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| 2. |
- 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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| 3. |
- 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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| 5. |
- Adewumi, Oluseun, et al.
(författare)
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Characterization of human embryonic stem cell lines by the International Stem Cell Initiative
- 2007
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Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 25:7, s. 803-816
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Tidskriftsartikel (refereegranskat)abstract
- The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue- nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.
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| 7. |
- Mach, H., et al.
(författare)
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New structure information on Mg-30, Mg-31 and Mg-32
- 2005
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-601X .- 1434-6001. ; 25, s. 105-109
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Konferensbidrag (refereegranskat)abstract
- The fast timing beta gamma gamma(t) method was applied to investigate the level lifetimes in Mg-30,Mg-31,Mg-32. Levels in Mg have been populated in beta and beta-delayed neutron emission of Na, at the ISOLDE facility. From the gamma gamma coincidences a number of new states have been identified and new level schemes were constructed for 30 31,32 Mg. The following preliminary half lives have been determined: T-1/2 = 3.9(4) ns for the 1789 keV state in Mg-30, T-1/2 = 133(8) ps and 10.5(8) us for the 221 keV and 461 keV states in Mg-31, respectively, and T1/2 = 16(4) ps for the 885 keV level in 32Mg. The 1789 keV level was established as a candidate for the intruder 0(+) configuration in Mg-30 with a possible strong E0 branch to the ground state.
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| 8. |
- Metra, M., et al.
(författare)
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Influence of heart rate, blood pressure, and beta-blocker dose on outcome and the differences in outcome between carvedilol and metoprolol tartrate in patients with chronic heart failure: results from the COMET trial
- 2005
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 26:21, s. 2259-68
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: We studied the influence of heart rate (HR), systolic blood pressure (SBP), and beta-blocker dose on outcome in the 2599 out of 3029 patients in Carvedilol Or Metoprolol European Trial (COMET) who were alive and on study drug at 4 months after randomization (time of first visit on maintenance therapy). METHODS AND RESULTS: By multivariable analysis, baseline HR, baseline SBP, and their change after 4 months were not independently related to subsequent outcome. In a multivariable analysis including clinical variables, HR above and SBP below the median value achieved at 4 months predicted subsequent increased mortality [relative risk (RR) for HR>68 b.p.m. 1.333; 95% confidence intervals (CI) 1.152-1.542; P<0.0001 and RR for SBP>120 mmHg 0.78; 95% CI 0.671-0.907; P<0.0013]. Achieving target beta-blocker dose was associated with a better outcome (RR 0.779; 95% CI 0.662-0.916; P<0.0025). The superiority of carvedilol as compared to metoprolol tartrate was maintained in a multivariable model (RR 0.767; 95% CI 0.663-0.887; P=0.0004) and there was no interaction with HR, SBP, or beta-blocker dose. CONCLUSION: Beta-blocker dose, HR, and SBP achieved during beta-blocker therapy have independent prognostic value in heart failure. None of these factors influenced the beneficial effects of carvedilol when compared with metoprolol tartrate at the pre-defined target doses used in COMET.
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| 9. |
- Pedersen, A., et al.
(författare)
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Electron density estimations derived from spacecraft potential measurements on Cluster in tenuous plasma regions
- 2008
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 113:A7, s. A07S33-
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Tidskriftsartikel (refereegranskat)abstract
- Spacecraft potential measurements by the EFW electric field experiment on the Cluster satellites can be used to obtain plasma density estimates in regions barely accessible to other type of plasma experiments. Direct calibrations of the plasma density as a function of the measured potential difference between the spacecraft and the probes can be carried out in the solar wind, the magnetosheath, and the plasmashere by the use of CIS ion density and WHISPER electron density measurements. The spacecraft photoelectron characteristic ( photoelectrons escaping to the plasma in current balance with collected ambient electrons) can be calculated from knowledge of the electron current to the spacecraft based on plasma density and electron temperature data from the above mentioned experiments and can be extended to more positive spacecraft potentials by CIS ion and the PEACE electron experiments in the plasma sheet. This characteristic enables determination of the electron density as a function of spacecraft potential over the polar caps and in the lobes of the magnetosphere, regions where other experiments on Cluster have intrinsic limitations. Data from 2001 to 2006 reveal that the photoelectron characteristics of the Cluster spacecraft as well as the electric field probes vary with the solar cycle and solar activity. The consequences for plasma density measurements are addressed. Typical examples are presented to demonstrate the use of this technique in a polar cap/lobe plasma.
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| 10. |
- Torp-Pedersen, C., et al.
(författare)
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Effects of metoprolol and carvedilol on preexisting and new on-set diabetes in patients with chronic heart failure {inverted exclamation}V data from the Carvedilol or metoprolol European Trial (COMET)
- 2007
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Ingår i: Heart. - 1468-201X. ; 93:8, s. 968-973
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Tidskriftsartikel (refereegranskat)abstract
- Objective Beta-blocker therapy may worsen glucose metabolism. We studied the development of new onset diabetes in a large cohort of heart failure patients treated with either metoprolol or carvedilol. Design Prospective and retrospective analysis of a controlled clinical trial. Setting Multinational multicenter study Patients 3029 patients with chronic heart failure. Interventions Randomly assigned treatment with carvedilol (n=1511, target dose 50 mg daily) or metoprolol tartrate (n=1518, target dose 100 mg daily). Results Diabetic events (diabetic coma, peripheral gangrene, diabetic foot, de-creased glucose tolerance or hyperglycemia) and new onset diabetes (clinical di-agnosis, repeated high random glucose level or glucose lowering medication) were assessed in 2298 patients without diabetes at baseline. Diabetic events oc-curred in 122/1151 (10.6%) patients in the carvedilol group and 149/1147 (13.0%) patients in the metoprolol group (hazard ratio (HR) 0.78; 95% confi-dence interval (CI) 0.61-0.99, p=0.039). New onset diabetes was diagnosed in 119/1151 (10.4%) versus 145/1147 (12.6%) cases in the carvedilol and metoprolol treatment groups (HR 0.78, CI 0.61-0.998, p=0.048). Patients with diabetes at baseline had an increased mortality, compared to non-diabetics (45.3% versus, 33.9%; HR 1.45, CI 1.28-1.65). Both diabetics and non-diabetics at baseline had a similar reduction in mortality with carvedilol compared to metoprolol (RR 0.85; CI 0.69-1.06 and RR 0.82; CI, 0.71-0.94, respectively). Conclusion This study demonstrates both a high prevalence and incidence of diabetes in patients with heart failure over a course of 5 years. New onset diabe-tes was more likely to occur during treatment with metoprolol than during treat-ment with carvedilol.
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