| 1. |
- van Haarlem, M. P., et al.
(författare)
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LOFAR : The LOw-Frequency ARray
- 2013
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 556, s. 1-53
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Tidskriftsartikel (refereegranskat)abstract
- LOFAR, the LOw-Frequency ARray, is a new-generation radio interferometer constructed in the north of the Netherlands and across europe. Utilizing a novel phased-array design, LOFAR covers the largely unexplored low-frequency range from 10–240 MHz and provides a number of unique observing capabilities. Spreading out from a core located near the village of Exloo in the northeast of the Netherlands, a total of 40 LOFAR stations are nearing completion. A further five stations have been deployed throughout Germany, and one station has been built in each of France, Sweden, and the UK. Digital beam-forming techniques make the LOFAR system agile and allow for rapid repointing of the telescope as well as the potential for multiple simultaneous observations. With its dense core array and long interferometric baselines, LOFAR achieves unparalleled sensitivity and angular resolution in the low-frequency radio regime. The LOFAR facilities are jointly operated by the International LOFAR Telescope (ILT) foundation, as an observatory open to the global astronomical community. LOFAR is one of the first radio observatories to feature automated processing pipelines to deliver fully calibrated science products to its user community. LOFAR’s new capabilities, techniques and modus operandi make it an important pathfinder for the Square Kilometre Array (SKA). We give an overview of the LOFAR instrument, its major hardware and software components, and the core science objectives that have driven its design. In addition, we present a selection of new results from the commissioning phase of this new radio observatory.
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| 2. |
- De Gasperin, F., et al.
(författare)
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M 87 at metre wavelengths: the LOFAR picture
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 547, s. article no. 56-
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Tidskriftsartikel (refereegranskat)abstract
- Context. M87 is a giant elliptical galaxy located in the centre of the Virgo cluster, which harbours a supermassive black hole of mass 6.4x10(9) M-circle dot, whose activity is responsible for the extended (80 kpc) radio lobes that surround the galaxy. The energy generated by matter falling onto the central black hole is ejected and transferred to the intra-cluster medium via a relativistic jet and morphologically complex systems of buoyant bubbles, which rise towards the edges of the extended halo. Aims. To place constraints on past activity cycles of the active nucleus, images of M 87 were produced at low radio frequencies never explored before at these high spatial resolution and dynamic range. To disentangle different synchrotron models and place constraints on source magnetic field, age and energetics, we also performed a detailed spectral analysis of M 87 extended radio-halo. Methods. We present the first observations made with the new Low-Frequency Array (LOFAR) of M 87 at frequencies down to 20 MHz. Three observations were conducted, at 15-30 MHz, 30-77 MHz and 116-162 MHz. We used these observations together with archival data to produce a low-frequency spectral index map and to perform a spectral analysis in the wide frequency range 30 MHz-10 GHz. Results. We do not find any sign of new extended emissions; on the contrary the source appears well confined by the high pressure of the intra-cluster medium. A continuous injection of relativistic electrons is the model that best fits our data, and provides a scenario in which the lobes are still supplied by fresh relativistic particles from the active galactic nuclei. We suggest that the discrepancy between the low-frequency radio-spectral slope in the core and in the halo implies a strong adiabatic expansion of the plasma as soon as it leaves the core area. The extended halo has an equipartition magnetic field strength of similar or equal to 10 mu G, which increases to similar or equal to 13 mu G in the zones where the particle flows are more active. The continuous injection model for synchrotron ageing provides an age for the halo of similar or equal to 40 Myr, which in turn provides a jet kinetic power of 6-10 x 10(44) erg s(-1).
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| 3. |
- Sobey, C., et al.
