| 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. |
- Hillier, Ladeana W, et al.
(författare)
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Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Chaney, Aisling M., et al.
(författare)
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Prodromal neuroinflammatory, cholinergic and metabolite dysfunction detected by PET and MRS in the TgF344-AD transgenic rat model of AD : a collaborative multi-modal study
- 2021
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Ingår i: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 11:14, s. 6644-6667
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Tidskriftsartikel (refereegranskat)abstract
- Mouse models of Alzheimer's disease (AD) are valuable but do not fully recapitulate human AD pathology, such as spontaneous Tau fibril accumulation and neuronal loss, necessitating the development of new AD models. The transgenic (TG) TgF344-AD rat has been reported to develop age-dependent AD features including neuronal loss and neurofibrillary tangles, despite only expressing APP and PSEN1 mutations, suggesting an improved modelling of AD hallmarks. Alterations in neuronal networks as well as learning performance and cognition tasks have been reported in this model, but none have combined a longitudinal, multimodal approach across multiple centres, which mimics the approaches commonly taken in clinical studies. We therefore aimed to further characterise the progression of AD-like pathology and cognition in the TgF344-AD rat from young-adults (6 months (m)) to mid- (12 m) and advanced-stage (18 m, 25 m) of the disease.Methods: TgF344-AD rats and wild-type (WT) littermates were imaged at 6 m, 12 m and 18 m with [18F]DPA-714 (TSPO, neuroinflammation), [18F]Florbetaben (Aβ) and [18F]ASEM (α7-nicotinic acetylcholine receptor) and with magnetic resonance spectroscopy (MRS) and with (S)-[18F]THK5117 (Tau) at 15 and 25 m. Behaviour tests were also performed at 6 m, 12 m and 18 m. Immunohistochemistry (CD11b, GFAP, Aβ, NeuN, NeuroChrom) and Tau (S)-[18F]THK5117 autoradiography, immunohistochemistry and Western blot were also performed.Results: [18F]DPA-714 positron emission tomography (PET) showed an increase in neuroinflammation in TG vs wildtype animals from 12 m in the hippocampus (+11%), and at the advanced-stage AD in the hippocampus (+12%), the thalamus (+11%) and frontal cortex (+14%). This finding coincided with strong increases in brain microgliosis (CD11b) and astrogliosis (GFAP) at these time-points as assessed by immunohistochemistry. In vivo [18F]ASEM PET revealed an age-dependent increase uptake in the striatum and pallidum/nucleus basalis of Meynert in WT only, similar to that observed with this tracer in humans, resulting in TG being significantly lower than WT by 18 m. In vivo [18F]Florbetaben PET scanning detected Aβ accumulation at 18 m, and (S)-[18F]THK5117 PET revealed subsequent Tau accumulation at 25m in hippocampal and cortical regions. Aβ plaques were low but detectable by immunohistochemistry from 6 m, increasing further at 12 and 18 m with Tau-positive neurons adjacent to Aβ plaques at 18 m. NeuroChrom (a pan neuronal marker) immunohistochemistry revealed a loss of neuronal staining at the Aβ plaques locations, while NeuN labelling revealed an age-dependent decrease in hippocampal neuron number in both genotypes. Behavioural assessment using the novel object recognition task revealed that both WT & TgF344-AD animals discriminated the novel from familiar object at 3 m and 6 m of age. However, low levels of exploration observed in both genotypes at later time-points resulted in neither genotype successfully completing the task. Deficits in social interaction were only observed at 3 m in the TgF344-AD animals. By in vivo MRS, we showed a decrease in neuronal marker N-acetyl-aspartate in the hippocampus at 18 m (-18% vs age-matched WT, and -31% vs 6 m TG) and increased Taurine in the cortex of TG (+35% vs age-matched WT, and +55% vs 6 m TG).Conclusions: This multi-centre multi-modal study demonstrates, for the first time, alterations in brain metabolites, cholinergic receptors and neuroinflammation in vivo in this model, validated by robust ex vivo approaches. Our data confirm that, unlike mouse models, the TgF344-AD express Tau pathology that can be detected via PET, albeit later than by ex vivo techniques, and is a useful model to assess and longitudinally monitor early neurotransmission dysfunction and neuroinflammation in AD.
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| 4. |
- Sumaila, U. Rashid, et al.
(författare)
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WTO must ban harmful fisheries subsidies
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Abbott, Benjamin W., et al.
