1,231 research outputs found

    Demand Uncertainty: Exporting Delays and Exporting Failures

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    This paper presents a model of trade that explains why firms wait to export and why many exporters fail. Firms face uncertain demands that are only realized after the firm enters the destination. The model retools the timing of uncertainty resolution found in productivity heterogeneity models. This retooling addresses several shortcomings. First, the imperfect correlation of demands reconciles the sales variation observed in and across destinations. Second, since demands for the firm's output are correlated across destinations, a firm can use previously realized demands to forecast unknown demands in untested destinations. The option to forecast demands causes firms to delay exporting in order to gather more information about foreign demand. Third, since uncertainty is resolved after entry, many firms enter a destination and then exit after learning that they cannot profit. This prediction reconciles the high rate of exit seen in the first years of exporting. Finally, when faced with multiple countries in which to export, some firms will choose to sequentially export in order to slowly learn more about its chances for success in untested markets.firm heterogeneity; exporting; trade failures; trade delay

    The Desire for (Danish) Quality in High and Low Income Countries

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    We estimate the correlation between firm prices and sales within a CN8 product-country-year market. We do this for every market to which at least 16 different Danish firms exported between 1999 and 2006. Approximately 60% of Danish exports are to markets in which the price is negatively correlated with sales. These correlations are significantly different across destination countries within product categories, but across years for a given product-destination pair. While some existing theories perform better than others at predicting these patterns, none can reconcile the variation across countries. To fully explain the patterns, We introduce a model in which the price-sales correlation can be interpreted as the market's desire for high quality goods over low cost substitutes. We discover an inverted U shaped relation between a country's desire for quality and its per capita GDP, which we term a Quality Kuznets Curve. This curve has a turning point around 10 000 Euros for Danish exports. The Quality Kuznets Curve appears both when looking across products and within products.exports; firm heterogeneity; quality; productivity; Kuznets

    Cost Linkages Transmit Volatility Across Markets

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    We present and test a model relating a firm's idiosyncratic cost, its exporting status, and the volatilities of its domestic and export sales. In prior models of trade, supply costs for domestic and exports were linear and thus additively separable. We introduce a nonlinear cost function in order to link the domestic and export supply costs. This theoretical contribution has two new implications for the exporting firm. First, the demand volatility in the foreign market now directly affects the firm's domestic sales volatility. Second, firms hedge domestic demand volatility with exports. The model has several testable predictions. First, larger firms have lower total and domestic sales volatilities. Second, foreign market volatility increases domestic sales volatilities for exporters. Third, exporters allocate output across both markets in order to reduce total sales volatility. We find evidence for these predictions with Danish firms operating between 1992 and 2006.

    Dynamics and control of relative motion in an unstable orbit

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76446/1/AIAA-2000-4135-333.pd

    Very Low Mass Stellar and Substellar Companions to Solar-Like Stars From MARVELS V: A Low Eccentricity Brown Dwarf from the Driest Part of the Desert, MARVELS-6b

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    We describe the discovery of a likely brown dwarf (BD) companion with a minimum mass of 31.7 +/- 2.0 M_Jup to GSC 03546-01452 from the MARVELS radial velocity survey, which we designate as MARVELS-6b. For reasonable priors, our analysis gives a probability of 72% that MARVELS-6b has a mass below the hydrogen-burning limit of 0.072 M_Sun, and thus it is a high-confidence BD companion. It has a moderately long orbital period of 47.8929 +0.0063/-0.0062 days with a low eccentricty of 0.1442 +0.0078/-0.0073, and a semi-amplitude of 1644 +12/-13 m/s. Moderate resolution spectroscopy of the host star has determined the following parameters: T_eff = 5598 +/- 63, log g = 4.44 +/- 0.17, and [Fe/H] = +0.40 +/- 0.09. Based upon these measurements, GSC 03546-01452 has a probable mass and radius of M_star = 1.11 +/- 0.11 M_Sun and R_star = 1.06 +/- 0.23 R_Sun with an age consistent with less than ~6 Gyr at a distance of 219 +/- 21 pc from the Sun. Although MARVELS-6b is not observed to transit, we cannot definitively rule out a transiting configuration based on our observations. There is a visual companion detected with Lucky Imaging at 7.7 arcsec from the host star, but our analysis shows that it is not bound to this system. The minimum mass of MARVELS-6b exists at the minimum of the mass functions for both stars and planets, making this a rare object even compared to other BDs.Comment: 15 pages, 15 figures, 5 tables. Accepted for publication in The Astronomical Journa

    Very-High-Energy γ\gamma-Ray Observations of the Blazar 1ES 2344+514 with VERITAS

