362 research outputs found

    Servitisation and value co-production in the UK music industry

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    Since the rise of music on the internet, record companies have reported falling sales of physical products. This has occurred at a time when technology has radically increased choice, availability and the opportunity for the consumer to purchase music. As the music industry has moved from a product to a service business model, has the loss of sales meant they have not taken their customers with them? This paper provides a description of different music consumers based upon quantitative analysis of consumer characteristics. The paper then undertakes an exploration of the relationship between the consumer groups and their purchasing preference in relation to intangible ‘service’ purchase such as downloaded music and the purchase of a tangible physical product such as CDs or vinyl. In addition, we analyse the relationship between consumer types and their propensity to actively engage with music communities, such as through engagement with social media, and thus their willingness to coproduce greater value. Finally we explore the moderating effects of age and time devoted to listening to music on purchasing preferences and music discovery

    Reviews

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    The International Relations of Middle-earth: Learning from The Lord of the Rings. Abigail E. Ruane and Patrick James. Reviewed by Robert T. Tally Jr Moments of Grace and Spiritual Warfare in The Lord of the Rings. Anne Marie Gazzolo. Reviewed by Damien Bador. The Wizard of Oz as American Myth: A Critical Study of Six Versions of the Story, 1900-2007. Alissa Burger. Reviewed by Hugh H. Davis. Plain to the Inward Eye: Selected Essays on C.S. Lewis. Don W. King. Reviewed by Holly Ordway. Tolkien\u27s Poetry. Ed. Julian Eilmann and Allan Turner. Reviewed by Joe R. Christopher. The Lion\u27s World: A Journey into the Heart of Narnia. Rowan Williams. Reviewed by Melody Green. C. S. Lewis - A Life: Eccentric Genius, Reluctant Prophet. Alister McGrath. Reviewed by Gregory Bassham. Seven: An Anglo-American Literary Review. Ed. Marjorie Lamp Mead. Reviewed by Janet Brennan Croft. Supernatural Studies: Official Publication of the Supernatural Studies Association. Ed. Margo Collins and Deborah Christie. Reviewed by Janet Brennan Croft. Fastitocalon: Studies in Fantasticism Ancient to Modern. Ed. Thomas Honegger and Fanfan Chen. Reviewed by Janet Brennan Croft. Wormwood: Literature of the Fantastic, Supernatural and Decadent. Edited by Mark Valentine. Reviewed by Janet Brennan Croft

    Structure of silent transcription intervals and noise characteristics of mammalian genes

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    Mammalian transcription occurs stochastically in short bursts interspersed by silent intervals showing a refractory period. However, the underlying processes and consequences on fluctuations in gene products are poorly understood. Here, we use single allele time-lapse recordings in mouse cells to identify minimal models of promoter cycles, which inform on the number and durations of rate-limiting steps responsible for refractory periods. The structure of promoter cycles is gene specific and independent of genomic location. Typically, five rate-limiting steps underlie the silent periods of endogenous promoters, while minimal synthetic promoters exhibit only one. Strikingly, endogenous or synthetic promoters with TATA boxes show simplified two-state promoter cycles. Since transcriptional bursting constrains intrinsic noise depending on the number of promoter steps, this explains why TATA box genes display increased intrinsic noise genome-wide in mammals, as revealed by single-cell RNA-seq. These findings have implications for basic transcription biology and shed light on interpreting single-cell RNA-counting experiments

    Phase-plane analysis of Friedmann-Robertson-Walker cosmologies in Brans-Dicke gravity

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    We present an autonomous phase-plane describing the evolution of Friedmann-Robertson-Walker models containing a perfect fluid (with barotropic index gamma) in Brans-Dicke gravity (with Brans-Dicke parameter omega). We find self-similar fixed points corresponding to Nariai's power-law solutions for spatially flat models and curvature-scaling solutions for curved models. At infinite values of the phase-plane variables we recover O'Hanlon and Tupper's vacuum solutions for spatially flat models and the Milne universe for negative spatial curvature. We find conditions for the existence and stability of these critical points and describe the qualitative evolution in all regions of the (omega,gamma) parameter space for 0-3/2. We show that the condition for inflation in Brans-Dicke gravity is always stronger than the general relativistic condition, gamma<2/3.Comment: 24 pages, including 9 figures, LaTe

    Mitotic chromosomes are compacted laterally by KIF4 and condensin and axially by topoisomerase IIα

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    © 2012 Samejima et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication dateMitotic chromosome formation involves a relatively minor condensation of the chromatin volume coupled with a dramatic reorganization into the characteristic "X" shape. Here we report results of a detailed morphological analysis, which revealed that chromokinesin KIF4 cooperated in a parallel pathway with condensin complexes to promote the lateral compaction of chromatid arms. In this analysis, KIF4 and condensin were mutually dependent for their dynamic localization on the chromatid axes. Depletion of either caused sister chromatids to expand and compromised the "intrinsic structure" of the chromosomes (defined in an in vitro assay), with loss of condensin showing stronger effects. Simultaneous depletion of KIF4 and condensin caused complete loss of chromosome morphology. In these experiments, topoisomerase IIα contributed to shaping mitotic chromosomes by promoting the shortening of the chromatid axes and apparently acting in opposition to the actions of KIF4 and condensins. These three proteins are major determinants in shaping the characteristic mitotic chromosome morphology

    Self-similar cosmological solutions with a non-minimally coupled scalar field

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    We present self-similar cosmological solutions for a barotropic fluid plus scalar field with Brans-Dicke-type coupling to the spacetime curvature and an arbitrary power-law potential energy. We identify all the fixed points in the autonomous phase-plane, including a scaling solution where the fluid density scales with the scalar field's kinetic and potential energy. This is related by a conformal transformation to a scaling solution for a scalar field with exponential potential minimally coupled to the spacetime curvature, but non-minimally coupled to the barotropic fluid. Radiation is automatically decoupled from the scalar field, but energy transfer between the field and non-relativistic dark matter can lead to a change to an accelerated expansion at late times in the Einstein frame. The scalar field density can mimic a cosmological constant even for steep potentials in the strong coupling limit.Comment: 10 pages, 1 figure, revtex version to appear in Phys Rev D, references adde

    The role of gonadotrophin-releasing hormone antagonists in the treatment of patients with advanced hormone-dependent prostate cancer in the UK.