(författare)
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Biomass offsets little or none of permafrost carbon release from soils, streams, and wildfire : an expert assessment
- 2016
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Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- As the permafrost region warms, its large organic carbon pool will be increasingly vulnerable to decomposition, combustion, and hydrologic export. Models predict that some portion of this release will be offset by increased production of Arctic and boreal biomass; however, the lack of robust estimates of net carbon balance increases the risk of further overshooting international emissions targets. Precise empirical or model-based assessments of the critical factors driving carbon balance are unlikely in the near future, so to address this gap, we present estimates from 98 permafrost-region experts of the response of biomass, wildfire, and hydrologic carbon flux to climate change. Results suggest that contrary to model projections, total permafrost-region biomass could decrease due to water stress and disturbance, factors that are not adequately incorporated in current models. Assessments indicate that end-of-the-century organic carbon release from Arctic rivers and collapsing coastlines could increase by 75% while carbon loss via burning could increase four-fold. Experts identified water balance, shifts in vegetation community, and permafrost degradation as the key sources of uncertainty in predicting future system response. In combination with previous findings, results suggest the permafrost region will become a carbon source to the atmosphere by 2100 regardless of warming scenario but that 65%-85% of permafrost carbon release can still be avoided if human emissions are actively reduced.
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| 6. |
- Berner, Logan T., et al.
(författare)
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The Arctic plant aboveground biomass synthesis dataset
- 2024
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Ingår i: Scientific Data. - : Springer Nature. - 2052-4463. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Plant biomass is a fundamental ecosystem attribute that is sensitive to rapid climatic changes occurring in the Arctic. Nevertheless, measuring plant biomass in the Arctic is logistically challenging and resource intensive. Lack of accessible field data hinders efforts to understand the amount, composition, distribution, and changes in plant biomass in these northern ecosystems. Here, we present The Arctic plant aboveground biomass synthesis dataset, which includes field measurements of lichen, bryophyte, herb, shrub, and/or tree aboveground biomass (g m−2) on 2,327 sample plots from 636 field sites in seven countries. We created the synthesis dataset by assembling and harmonizing 32 individual datasets. Aboveground biomass was primarily quantified by harvesting sample plots during mid- to late-summer, though tree and often tall shrub biomass were quantified using surveys and allometric models. Each biomass measurement is associated with metadata including sample date, location, method, data source, and other information. This unique dataset can be leveraged to monitor, map, and model plant biomass across the rapidly warming Arctic.
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| 7. |
- Cristescu, Carmen, et al.
(författare)
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Design for deconstruction and reuse of timber structures – state of the art review
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report is a state-of-the-art on timber construction in selected european countries and and discusses technical premises for a potential circular use of timber in building construction, focusing on Design for Deconstruction and Reuse (DfDR) in low-rise timber buildings, up to 3 storeys. It describes the historic and contemporary building techniques of timber buildings in all project countries (Sweden, Finland, Ireland, UK, Spain, Germany, Slovenia) and finds, that all of these countries have a long history of building with timber, but in most regions other materials dominated the housing output from the beginning of the 20th century. Only in the second half of the 20th century timber started gaining importance as a building material in Europe again, with light timber frame construction becoming an important construction system. From the beginning of the 21st century, innovations in the sector started transforming the construction industry. Mass timber products like CLT opened the market for high-rise timber buildings and in some countries office blocks, schools and hotels are built using timber, although the majority of timber construction remains residential. An even more important development might be the uptake of offsite construction, that makes timber construction more accurate, material efficient, fast and it reduces waste. These modern methods of construction are gaining importance in the construction sector of all partner countries and are likely to dominate the European housing output in the future. There will be some regional differences in the level of prefabrication, material choices and designs, so that any design guidelines for DfDR need to be adapted to the regional context. However, modern timber construction is not currently aligned with circular economy principles and is seldomly taking buildings endof-life-into account.Therefore, the report continues to summarise novel design concepts for deconstruction and reuse, that could be used in modern timber buildings. It outlines that the feasibility as well as the reuse potential depends on the scale of reclaimed components, where larger components and assemblies are often considered beneficial in terms of time, greenhouse gas emissions and waste