113 research outputs found

    A multi-sensor approach towards a global vegetation corrected SRTM DEM product

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    AbstractWe develop the first global ‘Bare-Earth’ Digital Elevation Model (DEM) based on the Shuttle Radar Topography Mission (SRTM) for all landmasses between 60N and 54S. Our new ‘Bare-Earth’ SRTM DEM combines multiple remote sensing datasets, including point-ground elevations from NASA's laser altimeter ICESat, a database of percentage of tree cover from the MODIS satellite as a proxy for penetration depth of SRTM and a global vegetation height map in order to remove the vegetation artefacts present in the original SRTM DEM. We test multiple methods of removing vegetation artefacts and investigate the use of regionalization. Our final ‘Bare-Earth’ SRTM product shows global improvements greater than 10m in the bias over the original SRTM DEM in vegetated areas compared with ground elevations determined from ICESat data with a significant reduction in the root mean square error from over 14m to 6m globally. Therefore, our DEM will be valuable for any global applications, such as large scale flood modelling requiring a ‘Bare-Earth’ DEM

    Overspill avalanching in a dense reservoir network

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    Sustainability of communities, agriculture, and industry is strongly dependent on an effective storage and supply of water resources. In some regions the economic growth has led to a level of water demand which can only be accomplished through efficient reservoir networks. Such infrastructures are not always planned at larger scale but rather made by farmers according to their local needs of irrigation during droughts. Based on extensive data from the upper Jaguaribe basin, one of the world's largest system of reservoirs, located in the Brazilian semiarid northeast, we reveal that surprisingly it self-organizes into a scale-free network exhibiting also a power-law in the distribution of the lakes and avalanches of discharges. With a new self-organized-criticality-type model we manage to explain the novel critical exponents. Implementing a flow model we are able to reproduce the measured overspill evolution providing a tool for catastrophe mitigation and future planning

    Efficacy and safety of high-dose chemotherapy as the first or subsequent salvage treatment line in patients with relapsed or refractory germ cell cancer: an international multicentric analysis

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    \ua9 2024 The Author(s)Background: In relapsed or refractory (RR) metastatic germ cell cancer (GCC), high-dose (HD) chemotherapy (CTX) plus autologous stem cell transplantation is considered the standard of care. Limited data exist regarding the efficacy of HD-CTX following conventionally dosed salvage regimens (CDRs). This analysis explores and contrasts the efficacy of HD-CTX as the first or subsequent salvage regimen. Patients and methods: Data were retrospectively collected to explore the efficacy of HD-CTX administered as the first (group A) or subsequent salvage CTX (group B) after a CDR. The primary endpoint was OS from the time of HD-CTX. Associations of survival, overall response rate (ORR), and toxicity with clinical characteristics were explored using stratified Kaplan–Meier and Cox regression models. Results: Overall, 283 patients with GCC were included from 11 international centers, with 159 patients (56%) in group A and 124 patients (44%) in group B. The first salvage treatment was administered between 1998 and 2022, with a median follow-up of 27.0 [standard deviation (SD) 46.2] months for group A and 17.0 (SD 48.5) months for group B. The median OS from HD-CTX treatment initiation was not reached in group A, compared with 25 months in group B (P = 0.00027), associated with 2- and 5-year OS rates of 74% and 63% (group A) versus 53% and 37% (group B), respectively. When administered as the first salvage treatment, HD-CTX was associated with a higher ORR (79% versus 60%; P = 0.013) and lower nonhematologic grade ≥3 toxicity rate (78% versus 97%; P < 0.001). Concerning risk factor analysis for the total cohort, the International Prognostic Factors Study Group score was the only independent predictor of OS in multivariable analysis (P = 0.006). Conclusions: When administered as the initial salvage treatment or after CDR, HD-CTX exhibits curative potential for patients with RR GCC. The efficacy and safety outcomes were more favorable when HD-CTX was conducted as the first salvage treatment line

    [3H]Adenine is a suitable radioligand for the labeling of G protein-coupled adenine receptors but shows high affinity to bacterial contaminations in buffer solutions

