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4. |
- 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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6. |
- Griffin, M. J., et al.
(author)
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The Herschel-SPIRE instrument and its in-flight performance
- 2010
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L3-
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Journal article (peer-reviewed)abstract
- The Spectral and Photometric Imaging REceiver (SPIRE), is the Herschel Space Observatory`s submillimetre camera and spectrometer. It contains a three-band imaging photometer operating at 250, 350 and 500 mu m, and an imaging Fourier-transform spectrometer (FTS) which covers simultaneously its whole operating range of 194-671 mu m (447-1550 GHz). The SPIRE detectors are arrays of feedhorn-coupled bolometers cooled to 0.3 K. The photometer has a field of view of 4' x 8', observed simultaneously in the three spectral bands. Its main operating mode is scan-mapping, whereby the field of view is scanned across the sky to achieve full spatial sampling and to cover large areas if desired. The spectrometer has an approximately circular field of view with a diameter of 2.6'. The spectral resolution can be adjusted between 1.2 and 25 GHz by changing the stroke length of the FTS scan mirror. Its main operating mode involves a fixed telescope pointing with multiple scans of the FTS mirror to acquire spectral data. For extended source measurements, multiple position offsets are implemented by means of an internal beam steering mirror to achieve the desired spatial sampling and by rastering of the telescope pointing to map areas larger than the field of view. The SPIRE instrument consists of a cold focal plane unit located inside the Herschel cryostat and warm electronics units, located on the spacecraft Service Module, for instrument control and data handling. Science data are transmitted to Earth with no on-board data compression, and processed by automatic pipelines to produce calibrated science products. The in-flight performance of the instrument matches or exceeds predictions based on pre-launch testing and modelling: the photometer sensitivity is comparable to or slightly better than estimated pre-launch, and the spectrometer sensitivity is also better by a factor of 1.5-2.
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7. |
- Bellenguez, C, et al.
(author)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Journal article (peer-reviewed)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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8. |
- Clark, Andrew G., et al.
(author)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Journal article (peer-reviewed)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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9. |
- Birney, Ewan, et al.
(author)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Journal article (peer-reviewed)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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10. |
- Agudo, I., et al.
(author)
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Panning for gold, but finding helium: Discovery of the ultra-stripped supernova SN 2019wxt from gravitational-wave follow-up observations
- 2023
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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 675
-
Journal article (peer-reviewed)abstract
- We present the results from multi-wavelength observations of a transient discovered during an intensive follow-up campaign of S191213g, a gravitational wave (GW) event reported by the LIGO-Virgo Collaboration as a possible binary neutron star merger in a low latency search. This search yielded SN 2019wxt, a young transient in a galaxy whose sky position (in the 80% GW contour) and distance (∼150 Mpc) were plausibly compatible with the localisation uncertainty of the GW event. Initially, the transienta's tightly constrained age, its relatively faint peak magnitude (Mi ∼ -16.7 mag), and the r-band decline rate of ∼1 mag per 5 days appeared suggestive of a compact binary merger. However, SN 2019wxt spectroscopically resembled a type Ib supernova, and analysis of the optical-near-infrared evolution rapidly led to the conclusion that while it could not be associated with S191213g, it nevertheless represented an extreme outcome of stellar evolution. By modelling the light curve, we estimated an ejecta mass of only ∼0.1 M·, with 56Ni comprising ∼20% of this. We were broadly able to reproduce its spectral evolution with a composition dominated by helium and oxygen, with trace amounts of calcium. We considered various progenitor channels that could give rise to the observed properties of SN 2019wxt and concluded that an ultra-stripped origin in a binary system is the most likely explanation. Disentangling genuine electromagnetic counterparts to GW events from transients such as SN 2019wxt soon after discovery is challenging: in a bid to characterise this level of contamination, we estimated the rate of events with a volumetric rate density comparable to that of SN 2019wxt and found that around one such event per week can occur within the typical GW localisation area of O4 alerts out to a luminosity distance of 500 Mpc, beyond which it would become fainter than the typical depth of current electromagnetic follow-up campaigns.
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11. |
- Ding, Li, et al.
(author)
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Somatic mutations affect key pathways in lung adenocarcinoma
- 2008
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7216, s. 1069-1075
-
Journal article (peer-reviewed)abstract
- Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
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12. |
- Weinstein, John N., et al.
(author)
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The cancer genome atlas pan-cancer analysis project
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:10, s. 1113-1120
-
Research review (peer-reviewed)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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13. |
- Hillier, Ladeana W, et al.