(författare)
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LOFAR discovery of a quiet emission mode in PSR B0823+26
- 2015
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 451, s. 2493-2506
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Tidskriftsartikel (refereegranskat)abstract
- PSR B0823+26, a 0.53-s radio pulsar, displays a host of emission phenomena over time-scales of seconds to (at least) hours, including nulling, subpulse drifting, and mode-changing. Studying pulsars like PSR B0823+26 provides further insight into the relationship between these various emission phenomena and what they might teach us about pulsar magnetospheres. Here we report on the LOFAR (Low-Frequency Array) discovery that PSR B0823+26 has a weak and sporadically emitting ‘quiet’ (Q) emission mode that is over 100 times weaker (on average) and has a nulling fraction forty-times greater than that of the more regularly-emitting ‘bright’ (B) mode. Previously, the pulsar has been undetected in the Q mode, and was assumed to be nulling continuously. PSR B0823+26 shows a further decrease in average flux just before the transition into the B mode, and perhaps truly turns off completely at these times. Furthermore, simultaneous observations taken with the LOFAR, Westerbork, Lovell, and Effelsberg telescopes between 110 MHz and 2.7 GHz demonstrate that the transition between the Q mode and B mode occurs within one single rotation of the neutron star, and that it is concurrent across the range of frequencies observed.
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| 4. |
- Offringa, A. R., et al.
(författare)
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The LOFAR radio environment
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 549
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Tidskriftsartikel (refereegranskat)abstract
- Aims. This paper discusses the spectral occupancy for performing radio astronomy with the Low-Frequency Array (LOFAR), with a focus on imaging observations.Methods. We have analysed the radio-frequency interference (RFI) situation in two 24-h surveys with Dutch LOFAR stations, covering 30-78 MHz with low-band antennas and 115-163 MHz with high-band antennas. This is a subset of the full frequency range of LOFAR. The surveys have been observed with a 0.76 kHz/1 s resolution.Results. We measured the RFI occupancy in the low and high frequency sets to be 1.8% and 3.2% respectively. These values are found to be representative values for the LOFAR radio environment. Between day and night, there is no significant difference in the radio environment. We find that lowering the current observational time and frequency resolutions of LOFAR results in a slight loss of flagging accuracy. At LOFAR's nominal resolution of 0.76 kHz and 1 s, the false-positives rate is about 0.5%. This rate increases approximately linearly when decreasing the data frequency resolution.Conclusions. Currently, by using an automated RFI detection strategy, the LOFAR radio environment poses no perceivable problems for sensitive observing. It remains to be seen if this is still true for very deep observations that integrate over tens of nights, but the situation looks promising. Reasons for the low impact of RFI are the high spectral and time resolution of LOFAR; accurate detection methods; strong filters and high receiver linearity; and the proximity of the antennas to the ground. We discuss some strategies that can be used once low-level RFI starts to become apparent. It is important that the frequency range of LOFAR remains free of broadband interference, such as DAB stations and windmills.
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| 5. |
- Stappers, B. W., et al.
(författare)
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Observing pulsars and fast transients with LOFAR
- 2011
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 530
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Tidskriftsartikel (refereegranskat)abstract
- Low frequency radio waves, while challenging to observe, are a rich source of information about pulsars. The LOw Frequency ARray (LOFAR) is a new radio interferometer operating in the lowest 4 octaves of the ionospheric "radio window": 10-240 MHz, that will greatly facilitate observing pulsars at low radio frequencies. Through the huge collecting area, long baselines, and flexible digital hardware, it is expected that LOFAR will revolutionize radio astronomy at the lowest frequencies visible from Earth. LOFAR is a next-generation radio telescope and a pathfinder to the Square Kilometre Array (SKA), in that it incorporates advanced multi-beaming techniques between thousands of individual elements. We discuss the motivation for low-frequency pulsar observations in general and the potential of LOFAR in addressing these science goals. We present LOFAR as it is designed to perform high-time-resolution observations of pulsars and other fast transients, and outline the various relevant observing modes and data reduction pipelines that are already or will soon be implemented to facilitate these observations. A number of results obtained from commissioning observations are presented to demonstrate the exciting potential of the telescope. This paper outlines the case for low frequency pulsar observations and is also intended to serve as a reference for upcoming pulsar/fast transient science papers with LOFAR.
