| 1. |
- Wang, Z., et al.
(författare)
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Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
- 2022
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 54:9, s. 1332-1344
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Tidskriftsartikel (refereegranskat)abstract
- Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention. Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.
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| 2. |
- Kostopoulou, ON, et al.
(författare)
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Targeted Therapy of HPV Positive and Negative Tonsillar Squamous Cell Carcinoma Cell Lines Reveals Synergy between CDK4/6, PI3K and Sometimes FGFR Inhibitors, but Rarely between PARP and WEE1 Inhibitors
- 2022
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- Human papillomavirus positive (HPV+) tonsillar and base of tongue squamous cell carcinoma (TSCC/BOTSCC) have a favorable outcome, but upon relapse, survival is poor and new therapeutical options are needed. Recently, we found synergistic effects by combining the food and drug administration approved (FDA) phosphoinositide 3-kinase (PI3K) and fibroblast-growth-factor-receptor (FGFR) inhibitors BYL719 and JNJ-42756493 on TSCC cell lines. Here this approach was extended and Cyclin-Dependent-Kinase-4/6 (CDK4/6) and Poly-ADP-ribose-polymerase (PARP) and WEE1 inhibitors PD-0332991, and MK-1775 respectively were also examined. HPV+ CU-OP-2, -3, -20, and HPV− CU-OP-17 TSCC cell lines were treated with either BYL719 and JNJ-42756493, PD-0332991 BMN-673 and MK-1775 alone or in different combinations. Viability, proliferation, and cytotoxicity were followed by WST-1 assays and the IncuCyte S3 Live® Cell Analysis System. All inhibitors presented dose-dependent inhibitory effects on tested TSCC lines. Synergy was frequently obtained when combining CDK4/6 with PI3K inhibitors, but only sometimes or rarely when combining CDK4/6 with FGFR inhibitors or PARP with WEE1 inhibitors. To conclude, using CDK4/6 with PI3K or FGFR inhibitors, especially PD-0332991 with BYL719 presented synergy and enhanced the decrease of viability considerably, while although dose dependent responses were obtained with PARP and WEE1 inhibitors (BMN-673 and MK-1775 resp.), synergy was rarely disclosed.
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| 3. |
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| 4. |
- Krege, Susanne, et al.
(författare)
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European consensus conference on diagnosis and treatment of germ cell cancer: A report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): Part I
- 2008
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 53:3, s. 478-496
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Forskningsöversikt (refereegranskat)abstract
- Objectives: The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, Amsterdam, The Netherlands. Methods: Medical oncologists, urological surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference, and incorporated the new data into updated and revised guidelines. As for the first meeting, the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. Results: The first part of the consensus paper describes the clinical presentation of the primary tumor, its treatment, the importance and treatment of testicular intraepithelial neoplasia (TIN), histological classification, staging and prognostic factors, and treatment of stage I seminoma and non-seminoma. Conclusions: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early- and advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged. (C) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 5. |
- Krege, Susanne, et al.
(författare)
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European consensus conference on diagnosis and treatment of germ cell cancer: A report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): Part II
- 2008
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 53:3, s. 497-513
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Forskningsöversikt (refereegranskat)abstract
- Objectives: The first consensus report that had been presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, The Netherlands. Methods: Medical oncologists, urologic surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference and incorporated the new data into updated and revised guidelines. As for the first meeting the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. Results: The second part of the consensus paper includes the treatment of metastasised disease, residual tumour resection, salvage therapy, follow-up, and late toxicities. Conclusions: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early-stage as well as of advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. in addition, the particular needs of testicular cancer survivors have been acknowledged. (C) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 6. |
- Bacchin, Taneha K., et al.
(författare)
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A multi-scale approach in the planning and design of water sensitive environments
- 2013
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Ingår i: Proceedings 8th International Conference NOVATECH Lyon.
