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Träfflista för sökning "WFRF:(Isaksson A) srt2:(2020)"

Sökning: WFRF:(Isaksson A) > (2020)

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1.
  • Saunois, Marielle, et al. (författare)
  • The Global Methane Budget 2000–2017
  • 2020
  • Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3516 .- 1866-3508. ; 12:3, s. 1561-1623
  • 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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  • Claesson, Elin, 1989, et al. (författare)
  • The primary structural photoresponse of phytochrome proteins captured by a femtosecond X-ray laser
  • 2020
  • Ingår i: eLife. - 2050-084X. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Phytochrome proteins control the growth, reproduction, and photosynthesis of plants, fungi, and bacteria. Light is detected by a bilin cofactor, but it remains elusive how this leads to activation of the protein through structural changes. We present serial femtosecond X-ray crystallographic data of the chromophore-binding domains of a bacterial phytochrome at delay times of 1 ps and 10 ps after photoexcitation. The data reveal a twist of the D-ring, which leads to partial detachment of the chromophore from the protein. Unexpectedly, the conserved so-called pyrrole water is photodissociated from the chromophore, concomitant with movement of the A-ring and a key signaling aspartate. The changes are wired together by ultrafast backbone and water movements around the chromophore, channeling them into signal transduction towards the output domains. We suggest that the observed collective changes are important for the phytochrome photoresponse, explaining the earliest steps of how plants, fungi and bacteria sense red light.
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  • Hatschek, T., et al. (författare)
  • PREDIX HER2 trial : Event-free survival and pathologic complete response in clinical subgroups and stromal TILs levels
  • 2020
  • Ingår i: Annals of Oncology. - : Elsevier. - 0923-7534 .- 1569-8041. ; 31:Suppl. 2, s. S49-S49
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Neoadjuvant treatment with Trastuzumab-emtansine was associated with similar rates of pathological complete remission (pCR) as standard therapy withd ocetaxel, trastuzumab and pertuzumab in the PREDIX HER2 trial. Here, results of event-free survival (EFS), and pCR rates in key clinical-pathological subgroups and biomarkers including the abundance of stromal tumor infiltrating lymphocytes (TILs) are presented.Methods: PREDIX HER2 is a randomized, multicenter, open-label, phase 2 study involving 9 Swedish sites. Patients with HER2 positive breast cancer, verified by ISH, T>20 mm and/or verified lymph node metastases were randomized to six three-weekly courses of either docetaxel, trastuzumab SC and pertuzumab (group A), or trastuzumab emtansine (T-DM1, group B). Switch of treatment to the opposite arm was allowed in case of lack of response or severe toxicity. Radiological evaluation included 18F-FDG PET/CT. Patients in both groups received adjuvant chemotherapy with epirubicin and cyclophosphamide. TILs were evaluated using standard methodology, median 10%.Results: In total 197 pts. were evaluable, 99 in group A, and 98 in group B. pCR (ypT0/is ypN0) was achieved in 90 pts, 45.7%, with no significant difference between the two treatment groups. pCR rates were lower in the group of patients with hormone receptor (HR)epositive compared with HR-negative tumors but similar in both treatment groups. pCR rates did not differ between the two treatments in subgroups defined by age, menopausal status, tumor grade, T size, node status, HR-status, HER2 status and Ki67. Progressive disease was observed in 3 pts. (3%) during treatment with T-DM1, none in group A. After a median follow-up of 2.4 years 13 EFS events occurred, with no significant differences between the treatment groups. The presence of 10% TILs predicted pCR significantly (p¼0.009), similar in both treatment groups. We also found that a decrease of SUVmax by more than 80% was highly predictive of pCR. HRQoL was significantly better in pts. receiving T-DM1.Conclusions: Our data suggest that neoadjuvant T-DM1 may be as effective as standard neoadjuvant treatment in all clinical subgroups evaluated. Both TILs and PET/CT showed potential to predict pCR.Clinical trial identification: NCT02568839.
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5.
  • Neufeld, Janina, et al. (författare)
  • Global and local visual processing in autism - a co-twin-control study
  • 2020
  • Ingår i: Journal of Child Psychology and Psychiatry. - : Wiley. - 0021-9630 .- 1469-7610. ; 61:4, s. 470-479
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Autism Spectrum Disorder (ASD) is associated with altered global and local visual processing. However, the nature of these alterations remains controversial, with contradictory findings and notions ranging from a reduced drive to integrate information into a coherent 'gestalt' ("weak central coherence" = WCC) to an enhanced perceptual functioning (EPF) in local processing.METHODS: This study assessed the association between autism and global/local visual processing, using a large sample of monozygotic (MZ) and dizygotic (DZ) twins (N = 290, 48% females, age = 8-31 years). The Fragmented Pictures Test (FPT) assessed global processing, whereas local processing was estimated with the Embedded Figures Test (EFT) and the Block Design Test (BDT). Autism was assessed both categorically (clinical diagnosis), and dimensionally (autistic traits). Associations between visual tasks and autism were estimated both across the cohort and within-twin pairs where all factors shared between twins are implicitly controlled.RESULTS: Clinical diagnosis and autistic traits predicted a need for more visual information for gestalt processing in the FPT across the cohort. For clinical diagnosis, this association remained within-pairs and at trend-level even within MZ twin pairs alone. ASD and higher autistic traits predicted lower EFT and BDT performance across the cohort, but these associations were lost within-pairs.CONCLUSIONS: In line with the WCC account, our findings indicate an association between autism and reduced global visual processing in children, adolescents and young adults (but no evidence for EPF). Observing a similar association within MZ twins suggests a non-shared environmental contribution.
