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| 2. |
- Abolfathi, Bela, et al.
(författare)
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The LSST DESC DC2 Simulated Sky Survey
- 2021
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 253:31
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Tidskriftsartikel (refereegranskat)abstract
- We describe the simulated sky survey underlying the second data challenge (DC2) carried out in preparation for analysis of the Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST) by the LSST Dark Energy Science Collaboration (LSST DESC). Significant connections across multiple science domains will be a hallmark of LSST; the DC2 program represents a unique modeling effort that stresses this interconnectivity in a way that has not been attempted before. This effort encompasses a full end-to-end approach: starting from a large N-body simulation, through setting up LSST-like observations including realistic cadences, through image simulations, and finally processing with Rubin's LSST Science Pipelines. This last step ensures that we generate data products resembling those to be delivered by the Rubin Observatory as closely as is currently possible. The simulated DC2 sky survey covers six optical bands in a wide-fast-deep area of approximately 300 deg2, as well as a deep drilling field of approximately 1 deg2. We simulate 5 yr of the planned 10 yr survey. The DC2 sky survey has multiple purposes. First, the LSST DESC working groups can use the data set to develop a range of DESC analysis pipelines to prepare for the advent of actual data. Second, it serves as a realistic test bed for the image processing software under development for LSST by the Rubin Observatory. In particular, simulated data provide a controlled way to investigate certain image-level systematic effects. Finally, the DC2 sky survey enables the exploration of new scientific ideas in both static and time domain cosmology.
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| 4. |
- Cohen, Tim J., et al.
(författare)
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Hydrological transformation coincided with megafaunal extinction in central Australia
- 2015
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Ingår i: Geology. - 0091-7613 .- 1943-2682. ; 43:3, s. 195-198
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Tidskriftsartikel (refereegranskat)abstract
- Central to the debate over the extinction of many of Australia's last surviving megafauna is the question: Was climate changing significantly when humans arrived and megafauna went extinct? Here we present a new perspective on variations in climate and water resources over the last glacial cycle in arid Australia based on the study of the continent's largest lake basin and its tributaries. By dating paleoshorelines and river deposits in the Lake Eyre basin, we show that major hydrological change caused previously overflowing megalakes to enter a final and catastrophic drying phase at 48 +/- 2 ka just as the giant bird, Genyornis newtoni, went extinct (50-45 ka). The disappearance of Genyornis and other megafauna has been previously attributed to ecosystem collapse coincident with the spread of fire-wielding humans. Our findings suggest a climate-driven hydrological transformation in the critical window of human arrival and megafaunal extinction, and the results call for a re-evaluation of a human-mediated cause for such extinctions in arid Australia.
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| 5. |
- Cohen, Timothy, et al.
(författare)
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Late Quaternary mega-lakes fed by the northern and southern river systems of central Australia : varying moisture sources and increased continental aridity
- 2012
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Ingår i: Palaeogeography, Palaeoclimatology, Palaeoecology. - : Elsevier BV. - 0031-0182 .- 1872-616X. ; 356:Special Issue, s. 89-108
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Tidskriftsartikel (refereegranskat)abstract
- Optically stimulated and thermoluminescence ages from relict shorelines, along with accelerator mass spectrometer 14C ages from freshwater molluscs reveal a record of variable moisture sources supplied by northern and southern river systems to Lake Mega-Frome in southern central Australia during the late Quaternary. Additional lacustrine, palynological and terrestrial proxies are used to reconstruct a record that extends back to 105 ka, confirming that Lakes Mega-Frome and Mega-Eyre were joined to create the largest system of palaeolakes on the Australian continent as recently as 50–47 ka. The palaeohydrological record indicates a progressive shift to more arid conditions, with marked drying after 45 ka. Subsequently, Lake Mega-Frome has filled independently at 33–31 ka and at the termination of the Last Glacial Maximum to volumes some 40 times those of today. Further sequentially declining filling episodes (to volumes 25–10 those of today) occurred immediately prior to the Younger Dryas stadial, in the mid Holocene and during the medieval climatic anomaly. Southern hemisphere summer insolation maxima are a poor predictor of palaeolake-filling episodes. An examination of multiple active moisture sources suggests that palaeolake phases were driven independently of insolation and at times by some combination of enhanced Southern Ocean circulation and strengthened tropical moisture sources.
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| 6. |
- Entrop, Joshua P., et al.
