| 1. |
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| 2. |
- Clark, DW, et al.
(författare)
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Associations of autozygosity with a broad range of human phenotypes
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
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Tidskriftsartikel (refereegranskat)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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| 3. |
- Ruiz-Ramos, Miguel, et al.
(författare)
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Adaptation response surfaces for managing wheat under perturbed climate and CO2 in a Mediterranean environment
- 2018
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Ingår i: Agricultural Systems. - : Elsevier BV. - 0308-521X. ; 159, s. 260-274
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Tidskriftsartikel (refereegranskat)abstract
- Adaptation of crops to climate change has to be addressed locally due to the variability of soil, climate and the specific socio-economic settings influencing farm management decisions. Adaptation of rainfed cropping systems in the Mediterranean is especially challenging due to the projected decline in precipitation in the coming decades, which will increase the risk of droughts. Methods that can help explore uncertainties in climate projections and crop modelling, such as impact response surfaces (IRSs) and ensemble modelling, can then be valuable for identifying effective adaptations. Here, an ensemble of 17 crop models was used to simulate a total of 54 adaptation options for rainfed winter wheat (Triticum aestivum) at Lleida (NE Spain). To support the ensemble building, an ex post quality check of model simulations based on several criteria was performed. Those criteria were based on the "According to Our Current Knowledge" (AOCK) concept, which has been formalized here. Adaptations were based on changes in cultivars and management regarding phenology, vernalization, sowing date and irrigation. The effects of adaptation options under changed precipitation (P), temperature (T), [CO2] and soil type were analysed by constructing response surfaces, which we termed, in accordance with their specific purpose, adaptation response surfaces (ARSs). These were created to assess the effect of adaptations through a range of plausible P, T and [CO2] perturbations. The results indicated that impacts of altered climate were predominantly negative. No single adaptation was capable of overcoming the detrimental effect of the complex interactions imposed by the P, T and [CO2] perturbations except for supplementary irrigation (sI), which reduced the potential impacts under most of the perturbations. Yet, a combination of adaptations for dealing with climate change demonstrated that effective adaptation is possible at Lleida. Combinations based on a cultivar without vernalization requirements showed good and wide adaptation potential. Few combined adaptation options performed well under rainfed conditions. However, a single sI was sufficient to develop a high adaptation potential, including options mainly based on spring wheat, current cycle duration and early sowing date. Depending on local environment (e.g. soil type), many of these adaptations can maintain current yield levels under moderate changes in T and P, and some also under strong changes. We conclude that ARSs can offer a useful tool for supporting planning of field level adaptation under conditions of high uncertainty.
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| 4. |
- Sakornsakolpat, Phuwanat, et al.
(författare)
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Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 494-505
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 x 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.
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| 5. |
- Janssen, S., et al.
(författare)
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Defining assessment projects and scenarios for policy support: Use of ontology in Integrated Assessment and Modelling
- 2009
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Ingår i: Environmental Modelling & Software. - : Elsevier BV. - 1873-6726 .- 1364-8152. ; 24:12, s. 1491-1500
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Konferensbidrag (refereegranskat)abstract
- Integrated Assessment and Modelling (IAM) provides an interdisciplinary approach to support ex-ante decision-making by combining quantitative models representing different systems and scales into a framework for integrated assessment. Scenarios in IAM are developed in the interaction between scientists and stakeholders to explore possible pathways of future development. As IAM typically combines models from different disciplines, there is a clear need for a consistent definition and implementation of scenarios across models, policy problems and scales. This paper presents such a unified conceptualization for scenario and assessment projects. We demonstrate the use of common ontologies in building this unified conceptualization, e.g. a common ontology on assessment projects and scenarios. The common ontology and the process of ontology engineering are used in a case study, which refers to the development of SEAMLESS-IF, an integrated modelling framework to assess agricultural and environmental policy options as to their contribution to sustainable development. The presented common ontology on assessment projects and scenarios can be reused by IAM consortia and if required, adapted by using the process of ontology engineering as proposed in this paper. (C) 2009 Elsevier Ltd. All rights reserved.
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| 6. |
- Rodríguez, A., et al.
