176 research outputs found

    A Consistent Orbital Stability Analysis for the GJ 581 System

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    We apply a combination of N-body modeling techniques and automated data fitting with Monte Carlo Markov Chain uncertainty analysis of Keplerian orbital models to radial velocity data to determine long term stability of the planetary system GJ 581. We find that while there are stability concerns with the 4-planet model as published by Forveille et al. (2011), when uncertainties in the system are accounted for, particularly stellar jitter, the hypothesis that the 4-planet model is gravitationally unstable is not statistically significant. Additionally, the system including proposed planet g by Vogt et al. (2012) also shows some stability concerns when eccentricities are allowed to float in the orbital fit, yet when uncertainties are included in the analysis the system including planet g also can not be proven to be unstable. We present revised reduced chi-squared values for Keplerian astrocentric orbital fits assuming 4-planet and 5-planet models for GJ~581 under the condition that best fits must be stable, and find no distinguishable difference by including planet g in the model. Additionally we present revised orbital element estimates for each assuming uncertainties due to stellar jitter under the constraint of the system being gravitationally stable.Comment: 26 pages, 8 figures, 6 tables, accepted for publication in the Astrophysical Journa

    Secretory traffic in the eukaryotic parasite Toxoplasma gondii: less is more

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    Name a single-celled eukaryote that boasts a small genome size, is easily cultivated in haploid form, for which a wide variety of molecular genetic tools are available, and that exhibits a simple, polarized secretory apparatus with a well-defined endoplasmic reticulum and Golgi that can serve as a model for understanding secretion. Got it? Now name a cell with all these attributes that contains at least a dozen distinct and morphologically well-defined intracellular organelles, including three distinct types of secretory vesicles and two endosymbiotic organelles. Not so sure anymore

    Peachy Parallel Assignments (EduHPC 2018)

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    Peachy Parallel Assignments are a resource for instructors teaching parallel and distributed programming. These are high-quality assignments, previously tested in class, that are readily adoptable. This collection of assignments includes implementing a subset of OpenMP using pthreads, creating an animated fractal, image processing using histogram equalization, simulating a storm of high-energy particles, and solving the wave equation in a variety of settings. All of these come with sample assignment sheets and the necessary starter code.Departamento de Informática (Arquitectura y Tecnología de Computadores, Ciencias de la Computación e Inteligencia Artificial, Lenguajes y Sistemas Informáticos)Facilitar la inclusión de ejercicios prácticos de programación paralela en cursos de Computación Paralela o de alto rendimiento (HPC)Comunicación en congreso: Descripción de ejercicios prácticos con acceso a material ya desarrollado y probado

    A Randomized Experiment of the Split Benefit Health Insurance Reform to Reduce High-Cost, Low-Value Consumption

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    Traditional cost sharing for health care is stymied by limited patient wealth. The “split benefit” is a new way to reduce consumption of high-cost, low-value treatments for which the risk/benefit ratio is uncertain. When a physician prescribes a costly unproven procedure, the insurer could pay a portion of the benefit directly to the patient, creating a decision opportunity for the patient. The insurer saves the remainder, unless the patient consumes. In this paper, a vignette-based randomized controlled experiment with 1,800 respondents sought to test the potential efficacy of the split benefit. The intervention reduced the odds of consumption by about half. It did so regardless of scenario (cancer or cardiac stent), type of split (rebate, prepay, or health savings account), or amount of split (US5,000orUS5,000 or US15,000). Respondents viewed the insurer that paid a split as behaving fairly, as it preserved access and choice. Three-quarters of respondents supported such use in Medicare, which did not depend on political party affiliation. The reform is promising for further testing since it has the potential to decrease spending on low-value interventions, and thereby increase the value of the health care dollar

    A survey of current and past Pediatric Infectious Diseases fellows regarding training

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    <p>Abstract</p> <p>Background</p> <p>The objectives of this study were to characterize the satisfaction of Pediatric Infectious Diseases fellows with their training and to understand how opinions about training have changed over time.</p> <p>Methods</p> <p>Anonymous survey studies were conducted with questions designed to include areas related to the 6 ACGME core competencies. Surveys for current fellows were distributed by fellowship directors, while surveys for graduates were mailed to all individuals with Pediatric Infectious Diseases certification.</p> <p>Results</p> <p>Response rates for current fellows and graduates were 50% and 52%, respectively. Most fellows (98%) and graduates (92%) perceived their overall training favorably. Training in most clinical care areas was rated favorably, however both groups perceived relative deficiencies in several areas. Current fellows rated their training in other competency areas (e.g., systems-based practice, research, and ethics) more favorably when compared to past graduates. Recent graduates perceived their training more favorably in many of these areas compared to past graduates.</p> <p>Conclusions</p> <p>Pediatric Infectious Diseases fellowship training is well regarded by the majority of current and past trainees. Views of current fellows reflect improved satisfaction with training in a variety of competency areas. Persistent deficiencies in clinical training likely reflect active barriers to education. Additional study is warranted to validate perceived deficiencies and to establish consensus on the importance of these areas to infectious diseases training.</p

