| 1. |
- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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| 2. |
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| 3. |
- Alexandrov, Ludmil B., et al.
(författare)
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Signatures of mutational processes in human cancer
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 500:7463, s. 415-421
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Tidskriftsartikel (refereegranskat)abstract
- All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
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| 4. |
- Lindberg, Fredrik, 1974, et al.
(författare)
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3D modelling of vegetation within a 2D model – evaluation and application
- 2012
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Ingår i: The Eight International Conference on Urban Climates.. ; :abstract nr 180
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The SOlar and LongWave Environmental Irradiance Geometry (SOLWEIG) model simulates spatial variations of 3D radiation fluxes and mean radiant temperature (Tmrt) as well as shadow patterns in complex urban settings. Here, a new vegetation scheme is presented and evaluated. A new shadow casting algorithm for complex vegetation structures makes it possible to obtain continuous images of shadow patterns and sky view factors taking both buildings and vegetation into account. The model is evaluated using 5 days of integral radiation measurements at two sites within a square surrounded by low-rise buildings and vegetation in Göteborg, Sweden (57°N). There is good agreement between modelled and observed values of Tmrt. Furthermore, SOLWEIG is used to examine vegetation and building morphology characteristics through a north-south LiDAR transect across the megacity of London. It is shown that the contribution of vegetation to the shadowing and reduction of Tmrt at ground level is higher during summer than in autumn. The results from these simulations highlight that vegetation can be most effective at reducing heat stress within dense urban environments in summer. The daytime average Tmrt is found to be lowest in the densest urban environments due to shadowing; foremost from buildings but also from trees. It is clearly shown that this method could be used to quantify the influence of vegetation on Tmrt within the urban environment. The results presented in this paper highlight a number of possible climate sensitive planning practices for urban areas at the local scale.
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| 5. |
- Lindberg, Fredrik, 1974, et al.
(författare)
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Nature of vegetation and building morphology characteristics across a city: Influence on shadow patterns and mean radiant temperatures in London
- 2011
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Ingår i: Urban Ecosystems. - : Springer Science and Business Media LLC. - 1083-8155 .- 1573-1642. ; 14:4, s. 617-634
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Tidskriftsartikel (refereegranskat)abstract
- Vegetation and building morphology characteristics are investigated at 19 sites on a north-south LiDAR transect across the megacity of London. Local maxima of mean building height and building plan area density at the city centre are evident. Surprisingly, the mean vegetation height (zv3) is also found to be highest in the city centre. From the LiDAR data various morphological parameters are derived as well as shadow patterns. Continuous images of the effects of buildings and of buildings plus vegetation on sky view factor (SVF) are derived. A general reduction of SVF is found, indicating the importance of including vegetation when deriving SVF in urban areas. The contribution of vegetation to the shadowing at ground level is higher during summer than in autumn. Using these 3D data the influence on urban climate and mean radiant temperature (Tmrt) is calculated with SOLWEIG. The results from these simulations highlight that vegetation can be most effective at reducing heat stress within dense urban environments in summer. The daytime average Tmrt is found to be lowest in the densest urban environments due to shadowing, foremost from buildings but also from trees. It is clearly shown that this method could be used to quantify the influence of vegetation on Tmrt within the urban environment. The results presented in this paper highlight a number of possible climate sensitive planning practices for urban areas at the local scale (i.e. 102- 5×10^3 m).
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| 6. |
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| 7. |
- Lordian, Thomas, et al.
(författare)
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Local-Scale Urban Meteorological Parameterization Scheme (LUMPS): longwave radiation parameterization and seasonality related developments
- 2011
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Ingår i: Journal of Applied Meteorology and Climatology. - 1558-8424 .- 1558-8432. ; 50, s. 185-202
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Tidskriftsartikel (refereegranskat)abstract
- Recent developments to the Local-scale Urban Meteorological Parameterization Scheme (LUMPS), a simple model able to simulate the urban energy balance are presented. The major development is the coupling of LUMPS to the Net All-Wave Radiation Parameterization (NARP). Others include that the model now accounts for: changing availability of water at the surface; seasonal variations of active vegetation; and the anthropogenic heat flux; while maintaining the need for only commonly available meteorological observations and basic surface characteristics. The incoming component of the longwave radiation (L↓) in NARP is improved through a simple relation derived using cloud cover observations from a ceilometer collected in central London. The new L↓ formulation is evaluated with two independent multi-year datasets (Łódź, Poland and Baltimore, USA) and compared to alternatives that include: the original NARP and a simpler one using the U. S. National Climatic Data Center cloud observation database as input. The performance for the surface energy balance fluxes is assessed using a two year dataset (Łódź). Results have an overall RMSE
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| 8. |
- Loridan, Thomas, et al.