(author)
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Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
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In: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
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Journal article (peer-reviewed)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
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14. |
- Turtelboom,, et al.
(author)
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The TESS-Keck Survey. XI. Mass Measurements for Four Transiting Sub-Neptunes Orbiting K Dwarf TOI-1246
- 2022
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In: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 163:6
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Journal article (peer-reviewed)abstract
- Multiplanet systems are valuable arenas for investigating exoplanet architectures and comparing planetary siblings. TOI-1246 is one such system, with a moderately bright K dwarf (V = 11.6, K = 9.9) and four transiting sub-Neptunes identified by TESS with orbital periods of 4.31, 5.90, 18.66, and 37.92 days. We collected 130 radial velocity observations with Keck/HIRES and TNG/HARPS-N to measure planet masses. We refit the 14 sectors of TESS photometry to refine planet radii (2.97 +/- 0.06 R (circle plus), 2.47 +/- 0.08 R (circle plus), 3.46 +/- 0.09 R (circle plus), and 3.72 +/- 0.16 R (circle plus)) and confirm the four planets. We find that TOI-1246 e is substantially more massive than the three inner planets (8.1 +/- 1.1 M (circle plus), 8.8 +/- 1.2 M (circle plus), 5.3 +/- 1.7 M (circle plus), and 14.8 +/- 2.3 M (circle plus)). The two outer planets, TOI-1246 d and TOI-1246 e, lie near to the 2:1 resonance (P (e)/P ( d ) = 2.03) and exhibit transit-timing variations. TOI-1246 is one of the brightest four-planet systems, making it amenable for continued observations. It is one of only five systems with measured masses and radii for all four transiting planets. The planet densities range from 0.70 +/- 0.24 to 3.21 +/- 0.44 g cm(-3), implying a range of bulk and atmospheric compositions. We also report a fifth planet candidate found in the RV data with a minimum mass of 25.6 +/- 3.6 M (circle plus). This planet candidate is exterior to TOI-1246 e, with a candidate period of 93.8 days, and we discuss the implications if it is confirmed to be planetary in nature.
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15. |
- Carleo, Ilaria, et al.
(author)
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The Multiplanet System TOI-421*
- 2020
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In: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 160:3
-
Journal article (peer-reviewed)abstract
- We report the discovery of a warm Neptune and a hot sub-Neptune transiting TOI-421 (BD-14 1137, TIC 94986319), a bright (V = 9.9) G9 dwarf star in a visual binary system observed by the Transiting Exoplanet Survey Satellite (TESS) space mission in Sectors 5 and 6. We performed ground-based follow-up observations-comprised of Las Cumbres Observatory Global Telescope transit photometry, NIRC2 adaptive optics imaging, and FIbre-fed Echelle Spectrograph, CORALIE, High Accuracy Radial velocity Planet Searcher, High Resolution echelle Spectrometer, and Planet Finder Spectrograph high-precision Doppler measurements-and confirmed the planetary nature of the 16 day transiting candidate announced by the TESS team. We discovered an additional radial velocity signal with a period of five days induced by the presence of a second planet in the system, which we also found to transit its host star. We found that the inner mini-Neptune, TOI-421 b, has an orbital period of P-b = 5.19672 +/- 0.00049 days, a mass of M-b = 7.17 +/- 0.66 M-circle plus, and a radius of R-b = R-circle plus, whereas the outer warm Neptune, TOI-421 c, has a period of P-c = 16.06819 +/- 0.00035 days, a mass of M-c = 16.42(-1.04)(+1.06)M(circle plus), a radius of R-c = 5.09(-0.15)(+0.16)R(circle plus), and a density of rho(c) = 0.685(-0.072)(+0.080) cm(-3). With its characteristics, the outer planet (rho(c) = 0.685(-0.0072)(+0.080) cm(-3)) is placed in the intriguing class of the super-puffy mini-Neptunes. TOI-421 b and TOI-421 c are found to be well-suited for atmospheric characterization. Our atmospheric simulations predict significant Ly alpha transit absorption, due to strong hydrogen escape in both planets, as well as the presence of detectable CH4 in the atmosphere of TOI-421 c if equilibrium chemistry is assumed.
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16. |
- Hyldegaard, S., et al.
