BionoiNet: Ligand-binding site classification with off-the-shelf deep neural network

© The 2020 Author(s). Published by Oxford University Press. All rights reserved. Motivation: Fast and accurate classification of ligand-binding sites in proteins with respect to the class of binding molecules is invaluable not only to the automatic functional annotation of large datasets of protein structures but also to projects in protein evolution, protein engineering and drug development. Deep learning techniques, which have already been successfully applied to address challenging problems across various fields, are inherently suitable to classify ligand-binding pockets. Our goal is to demonstrate that off-the-shelf deep learning models can be employed with minimum development effort to recognize nucleotide-and heme-binding sites with a comparable accuracy to highly specialized, voxel-based methods. Results: We developed BionoiNet, a new deep learning-based framework implementing a popular ResNet model for image classification. BionoiNet first transforms the molecular structures of ligand-binding sites to 2D Voronoi diagrams, which are then used as the input to a pretrained convolutional neural network classifier. The ResNet model generalizes well to unseen data achieving the accuracy of 85.6% for nucleotide-and 91.3% for heme-binding pockets. BionoiNet also computes significance scores of pocket atoms, called BionoiScores, to provide meaningful insights into their interactions with ligand molecules. BionoiNet is a lightweight alternative to computationally expensive 3D architectures

Beryllium and Alpha-Element Abundances in a Large Sample of Metal-Poor Stars

The light elements, Li, Be, and B, provide tracers for many aspects of astronomy including stellar structure, Galactic evolution, and cosmology. We have taken spectra of Be in 117 metal-poor stars ranging in metallicity from [Fe/H] = -0.5 to -3.5 with Keck I + HIRES at a resolution of 42,000 and signal-to-noise ratios of near 100. We have determined the stellar parameters spectroscopically from lines of Fe I, Fe II, Ti I and Ti II. The abundances of Be and O were derived by spectrum synthesis techniques, while abundances of Fe, Ti, and Mg were found from many spectral line measurements. There is a linear relationship between [Fe/H] and A(Be) with a slope of +0.88 +-0.03 over three orders of magnitude in [Fe/H]. We fit the relationship between A(Be) and [O/H] with both a single slope and with two slopes. The relationship between [Fe/H] and [O/H] seems robustly linear and we conclude that the slope change in Be vs. O is due to the Be abundance. Although Be is a by-product of CNO, we have used Ti and Mg abundances as alpha-element surrogates for O in part because O abundances are rather sensitive to both stellar temperature and surface gravity. We find that A(Be) tracks [Ti/H] very well with a slope of 1.00 +-0.04. It also tracks [Mg/H] very well with a slope of 0.88 +-0.03. We find that there are distinct differences in the relationships of A(Be) and [Fe/H] and of A(Be) and [O/H] for our dissipative stars and our accretive stars. We suggest that the Be in the dissipative stars was primarily formed by GCR spallation and Be in the accretive stars was formed in the vicinity of SN II.Comment: Accepted for Ap.J. Nov. 10, 2011, v. 741 70 pages, 27 figures, 5 table

The Structure of the Local Interstellar Medium V: Electron Densities

We present a comprehensive survey of CII* absorption detections toward stars within 100 pc in order to measure the distribution of electron densities present in the local interstellar medium (LISM). Using high spectral resolution observations of nearby stars obtained by GHRS and STIS onboard the Hubble Space Telescope, we identify 13 sight lines with 23 individual CII* absorption components, which provide electron density measurements, the vast majority of which are new. We employ several strategies to determine more accurate CII column densities from the saturated CII resonance line, including, constraints of the line width from the optically thin CII* line, constraints from independent temperature measurements of the LISM gas based on line widths of other ions, and third, using measured SII column densities as a proxy for CII column densities. The sample of electron densities appears consistent with a log-normal distribution and an unweighted mean value of n_e(CII_SII) = 0.11^+0.10_-0.05 cm^-3. Seven individual sight lines probe the Local Interstellar Cloud (LIC), and all present a similar value for the electron density, with a weighted mean of n_e(LIC) = 0.12 +/- 0.04 cm^-3. The Hyades Cloud, a decelerated cloud at the leading edge of the platoon of LISM clouds, has a significantly higher electron density than the LIC. Observed toward G191-B2B, the high electron density may be caused by the lack of shielding from such a strong radiation source. Given some simple assumptions, the range of observed electron densities translates into a range of thermal pressures, P/k = 3300^+5500_-1900 K cm^-3. This work greatly expands the number of electron density measurements and provides important constraints on the ionization, abundance, and evolutionary models of the local interstellar medium. (abridged)Comment: 41 pages, 9 figures; Accepted for publication in Ap

