Genetic variation can affect drug response in multiple ways, although it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, ...collaborating with the Pharmacogenomics Research Network, began eMERGE‐PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of “precision medicine.” The February 2015 eMERGE‐PGx data release includes sequence‐derived data from ∼5,000 clinical subjects. We present the variant frequency spectrum categorized by variant type, ancestry, and predicted function. We found 95.12% of genes have variants with a scaled Combined Annotation‐Dependent Depletion score above 20, and 96.19% of all samples had one or more Clinical Pharmacogenetics Implementation Consortium Level A actionable variants. These data highlight the distribution and scope of genetic variation in relevant pharmacogenes, identifying challenges associated with implementing clinical sequencing for drug treatment at a broader level, underscoring the importance for multifaceted research in the execution of precision medicine.
Abstract
We present the star cluster catalogues for 17 dwarf and irregular galaxies in the HST Treasury Program ‘Legacy ExtraGalactic UV Survey’ (LEGUS). Cluster identification and photometry in this ...sub-sample are similar to that of the entire LEGUS sample, but special methods were developed to provide robust catalogues with accurate fluxes due to low cluster statistics. The colours and ages are largely consistent for two widely used aperture corrections, but a significant fraction of the clusters are more compact than the average training cluster. However, the ensemble luminosity, mass, and age distributions are consistent suggesting that the systematics between the two methods are less than the random errors. When compared with the clusters from previous dwarf galaxy samples, we find that the LEGUS catalogues are more complete and provide more accurate total fluxes. Combining all clusters into a composite dwarf galaxy, we find that the luminosity and mass functions can be described by a power law with the canonical index of −2 independent of age and global SFR binning. The age distribution declines as a power law, with an index of ≈− 0.80 ± 0.15, independent of cluster mass and global SFR binning. This decline of clusters is dominated by cluster disruption since the combined star formation histories and integrated-light SFRs are both approximately constant over the last few hundred Myr. Finally, we find little evidence for an upper-mass cut-off (<2σ) in the composite cluster mass function, and can rule out a truncation mass below ≈104.5M⊙ but cannot rule out the existence of a truncation at higher masses.
Social network analysis provides a broad and complex perspective on animal sociality that is widely applicable to almost any species. Recent applications demonstrate the utility of network analysis ...for advancing our understanding of the dynamics, selection pressures, development, and evolution of complex social systems. However, most studies of animal social networks rely primarily on a descriptive approach. To propel the field of animal social networks beyond exploratory analyses and to facilitate the integration of quantitative methods that allow for the testing of ecologically and evolutionarily relevant hypotheses, we review methodological and conceptual advances in network science, which are underutilized in studies of animal sociality. First, we highlight how the use of statistical modeling and triadic motifs analysis can advance our understanding of the processes that structure networks. Second, we discuss how the consideration of temporal changes and spatial constraints can shed light on the dynamics of social networks. Third, we consider how the study of variation at multiple scales can potentially transform our understanding of the structure and function of animal networks. We direct readers to analytical tools that facilitate the adoption of these new concepts and methods. Our goal is to provide behavioral ecologists with a toolbox of current methods that can stimulate novel insights into the ecological influences and evolutionary pressures structuring networks and advance our understanding of the proximate and ultimate processes that drive animal sociality.
Abstract
We report the large effort that is producing comprehensive high-level young star cluster (YSC) catalogs for a significant fraction of galaxies observed with the Legacy ExtraGalactic UV ...Survey (LEGUS)
Hubble
treasury program. We present the methodology developed to extract cluster positions, verify their genuine nature, produce multiband photometry (from NUV to NIR), and derive their physical properties via spectral energy distribution fitting analyses. We use the nearby spiral galaxy NGC 628 as a test case for demonstrating the impact that LEGUS will have on our understanding of the formation and evolution of YSCs and compact stellar associations within their host galaxy. Our analysis of the cluster luminosity function from the UV to the NIR finds a steepening at the bright end and at all wavelengths suggesting a dearth of luminous clusters. The cluster mass function of NGC 628 is consistent with a power-law distribution of slopes
and a truncation of a few times 10
5
. After their formation, YSCs and compact associations follow different evolutionary paths. YSCs survive for a longer time frame, confirming their being potentially bound systems. Associations disappear on timescales comparable to hierarchically organized star-forming regions, suggesting that they are expanding systems. We find mass-independent cluster disruption in the inner region of NGC 628, while in the outer part of the galaxy there is little or no disruption. We observe faster disruption rates for low mass (≤10
4
) clusters, suggesting that a mass-dependent component is necessary to fully describe the YSC disruption process in NGC 628.
We tested if rates of brain atrophy accelerate in individuals with amnestic mild cognitive impairment (aMCI) as they progress to typical late onset Alzheimer disease (AD). We included comparisons to ...subjects with aMCI who did not progress (labeled aMCI-S) and also to cognitively normal elderly subjects (CN).
