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Sökning: WFRF:(Barthel S)

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2.
  • van Rheenen, W, et al. (författare)
  • Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
  • 2021
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 53:12, s. 1636-
  • Tidskriftsartikel (refereegranskat)abstract
    • Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
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  • Cilliers, S. S., et al. (författare)
  • Garden ecosystem services of Sub-Saharan Africa and the role of health clinic gardens as social-ecological systems
  • 2018
  • Ingår i: Landscape and Urban Planning. - : Elsevier BV. - 0169-2046 .- 1872-6062. ; 180, s. 294-307
  • Tidskriftsartikel (refereegranskat)abstract
    • Rapid urbanization is predicted to take place in Africa in the near future and currently stressed cities will be even more overburdened in terms of pressure on green areas and increasing urban poverty. Effectively planning for and conserving current urban green infrastructure will be essential to ensure resilience and maintenance of quality urban environments. Gardens represent major portions of urban green infrastructure. In this paper we review literature to determine the current status of garden ecosystem services under the main themes of provisioning, regulating, supporting and cultural services in sub-Saharan Africa and identify the current challenges in optimizing these ecosystem services. Studying gardens as social-ecological systems might be the key to promote and enhance their resilience capacity in a changing world, acknowledging the fact that gardens are communities of practice in which social learning may occur. Studies on health clinic gardens in the North-West Province of South Africa have indicated how some of the challenges in terms of optimizing garden ecosystem services can be addressed. Multiple stakeholders involved in the health clinic gardens contribute towards a co-production of knowledge that could lead to social learning on aspects such as cultivation of nutritious food. More detailed studies on health clinic gardens are however, necessary to be able to develop a community-based resource management framework that can be implemented in the North-West Province and potentially in other South African provinces and countries in Sub-Saharan Africa.
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  • Wild, W., et al. (författare)
  • Millimetron—a large Russian-European submillimeter space observatory
  • 2009
  • Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 23:1, s. 221-244
  • Tidskriftsartikel (refereegranskat)abstract
    • Millimetron is a Russian-led 12 m diameter submillimeter and far-infrared space observatory which is included in the Space Plan of the Russian Federation for launch around 2017. With its large collecting area and state-of-the-art receivers, it will enable unique science and allow at least one order of magnitude improvement with respect to the Herschel Space Observatory. Millimetron will be operated in two basic observing modes: as a single-dish observatory, and as an element of a ground-space very long baseline interferometry (VLBI) system. As single-dish, angular resolutions on the order of 3 to 12 arc sec will be achieved and spectral resolutions of up to a million employing heterodyne techniques. As VLBI antenna, the chosen elliptical orbit will provide extremely large VLBI baselines (beyond 300,000 km) resulting in micro-arc second angular resolution.
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  • Chetelat, G., et al. (författare)
  • Amyloid-PET and 18-F-FDG-PET in the diagnostic investigation of Alzheimer's disease and other dementias
  • 2020
  • Ingår i: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 19:11, s. 951-962
  • Forskningsöversikt (refereegranskat)abstract
    • Various biomarkers are available to support the diagnosis of neurodegenerative diseases in clinical and research settings. Among the molecular imaging biomarkers, amyloid-PET, which assesses brain amyloid deposition, and F-18-fluorodeoxyglucose (F-18-FDG) PET, which assesses glucose metabolism, provide valuable and complementary information. However, uncertainty remains regarding the optimal timepoint, combination, and an order in which these PET biomarkers should be used in diagnostic evaluations because conclusive evidence is missing. Following an expert panel discussion, we reached an agreement on the specific use of the individual biomarkers, based on available evidence and clinical expertise. We propose a diagnostic algorithm with optimal timepoints for these PET biomarkers, also taking into account evidence from other biomarkers, for early and differential diagnosis of neurodegenerative diseases that can lead to dementia. We propose three main diagnostic pathways with distinct biomarker sequences, in which amyloid-PET and F-18-FDG-PET are placed at different positions in the order of diagnostic evaluations, depending on clinical presentation. We hope that this algorithm can support diagnostic decision making in specialist clinical settings with access to these biomarkers and might stimulate further research towards optimal diagnostic strategies.
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  • Jansen, Willemijn J, et al. (författare)
  • Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
  • 2018
  • Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 84-95
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P=.16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P<.001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P<.001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
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8.
  • Jansen, Willemijn J, et al. (författare)
  • Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
  • 2015
  • Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
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9.
