| 51. |
- Freitag, Daniel F., et al.
(författare)
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Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis
- 2015
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Ingår i: The Lancet Diabetes & Endocrinology. - 2213-8595. ; 3:4, s. 243-253
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Tidskriftsartikel (refereegranskat)abstract
- Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1.03 (1.02-1.04; p=3.9 x 10(-10)). Perallele odds ratios were 0.97 (0.95-0.99; p=9.9 x 10(-4)) for rheumatoid arthritis, 0.99 (0.97-1.01; p=0.47) for type 2 diabetes, 1.00 (0.98-1.02; p=0.92) for ischaemic stroke, and 1.08 (1.04-1.12; p=1.8 x 10(-5)) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1 alpha/beta inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Copyright (C) The Interleukin 1 Genetics Consortium. Open Access article distributed under the terms of CC-BY-NC-ND.
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| 52. |
- Fröling, Morgan, 1966-, et al.
(författare)
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Appearances of Ecosystem Services in Environmental Impact Assessment - learnings from two Swedish case studies
- 2016
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Ingår i: Proceedings of Linnaeus Eco-Tech 2016.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Ecosystem Services is an increasingly used concept to understand and describe the dependencies of socio-technical systems on the ecosystems in which they exist. We have studied to what extent ecosystem services are appearing in Environmental Impact Assessments (EIA) in two Swedish cases, the improvement of ecological status in a river used for small scale hydropower and the mining operations of the MM mine. In neither of the two cases ecosystem services have been intentionally included in the work with the EIAs. The goal of the studies has been to examine to what extent ecosystem services are appearing anyway in the EIAs, to what extent data in the EIAs are sufficient to perform more structured ecosystem service assessments, and if the use of a more structured ecosystem services review during the EIA process could have contributed positively to the EIA work. Both EIAs in this study holds some information on impacts on ecosystem services, and more information on affected ecosystem functions that could be translated into ecosystems services and probably to full ecosystem service reviews with additional data gathering. Cases of ecosystem functions and services impacting other ecosystem functions and services, sometimes in several stages, were found, indicating that such functions or services could be of special importance to protect and / or support.
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| 53. |
- Furze, Morgan E., et al.
(författare)
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Seasonal patterns of nonstructural carbohydrate reserves in four woody boreal species
- 2018
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Ingår i: Journal of the Torrey Botanical Society. - 1095-5674 .- 1940-0616. ; 145:4, s. 332-339
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Tidskriftsartikel (refereegranskat)abstract
- Plants store nonstructural carbohydrates (NSCs), such as sugars and starch, to use as carbon and energy sources for daily maintenance and growth needs as well as during times of stress. Allocation of NSCs to storage provides an important physiological strategy associated with future growth and survival, and thus understanding the seasonal patterns of NSC reserves provides insight into how species with different traits (e.g., growth form, leaf habit, wood anatomy) may respond to stress. We characterized the seasonal patterns of NSCs in four woody boreal plant species in Minnesota, USA. Sugar and starch concentrations were measured across the year in the roots and branches of two conifer trees, black spruce (Picea mariana (Mill.) B.S.P.) and eastern tamarack (Larix laricina (Du Roi) K. Koch), as well as in the leaves and branches of two evergreen broadleaf shrubs, bog Labrador tea (Rhododendron groenlandicum (Oeder) Kron & Judd) and leatherleaf (Chamaedaphne calyculata (L.) Moench). In general, seasonal variation was dominated by changes in starch across all organs and species. While similar seasonal patterns of NSCs were observed in the shrubs, different seasonal patterns were observed between the trees, particularly in the roots. Our results suggest that species-specific traits likely have consequences for organ-level storage dynamics, which may influence whole-plant growth and survival under global change
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| 54. |
- Giordanetto, Fabrizio, et al.
(författare)
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Discovery of cyclopentane- and cyclohexane-trans-1,3-diamines as potent melanin-concentrating hormone receptor 1 antagonists
- 2007
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Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X. ; 17:15, s. 4232-41
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Tidskriftsartikel (refereegranskat)abstract
- We herein report the optimization of cyclopentane- and cyclohexane-1,3-diamine derivatives as novel and potent MCH-R1 antagonists. Structural modifications of the 2-amino-quinoline and thiophene moieties found in the initial lead compound served to improve its metabolic stability profile and MCH-R1 affinity, and revealed unprecedented SAR when compared to other 2-amino-quinoline-containing MCH-R1 antagonists.
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| 55. |
- Goodfellow, IG, et al.