Oxford SWIFT IFS and multi-wavelength observations of the Eagle galaxy at z=0.77

The `Eagle' galaxy at a redshift of 0.77 is studied with the Oxford Short Wavelength Integral Field Spectrograph (SWIFT) and multi-wavelength data from the All-wavelength Extended Groth strip International Survey (AEGIS). It was chosen from AEGIS because of the bright and extended emission in its slit spectrum. Three dimensional kinematic maps of the Eagle reveal a gradient in velocity dispersion which spans 35-75 +/- 10 km/s and a rotation velocity of 25 +/- 5 km/s uncorrected for inclination. Hubble Space Telescope images suggest it is close to face-on. In comparison with galaxies from AEGIS at similar redshifts, the Eagle is extremely bright and blue in the rest-frame optical, highly star-forming, dominated by unobscured star-formation, and has a low metallicity for its size. This is consistent with its selection. The Eagle is likely undergoing a major merger and is caught in the early stage of a star-burst when it has not yet experienced metal enrichment or formed the mass of dust typically found in star-forming galaxies.Comment: accepted for publication in MNRA

Overfishing and nutrient pollution interact with temperature to disrupt coral reefs down to microbial scales

Losses of corals worldwide emphasize the need to understand what drives reef decline. Stressors such as overfishing and nutrient pollution may reduce resilience of coral reefs by increasing coral?algal competition and reducing coral recruitment, growth and survivorship. Such effects may themselves develop via several mechanisms, including disruption of coral microbiomes. Here we report the results of a 3-year field experiment simulating overfishing and nutrient pollution. These stressors increase turf and macroalgal cover, destabilizing microbiomes, elevating putative pathogen loads, increasing disease more than twofold and increasing mortality up to eightfold. Above-average temperatures exacerbate these effects, further disrupting microbiomes of unhealthy corals and concentrating 80% of mortality in the warmest seasons. Surprisingly, nutrients also increase bacterial opportunism and mortality in corals bitten by parrotfish, turning normal trophic interactions deadly for corals. Thus, overfishing and nutrient pollution impact reefs down to microbial scales, killing corals by sensitizing them to predation, above-average temperatures and bacterial opportunism

Lentivirus-mediated gene therapy for Fabry disease

Enzyme and chaperone therapies are used to treat Fabry disease. Such treatments are expensive and require intrusive biweekly infusions; they are also not particularly efficacious. In this pilot, single-arm study (NCT02800070), five adult males with Type 1 (classical) phenotype Fabry disease were infused with autologous lentivirus-transduced, CD34+-selected, hematopoietic stem/progenitor cells engineered to express alpha-galactosidase A (α-gal A). Safety and toxicity are the primary endpoints. The non-myeloablative preparative regimen consisted of intravenous melphalan. No serious adverse events (AEs) are attributable to the investigational product. All patients produced α-gal A to near normal levels within one week. Vector is detected in peripheral blood and bone marrow cells, plasma and leukocytes demonstrate α-gal A activity within or above the reference range, and reductions in plasma and urine globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) are seen. While the study and evaluations are still ongoing, the first patient is nearly three years post-infusion. Three patients have elected to discontinue enzyme therapy

Interstellar Deuterium, Nitrogen, and Oxygen Abundances Toward BD +28 4211: Results from the Far Ultraviolet Spectroscopic Explorer

