14 research outputs found

    Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood

    Get PDF
    Idiopathic pulmonary arterial hypertension (IPAH) is a rare but fatal disease diagnosed by right heart catheterisation and the exclusion of other forms of pulmonary arterial hypertension, producing a heterogeneous population with varied treatment response. Here we show unsupervised machine learning identification of three major patient subgroups that account for 92% of the cohort, each with unique whole blood transcriptomic and clinical feature signatures. These subgroups are associated with poor, moderate, and good prognosis. The poor prognosis subgroup is associated with upregulation of the ALAS2 and downregulation of several immunoglobulin genes, while the good prognosis subgroup is defined by upregulation of the bone morphogenetic protein signalling regulator NOG, and the C/C variant of HLA-DPA1/DPB1 (independently associated with survival). These findings independently validated provide evidence for the existence of 3 major subgroups (endophenotypes) within the IPAH classification, could improve risk stratification and provide molecular insights into the pathogenesis of IPAH

    Appendix B. Table showing mass-based and leaf area-based N and P concentrations in live and senesced Pentaclethra macroloba leaves (proficiency) by soil P fertility in La Selva, Costa Rica.

    No full text
    Table showing mass-based and leaf area-based N and P concentrations in live and senesced Pentaclethra macroloba leaves (proficiency) by soil P fertility in La Selva, Costa Rica

    Appendix C. Figure showing leaf-area-based senesced-leaf P and N an live-leaf P and N in P. macroloba in fruiting and non-fruiting trees as a function of tree-level soil P in La Selva, Costa Rica.

    No full text
    Figure showing leaf-area-based senesced-leaf P and N an live-leaf P and N in P. macroloba in fruiting and non-fruiting trees as a function of tree-level soil P in La Selva, Costa Rica

    Appendix A. Table showing soil characteristics (0–15 cm) surrounding target trees within the three stands in La Selva, Costa Rica.

    No full text
    Table showing soil characteristics (0–15 cm) surrounding target trees within the three stands in La Selva, Costa Rica

    Integrating Drone Imagery into High Resolution Satellite Remote Sensing Assessments of Estuarine Environments

    No full text
    Very high-resolution satellite imagery (≤5 m resolution) has become available on a spatial and temporal scale appropriate for dynamic wetland management and conservation across large areas. Estuarine wetlands have the potential to be mapped at a detailed habitat scale with a frequency that allows immediate monitoring after storms, in response to human disturbances, and in the face of sea-level rise. Yet mapping requires significant fieldwork to run modern classification algorithms and estuarine environments can be difficult to access and are environmentally sensitive. Recent advances in unoccupied aircraft systems (UAS, or drones), coupled with their increased availability, present a solution. UAS can cover a study site with ultra-high resolution (<5 cm) imagery allowing visual validation. In this study we used UAS imagery to assist training a Support Vector Machine to classify WorldView-3 and RapidEye satellite imagery of the Rachel Carson Reserve in North Carolina, USA. UAS and field-based accuracy assessments were employed for comparison across validation methods. We created and examined an array of indices and layers including texture, NDVI, and a LiDAR DEM. Our results demonstrate classification accuracy on par with previous extensive fieldwork campaigns (93% UAS and 93% field for WorldView-3; 92% UAS and 87% field for RapidEye). Examining change between 2004 and 2017, we found drastic shoreline change but general stability of emergent wetlands. Both WorldView-3 and RapidEye were found to be valuable sources of imagery for habitat classification with the main tradeoff being WorldView’s fine spatial resolution versus RapidEye’s temporal frequency. We conclude that UAS can be highly effective in training and validating satellite imagery

    FY 2009 Progress: Process Monitoring Technology Demonstration at PNNL

    No full text
    Pacific Northwest National Laboratory (PNNL) is developing and demonstrating three technologies designed to assist in the monitoring of reprocessing facilities in near-real time. These technologies include 1) a multi-isotope process monitor (MIP), 2) a spectroscopy-based monitor that uses UV-Vis-NIR (ultraviolet-visible-near infrared) and Raman spectrometers, and 3) an electrochemically modulated separations approach (EMS). The MIP monitor uses gamma spectroscopy and pattern recognition software to identify off-normal conditions in process streams. The UV-Vis-NIR and Raman spectroscopic monitoring continuously measures chemical compositions of the process streams including actinide metal ions (uranium, plutonium, neptunium), selected fission products, and major cold flow sheet chemicals. The EMS approach provides an on-line means for separating and concentrating elements of interest out of complex matrices prior to detection via nondestructive assay by gamma spectroscopy or destructive analysis with mass spectrometry. A general overview of the technologies and ongoing demonstration results are described in this report

    SOX17 Deficiency Mediates Pulmonary Hypertension: At the Crossroads of Sex, Metabolism, and Genetics

    No full text
    RATIONALE/OBJECTIVES: Genetic studies suggest SOX17 deficiency increases pulmonary arterial hypertension (PAH) risk. Based on pathological roles of estrogen and hypoxia inducible factor 2α (HIF-2α) signaling in PA endothelial cells (PAECs), we hypothesized that SOX17 is a target of estrogen signaling that promotes mitochondrial function and attenuates PAH development via HIF-2α inhibition. METHODS: We used metabolic (seahorse) and promoter lucifer assays in PAECs along with the chronic hypoxia murine model to test the hypothesis. MEASUREMENTS AND MAIN RESULTS: Sox17 expression was reduced in PAH tissues (rodent models and from patients). Chronic hypoxic PH was exacerbated by mice with conditional Tie2-Sox17 (Sox17EC-/-) deletion and attenuated by transgenic Tie2-Sox17 over-expression (Sox17Tg). Based on untargeted proteomics, metabolism was the top pathway altered by SOX17 deficiency in PAECs. Mechanistically, we found HIF-2α levels were increased in the lungs of Sox17EC-/- and reduced in those from Sox17Tg mice. Increased SOX17 promoted oxidative phosphorylation and mitochondrial function in PAECs, which were partly attenuated by HIF-2α overexpression. Rat lungs in males displayed higher Sox17 expression versus females, suggesting repression by estrogen signaling. Supporting 16alpha-hydroxyestrone (16αOHE, a pathologic estrogen metabolite)-mediated repression of SOX17 promoter activity, Sox17Tg mice attenuated 16αOHE-mediated exacerbations of chronic hypoxic PH. Finally, in adjusted analyses in patients with PAH, we report novel associations between a SOX17 risk variant, rs10103692, with reduced plasma citrate levels (n=1326). CONCLUSIONS: Cumulatively, SOX17 promotes mitochondrial bioenergetics and attenuates PAH, in part, via inhibition of HIF-2α. 16αOHE mediates PAH development via downregulation of SOX17, linking sexual dimorphism and SOX17 genetics in PAH. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)
    corecore