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| 2. |
- Fischer, Hubertus, et al.
(författare)
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Palaeoclimate constraints on the impact of 2 °C anthropogenic warming and beyond
- 2018
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Ingår i: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 11:7, s. 474-485
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Tidskriftsartikel (refereegranskat)abstract
- Over the past 3.5 million years, there have been several intervals when climate conditions were warmer than during the pre-industrial Holocene. Although past intervals of warming were forced differently than future anthropogenic change, such periods can provide insights into potential future climate impacts and ecosystem feedbacks, especially over centennial-to-millennial timescales that are often not covered by climate model simulations. Our observation-based synthesis of the understanding of past intervals with temperatures within the range of projected future warming suggests that there is a low risk of runaway greenhouse gas feedbacks for global warming of no more than 2 °C. However, substantial regional environmental impacts can occur. A global average warming of 1–2 °C with strong polar amplification has, in the past, been accompanied by significant shifts in climate zones and the spatial distribution of land and ocean ecosystems. Sustained warming at this level has also led to substantial reductions of the Greenland and Antarctic ice sheets, with sea-level increases of at least several metres on millennial timescales. Comparison of palaeo observations with climate model results suggests that, due to the lack of certain feedback processes, model-based climate projections may underestimate long-term warming in response to future radiative forcing by as much as a factor of two, and thus may also underestimate centennial-to-millennial-scale sea-level rise.
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| 3. |
- Gerold, Gisa, 1979-, et al.
(författare)
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Quantitative Proteomics Identifies Serum Response Factor Binding Protein 1 as a Host Factor for Hepatitis C Virus Entry
- 2015
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 12:5, s. 864-878
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis C virus (HCV) enters human hepatocytes through a multistep mechanism involving, among other host proteins, the virus receptor CD81. How CD81 governs HCV entry is poorly characterized, and CD81 protein interactions after virus binding remain elusive. We have developed a quantitative proteomics protocol to identify HCV-triggered CD81 interactions and found 26 dynamic binding partners. At least six of these proteins promote HCV infection, as indicated by RNAi. We further characterized serum response factor binding protein 1 (SRFBP1), which is recruited to CD81 during HCV uptake and supports HCV infection in hepatoma cells and primary human hepatocytes. SRFBP1 facilitates host cell penetration by all seven HCV genotypes, but not of vesicular stomatitis virus and human coronavirus. Thus, SRFBP1 is an HCV-specific, pan-genotypic host entry factor. These results demonstrate the use of quantitative proteomics to elucidate pathogen entry and underscore the importance of host protein-protein interactions during HCV invasion.
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| 4. |
- Wenning, Gregor K., et al.
(författare)
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The natural history of multiple system atrophy: a prospective European cohort study
- 2013
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Ingår i: Lancet Neurology. - 1474-4465. ; 12:3, s. 264-274
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Tidskriftsartikel (refereegranskat)abstract
- Background Multiple system atrophy (MSA) is a fatal and still poorly understood degenerative movement disorder that is characterised by autonomic failure, cerebellar ataxia, and parkinsonism in various combinations. Here we present the final analysis of a prospective multicentre study by the European MSA Study Group to investigate the natural history of MSA. Methods Patients with a clinical diagnosis of MSA were recruited and followed up clinically for 2 years. Vital status was ascertained 2 years after study completion. Disease progression was assessed using the unified MSA rating scale (UMSARS), a disease-specific questionnaire that enables the semiquantitative rating of autonomic and motor impairment in patients with MSA. Additional rating methods were applied to grade global disease severity, autonomic symptoms, and quality of life. Survival was calculated using a Kaplan-Meier analysis and predictors were identified in a Cox regression model. Group differences were analysed by parametric tests and non-parametric tests as appropriate. Sample size estimates were calculated using a paired two-group t test. Findings 141 patients with moderately severe disease fulfilled the consensus criteria for MSA. Mean age at symptom onset was 56.2 (SD 8.4) years. Median survival from symptom onset as determined by Kaplan-Meier analysis was 9.8 years (95% CI 8.1-11.4). The parkinsonian variant of MSA (hazard ratio [HR] 2.08,95% CI 1.09-3.97; p=0.026) and incomplete bladder emptying (HR 2.10,1.02-4.30; p=0.044) predicted shorter survival. 24-month progression rates of UMSARS activities of daily living, motor examination, and total scores were 49% (9.4 [SD 5.9]), 74% (12.9 [8.5]), and 57% (21.9 [11.9]), respectively, relative to baseline scores. Autonomic symptom scores progressed throughout the follow-up. Shorter symptom duration at baseline (OR 0.68, 0.5-0.9; p=0.006) and absent levodopa response (OR 3.4, 1.1-10.2; p=0.03) predicted rapid UMSARS progression. Sample size estimation showed that an interventional trial with 258 patients (129 per group) would be able to detect a 30% effect size in 1-year UMSARS motor examination decline rates at 80% power. Interpretation Our prospective dataset provides new insights into the evolution of MSA based on a follow-up period that exceeds that of previous studies. It also represents a useful resource for patient counselling and planning of multicentre trials.
