| 1. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Wohlfarth, B, et al.
(författare)
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Unstable early-Holocene climatic and environmental conditions in northwestern Russia derived from a multidisciplinary study of a lake-sediment sequence from Pichozero, southeastern Russian Karelia
- 2004
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Ingår i: The Holocene. - : SAGE Publications. - 0959-6836 .- 1477-0911. ; 14:5, s. 732-746
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Tidskriftsartikel (refereegranskat)abstract
- A sediment core from Lake Pichozero (61degrees46'; N, 37degrees25'; E 118 m a.s.l.) provides information on the environmental and climatic conditions in southeastern Russian Karelia during the Lateglacial and early Holocene (12800-9300 cal. BP). The chronology of the sequence is constrained by varve counting and AMS C-14 measurement of terrestrial plant macrofossils. Multiproxy analyses (magnetic susceptibility, grain size, TOC, TN, TS, Rock Eval, pollen and macrofossils) imply that cold and dry regional climatic conditions with sparse Arctic vegetation prevailed prior to 11500 cal. BP. Coincident with the transition to the Holocene at 11500 cal. BP, air temperatures and lake productivity increased and Betula pubescens and Populus tremula started to migrate into the area, followed by Picea abies at 10750 cal. BP. Although lake productivity decreased at around 11000 cal. BP and remained low until 9600 cal. BP, pollen-based climate reconstructions imply variable climatic conditions in the region over time. Drier and colder summers prevailed from similar to11200 to 10900 cal. BP, followed by an interval of higher annual temperatures and precipitation from 10900 to 10750 cal. BP. Lower annual temperatures and drier conditions existed from 10750 to 10200 cal. BP, and higher temperatures and precipitation are inferred between 10200 and 10000 cal. BP. Finally, declining temperatures and precipitation occurred from 10000 cal. BP onwards, with a minimum at around 9600 cal. BP. These climatic shifts are temporally coincident with those recorded in North Atlantic terrestrial, marine and ice-core archives and indicate that relatively minor climate signals were transmitted further to the east.
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| 4. |
- Schadendorf, D., et al.
(författare)
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Functional and symptom impact of trametinib versus chemotherapy in BRAF V600E advanced or metastatic melanoma : quality-of-life analyses of the METRIC study
- 2014
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 25:3, s. 700-706
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Tidskriftsartikel (refereegranskat)abstract
- We report the first quality-of-life assessment of a MEK inhibitor in metastatic melanoma from a phase III study. Trametinib prolonged progression-free survival and improved overall survival versus chemotherapy in patients with BRAF V600 mutation-positive melanoma. Less functional impairment, smaller declines in health status, and less exacerbation of symptoms were observed with trametinib.In a randomized phase III study, trametinib prolonged progression-free survival and improved overall survival versus chemotherapy in patients with BRAF V600 mutation-positive melanoma. Patients' quality of life (QOL) was assessed at baseline and follow-up visits using the European Organisation for Research and Treatment of Cancer Core QOL questionnaire. In the primary efficacy population (BRAF V600E+, no brain metastases) from baseline to weeks 6 and 12, patients' global health status scores worsened by 4-5 points with chemotherapy but improved by 2-3 points with trametinib. Rapid and substantive reductions in QOL functionality (e.g. role functioning, 8-11 points at weeks 6 and 12) and symptom exacerbation (e.g. fatigue, 4-8 points; nausea and vomiting, 5 points, both at weeks 6 and 12) were observed in chemotherapy-treated patients. In contrast, trametinib-treated patients reported small improvements or slight worsening from baseline at week 12, depending on the functional dimension and symptom. The mean symptom-scale scores for chemotherapy-treated patients increased from baseline (symptoms worsened) for seven of eight symptoms at week 6 (except insomnia) and six of eight symptoms at week 12 (except dyspnea and insomnia). In contrast, at weeks 6 and 12, the mean symptom-scale scores for trametinib decreased from baseline (symptoms improved) for pain (11-12 points), insomnia (10-12 points), and appetite loss (1-5 points), whereas those for diarrhea worsened (15-16 points). Mixed-model repeated-measures analyses showed significant (P < 0.05) and/or clinically meaningful improvements (small to moderate) from baseline in favor of trametinib for global health; physical, role, and social functioning; fatigue; pain; insomnia; nausea and vomiting; constipation; dyspnea; and appetite at weeks 6 and/or 12. QOL results for the intent-to-treat population were consistent. This first QOL assessment for a MEK inhibitor in metastatic melanoma demonstrated that trametinib was associated with less functional impairment, smaller declines in health status, and less exacerbation of symptoms versus chemotherapy.
