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  • Klionsky, Daniel J., et al. (author)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Research review (peer-reviewed)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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  • Ageron, M., et al. (author)
  • Studies of a full-scale mechanical prototype line for the ANTARES neutrino telescope and tests of a prototype instrument for deep-sea acoustic measurements
  • 2007
  • In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 581:3, s. 695-708
  • Journal article (peer-reviewed)abstract
    • full-scale mechanical prototype line was deployed to a depth of 2500 m to test the leak tightness of the electronics containers and the pressure-resistant properties of an electromechanical cable under evaluation for use in the ANTARES deep-sea neutrino telescope. During a month-long immersion study, line parameter data were taken using miniature autonomous data loggers and shore-based optical time domain reflectometry. Details of the mechanical prototype line, the electromechanical cable and data acquisition are presented. Data taken during the immersion study revealed deficiencies in the pressure resistance of the electromechanical cable terminations at the entry points to the electronics containers. The improvements to the termination, which have been integrated into subsequent detection lines, are discussed. The line also allowed deep-sea acoustic measurements with a prototype hydrophone system. The technical setup of this system is described, and the first results of the data analysis are presented. (c) 2007 Elsevier B.V. All rights reserved.
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  • Jentschel, M., et al. (author)
  • EXILL - a high-efficiency, high-resolution setup for gamma-spectroscopy at an intense cold neutron beam facility
  • 2017
  • In: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12
  • Journal article (peer-reviewed)abstract
    • In the EXILL campaign a highly efficient array of high purity germanium (HPGe) detectors was operated at the cold neutron beam facility PF1B of the Institut Laue-Langevin (ILL) to carry out nuclear structure studies, via measurements of gamma-rays following neutron-induced capture and fission reactions. The setup consisted of a collimation system producing a pencil beam with a thermal capture equivalent flux of about 10(8) ns(-1)cm(2) at the target position and negligible neutron halo. The targetwas surrounded by an array of eight to ten anti-Compton shielded EXOGAMClover detectors, four to six anti-Compton shielded large coaxial GASP detectors and two standard Clover detectors. For a part of the campaign the array was combined with 16 LaBr3:(Ce) detectors from the FATIMA collaboration. The detectorswere arranged in an array of rhombicuboctahedron geometry, providing the possibility to carry out very precise angular correlation and directional-polarization correlation measurements. The triggerless acquisition system allowed a signal collection rate of up to 6 x 10(5) Hz. The data allowed to set multi-fold coincidences to obtain decay schemes and in combination with the FATIMA array of LaBr3:(Ce) detectors to analyze half-lives of excited levels in the pico-to microsecond range. Precise energy and efficiency calibrations of EXILL were performed using standard calibration sources of Ba-133, Co-60 and Eu-152 as well as data from the reactions Al-27(n, gamma)Al-28 and Cl-35(n,gamma)Cl-36 in the energy range from 30 keV up to 10MeV.
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  • Regnier, M., et al. (author)
  • Inulin increases the beneficial effects of rhubarb supplementation on high-fat high-sugar diet-induced metabolic disorders in mice: impact on energy expenditure, brown adipose tissue activity, and microbiota
  • 2023
  • In: Gut Microbes. - : Informa UK Limited. - 1949-0976 .- 1949-0984. ; 15:1
  • Journal article (peer-reviewed)abstract
    • Consumption of prebiotics and plant-based compounds have many beneficial health effects through modulation of gut microbiota composition and are considered as promising nutritional strategy for the treatment of metabolic diseases. In the present study, we assessed the separated and combined effects of inulin and rhubarb on diet-induced metabolic disease in mice. We showed that supplementation with both inulin and rhubarb abolished the total body and fat mass gain upon high-fat and high-sucrose diet (HFHS) as well as several obesity-associated metabolic disorders. These effects were associated with increased energy expenditure, lower whitening of the brown adipose tissue, higher mitochondria activity and increased expression of lipolytic markers in white adipose tissue. Despite modifications of intestinal gut microbiota and bile acid compositions by inulin or rhubarb alone, combination of both inulin and rhubarb had minor additional impact on these parameters. However, the combination of inulin and rhubarb increased the expression of several antimicrobial peptides and higher goblet cell numbers, thereby suggesting a reinforcement of the gut barrier. Together, these results suggest that the combination of inulin and rhubarb in mice potentiates beneficial effects of separated rhubarb and inulin on HFHS-related metabolic disease and could be considered as nutritional strategy for the prevention and treatment of obesity and related pathologies.
