| 1. |
- Ackermann, M., et al.
(author)
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MINUTE-TIMESCALE > 100 MeV gamma-RAY VARIABILITY DURING THE GIANT OUTBURST OF QUASAR 3C 279 OBSERVED BY FERMI-LAT IN 2015 JUNE
- 2016
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In: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 824:2
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Journal article (peer-reviewed)abstract
- On 2015 June 16, Fermi- LAT observed a giant outburst from the flat spectrum radio quasar 3C 279 with a peak >100 MeV flux of similar to 3.6 x 10(-5) photons cm(-2) s(-1), averaged over orbital period intervals. It is historically the highest gamma-ray flux observed from the source, including past EGRET observations, with the gamma-ray isotropic luminosity reaching similar to 10(49) erg s(-1). During the outburst, the Fermi spacecraft, which has an orbital period of 95.4 minutes, was operated in a special pointing mode to optimize the exposure for 3C 279. For the first time, significant flux variability at sub-orbital timescales was found in blazar observations by Fermi- LAT. The source flux variability was resolved down to 2-minute binned timescales, with flux doubling times of less than 5 minutes. The observed minute-scale variability suggests a very compact emission region at hundreds of Schwarzschild radii from the central engine in conical jet models. A minimum bulk jet Lorentz factor (Gamma) of 35 is necessary to avoid both internal gamma-ray absorption and super-Eddington jet power. In the standard external radiation Comptonization scenario, G should be at least 50 to avoid overproducing the synchrotron self-Compton component. However, this predicts extremely low magnetization (similar to 5 x 10(-4)). Equipartition requires Gamma as high as 120, unless the emitting region is a small fraction of the dissipation region. Alternatively, we consider. rays originating as synchrotron radiation of gamma e similar to 1.6 x 10(6) electrons, in a magnetic field B similar to 1.3 kG, accelerated by strong electric fields E similar to B in the process of magnetoluminescence. At such short distance scales, one cannot immediately exclude the production of gamma-rays in hadronic processes.
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| 2. |
- Allentoft, M. E., et al.
(author)
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Population genomics of Bronze Age Eurasia
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 522:7555
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Journal article (peer-reviewed)abstract
- The Bronze Age of Eurasia (around 3000-1000 BC) was a period of major cultural changes. However, there is debate about whether these changes resulted from the circulation of ideas or from human migrations, potentially also facilitating the spread of languages and certain phenotypic traits. We investigated this by using new, improved methods to sequence low-coverage genomes from 101 ancient humans from across Eurasia. We show that the Bronze Age was a highly dynamic period involving large-scale population migrations and replacements, responsible for shaping major parts of present-day demographic structure in both Europe and Asia. Our findings are consistent with the hypothesized spread of Indo-European languages during the Early Bronze Age. We also demonstrate that light skin pigmentation in Europeans was already present at high frequency in the Bronze Age, but not lactose tolerance, indicating a more recent onset of positive selection on lactose tolerance than previously thought.
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| 4. |
- Sikora, M., et al.
(author)
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The population history of northeastern Siberia since the Pleistocene
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 570:7760
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Journal article (peer-reviewed)abstract
- Northeastern Siberia has been inhabited by humans for more than 40,000 years but its deep population history remains poorly understood. Here we investigate the late Pleistocene population history of northeastern Siberia through analyses of 34 newly recovered ancient genomes that date to between 31,000 and 600 years ago. We document complex population dynamics during this period, including at least three major migration events: an initial peopling by a previously unknown Palaeolithic population of 'Ancient North Siberians' who are distantly related to early West Eurasian hunter-gatherers; the arrival of East Asian-related peoples, which gave rise to 'Ancient Palaeo-Siberians' who are closely related to contemporary communities from far-northeastern Siberia (such as the Koryaks), as well as Native Americans; and a Holocene migration of other East Asian-related peoples, who we name 'Neo-Siberians', and from whom many contemporary Siberians are descended. Each of these population expansions largely replaced the earlier inhabitants, and ultimately generated the mosaic genetic make-up of contemporary peoples who inhabit a vast area across northern Eurasia and the Americas.
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| 7. |
- Bemark, Mats, 1967, et al.