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Konferensbidrag (refereegranskat)abstract
- A spatial analytical framework to support landscape planning and urban design practices was introduced in this study aiming to integrate different scales of analysis and their effect when retrofitting Water Sensitive Urban Design (WSUD) in the existing urban environment. The multi-scale analyses are performed using a geographic information system (GIS) platform to capture landscape patterns (spatial structure and composition) and processes (e.g. water cycle). The macro-scale analysis at the urban catchment level allows the development of planning strategies and performance objectives for the urbanized landscape, whilst the meso-scale, comprising the ecological (green) corridors, connects core areas conveying surface flows across the sub-catchments. At the neighbourhood scale, urban form parameters measured the territorial depth (permeability) between public and private land and the suitability of each site to retrofit Water Sensitive Urban Design. The feasibility to improve or extend the existing green-blue landscape matrix is assessed, and its implications discussed, by using a sequence of landscape metrics, land suitability and network analysis techniques. The study focused on modelling opportunities for the introduction of landscape features designed to improve surface stormwater management and, at the same time, provide multiple ecosystem services.
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| 7. |
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| 8. |
- Berghauser Pont, Meta, 1972, et al.
(författare)
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Quantitative comparison of cities : Distribution of street and building types based on density and centrality measures
- 2017
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Ingår i: Proceedings - 11th International Space Syntax Symposium, SSS 2017. - : Instituto Superior Tecnico, Departamento de Engenharia Civil, Arquitetura e Georrecursos. - 9789729899447 ; 2, s. 44.1-44.18
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Konferensbidrag (refereegranskat)abstract
- It has been argued that different urban configurations-planned vs. organic, treelike vs. grid like-perform differently when it comes to the intensity and distribution of pedestrian flows, built density and land uses. However, definitions of urban configurations are often rather abstract, ill-defined and at worse end in fixed stereotypes hiding underlying spatial complexity. Recent publications define morphological typologies based on quantitative variables (e.g. Barthelemy, 2015; Serra, 2013a; Gil et al., 2012; Berghauser Pont and Haupt, 2010) and solve some of these shortcomings. These approaches contribute to the discussion of types in two ways: firstly, they allow for the definition of types based on multiple variables in a precise and repeattable manner, enabling the study of large samples and the comparison between both cities and regions; secondly, they frame design choices in terms of types without being fixed and so open up for design explorations where the relation between the variables can be challenged to propose new types. This paper explores the typologies defined by Serra (2013a) and Berghauser Pont and Haupt (2010) further, as these target two of the most important morphological entities of urban form, namely the street network and the building structure. The purpose is to gain a better understanding of how types are composed and distributed within and across different cities. The method is based on GIS and statistical modeling of four cities to allow for a comparative analysis of four cities: Amsterdam, London, Stockholm and Gothenburg. For the street network, we process the Road-Centre-line maps to obtain a clean network model, then run segment angular analysis to calculate the space syntax measures of betweenness at different metric radii, defining the "centrality palimpsest" (Serra, 2013a). For the building structure, we process elevation data to obtain building height, then run accessible density analysis for all building density metrics (FSI, GSI, OSR, L) using the Place Syntax Tool (Berghauser Pont and Marcus, 2014). The street and building types are defined using cluster analysis (unsupervised classification), following a similar approach to Serra (2013a). The result is a typology of street ('paths') and building types ('places'), with different profiles of centrality and density across scales. The spatial distribution and frequency of these types across the four cities gives an objective summary of their spatial structure, identifying common as well as unique traits.
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| 9. |
- Berghauser Pont, Meta, 1972, et al.
