimation, where estimation-by-analogy is already a proven method

    Modulation of TGF-beta signaling by proinflammatory cytokines in articular chondrocytes.

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    OBJECTIVE: The normal structure and function of articular cartilage are the result of a precisely balanced interaction between anabolic and catabolic processes. The transforming growth factor-beta (TGF-beta) family of growth factors generally exerts an anabolic or repair response; in contrast, proinflammatory cytokines such as interleukin 1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) exert a strong catabolic effect. Recent evidence has shown that IL-1beta, and TNF-alpha, and the TGF-beta signaling pathways share an antagonistic relationship. The aim of this study was to determine whether the modulation of the response of articular chondrocytes to TGF-beta by IL-1beta or TNF-alpha signaling pathways occurs through regulation of activity and availability of mothers against DPP (Drosophila) human homologue (Smad) proteins. METHODS: Human articular chondrocytes isolated from knee joints from patients with osteoarthritis (OA) or normal bovine chondrocytes were cultured in suspension in poly-(2-hydroxyethyl methacrylate)-coated dishes with either 10% fetal bovine serum media or serum-deprived media 6h before treatment with IL-1beta alone, TNF-alpha alone or IL-1beta followed by TGF-beta. Nuclear extracts were examined by electrophoretic mobility-shift assays (EMSA) for nuclear factor-kappa B (NF-kappaB) and Smad3/4 deoxyribonucleic acid (DNA) binding. Nuclear extracts were also subjected to the TranSignal Protein/DNA array (Panomics, Redwood City, CA) enabling the simultaneous semiquantitative assessment of DNA-binding activity of 54 different transcription factors. Nuclear phospho-Smad2/3 and total Smad7 protein expression in whole cell lysates were studied by Western blot. Cytoplasmic Smad7, type II collagen alpha 1 (COL2A1), aggrecan and SRY-related high mobility group-Box gene 9 (SOX-9) mRNA expression were measured by real-time polymerase chain reaction (PCR). RESULTS: The DNA-binding activity of Smad3/4 in the TranSignal Protein/DNA array was downregulated by TNF-alpha (46%) or IL-1beta treatment (42%). EMSA analysis showed a consistent reduction in Smad3/4 DNA-binding activity in human articular chondrocytes treated with IL-1beta or TNF-alpha. TGF-beta-induced Smad3/4 DNA-binding activity and Smad2/3 phosphorylation were also reduced following pretreatment with IL-1beta in human OA and bovine chondrocytes. Real-time PCR and Western blot analysis showed that IL-1beta partially reversed the TGF-beta stimulation of Smad7 mRNA and protein levels in TGF-beta-treated human OA cells. In contrast, TGF-beta-stimulated COL2A1, aggrecan, and SOX-9 mRNA levels were abrogated by IL-1beta. CONCLUSIONS: IL-1beta or TNF-alpha exerted a suppressive effect on Smad3/4 DNA-binding activity in human articular chondrocytes, as well as on TGF-beta-induced stimulation of Smad3/4 DNA-binding activity and Smad2/3 phosphorylation in human OA and bovine articular chondrocytes. IL-1beta partially reversed the increase in TGF-beta-stimulated Smad7 mRNA or protein levels suggesting that Smad7 may not be involved in the suppression of TGF-beta signaling induced by IL-1beta or TNF-alpha in articular chondrocytes. The balance between the IL-1beta or TNF-alpha and the TGF-beta signaling pathways is crucial for maintenance of articular cartilage homeostasis and its disruption likely plays a substantial role in the pathogenesis of OA

    Innovative approaches to selective detection and remote analysis : developments in surface-enhanced raman scattering (sers)-based and separations-based fiberoptic chemical sensors

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    This two-part study investigates the feasibility of selective detection in remote analysis based on 1) surface-enhanced Raman scattering (SERS), and 2) separations-based fiberoptic sensing (SBFOS). For the first case, the extremely sharp spectral features of Raman scattering can sometimes allow the analysis of multicomponent samples without complicated sample pretreatment steps. Furthermore, the giant signal-enhancing effect of SERS can enable trace level detection. A solid, surface-based metallic substrate approach is taken for the development of a practical SERS technology. Various substrates are described, including silver-coated alumina, silver-coated Ti02, and silver islands. These substrates are economical and easy to fabricate with a high degree of reproducibility. Furthermore, they are readily integrated with fiberoptic sensors for remote SERS detection. Three fiberoptic SERS sensor systems are described in this work. The surface-based substrates are also applied to the detection of organic vapors. In the latter case, the high separation efficiency of capillary electrophoresis is coupled with laser-induced fluorescence (LIF) detection in the development of a fiberoptic sensor. Although LIF can offer exceptional detectability, its application to the analysis of complex samples can be difficult due to the broadband nature of fluorescence. It often requires sample pretreatment steps such as separations. In the SBFOS approach, separations can be performed remotely. Several complications are associated with the development of CE-based SBFOSs and are described in this work. Four SBFOS designs are described and applied to analysis environmentally and biomedically significant samples

    Design and Initial Verification of a Novel Total Knee Replacement that Incorporates Synthetic Ligaments to Influence Knee Stability

