| 21. |
- Aswad, Amr, et al.
(författare)
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Evolutionary history of endogenous Human Herpesvirus 6 reflects human migration out of Africa
- 2021
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Ingår i: Molecular biology and evolution. - : Oxford University Press. - 0737-4038 .- 1537-1719. ; 38:1, s. 96-107
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Tidskriftsartikel (refereegranskat)abstract
- Human herpesvirus 6A and 6B (HHV-6) can integrate into the germline, and as a result about 70 million people harbour the genome of one of these viruses in every cell of their body. Until now, it has been largely unknown if i) these integrations are ancient, ii) if they still occur, and iii) whether circulating virus strains differ from integrated ones. Here we used next generation sequencing and mining of public human genome datasets to generate the largest and most diverse collection of circulating and integrated HHV-6 genomes studied to date. In genomes of geographically dispersed, only distantly-related people, we identified clades of integrated viruses that originated from a single ancestral event, confirming this with fluorescent in situ hybridization to directly observe the integration locus. In contrast to HHV-6B, circulating and integrated HHV-6A sequences form distinct clades, arguing against ongoing integration of circulating HHV-6A or "reactivation" of integrated HHV-6A. Taken together, our study provides the first comprehensive picture of the evolution of HHV-6, and reveals that integration of heritable HHV-6 has occurred since the time of, if not before, human migrations out of Africa.
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| 22. |
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| 23. |
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| 24. |
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| 25. |
- Breuer, Judith, et al.
(författare)
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A proposal for a common nomenclature for viral clades that form the genus varicella-zoster virus.
- 2010
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Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 91:4, s. 821-828
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Tidskriftsartikel (refereegranskat)abstract
- Varicella zoster virus (VZV), the cause of chickenpox and zoster, was the first human herpesvirus to be sequenced fully and the first for which vaccines have been licensed and widely used. Three groups have published genotyping schemes based on single nucleotide polymorphisms (SNP) and between them identified five distinct phylogenetic clades, with an additional two putative clades . Sequencing of over 23 whole VZV genomes from around the world further refined the phylogenic distinctions between SNP genotypes. Widespread surveillance in countries in which varicella vaccine is now in use and the difficulties posed by three unique genotyping approaches, prompted an international meeting at which a common nomenclature based on phylogenetic clades , was agreed upon. In this paper we review the original genotyping schemes and discuss the basis for a novel common nomenclature for VZV viruses. We propose a minimum set of SNPs which we recommend should be used to genotype viruses. Finally, we suggest criteria by which new clades can be recognized.
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| 26. |
- Breuer, L., et al.
(författare)
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Assessing the impact of land use change on hydrology by ensemble modeling (LUCHEM). I : Model intercomparison with current land use
- 2009
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Ingår i: Advances in Water Resources. - : Elsevier BV. - 0309-1708 .- 1872-9657. ; 32:2, s. 129-146
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Tidskriftsartikel (refereegranskat)abstract
- This paper introduces the project on 'Assessing the impact of land use change on hydrology by ensemble modeling (LUCHEM)' that aims at investigating the envelope of predictions on changes in hydrological fluxes due to land use change. As part of a series of four papers, this paper outlines the motivation and setup of LUCHEM, and presents a model intercomparison for the present-day simulation results. Such an intercomparison provides a valuable basis to investigate the effects of different model structures on model predictions and paves the ground for the analysis of the performance of multi-model ensembles and the reliability of the scenario predictions in companion papers. in this study, we applied a set of 10 lumped, semi-lumped and fully distributed hydrological models that have been previously used in land use change studies to the low mountainous Dill catchment. Germany. Substantial differences in model performance were observed with Nash-Sutcliffe efficiencies ranging from 0.53 to 0.92. Differences in model performance were attributed to (1) model input data, (2) model calibration and (3) the physical basis of the models. The models were applied with two sets of input data: an original and a homogenized data set. This homogenization of precipitation, temperature and leaf area index was performed to reduce the variation between the models. Homogenization improved the comparability of model simulations and resulted in a reduced average bias, although some variation in model data input remained. The effect of the physical differences between models on the long-term water balance was mainly attributed to differences in how models represent evapotranspiration. Semi-lumped and lumped conceptual models slightly outperformed the fully distributed and physically based models. This was attributed to the automatic model calibration typically used for this type of models. Overall, however, we conclude that there was no superior model if several measures of model performance are considered and that all models are suitable to participate in further multi-model ensemble set-ups and land use change scenario investigations.
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| 27. |
- Breuer, O, et al.