(författare)
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The spatial distribution and frequency of street, plot and building types across five European cities
- 2019
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Ingår i: Environment and Planning B-Urban Analytics and City Science. - : SAGE Publications. - 2399-8083 .- 2399-8091. ; 46:7, s. 1226-1242
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Tidskriftsartikel (refereegranskat)abstract
- Typologies have always played an important role in urban planning and design practice and formal studies have been central to the field of urban morphology. These studies have predominantly been of a historical-qualitative nature and do not support quantitative comparisons between urban areas and between different cities, nor offer the precise and comprehensive descriptions needed by those engaged in urban planning and design practice. To describe contemporary urban forms, which are more diffuse and often elude previous historic typologies, systematic quantitative methods can be useful but, until recently, these have played a limited role in typo-morphological studies. This paper contributes to recent developments in this field by integrating multi-variable geometric descriptions with inter-scalar relational descriptions of urban form. It presents typologies for three key elements of urban form (streets, plots and buildings) in five European cities, produced using statistical clustering methods. In a first instance, the resulting typologies contribute to a better understanding of the characteristics of streets, plots and buildings. In particular, the results offer insight into patterns between the types (i.e. which types are found in combination and which not) and provide a new large scale comparative analysis across five European cities. To conclude, a link between quantitative analysis and theory is established, by testing two well-known theoretical propositions in urban morphology: the concept of the burgage cycle and the theory of natural movement.
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| 10. |
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| 11. |
- Eldesoky, Ahmed H.M., et al.
(författare)
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The suitability of the urban local climate zone classification scheme for surface temperature studies in distinct macroclimate regions
- 2021
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Ingår i: Urban Climate. - : Elsevier BV. - 2212-0955. ; 37
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Tidskriftsartikel (refereegranskat)abstract
- The Local Climate Zone (LCZ) classification scheme, initially designed to distinguish between standard built (urban) and non-built (land cover) types in terms of screen-level air temperature relevant for urban heat island (UHI) studies, has been widely used for land surface temperature (LST) and surface urban heat island (SUHI) studies. However, some concerns remain about the global suitability of the scheme for LST and SUHI studies in different macroclimate regions. By analyzing and comparing a large number of representative LCZ sites and multi-year remotely-sensed LST data, the aim of this work is twofold. Firstly, to study the suitability of the LCZ scheme, with a focus on the built types, for surface temperature studies in four distinct macroclimate regions, namely, the tropical, the arid, the temperate and the cold. Secondly, to understand the influence of the macroclimate region on the LST and SUHI characteristics of the standard LCZ built types. Results show that the urban LCZ standard scheme is applicable, with varying degrees, to all macroclimate regions other than the arid, where a LCZ subclassification might be essential. Also, it has been demonstrated that most LCZ built types exhibit significantly different LST and SUHI characteristics across the remaining macroclimate regions.
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| 12. |
- Gordon, Euan, 1971, et al.
(författare)
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Effective high-throughput overproduction of membrane proteins in Escherichia coli
- 2008
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Ingår i: Protein Expression and Purification. - : Elsevier BV. - 1096-0279 .- 1046-5928. ; 62:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Structural biology is increasingly reliant on elevated throughput methods for protein production. In particular, development of efficient methods of heterologous production of membrane proteins is essential. Here, we describe the heterologous overproduction of 24 membrane proteins from the human pathogen Legionella pneumophila in Escherichia coli. Protein production was performed in 0.5 ml cultures in standard 24-well plates, allowing increased throughput with minimal effort. The effect of the location of a histidine purification tag was analyzed, and the effect of decreasing the length of the N- and C-terminal extensions introduced by the Gateway cloning strategy is presented. We observed that the location and length of the purification tag significantly affected protein production levels. In addition, an auto-induction protocol for membrane protein expression was designed to enhance the overproduction efficiency such that, regardless of the construct used, much higher expression was achieved when compared with standard induction approaches such as isopropyl-β-d-thiogalactopyranoside (IPTG). All 24 targets were produced at levels exceeding 2 mg/l, with 18 targets producing at levels of 5 mg/l or higher. In summary, we have designed a fast and efficient process for the production of medically relevant membrane proteins with a minimum number of screening parameters.
