| 1. |
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| 2. |
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| 3. |
- Wang, J., et al.
(författare)
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Final report of the CCQM-K145 : Toxic and essential elements in bovine liver
- 2020
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Ingår i: Metrologia. - : IOP Publishing Ltd. - 0026-1394 .- 1681-7575. ; 57:1 A
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Tidskriftsartikel (refereegranskat)abstract
- Liver plays a major role in metabolism and acts as a source of energy for the body by storing glycogen. With the growing interest and investigation in the biological effects in recent years, it is important and necessary to develop accurate and comparable analytical methods for elements in bio-samples. It has, however, been 10 years since the tissue sample (bovine liver) of CCQM-K49 key comparison. The purpose of CCQM-K145 is to ensure the comparable and traceable measurement results for essential and toxic elements such as P, S, Zn, Mn, Ni, Mo, Sr, Cr, Co, Pb, As and Hg in bovine liver among NMIs and other designated measurement bodies worldwide. The comparison was agreed by IAWG as 6th IAWG Benchmarking Exercise with Zn and Ni as exemplary elements at the meeting in Korea in the early October 2016. The results of CCQM-K145 are expected to cover the measurement capability and support CMCs claiming for inorganic elements in the similar biological tissue materials and food samples. 30 NMIs and DIs registered in CCQM-K145. With respect to the methodology, a variety of techniques such as IDMS, ICP-OES, ICP-MS(non-ID), AAS and NAA were adopted by the participants. For Zn, Ni, Sr, Pb and Hg measurements, most participants chose ID-ICP-MS method, which showed the better performance in terms of consistency and reliability of the measurement results. In aspect of the traceability for the measurement results in CCQM-K145, most participants used their own (in house) CRMs or other NMI's CRMs to guarantee trace to SI unit. Most participants used similar matrix CRMs for quality control or method validation. Base on different statistic way to calculate the reference mass fraction values and associated uncertainties for each measurand, removal of the suspected extreme values, and discussion at the IAWG meetings, the median values are proposed as the KCRV for Zn, Ni, Mn, Mo, Cr, Pb and Hg; the arithmetic mean values are proposed as the KCRV for P, S, Sr, Co and As. In general, the performances of the majority of CCQM-K145 participants are very good, illustrating their measurement capabilities for Zn, Ni, P, S, Mn, Mo, Sr, Cr, As, Co, Pb and Hg in a complex biological tissue matrix. Bovine liver contains many kinds of nutrients and microelements, it can be regarded as a typical representative material of biological tissue and food. In CCQM-K145, the analytes involved alkali metals and transition elements, metalloids/semi-metals and non metals with a range of mass fraction from mg/g to μg/kg. CCQM-K145 also tested the ability of NMIs/DIs to determine elements that were easy to be lost and polluted, and interfered significantly. The chemical pretreatment methods of samples used in the comparison is suitable for general food and biological matrix samples. A variety of measurement methods used in the comparison represent the main instrumental technology for elemental analysis. Therefore, for supporting CMC claim, CCQM-K145 is readily applicable to measurement of more elements in a wide range of biological materials (including liquids and solids) and meat products. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
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| 4. |
- Sawcer, Stephen, et al.
(författare)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 5. |
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| 6. |
- Kuhle, J., et al.
(författare)
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Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study
- 2015
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Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 21:8, s. 1013-1024
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. Methods: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. Results: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. Conclusions: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.
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| 7. |
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| 8. |
- Ramonet, M., et al.