(författare)
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Implications of crop model ensemble size and composition for estimates of adaptation effects and agreement of recommendations
- 2019
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Ingår i: Agricultural and Forest Meteorology. - : Elsevier BV. - 0168-1923 .- 1873-2240. ; 264, s. 351-362
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Tidskriftsartikel (refereegranskat)abstract
- Climate change is expected to severely affect cropping systems and food production in many parts of the world unless local adaptation can ameliorate these impacts. Ensembles of crop simulation models can be useful tools for assessing if proposed adaptation options are capable of achieving target yields, whilst also quantifying the share of uncertainty in the simulated crop impact resulting from the crop models themselves. Although some studies have analysed the influence of ensemble size on model outcomes, the effect of ensemble composition has not yet been properly appraised. Moreover, results and derived recommendations typically rely on averaged ensemble simulation results without accounting sufficiently for the spread of model outcomes. Therefore, we developed an Ensemble Outcome Agreement (EOA) index, which analyses the effect of changes in composition and size of a multi-model ensemble (MME) to evaluate the level of agreement between MME outcomes with respect to a given hypothesis (e.g. that adaptation measures result in positive crop responses). We analysed the recommendations of a previous study performed with an ensemble of 17 crop models and testing 54 adaptation options for rainfed winter wheat (Triticum aestivum L.) at Lleida (NE Spain) under perturbed conditions of temperature, precipitation and atmospheric CO2 concentration. Our results confirmed that most adaptations recommended in the previous study have a positive effect. However, we also showed that some options did not remain recommendable in specific conditions if different ensembles were considered. Using EOA, we were able to identify the adaptation options for which there is high confidence in their effectiveness at enhancing yields, even under severe climate perturbations. These include substituting spring wheat for winter wheat combined with earlier sowing dates and standard or longer duration cultivars, or introducing supplementary irrigation, the latter increasing EOA values in all cases. There is low confidence in recovering yields to baseline levels, although this target could be attained for some adaptation options under moderate climate perturbations. Recommendations derived from such robust results may provide crucial information for stakeholders seeking to implement adaptation measures.
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| 7. |
- Shrine, Nick, et al.
(författare)
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New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 481-493
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Tidskriftsartikel (refereegranskat)abstract
- Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.
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| 8. |
- Coucheney, Elsa, et al.
(författare)
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Key functional soil types explain data aggregation effects on simulated yield, soil carbon, drainage and nitrogen leaching at a regional scale
- 2018
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Ingår i: Geoderma. - : Elsevier. - 0016-7061 .- 1872-6259. ; 318, s. 167-181
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Tidskriftsartikel (refereegranskat)abstract
- The effects of aggregating soil data (DAE) by areal majority of soil mapping units was explored for regional simulations with the soil-vegetation model CoupModel for a region in Germany (North Rhine-Westphalia). DAE were analysed for wheat yield, drainage, soil carbon mineralisation and nitrogen leaching below the root zone. DAE were higher for soil C mineralization and N leaching than for yield and drainage and were strongly related to the presence of specific soils within the study region. These soil types were associated to extreme simulated output variables compared to the mean variable in the region. The spatial aggregation of these key functional soils within sub-regions additionally influenced the DAE. A spatial analysis of their spatial pattern (i.e. their presence/absence, coverage and aggregation) can help in defining the appropriate grid resolution that would minimize the error caused by aggregating soil input data in regional simulations.
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| 9. |
- Drewes, F., et al.
(författare)
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Bag Context Tree Grammars
- 2008
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Ingår i: Fundamenta Informaticae. ; 86:4, s. 459-480
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Tidskriftsartikel (refereegranskat)abstract
- We introduce bag context as a device for regulated rewriting in tree grammars. Bag context represents information that is not part of a developing tree, but instead evolves separately during a derivation. We present several results. First, we give some normal forms and equivalent formulations for bag context tree grammars. Then we compare bag context tree grammars to their random context counterparts. We show that bag context is strictly more powerful than random context; in doing so, we show that the class of bag context tree languages is the closure of the class of random context tree languages under linear top-down tree transductions. Finally, we consider the structural limitations of bag context tree grammars. We establish a necessary condition for languages generated by bag context tree grammars, and use it to present a tree language that cannot be generated by such a grammar. Moreover, we show that the class of bag context tree languages is incomparable with the class of branching synchronization tree languages.
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| 10. |
- Ewert, Sara, 1974, et al.
(författare)
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The bradykinin BK2 receptor mediates angiotensin II receptor type 2 stimulated rat duodenal mucosal alkaline secretion.
- 2003
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Ingår i: BMC physiology. - 1472-6793. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This study investigates bradykinin and nitric oxide as potential mediators of AT2-receptor-stimulated duodenal mucosal alkaline secretion. Duodenal mucosal alkaline secretion was measured in methohexital- and alpha-chloralose-anaesthetised rats by means of in situ pH-stat titration. Immunohistochemistry and Western blot were used to identify the BK2 receptors. RESULTS: The AT2 receptor agonist CGP42112A (0.1 microg kg(-1) min(-1)) administered intravenously increased the duodenal mucosal alkaline secretion by approximately 50 %. This increase was sensitive to the selective BK2 receptor blocker HOE140 (100 ng/kg i.v.), but not to luminal administration of the NOS blocker L-NAME (0.3 mM). Mean arterial pressure did not differ between groups during the procedures. Immunohistochemistry showed a distinct staining of the crypt epithelium and a moderate staining of basal cytoplasm in villus enterocytes. CONCLUSION: The results suggest that the AT2-receptor-stimulated alkaline secretion is mediated via BK2 receptors located in the duodenal cryptal mucosal epithelium.