  • Penston, M. V., et al. (författare)
  • The extended narrow line region of NGC 4151. I. Emission line ratios and their implications
  • 1990
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 236:1, s. 53-6262
  • Tidskriftsartikel (refereegranskat)abstract
    • The paper presents the first results from long-slit spectra of the Seyfert galaxy NGC 4151 which give average diagnostic ratios of weak lines in the extended narrow line region (ENLR) of that galaxy and the first direct density measurement in an ENLR. These data confirm that the ENLR is kinematically undisturbed gas in the disc of the galaxy which is illuminated by an ionizing continuum stronger by a factor of 13 than a power law interpolated between observed ultraviolet and X-ray fluxes. Explanations of this apparent excess include a hot thermal continuum, time variations and an anisotropic radiation field. The authors give reasons for favouring anisotropy which might be caused by shadowing by a thick accretion disc or by relativistic beaming. Shadowing by a molecular torus is unlikely, given the absence of an infrared signal from the reradiated flux absorbed by any torus. Anisotropy would have important implications for the bolometric luminosity and nature of active galactic nuclei
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  • Terenius, Olle, et al. (författare)
  • RNA interference in Lepidoptera : An overview of successful and unsuccessful studies and implications for experimental design
  • 2011
  • Ingår i: Journal of insect physiology. - : Elsevier BV. - 0022-1910 .- 1879-1611. ; 57:2, s. 231-245
  • Tidskriftsartikel (refereegranskat)abstract
    • Gene silencing through RNA interference (RNAi) has revolutionized the study of gene function, particularly in non-model insects. However, in Lepidoptera (moths and butterflies) RNAi has many times proven to be difficult to achieve. Most of the negative results have been anecdotal and the positive experiments have not been collected in such a way that they are possible to analyze. In this review, we have collected detailed data from more than 150 experiments including all to date published and many unpublished experiments. Despite a large variation in the data, trends that are found are that RNAi is particularly successful in the family Saturniidae and in genes involved in immunity. On the contrary, gene expression in epidermal tissues seems to be most difficult to silence. In addition, gene silencing by feeding dsRNA requires high concentrations for success. Possible causes for the variability of success in RNAi experiments in Lepidoptera are discussed. The review also points to a need to further investigate the mechanism of RNAi in lepidopteran insects and its possible connection to the innate immune response. Our general understanding of RNAi in Lepidoptera will be further aided in the future as our public database at http://insectacentral.org/RNAi will continue to gather information on RNAi experiments.
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  • Bailey, D. L., et al. (författare)
  • Combined PET/MRI : Global Warming-Summary Report of the 6th International Workshop on PET/MRI, March 27-29, 2017, Tubingen, Germany
  • 2018
  • Ingår i: Molecular Imaging and Biology. - : SPRINGER. - 1536-1632 .- 1860-2002. ; 20:1, s. 4-20
  • Forskningsöversikt (refereegranskat)abstract
    • The 6th annual meeting to address key issues in positron emission tomography (PET)/magnetic resonance imaging (MRI) was held again in Tubingen, Germany, from March 27 to 29, 2017. Over three days of invited plenary lectures, round table discussions and dialogue board deliberations, participants critically assessed the current state of PET/MRI, both clinically and as a research tool, and attempted to chart future directions. The meeting addressed the use of PET/MRI and workflows in oncology, neurosciences, infection, inflammation and chronic pain syndromes, as well as deeper discussions about how best to characterise the tumour microenvironment, optimise the complementary information available from PET and MRI, and how advanced data mining and bioinformatics, as well as information from liquid biomarkers (circulating tumour cells and nucleic acids) and pathology, can be integrated to give a more complete characterisation of disease phenotype. Some issues that have dominated previous meetings, such as the accuracy of MR-based attenuation correction (AC) of the PET scan, were finally put to rest as having been adequately addressed for the majority of clinical situations. Likewise, the ability to standardise PET systems for use in multicentre trials was confirmed, thus removing a perceived barrier to larger clinical imaging trials. The meeting openly questioned whether PET/MRI should, in all cases, be used as a whole-body imaging modality or whether in many circumstances it would best be employed to give an in-depth study of previously identified disease in a single organ or region. The meeting concluded that there is still much work to be done in the integration of data from different fields and in developing a common language for all stakeholders involved. In addition, the participants advocated joint training and education for individuals who engage in routine PET/MRI. It was agreed that PET/MRI can enhance our understanding of normal and disrupted biology, and we are in a position to describe the in vivo nature of disease processes, metabolism, evolution of cancer and the monitoring of response to pharmacological interventions and therapies. As such, PET/MRI is a key to advancing medicine and patient care.