(författare)
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Inhibition of coxsackie B virus infection by soluble forms of its receptors: Binding affinities, altered particle formation, and competition with cellular receptors
- 2005
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Ingår i: Journal of Virology. - 1098-5514. ; 79:18, s. 12016-12024
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Tidskriftsartikel (refereegranskat)abstract
- We previously reported that soluble decay-accelerating factor (DAF) and coxsackievirus-adenovirus receptor (CAR) blocked coxsackievirus 133 (CVB3) myocarditis in mice, but only soluble CAR blocked CVB3-mediated pancreatitis. Here, we report that the in vitro mechanisms of viral inhibition by these soluble receptors also differ. Soluble DAF inhibited virus infection through the formation of reversible complexes with CVB3, while binding of soluble CAR to CVB induced the formation of altered (A) particles with a resultant irreversible loss of infectivity. A-particle formation was characterized by loss of VP4 from the virions and required incubation of CVB3-CAR complexes at 37 degrees C. Dimeric soluble DAF (DAF-Fc) was found to be 125-fold-more effective at inhibiting CVB3 than monomeric DAF, which corresponded to a 100-fold increase in binding affinity as determined by surface plasmon resonance analysis. Soluble CAR and soluble dimeric CAR (CAR-Fc) bound to CVB3 with 5,000- and 10,000-fold-higher affinities than the equivalent forms of DAF. While DAF-Fc was 125-fold-more effective at inhibiting virus than monomeric DAF, complement regulation by DAF-Fc was decreased 4 fold. Therefore, while the virus binding was a cooperative event, complement regulation was hindered by the molecular orientation of DAF-Fc, indicating that the regions responsible for complement regulation and virus binding do not completely overlap. Relative contributions of CVB binding affinity, receptor binding footprint on the virus capsid, and induction of capsid conformation alterations for the ability of cellular DAF and CAR to act as receptors are discussed.
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| 56. |
- Haas, Brian J., et al.
(författare)
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Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans
- 2009
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7262, s. 393-398
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Tidskriftsartikel (refereegranskat)abstract
- Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.
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| 57. |
- Hansson, Linnea J., et al.
(författare)
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Autoplant—Autonomous Site Preparation and Tree Planting for a Sustainable Bioeconomy
- 2024
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Ingår i: Forests. - : MDPI. - 1999-4907 .- 1999-4907. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- Sustainable forestry requires efficient regeneration methods to ensure that new forests are established quickly. In Sweden, 99% of the planting is manual, but finding labor for this arduous work is difficult. An autonomous scarifying and planting machine with high precision, low environmental impact, and a good work environment would meet the needs of the forest industry. For two years, a collaborative group of researchers, manufacturers, and users (forest companies) has worked together on developing and testing a new concept for autonomous forest regeneration (Autoplant). The concept comprises several subsystems, i.e., regeneration and route planning, autonomous driving (path planning), new technology for forest regeneration with minimal environmental impact, automatic plant management, crane motion planning, detection of planting spots, and follow-up. The subsystems were tested separately and integrated together during a field test at a clearcut. The concept shows great potential, especially from an environmental perspective, with significantly reduced soil disturbances, from approximately 50% (the area proportion of the area disturbed by disc trenching) to less than 3%. The Autoplant project highlights the challenges and opportunities related to future development, e.g., the relation between machine cost and operating speed, sensor robustness in response to vibrations and weather, and precision in detecting the size and type of obstacles during autonomous driving and planting.
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| 58. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 59. |
- Hudson, Lawrence N., et al.
(författare)
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The PREDICTS database : a global database of how local terrestrial biodiversity responds to human impacts
- 2014
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:24, s. 4701-4735
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Tidskriftsartikel (refereegranskat)abstract
- Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
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| 60. |
- Hönel, Sebastian, et al.
(författare)
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A changeset-based approach to assess source code density and developer efficacy
- 2018
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Ingår i: ICSE '18 Proceedings of the 40th International Conference on Software Engineering: Companion Proceeedings. - New York, NY, USA : IEEE. - 9781450356633 ; , s. 220-221
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Konferensbidrag (refereegranskat)abstract
- The productivity of a (team of) developer(s) can be expressed as a ratio between effort and delivered functionality. Several different estimation models have been proposed. These are based on statistical analysis of real development projects; their accuracy depends on the number and the precision of data points. We propose a data-driven method to automate the generation of precise data points. Functionality is proportional to the code size and Lines of Code (LoC) is a fundamental metric of code size. However, code size and LoC are not well defined as they could include or exclude lines that do not affect the delivered functionality. We present a new approach to measure the density of code in software repositories. We demonstrate how the accuracy of development time spent in relation to delivered code can be improved when basing it on net-instead of the gross-size measurements. We validated our tool by studying ca. 1,650 open-source software projects.
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