1,899 research outputs found

    Unicorns and agency theory: Agreeable moral hazard?

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    The number of unicorns, startups valued over $1 billion, has steadily risen over the past decade. The abnormally high valuation of a unicorn from investors is based on their potential to disrupt a market and create a new paradigm. With this as the backdrop, this piece asks the question, what theoretical tools do we have to understand unicorns? Specifically, we explore agency theory. We argue that if principals and agents agree on the goal of disruption, then perhaps the agency problem that does occur in unicorns is beneficial, not a cost. Further, we argue that the principals of unicorns do want agents to take higher than normal risks with their investment to disrupt a given market. From this phenomenon, we introduce the concept of agreeable moral hazard and its use in the unicorn setting. Not only does the concept of agreeable moral hazard provide theoretical implications for future research, but it also highlights the need for more research to test existing theory on the unicorn population

    Critical pedagogy/popular education group

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    Few today doubt that English Higher Education (HE), like the wider world in which it is located, is in crisis. This is, in part, an economic crisis, as the government response to the current recession seems to be that of introducing the kind of neoliberal ‘shock doctrine’ (Klein 2007) or ‘shock therapy’ (Harvey 2005) that previously resulted in swingeing cuts in public services in Southern nations. Our aim in producing this volume is that these contributions help develop a collective response to the seeming limits of these conditions. We view the strength of these contributions in part as providing palpable evidence of how we and our colleagues are acting with critical hope under current conditions so that we might encourage others to work with us to build, together, more progressive formal and informal education systems that address and seek to redress multiple injustices of the world today

    Targeted Decorin Gene Therapy Delivered with Adeno-Associated Virus Effectively Retards Corneal Neovascularization \u3cem\u3ein vivo\u3c/em\u3e

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    Decorin, small leucine-rich proteoglycan, has been shown to modulate angiogenesis in nonocular tissues. This study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the rabbit stroma with adeno-associated virus serotype 5 (AAV5) impedes corneal neovascularization (CNV) in vivo without significant side effects. An established rabbit CNV model was used. Targeted decorin gene therapy in the rabbit stroma was delivered with a single topical AAV5 titer (100 μl; 5x10^12 vg/ml) application onto the stroma for two minutes after removing corneal epithelium. The levels of CNV were examined with stereomicroscopy, H&E staining, lectin, collagen type IV, CD31 immunocytochemistry and CD31 immunoblotting. Real-time PCR quantified mRNA expression of pro- and anti-angiogenic genes. Corneal health in live animals was monitored with clinical, slit-lamp and optical coherence tomography biomicroscopic examinations. Selective decorin delivery into stroma showed significant 52% (p\u3c0.05), 66% (p\u3c0.001), and 63% (p\u3c0.01) reduction at early (day 5), mid (day 10), and late (day 14) stages of CNV in decorin-delivered rabbit corneas compared to control (no decorin delivered) corneas in morphometric analysis. The H&E staining, lectin, collagen type IV, CD31 immunostaining (57–65, p\u3c0.5), and CD31 immunoblotting (62–67%, p\u3c0.05) supported morphometric findings. Quantitative PCR studies demonstrated decorin gene therapy down-regulated expression of VEGF, MCP1 and angiopoietin (pro-angiogenic) and up-regulated PEDF (anti-angiogenic) genes. The clinical, biomicroscopy and transmission electron microscopy studies revealed that AAV5– mediated decorin gene therapy is safe for the cornea. Tissue-targeted AAV5-mediated decorin gene therapy decreases CNV with no major side effects, and could potentially be used for treating patients