(författare)
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Intravenous Infusion of High Dose Selenite in End-Stage Cancer Patients: Analysis of Systemic Exposure to Selenite and Seleno-Metabolites
- 2023
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is one of the main causes of human death globally and novel chemotherapeutics are desperately required. As a simple selenium oxide, selenite is a very promising chemotherapeutic because of pronounced its dose-dependent tumor-specific cytotoxicity. We previously published a first-in-man systematic phase I clinical trial in patients with cancer (from IV to end-stage) (the SECAR trial) showing that selenite is safe and tolerable with an unexpectable high maximum tolerated dose (MTD) and short half-life. In the present study, we analyzed the selenium species in plasma samples, from the patients participating in the SECAR trial and from various time points and dose cohorts using LC-ICP-MS. In conclusion, selenite, selenosugars, and 1–2 unidentified peaks that did not correspond to any standard, herein denoted ui-selenium, were detected in the plasma. However, trimethylated selenium (trimethylselenonoium) was not detected. The unidentified ui-selenium was eluting close to the selenium-containing amino acids (selenomethionine and selenocysteine) but was not part of a protein fraction. Our data demonstrate that the major metabolite detected was selenosugar. Furthermore, the identification of selenite even long after the administration is remarkable and unexpected. The kinetic analysis did not support that dosing per the body surface area would reduce interindividual variability of the systemic exposure in terms of trough concentrations.
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| 28. |
- Breuer, Wolfgang, et al.
(författare)
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Decomposing industry leverage : The special cases of real estate investment trusts and technology & hardware companies
- 2023
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Ingår i: Journal of Financial Research. - : Wiley. - 0270-2592 .- 1475-6803. ; 46:3, s. 791-823
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Tidskriftsartikel (refereegranskat)abstract
- Different industries exhibit significantly different leverage; companies in the real estate investment trust (REIT) and technology/hardware sectors are extreme examples. In the United States, the leverage ratio is twice as high for REITs (50%) as compared to non-real-estate firms (around 25%), and the technology/hardware sector has the lowest ratio (around 17%). We theoretically and empirically analyze their differences. By decomposing the difference into three channels, we find that the industry-specific channel explains around 67% for REITs and 68% for technology/hardware firms; the value-based channel is mostly responsible for the remaining portion. Taking the nonlinear influences of extreme values into account, the relevance of the industry-specific channel is considerably reduced.
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| 29. |
- Breuer, Wolfgang, et al.
(författare)
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Decomposing Industry Leverage: the Special Cases of Real Estate Investment Trusts and Technology & Hardware Companies
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Different industries exhibit significantly different leverage – companies in the REIT and technology/hardware sectors are extreme examples. The leverage ratio is twice as high with 50% for REITs as for non-real estate firms with around 25% in the U.S.; whereas the technology/hardware sector has the lowest ratio with around 17%. We theoretically and empirically analyse their differences. By decomposing the difference into three channels, we find that the industry-specific channel explains around 67% for REITs and 68% for technology/hardware firms; the value-based channel is mostly responsible for the remaining part. When taking non-linear influences of extreme values into account, the relevance of the industry-specific channel is considerably reduced.
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| 30. |
- Depledge, D. P., et al.
(författare)
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High Viral Diversity and Mixed Infections in Cerebral Spinal Fluid from Cases of Varicella Zoster Virus Encephalitis
- 2018
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 218:10, s. 1592-1601
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Tidskriftsartikel (refereegranskat)abstract
- Background. Varicella zoster virus (VZV) may cause encephalitis, both with and without rash. Here we investigate whether viruses recovered from the central nervous system (CNS; encephalitis or meningitis) differ genetically from those recovered from non-CNS samples. Methods. Enrichment-based deep sequencing of 45 VZV genomes from cerebral spinal fluid (CSF), plasma, bronchoalveolar lavage (BAL), and vesicles was carried out with samples collected from 34 patients with and without VZV infection of the CNS. Results. Viral sequences from multiple sites in the same patient were identical at the consensus level. Virus from vesicle fluid and CSF in cases of meningitis showed low-level diversity. By contrast, plasma, BAL, and encephalitis had higher numbers of variant alleles. Two CSF-encephalitis samples had high genetic diversity, with variant frequency patterns typical of mixed infections with different clades. Conclusions. Low viral genetic diversity in vesicle fluid is compatible with previous observations that VZV skin lesions arise from single or low numbers of virions. A similar result was observed in VZV from cases of VZV meningitis, a generally self-limiting infection. CSF from cases of encephalitis had higher diversity with evidence for mixed clade infections in 2 cases. We hypothesize that reactivation from multiple neurons may contribute to the pathogenesis of VZV encephalitis.
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