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| 6. |
- Berthelsen, A., et al.
(författare)
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Recording marine airgun shots at offsets between 300 and 700 km
- 1991
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 18:4, s. 645-648
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Tidskriftsartikel (refereegranskat)abstract
- This paper demonstrates that - under favorable conditions - by using multichannel recording and subsequent stacking of adjacent records marine airgun shots have been detected at offset distances up to 700 km, the maximum offset at which the authors attempted to record data.^Besides a powerful airgun array, a low noise environment at the recording site and the elimination of static shifts are the prerequisites to obtain refracted and reflected arrivals from the crust and upper mantle at such large offsets.^Primary arrivals detected at offsets between 400 and 700 km image the upper mantle from 70 to about 120 km depth.^Stacking of neighboring shots and/or receivers successfully increases the signal-to-noise ratio, if the traces have been corrected for offset differences, which requires knowledge of the apparent phase velocities.^The data presented here were collected in autumn 1989 during the BABEL Project on the Baltic Shield.
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| 7. |
- Bruening, Janina, et al.
(författare)
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Hepatitis C virus enters liver cells using the CD81 receptor complex proteins calpain-5 and CBLB
- 2018
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis C virus (HCV) and the malaria parasite Plasmodium use the membrane protein CD81 to invade human liver cells. Here we mapped 33 host protein interactions of CD81 in primary human liver and hepatoma cells using high-resolution quantitative proteomics. In the CD81 protein network, we identified five proteins which are HCV entry factors or facilitators including epidermal growth factor receptor (EGFR). Notably, we discovered calpain-5 (CAPN5) and the ubiquitin ligase Casitas B-lineage lymphoma proto-oncogene B (CBLB) to form a complex with CD81 and support HCV entry. CAPN5 and CBLB were required for a post-binding and pre-replication step in the HCV life cycle. Knockout of CAPN5 and CBLB reduced susceptibility to all tested HCV genotypes, but not to other enveloped viruses such as vesicular stomatitis virus and human coronavirus. Furthermore, Plasmodium sporozoites relied on a distinct set of CD81 interaction partners for liver cell entry. Our findings reveal a comprehensive CD81 network in human liver cells and show that HCV and Plasmodium highjack selective CD81 interactions, including CAPN5 and CBLB for HCV, to invade cells.
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| 8. |
- Durante, M., et al.
