Hubble PanCET: An isothermal day-side atmosphere for the bloated gas-giant HAT-P-32Ab

This is the author accepted manuscript. The final version is available from OUP via the DOI in this recordWe present a thermal emission spectrum of the bloated hot Jupiter HAT-P-32Ab from a single eclipse observation made in spatial scan mode with the Wide Field Camera 3 (WFC3) aboard the Hubble Space Telescope (HST). The spectrum covers the wavelength regime from 1.123 to 1.644 microns which is binned into 14 eclipse depths measured to an averaged precision of 104 parts-per million. The spectrum is unaffected by a dilution from the close M-dwarf companion HAT-P-32B, which was fully resolved. We complemented our spectrum with literature results and performed a comparative forward and retrieval analysis with the 1D radiative-convective ATMO model. Assuming solar abundance of the planet atmosphere, we find that the measured spectrum can best be explained by the spectrum of a blackbody isothermal atmosphere with Tp = 1995 +/- 17K, but can equally-well be described by a spectrum with modest thermal inversion. The retrieved spectrum suggests emission from VO at the WFC3 wavelengths and no evidence of the 1.4 micron water feature. The emission models with temperature profiles decreasing with height are rejected at a high confidence. An isothermal or inverted spectrum can imply a clear atmosphere with an absorber, a dusty cloud deck or a combination of both. We find that the planet can have continuum of values for the albedo and recirculation, ranging from high albedo and poor recirculation to low albedo and efficient recirculation. Optical spectroscopy of the planet's day-side or thermal emission phase curves can potentially resolve the current albedo with recirculation degeneracy.NN, DKS and TME acknowledge funding from the European Research Council under the European Unions Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 336792. JG acknowledges support from a Leverhulme Trust Research Project Grant. G.W.H. and M.H.W. acknowledge long-term support from Tennessee State University and the State of Tennessee through its Centers of Excellence program and from the Space Telescope Science Institue under HST-GO-14767. This work has been carried out in the frame of the National Centre for Competence in Research PlanetS supported by the Swiss National Science Foundation (SNSF). DE and VB acknowledge the financial support of the SNSF. This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (project FOUR ACES; grant agreement No 724427)

Ambient heat exposure and COPD hospitalisations in England: a nationwide case-crossover study during 2007-2018

Background: There is emerging evidence suggesting a link between ambient heat exposure and chronic obstructive pulmonary disease (COPD) hospitalisations. Individual and contextual characteristics can affect population vulnerabilities to COPD hospitalisation due to heat exposure. This study quantifies the effect of ambient heat on COPD hospitalisations and examines population vulnerabilities by age, sex and contextual characteristics. Methods: Individual data on COPD hospitalisation at high geographical resolution (postcodes) during 2007–2018 in England was retrieved from the small area health statistics unit. Maximum temperature at 1 km ×1 km resolution was available from the UK Met Office. We employed a case-crossover study design and fitted Bayesian conditional Poisson regression models. We adjusted for relative humidity and national holidays, and examined effect modification by age, sex, green space, average temperature, deprivation and urbanicity. Results: After accounting for confounding, we found 1.47% (95% Credible Interval (CrI) 1.19% to 1.73%) increase in the hospitalisation risk for every 1°C increase in temperatures above 23.2°C (lags 0–2 days). We reported weak evidence of an effect modification by sex and age. We found a strong spatial determinant of the COPD hospitalisation risk due to heat exposure, which was alleviated when we accounted for contextual characteristics. 1851 (95% CrI 1 576 to 2 079) COPD hospitalisations were associated with temperatures above 23.2°C annually. Conclusion: Our study suggests that resources should be allocated to support the public health systems, for instance, through developing or expanding heat-health alerts, to challenge the increasing future heat-related COPD hospitalisation burden

Lipids modulate the conformational dynamics of a secondary multidrug transporter

Direct interactions with lipids have emerged as key determinants of the folding, structure and function of membrane proteins, but an understanding of how lipids modulate protein dynamics is still lacking. Here, we systematically explored the effects of lipids on the conformational dynamics of the proton-powered multidrug transporter LmrP from Lactococcus lactis, using the pattern of distances between spin-label pairs previously shown to report on alternating access of the protein. We uncovered, at the molecular level, how the lipid headgroups shape the conformational-energy landscape of the transporter. The model emerging from our data suggests a direct interaction between lipid headgroups and a conserved motif of charged residues that control the conformational equilibrium through an interplay of electrostatic interactions within the protein. Together, our data lay the foundation for a comprehensive model of secondary multidrug transport in lipid bilayers

Enriching Peptide Libraries for Binding Affinity and Specificity Through Computationally Directed Library Design

Peptide reagents with high affinity or specificity for their target protein interaction partner are of utility for many important applications. Optimization of peptide binding by screening large libraries is a proven and powerful approach. Libraries designed to be enriched in peptide sequences that are predicted to have desired affinity or specificity characteristics are more likely to yield success than random mutagenesis. We present a library optimization method in which the choice of amino acids to encode at each peptide position can be guided by available experimental data or structure-based predictions. We discuss how to use analysis of predicted library performance to inform rounds of library design. Finally, we include protocols for more complex library design procedures that consider the chemical diversity of the amino acids at each peptide position and optimize a library score based on a user-specified input model.National Institute of General Medical Sciences (U.S.) (Award R01 GM110048