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    We present very-high-energy γ\gamma-ray observations of the BL Lac object 1ES 2344+514 taken by the Very Energetic Radiation Imaging Telescope Array System (VERITAS) between 2007 and 2015. 1ES 2344+514 is detected with a statistical significance above background of 20.8σ20.8\sigma in 47.247.2 hours (livetime) of observations, making this the most comprehensive very-high-energy study of 1ES 2344+514 to date. Using these observations the temporal properties of 1ES 2344+514 are studied on short and long times scales. We fit a constant flux model to nightly- and seasonally-binned light curves and apply a fractional variability test, to determine the stability of the source on different timescales. We reject the constant-flux model for the 2007-2008 and 2014-2015 nightly-binned light curves and for the long-term seasonally-binned light curve at the >3σ> 3\sigma level. The spectra of the time-averaged emission before and after correction for attenuation by the extragalactic background light are obtained. The observed time-averaged spectrum above 200 GeV is satisfactorily fitted (χ2/NDF=7.89/6{\chi^2/NDF = 7.89/6}) by a power-law function with index Γ=2.46±0.06stat±0.20sys\Gamma = 2.46 \pm 0.06_{stat} \pm 0.20_{sys} and extends to at least 8 TeV. The extragalactic-background-light-deabsorbed spectrum is adequately fit (χ2/NDF=6.73/6{\chi^2/NDF = 6.73/6}) by a power-law function with index Γ=2.15±0.06stat±0.20sys\Gamma = 2.15 \pm 0.06_{stat} \pm 0.20_{sys} while an F-test indicates that the power-law with exponential cutoff function provides a marginally-better fit (χ2/NDF\chi^2/NDF = 2.56/52.56 / 5 ) at the 2.1σ\sigma level. The source location is found to be consistent with the published radio location and its spatial extent is consistent with a point source.Comment: 7 pages, 2 figures. Published in Monthly Notices of the Royal Astronomical Societ

    Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine.

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    OBJECTIVE: Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock. METHODS: The European Society of Intensive Care Medicine invited 12 experts to form a Task Force to update a previous consensus (Antonelli et al.: Intensive Care Med 33:575-590, 2007). The same five questions addressed in the earlier consensus were used as the outline for the literature search and review, with the aim of the Task Force to produce statements based on the available literature and evidence. These questions were: (1) What are the epidemiologic and pathophysiologic features of shock in the intensive care unit ? (2) Should we monitor preload and fluid responsiveness in shock ? (3) How and when should we monitor stroke volume or cardiac output in shock ? (4) What markers of the regional and microcirculation can be monitored, and how can cellular function be assessed in shock ? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock ? Four types of statements were used: definition, recommendation, best practice and statement of fact. RESULTS: Forty-four statements were made. The main new statements include: (1) statements on individualizing blood pressure targets; (2) statements on the assessment and prediction of fluid responsiveness; (3) statements on the use of echocardiography and hemodynamic monitoring. CONCLUSIONS: This consensus provides 44 statements that can be used at the bedside to diagnose, treat and monitor patients with shock

    The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis.

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    Ferroptosis is a form of regulated cell death that is caused by the iron-dependent peroxidation of lipids1,2. The glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4) prevents ferroptosis by converting lipid hydroperoxides into non-toxic lipid alcohols3,4. Ferroptosis has previously been implicated in the cell death that underlies several degenerative conditions2, and induction of ferroptosis by the inhibition of GPX4 has emerged as a therapeutic strategy to trigger cancer cell death5. However, sensitivity to GPX4 inhibitors varies greatly across cancer cell lines6, which suggests that additional factors govern resistance to ferroptosis. Here, using a synthetic lethal CRISPR-Cas9 screen, we identify ferroptosis suppressor protein 1 (FSP1) (previously known as apoptosis-inducing factor mitochondrial 2 (AIFM2)) as a potent ferroptosis-resistance factor. Our data indicate that myristoylation recruits FSP1 to the plasma membrane where it functions as an oxidoreductase that reduces coenzyme Q10 (CoQ) (also known as ubiquinone-10), which acts as a lipophilic radical-trapping antioxidant that halts the propagation of lipid peroxides. We further find that FSP1 expression positively correlates with ferroptosis resistance across hundreds of cancer cell lines, and that FSP1 mediates resistance to ferroptosis in lung cancer cells in culture and in mouse tumour xenografts. Thus, our data identify FSP1 as a key component of a non-mitochondrial CoQ antioxidant system that acts in parallel to the canonical glutathione-based GPX4 pathway. These findings define a ferroptosis suppression pathway and indicate that pharmacological inhibition of FSP1 may provide an effective strategy to sensitize cancer cells to ferroptosis-inducing chemotherapeutic agents

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
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