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  • Cronin, T. M., et al. (author)
  • Holocene paleoceanography and glacial history of Lincoln Sea, Ryder Glacier, Northern Greenland, based on foraminifera and ostracodes
  • 2022
  • In: Marine Micropaleontology. - : Elsevier BV. - 0377-8398 .- 1872-6186. ; 175
  • Journal article (peer-reviewed)abstract
    • We reconstructed Holocene paleoceanography of the Sherard Osborn Fjord (SOF), N Greenland, and Lincoln Sea in the eastern Arctic Ocean using sediment properties and micropaleontology from cores obtained during the Ryder 2019 Expedition. Our aims were to better understand faunal indicators of water mass influence on Ryder Glacier and the Lincoln Sea at water depths >500 m. Benthic microfaunal reflect glacio-marine interval during late deglaciation ~10.5 to 8.5 ka (kiloannum) during the Holocene Thermal Maximum (HTM) with dominant benthic foraminiferal species Cassidulina neoteretis, Cassidulina reniforme, and the ostracode Rabilimis mirabilis. Casssidulina neoteretis is considered an indicator of Atlantic Water (AW) throughout the Arctic Ocean and Nordic Seas; C. reniforme reflects glacio-marine conditions from the retreating Ryder Glacier. Deglaciation was followed by a period of elevated productivity and diverse ostracode faunal assemblages that suggest AW influence from 8.5 to 6 ka in the Lincoln Sea and inside SOF. The Holocene occurrence of the ostracode species Acetabulastoma arcticum, that appears in low numbers in the Lincoln Sea and briefly (~ 4–3 ka) in SOF, reflects the presence of variable sea ice in this region. Based on the similarities of the Lincoln Sea and fjord ostracodes to modern and glacial-deglacial faunas from the central Arctic Ocean, the AW influence likely originates from recirculation of AW water from the central Arctic Basin. In general, our results suggest a strong but temporally varying influence of AW during the entire 10.5 kyr record of the Lincoln Sea and SOF.
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  • Smati, S., et al. (author)
  • Integrative study of diet-induced mouse models of NAFLD identifies PPARα as a sexually dimorphic drug target
  • 2022
  • In: Gut. - : BMJ Publishing Group. - 0017-5749 .- 1468-3288. ; 71:4, s. 807-821
  • Journal article (peer-reviewed)abstract
    • We evaluated the influence of sex on the pathophysiology of non-alcoholic fatty liver disease (NAFLD). We investigated diet-induced phenotypic responses to define sex-specific regulation between healthy liver and NAFLD to identify influential pathways in different preclinical murine models and their relevance in humans. Different models of diet-induced NAFLD (high-fat diet, choline-deficient high-fat diet, Western diet or Western diet supplemented with fructose and glucose in drinking water) were compared with a control diet in male and female mice. We performed metabolic phenotyping, including plasma biochemistry and liver histology, untargeted large-scale approaches (liver metabolome, lipidome and transcriptome), gene expression profiling and network analysis to identify sex-specific pathways in the mouse liver. The different diets induced sex-specific responses that illustrated an increased susceptibility to NAFLD in male mice. The most severe lipid accumulation and inflammation/fibrosis occurred in males receiving the high-fat diet and Western diet, respectively. Sex-biased hepatic gene signatures were identified for these different dietary challenges. The peroxisome proliferator-activated receptor α (PPARα) co-expression network was identified as sexually dimorphic, and in vivo experiments in mice demonstrated that hepatocyte PPARα determines a sex-specific response to fasting and treatment with pemafibrate, a selective PPARα agonist. Liver molecular signatures in humans also provided evidence of sexually dimorphic gene expression profiles and the sex-specific co-expression network for PPARα. These findings underscore the sex specificity of NAFLD pathophysiology in preclinical studies and identify PPARα as a pivotal, sexually dimorphic, pharmacological target. NCT02390232.
