Deep learning is revolutionizing many areas of science and technology, especially image, text, and speech recognition. In this paper, we demonstrate how a deep neural network (NN) trained on quantum ...mechanical (QM) DFT calculations can learn an accurate and transferable potential for organic molecules. We introduce ANAKIN-ME (Accurate NeurAl networK engINe for Molecular Energies) or ANI for short. ANI is a new method designed with the intent of developing transferable neural network potentials that utilize a highly-modified version of the Behler and Parrinello symmetry functions to build single-atom atomic environment vectors (AEV) as a molecular representation. AEVs provide the ability to train neural networks to data that spans both configurational and conformational space, a feat not previously accomplished on this scale. We utilized ANI to build a potential called ANI-1, which was trained on a subset of the GDB databases with up to 8 heavy atoms in order to predict total energies for organic molecules containing four atom types: H, C, N, and O. To obtain an accelerated but physically relevant sampling of molecular potential surfaces, we also proposed a Normal Mode Sampling (NMS) method for generating molecular conformations. Through a series of case studies, we show that ANI-1 is chemically accurate compared to reference DFT calculations on much larger molecular systems (up to 54 atoms) than those included in the training data set.
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IJS, KILJ, NUK, UL, UM, UPUK
Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital ...to inform future control planning. However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015, and quantify the attributable effect of malaria disease control efforts. We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015. We estimate that interventions have averted 663 (542-753 credible interval) million clinical cases since 2000. Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted). Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent. Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
We present optical light curves, redshifts, and classifications for spectroscopically confirmed Type Ia supernovae (SNe Ia) discovered by the Pan-STARRS1 (PS1) Medium Deep Survey. We detail ...improvements to the PS1 SN photometry, astrometry, and calibration that reduce the systematic uncertainties in the PS1 SN Ia distances. We combine the subset of PS1 SNe Ia (0.03 < z < 0.68) with useful distance estimates of SNe Ia from the Sloan Digital Sky Survey (SDSS), SNLS, and various low-z and Hubble Space Telescope samples to form the largest combined sample of SNe Ia, consisting of a total of SNe Ia in the range of 0.01 < z < 2.3, which we call the "Pantheon Sample." When combining Planck 2015 cosmic microwave background (CMB) measurements with the Pantheon SN sample, we find and for the wCDM model. When the SN and CMB constraints are combined with constraints from BAO and local H0 measurements, the analysis yields the most precise measurement of dark energy to date: and for the CDM model. Tension with a cosmological constant previously seen in an analysis of PS1 and low-z SNe has diminished after an increase of 2× in the statistics of the PS1 sample, improved calibration and photometry, and stricter light-curve quality cuts. We find that the systematic uncertainties in our measurements of dark energy are almost as large as the statistical uncertainties, primarily due to limitations of modeling the low-redshift sample. This must be addressed for future progress in using SNe Ia to measure dark energy.
Summary
Background
Pachyonychia congenita (PC) is a rare autosomal dominant keratinizing disorder characterized by severe, painful, palmoplantar keratoderma and nail dystrophy, often accompanied by ...oral leucokeratosis, cysts and follicular keratosis. It is caused by mutations in one of five keratin genes: KRT6A, KRT6B, KRT6C, KRT16 or KRT17.
Objectives
To identify mutations in 84 new families with a clinical diagnosis of PC, recruited by the International Pachyonychia Congenita Research Registry during the last few years.
Methods
Genomic DNA isolated from saliva or peripheral blood leucocytes was amplified using primers specific for the PC‐associated keratin genes and polymerase chain reaction products were directly sequenced.
Results
Mutations were identified in 84 families in the PC‐associated keratin genes, comprising 46 distinct keratin mutations. Fourteen were previously unreported mutations, bringing the total number of different keratin mutations associated with PC to 105.
Conclusions
By identifying mutations in KRT6A, KRT6B, KRT6C, KRT16 or KRT17, this study has confirmed, at the molecular level, the clinical diagnosis of PC in these families.
What's already known about this topic?
Pachyonychia congenita (PC) is caused by autosomal dominant mutations in KRT6A, KRT6B, KRT6C, KRT16 or KRT17.
Plantar pain is the main symptom.
Palmoplantar keratoderma and nail dystrophy are the predominant characteristics, often accompanied by oral leucokeratosis, cysts and follicular keratosis.
What does this study add?
This study identifies PC‐associated keratin mutations in 84 new families with PC recruited by the International Pachyonychia Congenita Research Registry.
Fourteen of the 46 distinct keratin mutations were previously unreported.