Shared midgut binding sites for Cry1A.105, Cry1Aa, Cry1Ab, Cry1Ac and Cry1Fa proteins from Bacillus thuringiensis in two important corn pests, Ostrinia nubilalis and Spodoptera frugiperda

First generation of insect-protected transgenic corn (Bt-corn) was based on the expression of Cry1Ab or Cry1Fa proteins. Currently, the trend is the combination of two or more genes expressing proteins that bind to different targets. In addition to broadening the spectrum of action, this strategy helps to delay the evolution of resistance in exposed insect populations. One of such examples is the combination of Cry1A.105 with Cry1Fa and Cry2Ab to control O. nubilalis and S. frugiperda. Cry1A.105 is a chimeric protein with domains I and II and the C-terminal half of the protein from Cry1Ac, and domain III almost identical to Cry1Fa. The aim of the present study was to determine whether the chimeric Cry1A.105 has shared binding sites either with Cry1A proteins, with Cry1Fa, or with both, in O. nubilalis and in S. frugiperda. Brush-border membrane vesicles (BBMV) from last instar larval midguts were used in competition binding assays with 125I-labeled Cry1A.105, Cry1Ab, and Cry1Fa, and unlabeled Cry1A.105, Cry1Aa, Cry1Ab, Cry1Ac, Cry1Fa, Cry2Ab and Cry2Ae. The results showed that Cry1A.105, Cry1Ab, Cry1Ac and Cry1Fa competed with high affinity for the same binding sites in both insect species. However, Cry2Ab and Cry2Ae did not compete for the binding sites of Cry1 proteins. Therefore, according to our results, the development of cross-resistance among Cry1Ab/Ac, Cry1A.105, and Cry1Fa proteins is possible in these two insect species if the alteration of shared binding sites occurs. Conversely, cross-resistance between these proteins and Cry2A proteins is very unlikely in such case

Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells

Qubit-flip-induced cavity mode squeezing in the strong dispersive regime of the quantum Rabi model

Squeezed states of light are a set of nonclassical states in which the quantum fluctuations of one quadrature component are reduced below the standard quantum limit. With less noise than the best stabilised laser sources, squeezed light is a key resource in the field of quantum technologies and has already improved sensing capabilities in areas ranging from gravitational wave detection to biomedical applications. In this work we propose a novel technique for generating squeezed states of a confined light field strongly coupled to a two-level system, or qubit, in the dispersive regime. Utilising the dispersive energy shift caused by the interaction, control of the qubit state produces a time-dependent change in the frequency of the light field. An appropriately timed sequence of sudden frequency changes reduces the quantum noise fluctuations in one quadrature of the field well below the standard quantum limit. The degree of squeezing and the time of generation are directly controlled by the number of frequency shifts applied. Even in the presence of realistic noise and imperfections, our protocol promises to be capable of generating a useful degree of squeezing with present experimental capabilities

Advances in quantum metrology

The statistical error in any estimation can be reduced by repeating the measurement and averaging the results. The central limit theorem implies that the reduction is proportional to the square root of the number of repetitions. Quantum metrology is the use of quantum techniques such as entanglement to yield higher statistical precision than purely classical approaches. In this Review, we analyse some of the most promising recent developments of this research field and point out some of the new experiments. We then look at one of the major new trends of the field: analyses of the effects of noise and experimental imperfections

The Complete transmission spectrum of WASP-39b with a precise water constraint

This is the author accepted manuscript. The final version is available from American Astronomical Society via the DOI in this record.WASP-39b is a hot Saturn-mass exoplanet with a predicted clear atmosphere based on observations in the optical and infrared. Here we complete the transmission spectrum of the atmosphere with observations in the near-infrared (NIR) over three water absorption features with the Hubble Space Telescope (HST) Wide Field Camera 3 (WFC3) G102 (0.8-1.1 microns) and G141 (1.1-1.7 microns) spectroscopic grisms. We measure the predicted high amplitude H2O feature centered at 1.4 microns, and the smaller amplitude features at 0.95 and 1.2 microns, with a maximum water absorption amplitude of 2.4 planetary scale heights. We incorporate these new NIR measurements into previously published observational measurements to complete the transmission spectrum from 0.3-5 microns. From these observed water features, combined with features in the optical and IR, we retrieve a well constrained temperature Teq = 1030(+30,-20) K, and atmospheric metallicity 151 (+48,-46)x solar which is relatively high with respect to the currently established mass-metallicity trends. This new measurement in the Saturn-mass range hints at further diversity in the planet formation process relative to our solar system giants.This work is based on observations made with the NASA/ESA Hubble Space Telescope that were obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc. These observations are associated with programs GO-14169 (PI. HR Wakeford) and GO-14260 (PI. D Deming). D.K.S., H.R.W., T.E., B.D., and N.N., acknowledge funding from the European Research Council (ERC) under the European Unions Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 336792. J.G. acknowledges support from Leverhulme Trust. A.L.C. acknowledges support from the STFC. H.R.W. also acknowledges support from the Giacconi Fellowship at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc