Resolving the Surfaces of Extrasolar Planets With Secondary Eclipse Light Curves

We present a method that employs the secondary eclipse light curves of transiting extrasolar planets to probe the spatial variation of their thermal emission. This technique permits an observer to resolve the surface of the planet without the need to spatially resolve its central star. We evaluate the feasibility of this technique for the HD 209458 system [..]. We consider two representations of the planetary thermal emission; a simple model parameterized by a sinusoidal dependence on longitude and latitude, as well as the results of a three-dimensional dynamical simulation of the planetary atmosphere previously published by Cooper & Showman. We find that observations of the secondary eclipse light curve are most sensitive to a longitudinal offset in the geometric and photometric centroids of the hemisphere of the planet visible near opposition. To quantify this signal, we define a new parameter, the ``uniform time offset,'' which measures the time lag between the observed secondary eclipse and that predicted by a planet with a uniform surface flux distribution. We compare the predicted amplitude of this parameter for HD 209458 with the precision with which it could be measured with IRAC. We find that IRAC observations at 3.6um a single secondary eclipse should permit sufficient precision to confirm or reject the Cooper & Showman model of the surface flux distribution for this planet. We quantify the signal-to-noise ratio for this offset in the remaining IRAC bands (4.5um, 5.8um, and 8.0um), and find that a modest improvement in photometric precision (as might be realized through observations of several eclipse events) should permit a similarly robust detection.Comment: AASTeX 5.2, 24 pages, 5 figures, accepted for publication in ApJ; v2: clarifications, updated to version accepted by ApJ; v3: try to reduce spacin

Three-dimensional structural modelling and calculation of electrostatic potentials of HLA Bw4 and Bw6 epitopes to explain the molecular basis for alloantibody binding: toward predicting HLA antigenicity and immunogenicity.

BACKGROUND: We have previously shown that qualitative assessment of surface electrostatic potential of HLA class I molecules helps explain serological patterns of alloantibody binding. We have now used a novel computational approach to quantitate differences in surface electrostatic potential of HLA B-cell epitopes and applied this to explain HLA Bw4 and Bw6 antigenicity. METHODS: Protein structure models of HLA class I alleles expressing either the Bw4 or Bw6 epitope (defined by sequence motifs at positions 77 to 83) were generated using comparative structure prediction. The electrostatic potential in 3-dimensional space encompassing the Bw4/Bw6 epitope was computed by solving the Poisson-Boltzmann equation and quantitatively compared in a pairwise, all-versus-all fashion to produce distance matrices that cluster epitopes with similar electrostatics properties. RESULTS: Quantitative comparison of surface electrostatic potential at the carboxyl terminal of the α1-helix of HLA class I alleles, corresponding to amino acid sequence motif 77 to 83, produced clustering of HLA molecules in 3 principal groups according to Bw4 or Bw6 epitope expression. Remarkably, quantitative differences in electrostatic potential reflected known patterns of serological reactivity better than Bw4/Bw6 amino acid sequence motifs. Quantitative assessment of epitope electrostatic potential allowed the impact of known amino acid substitutions (HLA-B*07:02 R79G, R82L, G83R) that are critical for antibody binding to be predicted. CONCLUSIONS: We describe a novel approach for quantitating differences in HLA B-cell epitope electrostatic potential. Proof of principle is provided that this approach enables better assessment of HLA epitope antigenicity than amino acid sequence data alone, and it may allow prediction of HLA immunogenicity.This is the author accepted manuscript. The final version is available from Wolters Kluwer via http://dx.doi.org/10.1097/TP.000000000000054

Cost-Utility Analysis of Cancer Prevention, Treatment, and Control

Substantial innovation related to cancer prevention and treatment has occurred in recent decades. However, these innovations have often come at a significant cost. Cost-utility analysis provides a useful framework to assess if the benefits from innovation are worth the additional cost. This systematic review on published cost-utility analyses related to cancer care is from 1988 through 2013. Analyses were conducted in 2013–2015

Determinants of Functionality in the Ubiquitin Conjugating Enzyme Family

AbstractThe E2 enzymes are key enzymes in the ubiquitin and ubiquitin-like protein ligation pathways. To understand the functionality of the different E2 enzymes, we analyzed 190 protein sequences and 211 structures and electrostatic potentials. Key findings include: The ScUbc1 orthologs are defined by a C-terminal UBA domain. An N-terminal sequence motif that is highly conserved in all E2s except for Cdc34 orthologs is important for the stabilization of the L7 loop and is likely to be involved in E1 binding. ScUbc11p has a different electrostatic potential from E2-Cp and other proteins with which it has high sequence similarity but different functionality. All the E2s known to ubiquitinate histones have a negative potential. The members of the NCUBE family have a positive electrostatic potential, although its form is different from that of the SUMO conjugating E2s. The specificities of only the ScUbc4/Ubc5 and ScUbc1p orthologs are reflected in their L4 and L7 loops

