2,179 research outputs found

    Transit Timing and Duration Variations for the Discovery and Characterization of Exoplanets

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    Transiting exoplanets in multi-planet systems have non-Keplerian orbits which can cause the times and durations of transits to vary. The theory and observations of transit timing variations (TTV) and transit duration variations (TDV) are reviewed. Since the last review, the Kepler spacecraft has detected several hundred perturbed planets. In a few cases, these data have been used to discover additional planets, similar to the historical discovery of Neptune in our own Solar System. However, the more impactful aspect of TTV and TDV studies has been characterization of planetary systems in which multiple planets transit. After addressing the equations of motion and parameter scalings, the main dynamical mechanisms for TTV and TDV are described, with citations to the observational literature for real examples. We describe parameter constraints, particularly the origin of the mass/eccentricity degeneracy and how it is overcome by the high-frequency component of the signal. On the observational side, derivation of timing precision and introduction to the timing diagram are given. Science results are reviewed, with an emphasis on mass measurements of transiting sub-Neptunes and super-Earths, from which bulk compositions may be inferred.Comment: Revised version. Invited review submitted to 'Handbook of Exoplanets,' Exoplanet Discovery Methods section, Springer Reference Works, Juan Antonio Belmonte and Hans Deeg, Eds. TeX and figures may be found at https://github.com/ericagol/TTV_revie

    Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin

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    One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution

    Problems in dealing with missing data and informative censoring in clinical trials

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    A common problem in clinical trials is the missing data that occurs when patients do not complete the study and drop out without further measurements. Missing data cause the usual statistical analysis of complete or all available data to be subject to bias. There are no universally applicable methods for handling missing data. We recommend the following: (1) Report reasons for dropouts and proportions for each treatment group; (2) Conduct sensitivity analyses to encompass different scenarios of assumptions and discuss consistency or discrepancy among them; (3) Pay attention to minimize the chance of dropouts at the design stage and during trial monitoring; (4) Collect post-dropout data on the primary endpoints, if at all possible; and (5) Consider the dropout event itself an important endpoint in studies with many

    Rounding of low serum creatinine levels and consequent impact on accuracy of bedside estimates of renal function in cancer patients

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    To compare glomerular filtration rate measured by technetium-99m ([Tc(99m)]) DTPA clearance with estimated creatinine clearance (CrCl) (Cockcroft and Gault (C&G) method) in patients with serum creatinine (Scr) levels 100 ml min(-1). This work indicates that when bedside estimates of renal function are calculated using the C&G formula actual Scr should be used first to estimate CrCl. If the resultant CrCl is </=100 ml min(-1), then the Scr should be rounded up to 0.06 mmol l(-1) and CrCl recalculated. Further assessment of this approach is warranted in a larger cohort of patients
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