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  • Barthel, Roland, 1967, et al. (författare)
  • Global change impacts on groundwater in Southern Germany-Part 2: Socioeconomic aspects
  • 2011
  • Ingår i: Grundwasser. - : Springer Science and Business Media LLC. - 1430-483X .- 1432-1165. ; 16:4, s. 259-268
  • Tidskriftsartikel (refereegranskat)abstract
    • In order to account for complex interactions between humans climate and the water cycle, the research consortium GLOWA-Danube http://www. glowa-danube. de has developed the simulation system DANUBIA which consists of 17 coupled models. DANUBIA was applied to investigate various impacts of global-change between 2011 and 2060 in the Upper Danube Catchment. This article describes part 2 of an article series with investigations of socio-economic aspects, while part 1 (Barthel et al. in Grundwasser 16(4), doi:10. 1007/s007-011-01794, 2011) deals with natural-spatial aspects. The principles of socio-economic actor-modeling and interactions between socio-economic and natural science model components are described here. We present selected simulations that show impacts on groundwater from changes in agriculture, tourism, economy, domestic water users and water supply. Despite decreases in water consumption, the scenario simulations show significant decreases in groundwater quantity. On the other hand, groundwater quality will likely be influenced more severely by land use changes compared to direct climatic causes. However, overall changes will not be dramatic. © 2011 Springer-Verlag.
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  • Lima, Gustavo M.A., et al. (författare)
  • FragMAXapp : Crystallographic fragment-screening data-analysis and project-management system
  • 2021
  • Ingår i: Acta Crystallographica Section D: Structural Biology. - 2059-7983. ; 77, s. 799-808
  • Tidskriftsartikel (refereegranskat)abstract
    • Crystallographic fragment screening (CFS) has become one of the major techniques for screening compounds in the early stages of drug-discovery projects. Following the advances in automation and throughput at modern macromolecular crystallography beamlines, the bottleneck for CFS has shifted from collecting data to organizing and handling the analysis of such projects. The complexity that emerges from the use of multiple methods for processing and refinement and to search for ligands requires an equally sophisticated solution to summarize the output, allowing researchers to focus on the scientific questions instead of on software technicalities. FragMAXapp is the fragment-screening project-management tool designed to handle CFS projects at MAX IV Laboratory. It benefits from the powerful computing infrastructure of large-scale facilities and, as a web application, it is accessible from everywhere.
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  • Ostensen, R, et al. (författare)
  • ESO & NOT photometric monitoring of the Cloverleaf quasar
  • 1997
  • Ingår i: ASTRONOMY & ASTROPHYSICS SUPPLEMENT SERIES. - : E D P SCIENCES. - 0365-0138. ; 126:3, s. 393-400
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The Cloverleaf quasar, H1413+117, has been photometrically monitored at ESO (La Silla, Chile) and with the NOT (La Palma, Spain) during the period 1987-1994. All good quality CCD frames have been successfully analysed using two independent methods (i.e. a
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  • Altincekic, Nadide, et al. (författare)
  • Targeting the Main Protease (Mpro, nsp5) by Growth of Fragment Scaffolds Exploiting Structure-Based Methodologies
  • 2024
  • Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 19:2, s. 563-574
  • Tidskriftsartikel (refereegranskat)abstract
    • The main protease Mpro, nsp5, of SARS-CoV-2 (SCoV2) is one of its most attractive drug targets. Here, we report primary screening data using nuclear magnetic resonance spectroscopy (NMR) of four different libraries and detailed follow-up synthesis on the promising uracil-containing fragment Z604 derived from these libraries. Z604 shows time-dependent binding. Its inhibitory effect is sensitive to reducing conditions. Starting with Z604, we synthesized and characterized 13 compounds designed by fragment growth strategies. Each compound was characterized by NMR and/or activity assays to investigate their interaction with Mpro. These investigations resulted in the four-armed compound 35b that binds directly to Mpro. 35b could be cocrystallized with Mpro revealing its noncovalent binding mode, which fills all four active site subpockets. Herein, we describe the NMR-derived fragment-to-hit pipeline and its application for the development of promising starting points for inhibitors of the main protease of SCoV2.