(author)
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R-matrix analysis of the beta decays of 12N and 12B
- 2010
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In: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 81:2
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Journal article (peer-reviewed)abstract
- The β decays of 12N and 12B have been studied at KVI and JYFL to resolve the composition of the broad and interfering 0+ and 2+ strengths in the triple-α continuum. For the first time a complete treatment of 3α decay is presented including all major breakup channels. A multilevel, many-channel R-matrix formalism has been developed for the complete description of the breakup in combination with the recently published separate analysis of angular correlations. We find that, in addition to the Hoyle state at 7.65 MeV, more than one 0+ and 2+ state is needed to reproduce the spectra. Broad 03+ and 22+ states are found between 10.5 and 12 MeV in this work. The presence of β strength up to the 12N Q-value window suggests the presence of additional 0+ and 2+ components in the 12C structure at energies above 12.7 MeV.
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17. |
- Margulies, Elliott H, et al.
(author)
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Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome
- 2007
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In: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:6, s. 760-774
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Journal article (peer-reviewed)abstract
- A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for the initially targeted 1% of the human genome. Here, we present orthologous sequence generation, alignment, and evolutionary constraint analyses of 23 mammalian species for all ENCODE targets. Alignments were generated using four different methods; comparisons of these methods reveal large-scale consistency but substantial differences in terms of small genomic rearrangements, sensitivity (sequence coverage), and specificity (alignment accuracy). We describe the quantitative and qualitative trade-offs concomitant with alignment method choice and the levels of technical error that need to be accounted for in applications that require multisequence alignments. Using the generated alignments, we identified constrained regions using three different methods. While the different constraint-detecting methods are in general agreement, there are important discrepancies relating to both the underlying alignments and the specific algorithms. However, by integrating the results across the alignments and constraint-detecting methods, we produced constraint annotations that were found to be robust based on multiple independent measures. Analyses of these annotations illustrate that most classes of experimentally annotated functional elements are enriched for constrained sequences; however, large portions of each class (with the exception of protein-coding sequences) do not overlap constrained regions. The latter elements might not be under primary sequence constraint, might not be constrained across all mammals, or might have expendable molecular functions. Conversely, 40% of the constrained sequences do not overlap any of the functional elements that have been experimentally identified. Together, these findings demonstrate and quantify how many genomic functional elements await basic molecular characterization.
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18. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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23. |
- Hyldegaard, S., et al.
(author)
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Precise branching ratios to unbound 12C states from 12N and 12B [beta]-decays
- 2009
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In: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 678:5, s. 459 - 464
-
Journal article (peer-reviewed)abstract
- Two complementary experimental techniques have been used to extract precise branching ratios to unbound states in 12C from 12N and 12B [beta]-decays. In the first the three [alpha]-particles emitted after [beta]-decay are measured in coincidence in separate detectors, while in the second method 12N and 12B are implanted in a detector and the summed energy of the three [alpha]-particles is measured directly. For the narrow states at 7.654 MeV (0+) and 12.71 MeV (1+) the resulting branching ratios are both smaller than previous measurements by a factor of [similar, equals]2. The experimental results are compared to no-core shell model calculations with realistic interactions from chiral perturbation theory, and inclusion of three-nucleon forces is found to give improved agreement.
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25. |
- Andersen, T. C. B., et al.
(author)
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The SH3 domains of the protein kinases ITK and LCK compete for adjacent sites on T cell?specific adapter protein
- 2019
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In: Journal of Biological Chemistry. - 0021-9258. ; 294:42, s. 15480-15494
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Journal article (peer-reviewed)abstract
- T-cell activation requires stimulation of specific intracellular signaling pathways in which protein-tyrosine kinases, phosphatases, and adapter proteins interact to transmit signals from the T-cell receptor to the nucleus. Interactions of LCK proto-oncogene, SRC family tyrosine kinase (LCK), and the IL-2?inducible T cell kinase (ITK) with the T cell-specific adapter protein (TSAD) promotes LCK-mediated phosphorylation and thereby ITK activation. Both ITK and LCK interact with TSAD's proline-rich region (PRR) through their Src homology 3 (SH3) domains. Whereas LCK may also interact with TSAD through its SH2 domain, ITK interacts with TSAD only through its SH3 domain. To begin to understand on a molecular level how the LCK SH3 and ITK SH3 domains interact with TSAD in human HEK293T cells, here we combined biochemical analyses with NMR spectroscopy. We found that the ITK and LCK SH3 domains potentially have adjacent and overlapping binding sites within the TSAD PRR amino acids (aa) 239?274. Pulldown experiments and NMR spectroscopy revealed that both domains may bind to TSAD aa 239?256 and aa 257?274. Co-immunoprecipitation experiments further revealed that both domains may also bind simultaneously to TSAD aa 242?268. Accordingly, NMR spectroscopy indicated that the SH3 domains may compete for these two adjacent binding sites. We propose that once the associations of ITK and LCK with TSAD promote the ITK and LCK interaction, the interactions among TSAD, ITK, and LCK are dynamically altered by ITK phosphorylation status.