(författare)
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The fingerprint of the summer 2018 drought in Europe on ground-based atmospheric CO 2 measurements : Atmospheric CO 2 anomaly
- 2020
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Ingår i: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 375:1810
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Tidskriftsartikel (refereegranskat)abstract
- During the summer of 2018, a widespread drought developed over Northern and Central Europe. The increase in temperature and the reduction of soil moisture have influenced carbon dioxide (CO 2) exchange between the atmosphere and terrestrial ecosystems in various ways, such as a reduction of photosynthesis, changes in ecosystem respiration, or allowing more frequent fires. In this study, we characterize the resulting perturbation of the atmospheric CO 2 seasonal cycles. 2018 has a good coverage of European regions affected by drought, allowing the investigation of how ecosystem flux anomalies impacted spatial CO 2 gradients between stations. This density of stations is unprecedented compared to previous drought events in 2003 and 2015, particularly thanks to the deployment of the Integrated Carbon Observation System (ICOS) network of atmospheric greenhouse gas monitoring stations in recent years. Seasonal CO 2 cycles from 48 European stations were available for 2017 and 2018. Earlier data were retrieved for comparison from international databases or national networks. Here, we show that the usual summer minimum in CO 2 due to the surface carbon uptake was reduced by 1.4 ppm in 2018 for the 10 stations located in the area most affected by the temperature anomaly, mostly in Northern Europe. Notwithstanding, the CO 2 transition phases before and after July were slower in 2018 compared to 2017, suggesting an extension of the growing season, with either continued CO 2 uptake by photosynthesis and/or a reduction in respiration driven by the depletion of substrate for respiration inherited from the previous months due to the drought. For stations with sufficiently long time series, the CO 2 anomaly observed in 2018 was compared to previous European droughts in 2003 and 2015. Considering the areas most affected by the temperature anomalies, we found a higher CO 2 anomaly in 2003 (+3 ppm averaged over 4 sites), and a smaller anomaly in 2015 (+1 ppm averaged over 11 sites) compared to 2018. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.
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| 9. |
- Verra, L., et al.
(författare)
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Development of the self-modulation instability of a relativistic proton bunch in plasma
- 2023
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Ingår i: Physics of Plasmas. - : American Institute of Physics (AIP). - 1070-664X .- 1089-7674. ; 30:8
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Tidskriftsartikel (refereegranskat)abstract
- Self-modulation is a beam-plasma instability that is useful to drive large-amplitude wakefields with bunches much longer than the plasma skin depth. We present experimental results showing that, when increasing the ratio between the initial transverse size of the bunch and the plasma skin depth, the instability occurs later along the bunch, or not at all, over a fixed plasma length because the amplitude of the initial wakefields decreases. We show cases for which self-modulation does not develop, and we introduce a simple model discussing the conditions for which it would not occur after any plasma length. Changing bunch size and plasma electron density also changes the growth rate of the instability. We discuss the impact of these results on the design of a particle accelerator based on the self-modulation instability seeded by a relativistic ionization front, such as the future upgrade of the Advanced WAKefield Experiment.
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| 10. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 11. |
- Nechaeva, T., et al.
(författare)
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Hosing of a Long Relativistic Particle Bunch in Plasma
- 2024
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 132:7
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Tidskriftsartikel (refereegranskat)abstract
- Experimental results show that hosing of a long particle bunch in plasma can be induced by wakefields driven by a short, misaligned preceding bunch. Hosing develops in the plane of misalignment, selfmodulation in the perpendicular plane, at frequencies close to the plasma electron frequency, and are reproducible. Development of hosing depends on misalignment direction, its growth on misalignment extent and on proton bunch charge. Results have the main characteristics of a theoretical model, are relevant to other plasma -based accelerators and represent the first characterization of hosing.
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| 12. |
- Verra, L., et al.
(författare)
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Controlled Growth of the Self-Modulation of a Relativistic Proton Bunch in Plasma
- 2022
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Ingår i: Physical Review Accelerators and Beams. - : American Physical Society. - 2469-9888. ; 25:7
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Tidskriftsartikel (refereegranskat)abstract
- A long, narrow, relativistic charged particle bunch propagating in plasma is subject to the self -modulation (SM) instability. We show that SM of a proton bunch can be seeded by the wakefields driven by a preceding electron bunch. SM timing reproducibility and control are at the level of a small fraction of the modulation period. With this seeding method, we independently control the amplitude of the seed wakefields with the charge of the electron bunch and the growth rate of SM with the charge of the proton bunch. Seeding leads to larger growth of the wakefields than in the instability case.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Martin, S, et al.
