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| 2. |
- Allentoft, Morten E., et al.
(författare)
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Population genomics of post-glacial western Eurasia
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 3. |
- Björkman, Anne, 1981, et al.
(författare)
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Plant functional trait change across a warming tundra biome
- 2018
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 562:7725, s. 57-62
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Tidskriftsartikel (refereegranskat)abstract
- The tundra is warming more rapidly than any other biome on Earth, and the potential ramifications are far-reaching because of global feedback effects between vegetation and climate. A better understanding of how environmental factors shape plant structure and function is crucial for predicting the consequences of environmental change for ecosystem functioning. Here we explore the biome-wide relationships between temperature, moisture and seven key plant functional traits both across space and over three decades of warming at 117 tundra locations. Spatial temperature–trait relationships were generally strong but soil moisture had a marked influence on the strength and direction of these relationships, highlighting the potentially important influence of changes in water availability on future trait shifts in tundra plant communities. Community height increased with warming across all sites over the past three decades, but other traits lagged far behind predicted rates of change. Our findings highlight the challenge of using space-for-time substitution to predict the functional consequences of future warming and suggest that functions that are tied closely to plant height will experience the most rapid change. They also reveal the strength with which environmental factors shape biotic communities at the coldest extremes of the planet and will help to improve projections of functional changes in tundra ecosystems with climate warming.
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| 4. |
- Allentoft, Morten E., et al.
(författare)
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100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
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| 5. |
- Beer, Tomasz M., et al.
(författare)
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Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer : Extended Analysis of the Phase 3 PREVAIL Study
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 71:2, s. 151-154
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Tidskriftsartikel (refereegranskat)abstract
- Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naïve metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated the longer-term efficacy and safety of enzalutamide up to the prespecified number of deaths in the final analysis, which included an additional 20 mo of follow-up for investigator-assessed rPFS, 9 mo of follow-up for OS, and 4 mo of follow-up for safety. Enzalutamide reduced the risk of radiographic progression or death by 68% (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.28–0.37; p < 0.0001) and the risk of death by 23% (HR 0.77, 95% CI 0.67–0.88; p = 0.0002). Median investigator-assessed rPFS was 20.0 mo (95% CI 18.9–22.1) in the enzalutamide arm and 5.4 mo (95% CI 4.1–5.6) in the placebo arm. Median OS was 35.3 mo (95% CI 32.2–not yet reached) in the enzalutamide arm and 31.3 mo (95% CI 28.8–34.2) in the placebo arm. At the time of the OS analysis, 167 patients in the placebo arm had crossed over to receive enzalutamide. The most common adverse events in the enzalutamide arm were fatigue, back pain, constipation, and arthralgia. This final analysis of PREVAIL provides more complete assessment of the clinical benefit of enzalutamide. PREVAIL is registered on ClinicalTrials.gov as NCT01212991. Patient summary According to data from longer follow-up, enzalutamide continued to provide benefit over placebo in patients with metastatic castration-resistant prostate cancer.
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| 6. |
- Beer, Tomasz M, et al.
(författare)
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Enzalutamide in metastatic prostate cancer before chemotherapy
- 2014
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 371:5, s. 33-424
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have not received chemotherapy, in whom the disease has progressed despite androgen-deprivation therapy.METHODS: In this double-blind, phase 3 study, we randomly assigned 1717 patients to receive either enzalutamide (at a dose of 160 mg) or placebo once daily. The coprimary end points were radiographic progression-free survival and overall survival.RESULTS: The study was stopped after a planned interim analysis, conducted when 540 deaths had been reported, showed a benefit of the active treatment. The rate of radiographic progression-free survival at 12 months was 65% among patients treated with enzalutamide, as compared with 14% among patients receiving placebo (81% risk reduction; hazard ratio in the enzalutamide group, 0.19; 95% confidence interval [CI], 0.15 to 0.23; P<0.001). A total of 626 patients (72%) in the enzalutamide group, as compared with 532 patients (63%) in the placebo group, were alive at the data-cutoff date (29% reduction in the risk of death; hazard ratio, 0.71; 95% CI, 0.60 to 0.84; P<0.001). The benefit of enzalutamide was shown with respect to all secondary end points, including the time until the initiation of cytotoxic chemotherapy (hazard ratio, 0.35), the time until the first skeletal-related event (hazard ratio, 0.72), a complete or partial soft-tissue response (59% vs. 5%), the time until prostate-specific antigen (PSA) progression (hazard ratio, 0.17), and a rate of decline of at least 50% in PSA (78% vs. 3%) (P<0.001 for all comparisons). Fatigue and hypertension were the most common clinically relevant adverse events associated with enzalutamide treatment.CONCLUSIONS: Enzalutamide significantly decreased the risk of radiographic progression and death and delayed the initiation of chemotherapy in men with metastatic prostate cancer. (Funded by Medivation and Astellas Pharma; PREVAIL ClinicalTrials.gov number, NCT01212991.).
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| 7. |
- Margaryan, Ashot, et al.