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| 6. |
- Went, M, et al.
(författare)
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Author Correction: Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 213-
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Tidskriftsartikel (refereegranskat)abstract
- The original version of this Article contained an error in the spelling of a member of the PRACTICAL Consortium, Manuela Gago-Dominguez, which was incorrectly given as Manuela Gago Dominguez. This has now been corrected in both the PDF and HTML versions of the Article. Furthermore, in the original HTML version of this Article, the order of authors within the author list was incorrect. The PRACTICAL consortium was incorrectly listed after Richard S. Houlston and should have been listed after Nora Pashayan. This error has been corrected in the HTML version of the Article; the PDF version was correct at the time of publication.
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| 7. |
- Went, M, et al.
(författare)
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Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 3707-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM.
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| 8. |
- Le Guen, Yann, et al.
(författare)
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Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes.
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 1091-6490 .- 0027-8424. ; 120:36
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Tidskriftsartikel (refereegranskat)abstract
- Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
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| 9. |
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| 10. |
- van Duin, Titia S., et al.
(författare)
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Junior doctors' experiences with interprofessional collaboration : Wandering the landscape
- 2022
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Ingår i: Medical Education. - : John Wiley & Sons. - 0308-0110 .- 1365-2923. ; 56:4, s. 418-431
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Tidskriftsartikel (refereegranskat)abstract
- Context The transition from medical student to junior doctor is challenging. Junior doctors need to become part of the physician community of practice (CoP), while dealing with new responsibilities, tasks and expectations. At the same time, they need to learn how to navigate the frontiers and intersections with the other communities of practice that form the Landscape of Practice (LoP). This study aims to understand how junior doctors experience interprofessional collaboration (IPC) and what elements shape these experiences considering their transition to clinical practice. Methods In this multicentre qualitative study, 13 junior doctors individually drew two rich pictures of IPC experiences, one positive and one negative. A rich picture is a visual representation, a drawing of a particular situation intended to capture the complex and non-verbal elements of an experience. We used semi-structured interviews to deepen the understanding of junior doctors' depicted IPC experiences. We analysed both visual materials and interview transcripts iteratively, for which we adopted an inductive constructivist thematic analysis. Results While transitioning into a doctor, junior doctors become foremost members of the physician CoP and shape their professional identity based on perceived values in their physician community. Interprofessional learning occurs implicitly, without input from the interprofessional team. As a result, junior doctors struggle to bridge the gap between themselves and the interprofessional team, preventing IPC learning from developing into an integrative process. This professional isolation leaves junior doctors wandering the landscape of practice without understanding roles, attitudes and expectations of others. Conclusions Learning IPC needs to become a collective endeavour and an explicit learning goal, based on multisource feedback to take advantage of the expertise already present in the LoP. Furthermore, junior doctors need a safe environment to embrace and reflect on the emotions aroused by interprofessional interactions, under the guidance of experienced facilitators.
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| 11. |
- Mitchell, Jonathan S., et al.
(författare)
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Genome-wide association study identifies multiple susceptibility loci for multiple myeloma
- 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
- Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P = 1.31 x 10(-8)), 6q21 (rs9372120, P = 9.09 x 10(-15)), 7q36.1 (rs7781265, P = 9.71 x 10(-9)), 8q24.21 (rs1948915, P = 4.20 x 10(-11)), 9p21.3 (rs2811710, P = 1.72 x 10(-13)), 10p12.1 (rs2790457, P = 1.77 x 10(-8)), 16q23.1 (rs7193541, P = 5.00 x 10(-12)) and 20q13.13 (rs6066835, P = 1.36 x 10(-13)), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development.
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| 12. |
- Persson, Petter, et al.
