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1.
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2.
  • Karlsson, Anna K, et al. (författare)
  • Genome-wide DNA methylation analysis of lung carcinoma reveals one neuroendocrine and four adenocarcinoma epitypes associated with patient outcome.
  • 2014
  • Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - AMER ASSOC CANCER RESEARCH. - 1078-0432. ; 20:23, s. 6127-6140
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Lung cancer is the worldwide leading cause of death from cancer. DNA methylation in gene promoter regions is a major mechanism of gene expression regulation that may promote tumorigenesis. However, whether clinically relevant subgroups based on DNA methylation patterns exist in lung cancer remains unclear. Experimental Design: Whole-genome DNA methylation analysis using 450K Illumina BeadArrays was performed on 12 normal lung tissues and 124 tumors including 83 adenocarcinomas, 23 squamous cell carcinomas (SqCC), one adenosquamous cancer, five large cell carcinomas, nine large cell neuroendocrine carcinomas (LCNEC), and three small cell carcinomas (SCLC). Unsupervised bootstrap clustering was performed to identify DNA methylation subgroups, which were validated in 695 adenocarcinomas and 122 SqCCs. Subgroups were characterized by clinicopathological factors, whole-exome sequencing data, and gene expression profiles. Results: Unsupervised analysis identified five DNA methylation subgroups (epitypes). One epitype was distinctly associated with neuroendocrine tumors (LCNEC and SCLC). For adenocarcinoma, remaining four epitypes were associated with unsupervised and supervised gene expression phenotypes, and differences in molecular features including global hypomethylation, promoter hypermethylation, genomic instability, expression of proliferation-associated genes, and mutations in KRAS, TP53, KEAP1, SMARCA4, and STK11. Furthermore, these epitypes were associated with clinicopathological features such as smoking history, and patient outcome. Conclusions: Our findings highlight one neuroendocrine and four adenocarcinoma epitypes associated with molecular and clinicopathological characteristics, including patient outcome. This study highlights the possibility to further subgroup lung cancer, and more specifically adenocarcinomas, based on epigenetic/molecular classification that could lead to more accurate tumor classification, prognostication, and tailored patient therapy.
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3.
  • Staaf, Johan, et al. (författare)
  • Relation between smoking history and gene expression profiles in lung adenocarcinomas
  • 2012
  • Ingår i: BMC Medical Genomics. - BioMed Central. - 1755-8794. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Lung cancer is the worldwide leading cause of death from cancer. Tobacco usage is the major pathogenic factor, but all lung cancers are not attributable to smoking. Specifically, lung cancer in never-smokers has been suggested to represent a distinct disease entity compared to lung cancer arising in smokers due to differences in etiology, natural history and response to specific treatment regimes. However, the genetic aberrations that differ between smokers and never-smokers' lung carcinomas remain to a large extent unclear. Methods: Unsupervised gene expression analysis of 39 primary lung adenocarcinomas was performed using Illumina HT-12 microarrays. Results from unsupervised analysis were validated in six external adenocarcinoma data sets (n=687), and six data sets comprising normal airway epithelial or normal lung tissue specimens (n=467). Supervised gene expression analysis between smokers and never-smokers were performed in seven adenocarcinoma data sets, and results validated in the six normal data sets. Results: Initial unsupervised analysis of 39 adenocarcinomas identified two subgroups of which one harbored all never-smokers. A generated gene expression signature could subsequently identify never-smokers with 79-100% sensitivity in external adenocarcinoma data sets and with 76-88% sensitivity in the normal materials. A notable fraction of current/former smokers were grouped with never-smokers. Intriguingly, supervised analysis of never-smokers versus smokers in seven adenocarcinoma data sets generated similar results. Overlap in classification between the two approaches was high, indicating that both approaches identify a common set of samples from current/former smokers as potential never-smokers. The gene signature from unsupervised analysis included several genes implicated in lung tumorigenesis, immune-response associated pathways, genes previously associated with smoking, as well as marker genes for alveolar type II pneumocytes, while the best classifier from supervised analysis comprised genes strongly associated with proliferation, but also genes previously associated with smoking. Conclusions: Based on gene expression profiling, we demonstrate that never-smokers can be identified with high sensitivity in both tumor material and normal airway epithelial specimens. Our results indicate that tumors arising in never-smokers, together with a subset of tumors from smokers, represent a distinct entity of lung adenocarcinomas. Taken together, these analyses provide further insight into the transcriptional patterns occurring in lung adenocarcinoma stratified by smoking history.
4.
  • Alström, Per, et al. (författare)
  • Dramatic niche shifts and morphological change in two insular bird species
  • 2015
  • Ingår i: Royal Society Open Science. - 2054-5703. ; 2
  • Tidskriftsartikel (refereegranskat)abstract
    • Colonizations of islands are often associated with rapid morphological divergence. We present two previously unrecognized cases of dramatic morphological change and niche shifts in connection with colonization of tropical forest-covered islands. These evolutionary changes have concealed the fact that the passerine birds madanga, Madanga ruficollis, from Buru, Indonesia, and São Tomé shorttail, Amaurocichla bocagii, from São Tomé, Gulf of Guinea, are forest-adapted members of the family Motacillidae (pipits and wagtails). We show that Madanga has diverged mainly in plumage, which may be the result of selection for improved camouflage in its new arboreal niche, while selection pressures for other morphological changes have probably been weak owing to preadaptations for the novel niche. By contrast, we suggest that Amaurocichla's niche change has led to divergence in both structure and plumage.
