| 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. |
- Meyer, Peter A., et al.
(författare)
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Data publication with the structural biology data grid supports live analysis
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Access to experimental X-ray diffraction image data is fundamental for validation and reproduction of macromolecular models and indispensable for development of structural biology processing methods. Here, we established a diffraction data publication and dissemination system, Structural Biology Data Grid (SBDG; data. sbgrid. org), to preserve primary experimental data sets that support scientific publications. Data sets are accessible to researchers through a community driven data grid, which facilitates global data access. Our analysis of a pilot collection of crystallographic data sets demonstrates that the information archived by SBDG is sufficient to reprocess data to statistics that meet or exceed the quality of the original published structures. SBDG has extended its services to the entire community and is used to develop support for other types of biomedical data sets. It is anticipated that access to the experimental data sets will enhance the paradigm shift in the community towards a much more dynamic body of continuously improving data analysis.
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| 3. |
- Ahmad, Yousif, et al.
(författare)
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Coronary Hemodynamics in Patients With Severe Aortic Stenosis and Coronary Artery Disease Undergoing Transcatheter Aortic Valve Replacement : Implications for Clinical Indices of Coronary Stenosis Severity
- 2018
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Ingår i: JACC: Cardiovascular Interventions. - : Elsevier BV. - 1876-7605 .- 1936-8798. ; 11:20, s. 2019-2031
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: In this study, a systematic analysis was conducted of phasic intracoronary pressure and flow velocity in patients with severe aortic stenosis (AS) and coronary artery disease, undergoing transcatheter aortic valve replacement (TAVR), to determine how AS affects: 1) phasic coronary flow; 2) hyperemic coronary flow; and 3) the most common clinically used indices of coronary stenosis severity, instantaneous wave-free ratio and fractional flow reserve.BACKGROUND: A significant proportion of patients with severe aortic stenosis (AS) have concomitant coronary artery disease. The effect of the valve on coronary pressure, flow, and the established invasive clinical indices of stenosis severity have not been studied.METHODS: Twenty-eight patients (30 lesions, 50.0% men, mean age 82.1 ± 6.5 years) with severe AS and coronary artery disease were included. Intracoronary pressure and flow assessments were performed at rest and during hyperemia immediately before and after TAVR.RESULTS: Flow during the wave-free period of diastole did not change post-TAVR (29.78 ± 14.9 cm/s vs. 30.81 ± 19.6 cm/s; p = 0.64). Whole-cycle hyperemic flow increased significantly post-TAVR (33.44 ± 13.4 cm/s pre-TAVR vs. 40.33 ± 17.4 cm/s post-TAVR; p = 0.006); this was secondary to significant increases in systolic hyperemic flow post-TAVR (27.67 ± 12.1 cm/s pre-TAVR vs. 34.15 ± 17.5 cm/s post-TAVR; p = 0.02). Instantaneous wave-free ratio values did not change post-TAVR (0.88 ± 0.09 pre-TAVR vs. 0.88 ± 0.09 post-TAVR; p = 0.73), whereas fractional flow reserve decreased significantly post-TAVR (0.87 ± 0.08 pre-TAVR vs. 0.85 ± 0.09 post-TAVR; p = 0.001).CONCLUSIONS: Systolic and hyperemic coronary flow increased significantly post-TAVR; consequently, hyperemic indices that include systole underestimated coronary stenosis severity in patients with severe AS. Flow during the wave-free period of diastole did not change post-TAVR, suggesting that indices calculated during this period are not vulnerable to the confounding effect of the stenotic aortic valve.
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| 4. |
- Ahmad, Yousif, et al.