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  • Bailey, D. L., et al. (författare)
  • Combined PET/MRI : from Status Quo to Status Go. Summary Report of the Fifth International Workshop on PET/MR Imaging; February 15-19, 2016; Tubingen, Germany
  • 2016
  • Ingår i: Molecular Imaging and Biology. - : Springer Science and Business Media LLC. - 1536-1632 .- 1860-2002. ; 18:5, s. 637-650
  • Tidskriftsartikel (refereegranskat)abstract
    • This article provides a collaborative perspective of the discussions and conclusions from the fifth international workshop of combined positron emission tomorgraphy (PET)/magnetic resonance imaging (MRI) that was held in Tubingen, Germany, from February 15 to 19, 2016. Specifically, we summarise the second part of the workshop made up of invited presentations from active researchers in the field of PET/MRI and associated fields augmented by round table discussions and dialogue boards with specific topics. This year, this included practical advice as to possible approaches to moving PET/MRI into clinical routine, the use of PET/MRI in brain receptor imaging, in assessing cardiovascular diseases, cancer, infection, and inflammatory diseases. To address perceived challenges still remaining to innovatively integrate PET and MRI system technologies, a dedicated round table session brought together key representatives from industry and academia who were engaged with either the conceptualisation or early adoption of hybrid PET/MRI systems. Discussions during the workshop highlighted that emerging unique applications of PET/MRI such as the ability to provide multi-parametric quantitative and visual information which will enable not only overall disease detection but also disease characterisation would eventually be regarded as compelling arguments for the adoption of PET/MR. However, as indicated by previous workshops, evidence in favour of this observation is only growing slowly, mainly due to the ongoing inability to pool data cohorts from independent trials as well as different systems and sites. The participants emphasised that moving from status quo to status go entails the need to adopt standardised imaging procedures and the readiness to act together prospectively across multiple PET/MRI sites and vendors.
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  • Barthel, J., et al. (författare)
  • Understanding electron magnetic circular dichroism in a transition potential approach
  • 2018
  • Ingår i: Physical Review B. - 2469-9950 .- 2469-9969. ; 97:14
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper introduces an approach based on transition potentials for inelastic scattering to understand the underlying physics of electron magnetic circular dichroism (EMCD). The transition potentials are sufficiently localized to permit atomic-scale EMCD. Two-beam and three-beam systematic row cases are discussed in detail in terms of transition potentials for conventional transmission electron microscopy, and the basic symmetries which arise in the three-beam case are confirmed experimentally. Atomic-scale EMCD in scanning transmission electron microscopy (STEM), using both a standard STEM probe and vortex beams, is discussed.
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  • Barthel, Roland, 1967, et al. (författare)
  • An integrated modelling framework for simulating regional-scale actor responses to global change in the water domain
  • 2008
  • Ingår i: Environmental Modelling & Software. - : Elsevier BV. - 1364-8152. ; 23:9, s. 1095-1121
  • Tidskriftsartikel (refereegranskat)abstract
    • Within coupled hydrological simulation systems, taking socio-economic processes into account is still a challenging task. In particular, systems that aim at evaluating impacts of climatic change on large spatial and temporal scales cannot be based on the assumption that infrastructure, economy, demography and other human factors remain constant while physical boundary conditions change. Therefore, any meaningful simulation of possible future scenarios needs to enable socio-economic systems to react and to adapt to climatic changes. To achieve this it is necessary to simulate decision-making processes of the relevant actors in a way which is adequate for the scale, the catchment specific management problems to be investigated and finally the data availability. This contribution presents the DEEPACTOR approach for representing such human decision processes, which makes use of a multi-actor simulation framework and has similarities to agent-based approaches. This DEEPACTOR approach is embedded in DANUBIA, a coupled simulation system comprising 16 individual models to simulate Global Change impacts on the entire water cycle of the Upper Danube Catchment (Germany, 77,000 km(2)). The applicability of DANUBIA and in particular the DEEPACTOR approach for treating the socio-economic part of the water cycle in a process-based way is demonstrated by means of concrete simulation models of the water supply sector and of the domestic water users. Results from scenario simulations are used to demonstrate the capabilities and limitations of the approach. (c) 2008 Elsevier Ltd. All rights reserved.