(författare)
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Reproduction patterns among non-Hodgkin lymphoma survivors by subtype in Sweden, Denmark and Norway : A population-based matched cohort study
- 2023
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Ingår i: British Journal of Haematology. - : John Wiley & Sons. - 0007-1048 .- 1365-2141. ; 202:4, s. 785-795
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies concerning reproductive patterns among non-Hodgkin lymphoma (NHL) survivors are scarce and those available have reported conflicting results. Treatment regimens vary considerably between aggressive and indolent NHL and studies of reproductive patterns by subtypes are warranted. In this matched cohort study, we identified all NHL patients aged 18-40 years and diagnosed between 2000 and 2018 from the Swedish and Danish lymphoma registers, and the clinical database at Oslo University Hospital (n = 2090). Population comparators were matched on sex, birth year and country (n = 19 427). Hazard ratios (HRs) were estimated using Cox regression. Males and females diagnosed with aggressive lymphoma subtypes had lower childbirth rates (HRfemale: 0.43, 95% CI: 0.31-0.59, HRmale: 0.61, 95% CI: 0.47-0.78) than comparators during the first 3 years after diagnosis. For indolent lymphomas, childbirth rates were not significantly different from comparators (HRfemale: 0.71, 95% CI: 0.48-1.04, HRmale: 0.94, 95% CI: 0.70-1.27) during the same period. Childbirth rates reached those of comparators for all subtypes after 3 years but the cumulative incidence of childbirths was decreased throughout the 10-year follow-up for aggressive NHL. Children of NHL patients were more likely to be born following assisted reproductive technology than those of comparators, except for male indolent lymphoma patients. In conclusion, fertility counselling is particularly important for patients with aggressive NHL.
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| 7. |
- Fitzsimmons, Kathryn E., et al.
(författare)
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Late Quaternary palaeoenvironmental change in the Australian drylands
- 2013
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 74, s. 78-96
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we synthesise existing palaeoenvironmental data from the arid and semi-arid interior of the Australian continent for the period 40-0 ka. Moisture is the predominant variable controlling environmental change in the arid zone. Landscapes in this region respond more noticeably to changes in precipitation than to temperature. Depending on their location, arid zone records broadly respond to tropical monsoon-influenced climate regimes, the temperate latitude westerly systems, or a combination of both. The timing and extent of relatively arid and humid phases vary across the continent, in particular between the westerly wind-controlled temperate latitudes, and the interior and north which are influenced by tropically sourced precipitation. Relatively humid phases in the Murray-Darling Basin on the semi-arid margins, which were characterised by large rivers most likely fed by snow melt, prevailed from 40 ka to the Last Glacial Maximum (LGM), and from the deglacial to the mid Holocene. By contrast, the Lake Eyre basin in central Australia remained relatively dry throughout the last 40 ka, with lake high stands at lake Frome around 35-30 ka, and parts of the deglacial period and the mid-Holocene. The LGM was characterised by widespread relative aridity and colder conditions, as evidenced by extensive desert dune activity and dust transport, lake level fall, and reduced but episodic fluvial activity. The climate of the deglacial period was spatially divergent. The southern part of the continent experienced a brief humid phase around similar to 17-15 ka, followed by increased dune activity around similar to 14-10 ka. This contrasts with the post-LGM persistence of arid conditions in the north, associated with a lapsed monsoon and reflected in lake level lows and reduced fluvial activity, followed by intensification of the monsoon and increasingly effective precipitation from similar to 14 ka. Palaeoenvironmental change during the Holocene was also spatially variable. The early to mid-Holocene was, however, generally characterised by moderately humid conditions, demonstrated by lake level rise, source-bordering dune activity, and speleothem growth, persisting at different times across the continent. Increasingly arid conditions developed into the late Holocene, particularly in the central arid zone.
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| 8. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 9. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 10. |
- Wang, Kaituo, et al.
(författare)
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Cryo-EM reveals the architecture of placental malaria VAR2CSA and provides molecular insight into chondroitin sulfate binding
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Placental malaria can have severe consequences for both mother and child and effective vaccines are lacking. Parasite-infected red blood cells sequester in the placenta through interaction between parasite-expressed protein VAR2CSA and the glycosaminoglycan chondroitin sulfate A (CS) abundantly present in the intervillous space. Here, we report cryo-EM structures of the VAR2CSA ectodomain at up to 3.1 Å resolution revealing an overall V-shaped architecture and a complex domain organization. Notably, the surface displays a single significantly electropositive patch, compatible with binding of negatively charged CS. Using molecular docking and molecular dynamics simulations as well as comparative hydroxyl radical protein foot-printing of VAR2CSA in complex with placental CS, we identify the CS-binding groove, intersecting with the positively charged patch of the central VAR2CSA structure. We identify distinctive conserved structural features upholding the macro-molecular domain complex and CS binding capacity of VAR2CSA as well as divergent elements possibly allowing immune escape at or near the CS binding site. These observations will support rational design of second-generation placental malaria vaccines.
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