682 research outputs found
The effects of entry on incumbent innovation and productivity
How does firm entry affect innovation incentives in incumbent firms? Microdata suggest that there is heterogeneity across industries. Specifically, incumbent productivity growth and patenting is positively correlated with lagged greenfield foreign firm entry in technologically advanced industries, but not in laggard industries. In this paper we provide evidence that these correlations arise from a causal effect predicted by Schumpeterian growth theoryâthe threat of technologically advanced entry spurs innovation incentives in sectors close to the technology frontier, where successful innovation allows incumbents to survive the threat, but discourages innovation in laggard sectors, where the threat reduces incumbents' expected rents from innovating. We find that the empirical patterns hold using rich micro panel data for the United Kingdom. We control for the endogeneity of entry by exploiting major European and U.K. policy reforms, and allow for endogeneity of additional factors. We complement the analysis for foreign entry with evidence for domestic entry and entry through imports
Complete remission of widely metastatic human epidermal growth factor receptor 2-amplified pancreatic adenocarcinoma after precision immune and targeted therapy with description of sequencing and organoid correlates
Structural Relationships Across the Sevier Gravity Slide of Southwest Utah and Implications for Catastrophic Translation and Emplacement Processes of Long Runout Landslides
The physical processes that facilitate long-distance translation of large-volume gravity slides remain poorly understood. To better understand these processes and the controls on runout distance, we conducted an outcrop and microstructural characterization of the Sevier gravity slide across the former land surface and summarize findings of four key sites. The Sevier gravity slide is the oldest of three mega-scale (\u3e1,000 km2) collapse events of the Marysvale volcanic field (Utah, USA). Field observations of intense deformation, clastic dikes, pseudotachylyte, and consistency of kinematic indicators support the interpretation of rapid emplacement during a single event. Furthermore, clastic dikes and characteristics of the slip zone suggest emplacement involved mobilization and pressurized injection of basal material. Across the runout distance, we observe evidence for progressive slip delocalization along the slide base. This manifests as centimeter- to decimeter-thick cataclastic basal zones and abundant clastic dikes in the north and tens of meters thick basal zones characterized by widespread deformation of both slide blocks and underlying rock near the southern distal end of the gravity slide. Superimposed on this transition are variations in basal zone characteristics and slide geometry arising from interactions between slide blocks during dynamic wear and deposition processes and pre-existing topography of the former land surface. These observations are synthesized into a conceptual model in which the presence of highly pressurized fluids reduced the frictional resistance to sliding during the emplacement of the Sevier gravity slide, and basal zone evolution controlled the effectiveness of dynamic weakening mechanisms across the former land surface
The clonal evolution of metastatic colorectal cancer
Tumor heterogeneity and evolution drive treatment resistance in metastatic colorectal cancer (mCRC). Patient-derived xenografts (PDXs) can model mCRC biology; however, their ability to accurately mimic human tumor heterogeneity is unclear. Current genomic studies in mCRC have limited scope and lack matched PDXs. Therefore, the landscape of tumor heterogeneity and its impact on the evolution of metastasis and PDXs remain undefined. We performed whole-genome, deep exome, and targeted validation sequencing of multiple primary regions, matched distant metastases, and PDXs from 11 patients with mCRC. We observed intricate clonal heterogeneity and evolution affecting metastasis dissemination and PDX clonal selection. Metastasis formation followed both monoclonal and polyclonal seeding models. In four cases, metastasis-seeding clones were not identified in any primary region, consistent with a metastasis-seeding-metastasis model. PDXs underrepresented the subclonal heterogeneity of parental tumors. These suggest that single sample tumor sequencing and current PDX models may be insufficient to guide precision medicine
Carbon budget of tidal wetlands, estuaries, and shelf waters of eastern North America
Author Posting. © American Geophysical Union, 2018. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 32 (2018): 389-416, doi:10.1002/2017GB005790.Carbon cycling in the coastal zone affects global carbon budgets and is critical for understanding the urgent issues of hypoxia, acidification, and tidal wetland loss. However, there are no regional carbon budgets spanning the three main ecosystems in coastal waters: tidal wetlands, estuaries, and shelf waters. Here we construct such a budget for eastern North America using historical data, empirical models, remote sensing algorithms, and processâbased models. Considering the net fluxes of total carbon at the domain boundaries, 59 ± 12% (± 2 standard errors) of the carbon entering is from rivers and 41 ± 12% is from the atmosphere, while 80 ± 9% of the carbon leaving is exported to the open ocean and 20 ± 9% is buried. Net lateral carbon transfers between the three main ecosystem types are comparable to fluxes at the domain boundaries. Each ecosystem type contributes substantially to exchange with the atmosphere, with CO2 uptake split evenly between tidal wetlands and shelf waters, and estuarine CO2 outgassing offsetting half of the uptake. Similarly, burial is about equal in tidal wetlands and shelf waters, while estuaries play a smaller but still substantial role. The importance of tidal wetlands and estuaries in the overall budget is remarkable given that they, respectively, make up only 2.4 and 8.9% of the study domain area. This study shows that coastal carbon budgets should explicitly include tidal wetlands, estuaries, shelf waters, and the linkages between them; ignoring any of them may produce a biased picture of coastal carbon cycling.NASA Interdisciplinary Science program Grant Number: NNX14AF93G;
NASA Carbon Cycle Science Program Grant Number: NNX14AM37G;
NASA Ocean Biology and Biogeochemistry Program Grant Number: NNX11AD47G;
National Science Foundation's Chemical Oceanography Program Grant Number: OCEâ12605742018-10-0
Measurement of the cosmic ray spectrum above eV using inclined events detected with the Pierre Auger Observatory
A measurement of the cosmic-ray spectrum for energies exceeding
eV is presented, which is based on the analysis of showers
with zenith angles greater than detected with the Pierre Auger
Observatory between 1 January 2004 and 31 December 2013. The measured spectrum
confirms a flux suppression at the highest energies. Above
eV, the "ankle", the flux can be described by a power law with
index followed by
a smooth suppression region. For the energy () at which the
spectral flux has fallen to one-half of its extrapolated value in the absence
of suppression, we find
eV.Comment: Replaced with published version. Added journal reference and DO
A chemical survey of exoplanets with ARIEL
Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planetâs birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25â7.8 ÎŒm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10â100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed â using conservative estimates of mission performance and a full model of all significant noise sources in the measurement â using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL â in line with the stated mission objectives â will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio
Act now against new NHS competition regulations: an open letter to the BMA and the Academy of Medical Royal Colleges calls on them to make a joint public statement of opposition to the amended section 75 regulations.
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