    A Cloud-Ozone Data Product from Aura OMI and MLS Satellite Measurements

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    Ozone within deep convective clouds is controlled by several factors involving photochemical reactions and transport. Gas-phase photochemical reactions and heterogeneous surface chemical reactions involving ice, water particles, and aerosols inside the clouds all contribute to the distribution and net production and loss of ozone. Ozone in clouds is also dependent on convective transport that carries low troposphereboundary layer ozone and ozone precursors upward into the clouds. Characterizing ozone in thick clouds is an important step for quantifying relationships of ozone with tropospheric H2O, OH production, and cloud microphysicstransport properties. Although measuring ozone in deep convective clouds from either aircraft or balloon ozonesondes is largely impossible due to extreme meteorological conditions associated with these clouds, it is possible to estimate ozone in thick clouds using backscattered solar UV radiation measured by satellite instruments. Our study combines Aura Ozone Monitoring Instrument (OMI) and Microwave Limb Sounder (MLS) satellite measurements to generate a new research product of monthly-mean ozone concentrations in deep convective clouds between 30oS to 30oN for October 2004 April 2016. These measurements represent mean ozone concentration primarily in the upper levels of thick clouds and reveal key features of cloud ozone including: persistent low ozone concentrations in the tropical Pacific of 10 ppbv or less; concentrations of up to 60 pphv or greater over landmass regions of South America, southern Africa, Australia, and Indiaeast Asia; connections with tropical ENSO events; and intra-seasonalMadden-Julian Oscillation variability. Analysis of OMI aerosol measurements suggests a cause and effect relation between boundary layer pollution and elevated ozone inside thick clouds over land-mass regions including southern Africa and Indiaeast Asia

    Stereospecific Lasofoxifene Derivatives Reveal the Interplay between Estrogen Receptor Alpha Stability and Antagonistic Activity in <i>ESR1</i> Mutant Breast Cancer Cells

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    Chemical manipulation of estrogen receptor alpha ligand binding domain structural mobility tunes receptor lifetime and influences breast cancer therapeutic activities. Selective estrogen receptor modulators (SERMs) extend ERα cellular lifetime/accumulation. They are antagonists in the breast but agonists in the uterine epithelium and/or in bone. Selective estrogen receptor degraders/downregulators (SERDs) reduce ERα cellular lifetime/accumulation and are pure antagonists. Activating somatic ESR1 mutations Y537S and D538G enable resistance to first-line endocrine therapies. SERDs have shown significant activities in ESR1 mutant setting while few SERMs have been studied. To understand whether chemical manipulation of ERα cellular lifetime and accumulation influences antagonistic activity, we studied a series of methylpyrollidine lasofoxifene derivatives that maintained the drug’s antagonistic activities while uniquely tuning ERα cellular accumulation. These molecules were examined alongside a panel of antiestrogens in live cell assays of ERα cellular accumulation, lifetime, SUMOylation, and transcriptional antagonism. High-resolution x-ray crystal structures of WT and Y537S ERα ligand binding domain in complex with the methylated lasofoxifene derivatives or representative SERMs and SERDs show that molecules that favor a highly buried helix 12 antagonist conformation achieve the greatest transcriptional suppression activities in breast cancer cells harboring WT/Y537S ESR1. Together these results show that chemical reduction of ERα cellular lifetime is not necessarily the most crucial parameter for transcriptional antagonism in ESR1 mutated breast cancer cells. Importantly, our studies show how small chemical differences within a scaffold series can provide compounds with similar antagonistic activities, but with greatly different effects of the cellular lifetime of the ERα, which is crucial for achieving desired SERM or SERD profiles. SIGNIFICANCE This study shows that antiestrogens that enforce a wild-type-like estrogen receptor alpha antagonist conformation demonstrate improved therapeutic activities in hormone-resistant breast cancer cells harboring activating Y537S ESR1 mutant

    Customs Law

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    This article summarizes important developments in 2014 in customs law, including U.S. judicial decisions, trade, legislative, administrative, and executive developments, as well as Canadian and European legal developments

    Aerodynamic investigations of ventilated brake discs.

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    The heat dissipation and performance of a ventilated brake disc strongly depends on the aerodynamic characteristics of the flow through the rotor passages. The aim of this investigation was to provide an improved understanding of ventilated brake rotor flow phenomena, with a view to improving heat dissipation, as well as providing a measurement data set for validation of computational fluid dynamics methods. The flow fields at the exit of four different brake rotor geometries, rotated in free air, were measured using a five-hole pressure probe and a hot-wire anemometry system. The principal measurements were taken using two-component hot-wire techniques and were used to determine mean and unsteady flow characteristics at the exit of the brake rotors. Using phase-locked data processing, it was possible to reveal the spatial and temporal flow variation within individual rotor passages. The effects of disc geometry and rotational speed on the mean flow, passage turbulence intensity, and mass flow were determined. The rotor exit jet and wake flow were clearly observed as characterized by the passage geometry as well as definite regions of high and low turbulence. The aerodynamic flow characteristics were found to be reasonably independent of rotational speed but highly dependent upon rotor geometry
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