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| 13. |
- Karlsson, Stefan M., et al.
(författare)
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Illuminance Flow Estimation by Regression
- 2010
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Ingår i: International Journal of Computer Vision. - Amsterdam : Elsevier. - 0920-5691 .- 1573-1405. ; 90:3, s. 304-312
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the estimation of illuminance flow using Histograms of Oriented Gradient features (HOGs). In a regression setting, we found for both ridge regression and support vector machines, that the optimal solution shows close resemblance to the gradient based structure tensor (also known as the second moment matrix). Theoretical results are presented showing in detail how the structure tensor and the HOGs are connected. This relation will benefit computer vision tasks such as affine invariant texture/object matching using HOGs. Several properties of HOGs are presented, among others, how many bins are required for a directionality measure, and how to estimate HOGs through spatial averaging that requires no binning.
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| 14. |
- Mayer, Ludovic, et al.
(författare)
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Widespread Pesticide Distribution in the European Atmosphere Questions their Degradability in Air
- 2024
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Ingår i: Environmental Science and Technology. - 0013-936X. ; 58:7, s. 3342-3352
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Tidskriftsartikel (refereegranskat)abstract
- Risk assessment of pesticide impacts on remote ecosystems makes use of model-estimated degradation in air. Recent studies suggest these degradation rates to be overestimated, questioning current pesticide regulation. Here, we investigated the concentrations of 76 pesticides in Europe at 29 rural, coastal, mountain, and polar sites during the agricultural application season. Overall, 58 pesticides were observed in the European atmosphere. Low spatial variation of 7 pesticides suggests continental-scale atmospheric dispersal. Based on concentrations in free tropospheric air and at Arctic sites, 22 pesticides were identified to be prone to long-range atmospheric transport, which included 15 substances approved for agricultural use in Europe and 7 banned ones. Comparison between concentrations at remote sites and those found at pesticide source areas suggests long atmospheric lifetimes of atrazine, cyprodinil, spiroxamine, tebuconazole, terbuthylazine, and thiacloprid. In general, our findings suggest that atmospheric transport and persistence of pesticides have been underestimated and that their risk assessment needs to be improved.
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| 15. |
- Nordström, Birgitta, et al.
(författare)
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The Geneva-Copenhagen Survey of the Solar Neighbourhood
- 2004
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Ingår i: Publications Astronomical Society of Australia. - 1448-6083. ; 21:2, s. 129-133
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Tidskriftsartikel (refereegranskat)abstract
- We report on a new survey of metallicities, ages, and Galactic orbitsfor a complete, magnitude-limited, and kinematically unbiased all-skysample of 16682 nearby F- and G-dwarfs. Our~63000 new, accurate radialvelocities for nearly 13500 of the stars, combined with Hipparcosparallaxes and Tycho-2 proper motions, complete the kinematic data for14139 stars and allow us to identify most of the binary stars in thesample. Isochrone ages have been determined whenever reliable resultsare possible, with particular attention to realistic error estimates.Among the basic properties of the Galactic disk that can bereinvestigated from our data are the metallicity distribution ofG-dwarfs and the age-metallicity and age-velocity relations of the solarneighbourhood. We confirm the lack of metal-poor G-dwarfs relative toclassical model predictions (the `G-dwarf problem'), the near-constancyof the mean metallicity since the formation of the thin disk, and theappearance of the kinematic signature of the thick disk ~ 10Gyr ago.
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| 16. |
- Nordström, Birgitta, et al.
