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- Demichev, Vadim, et al.
(författare)
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A time-resolved proteomic and prognostic map of COVID-19
- 2021
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Ingår i: Cell Systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 12:8, s. 780-794.e7
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.
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- Martin, DP, et al.
(författare)
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Selection analysis identifies unusual clustered mutational changes in Omicron lineage BA.1 that likely impact Spike function
- 2022
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Ingår i: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Among the 30 non-synonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (i) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (ii) interactions of Spike with ACE2 receptors, and (iii) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations in intrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any genomes within which they occurred. We further propose that the mutations in each of the three clusters therefore cooperatively interact to both mitigate their individual fitness costs, and adaptively alter the function of Spike. Given the evident epidemic growth advantages of Omicron over all previously known SARS-CoV-2 lineages, it is crucial to determine both how such complex and highly adaptive mutation constellations were assembled within the Omicron S-gene, and why, despite unprecedented global genomic surveillance efforts, the early stages of this assembly process went completely undetected.
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- Tomic, S., et al.
(författare)
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Influence of conduction-band nonparabolicity on electron confinement and effective mass in GaNxAs1−x∕GaAs quantum wells
- 2004
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 69, s. 245305-
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Tidskriftsartikel (refereegranskat)abstract
- We derive an analytical model to describe the conduction-band states of GaNAs-based quantum well structures, including the band anticrossing effect between N resonant states and the conduction-band edge. The predictions of the model are compared to those obtained using a full ten-band k·p model based on the same set of parameters. Both methods are then tested by comparison with the experimentally determined ground- and excited-state interband transition energies of GaNxAs1−x quantum wells of different well widths and N composition x obtained at 300 K and under hydrostatic pressures up to 2.0 GPa . We show that the transition energies can be described by a consistent set of material parameters in all the samples studied, and present how the conduction to valence-band offset ratio varies strongly with x in GaNxAs1−x∕GaAs quantum well structures. We conclude that the model presented can be used to predict the transition energies and electron subband structure of any GaNxAs1−x∕GaAs quantum well with well width between 2 and 25 nm , and N composition x between 1 and 4% , although further work is still required to confirm the optimum choice for the variation of band offset ratio with composition.
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