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| 6. |
- Guerriero, S., et al.
(författare)
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Imaging of gynecological disease (6): clinical and ultrasound characteristics of ovarian dysgerminoma
- 2011
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Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 37:5, s. 596-602
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To describe the clinical history and ultrasound findings in patients with ovarian dysgerminoma. Methods This was a retrospective study of patients with a histological diagnosis of ovarian dysgerminoma who had undergone preoperative ultrasound examination. The patients were identified from the databases of 11 ultrasound centers. The tumors were described by the principal investigator at each contributing center on the basis of ultrasound images, ultrasound reports and research protocols (when applicable) using the terms and definitions of the International Ovarian Tumor Analysis (IOTA) group. In addition, three authors reviewed all available electronic ultrasound images (gray-scale images and color/power Doppler images were available for 18 patients and 14 patients, respectively) and described them using subjective evaluation of gray-scale and color Doppler ultrasound findings (here called pattern recognition). Results Twenty-one patients with ovarian dysgerminoma were identified (including one woman with bilateral masses). Twenty patients had a primary ovarian dysgerminoma (including the one with bilateral masses) and one patient had a recurrence of dysgerminoma in her retained ovary. One of the 21 patients was pregnant. All tumors except one were pure dysgerminomas, one being a mixed germinal cell tumor with 30% dysgerminoma component. Median age was 20 (range, 16-31) years. Information on clinical symptoms was available for 18 patients. In four patients, the tumor was detected incidentally, whereas 14 patients presented with one or more of the following symptoms: acute pain (n = 4), chronic pain (n = 8), bloating (n = 8), menstrual disorders (n = 5) and infertility problems (n = 1). One (5%) patient had ascites. Using the IOTA terms and definitions, all but one dysgerminoma were moderately (43%) or very well (50%) vascularized solid tumors. One tumor was multilocular-solid. According to pattern recognition, most dysgerminomas were highly vascularized, purely solid tumors with heterogeneous internal echogenicity divided into several lobules, had a smooth and sometimes lobulated contour and were well-defined relative to the surrounding organs. Conclusion The ultrasound finding of a highly vascularized, large, solid, lobulated adnexal mass with irregular internal echogenicity in a woman 20-30 years old should raise the suspicion of ovarian dysgerminoma. Copyright (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd.
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| 7. |
- Hubberten, HW, et al.
(författare)
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The periglacial climate and environment in northern Eurasia during the Last Glaciation
- 2004
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 23:11-13, s. 1333-1357
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Forskningsöversikt (refereegranskat)abstract
- This paper summarizes the results of studies of the Late Weichselian periglacial environments carried out in key areas of northern Eurasia by several QUEEN teams (European Science Foundation (ESF) programme: "Quaternary Environment of the Eurasian North"). The palaeoglaciological boundary conditions are defined by geological data on timing and extent of the last glaciation obtained in the course of the EU funded project "Eurasian Ice Sheets". These data prove beyond any doubt, that with the exception of the northwestern fringe of the Taymyr Peninsula, the rest of the Eurasian mainland and Severnaya Zemlya were not affected by the Barents-Kara Sea fee Sheet during the Last Glacial Maximum (LGM). Inversed modelling based on these results shows that a progressive cooling which started around 30 ka BP, caused ice growth in Scandinavia and the northwestern areas of the Barents-Kara Sea shelf, due to a maritime climate with relatively high precipitation along the western flank of the developing ice sheets. In the rest of the Eurasian Arctic extremely low precipitation rates (less than 50 mm yr(-1)), did not allow ice sheet growth in spite of the very cold temperatures. Palaeoclimatic and palaeoenvironmental conditions for the time prior to, during, and after the LGM have been reconstructed for the non-glaciated areas around the LGM ice sheet with the use of faunal and vegetation records, permafrost, eolian sediments, alluvial deposits and other evidences. The changing environment, from interstadial conditions around 30 ka BP to a much colder and drier environment at the culmination of the LGM at 20-15 ka BP, and the beginning of warming around 15 ka BP have been elaborated from the field data, which fits well with the modelling results. (C) 2003 Elsevier Ltd. All rights reserved.