5.
  • Aronsson, Per, et al. (författare)
  • An operational decision support tool for stump harvest
  • 2011
  • Konferensbidrag (övrigt vetenskapligt)abstract
    • A multi-criteria decision support tool was developed to optimise stump harvesting for energy in Sweden. The decision tool takes account of multiple, sometimes conflicting, criteria relating to stump harvest; energy and climate, economics, biodiversity, and soil and water. Data on harvested stems are used as primary input data in the tool. Such data are routinely collected in harvester computers. The tool effectively deals with mixed sets of data; quantitative harvest data are re-calculated to metric (e.g. stump biomass), and qualitative data (e.g. biodiversity implications) are incorporated. A digital terrain map derived from air-borne laser scanning provides basic data for estimating soil wetness, while digital maps of water courses, key habitats and protected areas, or other sensitive habitats, are used to identify potentially and practically harvestable stumps.In four sub-models, an index from 0 to 10 is calculated for each stump, with 0 representing ‘Not at all suitable’ and 10 ‘Highly suitable for extraction’. Through this, a stump of high value for wood-living species is assigned a low index in the biodiversity sub-model and a large, easily accessible stump is assigned a high index in the economic sub-model. When calculating the net index, the sub-indices can be weighted according to the preferences of the end-user.An energy and climate sub-model incorporates greenhouse gas (GHG) emissions from forest operations and the effect of advancing GHG emissions when stump biomass is incinerated instead of being left to decompose. In the economic sub-model the potential monetary return from each stump is calculated based on estimated revenue from harvested stump biomass and the costs of stump harvesting and forwarding operations (based on cost functions and GIS calculations of transport distances).The biodiversity sub-model considers four types of wood-dependent organisms (lichens, mosses, insects and fungi) in terms of their habitat requirements, vulnerability, sun exposure preferences, locality, etc. A panel of external experts has drawn up a grading scale of stump values for the different taxonomic groups. The proximity to key habitats and exposure to sunlight are derived from a spatial model.Soil and water issues are handled within a sub-model estimating the consequences for long-term soil fertility (nutrient cycling and soil compaction) and water (leaching of plant nutrients and mercury, and particle transport due to soil damage by heavy machinery).The tool offers the end-user possibilities to prioritise and plan for cost-effective stump harvesting, while minimising negative environmental impacts.
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6.
  • Blom, Kristin, et al. (författare)
  • Eosinophil associated genes in the inflammatory bowel disease 4 region : Correlation to inflammatory bowel disease revealed
  • 2012
  • Ingår i: World Journal of Gastroenterology. - 1007-9327. ; 18:44, s. 6409-6419
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: To study the association between inflammatory bowel disease (IBD) and genetic variations in eosinophil protein X (EPX) and eosinophil cationic protein (ECP). METHODS: DNA was extracted from ethylene diamine tetraacetic acid blood of 587 patients with Crohn's disease (CD), 592 with ulcerative colitis (UC) and 300 healthy subjects. The EPX405 (G > C, rs2013109), ECP434 (G > C, rs2073342) and ECP562 (G > C, rs2233860) gene polymorphisms were analysed, by the 5'-nuclease allelic discrimination assay. For determination of intracellular content of EPX and ECP in granulocytes, 39 blood samples was collected and extracted with a buffer containing cetyltrimethylammonium bromide. The intracellular content of EPX was analysed using an enzyme-linked immunosorbent assay. The intracellular content of ECP was analysed with the UniCAP (R) system as described by the manufacturer. Statistical tests for calculations of results were chi(2) test, Fisher's exact test, ANOVA, Student-Newman-Keuls test, and Kaplan-Meier survival curve with Log-rank test for trend, the probability values of P < 0.05 were considered statistically significant. RESULTS: The genotype frequency for males with UC and with an age of disease onset of >= 45 years (n = 57) was for ECP434 and ECP562, GG = 37%, GC = 60%, CC = 4% and GG = 51%, GC = 49%, CC = 0% respectively. This was significantly different from the healthy subject's genotype frequencies of ECP434 (GG = 57%, GC = 38%, CC = 5%; P = 0.010) and ECP562 (GG = 68%, GC = 29 /0,CC = 3%; P = 0.009). The genotype frequencies for females, with an age of disease onset of >= 45 years with CD (n = 62), was for the ECP434 and ECP562 genotypes GG = 37%, GC = 52%, CC = 11% and GG = 48%, GC = 47% and CC = 5% respectively. This was also statistically different from healthy controls for both ECP434 (P = 0.010) and ECP562 (P = 0.013). The intracellular protein concentration of EPX and ECP was calculated in mu g/10(6) eosinophils and then correlated to the EPX 405 genotypes. The protein content of EPX was highest in the patients with the CC genotype of EPX405 (GG = 4.65, GC = 5.93, and CC = 6.57) and for ECP in the patients with the GG genotype of EPX405 (GG = 2.70, GC = 2.47 and CC = 1.90). ANOVA test demonstrated