(författare)
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The Geneva-Copenhagen survey of the Solar neighbourhood. Ages, metallicities, and kinematic properties of ∼14 000 F and G dwarfs
- 2004
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 418:3, s. 989-1019
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Forskningsöversikt (refereegranskat)abstract
- We present and discuss new determinations of metallicity, rotation, age,kinematics, and Galactic orbits for a complete, magnitude-limited, andkinematically unbiased sample of 16 682 nearby F and G dwarf stars. Our∼63 000 new, accurate radial-velocity observations for nearly 13 500stars allow identification of most of the binary stars in the sampleand, together with published uvbyβ photometry, Hipparcosparallaxes, Tycho-2 proper motions, and a few earlier radial velocities,complete the kinematic information for 14 139 stars. These high-qualityvelocity data are supplemented by effective temperatures andmetallicities newly derived from recent and/or revised calibrations. Theremaining stars either lack Hipparcos data or have fast rotation. Amajor effort has been devoted to the determination of new isochrone agesfor all stars for which this is possible. Particular attention has beengiven to a realistic treatment of statistical biases and errorestimates, as standard techniques tend to underestimate these effectsand introduce spurious features in the age distributions. Our ages agreewell with those by Edvardsson et al. (cite{edv93}), despite severalastrophysical and computational improvements since then. We demonstrate,however, how strong observational and theoretical biases cause thedistribution of the observed ages to be very different from that of thetrue age distribution of the sample. Among the many basic relations ofthe Galactic disk that can be reinvestigated from the data presentedhere, we revisit the metallicity distribution of the G dwarfs and theage-metallicity, age-velocity, and metallicity-velocity relations of theSolar neighbourhood. Our first results confirm the lack of metal-poor Gdwarfs relative to closed-box model predictions (the ``G dwarfproblem''), the existence of radial metallicity gradients in the disk,the small change in mean metallicity of the thin disk since itsformation and the substantial scatter in metallicity at all ages, andthe continuing kinematic heating of the thin disk with an efficiencyconsistent with that expected for a combination of spiral arms and giantmolecular clouds. Distinct features in the distribution of the Vcomponent of the space motion are extended in age and metallicity,corresponding to the effects of stochastic spiral waves rather thanclassical moving groups, and may complicate the identification ofthick-disk stars from kinematic criteria. More advanced analyses of thisrich material will require careful simulations of the selection criteriafor the sample and the distribution of observational errors.Based on observations made with the Danish 1.5-m telescope at ESO, LaSilla, Chile, and with the Swiss 1-m telescope at Observatoire deHaute-Provence, France.Complete Tables 1 and 2 are only available in electronic form at the CDSvia anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or viahttp://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/418/989
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| 17. |
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| 18. |
- Pont, M. B., et al.
(författare)
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Using urban form to increase the capacity of cities to manage noise and air quality
- 2023
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Ingår i: Urban Morphology. - : International Seminar on Urban Form. - 1027-4278. ; 27:1, s. 51-69
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Tidskriftsartikel (refereegranskat)abstract
- The top two environmental factors adversely affecting human health in Europe are air and noise pollution, with road traffic being the largest source. Urban density plays an important role in reducing car traffic. However, the benefits of reduced emissions per capita can still mean higher emissions locally, because of the number of people in the area. Therefore, this paper investigates how morphological parameters influence the local distribution of noise and air pollution. A parametric approach, based on the Spacematrix method, is used to study the impact of morphological parameters on the distribution of air and noise pollution, controlling for traffic mode, flows and speed. To compare the impact of exposure to noise and air pollution, their respective health burden is calculated using disability-adjusted life years (DALYs). The results, based on 31 models of different forms, show that the degree of openness greatly affects performance with opposite effects for noise and air pollution. Building types with slightly open yards, like open corner blocks, may provide an attractive compromise solution due to their relatively good noise exposure situation at the same time as the dispersion of air pollutants improves. Adding sound absorbing vegetation is an effective measure to mitigate noise, especially for blocks with openings, limiting the propagation of sound into the yard. Further, densification is beneficial for health if the increase in density does not increase traffic volume in the same proportion. Densification by adding towers on a perimeter building block gives the best results for health as it combines a less noisy yard, thanks to the enclosure of the yard with towers, which enhances turbulent mixing of air within the street canyon.
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