The Transit Light Curve Project. VII. The Not-So-Bloated Exoplanet HAT-P-1b

We present photometry of the G0 star HAT-P-1 during six transits of its close-in giant planet, and we refine the estimates of the system parameters. Relative to Jupiter's properties, HAT-P-1b is 1.20 +/- 0.05 times larger and its surface gravity is 2.7 +/- 0.2 times weaker. Although it remains the case that HAT-P-1b is among the least dense of the known sample of transiting exoplanets, its properties are in accord with previously published models of strongly irradiated, coreless, solar-composition giant planets. The times of the transits have a typical accuracy of 1 min and do not depart significantly from a constant period.Comment: To appear in AJ [19pg, 3 figures]. New co-author added. Minor revisions to match published versio

Precise Estimates of the Physical Parameters for the Exoplanet System HD-17156 Enabled by HST FGS Transit and Asteroseismic Observations

We present observations of three distinct transits of HD 17156b obtained with the Fine Guidance Sensors (FGS) on board the Hubble Space Telescope} (HST). We analyzed both the transit photometry and previously published radial velocities to find the planet-star radius ratio R_p/R_s = 0.07454 +/- 0.00035, inclination i=86.49 +0.24/-0.20 deg, and scaled semi-major axis a/R = 23.19 +0.32/-0.27. This last value translates directly to a mean stellar density determination of 0.522 +0.021/-0.018 g cm^-3. Analysis of asteroseismology observations by the companion paper of Gilliland et al. (2009) provides a consistent but significantly refined measurement of the stellar mean density. We compare stellar isochrones to this density estimate and find M_s = 1.275 +/- 0.018 M_sun and a stellar age of $3.37 +0.20/-0.47 Gyr. Using this estimate of M_s and incorporating the density constraint from asteroseismology, we model both the photometry and published radial velocities to estimate the planet radius R_p= 1.0870 +/- 0.0066 Jupiter radii and the stellar radius R_s = 1.5007 +/- 0.0076 R_sun. The planet radius is larger than that found in previous studies and consistent with theoretical models of a solar-composition gas giant of the same mass and equilibrium temperature. For the three transits, we determine the times of mid-transit to a precision of 6.2 s, 7.6 s, and 6.9 s, and the transit times for HD 17156 do not show any significant departures from a constant period. The joint analysis of transit photometry and asteroseismology presages similar studies that will be enabled by the NASA Kepler Mission.Comment: Accepted for publication to Ap

The Transit Light Curve Project. IX. Evidence for a Smaller Radius of the Exoplanet XO-3b

We present photometry of 13 transits of XO-3b, a massive transiting planet on an eccentric orbit. Previous data led to two inconsistent estimates of the planetary radius. Our data strongly favor the smaller radius, with increased precision: R_p = 1.217 +/- 0.073 R_Jup. A conflict remains between the mean stellar density determined from the light curve, and the stellar surface gravity determined from the shapes of spectral lines. We argue the light curve should take precedence, and revise the system parameters accordingly. The planetary radius is about 1 sigma larger than the theoretical radius for a hydrogen-helium planet of the given mass and insolation. To help in planning future observations, we provide refined transit and occultation ephemerides.Comment: To appear in ApJ [22 pages

An assessment of the methodological quality of published network meta-analyses: a systematic review

Objective To assess the methodological quality of published network meta-analysis. Design Systematic review. Methods We searched the medical literature for network meta-analyses of pharmaceuticals. We assessed general study characteristics, study transparency and reproducibility, methodological approach, and reporting of findings. We compared studies published in journals with lower impact factors with those published in journals with higher impact factors, studies published prior to January 1st, 2013 with those published after that date, and studies supported financially by industry with those supported by non-profit institutions or that received no support. Results The systematic literature search identified 854 citations. Three hundred and eighteen studies met our inclusion criteria. The number of network meta-analyses has grown rapidly, with 48% of studies published since January 2013. The majority of network meta-analyses were supported by a non-profit institution or received no support (68%). We found considerable inconsistencies among reviewed studies. Eighty percent reported search terms, 61% a network diagram, 65% sufficient data to replicate the analysis, and 90% the characteristics of included trials. Seventy percent performed a risk of bias assessment of included trials, 40% an assessment of model fit, and 56% a sensitivity analysis. Among studies with a closed loop, 69% examined the consistency of direct and indirect evidence. Sixty-four percent of studies presented the full matrix of head-to-head treatment comparisons. For Bayesian studies, 41% reported the probability that each treatment was best, 31% reported treatment ranking, and 16% included the model code or referenced publicly-available code. Network meta-analyses published in higher impact factors journals and those that did not receive industry support performed better across the assessment criteria. We found few differences between older and newer studies. Conclusions There is substantial variation in the network meta-analysis literature. Consensus among guidelines is needed improve the methodological quality, transparency, and consistency of study conduct and reporting

Automatic generation of alignments for 3D QSAR analyses

Many 3D QSAR methods require the alignment of the molecules in a dataset, which can require a fair amount of manual effort in deciding upon a rational basis for the superposition. This paper describes the use of FBSS, a pro-ram for field-based similarity searching in chemical databases, for generating such alignments automatically. The CoMFA and CoMSIA experiments with several literature datasets show that the QSAR models resulting from the FBSS alignments are broadly comparable in predictive performance with the models resulting from manual alignments