    Vorinostat: A Potent Agent to Prevent and Treat Laser-Induced Corneal Haze

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    PURPOSE—This study investigated the efficacy and safety of vorinostat, a deacetylase (HDAC) inhibitor, in the treatment of laser-induced corneal haze following photorefractive keratectomy (PRK) in rabbits in vivo and transforming growth factor beta 1 (TGFβ1) -induced corneal fibrosis in vitro. METHODS—Corneal haze in rabbits was produced with −9.00 diopters (D) PRK. Fibrosis in cultured human and rabbit corneal fibroblasts was activated with TGFβ1. Vorinostat (25 μm) was topically applied once for 5 minutes on rabbit cornea immediately after PRK for in vivo studies. Vorinostat (0 to 25 μm) was given to human/rabbit corneal fibroblasts for 5 minutes or 48 hours for in vitro studies. Slit-lamp microscopy, TUNEL assay, and trypan blue were used to determined vorinostat toxicity, whereas real-time polymerase chain reaction, immunocytochemistry, and immunoblotting were used to measure its efficacy. RESULTS—Single 5-minute vorinostat (25 μm) topical application on the cornea following PRK significantly reduced corneal haze (Pin vivoscreened 4 weeks after PRK. Vorinostat reduced TGFβ1-induced fibrosis in human and rabbit corneas in vitro in a dose-dependent manner without altering cellular viability, phenotype, or proliferation. CONCLUSIONS—Vorinostat is non-cytotoxic and safe for the eye and has potential to prevent laser-induced corneal haze in patients undergoing PRK for high myopia

    Lateral Gene Expression in Drosophila Early Embryos Is Supported by Grainyhead-Mediated Activation and Tiers of Dorsally-Localized Repression

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    The general consensus in the field is that limiting amounts of the transcription factor Dorsal establish dorsal boundaries of genes expressed along the dorsal-ventral (DV) axis of early Drosophila embryos, while repressors establish ventral boundaries. Yet recent studies have provided evidence that repressors act to specify the dorsal boundary of intermediate neuroblasts defective (ind), a gene expressed in a stripe along the DV axis in lateral regions of the embryo. Here we show that a short 12 base pair sequence (“the A-box”) present twice within the ind CRM is both necessary and sufficient to support transcriptional repression in dorsal regions of embryos. To identify binding factors, we conducted affinity chromatography using the A-box element and found a number of DNA-binding proteins and chromatin-associated factors using mass spectroscopy. Only Grainyhead (Grh), a CP2 transcription factor with a unique DNA-binding domain, was found to bind the A-box sequence. Our results suggest that Grh acts as an activator to support expression of ind, which was surprising as we identified this factor using an element that mediates dorsally-localized repression. Grh and Dorsal both contribute to ind transcriptional activation. However, another recent study found that the repressor Capicua (Cic) also binds to the A-box sequence. While Cic was not identified through our A-box affinity chromatography, utilization of the same site, the A-box, by both factors Grh (activator) and Cic (repressor) may also support a “switch-like” response that helps to sharpen the ind dorsal boundary. Furthermore, our results also demonstrate that TGF-β signaling acts to refine ind CRM expression in an A-box independent manner in dorsal-most regions, suggesting that tiers of repression act in dorsal regions of the embryo

    Mental Toughness in South African Youth: Relationships With Forgivingness and Attitudes Towards Risk

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    Young people are particularly vulnerable to health risk behaviors and interpersonal violence, stimulating scholars’ attention towards identifying factors that may reduce the likelihood that these actions will occur. Associated with positive outcomes in a variety of domains, mental toughness in young people might protect them from engaging in potentially deleterious interpersonal or health-risk behaviors, while potentially promoting positive psychological behaviors. Within this framework, the present study investigated the relationships between mental toughness, attitudes towards physical and psychological risk-taking, and trait forgiveness in a sample of 123 (males = 54, females = 69) South African youth (M age = 23.97 years, SD = 4.46). Univariate and multivariate analyses indicated higher levels of mental toughness were associated with being more forgiving, (η2pηp2 = .036), perceiving physical risk-taking more positively (η2pηp2 = .062), but having more negative attitudes towards psychological risk-taking (η2pηp2 = .036). These findings give credence to mental toughness as a psychological characteristic involved in youth risk-taking perceptions and interpersonal functioning. Future research might explore the integration of mental toughness into the development of future youth risk behavior interventions

    Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

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    The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

    Standalone vertex nding in the ATLAS muon spectrometer

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    A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011
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