(författare)
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Quantum-chemical calculations of dye-sensitized semiconductor nanocrystals
- 2006
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Ingår i: Physical Chemistry of Interfaces and Nanomaterials V. - : SPIE. - 1996-756X .- 0277-786X. ; 6325, s. 3250-3250
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Konferensbidrag (refereegranskat)abstract
- Quantum chemical calculations providing detailed information of dye-sensitized semiconductor nanocrystals are presented. The calculations are used to elucidate both structural and electronic properties of photoelectrochemical devices, such as environmentally friendly Dye-Sensitized Solar Cells (DSSCs), at the molecular level. Quantum chemical calculations have recently been performed on both organic and organometallic dye molecules attached to titanium dioxide (TiO2) nanocrystals via different anchor and spacer groups. Strategies to make accurate quantum chemical calculations, e.g. at the DFT level of theory, on increasingly realistic models of such dye-sensitized semiconductor interfaces are presented. The ability of different anchor and spacer groups to act as mediators of ultrafast photo-induced electron injection from the dye molecules into the semiconductor nanocrystals is, in particular, discussed in terms of calculated electronic coupling strengths, and direct comparisons with experimental information are made whenever possible. Progress in the development of multi-scale simulation techniques using so called reactive force fields is illustrated for dye-sensitized solar cell systems.
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| 13. |
- Raymand, David, 1981-, et al.
(författare)
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Hydroxylation Structure and Proton Transfer Reactivity at the Zinc Oxide-Water Interface
- 2011
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Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society. - 1932-7447 .- 1932-7455. ; 115:17, s. 8573-8579
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Tidskriftsartikel (refereegranskat)abstract
- The hydroxylation structural features of the first adsorption layer and its connection to proton transfer reactivity has been studied for the ZnO–liquid water interface at room temperature. Molecular Dynamics simulations employing the ReaxFF forcefield were performed for water on seven ZnO surfaces with varying step concentration. At higher water coverage a higher level of hydroxylation was found, in agreement with previous experimental results. We have also calculated the free energy barrier for transferring a proton to the surface, showing that stepped surfaces stabilizes the hydroxylated state and decreases the water dissociation barrier. On highly stepped surfaces the barrier is only 2 kJ/mol or smaller. Outside the first adsorption layer no dissociation events were observed during almost 100 ns of simulation time; this indicates that these reactions are much more likely if catalysed by the metal oxide surface. Also, when exposed to a vacuum, the less stepped surfaces stabilizes adsorption beyond monolayer coverage.
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| 14. |
- Raymand, David, 1981-, et al.
(författare)
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Water adsorption on stepped ZnO surfaces from MD simulation
- 2010
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Ingår i: Surface Science. - : Elsevier B.V.. - 0039-6028 .- 1879-2758. ; 604:9-10, s. 741-752
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Tidskriftsartikel (refereegranskat)abstract
- This work presents a ReaxFF reactive force-field for use in molecular dynamics simulations of the ZnO–water system. The force-field parameters were fitted to a data-set of energies, geometries and charges derived from quantum-mechanical B3LYP calculations. The presented ReaxFF model provides a good fit to the QM reference data for the ZnO–water system that was present in the data-set. The force-field has been used to study how water is adsorbed, molecularly or dissociatively, at monolayer coverage on flat and stepped ZnO surfaces, at three different temperatures (10 K, 300 K, and 600 K). The stepped surfaces were created by introducing steps along the (0 0 0 1)-direction on the -surface. Equilibrium between molecular and dissociated water was observed on the terraces, resulting in a half dissociated, half molecular water monolayer. The equilibrium between dissociated and molecular water on the surface was found to be reached quickly (<10 ps). When water molecules desorb and the coverage falls, the 1:1 water–hydroxyl ratio is maintained on terraces, while steps remain largely hydroxylated. The results show that structures that promote hydrogen bonding are favored and that the presence of steps promotes an increased level of hydroxylation in the water monolayers.