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  • Barthel, Roland, 1967, et al. (författare)
  • Using the multiactor-approach in GLOWA-danube to simulate decisions for the water supply sector under conditions of global climate change
  • 2010
  • Ingår i: Water Resources Management. - : Springer Science and Business Media LLC. - 0920-4741 .- 1573-1650. ; 24:2, s. 239-275
  • Tidskriftsartikel (refereegranskat)abstract
    • Glowa-Danube (www.glowa-danube.de) is an interdisciplinary project that aims to develop integrated strategies and tools for water and land use management in the upper Danube catchment (Germany, Austria ~77,000 km2). The project is one of five within the Glowa research program (www.glowa.org) dealing with Global Change effects on the water cycle in six meso-scale catchments (up to 100,000 km2) in Central Europe, West Africa and the Middle East. In the Glowa-Danube project, 16 natural science and socio-economic simulation models are integrated in the coupled simulation system Danubia. This article describes the underlying concept and implementation of WaterSupply, a multiactor-based model of the water supply sector with a focus on water resource utilization and distribution of individual water supply companies. Within Danubia, WaterSupply represents the link between water supply and demand, where the former is simulated by a groundwater and a surface water model and the latter by water consumption models of four different sectors (domestic, industrial, agricultural and tourism). WaterSupply interprets the quantitative state of water resources for defined spatial and temporal units according to sustainability requirements and assesses the state of resources in relation to present water supply schemes and the dynamics of user demand. WaterSupply then seeks both to optimize the resource use of supply companies and to identify critical regions for which further adaptation of the water supply scheme will become necessary under changing climatic conditions. In this article, a brief description of the Glowa-Danube project and the integrated simulation system Danubia is followed by a short presentation of the DeepActor framework, which provides a common conceptual and technical basis for the socio-economic simulation models of Glowa-Danube. The main body of the article is devoted to the concept, the implementation and simulation results of WaterSupply. Results from different scenario calculations demonstrate the capabilities and the potential fields of application of the model. © Springer Science+Business Media B.V. 2009.
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  • Barthel, Tatjana, et al. (författare)
  • Large-Scale Crystallographic Fragment Screening Expedites Compound Optimization and Identifies Putative Protein-Protein Interaction Sites
  • 2022
  • Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 65:21, s. 14630-14641
  • Tidskriftsartikel (refereegranskat)abstract
    • The identification of starting points for compound development is one of the key steps in early-stage drug discovery. Information-rich techniques such as crystallographic fragment screening can potentially increase the efficiency of this step by providing the structural information of the binding mode of the ligands in addition to the mere binding information. Here, we present the crystallographic screening of our 1000-plus-compound F2X-Universal Library against the complex of the yeast spliceosomal Prp8 RNaseH-like domain and the snRNP assembly factor Aar2. The observed 269 hits are distributed over 10 distinct binding sites on the surface of the protein-protein complex. Our work shows that hit clusters from large-scale crystallographic fragment screening campaigns identify known interaction sites with other proteins and suggest putative additional interaction sites. Furthermore, the inherent binding pose validation within the hit clusters may accelerate downstream compound optimization.
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33.
  • Brandt, S. Anders, 1970-, et al. (författare)
  • Mapping Flood Risk Uncertainty Zones in Support of Urban Resilience Planning
  • 2021
  • Ingår i: Urban Planning. - Lisbon, Portugal : Cogitatio. - 2183-7635. ; 6:3, s. 258-271
  • Tidskriftsartikel (refereegranskat)abstract
    • River flooding and urbanization are processes of different character that take place worldwide. As the latter tends to make the consequences of the former worse, together with the uncertainties related to future climate change and flood‐risk modeling, there is a need to both use existing tools and develop new ones that help the management and planning of urban environments. In this article a prototype tool, based on estimated maximum land cover roughness variation, the slope of the ground, and the quality of the used digital elevation models, and that can produce flood ‘uncertainty zones’ of varying width around modeled flood boundaries, is presented. The concept of uncertainty, which urban planners often fail to consider in the spatial planning process, changes from something very difficult into an advantage in this way. Not only may these uncertainties be easier to understand by the urban planners, but the uncertainties may also function as a communication tool between the planners and other stakeholders. Because flood risk is something that urban planners always need to consider, these uncertainty zones can function both as buffer areas against floods, and as blue‐green designs of significant importance for a variety of ecosystem services. As the Earth is warming and the world is urbanizing at rates and scales unprecedented in history, we believe that new tools for urban resilience planning are not only urgently needed, but also will have a positive impact on urban planning.
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34.
  • Croke, B., et al. (författare)
  • Marrying Hydrological Modelling and Integrated Assessment for the needs of Water Resource Management
  • 2014
  • Ingår i: Proceedings of the International Association of Hydrological Sciences. - Bologna, Italy : IAHS. - 0144-7815 .- 2199-899X. - 9781907161421 ; 364, s. 351-356
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract This paper discusses the integration of hydrology with other disciplines using an Integrated Assessment (IA) and modelling approach to the management and allocation of water resources. Recent developments in the field of socio-hydrology aim to develop stronger relationships between hydrology and the human dimensions of Water Resource Management (WRM). This should build on an existing wealth of knowledge and experience of coupled human–water systems. To further strengthen this relationship and contribute to this broad body of knowledge, we propose a strong and durable “marriage” between IA and hydrology. The foundation of this marriage requires engagement with appropriate concepts, model structures, scales of analyses, performance evaluation and communication – and the associated tools and models that are needed for pragmatic deployment or operation. To gain insight into how this can be achieved, an IA case study in water allocation in the Lower Namoi catchment, NSW, Australia is presented.