(författare)
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Population genomics of the Viking world
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 585:7825, s. 390-396
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Tidskriftsartikel (refereegranskat)abstract
- The maritime expansion of Scandinavian populations during the Viking Age (about ad750–1050) was a far-flung transformation in world history1,2. Here we sequenced the genomes of 442humans from archaeological sites across Europe and Greenland (to a median depth of about 1×) to understand the global influence of this expansion. We find the Viking period involved gene flow into Scandinavia from the south and east. We observe genetic structure within Scandinavia, with diversity hotspots in the south and restricted gene flow within Scandinavia. We find evidence for a major influx of Danish ancestry into England; a Swedish influx into the Baltic; and Norwegian influx into Ireland, Iceland and Greenland. Additionally, we see substantial ancestry from elsewhere in Europe entering Scandinavia during the Viking Age. Our ancient DNA analysis also revealed that a Viking expedition included close family members. By comparing with modern populations, we find that pigmentation-associated loci have undergone strong population differentiation during the past millennium, and trace positively selected loci—including the lactase-persistence allele of LCT and alleles of ANKA that are associated with the immune response—in detail. We conclude that the Viking diaspora was characterized by substantial transregional engagement: distinct populations influenced the genomic makeup of different regions of Europe, and Scandinavia experienced increased contact with the rest of the continent.
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| 8. |
- Tyrsted, Christoffer, et al.
(författare)
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In-Situ Synchrotron Radiation Study of Formation and Growth of Crystalline CexZr1-xO2 Nanoparticles Synthesized in Supercritical Water
- 2010
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Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 22:5, s. 1814-1820
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Tidskriftsartikel (refereegranskat)abstract
- In situ synchrotron powder X-ray diffraction (PXRD) measurements have been conducted to follow the nucleation and growth of crystalline CexZr1-xO2 nanoparticles synthesized in supercritical water with a full substitution variation (x = 0, 0.2, 0.5, 0.8, and 1.0). Direction-dependent growth curves are determined and described using reaction kinetic models. A disctinct change in growth kinetics is observed with increasing cerium content. For x = 0.8 and 1.0 (high cerium content), the growth in initially limited by the surface reaction kinetics, however, at a size of similar to 6 nm, the growth changes and becomes limited by the diffusion of monomers toward the surface. For x = 0 and 0.2, the opposite behavior is observed with the growth initially being limited by diffusion (up to similar to 3.5 nm) and later by the surface reaction kinetics. Thus, although a continuous solid solution can be obtained for the ceria-zirconia system, the growth of ceria and zirconia nanoparticles is fundamentally different under supercritical flow reactor. The resulting samples were analyzed using PXRD, small-angle X-ray scattering (SAXS), and transmission electron microscopy (TEM). The nanoparticles with x = 0, 0.2, and 0.5 have very low polydispersities. The sizes range from 4 nm to 7 nm, and the particles exhibit a reversibly pH-dependent agglomeration.
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| 9. |
- Aguilar, J., et al.
(författare)
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Search for Leptonic CP Violation with the ESSnuSBplus Project
- 2024
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Ingår i: Letters in High Energy Physics. - : Andromeda Publishing And Academic Services LTD. - 2632-2714.
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Tidskriftsartikel (refereegranskat)abstract
- ESSνSB is a design study for a next-generation long-baseline neutrino experiment that aims at the precise measurement of the CP-violating phase, δCP, in the leptonic sector at the second oscillation maximum. The conceptual design report published from the first phase of the project showed that after 10 years of data taking, more than 70% of the possible δCP range will be covered with 5σ C.L. to reject the no-CP-violation hypothesis. The expected value of δCP precision is smaller than 8◦ for all δCP values. The next phase of the project, the ESSνSB+, aims at using the intense muon flux produced together with neutrinos to measure the neutrino-nucleus cross-section, the dominant term of the systematic uncertainty, in the energy range of 0.2–0.6 GeV, using a Low Energy neutrinos from STORed Muons (LEnuSTORM) and a Low Energy Monitored Neutrino Beam (LEMNB) facilities.
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| 10. |
- Andersen, Casper Welzel, et al.
(författare)
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Redox-Driven Migration of Copper Ions in the Cu-CHA Zeolite as Shown by the InSitu PXRD/XANES Technique
- 2017
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Ingår i: Angewandte Chemie - International Edition. - : Wiley. - 1433-7851. ; 56:35, s. 10367-10372
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Tidskriftsartikel (refereegranskat)abstract
- Using quasi-simultaneous insitu PXRD and XANES, the direct correlation between the oxidation state of Cu ions in the commercially relevant deNOx NH3-SCR zeolite catalyst Cu-CHA and the Cu ion migration in the zeolitic pores was revealed during catalytic activation experiments. A comparison with recent reports further reveals the high sensitivity of the redox-active centers concerning heating rates, temperature, and gas environment during catalytic activation. Previously, Cu+ was confirmed present only in the 6R. Results verify a novel 8R monovalent Cu site, an eventually large Cu+ presence upon heating to high temperatures in oxidative conditions, and demonstrate the unique potential in combining insitu PXRD and XANES techniques, with which both oxidation state and structural location of the redox-active centers in the zeolite framework could be tracked.
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