a difference in intracellular protein content for EPX (P = 0.009) and ECP (P = 0.022). The age of disease onset was linked to haplotypes of the EPX405, ECP434 and ECP562 genotypes. Kaplan Maier curve showed a difference between haplotype distributions for the females with CD (P = 0.003). The highest age of disease onset was seen in females with the EPX405CC, ECP434GC, ECP562CC haplotype (34 years) and the lowest in females with the EPX405GC, ECP434GC, ECP562GG haplotype (21 years). For males with UC there was also a difference between the highest and lowest age of the disease onset (EPX405CC, ECP434CC, ECP562CC, mean 24 years vs EPX405GC, ECP434GC, ECP562GG, mean 34 years, P = 0.0009). The relative risk for UC patients with ECP434 or ECP562-GC/CC genotypes to develop dysplasia/cancer was 2.5 (95%CI: 1.2-5.4, P = 0.01) and 2.5 (95%CI: 1.1-5.4, P = 0.02) respectively, compared to patients carrying the GG-genotypes. CONCLUSION: Polymorphisms of EPX and ECP are associated to IBD in an age and gender dependent manner, suggesting an essential role of eosinophils in the pathophysiology of IBD.
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7.
  • Brunnström, Hans, et al. (författare)
  • Immunohistochemistry in the differential diagnostics of primary lung cancer: an investigation within the southern Swedish lung cancer study.
  • 2013
  • Ingår i: American journal of clinical pathology. - AMER SOC CLINICAL PATHOLOGY. - 0002-9173 .- 1943-7722. ; 140:1, s. 37-46
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To assess immunohistochemical (IHC) stains differentially expressed between different types of lung cancer. Methods: We evaluated 16 different IHC stains in 209 prospectively included, surgically treated primary lung cancers, including 121 adenocarcinomas, 65 squamous cell carcinomas, 15 large-cell carcinomas, 5 adenosquamous carcinomas, 2 sarcomatoid carcinomas, and 1 small-cell carcinoma, using the tissue microarray technique. Results: Cytokeratin 5 (CK5) and P63 were both positive in 10% or more of the cells in 97% of the squamous cell carcinomas, with the former being positive (<10% of the cells) in only 2 non-squamous cell carcinomas. Thyroid transcription factor 1 (TTF1) and napsin A were positive in 10% or more of the cells in 88% and 87% of the adenocarcinomas, respectively, with 94% of the adenocarcinomas being positive in at least 1 marker. Fifteen percent of the adenocarcinomas were positive for estrogen receptor. Conclusions: CK5, TTF1, and napsin A are sensitive markers for squamous cell carcinoma and adenocarcinoma of the lung.
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8.
  • Grumer, Jon, et al. (författare)
  • Unexpected transitions induced by spin-dependent, hyperfine and external magnetic-field interactions
  • 2014
  • Ingår i: Physica Scripta. - IOP Publishing Ltd. - 0031-8949. ; 89:11, s. 114002
  • Tidskriftsartikel (refereegranskat)abstract
    • Unexpected transitions are induced by weaker interactions not included in the gross structure model of the ion under investigation. We discuss different examples of such decay channels, starting with relativistic spin-induced transitions. These represented an important field of study a few decades ago, and we illustrate how some challenging cases can be treated very accurately with today's computational techniques, while close degeneracy sometimes still prevents ab initio methods from obtaining accurate results. For hyperfine induced transitions we review some recent results and discuss remaining challenges for experiment and theory. Finally, we discuss the newly opened field of accurate calculations for transitions induced by an external magnetic field and point to some examples of where these are accessible for experimental tests.
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9.
  • Henningsson, Marianne, 1950-, et al. (författare)
  • Perceived landscape values and public participation in a road-planning process - a case study in Sweden
  • 2015
  • Ingår i: Journal of Environmental Planning and Management. - 0964-0568. ; 58:4, s. 631-653
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Landscape Convention indicates that assessment of different dimensions that exist in landscapes should be taken into account in planning. In this study, we first investigated ecological, cultural and social values as perceived by the local people in a highway-planning process in Sweden. Next, we explored which factors influenced the local people's participation in the road-planning process. We used questionnaires, planning documents and the Theory of Planned Behavior to investigate the relations between different factors and local people's participation in the planning process. The results showed that people presumed the ecological values in the landscape to be adversely affected by the new road, while the social values would remain the same. Landowners had heard of the participatory-process, but few participated. Those who lived within 300m of the road were more active in the planning process than people living further away. The findings suggest that people living within a few hundred metres of the road should be treated as key stakeholders in the planning process. The involvement of other stakeholders, and when in the public participation process stakeholders should be involved, is also discussed.
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