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- Holmquist Mengelbier, Linda, et al.
(författare)
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Intratumoral genome diversity parallels progression and predicts outcome in pediatric cancer.
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Genetic differences among neoplastic cells within the same tumour have been proposed to drive cancer progression and treatment failure. Whether data on intratumoral diversity can be used to predict clinical outcome remains unclear. We here address this issue by quantifying genetic intratumoral diversity in a set of chemotherapy-treated childhood tumours. By analysis of multiple tumour samples from seven patients we demonstrate intratumoral diversity in all patients analysed after chemotherapy, typically presenting as multiple clones within a single millimetre-sized tumour sample (microdiversity). We show that microdiversity often acts as the foundation for further genome evolution in metastases. In addition, we find that microdiversity predicts poor cancer-specific survival (60%; P=0.009), independent of other risk factors, in a cohort of 44 patients with chemotherapy-treated childhood kidney cancer. Survival was 100% for patients lacking microdiversity. Thus, intratumoral genetic diversity is common in childhood cancers after chemotherapy and may be an important factor behind treatment failure.
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- Hordoir, Robinson, et al.
(författare)
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Nemo-Nordic 1.0 : a NEMO-based ocean model for the Baltic and North seas - research and operational applications
- 2019
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 12:1, s. 363-386
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Tidskriftsartikel (refereegranskat)abstract
- We present Nemo-Nordic, a Baltic and North Sea model based on the NEMO ocean engine. Surrounded by highly industrialized countries, the Baltic and North seas and their assets associated with shipping, fishing and tourism are vulnerable to anthropogenic pressure and climate change. Ocean models providing reliable forecasts and enabling climatic studies are important tools for the shipping infrastructure and to get a better understanding of the effects of climate change on the marine ecosystems. Nemo-Nordic is intended to be a tool for both short-term and long-term simulations and to be used for ocean forecasting as well as process and climatic studies. Here, the scientific and technical choices within Nemo-Nordic are introduced, and the reasons behind the design of the model and its domain and the inclusion of the two seas are explained. The model's ability to represent barotropic and baroclinic dynamics, as well as the vertical structure of the water column, is presented. Biases are shown and discussed. The short-term capabilities of the model are presented, especially its capabilities to represent sea level on an hourly timescale with a high degree of accuracy. We also show that the model can represent longer timescales, with a focus on the major Baltic inflows and the variability in deep-water salinity in the Baltic Sea.
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- Pan, Gang, et al.
(författare)
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PATZ1 down-regulates FADS1 by binding to rs174557 and is opposed by SP1/SREBP1c
- 2017
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 45:5, s. 2408-2422
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Tidskriftsartikel (refereegranskat)abstract
- The FADS1 and FADS2 genes in the FADS cluster encode the rate-limiting enzymes in the synthesis of long-chain polyunsaturated fatty acids (LC-PUFAs). Genetic variation in this region has been associated with a large number of diseases and traits many of them correlated to differences in metabolism of PUFAs. However, the causative variants leading to these associations have not been identified. Here we find that the multiallelic rs174557 located in an AluYe5 element in intron 1 of FADS1 is functional and lies within a PATZ1 binding site. The derived allele of rs174557, which is the common variant in most populations, diminishes binding of PATZ1, a transcription factor conferring allele-specific downregulation of FADS1 The PATZ1 binding site overlaps with a SP1 site. The competitive binding between the suppressive PATZ1 and the activating complex of SP1 and SREBP1c determines the enhancer activity of this region, which regulates expression of FADS1.
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- Shehata, Adam, 1981, et al.
(författare)
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Television Channel Content Profiles and Differential Knowledge Growth : A Test of The Inadvertent Learing Hypothesis Using Panel Data
- 2015
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Ingår i: Political Communication. - : Informa UK Limited. - 1058-4609 .- 1091-7675. ; 32:3, s. 377-395
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Tidskriftsartikel (refereegranskat)abstract
- This study uses four waves of panel data to analyze inadvertent learning—that is, learning in the absence of interest or motivation—from watching public service television channels. Previous research suggests that motivation-based gaps in political knowledge are at least partly a function of the political information opportunities provided by the major television channels in a country, which influence the likelihood of being inadvertently exposed to news and current affairs programs. The present study puts the inadvertent learning hypothesis to a thorough empirical test by analyzing individual-level growth in knowledge over time, based on panel data collected during five months leading up to the Swedish 2010 national election. Using multilevel growth curve modeling and an extensive battery of surveillance knowledge questions, the results show not only (a) that public service channel viewing was related to learning, but also (b) that knowledge growth occurred among public service viewers independently of their political motivation and news attention, and (c) that such learning was even more pronounced among viewers lacking an interest in politics. The findings are discussed in light of ongoing media environmental transformations as well as cross-national comparative media systems research.
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- Zeng, Chenjie, et al.
(författare)
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Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus
- 2016
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.
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