We studied 46 subjects with aMCI who progressed to AD (labeled aMCI-P), 46 CN, and 23 aMCI-S. All subjects must have had three or more serial MRI scans. Rates of brain shrinkage and ventricular expansion were measured across all available serial MRI scans in each subject. Change in volumes relative to the point at which subjects progressed to a clinical diagnosis of AD (the index date) was modeled in aMCI-P. Change in volumes relative to age was modeled in all three clinical groups.
In aMCI-P the change in pre to post index rate (i.e., acceleration) of ventricular expansion was 1.7 cm(3)/year, and acceleration in brain shrinkage was 5.3 cm(3)/year. Brain volume declined and ventricular volume increased in all three groups with age. Volume changes decelerated with increasing age in aMCI-P, and to a lesser extent in aMCI-S, but were linear in the matched CN. Among all subjects with aMCI, rates of atrophy were greater in apolipoprotein E epsilon 4 carriers than noncarriers.
Rates of atrophy accelerate as individuals progress from amnestic mild cognitive impairment (aMCI) to typical late onset Alzheimer disease (AD). Rates of atrophy are greater in younger than older subjects with aMCI who progressed to AD and subjects with aMCI who did not progress. We did not find that atrophy rates varied with age in 70- to 90-year-old cognitively normal subjects.
With the advent of the Heliophysics/Geospace System Observatory (H/GSO), a complement of multi-spacecraft missions and ground-based observatories to study the space environment, data retrieval, ...analysis, and visualization of space physics data can be daunting. The Space Physics Environment Data Analysis System (SPEDAS), a grass-roots software development platform (
www.spedas.org
), is now officially supported by NASA Heliophysics as part of its data environment infrastructure. It serves more than a dozen space missions and ground observatories and can integrate the full complement of past and upcoming space physics missions with minimal resources, following clear, simple, and well-proven guidelines. Free, modular and configurable to the needs of individual missions, it works in both command-line (ideal for experienced users) and Graphical User Interface (GUI) mode (reducing the learning curve for first-time users). Both options have “crib-sheets,” user-command sequences in ASCII format that can facilitate record-and-repeat actions, especially for complex operations and plotting. Crib-sheets enhance scientific interactions, as users can move rapidly and accurately from exchanges of technical information on data processing to efficient discussions regarding data interpretation and science. SPEDAS can readily query and ingest all International Solar Terrestrial Physics (ISTP)-compatible products from the Space Physics Data Facility (SPDF), enabling access to a vast collection of historic and current mission data. The planned incorporation of Heliophysics Application Programmer’s Interface (HAPI) standards will facilitate data ingestion from distributed datasets that adhere to these standards. Although SPEDAS is currently Interactive Data Language (IDL)-based (and interfaces to Java-based tools such as Autoplot), efforts are under-way to expand it further to work with python (first as an interface tool and potentially even receiving an under-the-hood replacement). We review the SPEDAS development history, goals, and current implementation. We explain its “modes of use” with examples geared for users and outline its technical implementation and requirements with software developers in mind. We also describe SPEDAS personnel and software management, interfaces with other organizations, resources and support structure available to the community, and future development plans.
► PARAFAC analysis of the quenching of EEM of dissolved organic matter by Cu and Hg. ► Multiresponse model should be chosen to calculate the binding parameters. ► HMW DOM has stronger binding ...affinity to Cu2+ and Hg2+ than bulk and LMW DOM. ► DOM composition and size are important factors regulating metal complexation in freshwater.
The effects of water chemistry (i.e. pH and Ca2+ concentration) dissolved organic carbon (DOC) concentration) and DOM quality (i.e. composition and molecular weight) on metal complexation were successfully investigated by a combination of tangential flow filtration, excitation–emission matrix fluorescence, parallel factor analysis (PARAFAC), and fluorescence quenching on four freshwater samples and one extracted Suwannee River fulvic acid (SRFA). Two terrestrial and one microbial humic-like components were found in this study. Despite strong correlation between the Ryan–Weber model and the multiresponse model, the latter is more appropriate for the calculation of binding parameters in multiple-ligand DOM system. Decreasing pH from 6 to 4 significantly reduced logK-Cu2+ from 5.22±0.24 to 4.60±0.30 at pH 6 and 4, respectively (p<0.001), while the impacts of Ca2+ and DOC were not discernible at concentrations<100ppm and<2.06ppm, respectively. For natural freshwater DOM binding, the three humic-like components had similar logK values for both metals. High molecular weight (>1kDa) DOM generally had higher logK and binding fluorophore abundance than bulk (unfractionated) and low molecular weight (<1kDa) DOM for both metals. This trend however was not always true for Hg2+ where the binding parameters were quite variable. Overall the combined results provide evidence that binding parameters are not only affected by water chemistry, but also depend on DOM molecular weight.