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  • Laruelle, G. G., et al. (author)
  • Anthropogenic perturbations of the silicon cycle at the global scale: Key role of the land-ocean transition
  • 2009
  • In: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 23
  • Research review (peer-reviewed)abstract
    • Silicon (Si), in the form of dissolved silicate (DSi), is a key nutrient in marine and continental ecosystems. DSi is taken up by organisms to produce structural elements (e.g., shells and phytoliths) composed of amorphous biogenic silica (bSiO(2)). A global mass balance model of the biologically active part of the modern Si cycle is derived on the basis of a systematic review of existing data regarding terrestrial and oceanic production fluxes, reservoir sizes, and residence times for DSi and bSiO(2). The model demonstrates the high sensitivity of biogeochemical Si cycling in the coastal zone to anthropogenic pressures, such as river damming and global temperature rise. As a result, further significant changes in the production and recycling of bSiO(2) in the coastal zone are to be expected over the course of this century.
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  • Saunois, Marielle, et al. (author)
  • The Global Methane Budget 2000–2017
  • 2020
  • In: Earth System Science Data. - : Copernicus GmbH. - 1866-3516 .- 1866-3508. ; 12:3, s. 1561-1623
  • Journal article (peer-reviewed)abstract
    • Understanding and quantifying the global methane (CH4) budget is important for assessing realistic pathways to mitigate climate change. Atmospheric emissions and concentrations of CH4 continue to increase, making CH4 the second most important human-influenced greenhouse gas in terms of climate forcing, after carbon dioxide (CO2). The relative importance of CH4 compared to CO2 depends on its shorter atmospheric lifetime, stronger warming potential, and variations in atmospheric growth rate over the past decade, the causes of which are still debated. Two major challenges in reducing uncertainties in the atmospheric growth rate arise from the variety of geographically overlapping CH4 sources and from the destruction of CH4 by short-lived hydroxyl radicals (OH). To address these challenges, we have established a consortium of multidisciplinary scientists under the umbrella of the Global Carbon Project to synthesize and stimulate new research aimed at improving and regularly updating the global methane budget. Following Saunois et al. (2016), we present here the second version of the living review paper dedicated to the decadal methane budget, integrating results of top-down studies (atmospheric observations within an atmospheric inverse-modelling framework) and bottom-up estimates (including process-based models for estimating land surface emissions and atmospheric chemistry, inventories of anthropogenic emissions, and data-driven extrapolations).For the 2008–2017 decade, global methane emissions are estimated by atmospheric inversions (a top-down approach) to be 576 Tg CH4 yr−1 (range 550–594, corresponding to the minimum and maximum estimates of the model ensemble). Of this total, 359 Tg CH4 yr−1 or ∼ 60 % is attributed to anthropogenic sources, that is emissions caused by direct human activity (i.e. anthropogenic emissions; range 336–376 Tg CH4 yr−1 or 50 %–65 %). The mean annual total emission for the new decade (2008–2017) is 29 Tg CH4 yr−1 larger than our estimate for the previous decade (2000–2009), and 24 Tg CH4 yr−1 larger than the one reported in the previous budget for 2003–2012 (Saunois et al., 2016). Since 2012, global CH4 emissions have been tracking the warmest scenarios assessed by the Intergovernmental Panel on Climate Change. Bottom-up methods suggest almost 30 % larger global emissions (737 Tg CH4 yr−1, range 594–881) than top-down inversion methods. Indeed, bottom-up estimates for natural sources such as natural wetlands, other inland water systems, and geological sources are higher than top-down estimates. The atmospheric constraints on the top-down budget suggest that at least some of these bottom-up emissions are overestimated. The latitudinal distribution of atmospheric observation-based emissions indicates a predominance of tropical emissions (∼ 65 % of the global budget, < 30∘ N) compared to mid-latitudes (∼ 30 %, 30–60∘ N) and high northern latitudes (∼ 4 %, 60–90∘ N). The most important source of uncertainty in the methane budget is attributable to natural emissions, especially those from wetlands and other inland waters.Some of our global source estimates are smaller than those in previously published budgets (Saunois et al., 2016; Kirschke et al., 2013). In particular wetland emissions are about 35 Tg CH4 yr−1 lower due to improved partition wetlands and other inland waters. Emissions from geological sources and wild animals are also found to be smaller by 7 Tg CH4 yr−1 by 8 Tg CH4 yr−1, respectively. However, the overall discrepancy between bottom-up and top-down estimates has been reduced by only 5 % compared to Saunois et al. (2016), due to a higher estimate of emissions from inland waters, highlighting the need for more detailed research on emissions factors. Priorities for improving the methane budget include (i) a global, high-resolution map of water-saturated soils and inundated areas emitting methane based on a robust classification of different types of emitting habitats; (ii) further development of process-based models for inland-water emissions; (iii) intensification of methane observations at local scales (e.g., FLUXNET-CH4 measurements) and urban-scale monitoring to constrain bottom-up land surface models, and at regional scales (surface networks and satellites) to constrain atmospheric inversions; (iv) improvements of transport models and the representation of photochemical sinks in top-down inversions; and (v) development of a 3D variational inversion system using isotopic and/or co-emitted species such as ethane to improve source partitioning.The data presented here can be downloaded from https://doi.org/10.18160/GCP-CH4-2019 (Saunois et al., 2020) and from the Global Carbon Project.