This study expands the large well‐phenotyped and genotyped case series of patients with PC, which is an invaluable resource for the development of mutation‐specific and/or gene‐specific therapies and for future clinical trials.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Although next-generation sequencing has allowed for the detection of somatic mutations in myelodysplastic syndromes (MDS), the clinical relevance of variant allele frequency (VAF) for the majority of ...mutations is unknown. We profiled TP53 and 20 additional genes in our training set of 219 patients with MDS or secondary acute myeloid leukemia with findings confirmed in a validation cohort. When parsed by VAF, TP53 VAF predicted for complex cytogenetics in both the training (P=0.001) and validation set (P<0.0001). MDS patients with a TP53 VAF > 40% had a median overall survival (OS) of 124 days versus an OS that was not reached in patients with VAF <20% (hazard ratio (HR), 3.52; P=0.01) with validation in an independent cohort (HR, 4.94, P=0.01). TP53 VAF further stratified distinct prognostic groups independent of clinical prognostic scoring systems (P=0.0005). In multivariate analysis, only a TP53 VAF >40% was an independent covariate (HR, 1.61; P<0.0001). In addition, SRSF2 VAF predicted for monocytosis (P=0.003), RUNX1 VAF with thrombocytopenia (P=0.01) and SF3B1 with ringed sideroblasts (P=0.001). Together, our study indicates that VAF should be incorporated in patient management and risk stratification in MDS.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
We present two hydrogen-rich superluminous supernovae (SLSNe): SN2103hx and PS15br. These objects, together with SN2008es, are the only SLSNe showing a distinct, broad H α feature during the ...photospheric phase; also, they show no sign of strong interaction between fast moving ejecta and circumstellar shells in their early spectra. Despite the fact that the peak luminosity of PS15br is fainter than that of the other two objects, the spectrophotometric evolution is similar to SN2103hx and different from any other supernova in a similar luminosity space. We group all of them as SLSNe II and hence they are distinct from the known class of SLSN IIn. Both transients show a strong, multicomponent H α emission after 200 d past maximum, which we interpret as an indication of the interaction of the ejecta with an asymmetric, clumpy circumstellar material. The spectra and photometric evolution of the two objects are similar to Type II supernovae, although they have much higher luminosity and evolve on slower time-scales. This is qualitatively similar to how SLSNe I compare with normal type Ic, in that the former are brighter and evolve more slowly. We apply a magnetar and an interaction semi-analytical code to fit the light curves of our two objects and SN2008es. The overall observational data set would tend to favour the magnetar, or central engine, model as the source of the peak luminosity, although the clear signature of late-time interaction indicates that interaction can play a role in the luminosity evolution of SLSNe II at some phases.
Summary Background Tuberculosis incidence in the UK has risen in the past decade. Disease control depends on epidemiological data, which can be difficult to obtain. Whole-genome sequencing can detect ...microevolution within Mycobacterium tuberculosis strains. We aimed to estimate the genetic diversity of related M tuberculosis strains in the UK Midlands and to investigate how this measurement might be used to investigate community outbreaks. Methods In a retrospective observational study, we used Illumina technology to sequence M tuberculosis genomes from an archive of frozen cultures. We characterised isolates into four groups: cross-sectional, longitudinal, household, and community. We measured pairwise nucleotide differences within hosts and between hosts in household outbreaks and estimated the rate of change in DNA sequences. We used the findings to interpret network diagrams constructed from 11 community clusters derived from mycobacterial interspersed repetitive-unit–variable-number tandem-repeat data. Findings We sequenced 390 separate isolates from 254 patients, including representatives from all five major lineages of M tuberculosis . The estimated rate of change in DNA sequences was 0·5 single nucleotide polymorphisms (SNPs) per genome per year (95% CI 0·3–0·7) in longitudinal isolates from 30 individuals and 25 families. Divergence is rarely higher than five SNPs in 3 years. 109 (96%) of 114 paired isolates from individuals and households differed by five or fewer SNPs. More than five SNPs separated isolates from none of 69 epidemiologically linked patients, two (15%) of 13 possibly linked patients, and 13 (17%) of 75 epidemiologically unlinked patients (three-way comparison exact p<0·0001). Genetic trees and clinical and epidemiological data suggest that super-spreaders were present in two community clusters. Interpretation Whole-genome sequencing can delineate outbreaks of tuberculosis and allows inference about direction of transmission between cases. The technique could identify super-spreaders and predict the existence of undiagnosed cases, potentially leading to early treatment of infectious patients and their contacts. Funding Medical Research Council, Wellcome Trust, National Institute for Health Research, and the Health Protection Agency.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
HELP: the Herschel Extragalactic Legacy Project Shirley, R; Duncan, K; Campos Varillas, M C ...
Monthly Notices of the Royal Astronomical Society,
10/2021, Volume:
507, Issue:
1
Journal Article
Peer reviewed
Open access
ABSTRACT
We present the Herschel Extragalactic Legacy Project (HELP). This project collates, curates, homogenizes, and creates derived data products for most of the premium multiwavelength ...extragalactic data sets. The sky boundaries for the first data release cover 1270 deg2 defined by the Herschel SPIRE extragalactic survey fields; notably the Herschel Multi-tiered Extragalactic Survey (HerMES) and the Herschel Atlas survey (H-ATLAS). Here, we describe the motivation and principal elements in the design of the project. Guiding principles are transparent or ‘open’ methodologies with care for reproducibility and identification of provenance. A key element of the design focuses around the homogenization of calibration, meta data, and the provision of information required to define the selection of the data for statistical analysis. We apply probabilistic methods that extract information directly from the images at long wavelengths, exploiting the prior information available at shorter wavelengths and providing full posterior distributions rather than maximum-likelihood estimates and associated uncertainties as in traditional catalogues. With this project definition paper, we provide full access to the first data release of HELP; Data Release 1 (DR1), including a monolithic map of the largest SPIRE extragalactic field at 385 deg2 and 18 million measurements of PACS and SPIRE fluxes. We also provide tools to access and analyse the full HELP data base. This new data set includes far-infrared photometry, photometric redshifts, and derived physical properties estimated from modelling the spectral energy distributions over the full HELP sky. All the software and data presented is publicly available.
We demonstrate improved operation of exchange-coupled semiconductor quantum dots by substantially reducing the sensitivity of exchange operations to charge noise. The method involves biasing a double ...dot symmetrically between the charge-state anticrossings, where the derivative of the exchange energy with respect to gate voltages is minimized. Exchange remains highly tunable by adjusting the tunnel coupling. We find that this method reduces the dephasing effect of charge noise by more than a factor of 5 in comparison to operation near a charge-state anticrossing, increasing the number of observable exchange oscillations in our qubit by a similar factor. Performance also improves with exchange rate, favoring fast quantum operations.
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