(författare)
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Determining the Predominant Lesion in Patients With Severe Aortic Stenosis and Coronary Stenoses : A Multicenter Study Using Intracoronary Pressure and Flow
- 2019
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Ingår i: Circulation. Cardiovascular Interventions. - 1941-7632. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with severe aortic stenosis (AS) often have coronary artery disease. Both the aortic valve and the coronary disease influence the blood flow to the myocardium and its ability to respond to stress; leading to exertional symptoms. In this study, we aim to quantify the effect of severe AS on the coronary microcirculation and determine if this is influenced by any concomitant coronary disease. We then compare this to the effect of coronary stenoses on the coronary microcirculation. METHODS: Group 1: 55 patients with severe AS and intermediate coronary stenoses treated with transcatheter aortic valve implantation (TAVI) were included. Group 2: 85 patients with intermediate coronary stenoses and no AS treated with percutaneous coronary intervention were included. Coronary pressure and flow were measured at rest and during hyperemia in both groups, before and after TAVI (group 1) and before and after percutaneous coronary intervention (group 2). RESULTS: Microvascular resistance over the wave-free period of diastole increased significantly post-TAVI (pre-TAVI, 2.71±1.4 mm Hg·cm·s-1 versus post-TAVI 3.04±1.6 mm Hg·cm·s-1 [P=0.03]). Microvascular reserve over the wave-free period of diastole significantly improved post-TAVI (pre-TAVI 1.88±1.0 versus post-TAVI 2.09±0.8 [P=0.003]); this was independent of the severity of the underlying coronary stenosis. The change in microvascular resistance post-TAVI was equivalent to that produced by stenting a coronary lesion with an instantaneous wave-free ratio of ≤0.74. CONCLUSIONS: TAVI improves microcirculatory function regardless of the severity of underlying coronary disease. TAVI for severe AS produces a coronary hemodynamic improvement equivalent to the hemodynamic benefit of stenting coronary stenoses with instantaneous wave-free ratio values <0.74. Future trials of physiology-guided revascularization in severe AS may consider using this value to guide treatment of concomitant coronary artery disease.
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| 5. |
- Gismelseed, A. M., et al.
(författare)
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Investigations of Al-Dalang and Al-Hawashat meteorites
- 2016
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Ingår i: Hyperfine Interactions. - : Springer Science and Business Media LLC. - 0304-3843 .- 1572-9540.
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Konferensbidrag (refereegranskat)abstract
- Mossbauer spectroscopy, X-ray diffraction (XRD) measurements, and electron microprobe analysis (EMPA) have been performed on two meteorites named Al-Dalang and Al-Hawashat after identifying their falling sites in the Western region of Sudan. These two meteorites are ordinary chondrites with similar mineralogy. XRD and EMPA show that the two specimens consist of primary olivine, ortho-pyroxene and later crystallising clino-pyroxene as reaction rims against plagioclase. Fe-metal phases are dominated by kamacite (approximate to 6 wt.% Ni) and minor amounts of tetrataenite (approximate to 52 wt.% Ni). Troilite (FeS) and alabandite (MnS) are optically observed as sulphide phases. The Mossbauer measurements at 295 and 78 K are in agreement with the above characterizations, showing at least two paramagnetic doublets which are assigned to olivine and pyroxene and magnetic sextets assigned to kamacite (hyperfine field approximate to 33.5 T) and troilite FeS (hyperfine field approximate to 31 T).
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| 6. |
- Henningsson-Yousif, Anna, et al.
(författare)
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Making teachers' pedagogical capital visible and useful
- 2015
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Ingår i: Journal of Workplace Learning. - : Emerald Group Publishing Limited. - 1366-5626 .- 1758-7859. ; 27:5, s. 332-344
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Tidskriftsartikel (refereegranskat)abstract
- Purpose – The purpose of this paper is to compare methods of working with pedagogical capital in teacher and mentor education. The authors make an account of the development of the concept of pedagogical capital and relate it to the theoretical context of practice theory. Empirical data will substantiate the theoretical discussion of teachers ' pedagogical capital. Design/methodology/approach – Comparative analyses of the authors ' research and empirical data were undertaken. Findings – Three dimensions of pedagogical capital have been identified: an experience content dimension, an analysis dimension and an acting dimension. Research limitations/implications – The authors find potential in using and further developing the concept of pedagogical capital in its various dimensions and in relation to other similar concepts. Practical implications – The authors ' methods could be used for school development purposes as well as in teacher education. Social implications – The aim of the paper is to underline the value of the contributions people can make to society as a whole and as teachers in school, in particular. The recognition of the ability to analyse and contribute is the essence of this work. Originality/value – The value of the paper is the introduction and development of pedagogical capital in an international context. The value is also the common analyses of educational work in Sweden and Norway.
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| 7. |
- Henningsson-Yousif, Anna, et al.