Very low Earth orbits (VLEO), typically classified as orbits below approximately 450 km in altitude, have the potential to provide significant benefits to spacecraft over those that operate in higher ...altitude orbits. This paper provides a comprehensive review and analysis of these benefits to spacecraft operations in VLEO, with parametric investigation of those which apply specifically to Earth observation missions. The most significant benefit for optical imaging systems is that a reduction in orbital altitude improves spatial resolution for a similar payload specification. Alternatively mass and volume savings can be made whilst maintaining a given performance. Similarly, for radar and lidar systems, the signal-to-noise ratio can be improved. Additional benefits include improved geospatial position accuracy, improvements in communications link-budgets, and greater launch vehicle insertion capability. The collision risk with orbital debris and radiation environment can be shown to be improved in lower altitude orbits, whilst compliance with IADC guidelines for spacecraft post-mission lifetime and deorbit is also assisted. Finally, VLEO offers opportunities to exploit novel atmosphere-breathing electric propulsion systems and aerodynamic attitude and orbit control methods.
However, key challenges associated with our understanding of the lower thermosphere, aerodynamic drag, the requirement to provide a meaningful orbital lifetime whilst minimising spacecraft mass and complexity, and atomic oxygen erosion still require further research. Given the scope for significant commercial, societal, and environmental impact which can be realised with higher performing Earth observation platforms, renewed research efforts to address the challenges associated with VLEO operations are required.
•Very low Earth orbit (VLEO) can provide significant benefits over higher altitudes.•Higher resolution or lower cost missions can enabled by operating in VLEO.•Orbital debris collision risk and radiation damage are also shown to be reduced.•Launch vehicle capability is increased and end-of-life deorbit is facilitated.
The Global Carbon Budget 2018 (GCB2018) estimated by the atmospheric CO
2 growth rate, fossil fuel emissions, and modeled (bottom‐up) land and ocean fluxes cannot be fully closed, leading to a ...“budget imbalance,” highlighting uncertainties in GCB components. However, no systematic analysis has been performed on which regions or processes contribute to this term. To obtain deeper insight on the sources of uncertainty in global and regional carbon budgets, we analyzed differences in Net Biome Productivity (NBP) for all possible combinations of bottom‐up and top‐down data sets in GCB2018: (i) 16 dynamic global vegetation models (DGVMs), and (ii) 5 atmospheric inversions that match the atmospheric CO
2 growth rate. We find that the global mismatch between the two ensembles matches well the GCB2018 budget imbalance, with Brazil, Southeast Asia, and Oceania as the largest contributors. Differences between DGVMs dominate global mismatches, while at regional scale differences between inversions contribute the most to uncertainty. At both global and regional scales, disagreement on NBP interannual variability between the two approaches explains a large fraction of differences. We attribute this mismatch to distinct responses to El Niño–Southern Oscillation variability between DGVMs and inversions and to uncertainties in land use change emissions, especially in South America and Southeast Asia. We identify key needs to reduce uncertainty in carbon budgets: reducing uncertainty in atmospheric inversions (e.g., through more observations in the tropics) and in land use change fluxes, including more land use processes and evaluating land use transitions (e.g., using high‐resolution remote‐sensing), and, finally, improving tropical hydroecological processes and fire representation within DGVMs.
Key Points
Top‐down and bottom‐up estimates of net land‐atmosphere CO
2 fluxes agree well globally but show important mismatches at regional scales
Regional mismatches are dominated by differences between inversions and interannual variability in CO
2 fluxes
Mismatches between top‐down and bottom‐up data sets are explained by sensitivity to climate and by uncertainty in land use change forcing
Many extensions of the standard model of particle physics suggest that neutrinos should be Majorana-type fermions-that is, that neutrinos are their own anti-particles-but this assumption is difficult ...to confirm. Observation of neutrinoless double-β decay (0νββ), a spontaneous transition that may occur in several candidate nuclei, would verify the Majorana nature of the neutrino and constrain the absolute scale of the neutrino mass spectrum. Recent searches carried out with (76)Ge (the GERDA experiment) and (136)Xe (the KamLAND-Zen and EXO (Enriched Xenon Observatory)-200 experiments) have established the lifetime of this decay to be longer than 10(25) years, corresponding to a limit on the neutrino mass of 0.2-0.4 electronvolts. Here we report new results from EXO-200 based on a large (136)Xe exposure that represents an almost fourfold increase from our earlier published data sets. We have improved the detector resolution and revised the data analysis. The half-life sensitivity we obtain is 1.9 × 10(25) years, an improvement by a factor of 2.7 on previous EXO-200 results. We find no statistically significant evidence for 0νββ decay and set a half-life limit of 1.1 × 10(25) years at the 90 per cent confidence level. The high sensitivity holds promise for further running of the EXO-200 detector and future 0νββ decay searches with an improved Xe-based experiment, nEXO.
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