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  • Bender, Michael, et al. (author)
  • Future of nuclear fission theory
  • 2020
  • In: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:11
  • Research review (peer-reviewed)abstract
    • There has been much recent interest in nuclear fission, due in part to a new appreciation of its relevance to astrophysics, stability of superheavy elements, and fundamental theory of neutrino interactions. At the same time, there have been important developments on a conceptual and computational level for the theory. The promising new theoretical avenues were the subject of a workshop held at the University of York in October 2019; this report summarises its findings and recommendations.
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  • Ciais, Philippe, et al. (author)
  • Definitions and methods to estimate regional land carbon fluxes for the second phase of the REgional Carbon Cycle Assessment and Processes Project (RECCAP-2)
  • 2022
  • In: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 15:3, s. 1289-1316
  • Journal article (peer-reviewed)abstract
    • Regional land carbon budgets provide insights into the spatial distribution of the land uptake of atmospheric carbon dioxide and can be used to evaluate carbon cycle models and to define baselines for land-based additional mitigation efforts. The scientific community has been involved in providing observation-based estimates of regional carbon budgets either by downscaling atmospheric CO2 observations into surface fluxes with atmospheric inversions, by using inventories of carbon stock changes in terrestrial ecosystems, by upscaling local field observations such as flux towers with gridded climate and remote sensing fields, or by integrating data-driven or process-oriented terrestrial carbon cycle models. The first coordinated attempt to collect regional carbon budgets for nine regions covering the entire globe in the RECCAP-1 project has delivered estimates for the decade 2000–2009, but these budgets were not comparable between regions due to different definitions and component fluxes being reported or omitted. The recent recognition of lateral fluxes of carbon by human activities and rivers that connect CO2 uptake in one area with its release in another also requires better definitions and protocols to reach harmonized regional budgets that can be summed up to a globe scale and compared with the atmospheric CO2 growth rate and inversion results. In this study, using the international initiative RECCAP-2 coordinated by the Global Carbon Project, which aims to be an update to regional carbon budgets over the last 2 decades based on observations for 10 regions covering the globe with a better harmonization than the precursor project, we provide recommendations for using atmospheric inversion results to match bottom-up carbon accounting and models, and we define the different component fluxes of the net land atmosphere carbon exchange that should be reported by each research group in charge of each region. Special attention is given to lateral fluxes, inland water fluxes, and land use fluxes.
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  • Clish, Clary B., et al. (author)
  • Integrative biological analysis of the APOE*3-leiden transgenic mouse
  • 2004
  • In: Omics. - : Mary Ann Liebert. - 1536-2310 .- 1557-8100. ; 8:1, s. 3-13
  • Journal article (peer-reviewed)abstract
    • Integrative (or systems biology) is a new approach to analyzing biological entities as integrated systems of genetic, genomic, protein, metabolite, cellular, and pathway events that are in flux and interdependent. Here, we demonstrate the application of intregrative biological analysis to a mammalian disease model, the apolipoprotein E3-Leiden (APO*E3) transgenic mouse. Mice selected for the study were fed a normal chow diet and sacrificed at 9 weeks of age-conditions under which they develop only mild type I and II atherosclerotic lesions. Hepatic mRNA expression analysis showed a 25% decrease in APO A1 and a 43% increase in liver fatty acid binding protein expression between transgenic and wild type control mice, while there was no change in PPAR-alpha expression. On-line high performance liquid chromatography-mass spectrometry quantitative profiling of tryptic digests of soluble liver proteins and liver lipids, coupled with principle component analysis, enabled rapid identification of early protein and metabolite markers of disease pathology. These included a 44% increase in L-FABP in transgenic animals compared to controls, as well as an increase in triglycerides and select bioactive lysophosphatidylcholine species. A correlation analysis of identified genes, proteins, and lipids was used to construct an interaction network. Taken together, these results indicate that integrative biology is a powerful tool for rapid identification of early markers and key components of pathophysiologic processes, and constitute the first application of this approach to a mammalian system.