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  • Guedj, E, et al. (författare)
  • EANM procedure guidelines for brain PET imaging using [18F]FDG, version 3
  • 2022
  • Ingår i: European journal of nuclear medicine and molecular imaging. - : Springer Science and Business Media LLC. - 1619-7089 .- 1619-7070. ; 49:62, s. 632-651
  • Tidskriftsartikel (refereegranskat)abstract
    • The present procedural guidelines summarize the current views of the EANM Neuro-Imaging Committee (NIC). The purpose of these guidelines is to assist nuclear medicine practitioners in making recommendations, performing, interpreting, and reporting results of [18F]FDG-PET imaging of the brain. The aim is to help achieve a high-quality standard of [18F]FDG brain imaging and to further increase the diagnostic impact of this technique in neurological, neurosurgical, and psychiatric practice. The present document replaces a former version of the guidelines that have been published in 2009. These new guidelines include an update in the light of advances in PET technology such as the introduction of digital PET and hybrid PET/MR systems, advances in individual PET semiquantitative analysis, and current broadening clinical indications (e.g., for encephalitis and brain lymphoma). Further insight has also become available about hyperglycemia effects in patients who undergo brain [18F]FDG-PET. Accordingly, the patient preparation procedure has been updated. Finally, most typical brain patterns of metabolic changes are summarized for neurodegenerative diseases. The present guidelines are specifically intended to present information related to the European practice. The information provided should be taken in the context of local conditions and regulations.
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  • Hetze, S, et al. (författare)
  • Rodent Models to Analyze the Glioma Microenvironment
  • 2021
  • Ingår i: ASN neuro. - : SAGE Publications. - 1759-0914. ; 13, s. 17590914211005074-
  • Tidskriftsartikel (refereegranskat)abstract
    • Animal models are still indispensable for understanding the basic principles of glioma development and invasion. Preclinical approaches aim to analyze the treatment efficacy of new drugs before translation into clinical trials is possible. Various animal disease models are available, but not every approach is useful for addressing specific questions. In recent years, it has become increasingly evident that the tumor microenvironment plays a key role in the nature of glioma. In addition to providing an overview, this review evaluates available rodent models in terms of usability for research on the glioma microenvironment.
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40.
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41.
  • Jansen, Willemijn J, et al. (författare)
  • Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
  • 2022
  • Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
  • Tidskriftsartikel (refereegranskat)abstract
    • One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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42.
  • Lembrechts, Jonas J., et al. (författare)
  • Global maps of soil temperature
  • 2022
  • Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 28:9, s. 3110-3144
  • Tidskriftsartikel (refereegranskat)abstract
    • Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0–5 and 5–15cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean=3.0±2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6±2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (−0.7±2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications.
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43.
  • Makelele, I. A., et al. (författare)
  • Conservative N cycling despite high atmospheric deposition in early successional African tropical lowland forests
  • 2022
  • Ingår i: Plant and Soil. - : Springer Science and Business Media LLC. - 0032-079X .- 1573-5036. ; 477, s. 743-758
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Across the tropics, the share of secondary versus primary forests is strongly increasing. The high rate of biomass accumulation during this secondary succession relies on the availability of essential nutrients, such as nitrogen (N). Nitrogen primarily limits many young secondary forests in the tropics. However, recent studies have shown that forests of the Congo basin are subject to high inputs of atmospheric N deposition, potentially alleviating this N limitation in early succession. Methods To address this hypothesis, we assessed the N status along a successional gradient of secondary forests in the Congo basin. In a set-up of 18 plots implemented along six successional stages, we quantified year-round N deposition, N leaching, N2O emission and the N flux of litterfall and fine root assimilation. Additionally, we determined the N content and C:N stoichiometry for canopy leaves, fine roots, and litter, as well as delta N-15 of canopy leaves. Results We confirmed that these forests receive high amounts of atmospheric N deposition, with an increasing deposition as forest succession proceeds. Additionally, we noted lower C:N ratios, and higher N leaching losses, N2O emission, and foliar delta N-15 in older secondary forest (60 years). In contrast, higher foliar, litter and root C:N ratios, and lower foliar delta N-15, N leaching, and N2O emission in young (< 20 years) secondary forest were observed. Conclusions Altogether, we show that despite high N deposition, this early forest succession still shows conservative N cycling characteristics, which are likely indicating N limitation early on in secondary forest succession. As secondary succession advances, the N cycle gradually becomes more open.
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44.
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45.