(författare)
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Pre-validation of a reporter gene assay for oxidative stress for the rapid screening of nanobiomaterials
- 2022
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Ingår i: Frontiers in toxicology. - : Frontiers Media SA. - 2673-3080. ; 4, s. 974429-
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Tidskriftsartikel (refereegranskat)abstract
- Engineered nanomaterials have been found to induce oxidative stress. Cellular oxidative stress, in turn, can result in the induction of antioxidant and detoxification enzymes which are controlled by the nuclear erythroid 2-related factor 2 (NRF2) transcription factor. Here, we present the results of a pre-validation study which was conducted within the frame of BIORIMA (“biomaterial risk management”) an EU-funded research and innovation project. For this we used an NRF2 specific chemically activated luciferase expression reporter gene assay derived from the human U2OS osteosarcoma cell line to screen for the induction of the NRF2 mediated gene expression following exposure to biomedically relevant nanobiomaterials. Specifically, we investigated Fe3O4-PEG-PLGA nanomaterials while Ag and TiO2 “benchmark” nanomaterials from the Joint Research Center were used as reference materials. The viability of the cells was determined by using the Alamar blue assay. We performed an interlaboratory study involving seven different laboratories to assess the applicability of the NRF2 reporter gene assay for the screening of nanobiomaterials. The latter work was preceded by online tutorials to ensure that the procedures were harmonized across the different participating laboratories. Fe3O4-PEG-PLGA nanomaterials were found to induce very limited NRF2 mediated gene expression, whereas exposure to Ag nanomaterials induced NRF2 mediated gene expression. TiO2 nanomaterials did not induce NRF2 mediated gene expression. The variability in the results obtained by the participating laboratories was small with mean intra-laboratory standard deviation of 0.16 and mean inter laboratory standard deviation of 0.28 across all NRF2 reporter gene assay results. We conclude that the NRF2 reporter gene assay is a suitable assay for the screening of nanobiomaterial-induced oxidative stress responses.
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| 17. |
- Saunois, Marielle, et al.
(författare)
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The Global Methane Budget 2000–2017
- 2020
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3516 .- 1866-3508. ; 12:3, s. 1561-1623
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Tidskriftsartikel (refereegranskat)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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| 18. |
- Berchet, Antoine, et al.
(författare)
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The Community Inversion Framework v1.0 : A unified system for atmospheric inversion studies
- 2021
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 14:8, s. 5331-5354
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Tidskriftsartikel (refereegranskat)abstract
- Atmospheric inversion approaches are expected to play a critical role in future observation-based monitoring systems for surface fluxes of greenhouse gases (GHGs), pollutants and other trace gases. In the past decade, the research community has developed various inversion software, mainly using variational or ensemble Bayesian optimization methods, with various assumptions on uncertainty structures and prior information and with various atmospheric chemistry-Transport models. Each of them can assimilate some or all of the available observation streams for its domain area of interest: flask samples, in situ measurements or satellite observations. Although referenced in peer-reviewed publications and usually accessible across the research community, most systems are not at the level of transparency, flexibility and accessibility needed to provide the scientific community and policy makers with a comprehensive and robust view of the uncertainties associated with the inverse estimation of GHG and reactive species fluxes. Furthermore, their development, usually carried out by individual research institutes, may in the future not keep pace with the increasing scientific needs and technical possibilities. We present here the Community Inversion Framework (CIF) to help rationalize development efforts and leverage the strengths of individual inversion systems into a comprehensive framework. The CIF is primarily a programming protocol to allow various inversion bricks to be exchanged among researchers. In practice, the ensemble of bricks makes a flexible, transparent and open-source Python-based tool to estimate the fluxes of various GHGs and reactive species both at the global and regional scales. It will allow for running different atmospheric transport models, different observation streams and different data assimilation approaches. This adaptability will allow for a comprehensive assessment of uncertainty in a fully consistent framework. We present here the main structure and functionalities of the system, and we demonstrate how it operates in a simple academic case.
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| 19. |
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| 20. |
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| 21. |
- Saunois, M., et al.
