| 1. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 2. |
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Overview of the JET results
- 2015
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In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 55:10
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Journal article (peer-reviewed)
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| 3. |
- Angelopoulos, V., et al.
(author)
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First Results from the THEMIS Mission
- 2008
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In: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 141:1-4, s. 453-476
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Research review (peer-reviewed)abstract
- THEMIS was launched on February 17, 2007 to determine the trigger and large-scale evolution of substorms. During the first seven months of the mission the five satellites coasted near their injection orbit to avoid differential precession in anticipation of orbit placement, which started in September 2007 and led to a commencement of the baseline mission in December 2007. During the coast phase the probes were put into a string-of-pearls configuration at 100 s of km to 2 R-E along-track separations, which provided a unique view of the magnetosphere and enabled an unprecedented dataset in anticipation of the first tail season. In this paper we describe the first THEMIS substorm observations, captured during instrument commissioning on March 23, 2007. THEMIS measured the rapid expansion of the plasma sheet at a speed that is commensurate with the simultaneous expansion of the auroras on the ground. These are the first unequivocal observations of the rapid westward expansion process in space and on the ground. Aided by the remote sensing technique at energetic particle boundaries and combined with ancillary measurements and MHD simulations, they allow determination and mapping of space currents. These measurements show the power of the THEMIS instrumentation in the tail and the radiation belts. We also present THEMIS Flux Transfer Events (FTE) observations at the magnetopause, which demonstrate the importance of multi-point observations there and the quality of the THEMIS instrumentation in that region of space.
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| 4. |
- Bärebring, Linnea, et al.
(author)
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Use of bioelectrical impedance analysis to monitor changes in fat-free mass during recovery from colorectal cancer– a validation study
- 2020
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In: Clinical Nutrition ESPEN. - : Elsevier BV. - 2405-4577. ; 40, s. 201-207
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Journal article (peer-reviewed)abstract
- Background & aims: Although previous research show high correlation between fat-free mass (FFM) measured by bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA), the validity of BIA to track longitudinal changes in FFM is uncertain. Thus, the aim of this study was to validate the ability of BIA to assess changes in FFM during 6 months of recovery from non-metastatic colorectal cancer (CRC). Methods: A total of 136 women and men (50–80 years) with stage I-III CRC and a wide range of baseline FFM (35.7–73.5 kg) were included in the study. Body composition was measured at study baseline within 2–9 months of surgery and again 6 months later. Whole-body BIA FFM estimates (FFMBIA) were calculated using three different equations (manufacturer's, Schols' and Gray's) before comparison to FFM estimates obtained by DXA (FFMDXA). Results: Correlation between changes in FFMBIA and FFMDXA was intermediate regardless of equation (r ≈ 0.6). The difference in change of FFMBIA was significant compared to FFMDXA, using all three equations and BIA overestimated both loss and gain. However, BIA showed 100% sensitivity and about 90% specificity to identify individuals with ≥5% loss in FFM, using all three equations. Sensitivity of FFMBIA to detect a smaller loss of FFM (60–76%) or a gain in FFM of ≥5% (33–62%) was poor. Conclusion: In a well-nourished population of non-metastatic CRC patients, a single-frequency whole-body BIA device yielded imprecise data on changes in FFM, regardless of equation. BIA is thus not a valid option for quantifying changes in FFM in individuals. However, BIA could be used to identify patients with loss in FFM ≥5% in this population. The validity of BIA to monitor changes in FFM warrants further investigation before implementation in clinical praxis. © 2020 The Author(s)
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| 5. |
- Northcott, Paul A, et al.
(author)
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Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma.
- 2014
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 511:7510, s. 428-428
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Journal article (peer-reviewed)abstract
- Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.
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| 6. |
- Heinke, Reinhard, et al.
(author)
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First on-line application of the high-resolution spectroscopy laser ion source PI-LIST at ISOLDE
- 2023
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In: Nuclear Instruments and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms. - 0168-583X. ; 541, s. 8-12
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Journal article (peer-reviewed)abstract
- We report on the development, characterization, and first application of a specialized resonance ionization laser ion source for high-resolution spectroscopy applications below usual hot cavity Doppler broadening limitations, for on-line experiments at CERN-ISOLDE. The new PI-LIST ion source comprises perpendicular laser/atom beam interaction in a radio-frequency quadrupole unit directly downstream the hot atomizer cavity. A spectral linewidth of 200–300 MHz is demonstrated, with the potential to achieve below 100 MHz. Compared to standard in-source laser ionization, the efficiency reduction factor ranges from a few 100 to above 1000. The implementation of this ion source concept at thick target radioactive ion beam facilities will greatly enhance capabilities for nuclear structure investigations without demanding dedicated experimental beam line setups, and will facilitate the delivery of isomer-pure beams to experimental stations.