(författare)
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Ways of making teachers' pedagogical capital visible and useful
- 2013
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The starting point of our reasoning is that development of society is dependent on the contributions of its members in a crucial way. In society we carry out different tasks, hold different positions, dwell in different places etc, more or less voluntarily. We have different backgrounds and perspectives. Likewise the development of the school is dependent on the contributions of teachers, leaders and pupils. In this paper we will concentrate on schools and the persons who work there. It is possible to regard schools as the perfect arena for asking for, expressing and making use of the assets of people. These assets include ways of regarding the role of the school in the lives of people and in society, as well as experiences of learning situations etc. We discuss different ways to ask for and make use of the contributions of teachers, i e the analyses that teachers can contribute with in everyday situations as well as in long -term planning. We discuss ways of expressing these analyses, using the concept of pedagogical capital (Henningsson-Yousif & Viggosson, 2009, Henningsson-Yousif, 2011, 2012, Viggosson, 2011). The concept of pedagogical capital is used to name the assets of individuals that are activated in pedagogical situations. Other kinds of capitals could be activated in other situations. While the use by Bourdieu of the concept of capital consists of assets of symbolic value and are of importance for power relations and for capturing of positions in society (Carle, 2007), we are interested in the capitals in a more democratic sense. The idea is that everyone at any moment has a pedagogical capital that can be asked for, expressed and made use of in people's own lives as well as in school and in society as a whole. We are especially interested in the analysis of situations that are expressions here and now of the versatile pedagogical capitals of teachers. These contributions can be communicated in many ways. In this paper we will discuss two modes of expressing the pedagogical capitals: in written language and with sketches. Especially sketches can be used to make visible different aspects of the teachers' pedagogical capitals. We thus use our own empirical research and experiences from Sweden and Norway. We discuss possibilities and methods to ask for, express and make use of the pedagogical capitals in the contexts of Teacher Education and of Development Work in Schools. We discuss the similarities of the concept of pedagogical capital with the concepts of praxis theory (Handal & Lauvås, 1983) and the concept of teachers’ knowledge base (Engen, 2011). We do not elaborate further on the theory of Bourdieu. Vital questions are: How do the teachers value their own pedagogical capitals and how do they use them? How do the leaders value the pedagogical capitals of their teachers and how do they use them? How are the pedagogical capitals used in Teacher Education and in School Development situations?
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| 8. |
- Mohammad, Yousif, 1976, et al.
(författare)
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Geochemistry and Ar-Ar muscovite ages of the Daraban Leucogranite, Mawat ophiolite, northeastern Iraq: Implications for Arabia-Eurasia continental collision
- 2014
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Ingår i: Journal of Asian Earth Sciences. - : Elsevier BV. - 1367-9120. ; 86, s. 151-165
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Tidskriftsartikel (refereegranskat)abstract
- Daraban Leucogranite dykes intruded discordantly into the basal serpentinized harzburgite of the Mawat Ophiolite, Kurdistan region, NE Iraq. These coarse grained muscovite-tourmaline leucogranites are the first leucogranite dykes identified within the Mawat Ophiolite. They are mainly composed of quartz, K-feldspar, plagioclase, tourmaline, muscovite, and secondary phologopite, while zircon, xenotime, corundum, mangano-ilemnite and cassiterite occur as accessories. The A/CNK value of the granite dyke samples varies from 1.10 to 1.22 indicating a strongly peraluminous composition. CaO/Na2O ranges from 0.11 to 0.15 and Al2O3/TiO2 from 264 to 463, similar to the strongly peraluminous (SP) granites exposed in ‘high-pressure’ collision zones such as the Himalayas. Ar–Ar muscovite step-heating dating yields 37.57 ± 0.25 and 38.02 ± 0.53 Ma plateau ages for two samples which are thought to reflect either their magmatic emplacement or resetting during collision-related metamorphism. Mineral chemistry shows evidence of both primary and secondary types of muscovite, with cores favouring the magmatic interpretation and slight effects of a late syn-serpentinization fluid seen at the rims. Geochemical features of Daraban Leucogranite dykes favour a syn-collisional tectonic setting. They probably formed in response to the continental collision between Eurasia and Arabia during the initial stage of the opening of the Gulf of Aden at 37 Ma. The muscovite ages and geochemical features of Daraban Leucogranite are strong evidence for the timing of the continental collision between northeastern Arabia and Eurasia in Kurdistan region of Iraq.
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