(författare)
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The global methane budget 2000–2012
- 2016
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 8:2, s. 697-751
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Tidskriftsartikel (refereegranskat)abstract
- The global methane (CH4) budget is becoming an increasingly important component for managing realistic pathways to mitigate climate change. This relevance, due to a shorter atmospheric lifetime and a stronger warming potential than carbon dioxide, is challenged by the still unexplained changes of atmospheric CH4 over the past decade. Emissions and concentrations of CH4 are continuing to increase, making CH4 the second most important human-induced greenhouse gas after carbon dioxide. Two major difficulties in reducing uncertainties come from the large variety of diffusive CH4 sources that overlap geographically, and from the destruction of CH4 by the very short-lived hydroxyl radical (OH). To address these difficulties, we have established a consortium of multi-disciplinary scientists under the umbrella of the Global Carbon Project to synthesize and stimulate research on the methane cycle, and producing regular (∼ biennial) updates of the global methane budget. This consortium includes atmospheric physicists and chemists, biogeochemists of surface and marine emissions, and socio-economists who study anthropogenic emissions. Following Kirschke et al. (2013), we propose here the first version of a living review paper that integrates results of top-down studies (exploiting atmospheric observations within an atmospheric inverse-modelling framework) and bottom-up models, inventories and data-driven approaches (including process-based models for estimating land surface emissions and atmospheric chemistry, and inventories for anthropogenic emissions, data-driven extrapolations). For the 2003–2012 decade, global methane emissions are estimated by top-down inversions at 558 Tg CH4 yr−1, range 540–568. About 60 % of global emissions are anthropogenic (range 50–65 %). Since 2010, the bottom-up global emission inventories have been closer to methane emissions in the most carbon-intensive Representative Concentrations Pathway (RCP8.5) and higher than all other RCP scenarios. Bottom-up approaches suggest larger global emissions (736 Tg CH4 yr−1, range 596–884) mostly because of larger natural emissions from individual sources such as inland waters, natural wetlands and geological sources. Considering the atmospheric constraints on the top-down budget, it is likely that some of the individual emissions reported by the bottom-up approaches are overestimated, leading to too large global emissions. Latitudinal data from top-down emissions indicate a predominance of tropical emissions (∼ 64 % of the global budget, < 30° N) as compared to mid (∼ 32 %, 30–60° N) and high northern latitudes (∼ 4 %, 60–90° N). Top-down inversions consistently infer lower emissions in China (∼ 58 Tg CH4 yr−1, range 51–72, −14 %) and higher emissions in Africa (86 Tg CH4 yr−1, range 73–108, +19 %) than bottom-up values used as prior estimates. Overall, uncertainties for anthropogenic emissions appear smaller than those from natural sources, and the uncertainties on source categories appear larger for top-down inversions than for bottom-up inventories and models. The most important source of uncertainty on the methane budget is attributable to emissions from wetland and other inland waters. We show that the wetland extent could contribute 30–40 % on the estimated range for wetland emissions. Other priorities for improving the methane budget include the following: (i) the development of process-based models for inland-water emissions, (ii) the intensification of methane observations at local scale (flux measurements) to constrain bottom-up land surface models, and at regional scale (surface networks and satellites) to constrain top-down inversions, (iii) improvements in the estimation of atmospheric loss by OH, and (iv) improvements of the transport models integrated in top-down inversions. The data presented here can be downloaded from the Carbon Dioxide Information Analysis Center (http://doi.org/10.3334/CDIAC/GLOBAL_METHANE_BUDGET_2016_V1.1) and the Global Carbon Project.
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| 22. |
- Saunois, M., et al.
(författare)
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Variability and quasi-decadal changes in the methane budget over the period 2000–2012
- 2017
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 17:18, s. 11135-11161
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Tidskriftsartikel (refereegranskat)abstract
- Following the recent Global Carbon Project (GCP) synthesis of the decadal methane (CH4) budget over 2000–2012 (Saunois et al., 2016), we analyse here the same dataset with a focus on quasi-decadal and inter-annual variability in CH4 emissions. The GCP dataset integrates results from top-down studies (exploiting atmospheric observations within an atmospheric inverse-modelling framework) and bottom-up models (including process-based models for estimating land surface emissions and atmospheric chemistry), inventories of anthropogenic emissions, and data-driven approaches. The annual global methane emissions from top-down studies, which by construction match the observed methane growth rate within their uncertainties, all show an increase in total methane emissions over the period 2000–2012, but this increase is not linear over the 13 years. Despite differences between individual studies, the mean emission anomaly of the top-down ensemble shows no significant trend in total methane emissions over the period 2000–2006, during the plateau of atmospheric methane mole fractions, and also over the period 2008–2012, during the renewed atmospheric methane increase. However, the top-down ensemble mean produces an emission shift between 2006 and 2008, leading to 22 [16–32] Tg CH4 yr−1 higher methane emissions over the period 2008–2012 compared to 2002–2006. This emission increase mostly originated from the tropics, with a smaller contribution from mid-latitudes and no significant change from boreal regions. The regional contributions remain uncertain in top-down studies. Tropical South America and South and East Asia seem to contribute the most to the emission increase in the tropics. However, these two regions have only limited atmospheric measurements and remain therefore poorly constrained. The sectorial partitioning of this emission increase between the periods 2002–2006 and 2008–2012 differs from one atmospheric inversion study to another. However, all top-down studies suggest smaller changes in fossil fuel emissions (from oil, gas, and coal industries) compared to the mean of the bottom-up inventories included in this study. This difference is partly driven by a smaller emission change in China from the top-down studies compared to the estimate in the Emission Database for Global Atmospheric Research (EDGARv4.2) inventory, which should be revised to smaller values in a near future. We apply isotopic signatures to the emission changes estimated for individual studies based on five emission sectors and find that for six individual top-down studies (out of eight) the average isotopic signature of the emission changes is not consistent with the observed change in atmospheric 13CH4. However, the partitioning in emission change derived from the ensemble mean is consistent with this isotopic constraint. At the global scale, the top-down ensemble mean suggests that the dominant contribution to the resumed atmospheric CH4 growth after 2006 comes from microbial sources (more from agriculture and waste sectors than from natural wetlands), with an uncertain but smaller contribution from fossil CH4 emissions. In addition, a decrease in biomass burning emissions (in agreement with the biomass burning emission databases) makes the balance of sources consistent with atmospheric 13CH4 observations. In most of the top-down studies included here, OH concentrations are considered constant over the years (seasonal variations but without any inter-annual variability). As a result, the methane loss (in particular through OH oxidation) varies mainly through the change in methane concentrations and not its oxidants. For these reasons, changes in the methane loss could not be properly investigated in this study, although it may play a significant role in the recent atmospheric methane changes as briefly discussed at the end of the paper.