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26. |
- Diget, C. A., et al.
(author)
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Breakup channels for C-12 triple-alpha continuum states
- 2009
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In: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 80:3
-
Journal article (peer-reviewed)abstract
- The triple-alpha-particle breakup of states in the triple-alpha continuum of C-12 has been investigated by way of coincident detection of all three alpha particles of the breakup. The states have been fed in the beta decay of N-12 and B-12, and the alpha particles measured using a setup that covers all of the triple-alpha phase space. Contributions from the breakup through the Be-8(0(+)) ground state as well as other channels-interpreted as breakup through excited energies in Be-8-have been identified. Spins and parities of C-12 triple-alpha continuum states are deduced from the measured phase-space distributions for breakup through Be-8 above the ground state by comparison to a fully symmetrized sequential R-matrix description of the breakup. At around 10 MeV in C-12, the breakup is found to be dominated by 0(+) strength breaking up through the ghost of the Be-8(0(+)) ground state with L = 0 angular momentum between the first emitted alpha particle and the intermediate Be-8 nucleus. For C-12 energies above the 12.7 MeV 1(+) state, however, L = 2 breakup of a C-12 2(+) state through the Be-8(2(+)) excited state dominates. Furthermore, the possibility of a 2(+) excited state in the 9-12 MeV region of C-12 is investigated.
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27. |
- Faber, Zachary J, et al.
(author)
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The genomic landscape of core-binding factor acute myeloid leukemias
- 2016
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 48, s. 1551-1556
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Journal article (peer-reviewed)abstract
- Acute myeloid leukemia (AML) comprises a heterogeneous group of leukemias frequently defined by recurrent cytogenetic abnormalities, including rearrangements involving the core-binding factor (CBF) transcriptional complex. To better understand the genomic landscape of CBF-AMLs, we analyzed both pediatric (n = 87) and adult (n = 78) samples, including cases with RUNX1-RUNX1T1 (n = 85) or CBFB-MYH11 (n = 80) rearrangements, by whole-genome or whole-exome sequencing. In addition to known mutations in the Ras pathway, we identified recurrent stabilizing mutations in CCND2, suggesting a previously unappreciated cooperating pathway in CBF-AML. Outside of signaling alterations, RUNX1-RUNX1T1 and CBFB-MYH11 AMLs demonstrated remarkably different spectra of cooperating mutations, as RUNX1-RUNX1T1 cases harbored recurrent mutations in DHX15 and ZBTB7A, as well as an enrichment of mutations in epigenetic regulators, including ASXL2 and the cohesin complex. This detailed analysis provides insights into the pathogenesis and development of CBF-AML, while highlighting dramatic differences in the landscapes of cooperating mutations for these related AML subtypes.
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28. |
- Fynbo, H. O. U., et al.
(author)
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Revised rates for the stellar triple-alpha process from measurement of C-12 nuclear resonances
- 2005
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687 .- 1476-4679. ; 433:7022, s. 136-139
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Journal article (peer-reviewed)abstract
- In the centres of stars where the temperature is high enough, three alpha-particles (helium nuclei) are able to combine to form C-12 because of a resonant reaction leading to a nuclear excited state(1). (Stars with masses greater than similar to0.5 times that of the Sun will at some point in their lives have a central temperature high enough for this reaction to proceed.) Although the reaction rate is of critical significance for determining elemental abundances in the Universe(1), and for determining the size of the iron core of a star just before it goes supernova(2), it has hitherto been insufficiently determined(2). Here we report a measurement of the inverse process, where a C-12 nucleus decays to three alpha-particles. We find a dominant resonance at an energy of similar to11 MeV, but do not confirm the presence of a resonance at 9.1 MeV (ref. 3). We show that interference between two resonances has important effects on our measured spectrum. Using these data, we calculate the triple-a rate for temperatures from 10(7) K to 10(10) K and find significant deviations from the standard rates(3). Our rate below similar to5 x 10(7) K is higher than the previous standard, implying that the critical amounts of carbon that catalysed hydrogen burning in the first stars are produced twice as fast as previously believed(4). At temperatures above 10(9) K, our rate is much less, which modifies predicted nucleosynthesis in supernovae(5,6).