(author)
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Limited clonal relatedness between gut IgA plasma cells and memory B cells after oral immunization
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- Understanding how memory B cells are induced and relate to long-lived plasma cells is important for vaccine development. Immunity to oral vaccines has been considered short-lived because of a poor ability to develop IgA B-cell memory. Here we demonstrate that long-lived mucosal IgA memory is readily achieved by oral but not systemic immunization in mouse models with NP hapten conjugated with cholera toxin and transfer of B1-8high /GFP+ NP-specific B cells. Unexpectedly, memory B cells are poorly related to long-lived plasma cells and less affinity-matured. They are α4β7-integrin+ CD73+ PD-L2+ CD80+ and at systemic sites mostly IgM+, while 80% are IgA+ in Peyer's patches. On reactivation, most memory B cells in Peyer's patches are GL7+, but expand in germinal centres and acquire higher affinity and more mutations, demonstrating strong clonal selection. CCR9 expression is found only in Peyer's patches and appears critical for gut homing. Thus, gut mucosal memory possesses unique features not seen after systemic immunization. © 2016 The Author(s).
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| 8. |
- Blomqvist, Maria K., 1975, et al.
(author)
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beta-Mannosidosis caused by a novel homozygous intragenic inverted duplication in MANBA
- 2019
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In: Cold Spring Harbor Molecular Case Studies. - : Cold Spring Harbor Laboratory. - 2373-2873. ; 5:3
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Journal article (peer-reviewed)abstract
- beta-Mannosidosis is a lysosomal storage disorder characterized by accumulation of disaccharides due to deficiency of the lysosomal enzyme beta-mannosidase. The disease is caused by mutations in MANBA and is extremely rare in humans. Although the clinical presentation is heterogeneous, common symptoms include various degrees of developmental delay, behavioral disturbances, hearing loss, and frequent infections. We report a 15-yr-old girl presenting with mild intellectual disability, sensorineural hearing loss, severe behavioral disturbances, dysmorphic traits, and evolving angiokeratomas. Copy-number variation analysis of next-generation sequencing (NGS) data indicated increased coverage in exons 8-11 of MANBA. Low beta-mannosidase activity (1 mu katal/kg protein, refv 25-40) established the diagnosis of beta-mannosidosis. Whole-genome sequencing (WGS) and cDNA analysis revealed a novel homozygous intragenic inverted duplication in MANBA, where a 13.1-kb region between introns 7 and 11 was duplicated and inserted in an inverted orientation, creating a 67-base nonduplicated gap at the insertion point. Both junctions showed micro-homology regions. The inverted duplication resulted in exon skipping of exons 8-9 or 8-10. Our report highlights the importance of copy-number variation analysis of data from NGS and in particular the power of WGS in the identification and characterization of copy-number variants.
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| 9. |
- Damgaard, P. D., et al.
(author)
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137 ancient human genomes from across the Eurasian steppes
- 2018
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 557:7705, s. 369-374
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Journal article (peer-reviewed)abstract
- For thousands of years the Eurasian steppes have been a centre of human migrations and cultural change. Here we sequence the genomes of 137 ancient humans (about 1x average coverage), covering a period of 4,000 years, to understand the population history of the Eurasian steppes after the Bronze Age migrations. We find that the genetics of the Scythian groups that dominated the Eurasian steppes throughout the Iron Age were highly structured, with diverse origins comprising Late Bronze Age herders, European farmers and southern Siberian hunter-gatherers. Later, Scythians admixed with the eastern steppe nomads who formed the Xiongnu confederations, and moved westward in about the second or third century bc, forming the Hun traditions in the fourthfifth century ad, and carrying with them plague that was basal to the Justinian plague. These nomads were further admixed with East Asian groups during several short-term khanates in the Medieval period. These historical events transformed the Eurasian steppes from being inhabited by Indo-European speakers of largely West Eurasian ancestry to the mostly Turkic-speaking groups of the present day, who are primarily of East Asian ancestry.
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| 10. |
- Damgaard, P. D., et al.
(author)
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The first horse herders and the impact of early Bronze Age steppe expansions into Asia
- 2018
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 360:6396
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Journal article (peer-reviewed)abstract
- The Yamnaya expansions from the western steppe into Europe and Asia during the Early Bronze Age (similar to 3000 BCE) are believed to have brought with them Indo-European languages and possibly horse husbandry. We analyzed 74 ancient whole-genome sequences from across Inner Asia and Anatolia and show that the Botai people associated with the earliest horse husbandry derived from a hunter-gatherer population deeply diverged from the Yamnaya. Our results also suggest distinct migrations bringing West Eurasian ancestry into South Asia before and after, but not at the time of, Yamnaya culture. We find no evidence of steppe ancestry in Bronze Age Anatolia from when Indo-European languages are attested there. Thus, in contrast to Europe, Early Bronze Age Yamnaya-related migrations had limited direct genetic impact in Asia.
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