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| 23. |
- Alvarez, Mariano J., et al.
(författare)
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A precision oncology approach to the pharmacological targeting of mechanistic dependencies in neuroendocrine tumors
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:7, s. 979-989
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Tidskriftsartikel (refereegranskat)abstract
- We introduce and validate a new precision oncology framework for the systematic prioritization of drugs targeting mechanistic tumor dependencies in individual patients. Compounds are prioritized on the basis of their ability to invert the concerted activity of master regulator proteins that mechanistically regulate tumor cell state, as assessed from systematic drug perturbation assays. We validated the approach on a cohort of 212 gastroenteropancreatic neuroendocrine tumors (GEP-NETs), a rare malignancy originating in the pancreas and gastrointestinal tract. The analysis identified several master regulator proteins, including key regulators of neuroendocrine lineage progenitor state and immunoevasion, whose role as critical tumor dependencies was experimentally confirmed. Transcriptome analysis of GEP-NET-derived cells, perturbed with a library of 107 compounds, identified the HDAC class I inhibitor entinostat as a potent inhibitor of master regulator activity for 42% of metastatic GEP-NET patients, abrogating tumor growth in vivo. This approach may thus complement current efforts in precision oncology.
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| 24. |
- Buchwitz, M., et al.
(författare)
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The GHG-CCI project of ESA's climate change initiative : Data products and application
- 2016
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Ingår i: Proceedings of Living Planet Symposium 2016. - 9789292213053 ; SP-740
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Konferensbidrag (refereegranskat)abstract
- The goal of the GHG-CCI project (http://www.esa-ghg-cci.org/) of ESA's Climate Change Initiative (CCI) is to generate global atmospheric satellite-derived carbon dioxide (CO2) and methane (CH4) data sets as needed to improve our understanding of the regional sources and sinks of these important greenhouse gases (GHG). Here we present an overview about the latest data set called Climate Research Data Package No. 3 (CRDP3). We focus on the GHG-CCI project core data products, which are near-surface-sensitive column-averaged dry air mole fractions of CO2 and CH4, denoted XCO2 (in ppm) and XCH4 (in ppb) retrieved from SCIAMACHY/ENVISAT (2002-2012) and TANSO-FTS/GOSAT (2009-today) nadir mode radiance observations in the near-infrared/shortwave-infrared spectral region. The GHG-CCI products are primarily individual sensor Level 2 products. However, we also generate merged Level 2 products ("EMMA products"). Here we also present a first GHG-CCI Level 3 product, namely XCO2 and XCH4 in Obs4MIPs format (monthly, 5°×5°).
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| 25. |
- Gironella-Torrent, Marta, et al.