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| 7. |
- Hertel, J K, et al.
(author)
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Genetic analysis of recently identified type 2 diabetes loci in 1,638 unselected patients with type 2 diabetes and 1,858 control participants from a Norwegian population-based cohort (the HUNT study)
- 2008
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In: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 51:6, s. 971-977
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Journal article (peer-reviewed)abstract
- Aims/hypothesis Recent genome-wide association studies performed in selected patients and control participants have provided strong support for several new type 2 diabetes susceptibility loci. To get a better estimation of the true risk conferred by these novel loci, we tested a completely unselected population of type 2 diabetes patients from a Norwegian health survey (the HUNT study). Methods We genotyped single nucleotide polymorphisms (SNPs) in PKN2, IGFBP2, FLJ39370 (also known as C4ORF32), CDKAL1, SLC30A8, CDKN2B, HHEX and FTO using a Norwegian population-based sample of 1,638 patients with type 2 diabetes and 1,858 non-diabetic control participants (the HUNT Study), for all of whom data on BMI, WHR, cholesterol and triacylglycerol levels were available. We used diabetes, measures of obesity and lipid values as phenotypes in case-control and quantitative association study designs. Results We replicated the association with type 2 diabetes for rs10811661 in the vicinity of CDKN2B (OR 1.20, 95% CI: 1.06-1.37, p=0.004), rs9939609 in FTO (OR 1.14, 95% CI: 1.04-1.25, p=0.006) and rs13266634 in SLC30A8 (OR 1.20, 95% CI: 1.09-1.33, p=3.9x10(-4)). We found borderline significant association for the IGFBP2 SNP rs4402960 (OR 1.10, 95% CI: 0.99-1.22). Results for the HHEX SNP (rs1111875) and the CDKAL1 SNP (rs7756992) were non-significant, but the magnitude of effect was similar to previous estimates. We found no support for an association with the less consistently replicated FLJ39370 or PKN2 SNPs. In agreement with previous studies, FTO was most strongly associated with BMI (p=8.4x10(-4)). Conclusions/interpretation Our data show that SNPs near IGFBP2, CDKAL1, SLC30A8, CDKN2B, HHEX and FTO are also associated with diabetes in non-selected patients with type 2 diabetes.
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| 8. |
- Heyes, S. Burnett, et al.
(author)
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Mental Imagery-Based Training to Modify Mood and Cognitive Bias in Adolescents : Effects of Valence and Perspective
- 2017
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In: Cognitive Therapy and Research. - : SPRINGER/PLENUM PUBLISHERS. - 0147-5916 .- 1573-2819. ; 41:1, s. 73-88
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Journal article (peer-reviewed)abstract
- Mental imagery has a powerful impact on emotion and cognitive processing in adults, and is implicated in emotional disorders. Research suggests the perspective adopted in mental imagery modulates its emotional impact. However, little is known about the impact of mental imagery in adolescence, despite adolescence being the key time for the onset of emotional dysfunction. We administered computerised positive versus mixed valence picture-word mental imagery training to male adolescent participants (N = 60, aged 11-16 years) across separate field and observer perspective sessions. Positive mood increased more following positive than mixed imagery; pleasantness ratings of ambiguous pictures increased following positive versus mixed imagery generated from field but not observer perspective; negative interpretation bias on a novel scrambled sentences task was smaller following positive than mixed imagery particularly when imagery was generated from field perspective. These findings suggest positive mental imagery generation alters mood and cognition in male adolescents, with the latter moderated by imagery perspective. Identifying key components of such training, such as imagery perspective, extends understanding of the relationship between mental imagery, mood, and cognition in adolescence.
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| 9. |
- Johansson, T., et al.
(author)
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Observation of an inner magnetosphere electric field associated with a BBF-like flow and PBIs
- 2009
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In: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 27:4, s. 1489-1500
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Journal article (peer-reviewed)abstract
- Themis E observed a perpendicular (to the magnetic field) electric field associated with an Earthward plasma flow at XGSM=-9.6 R-E on 11 January 2008. The electric field observation resembles Cluster observations closer to Earth in the auroral region. The fast plasma flow shared some characteristics with bursty bulk flows (BBFs) but did not meet the usual criteria in maximum velocity and duration to qualify as one. Themis C observed the same flow further downtail but Themis D, separated by only 1 R-E in azimuthal direction from Themis E, did not. At the time of the electric field and ion flow event, the all-sky imager and ground-based magnetometer at Rankin Inlet observed Poleward Boundary Intensifications (PBIs) and a negative bay signature. None of the other Themis ground-based observatories recorded any significant auroral or magnetic field activity, indicating that this was a localized activity. The joint Themis in situ and ground-based observations suggest that the two observations are related. This indicates that auroral electric fields can extend to regions much farther out than previously seen in Cluster observations.
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| 10. |
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