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  • Strandberg, B., et al. (författare)
  • Near-threshold π-photoproduction on the deuteron
  • 2020
  • Ingår i: Physical Review C. - 2469-9985. ; 101:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The first experimental investigation of the near-threshold cross section for incoherent π-photoproduction on the deuteron γd→π-pp is presented. The experimental technique involved detection of the ≈131 MeV γ ray resulting from the radiative capture of photoproduced π-in the target. The total cross section was measured using an unpolarized tagged-photon beam, a liquid-deuterium target, and three very large NaI(Tl) spectrometers. The data are compared to theoretical models that give insight into the elementary reaction γn→π-p and pion-nucleon and nucleon-nucleon final-state interactions.
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  • Cabrita, Rita, et al. (författare)
  • Tertiary lymphoid structures improve immunotherapy and survival in melanoma
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 577:7791, s. 561-565
  • Tidskriftsartikel (refereegranskat)abstract
    • Checkpoint blockade therapies that reactivate tumour-associated T cells can induce durable tumour control and result in the long-term survival of patients with advanced cancers1. Current predictive biomarkers for therapy response include high levels of intratumour immunological activity, a high tumour mutational burden and specific characteristics of the gut microbiota2,3. Although the role of T cells in antitumour responses has thoroughly been studied, other immune cells remain insufficiently explored. Here we use clinical samples of metastatic melanomas to investigate the role of B cells in antitumour responses, and find that the co-occurrence of tumour-associated CD8+ T cells and CD20+ B cells is associated with improved survival, independently of other clinical variables. Immunofluorescence staining of CXCR5 and CXCL13 in combination with CD20 reveals the formation of tertiary lymphoid structures in these CD8+CD20+ tumours. We derived a gene signature associated with tertiary lymphoid structures, which predicted clinical outcomes in cohorts of patients treated with immune checkpoint blockade. Furthermore, B-cell-rich tumours were accompanied by increased levels of TCF7+ naive and/or memory T cells. This was corroborated by digital spatial-profiling data, in which T cells in tumours without tertiary lymphoid structures had a dysfunctional molecular phenotype. Our results indicate that tertiary lymphoid structures have a key role in the immune microenvironment in melanoma, by conferring distinct T cell phenotypes. Therapeutic strategies to induce the formation of tertiary lymphoid structures should be explored to improve responses to cancer immunotherapy.
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10.
  • Cabrita, Rita, et al. (författare)
  • Tertiary lymphoid structures improve immunotherapy and survival in melanoma.
  • 2020
  • Ingår i: Nature. - : Nature Publishing Group. - 1476-4687 .- 0028-0836. ; 577:7791, s. 561-565
  • Tidskriftsartikel (refereegranskat)abstract
    • Checkpoint blockade therapies that reactivate tumour-associated T cells can induce durable tumour control and result in the long-term survival of patients with advanced cancers1. Current predictive biomarkers for therapy response include high levels of intratumour immunological activity, a high tumour mutational burden and specific characteristics of the gut microbiota2,3. Although the role of T cells in antitumour responses has thoroughly been studied, other immune cells remain insufficiently explored. Here we use clinical samples of metastatic melanomas to investigate the role of B cells in antitumour responses, and find that the co-occurrence of tumour-associated CD8+ T cells and CD20+ B cells is associated with improved survival, independently of other clinical variables. Immunofluorescence staining of CXCR5 and CXCL13 in combination with CD20 reveals the formation of tertiary lymphoid structures in these CD8+CD20+ tumours. We derived a gene signature associated with tertiary lymphoid structures, which predicted clinical outcomes in cohorts of patients treated with immune checkpoint blockade. Furthermore, B-cell-rich tumours were accompanied by increased levels of TCF7+ naive and/or memory T cells. This was corroborated by digital spatial-profiling data, in which T cells in tumours without tertiary lymphoid structures had a dysfunctional molecular phenotype. Our results indicate that tertiary lymphoid structures have a key role in the immune microenvironment in melanoma, by conferring distinct T cell phenotypes. Therapeutic strategies to induce the formation of tertiary lymphoid structures should be explored to improve responses to cancer immunotherapy.
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