production. If volumetric or planar units could be salvaged in the future, they also need to be adaptable for altered regulations or standards or alternative functions. It is further necessary that assemblies can be altered within buildings, since different building components have different life expectancies. Various examples for DfDR in buildings with the accompanying design strategies are presented. The buildings in the examples are often designed to be in one place for a limited timeframe and can be deconstructed and re-erected elsewhere without replacement of components. Key-features often include modularity of components, reversible connections, adaptability of the floor-plan and circular procurement. Even though it is evidently possible, the structural reuse of timber is not a wide-spread approach to date. Barriers to the use of reclaimed structural components are mainly a lack in demand for salvaged materials, but also prohibitive building regulations and the lack of design standards. Demolition practices play a crucial role as well and need to be considered in the design of buildings, to avoid damage to the components.Finally, the report summarises principles and guidelines for DfDR by different authors. As a generic approach an indicator system for deconstructability and reusability could be introduced. Time, Separability, Risk and Safety, Simplicity and Interchangeability are identified5as the main indicators for DfDR, that remain somewhat abstract. As opposed to using a generic indicator system, a more practical approach of assessing DfDR on an individual basis could be taken. This way specific shortcomings of the design can be addressed. But if DfDR found a wider application in the future, this approach may be too time consuming and there is a need for a more directed decision-making tool that can be used during the design phase of buildings to enhance DfDR. As the InFutUReWood project proceeds, it will examine a more granular approach to DfDR, relating it to the actual construction stages used in practice, developing a general template to be appropriated and adjusted to account for regional variations in construction. A strategic matrix is in development which will provide designers with a methodology based on relating principles, strategies and specific tactics to the typical design stages, to aid design decisions that promote DfDR.
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| 8. |
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| 9. |
- Topping, Matthew, et al.
(författare)
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The effect of iron on dislocation evolution in model and commercial zirconium alloys
- 2018
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Ingår i: ASTM Special Technical Publication. - 0066-0558. ; STP 1597, s. 796-822
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Konferensbidrag (refereegranskat)abstract
- Although the evolution of irradiation-induced dislocation loops has been well correlated with irradiation-induced growth phenomena, the effect of alloying elements on this evolution remains elusive, especially at low fluences. To develop a more mechanistic understanding of the role iron has on loop formation, we used state-of-the-art techniques to study a proton-irradiated Zr-0.1Fe alloy and proton- and neutron-irradiated Zircaloy-2. The two alloys were irradiated with 2-MeV protons up to 7 dpa at 350°C and Zircaloy-2 up to 14.7 × 1025n • m-2, approximately 24 dpa, in a boiling water reactor at approximately 300°C. Baseline transmission electron microscopy showed that the Zr3Fe secondary-phase particles in the binary system were larger and fewer in number than the Zr (Fe, Cr)2and Zr2(Fe, Ni) particles in Zircaloy-2. An analysis of the irradiated binary alloy revealed only limited dissolution of Ze3Fe, suggesting little dispersion of iron into the matrix, while at the same time a higher 〈a〉-loop density was observed compared with Zircaloy-2 at equivalent proton dose levels. We also found that the redistribution of iron during irradiation led to the formation of iron nanoclusters. A delay in the onset of 〈c〉-loop nucleation in proton-irradiated Zircaloy-2 compared with the binary alloy was observed. The effect of iron redistributed from secondary-phase particles because of dissolution on the density and morphology of 〈a〉 and 〈c〉 loops is described. The implication this may have on irradiation-induced growth of zirconium fuel cladding is also discussed.
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| 10. |
- Zhang, Zhenbo, et al.
(författare)
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Strain localisation and failure at twin-boundary complexions in nickel-based superalloys
- 2020
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Twin boundaries (TBs) in Ni-based superalloys are vulnerable sites for failure in demanding environments, and a current lack of mechanistic understanding hampers the reliable lifetime prediction and performance optimisation of these alloys. Here we report the discovery of an unexpected gamma '' precipitation mechanism at TBs that takes the responsibility for alloy failure in demanding environments. Using multiscale microstructural and mechanical characterisations (from millimetre down to atomic level) and DFT calculations, we demonstrate that abnormal gamma '' precipitation along TBs accounts for the premature dislocation activities and pronounced strain localisation associated with TBs during mechanical loading, which serves as a precursor for crack initiation. We clarify the physical origin of the TBs-related cracking at the atomic level of gamma ''-strengthened Ni-based superalloys in a hydrogen containing environment, and provide practical methods to mitigate the adverse effect of TBs on the performance of these alloys.
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