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  • Kroeck, David M., et al. (author)
  • Morphological variability of peteinoid acritarchs from the Middle Ordovician of Öland, Sweden, and implications for acritarch classification
  • 2021
  • In: Palynology. - : Informa UK Limited. - 0191-6122 .- 1558-9188. ; 45:4, s. 705-715
  • Journal article (peer-reviewed)abstract
    • Investigation of large populations of peteinoid acritarchs recovered from Middle Ordovician strata of the Hälludden and Horns Udde quarry sections (Öland, Sweden) allows for statistical analyses based on morphometric measurements. The results indicate the presence of assemblages with a continuous variability of morphotypes, thus a distinction of different peteinoid acritarch taxa in the sections proved to be impossible. This challenges the currently accepted classification based on a differentiation into the three genera Peteinosphaeridium, Cycloposphaeridium and Liliosphaeridium, and a multitude of different species; individual taxa are essentially arbitrary as morphotypes intergrade. Investigations on modern dinoflagellates show that these can develop variable cyst morphologies depending on environmental factors. By analogy, it can be hypothesised that the different morphologies observed among the peteinoid acritarchs from Öland are cysts produced by only very few phytoplanktic organisms (or even a single species) with high morphological variability.
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  • Petrescu, Ana Maria Roxana, et al. (author)
  • The consolidated European synthesis of CO2emissions and removals for the European Union and United Kingdom : 1990-2018
  • 2021
  • In: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 13:5, s. 2363-2406
  • Research review (peer-reviewed)abstract
    • Reliable quantification of the sources and sinks of atmospheric carbon dioxide (CO2), including that of their trends and uncertainties, is essential to monitoring the progress in mitigating anthropogenic emissions under the Kyoto Protocol and the Paris Agreement. This study provides a consolidated synthesis of estimates for all anthropogenic and natural sources and sinks of CO2 for the European Union and UK (EU27 + UK), derived from a combination of state-of-the-art bottom-up (BU) and top-down (TD) data sources and models. Given the wide scope of the work and the variety of datasets involved, this study focuses on identifying essential questions which need to be answered to properly understand the differences between various datasets, in particular with regards to the less-well-characterized fluxes from managed ecosystems. The work integrates recent emission inventory data, process-based ecosystem model results, data-driven sector model results and inverse modeling estimates over the period 1990-2018. BU and TD products are compared with European national greenhouse gas inventories (NGHGIs) reported under the UNFCCC in 2019, aiming to assess and understand the differences between approaches. For the uncertainties in NGHGIs, we used the standard deviation obtained by varying parameters of inventory calculations, reported by the member states following the IPCC Guidelines. Variation in estimates produced with other methods, like atmospheric inversion models (TD) or spatially disaggregated inventory datasets (BU), arises from diverse sources including within-model uncertainty related to parameterization as well as structural differences between models. In comparing NGHGIs with other approaches, a key source of uncertainty is that related to different system boundaries and emission categories (CO2 fossil) and the use of different land use definitions for reporting emissions from land use, land use change and forestry (LULUCF) activities (CO2 land). At the EU27 + UK level, the NGHGI (2019) fossil CO2 emissions (including cement production) account for 2624 Tg CO2 in 2014 while all the other seven bottom-up sources are consistent with the NGHGIs and report a mean of 2588 (± 463 Tg CO2). The inversion reports 2700 Tg CO2 (± 480 Tg CO2), which is well in line with the national inventories. Over 2011-2015, the CO2 land sources and sinks from NGHGI estimates report-90 Tg C yr-1 ± 30 Tg C yr-1 while all other BU approaches report a mean sink of-98 Tg C yr-1 (± 362 Tg of C from dynamic global vegetation models only). For the TD model ensemble results, we observe a much larger spread for regional inversions (i.e., mean of 253 Tg C yr-1 ± 400 Tg C yr-1). This concludes that (a) current independent approaches are consistent with NGHGIs and (b) their uncertainty is too large to allow a verification because of model differences and probably also because of the definition of "CO2 flux"obtained from different approaches. The referenced datasets related to figures are visualized.
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