(författare)
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Viscoelastic phenotyping of red blood cells
- 2024
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Ingår i: BIOPHYSICAL JOURNAL. - 0006-3495 .- 1542-0086. ; 123:7, s. 770-781
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Tidskriftsartikel (refereegranskat)abstract
- Red blood cells (RBCs) are the simplest cell types with complex dynamical and viscoelastic phenomenology. While the mechanical rigidity and the flickering noise of RBCs have been extensively investigated, an accurate determination of the constitutive equations of the relaxational kinetics is lacking. Here we measure the force relaxation of RBCs under different types of tensional and compressive extension-jump protocols by attaching an optically trapped bead to the RBC membrane. Relaxational kinetics follows linear response from 60 pN (tensional) to similar to 20 pN (compressive) applied forces, exhibiting a triple exponential function with three well-separated timescales over four decades (0.01-100 s). While the fast timescale (tau(F) similar to 0.02(1) s) corresponds to the relaxation of the membrane, the intermediate and slow timescales (tau(I) = 4(1) s; tau(S) = 70(8) s) likely arise from the cortex dynamics and the cytosol viscosity. Relaxation is highly heterogeneous across the RBC population, yet the three relaxation times are correlated, showing dynamical scaling. Finally, we find that glucose depletion and laser illumination of RBCs lead to faster triple exponential kinetics and RBC rigidification. Viscoelastic phenotyping is a promising dynamical biomarker applicable to other cell types and active systems. SIGNIFICANCE This research shows the structured viscoelastic dynamics of red blood cells (RBCs) and highlights the significance of considering multiple timescales for understanding their mechanical behavior. The observed triple exponential relaxation behavior, coupled with the proposed viscoelastic model, provides valuable insights into the underlying processes governing RBC mechanics. Furthermore, our findings regarding the impact of glucose depletion and light illumination on RBC rigidity show how environmental factors affect RBC properties. Our results expand the current knowledge of RBC mechanics and pave the way for future investigations of relaxational phenomena in other cell types.
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| 26. |
- He, Anna, et al.
(författare)
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Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study.
- 2020
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Ingår i: The Lancet. Neurology. - 1474-4465. ; 19:4, s. 307-316
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Tidskriftsartikel (refereegranskat)abstract
- High-efficacy therapies in multiple sclerosis are traditionally used after unsuccessful treatment with first-line disease modifying therapies. We hypothesised that early commencement of high-efficacy therapy would be associated with reduced long-term disability. We therefore aimed to compare long-term disability outcomes between patients who started high-efficacy therapies within 2 years of disease onset with those who started 4-6 years after disease onset.In this retrospective international observational study, we obtained data from the MSBase registry and the Swedish MS registry, which prospectively collect patient data that are specific to multiple sclerosis as part of routine clinical care. We identified adult patients (aged ≥18 years) with relapsing-remitting multiple sclerosis, with at least 6 years of follow-up since disease onset, and who started the high-efficacy therapy (rituximab, ocrelizumab, mitoxantrone, alemtuzumab, or natalizumab) either 0-2 years (early) or 4-6 years (late) after clinical disease onset. We matched patients in the early and late groups using propensity scores calculated on the basis of their baseline clinical and demographic data. The primary outcome was disability, measured with the Expanded Disability Status Score (EDSS; an ordinal scale of 0-10, with higher scores indicating increased disability), at 6-10 years after disease onset, assessed with a linear mixed-effects model.We identified 6149 patients in the MSBase registry who had been given high-efficacy therapy, with data collected between Jan 1, 1975, and April 13, 2017, and 2626 patients in the Swedish MS Registry, with data collected between Dec 10, 1997, and Sept 16, 2019. Of whom, 308 in the MSBase registry and 236 in the Swedish MS registry were eligible for inclusion. 277 (51%) of 544 patients commenced therapy early and 267 (49%) commenced therapy late. For the primary analysis, we matched 213 patients in the early treatment group with 253 in the late treatment group. At baseline, the mean EDSS score was 2·2 (SD 1·2) in the early group and 2·1 (SD 1·2) in the late group. Median follow-up time for matched patients was 7·8 years (IQR 6·7-8·9). In the sixth year after disease onset, the mean EDSS score was 2·2 (SD 1·6) in the early group compared with 2·9 (SD 1·8) in the late group (p<0·0001). This difference persisted throughout each year of follow-up until the tenth year after disease onset (mean EDSS score 2·3 [SD 1·8] vs 3·5 [SD 2·1]; p<0·0001), with a difference between groups of -0·98 (95% CI -1·51 to -0·45; p<0·0001, adjusted for proportion of time on any disease-modifying therapy) across the 6-10 year follow-up period.High-efficacy therapy commenced within 2 years of disease onset is associated with less disability after 6-10 years than when commenced later in the disease course. This finding can inform decisions regarding optimal sequence and timing of multiple sclerosis therapy.National Health and Medical Research Council Australia and MS Society UK.