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29. |
- Fynbo, H. O. U., et al.
(author)
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The β-decay approach for studying 12C
- 2008
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In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 111:1
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Journal article (peer-reviewed)abstract
- The β-decays of the mirror nuclei 12B and 12N both populate states in 12C and they are therefore a precious source of information about this nucleus. Due to the selection rules of β-decay only 0+, 1+ and 2+ states are populated. This allows a very clean study of unbound states just above the 3α-threshold with those spin and parities. This probe has been applied in two experiments using two complementary experimental techniques: in the first the three α-particles emitted after β-decay are measured in coincidence in separate detectors using the ISOL method, while in the second method 12B and 12N are implanted in a detector and the summed energy of the three α-particles is measured directly. Preliminary results from the two approaches are presented. © 2008 IOP Publishing Ltd.
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30. |
- Hyldegaard, S., et al.
(author)
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Branching ratios in the beta decays of N-12 and B-12
- 2009
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In: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 80:4
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Journal article (peer-reviewed)abstract
- Absolute branching ratios to unbound states in C-12 populated in the beta decays of N-12 and B-12 are reported. Clean sources of N-12 and B-12 were obtained using the isotope separation on-line (ISOL) method. The relative branching ratios to the different populated states were extracted using single-alpha as well as complete kinematics triple-alpha spectra. These two largely independent methods give consistent results. Absolute normalization is achieved via the precisely known absolute branching ratio to the bound 4.44 MeV state in C-12. The extracted branching ratios to the unbound states are a factor of three more precise than previous measurements. Branching ratios in the decay of Na-20 are also extracted and used to check the results.
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31. |
- Kirsebom, O. S., et al.
(author)
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Observation of gamma-delayed 3 alpha breakup of the 15.11 and 12.71 MeV states in C-12
- 2009
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In: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 680:1, s. 44-49
-
Journal article (peer-reviewed)abstract
- The reactions B-10(He-3, p alpha alpha alpha) at 4.9 MeV and B-11(He-3, d alpha alpha alpha) at 8.5 MeV have been used to investigate the gamma decay of states in C-12. By measuring the four-body final state in complete kinematics we are able to detect gamma transitions indirectly. We find gamma transitions from the 15.11 MeV state in C-12 to the 12.71, 11.83, 10.3 and 7.65 MeV states followed by their breakup into three alpha particles. The relative gamma-ray branching ratios obtained are (1.2 +/- 0.3), (0.32 +/- 0.12), (1.4 +/- 0.2) and (4.4 +/- 0.8)%, respectively, with the remaining (92.7 +/- 1.0)% of the gamma decays going to the bound states. We obtain Gamma(alpha)/Gamma = (2.8 +/- 1.2)% for the isospinforbidden alpha decay of the 15.11 MeV state. From the 12.71 MeV state we find gamma transitions to the 10.3 and 7.65 MeV states. The relative gamma-ray branching ratios are (0.9(-0.5)(+0.6)) and (2.6(-1.2)(+1.6))%, respectively, with the remaining (96.6(-1.3)(+1.7))% of the gamma decays going to the bound states. Finally. we discuss the relation between the beta decay of N-12 and B-12 to states in C-12 and the gamma decay of the 15.11 MeV analog in C-12 to the same states. (C) 2009 Elsevier B.V. All rights reserved.
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32. |
- van der Werf, P.P., et al.
(author)
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Black hole accretion and star formation as drivers of gas excitation and chemistry in Markarian 231
- 2010
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L42
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Journal article (peer-reviewed)abstract
- We present a full high resolution SPIRE FTS spectrum of the nearby ultraluminous infrared galaxy Mrk 231. In total 25 lines are detected, including CO J = 5-4 through J = 13-12, 7 rotational lines of H2O, 3 of OH+ and one line each of H2O+, CH+, and HF. We find that the excitation of the CO rotational levels up to J = 8 can be accounted for by UV radiation from star formation. However, the approximately flat luminosity distribution of the CO lines over the rotational ladder above J = 8 requires the presence of a separate source of excitation for the highest CO lines. We explore X-ray heating by the accreting supermassive black hole in Mrk 231 as a source of excitation for these lines, and find that it can reproduce the observed luminosities. We also consider a model with dense gas in a strong UV radiation field to produce the highest CO lines, but find that this model strongly overpredicts the hot dust mass in Mrk 231. Our favoured model consists of a star forming disk of radius 560 pc, containing clumps of dense gas exposed to strong UV radiation, dominating the emission of CO lines up to J = 8. X-rays from the accreting supermassive black hole in Mrk 231 dominate the excitation and chemistry of the inner disk out to a radius of 160 pc, consistent with the X-ray power of the AGN in Mrk 231. The extraordinary luminosity of the OH+ and H2O+ lines reveals the signature of X-ray driven excitation and chemistry in this region.