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    [3H]Adenine has previously been used to label the newly discovered G protein-coupled murine adenine receptors. Recent reports have questioned the suitability of [3H]adenine for adenine receptor binding studies because of curious results, e.g. high specific binding even in the absence of mammalian protein. In this study, we showed that specific [3H]adenine binding to various mammalian membrane preparations increased linearly with protein concentration. Furthermore, we found that Tris-buffer solutions typically used for radioligand binding studies (50 mM, pH 7.4) that have not been freshly prepared but stored at 4°C for some time may contain bacterial contaminations that exhibit high affinity binding for [3H]adenine. Specific binding is abolished by heating the contaminated buffer or filtering it through 0.2-μm filters. Three different, aerobic, gram-negative bacteria were isolated from a contaminated buffer solution and identified as Achromobacter xylosoxidans, A. denitrificans, and Acinetobacter lwoffii. A. xylosoxidans, a common bacterium that can cause nosocomial infections, showed a particularly high affinity for [3H]adenine in the low nanomolar range. Structure–activity relationships revealed that hypoxanthine also bound with high affinity to A. xylosoxidans, whereas other nucleobases (uracil, xanthine) and nucleosides (adenosine, uridine) did not. The nature of the labeled site in bacteria is not known, but preliminary results indicate that it may be a high-affinity purine transporter. We conclude that [3H]adenine is a well-suitable radioligand for adenine receptor binding studies but that bacterial contamination of the employed buffer solutions must be avoided

    Reciprocal co-regulation of EGR2 and MECP2 is disrupted in Rett syndrome and autism

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    Mutations in MECP2, encoding methyl-CpG-binding protein 2 (MeCP2), cause the neurodevelopmental disorder Rett syndrome (RTT). Although MECP2 mutations are rare in idiopathic autism, reduced MeCP2 levels are common in autism cortex. MeCP2 is critical for postnatal neuronal maturation and a modulator of activity-dependent genes such as Bdnf (brain-derived neurotropic factor) and JUNB. The activity-dependent early growth response gene 2 (EGR2), required for both early hindbrain development and mature neuronal function, has predicted binding sites in the promoters of several neurologically relevant genes including MECP2. Conversely, MeCP2 family members MBD1, MBD2 and MBD4 bind a methylated CpG island in an enhancer region located in EGR2 intron 1. This study was designed to test the hypothesis that MECP2 and EGR2 regulate each other’s expression during neuronal maturation in postnatal brain development. Chromatin immunoprecipitation analysis showed EGR2 binding to the MECP2 promoter and MeCP2 binding to the enhancer region in EGR2 intron 1. Reduction in EGR2 and MeCP2 levels in cultured human neuroblastoma cells by RNA interference reciprocally reduced expression of both EGR2 and MECP2 and their protein products. Consistent with a role of MeCP2 in enhancing EGR2, Mecp2-deficient mouse cortex samples showed significantly reduced EGR2 by quantitative immunofluorescence. Furthermore, MeCP2 and EGR2 show coordinately increased levels during postnatal development of both mouse and human cortex. In contrast to age-matched Controls, RTT and autism postmortem cortex samples showed significant reduction in EGR2. Together, these data support a role of dysregulation of an activity-dependent EGR2/MeCP2 pathway in RTT and autism

    A global network for operational flood risk reduction

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    Every year riverine flooding affects millions of people in developing countries, due to the large population exposure in the floodplains and the lack of adequate flood protection measures. Preparedness and monitoring are effective ways to reduce flood risk. State-of-the-art technologies relying on satellite remote sensing as well as numerical hydrological and weather predictions can detect and monitor severe flood events at a global scale. This paper describes the emerging role of the Global Flood Partnership (GFP), a global network of scientists, users, private and public organizations active in global flood risk management. Currently, a number of GFP member institutes regularly share results from their experimental products, developed to predict and monitor where and when flooding is taking place in near real-time. GFP flood products have already been used on several occasions by national environmental agencies and humanitarian organizations to support emergency operations and to reduce the overall socio-economic impacts of disasters. This paper describes a range of global flood products developed by GFP partners, and how these provide complementary information to support and improve current global flood risk management for large scale catastrophes. We also discuss existing challenges and ways forward to turn current experimental products into an integrated flood risk management platform to improve rapid access to flood information and increase resilience to flood events at global scale
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