| 11. |
- 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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| 12. |
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| 13. |
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| 14. |
- Fitzmaurice, C, et al.
(författare)
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Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2016: A Systematic Analysis for the Global Burden of Disease Study
- 2018
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Ingår i: JAMA oncology. - : American Medical Association (AMA). - 2374-2445 .- 2374-2437. ; 4:11, s. 1553-1568
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Tidskriftsartikel (refereegranskat)
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| 15. |
- Parail, V., et al.
(författare)
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Integrated modelling of ITER reference scenarios
- 2009
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 49:7
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Tidskriftsartikel (refereegranskat)abstract
- The ITER Scenario Modelling Working Group (ISM WG) is organized within the European Task Force on Integrated Tokamak Modelling (ITM-TF). The main responsibility of the WG is to advance a pan-European approach to integrated predictive modelling of ITER plasmas with the emphasis on urgent issues, identified during the ITER Design Review. Three major topics are discussed, which are considered as urgent and where the WG has the best possible expertize. These are modelling of current profile control, modelling of density control and impurity control in ITER (the last two topics involve modelling of both core and SOL plasma). Different methods of heating and current drive are tested as controllers for the current profile tailoring during the current ramp-up in ITER. These include Ohmic, NBI, ECRH and LHCD methods. Simulation results elucidate the available operational margins and rank different methods according to their ability to meet different requirements. A range of ITER-relevant' plasmas from existing tokamaks were modelled. Simulations confirmed that the theory-based transport model, GLF23, reproduces the density profile reasonably well and can be used to assess ITER profiles with both pellet injection and gas puffing. In addition, simulations of the SOL plasma were launched using both H-mode and L-mode models for perpendicular transport within the edge barrier and in the SOL. Finally, an integrated approach was also used for the predictive modelling of impurity accumulation in ITER. This includes helium ash, extrinsic impurities (such as argon) and impurities coming from the wall (including tungsten). The relative importance of anomalous and neo-classical pinch contributions towards impurity penetration through the edge transport barrier and further accumulation in the core was assessed.
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| 16. |
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| 17. |
- Ranson, J. M., et al.
(författare)
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Modifiable risk factors for dementia and dementia risk profiling. A user manual for Brain Health Services-part 2 of 6
- 2021
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Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- We envisage the development of new Brain Health Services to achieve primary and secondary dementia prevention. These services will complement existing memory clinics by targeting cognitively unimpaired individuals, where the focus is on risk profiling and personalized risk reduction interventions rather than diagnosing and treating late-stage disease. In this article, we review key potentially modifiable risk factors and genetic risk factors and discuss assessment of risk factors as well as additional fluid and imaging biomarkers that may enhance risk profiling. We then outline multidomain measures and risk profiling and provide practical guidelines for Brain Health Services, with consideration of outstanding uncertainties and challenges. Users of Brain Health Services should undergo risk profiling tailored to their age, level of risk, and availability of local resources. Initial risk assessment should incorporate a multidomain risk profiling measure. For users aged 39-64, we recommend the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) Dementia Risk Score, whereas for users aged 65 and older, we recommend the Brief Dementia Screening Indicator (BDSI) and the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI). The initial assessment should also include potentially modifiable risk factors including sociodemographic, lifestyle, and health factors. If resources allow, apolipoprotein E e4 status testing and structural magnetic resonance imaging should be conducted. If this initial assessment indicates a low dementia risk, then low intensity interventions can be implemented. If the user has a high dementia risk, additional investigations should be considered if local resources allow. Common variant polygenic risk of late-onset AD can be tested in middle-aged or older adults. Rare variants should only be investigated in users with a family history of early-onset dementia in a first degree relative. Advanced imaging with 18-fluorodeoxyglucose positron emission tomography (FDG-PET) or amyloid PET may be informative in high risk users to clarify the nature and burden of their underlying pathologies. Cerebrospinal fluid biomarkers are not recommended for this setting, and blood-based biomarkers need further validation before clinical use. As new technologies become available, advances in artificial intelligence are likely to improve our ability to combine diverse data to further enhance risk profiling. Ultimately, Brain Health Services have the potential to reduce the future burden of dementia through risk profiling, risk communication, personalized risk reduction, and cognitive enhancement interventions.
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