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| 15. |
- van Duin, Adri, et al.
(författare)
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Development and validation of a ReaxFF reactive force field for Cu-cation/water interactions and copper metal/metal oxide/metal hydroxide condensed phases
- 2010
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Ingår i: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 114:35, s. 9507-9514
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Tidskriftsartikel (refereegranskat)abstract
- To enable large-scale reactive dynamic simulations of copper oxide/water and copper ion/water interactions we have extended the ReaxFF reactive force field framework to Cu/O/H interactions. To this end, we employed a multistage force field development strategy, where the initial training set (containing metal/metal oxide/metal hydroxide condensed phase data and [Cu(H2O)(n)](2+) cluster structures and energies) is augmented by single-point quantum mechanices (QM) energies from [Cu(H2O)](2+) clusters abstracted from a ReaxFF molecular dynamics simulation. This provides a convenient strategy to both enrich the training set and to validate the final force field. To further validate the force field description we performed molecular dynamics simulations on Cu2+/water systems. We found good agreement between our results and earlier experimental and QM-based molecular dynamics work for the average Cu/water coordination, Jahn-Teller distortion, and inversion in [Cu(H2O)(6)](2+) clusters and first- and second-shell O-Cu-O angular distributions, indicating that this force field gives a satisfactory description of the Cu-cation/water interactions. We believe that this force field provides a computationally convenient method for studying the solution and surface chemistry of metal cations and metal oxides and, as such, has applications for studying protein/metal cation complexes, pH-dependent crystal growth/dissolution, and surface catalysis.
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| 16. |
- Went, Molly, et al.
(författare)
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Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology
- 2018
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Ingår i: Blood Cancer Journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- The clustering of different types of B-cell malignancies in families raises the possibility of shared aetiology. To examine this, we performed cross-trait linkage disequilibrium (LD)-score regression of multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL) genome-wide association study (GWAS) data sets, totalling 11,734 cases and 29,468 controls. A significant genetic correlation between these two B-cell malignancies was shown (Rg = 0.4, P = 0.0046). Furthermore, four of the 45 known CLL risk loci were shown to associate with MM risk and five of the 23 known MM risk loci associate with CLL risk. By integrating eQTL, Hi-C and ChIP-seq data, we show that these pleiotropic risk loci are enriched for B-cell regulatory elements and implicate B-cell developmental genes. These data identify shared biological pathways influencing the development of CLL and, MM and further our understanding of the aetiological basis of these B-cell malignancies.
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| 17. |
- Went, Molly, et al.
(författare)
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Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes
- 2019
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Ingår i: Human Genomics. - : Springer Science and Business Media LLC. - 1479-7364. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundWhile genome-wide association studies (GWAS) of multiple myeloma (MM) have identified variants at 23 regions influencing risk, the genes underlying these associations are largely unknown. To identify candidate causal genes at these regions and search for novel risk regions, we performed a multi-tissue transcriptome-wide association study (TWAS).ResultsGWAS data on 7319 MM cases and 234,385 controls was integrated with Genotype-Tissue Expression Project (GTEx) data assayed in 48 tissues (sample sizes, N = 80–491), including lymphocyte cell lines and whole blood, to predict gene expression. We identified 108 genes at 13 independent regions associated with MM risk, all of which were in 1 Mb of known MM GWAS risk variants. Of these, 94 genes, located in eight regions, had not previously been considered as a candidate gene for that locus.ConclusionsOur findings highlight the value of leveraging expression data from multiple tissues to identify candidate genes responsible for GWAS associations which provide insight into MM tumorigenesis. Among the genes identified, a number have plausible roles in MM biology, notably APOBEC3C, APOBEC3H, APOBEC3D, APOBEC3F, APOBEC3G, or have been previously implicated in other malignancies. The genes identified in this TWAS can be explored for follow-up and validation to further understand their role in MM biology.
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