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33. |
- Yusuf, D, et al.
(author)
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The transcription factor encyclopedia
- 2012
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In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906. ; 13:3, s. R24-
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Journal article (peer-reviewed)
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34. |
- Alcorta, M., et al.
(author)
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Nuclear Structure of C-12 from Break-up Studies in Complete Kinematics
- 2009
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In: AIP Conference Proceedings. - : AIP. - 1551-7616 .- 0094-243X. - 9780735407022 ; 1165, s. 27-30 461
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Conference paper (peer-reviewed)abstract
- A complete kinematics study of the B-10(He-3,p alpha alpha alpha) and B-11(He-3,d alpha alpha alpha) reactions has been performed to study the multi-particle break-up of C-12 resonances above the triple-alpha threshold. Four-particle coincidence detection gives us complete information on the direction and energy of the individual alpha particles from the decay of C-12, allowing us to extract new information on the structure of C-12 which we shall present in this contribution. We have observed gamma de-excitation of the T=1 15.11 MeV resonance using charged particle detectors, and have constructed Dalitz plots of the individual resonances in C-12 using the complete kinematics information of the alpha particles which come from their break-up.
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35. |
- Alcorta, M., et al.
(author)
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Properties of resonances in 12C above the triple-alpha threshold
- 2011
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In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 312:SECTION 9, s. Art. no. 092013-
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Conference paper (peer-reviewed)abstract
- A complete kinematics study of the 10B(3He, pααα) and the 11B(3He, dααα) reactions has been performed to study the multi-particle break-up of 12C resonances above the triple-alpha threshold. The values of energy and widths of some states has been improved, and in states of natural parity partial branches of decay through the ground state of 8Be have been extracted. The influence of the "ghost" of the 8Be ground state has been taken into account in order to clarify the partial branches.
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36. |
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37. |
- Bammer, G., et al.
(author)
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Expertise in research integration and implementation for tackling complex problems: when is it needed, where can it be found and how can it be strengthened?
- 2020
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In: Palgrave Communications. - : Springer Science and Business Media LLC. - 2055-1045. ; 6
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Journal article (peer-reviewed)abstract
- Expertise in research integration and implementation is an essential but often overlooked component of tackling complex societal and environmental problems. We focus on expertise relevant to any complex problem, especially contributory expertise, divided into 'knowing-that' and 'knowing-how.' We also deal with interactional expertise and the fact that much expertise is tacit. We explore three questions. First, in examining 'when is expertise in research integration and implementation required?,' we review tasks essential (a) to developing more comprehensive understandings of complex problems, plus possible ways to address them, and (b) for supporting implementation of those understandings into government policy, community practice, business and social innovation, or other initiatives. Second, in considering 'where can expertise in research integration and implementation currently be found?,' we describe three realms: (a) specific approaches, including interdisciplinarity, transdisciplinarity, systems thinking and sustainability science; (b) case-based experience that is independent of these specific approaches; and (c) research examining elements of integration and implementation, specifically considering unknowns and fostering innovation. We highlight examples of expertise in each realm and demonstrate how fragmentation currently precludes clear identification of research integration and implementation expertise. Third, in exploring 'what is required to strengthen expertise in research integration and implementation?,' we propose building a knowledge bank. We delve into three key challenges: compiling existing expertise, indexing and organising the expertise to make it widely accessible, and understanding and overcoming the core reasons for the existing fragmentation. A growing knowledge bank of expertise in research integration and implementation on the one hand, and accumulating success in addressing complex societal and environmental problems on the other, will form a virtuous cycle so that each strengthens the other. Building a coalition of researchers and institutions will ensure this expertise and its application are valued and sustained.
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38. |
- Crossfield, Ian J. M., et al.