(författare)
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High Resolution Simulation of the Variability of Surface Energy Balance Fluxes Across Central London with Urban Zones for Energy Partitioning
- 2013
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Ingår i: Boundary-Layer Meteorology. - : Springer Netherlands. - 0006-8314 .- 1573-1472. ; 147:3, s. 493-523
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Tidskriftsartikel (refereegranskat)abstract
- The parameterization of surface heat-flux variability in urban areas relies on adequate representation of surface characteristics. Given the horizontal resolutions (e.g. ≈ 0.1–1 km) currently used in numerical weather prediction (NWP) models, properties of the urban surface (e.g. vegetated/built surfaces, street-canyon geometries) often have large spatial variability. Here, a new approach based on Urban Zones to characterize Energy partitioning (UZE) is tested within a NWP model (Weather Research and Forecasting model; WRF v3.2.1) for Greater London. The urban land-surface scheme is the Noah/Single-Layer Urban Canopy Model (SLUCM). Detailed surface information (horizontal resolution 1 km) in central London shows that the UZE offers better characterization of surface properties and their variability compared to default WRF-SLUCM input parameters. In situ observations of the surface energy fluxes and near-surface meteorological variables are used to select the radiation and turbulence parameterization schemes and to evaluate the land-surface scheme and choice of surface parameters. For radiative fluxes, improved performance (e.g. > 25 W m −2 root-mean-square error reduction for the net radiation) is attained with UZE parameters compared to the WRF v3.2.1 default for all three methods from the simplest to the most detailed. The UZE-based spatial fluxes reproduce a priori expectations of greater energy storage and less evaporation in the dense city centre compared to the residential surroundings. Problems in Noah/SLUCM partitioning of energy between the daytime turbulent fluxes are identified with the overestimation of the turbulent sensible heat and underestimation of the turbulent latent heat fluxes.
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| 9. |
- Oh, T. G., et al.
(författare)
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PRMT2 and ROR gamma Expression Are Associated With Breast Cancer Survival Outcomes
- 2014
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Ingår i: Molecular Endocrinology. - : The Endocrine Society. - 0888-8809 .- 1944-9917. ; 28:7, s. 1166-1185
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Tidskriftsartikel (refereegranskat)abstract
- Protein arginine methyltransferases (PRMTs) methylate arginine residues on histones and target transcription factors that play critical roles in many cellular processes, including gene transcription, mRNA splicing, proliferation, and differentiation. Recent studies have linked PRMT-dependent epigenetic marks and modifications to carcinogenesis and metastasis in cancer. However, the role of PRMT2-dependent signaling in breast cancer remains obscure. We demonstrate PRMT2 mRNA expression was significantly decreased in breast cancer relative to normal breast. Gene expression profiling, Ingenuity and protein-protein interaction network analysis after PRMT2-short interfering RNA transfection into MCF-7 cells, revealed that PRMT2-dependent gene expression is involved in cell-cycle regulation and checkpoint control, chromosomal instability, DNA repair, and carcinogenesis. For example, PRMT2 depletion achieved the following: 1) increased p21 and decreased cyclinD1 expression in (several) breast cancer cell lines, 2) decreased cell migration, 3) induced an increase in nucleotide excision repair and homologous recombination DNA repair, and 4) increased the probability of distance metastasis free survival (DMFS). The expression of PRMT2 and retinoid-related orphan receptor-gamma (ROR gamma) is inversely correlated in estrogen receptor-positive breast cancer and increased ROR gamma expression increases DMFS. Furthermore, we found decreased expression of the PRMT2-dependent signature is significantly associated with increased probability of DMFS. Finally, weighted gene coexpression network analysis demonstrated a significant correlation between PRMT2-dependent genes and cell-cycle checkpoint, kinetochore, and DNA repair circuits. Strikingly, these PRMT2-dependent circuits are correlated with pan-cancer metagene signatures associated with epithelial-mesenchymal transition and chromosomal instability. This study demonstrates the role and significant correlation between a histone methyltransferase (PRMT2)-dependent signature, ROR gamma, the cell-cycle regulation, DNA repair circuits, and breast cancer survival outcomes.
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