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    PURPOSE: Comparing gonadotrophin-releasing hormone (GnRH) antagonists and agonists as androgen deprivation therapy for advanced prostate cancer (PC). METHODS: This article stems from a round-table meeting in December 2014 to compare the properties of GnRH agonists and antagonists in the published literature in order to identify the patient groups most likely to benefit from GnRH antagonist therapy. A broad PubMed and congress abstract search was carried out in preparation for the meeting to ensure that the latest data and opinion were available for the discussions. RESULTS: In randomised, controlled trials, GnRH antagonist therapy provides more rapid suppression of luteinising hormone, follicle-stimulating hormone and testosterone than GnRH agonist treatment. Compared with the GnRH agonist, there is evidence of improved disease control by a GnRH antagonist, with longer interval to prostate-specific antigen progression and greater reduction of serum alkaline phosphatase. In a post hoc analysis of six randomised trials, the risk of cardiac events within 1 year of initiating therapy was significantly lower among men receiving GnRH antagonist than agonist. Pre-clinical laboratory data suggest a number of mechanisms whereby GnRH antagonist therapy may benefit men with pre-existing cardiovascular disease (CVD), the most plausible hypothesis being that, unlike GnRH agonists, GnRH antagonists do not activate T lymphocytes, which act to increase atherosclerotic plaque rupture. CONCLUSION: When making treatment decisions, clinicians should consider comorbidities, particularly CVD, in addition to effects on PC. GnRH antagonists may be appropriate in patients with significant CV risk, existing osteopenia, lower urinary tract symptoms and significant metastatic disease

    Skeletal Muscle Myofibrillar and Sarcoplasmic Protein Synthesis Rates Are Affected Differently by Altitude-Induced Hypoxia in Native Lowlanders

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    As a consequence to hypobaric hypoxic exposure skeletal muscle atrophy is often reported. The underlying mechanism has been suggested to involve a decrease in protein synthesis in order to conserve O2. With the aim to challenge this hypothesis, we applied a primed, constant infusion of 1-13C-leucine in nine healthy male subjects at sea level and subsequently at high-altitude (4559 m) after 7–9 days of acclimatization. Physical activity levels and food and energy intake were controlled prior to the two experimental conditions with the aim to standardize these confounding factors. Blood samples and expired breath samples were collected hourly during the 4 hour trial and vastus lateralis muscle biopsies obtained at 1 and 4 hours after tracer priming in the overnight fasted state. Myofibrillar protein synthesis rate was doubled; 0.041±0.018 at sea-level to 0.080±0.018%⋅hr−1 (p<0.05) when acclimatized to high altitude. The sarcoplasmic protein synthesis rate was in contrast unaffected by altitude exposure; 0.052±0.019 at sea-level to 0.059±0.010%⋅hr−1 (p>0.05). Trends to increments in whole body protein kinetics were seen: Degradation rate elevated from 2.51±0.21 at sea level to 2.73±0.13 µmol⋅kg−1⋅min−1 (p = 0.05) at high altitude and synthesis rate similar; 2.24±0.20 at sea level and 2.43±0.13 µmol⋅kg−1⋅min−1 (p>0.05) at altitude. We conclude that whole body amino acid flux is increased due to an elevated protein turnover rate. Resting skeletal muscle myocontractile protein synthesis rate was concomitantly elevated by high-altitude induced hypoxia, whereas the sarcoplasmic protein synthesis rate was unaffected by hypoxia. These changed responses may lead to divergent adaptation over the course of prolonged exposure

    Identification of Biofilm-Associated Cluster (bac) in Pseudomonas aeruginosa Involved in Biofilm Formation and Virulence

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    Biofilms are prevalent in diseases caused by Pseudomonas aeruginosa, an opportunistic and nosocomial pathogen. By a proteomic approach, we previously identified a hypothetical protein of P. aeruginosa (coded by the gene pA3731) that was accumulated by biofilm cells. We report here that a ΔpA3731 mutant is highly biofilm-defective as compared with the wild-type strain. Using a mouse model of lung infection, we show that the mutation also induces a defect in bacterial growth during the acute phase of infection and an attenuation of the virulence. The pA3731 gene is found to control positively the ability to swarm and to produce extracellular rhamnolipids, and belongs to a cluster of 4 genes (pA3729–pA3732) not previously described in P. aeruginosa. Though the protein PA3731 has a predicted secondary structure similar to that of the Phage Shock Protein, some obvious differences are observed compared to already described psp systems, e.g., this unknown cluster is monocistronic and no homology is found between the other proteins constituting this locus and psp proteins. As E. coli PspA, the amount of the protein PA3731 is enlarged by an osmotic shock, however, not affected by a heat shock. We consequently named this locus bac for biofilm-associated cluster
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