| 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. |
- Meyer, H., et al.
(författare)
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Overview of physics results from MAST
- 2009
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 49:10, s. 104017-
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Tidskriftsartikel (refereegranskat)abstract
- Several improvements to the MAST plant and diagnostics have facilitated new studies advancing the physics basis for ITER and DEMO, as well as for future spherical tokamaks (STs). Using the increased heating capabilities P-NBI <= 3.8 MW H-mode at I-P = 1.2 MA was accessed showing that the energy confinement on MAST scales more weakly with I-P and more strongly with B-t than in the ITER IPB98(y, 2) scaling. Measurements of the fuel retention of shallow pellets extrapolate to an ITER particle throughput of 70% of its original designed total throughput capacity. The anomalous momentum diffusion, chi(phi), is linked to the ion diffusion, chi(i), with a Prandtl number close to P-phi approximate to chi(phi)/chi(i) approximate to 1, although chi(i) approaches neoclassical values. New high spatial resolution measurements of the edge radial electric field, E-r, show that the position of steepest gradients in electron pressure and E-r (i.e. shearing rate) are coincident, but their magnitudes are not linked. The T-e pedestal width on MAST scales with root beta(ped)(pol) rather than rho(pol). The edge localized mode (ELM) frequency for type-IV ELMs, new in MAST, was almost doubled using n = 2 resonant magnetic perturbations from a set of four external coils (n = 1, 2). A new internal 12 coil set (n <= 3) has been commissioned. The filaments in the inter-ELM and L-mode phase are different from ELM filaments, and the characteristics in L-mode agree well with turbulence calculations. A variety of fast particle driven instabilities were studied from 10 kHz saturated fishbone like activity up to 3.8 MHz compressional Alfven eigenmodes. Fast particle instabilities also affect the off-axis NBI current drive, leading to fast ion diffusion of the order of 0.5 m(2) s(-1) and a reduction in the driven current fraction from 40% to 30%. EBW current drive start-up is demonstrated for the first time in a ST generating plasma currents up to 55 kA. Many of these studies contributed to the physics basis of a planned upgrade to MAST.
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| 3. |
- Newton-Cheh, Christopher, et al.
(författare)
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Genome-wide association study identifies eight loci associated with blood pressure
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:6, s. 666-676
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N <= 71,225 European ancestry, N <= 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
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| 4. |
- Lindgren, Cecilia M, et al.
(författare)
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Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.
- 2009
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:6, s. e1000508-
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Tidskriftsartikel (refereegranskat)abstract
- To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.
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| 5. |
- Prokopenko, Inga, et al.
(författare)
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Variants in MTNR1B influence fasting glucose levels
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 77-81
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Tidskriftsartikel (refereegranskat)abstract
- To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.
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| 6. |
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| 7. |
- Loos, Ruth J. F., et al.
(författare)
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Common variants near MC4R are associated with fat mass, weight and risk of obesity
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:6, s. 768-775
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Tidskriftsartikel (refereegranskat)abstract
- To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.
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| 8. |
- Regan, P H, et al.
(författare)
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Vibrational and rotational sequences in Mo-101 and Ru-103,Ru-4 studied via multinucleon transfer reactions
- 2005
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Ingår i: Acta Physica Polonica B. - 0587-4254 .- 1509-5770. ; 36:4, s. 1313-1322
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Tidskriftsartikel (refereegranskat)abstract
- The near-yrast states of Mo-101(42)59 and Ru-103,4(44)59,60 have been studied following their population via heavy-ion multinucleon transfer reactions between a Xe-136 beam and a thin, self-supporting Mo-100 target. The ground state sequence in Ru-104 can be understood as demonstrating a simple evolution from a quasi-vibrational structure at lower spins to statically deformed, quasi-rotational excitation involving the population of a pair of low-Omega h(11/2) neutron orbitals. The effect of the decoupled h(11/2) orbital on this vibration-to-rotational evolution is demonstrated by an extension of the "E-GOS" prescription to include odd-A nuclei. The experimental results are also compared with self-consistent Total Routhian Surface calculations which also highlight the polarising role of the highly aligned neutron h(11/2) orbital in these nuclei.
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| 9. |
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| 10. |
- Jiang, Q. H., et al.
(författare)
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High-temperature ferroelectric phase transition observed in multiferroic Bi0.91La0.05Tb0.04FeO3
- 2009
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 95:1, s. 12909-
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Tidskriftsartikel (refereegranskat)abstract
- A single-phase Bi0.91La0.05Tb0.04FeO3 polycrystalline ceramic was fabricated by spark-plasma-sintering the precursor powder prepared by a sol-gel method. Temperature-dependent properties of polycrystalline Bi0.91La0.05Tb0.04FeO3 were characterized by x-ray diffraction, dielectric, and piezoelectric measurement. The x-ray diffraction results revealed a phase transition near 700 degrees C. Especially, temperature-dependent dielectric behavior demonstrated that there was a dielectric abnormal peak at about 697 degrees C, in addition to those two well-known dielectric abnormal peaks at 337 degrees C (Neel temperature) and 831 degrees C (Curie temperature). The observations, together with thermal depoled behavior, suggest a ferroelectric-ferroelectric phase transition from R(3)c to Pbnm at around 700 degrees C.
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