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| 11. |
- Lidayová, Kristína, 1987-
(författare)
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Fast Methods for Vascular Segmentation Based on Approximate Skeleton Detection
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Modern medical imaging techniques have revolutionized health care over the last decades, providing clinicians with high-resolution 3D images of the inside of the patient's body without the need for invasive procedures. Detailed images of the vascular anatomy can be captured by angiography, providing a valuable source of information when deciding whether a vascular intervention is needed, for planning treatment, and for analyzing the success of therapy. However, increasing level of detail in the images, together with a wide availability of imaging devices, lead to an urgent need for automated techniques for image segmentation and analysis in order to assist the clinicians in performing a fast and accurate examination.To reduce the need for user interaction and increase the speed of vascular segmentation, we propose a fast and fully automatic vascular skeleton extraction algorithm. This algorithm first analyzes the volume's intensity histogram in order to automatically adapt the internal parameters to each patient and then it produces an approximate skeleton of the patient's vasculature. The skeleton can serve as a seed region for subsequent surface extraction algorithms. Further improvements of the skeleton extraction algorithm include the expansion to detect the skeleton of diseased arteries and the design of a convolutional neural network classifier that reduces false positive detections of vascular cross-sections. In addition to the complete skeleton extraction algorithm, the thesis presents a segmentation algorithm based on modified onion-kernel region growing. It initiates the growing from the previously extracted skeleton and provides a rapid binary segmentation of tubular structures. To provide the possibility of extracting precise measurements from this segmentation we introduce a method for obtaining a segmentation with subpixel precision out of the binary segmentation and the original image. This method is especially suited for thin and elongated structures, such as vessels, since it does not shrink the long protrusions. The method supports both 2D and 3D image data.The methods were validated on real computed tomography datasets and are primarily intended for applications in vascular segmentation, however, they are robust enough to work with other anatomical tree structures after adequate parameter adjustment, which was demonstrated on an airway-tree segmentation.
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| 12. |
- Niazi, Muhammad Khalid Khan, 1978-, et al.
(författare)
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Fully Automatic Heart Beat Rate Determination in Digital Video Recordings of Rat Embryos
- 2008
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Ingår i: ADVANCES IN MASS DATA ANALYSIS OF IMAGES AND SIGNALS IN MEDICINE, BIOTECHNOLOGY, CHEMISTRY AND FOOD INDUSTRY, PRCEEDINGS. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 9783540707141 ; , s. 27-37
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Konferensbidrag (refereegranskat)abstract
- Embryo cultures of rodents is an established technique for monitoring adverse effects of chemicals on embryonic development. The assessment involves determination of the heart rate of the embryo which is usually done visually, a technique which is tedious and error prone. We present a new method for fully automatic heart detection in digital videos of rat embryos. First it detects the heart location, and then it counts the number of heart beats for a predetermined period of time. Using this automated method many more embryos can be evaluated at reasonable cost.
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| 13. |
- Nilsson, Mats F., et al.
(författare)
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Improved methodology for identifying the teratogenic potential in early drug development of hERG channel blocking drugs
- 2010
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Ingår i: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 29:2, s. 156-163
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Tidskriftsartikel (refereegranskat)abstract
- Drugs blocking the potassium current IKr of the heart (via hERG channel-inhibition) have the potential to cause hypoxia-related teratogenic effects. However, this activity may be missed in conventional teratology studies because repeat dosing may cause resorptions. The aim of the present study was to investigate an alternative protocol to reveal the teratogenic potential of IKr-blocking drugs. The IKr blocker astemizole, given as a single dose (80mg/kg) on gestation day (GD) 13 to pregnant rats caused digital defects. In whole rat embryo culture (2h) on GD 13, astemizole caused a decrease in embryonic heart rate at 20nM, and arrhythmias at 200-400nM. Cetirizine, without IKr-blocking properties, did not affect the rat embryonic heart in vitro. The present study shows that single dose testing on sensitive days of development, together with whole embryo culture, can be a useful methodology to better characterize the teratogenic potential of IKr-blocking drugs.
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| 14. |
- Schroter, D, et al.
(författare)
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Ecosystem service supply and vulnerability to global change in Europe
- 2005
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 310:5752, s. 1333-1337
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Tidskriftsartikel (refereegranskat)abstract
- Global change will alter the supply of ecosystem services that are vital for human well-being. To investigate ecosystem service supply during the 21st century, we used a range of ecosystem models and scenarios of climate and land-use change to conduct a Europe-wide assessment. Large changes in climate and land use typically resulted in large changes in ecosystem service supply. Some of these trends may be positive (for example, increases in forest area and productivity) or offer opportunities (for example, "surplus land" for agricultural extensification and bioenergy production). However, many changes increase vulnerability as a result of a decreasing supply of ecosystem services (for example, declining soil fertility, declining water availability, increasing risk of forest fires), especially in the Mediterranean and mountain regions.
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