  • Morbelli, S, et al. (författare)
  • COVID-19 and the brain: impact on nuclear medicine in neurology
  • 2020
  • Ingår i: European journal of nuclear medicine and molecular imaging. - : Springer Science and Business Media LLC. - 1619-7089 .- 1619-7070. ; 47:11, s. 2487-2492
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
46.
  • Roemer, Sebastian N., et al. (författare)
  • Subcortical tau is linked to hypoperfusion in connected cortical regions in 4-repeat tauopathies
  • 2024
  • Ingår i: BRAIN. - 0006-8950 .- 1460-2156. ; 147:7, s. 2428-2439
  • Tidskriftsartikel (refereegranskat)abstract
    • Four-repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R tauopathies are progressive supranuclear palsy (PSP) and corticobasal degeneration characterized by subcortical tau accumulation and cortical neuronal dysfunction, as shown by PET-assessed hypoperfusion and glucose hypometabolism. Yet, there is a spatial mismatch between subcortical tau deposition patterns and cortical neuronal dysfunction, and it is unclear how these two pathological brain changes are interrelated. Here, we hypothesized that subcortical tau pathology induces remote neuronal dysfunction in functionally connected cortical regions to test a pathophysiological model that mechanistically links subcortical tau accumulation to cortical neuronal dysfunction in 4R tauopathies.We included 51 A beta-negative patients with clinically diagnosed PSP variants (n = 26) or corticobasal syndrome (n = 25) who underwent structural MRI and 18F-PI-2620 tau-PET. 18F-PI-2620 tau-PET was recorded using a dynamic one-stop-shop acquisition protocol to determine an early 0.5-2.5 min post tracer-injection perfusion window for assessing cortical neuronal dysfunction, as well as a 20-40 min post tracer-injection window to determine 4R-tau load. Perfusion-PET (i.e. early window) was assessed in 200 cortical regions, and tau-PET was assessed in 32 subcortical regions of established functional brain atlases. We determined tau epicentres as subcortical regions with the highest 18F-PI-2620 tau-PET signal and assessed the connectivity of tau epicentres to cortical regions of interest using a resting-state functional MRI-based functional connectivity template derived from 69 healthy elderly controls from the ADNI cohort. Using linear regression, we assessed whether: (i) higher subcortical tau-PET was associated with reduced cortical perfusion; and (ii) cortical perfusion reductions were observed preferentially in regions closely connected to subcortical tau epicentres.As hypothesized, higher subcortical tau-PET was associated with overall lower cortical perfusion, which remained consistent when controlling for cortical tau-PET. Using group-average and subject-level PET data, we found that the seed-based connectivity pattern of subcortical tau epicentres aligned with cortical perfusion patterns, where cortical regions that were more closely connected to the tau epicentre showed lower perfusion.Together, subcortical tau-accumulation is associated with remote perfusion reductions indicative of neuronal dysfunction in functionally connected cortical regions in 4R-tauopathies. This suggests that subcortical tau pathology may induce cortical dysfunction, which may contribute to clinical disease manifestation and clinical heterogeneity. Four-repeat tauopathies are rapidly progressive neurodegenerative diseases with mixed subcortical and cortical symptoms. Using advanced neuroimaging methods, Roemer et al. show that subcortical tau accumulation is associated with remote perfusion reductions indicative of neuronal dysfunction in functionally connected cortical regions.
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47.
  • Rottgering, H., et al. (författare)
  • The "Sausage" and "Toothbrush" clusters of galaxies and the prospects of LOFAR observations of clusters of galaxies
  • 2013
  • Ingår i: Astronomische Nachrichten. - : Wiley. - 0004-6337 .- 1521-3994. ; 334:4-5, s. 333-337
  • Tidskriftsartikel (refereegranskat)abstract
    • LOFAR, the Low Frequency Radio Array, is a new pan-European radio telescope that is almost fully operational. One of its main drivers is to make deep images of the low frequency radio sky. To be able to do this a number of challenges need to be addressed. These include the high data rates, removal of radio frequency interference, calibration of the beams and correcting for the corrupting influence of the ionosphere. One of the key science goals is to study merger shocks, particle acceleration mechanisms and the structure of magnetic fields in nearby and distant merging clusters. Recent studies with the GMRT and WSRT radio telescopes of the "Sausage" and the "Toothbrush" clusters have given a very good demonstration of the power of radio observations to study merging clusters. Recently we discovered that both clusters contain relic and halo sources, large diffuse regions of radio emission not associated with individual galaxies. The 2 Mpc northern relic in the Sausage cluster displays highly aligned magnetic fields and and exhibits a strong spectral index gradient that is a consequence of cooling of the synchrotron emitting particles in the post-shock region. We have argued that these observations provide strong evidence that shocks in merging clusters are capable of accelerating particles. For the Toothbrush cluster we observe a puzzling linear relic that extends over 2 Mpc. The proposed scenario is that a triple-merger can lead to such a structure. With LOFAR's sensitivity it will not only be possible to trace much weaker shocks, but also to study those shocks due to merging clusters up to redshifts of at least one. (C) 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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48.