(author)
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197 CANDIDATES AND 104 VALIDATED PLANETS IN K2's FIRST FIVE FIELDS
- 2016
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In: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 226:1
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Journal article (peer-reviewed)abstract
- We present 197 planet candidates discovered using data from the first year of the NASA K2 mission (Campaigns 0-4), along with the results of an intensive program of photometric analyses, stellar spectroscopy, high-resolution imaging, and statistical validation. We distill these candidates into sets of 104 validated planets (57 in multi-planet systems), 30 false positives, and 63 remaining candidates. Our validated systems span a range of properties, with median values of R-P = 2.3 R-circle plus, P = 8.6 days, T-eff = 5300 K, and Kp = 12.7 mag. Stellar spectroscopy provides precise stellar and planetary parameters for most of these systems. We show that K2 has increased by 30% the number of small planets known to orbit moderately bright stars (1-4 R-circle plus, Kp = 9-13. mag). Of particular interest are 76 planets smaller than 2 R-circle plus, 15 orbiting stars brighter than Kp = 11.5. mag, 5 receiving Earth-like irradiation levels, and several multi-planet systems-including 4 planets orbiting the M dwarf K2-72 near mean-motion resonances. By quantifying the likelihood that each candidate is a planet we demonstrate that our candidate sample has an overall false positive rate of 15%-30%, with rates substantially lower for small candidates (<2 R-circle plus) and larger for candidates with radii >8 R-circle plus and/or with P < 3 days. Extrapolation of the current planetary yield suggests that K2 will discover between 500 and 1000 planets in its planned four-year mission, assuming sufficient follow-up resources are available. Efficient observing and analysis, together with an organized and coherent follow-up strategy, are essential for maximizing the efficacy of planet-validation efforts for K2, TESS, and future large-scale surveys.
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39. |
- Cubero, M., et al.
(author)
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Do Halo Nuclei Follow Rutherford Elastic Scattering at Energies Below the Barrier? The Case of 11Li
- 2012
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In: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 109:26
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Journal article (peer-reviewed)abstract
- The first measurement of the elastic scattering of the halo nucleus 11Li and its core 9Li on 208Pb at energies near the Coulomb barrier is presented. The 11Li+208Pb elastic scattering shows a strong reduction with respect to the Rutherford cross section, even at energies well below the barrier and down to very small scattering angles. This drastic change of the elastic differential cross section observed in 11Li+208Pb is the consequence of the halo structure of 11Li, as it is not observed in the elastic scattering of its core 9Li at the same energies. Four-body continuum-discretized coupled-channels calculations, based on a three-body model of the 11Li projectile, are found to explain the measured angular distributions and confirm that the observed reduction is mainly due to the strong Coulomb coupling to the dipole states in the low-lying continuum of 11Li. These calculations suggest the presence of a low-lying dipole resonance in 11Li close to the breakup threshold.
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40. |
- Diget, C. A., et al.
(author)
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Properties of the C-12 10 MeV state determined through beta-decay
- 2005
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In: Nuclear Physics A. - : Elsevier BV. - 0375-9474. ; 760:1-2, s. 3-18
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Journal article (peer-reviewed)abstract
- The beta-delayed triple-alpha particle decay of B-12 has been measured with a setup that favours coincidence detection. A broad state in C-12, previously reported around 10 MeV, has been seen and its properties determined through R-matrix analysis of the excitation spectrum. The spin and parity are 0(+). Interference between this state and the Hoyle state at 7.654 MeV has a marked influence on the spectrum. The coupling between the two states makes it difficult to determine the resonance energy. (c) 2005 Elsevier B.V. All rights reserved.
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41. |
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42. |
- Fernandez-Garcia, J. P., et al.
(author)
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11Li Breakup on 208Pb at Energies Around the Coulomb Barrier
- 2013
-
In: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 110:14
-
Journal article (peer-reviewed)abstract
- The inclusive breakup for the Li-11 + Pb-208 reaction at energies around the Coulomb barrier has been measured for the first time. A sizable yield of Li-9 following the Li-11 dissociation has been observed, even at energies well below the Coulomb barrier. Using the first-order semiclassical perturbation theory of Coulomb excitation it is shown that the breakup probability data measured at small angles can be used to extract effective breakup energy as well as the slope of B(E1) distribution close to the threshold. Four-body continuum-discretized coupled-channels calculations, including both nuclear and Coulomb couplings between the target and projectile to all orders, reproduce the measured inclusive breakup cross sections and support the presence of a dipole resonance in the Li-11 continuum at low excitation energy.
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43. |
- Fernandez-Garcia, J. P., et al.
(author)
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Li-11 structural information from inclusive break-up measurements
- 2015
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In: EPJ Web of Conferences. - : EDP Sciences. - 2101-6275 .- 2100-014X. ; 88
-
Conference paper (peer-reviewed)abstract
- Structure information of Li-11 halo nucleus has been obtained from the inclusive break-up measurements of the Li-11+Pb-208 reactions at energies around the Coulomb barrier (E-lab = 24.3 and 29.8 MeV). The effective break-up energy and the slope of B(E1) distribution close to the threshold have been extracted from the experimental data.
