62 research outputs found

    Aglite: A 3-Wavelength Lidar System for Quantitative Assessment of Agricultural Air Quality and Whole Facility Emissions

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    Ground based remote sensing technologies such as scanning lidar systems (light detection and ranging) are increasingly being used to characterize ambient aerosols due to key advantages (i.e., wide area of regard (10 km2), fast response time (s-1), high spatial resolution (\u3c10 \u3em) and high sensitivity). Scanning lidar allows for 3D imaging of atmospheric motion and aerosol variability, which can be used to quantitatively evaluate particulate matter (PM) concentrations and emissions. Space Dynamics Laboratory, in conjunction with USDA ARS, has developed and successfully deployed a lidar system called Aglite to characterize PM in diverse settings. Aglite is a portable scanning elastic lidar system with three wavelengths (355, 532, and 1064 nm), 6 m long range bins, and an effective range from 0.5 to 15 km. Filter-based PM samplers, optical particle counters, and various meteorological instruments were deployed to provide environmental and PM conditions for use in the lidar retrieval method. The developed retrieval algorithm extracts aerosol optical parameters, which were constrained by the point measurements, and converts return signals to PM concentrations. Once calibrated, the Aglite system can map the spatial distribution and temporal variation of the PM concentrations. Whole facility or operation-based emission rates were calculated from the lidar PM data with a mass balance approach. Concentration comparisons with upwind and downwind point sensors were made to verify data quality; lidar-derived PM levels were usually in good agreement with point sensor measurements. Comparisons of lidar-based emissions with emissions estimated through other methods using point sensor data generally show good agreement

    Particulate-Matter Emission Estimates from Agricultural Spring-Tillage Operations Using LIDAR and Inverse Modeling

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    Particulate-matter (PM) emissions from a typical spring agricultural tillage sequence and a strip–till conservation tillage sequence in California’s San Joaquin Valley were estimated to calculate the emissions control efficiency (η) of the strip–till conservation management practice (CMP). Filter-based PM samplers, PM-calibrated optical particle counters (OPCs), and a PM-calibrated light detection and ranging (LIDAR) system were used to monitored upwind and downwind PM concentrations during May and June 2008. Emission rates were estimated through inverse modeling coupled with the filter and OPC measurements and through applying a mass balance to the PM concentrations derived from LIDAR data. Sampling irregularities and errors prevented the estimation of emissions from 42% of the sample periods based on filter samples. OPC and LIDAR datasets were sufficiently complete to estimate emissions and the strip–till CMP η, which were ∌90% for all size fractions in both datasets. Tillage time was also reduced by 84%. Calculated emissions for some operations were within the range of values found in published studies, while other estimates were significantly higher than literature values. The results demonstrate that both PM emissions and tillage time may be reduced by an order of magnitude through the use of a strip–till conservation tillage CMP when compared to spring tillage activities

    Broadening the horizon – level 2.5 of the HUPO-PSI format for molecular interactions

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    BACKGROUND: Molecular interaction Information is a key resource in modern biomedical research. Publicly available data have previously been provided in a broad array of diverse formats, making access to this very difficult. The publication and wide implementation of the Human Proteome Organisation Proteomics Standards Initiative Molecular Interactions (HUPO PSI-MI) format in 2004 was a major step towards the establishment of a single, unified format by which molecular interactions should be presented, but focused purely on protein-protein interactions. RESULTS: The HUPO-PSI has further developed the PSI-MI XML schema to enable the description of interactions between a wider range of molecular types, for example nucleic acids, chemical entities, and molecular complexes. Extensive details about each supported molecular interaction can now be captured, including the biological role of each molecule within that interaction, detailed description of interacting domains, and the kinetic parameters of the interaction. The format is supported by data management and analysis tools and has been adopted by major interaction data providers. Additionally, a simpler, tab-delimited format MITAB2.5 has been developed for the benefit of users who require only minimal information in an easy to access configuration. CONCLUSION: The PSI-MI XML2.5 and MITAB2.5 formats have been jointly developed by interaction data producers and providers from both the academic and commercial sector, and are already widely implemented and well supported by an active development community. PSI-MI XML2.5 enables the description of highly detailed molecular interaction data and facilitates data exchange between databases and users without loss of information. MITAB2.5 is a simpler format appropriate for fast Perl parsing or loading into Microsoft Excel

    Landscape of somatic mutations in 560 breast cancer whole-genome sequences.

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    We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer

    A Roadmap for HEP Software and Computing R&D for the 2020s

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    Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.Peer reviewe

    Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations

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    Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p < 5 × 10−9, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies. Delineation of the genetic architecture of hematological traits in a multi-ethnic dataset allows identification of rare variants with strong effects specific to non-European populations and improved fine mapping of GWAS variants using the trans-ethnic approach

    Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial

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    Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population

    Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients

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    Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation
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