  • Samuelsson, Karl, Postdoktor, et al. (författare)
  • Diverse experiences by active travel for carbon neutrality: A longitudinal study of residential context, daily travel and experience types
  • 2024
  • Ingår i: Geography and Sustainability. - : Elsevier. - 2666-6839. ; 5:3, s. 459-469
  • Tidskriftsartikel (refereegranskat)abstract
    • Two key goals for sustainable spatial planning are to promote low-carbon travel in daily life and to enhance human wellbeing through diverse human-environment interactions. Yet, the integration of these goals has been underexplored. This study investigates the potential for experiential diversity via active travel in different residential contexts within the Gävle city-region, Sweden. Over 15 months, we collected spatiotemporal data from 165 participants, analyzing 4,362 reported experiences and 13,192 GPS-derived travel trajectories. Our analysis uncovered a significant spatial discrepancy: while the travelled distances to locations of positive experiences typically ranged from 1.5 km to 5 km, active travel predominated only within 1.5 km. This discrepancy persisted across urban, suburban, and peripheral contexts. Although residents in different contexts reported the same types of experiences, urban dwellers travelled about 50 % farther for nature experiences compared with other positive experiences, whereas peripheral dwellers travelled twice the distance for urbanicity experiences compared with other positive experiences. Consequently, urban residents mostly relied on active travel for urbanicity experiences and motorised travel for nature experiences, with the reverse trend observed among peripheral dwellers. These results illustrate the importance of spatial scale for promoting diverse positive experiences via active travel, regardless of residential context. Effective planning strategies may include enhancing environmental diversity near homes and developing infrastructure that favours active over motorised travel for short to moderate distances.
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49.
  • Samuelsson, Karl, Postdoktor, et al. (författare)
  • Diverse experiences by active travel: Longitudinal study reveals a persistent discrepancy across residential contexts
  • 2023
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • To inform spatial planning promoting low-carbon travel and well-being, we investigate the potential for experiential diversity by active travel across different residential contexts. We use spatiotemporal tracking and experience data from the Gävle city-region, Sweden, generated by 165 participants over the course of 15 months. Findings reveal a discrepancy between typical travel distances to locations of positive experiences (1.5–5 km) and the distances at which active travel dominates (up to 1.5 km). This discrepancy largely persists across urban, suburban, and peripheral contexts, with urban dwellers travelling further for nature experiences, whereas peripheral dwellers travel further for urbanicity experiences. These results illustrate the importance of spatial scale for promoting diverse positive experiences by active travel, regardless of residential context. Planning strategies include enhancing environmental diversity close to people’s homes and providing infrastructure that promotes switching from motorised to active travel for trips of a few kilometres.
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50.
  • Samuelsson, Karl, et al. (författare)
  • Impact of environment on people’s everyday experiences in Stockholm
  • 2018
  • Ingår i: Landscape and Urban Planning. - : Elsevier BV. - 0169-2046 .- 1872-6062. ; 171, s. 7-17
  • Tidskriftsartikel (refereegranskat)abstract
    • In order to construct urban environments that limit negative impacts for global sustainability while supporting human wellbeing, there is a need to better understand how features of the environment influence people’s everyday experiences. We present a novel method for studying this combining accessibility analysis and public participatory GIS (PPGIS). Seven environment features are defined and accessibility to them analysed across Stockholm municipality. We estimate the probabilities of positive and negative experiences in places based on these environment features, by using spatial regression to extrapolate from the results of an online PPGIS survey (1784 experiences of 1032 respondents). Six of the seven studied environment features have significant impact on experiential outcome, after accounting for spatial autocorrelation among the data. The results show that number of residents and proximity of nature environments and water, all common quality indicators in urban planning and research, have weak statistically significant effects on people’s experiences. However, areas dominated by large working populations or proximity to major roads have very low rates of positive experiences, while areas with high natural temperature regulating capacities have very high rates, showing that there are considerable qualitative differences within urban environments as well as nature environments. Current urban planning practices need to acknowledge these differences to limit impacts on the biosphere while promoting human wellbeing. We suggest that a good way to start addressing this is through transformation of negatively experienced urban areas through designs that integrate closeness to urbanity with possibilities to have nature experiences on a daily basis. 
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