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| 8. |
- Ovsyannikov, Gennady, 1948, et al.
(författare)
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Magnetic proximity effect at the interface between a cuprate superconductor and an oxide spin valve
- 2016
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Ingår i: Journal of Experimental and Theoretical Physics. - : Pleiades Publishing Ltd. - 1090-6509 .- 1063-7761. ; 122:4, s. 738-747
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Tidskriftsartikel (refereegranskat)abstract
- A heterostructure that consists of the YBa2Cu3O7-delta cuprate superconductor and the SrRuO3/La0.7Sr0.3MnO3 ruthenate/manganite spin valve is investigated using SQUID magnetometry, ferromagnetic resonance, and neutron reflectometry. It is shown that a magnetic moment is induced due to the magnetic proximity effect in the superconducting part of the heterostructure, while the magnetic moment in the composite ferromagnetic interlayer is suppressed. The magnetization emerging in the superconductor coincides in order of magnitude with the results of calculations taking into account the induced magnetic moment of Cu atoms because of orbital reconstruction at the interface between the superconductor and the ferromagnet, as well as with the results of the model taking into account the variations in the density of states at a distance on the order of the coherence length in the superconductor. The experimentally obtained characteristic penetration depth of the magnetic moment in the superconductor considerably exceeds the coherence length of the cuprate superconductor, which indicates the predominance of the mechanism of induced magnetic moment of Cu atoms.
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| 9. |
- Petrzhik, A. M., et al.
(författare)
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Ferromagnetic state of LaMnO3 interlayer in La0.7Sr0.3MnO3/LaMnO3/SrRuO3 heterostructures
- 2015
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Ingår i: Solid State Phenomena. - 1662-9779 .- 1012-0394. - 9783038354826 ; 233-234, s. 439-442
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Konferensbidrag (refereegranskat)abstract
- Magnetic state of epitaxial heterostructures La0.7Sr0.3MnO3/LaMnO3/SrRuO3 (LSMO/LMO/SRO) was studied by SQUID magnetometer, ferromagnetic resonance (FMR) and polarized neutron reflectometry (PNR) techniques. The fit of PNR and FMR data give us the magnetization of each layer, while the SQUID gives the total magnetization of our structures. The magnetic moment of the LMO layer has the magnetization 4πMLMO=4.2kGs (2.4 μB/Mn) at T=140K according to our PNR data fitting.
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| 10. |
- Svendsen, JI, et al.
(författare)
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Late quaternary ice sheet history of northern Eurasia
- 2004
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 23:11-13, s. 1229-1271
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Forskningsöversikt (refereegranskat)abstract
- The maximum limits of the Eurasian ice sheets during four glaciations have been reconstructed: (1) the Late Saalian (> 140 ka), (2) the Early Weichselian (100-80 ka), (3) the Middle Weichselian (60-50 ka) and (4) the Late Weichselian (25-15 ka). The reconstructed ice limits are based on satellite data and aerial photographs combined with geological field investigations in Russia and Siberia, and with marine seismic- and sediment core data. The Barents-Kara Ice Sheet got progressively smaller during each glaciation, whereas the dimensions of the Scandinavian Ice Sheet increased. During the last Ice Age the Barents-Kara Ice Sheet attained its maximum size as early as 90-80,000 years ago when the ice front reached far onto the continent. A regrowth of the ice sheets occurred during the early Middle Weichselian, culminating about 60-50,000 years ago. During the Late Weichselian the Barents-Kara Ice Sheet did not reach the mainland east of the Kanin Peninsula, with the exception of the NW fringe of Taimyr. A numerical ice-sheet model, forced by global sea level and solar changes, was run through the full Weichselian glacial cycle. The modeling results are roughly compatible with the geological record of ice growth, but the model underpredicts the glaciations in the Eurasian Arctic during the Early and Middle Weichselian. One reason for this is that the climate in the Eurasian Arctic was not as dry then as during the Late Weichselian glacial maximum.
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