| 1. |
- Birney, Ewan, et al.
(författare)
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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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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Alcorta, M., et al.
(författare)
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Nuclear Structure of C-12 from Break-up Studies in Complete Kinematics
- 2009
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Ingår i: AIP Conference Proceedings. - : AIP. - 1551-7616 .- 0094-243X. - 9780735407022 ; 1165, s. 27-30 461
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Konferensbidrag (refereegranskat)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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| 4. |
- Fynbo, H. O. U., et al.
(författare)
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The β-decay approach for studying 12C
- 2008
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 111:1
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Hyldegaard, S., et al.
(författare)
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Precise branching ratios to unbound 12C states from 12N and 12B [beta]-decays
- 2009
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 678:5, s. 459 - 464
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Hyldegaard, S., et al.
(författare)
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STUDIES OF C-12 USING beta-DECAYS
- 2008
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Ingår i: International Journal of Modern Physics E. - 0218-3013. ; 17:10, s. 2182-2187
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Konferensbidrag (refereegranskat)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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| 7. |
- Kirsebom, O. S., et al.
(författare)
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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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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 680:1, s. 44-49
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Tidskriftsartikel (refereegranskat)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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| 8. |
- Margulies, Elliott H, et al.
(författare)
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Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome
- 2007
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:6, s. 760-774
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Tidskriftsartikel (refereegranskat)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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| 9. |
- Diget, C. A., et al.
(författare)
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Properties of the C-12 10 MeV state determined through beta-decay
- 2005
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Ingår i: Nuclear Physics A. - : Elsevier BV. - 0375-9474. ; 760:1-2, s. 3-18
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Tidskriftsartikel (refereegranskat)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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| 10. |
- Ding, Li, et al.
(författare)
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Somatic mutations affect key pathways in lung adenocarcinoma
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7216, s. 1069-1075
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Tidskriftsartikel (refereegranskat)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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