(författare)
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All the fun of the FAIR: fundamental physics at the facility for antiproton and ion research
- 2019
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Ingår i: Physica Scripta. - : IOP Publishing. - 1402-4896 .- 0031-8949. ; 94:3
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Forskningsöversikt (refereegranskat)abstract
- The Facility for Antiproton and Ion Research (FAIR) will be the accelerator-based flagship research facility in many basic sciences and their applications in Europe for the coming decades. FAIR will open up unprecedented research opportunities in hadron and nuclear physics, in atomic physics and nuclear astrophysics as well as in applied sciences like materials research, plasma physics and radiation biophysics with applications towards novel medical treatments and space science. FAIR is currently under construction as an international facility at the campus of the GSI Helmholtzzentrum for Heavy-Ion Research in Darmstadt, Germany. While the full science potential of FAIR can only be harvested once the new suite of accelerators and storage rings is completed and operational, some of the experimental detectors and instrumentation are already available and will be used starting in summer 2018 in a dedicated research program at GSI, exploiting also the significantly upgraded GSI accelerator chain. The current manuscript summarizes how FAIR will advance our knowledge in various research fields ranging from a deeper understanding of the fundamental interactions and symmetries in nature to a better understanding of the evolution of the Universe and the objects within.
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| 9. |
- Ekroos, Johan, et al.
(författare)
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Declines amongst breeding Eider Somateria mollissima numbers in the Baltic/Wadden Sea flyway
- 2012
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Ingår i: Ornis Fennica. - 0030-5685. ; 89:2, s. 81-90
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Tidskriftsartikel (refereegranskat)abstract
- We report on the status of the Baltic/Wadden Sea flyway Eider population based on trends in breeding and wintering numbers throughout the region, supplemented by changes in the sex ratio and proportion of young Eiders as monitored in the Danish hunting bag. At the flyway scale, total numbers of breeding pairs decreased by 48% during 2000-2009, after relatively stable breeding numbers in 1991-2000. The majority of the population nest in Finland and Sweden, where the number of breeding pairs has halved over the same period. After initial declines in winter numbers between 1991 and 2000, during 2000-2009, national wintering numbers increased in the Baltic Sea, but decreased in the Wadden Sea. The annual proportion of adult females in the Danish hunting bag data decreased from ca. 45% (1982) to ca. 25% (2009) and simultaneously the proportion of first-winter birds fell from ca. 70% to ca. 30%, indicating dramatic structural changes in the Danish wintering numbers. These results suggest that the total flyway population will experience further declines, unless productivity increases and the factors responsible for decreasing adult female survival are identified and ameliorated. We discuss potential population drivers and present some recommendations for improved flyway-level monitoring and management of Eiders.
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| 10. |
- Grimm, Max Joseph, et al.
(författare)
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Clinical Conditions “Suggestive of Progressive Supranuclear Palsy”—Diagnostic Performance
- 2020
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 35:12, s. 2301-2313
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Movement Disorder Society diagnostic criteria for progressive supranuclear palsy introduced the diagnostic certainty level “suggestive of progressive supranuclear palsy” for clinical conditions with subtle signs, suggestive of the disease. This category aims at the early identification of patients, in whom the diagnosis may be confirmed as the disease evolves. Objective: To assess the diagnostic performance of the defined clinical conditions suggestive of progressive supranuclear palsy in an autopsy-confirmed cohort. Methods: Diagnostic performance of the criteria was analyzed based on retrospective clinical data of 204 autopsy-confirmed patients with progressive supranuclear palsy and 216 patients with other neurological diseases. Results: The conditions suggestive of progressive supranuclear palsy strongly increased the sensitivity compared to the National Institute of Neurological Disorders and Stroke and Society for Progressive Supranuclear Palsy criteria. Within the first year after symptom onset, 40% of patients with definite progressive supranuclear palsy fulfilled criteria for suggestive of progressive supranuclear palsy. Two-thirds of patients suggestive of progressive supranuclear palsy evolved into probable progressive supranuclear palsy after an average of 3.6 years. Application of the criteria for suggestive of progressive supranuclear palsy reduced the average time to diagnosis from 3.8 to 2.2 years. Conclusions: Clinical conditions suggestive of progressive supranuclear palsy allow earlier identification of patients likely to evolve into clinically possible or probable progressive supranuclear and to have underlying progressive supranuclear palsy pathology. Further work needs to establish the specificity and positive predictive value of this category in real-life clinical settings, and to develop specific biomarkers that enhance their diagnostic accuracy in early disease stages.
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