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44. |
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45. |
- Fynbo, H. O. U., et al.
(author)
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News on C-12 from beta-decay studies
- 2004
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In: Nuclear Physics A. - : Elsevier BV. - 0375-9474. ; 738, s. 59-65
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Conference paper (peer-reviewed)abstract
- We discuss the importance of the spectroscopic properties of the resonances of C-12 just above the 3alpha-threshold, and review the existing experimental information of this region with emphasis on 0(+) and 2(+) states. A new experimental approach for studying the beta-decays of B-12 and N-12 is presented based on techniques developed in the context of Radioactive beam (rare isotope) physics. Finally preliminary results from an ongoing analysis of two recent experiments are given.
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46. |
- Hyldegaard, S., et al.
(author)
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STUDIES OF C-12 USING beta-DECAYS
- 2008
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In: International Journal of Modern Physics E. - 0218-3013. ; 17:10, s. 2182-2187
-
Conference paper (peer-reviewed)abstract
- The nuclear structure of states in C-12 have been a subject of interest for both theory and experiment since the early days of nuclear physics. Many open questions remain, especially concerning the existence and properties of 0(+) and 2(+) states in the triple alpha continuum. A series of experiments have been performed using beta-decay of N-12 and B-12 to probe these states. The latest experiment was performed at KVI using an implantation method, measuring the sum energy of the three alpha-particles directly. Preliminary results from this experiment will be presented.
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47. |
- Jensen, S. B., et al.
(author)
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A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact
- 2010
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In: SUPPORTIVE CARE IN CANCER. - 0941-4355. ; 18:8, s. 1061-1079
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Journal article (peer-reviewed)abstract
- Purpose This systematic review aimed to assess the literature for management strategies and economic impact of salivary gland hypofunction and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations. Methods The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. For each article, two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results, and conclusions. Results Seventy-two interventional studies met the inclusion criteria. In addition, 49 intensity-modulated radiation therapy (IMRT) studies were included as a management strategy aiming for less salivary gland damage. Management guideline recommendations were drawn up for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Conclusions There is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment. Management guideline recommendations are provided for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia.
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48. |
- Kirsebom, O. S., et al.
(author)
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Breakup of 12C resonances into three α particles
- 2010
-
In: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 81:6
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Journal article (peer-reviewed)abstract
- The reaction He-3 + B-11 -> d + C-12* has been used to populate resonances in C-12 up to an excitation energy of 15 MeV. The subsequent breakup to three alpha particles has been measured in complete kinematics. Dalitz plots are used to visualize and analyze the data. The Dalitz plot intensity distribution exhibits zero points characteristic of the total spin and parity of the 3 alpha system allowing us to determine the spin and parity of a state in C-12 at 13.35 MeV whose quantum numbers were hitherto not well established. The Dalitz plot intensity distributions of the 2(-) state at 11.83 MeV and the 1(+) state at 12.71 MeV are compared with the predictions of a recent three-body calculation as well as with simpler models. All are able to reproduce the gross structures seen in the Dalitz plot, but none give an accurate description of the detailed profile of the distributions.
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49. |
- Knudsen, H. H., et al.
(author)
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Beta-decay of 13O
- 2005
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In: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 72:4, s. 044312-
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Journal article (peer-reviewed)abstract
- The beta decay of O-13 has been studied at the IGISOL facility of the Jyvaskyla accelerator centre (Finland). By developing a low-energy isotope-separated beam of O-13 and using a modern segmented charged-particle detector array an improved measurement of the delayed proton spectrum was possible. Protons with energy up to more than 12 MeV are measured and the corresponding log(ft) values extracted. A revised decay scheme is constructed. The connection to molecular states and the shell model is discussed.
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50. |
- Prezado, Y., et al.
(author)
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Low-lying resonance states in the Be-9 continuum
- 2005
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In: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 618:1-4, s. 43-50
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Journal article (peer-reviewed)abstract
- Excited states in Be-9 from 2 to 9 MeV are studied via beta delayed particle emission from Li-9. The broad overlapping particle unbound states are investigated using an extension of an experimental method developed for dealing with three-body decays of broad isolated levels. The results confirm the existence of a broad state at 5 MeV, with a width of 2 MeV. Angular correlations are used for firm spin determinations for this and other levels.
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