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| 27. |
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| 28. |
- Kokalari, I, et al.
(författare)
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Efficacy, biocompatibility and degradability of carbon nanoparticles for photothermal therapy of lung cancer
- 2021
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Ingår i: Nanomedicine (London, England). - : Future Medicine Ltd. - 1748-6963 .- 1743-5889. ; 16:9, s. 689-707
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To investigate near infrared-induced phototoxicity toward lung cancer cells, and the biodegradability and effect on immune cells of glucose-derived carbon nanoparticles (CNPs). Methods: The human A549 lung adenocarcinoma cell line was used as a model to study the phototoxicity of CNPs. The biodegradability and the effect on immune cells was demonstrated in primary human neutrophils and macrophages. Results: Near infrared-activated CNPs elicited rapid cell death, characterized by the elevation of heat shock proteins and the induction of DNA damage. CNPs were found to be noncytotoxic toward primary human macrophages and were susceptible to biodegradation when cocultured with human neutrophils. Conclusions: Our results identify CNPs as promising platforms for photothermal therapy of lung cancer.
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| 29. |
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| 30. |
- Maurichi, A, et al.
(författare)
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Reply to E. Hindié
- 2020
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 38:27, s. 3238-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 31. |
- Petrescu, Ana Maria Roxana, et al.
(författare)
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The consolidated European synthesis of CH4 and N2O emissions for the European Union and United Kingdom: 1990-2017
- 2021
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 13:5, s. 2307-2362
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Tidskriftsartikel (refereegranskat)abstract
- Reliable quantification of the sources and sinks of greenhouse gases, together with trends and uncertainties, is essential to monitoring the progress in mitigating anthropogenic emissions under the Paris Agreement. This study provides a consolidated synthesis of CH4 and N2O emissions with consistently derived state-of-the-art bottom-up (BU) and top-down (TD) data sources for the European Union and UK (EU27 C UK). We integrate recent emission inventory data, ecosystem process-based model results and inverse modeling estimates over the period 1990-2017. BU and TD products are compared with European national greenhouse gas inventories (NGHGIs) reported to the UN climate convention UNFCCC secretariat in 2019. For uncertainties, we used for NGHGIs the standard deviation obtained by varying parameters of inventory calculations, reported by the member states (MSs) following the recommendations of the IPCC Guidelines. For atmospheric inversion models (TD) or other inventory datasets (BU), we defined uncertainties from the spread between different model estimates or model-specific uncertainties when reported. In comparing NGHGIs with other approaches, a key source of bias is the activities included, e.g., anthropogenic versus anthropogenic plus natural fluxes. In inversions, the separation between anthropogenic and natural emissions is sensitive to the geospatial prior distribution of emissions. Over the 2011-2015 period, which is the common denominator of data availability between all sources, the anthropogenic BU approaches are directly comparable, reporting mean emissions of 20.8 TgCH(4) yr (-1) (EDGAR v5.0) and 19.0 TgCH(4) yr(-1) (GAINS), consistent with the NGHGI estimates of 18.9 +/- 1.7 TgCH(4) yr(-1). The estimates of TD total inversions give higher emission estimates, as they also include natural emissions. Over the same period regional TD inversions with higher-resolution atmospheric transport models give a mean emission of 28.8 TgCH(4) yr(-1). Coarser-resolution global TD inversions are consistent with regional TD inversions, for global inversions with GOSAT satellite data (23.3 TgCH(4) yr(-1)) and surface network (24.4 TgCH(4) yr (-1)). The magnitude of natural peatland emissions from the JSBACH-HIMMELI model, natural rivers and lakes emissions, and geological sources together account for the gap between NGHGIs and inversions and account for 5.2 TgCH(4) yr(-1). For N2O emissions, over the 2011-2015 period, both BU approaches (EDGAR v5.0 and GAINS) give a mean value of anthropogenic emissions of 0.8 and 0.9 TgN(2)Oyr(-1), respectively, agreeing with the NGHGI data (0.9 0.6 TgN(2)Oyr(-1)). Over the same period, the average of the three total TD global and regional inversions was 1.3 +/- 0.4 and 1.3 +/- 0.1 TgN(2)Oyr(-1), respectively. The TD and BU comparison method defined in this study can be operationalized for future yearly updates for the calculation of CH4 and N2O budgets both at the EU CUK scale and at the national scale.
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