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    In the United States, the number of patients under the age of 65 who are receiving total knee replacements (TKRs) is rising due to increasing demand for and access to this life-changing orthopaedic procedure. Although this younger population tends to have a higher life expectancy, they have also been shown to have a lower implant survival rate than patients over the age of 65, possibly due to their more active lifestyles. Thus, there will be a rising demand for implants that have both a higher functionality and survivorship to meet performance demands of younger patient\u27s lifestyles. The purpose of this study was to design and initially verify a novel TKR design that incorporates artificial ligaments into a knee replacement whose stability and eventual kinematic performance will be driven by both geometry and ligamentous structure. A computational model was first developed that incorporated synthetic ligaments into an existing knee replacement within an anatomical knee model using the AnyBody modeling software system. Simulated A/P drawer tests at different flexion angles were analyzed for over 2,916 possible anterior and posterior cruciate ligament location and length combinations to determine the effects of ligament length and location on the A/P stability of the TKR. A complete physical model was then designed and constructed, and the computational model was verified by performing mechanical testing on an Instron system. A/P drawer tests were performed under 710 N of simulated body weight. Tibial A/P displacement was tracked for the TKR system with and without cruciate ligaments to determine the effect of ligament placement on resulting TKR stability. Ligament length and location were found to significantly influence knee laxity and knee flexion. Knee flexion was determined to be more sensitive to the ACL attachment location on the femur than on the tibia. As ACL insertion location moved posteriorly on the femur, it was found to decrease ACL ligament strain enabling a higher range of flexion. In general, as ACL and PCL length increased, the A/P laxity of the TKR system increased linearly. Interestingly, range of motion was found to be more dependent on ligament attachment location than ligament lengths. Knee replacement stability is clearly affected by synthetic ligament length and location within a TKR system. A knee replacement that incorporates synthetic ligaments with calibrated location and lengths should be able to significantly influence kinematic performance of the TKR system, possibly influencing long-term functional outcomes

    New Insight Into Desmosome Structure By Whole Cell Cryo-electron Tomography

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    Complex trajectory method in time-dependent WKB

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    We present a significant improvement to a time-dependent WKB (TDWKB) formulation developed by Boiron and Lombardi [JCP {\bf108}, 3431 (1998)] in which the TDWKB equations are solved along classical trajectories that propagate in the complex plane. Boiron and Lombardi showed that the method gives very good agreement with the exact quantum mechanical result as long as the wavefunction does not exhibit interference effects such as oscillations and nodes. In this paper we show that this limitation can be overcome by superposing the contributions of crossing trajectories. We also demonstrate that the approximation improves when incorporating higher order terms in the expansion. These improvements could make the TDWKB formulation a competitive alternative to current time-dependent semiclassical methods

    Harnessing Technology: new modes of technology-enhanced learning: opportunities and challenges

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    A report commissioned by Becta to explore the potential impact on education, staff and learners of new modes of technology enhanced learning, envisaged as becoming available in subsequent years. A generative framework, developed by the researchers is described, which was used as an analytical tool to relate the possibilities of the technology described to learning and teaching activities. This report is part of the curriculum and pedagogy strand of Becta's programme of managed research in support of the development of Harnessing Technology: Next Generation Learning 2008-14. A system-wide strategy for technology in education and skills. Between April 2008 and March 2009, the project carried out research, in three iterative phases, into the future of learning with technology. The research has drawn from, and aims to inform, all UK education sectors

    Extending the aridity record of the Southwest Kalahari: current problems and future perspectives

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    An extensive luminescence-based chronological framework has allowed the reconstruction of expansions and contractions of the Kalahari Desert over the last 50 ka. However, this chronology is largely based on near-surface pits and sediment exposures. These are the points on the landscape most prone to reactivation and resetting of the luminescence dating ‘clock’. This is proving to be a limiting feature for extending palaeoenvironmental reconstructions further back in time. One way to obviate this is to sample desert marginal areas that only become active during significant arid phases. An alternative is to find and sample deep stratigraphic exposures. The Mamatwan manganese mine at Hotazel in the SW Kalahari meets both these criteria. Luminescence dating of this site shows the upper sedimentary unit to span at least the last 60 ka with tentative age estimates from underlying cemented aeolian units dating back to the last interglacial and beyond. Results from Mamatwan are comparable to new and previously published data from linear dunes in the SW Kalahari but extend back much further. Analysis of the entire data set of luminescence ages for the SW Kalahari brings out important inferences that suggest that different aeolian forms (1) have been active over different time scales in the past, (2) have different sensitivities to environmental changes and (3) have different time scales over which they record and preserve the palaeoenvironmental record. This implies that future optically stimulated luminescence work and palaeoenvironmental reconstructions must consider both site location and its relationship to desert margins and sediment depositional styles, so that the resolution and duration of the aridity record can be optimally understood

    Evaluation of Recommended Sentencing Pilot Program

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    Missouri's prison population rose significantly through the 1990s and early 2000s. When compared nationally, Missouri's sentencing laws resulted in longer prison terms and in the imprisonment of a greater proportion of non-violent offenders. Imprisonment is the most costly alternative ($14,005 in Fiscal Year 05), but may not be the most effective alternative. In 2003, the Missouri General Assembly responded to these issues with the passage of Senate Bill 5 which, among other things, provided additional sentencing alternatives for nonviolent offenders. In partial response to the changes made in SB 5, the Missouri Sentencing Advisory Commission issued the Report on Recommended Sentencing, in 2004 which contained a proposed Sentencing Assessment Report, designed to replace the existing Pre-sentence Investigation Reports. The Sentencing Assessment Reports were implemented on a trial basis in six circuits in early 2005. This analysis provides an assessment of the new reports
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