High resolution far-ultraviolet spectra of the O-type subdwarf BD +28 4211 were obtained with the Far Ultraviolet Spectroscopic Explorer (FUSE) to measure the interstellar deuterium, nitrogen, and oxygen abundances in this direction. The interstellar D I transitions are analyzed down to Lyman iota at 920.7 A. The star was observed several times at different target offsets in the direction of spectral dispersion. The aligned and coadded spectra have high signal-to-noise ratios (S/N =50-100). D I, N I, and O I transitions were analyzed with curve-of-growth and profile fitting techniques. A model of interstellar molecular hydrogen on the line of sight was derived from H2 lines in the FUSE spectra and used to help analyze some features where blending with H2 was significant. The H I column density was determined from high resolution HST/STIS spectra of Lyman alpha to be log(N HI) = 19.846+/-0.035 (2 sigma), which is higher than is typical for sight lines in the local ISM studied for D/H. We found that D/H =(1.39+/-0.21) E-5 (2 sigma) and O/H = (2.37+/-0.55) E-4 (2 sigma). O/H toward BD +28 4211 appears to be significantly below the mean O/H ratio for the ISM and the Local Bubble.Comment: 33 pages, 12 figures, accepted for publication in The Astrophysical Journal Supplemen

A population of gamma-ray emitting globular clusters seen with the Fermi Large Area Telescope

Globular clusters with their large populations of millisecond pulsars (MSPs) are believed to be potential emitters of high-energy gamma-ray emission. Our goal is to constrain the millisecond pulsar populations in globular clusters from analysis of gamma-ray observations. We use 546 days of continuous sky-survey observations obtained with the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope to study the gamma-ray emission towards 13 globular clusters. Steady point-like high-energy gamma-ray emission has been significantly detected towards 8 globular clusters. Five of them (47 Tucanae, Omega Cen, NGC 6388, Terzan 5, and M 28) show hard spectral power indices $(0.7 < \Gamma <1.4)$ and clear evidence for an exponential cut-off in the range 1.0-2.6 GeV, which is the characteristic signature of magnetospheric emission from MSPs. Three of them (M 62, NGC 6440 and NGC 6652) also show hard spectral indices $(1.0 < \Gamma < 1.7)$, however the presence of an exponential cut-off can not be unambiguously established. Three of them (Omega Cen, NGC 6388, NGC 6652) have no known radio or X-ray MSPs yet still exhibit MSP spectral properties. From the observed gamma-ray luminosities, we estimate the total number of MSPs that is expected to be present in these globular clusters. We show that our estimates of the MSP population correlate with the stellar encounter rate and we estimate 2600-4700 MSPs in Galactic globular clusters, commensurate with previous estimates. The observation of high-energy gamma-ray emission from a globular cluster thus provides a reliable independent method to assess their millisecond pulsar populations that can be used to make constraints on the original neutron star X-ray binary population, essential for understanding the importance of binary systems in slowing the inevitable core collapse of globular clusters.Comment: Accepted for publication in A&A. Corresponding authors: J. Kn\"odlseder, N. Webb, B. Pancraz

Gravity Recovery and Interior Laboratory (GRAIL): Extended Mission and End-Game Status

The Gravity Recovery and Interior Laboratory (GRAIL) [1], NASA s eleventh Discovery mission, successfully executed its Primary Mission (PM) in lunar orbit between March 1, 2012 and May 29, 2012. GRAIL s Extended Mission (XM) initiated on August 30, 2012 and was successfully completed on December 14, 2012. The XM provided an additional three months of gravity mapping at half the altitude (23 km) of the PM (55 km), and is providing higherresolution gravity models that are being used to map the upper crust of the Moon in unprecedented detail

Preliminary Results on Lunar Interior Properties from the GRAIL Mission

The Gravity Recovery and Interior Laboratory (GRAIL) mission has provided lunar gravity with unprecedented accuracy and resolution. GRAIL has produced a high-resolution map of the lunar gravity field while also determining tidal response. We present the latest gravity field solution and its preliminary implications for the Moon's interior structure, exploring properties such as the mean density, moment of inertia of the solid Moon, and tidal potential Love number k2. Lunar structure includes a thin crust, a deep mantle, a fluid core, and a suspected solid inner core. An accurate Love number mainly improves knowledge of the fluid core and deep mantle. In the future GRAIL will search for evidence of tidal dissipation and a solid inner core