| 1. |
- Armengaud, Eric, et al.
(författare)
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Integrated tool chain for improving traceability during the development of automotive systems
- 2012
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Ingår i: ERTS2 2012 | Embedded Real Time Software and Systems.
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Konferensbidrag (refereegranskat)abstract
- Tool integration is a key factor for improving development efficiency and product quality during the development of safety-relevant embedded systems. We present in this work a demonstrator based on the most recent outcomes of the CESAR project. The proposed integrated tool-chain aims at better linking development activities together, thus improving traceability during requirements engineering, system design, safety analysis and V&V activities using a model-based development approach. We analyze the proposed tool-chain from three different points of view: (1) tool integrator, (2) technology provider, and (3) end-user. These different points of view enable the description of the different technologies used at the different levels and the analysis of the benefits for the end-user.
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| 2. |
- Felkel, Sabine, et al.
(författare)
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The horse Y chromosome as an informative marker for tracing sire lines
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of the Y chromosome is the best-established way to reconstruct paternal family history in humans. Here, we applied fine-scaled Y-chromosomal haplotyping in horses with biallelic markers and demonstrate the potential of our approach to address the ancestry of sire lines. We de novo assembled a draft reference of the male-specific region of the Y chromosome from Illumina short reads and then screened 5.8 million basepairs for variants in 130 specimens from intensively selected and rural breeds and nine Przewalski's horses. Among domestic horses we confirmed the predominance of a young'crown haplogroup' in Central European and North American breeds. Within the crown, we distinguished 58 haplotypes based on 211 variants, forming three major haplogroups. In addition to two previously characterised haplogroups, one observed in Arabian/Coldblooded and the other in Turkoman/Thoroughbred horses, we uncovered a third haplogroup containing Iberian lines and a North African Barb Horse. In a genealogical showcase, we distinguished the patrilines of the three English Thoroughbred founder stallions and resolved a historic controversy over the parentage of the horse 'Galopin', born in 1872. We observed two nearly instantaneous radiations in the history of Central and Northern European Y-chromosomal lineages that both occurred after domestication 5,500 years ago.
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| 3. |
- Gorski, Mathias, et al.
(författare)
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Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
- 2022
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639
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Tidskriftsartikel (refereegranskat)abstract
- Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
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| 4. |
- Jacoby, Wolfgang R., et al.
(författare)
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Temporal Gravity Variations near Shrinking Vatnajokull Ice Cap, Iceland
- 2009
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Ingår i: Pure and Applied Geophysics. - : Springer Science and Business Media LLC. - 0033-4553 .- 1420-9136. ; 166:8-9, s. 1283-1302
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Tidskriftsartikel (refereegranskat)abstract
- Repeated gravity measurements were carried out from 1991 until 1999 at sites SE of Vatnajokull, Iceland, to estimate the mass flow and deformation accompanying the shrinking of the ice cap. Published GPS data show an uplift of about 13 +/- A 5 mm/a near the ice margin. A gravity decrease of -2 +/- A 1 mu Gal/a relative to the Hofn base station, was observed for the same sites. Control measurements at the Hofn station showed a gravity decrease of -2 +/- A 0.5 A mu Gal/a relative to the station RVIK 5473 at Reykjavik (about 250 km from Hofn). This is compatible, as a Bouguer effect, with a 10 +/- A 3 mm/a uplift rate of the IGS point at Hofn and an uplift rate of similar to 20 mm/a near the ice margin. Although the derived gravity change rates at individual sites have large uncertainties, the ensemble of the rates varies systematically and significantly with distance from the ice. The relationship between gravity and elevation changes and the shrinking ice mass is modelled as response to the loading history. The GPS data can be explained by 1-D modelling (i.e., an earth model with a 15-km thick elastic lithosphere and a 7 center dot 10(17) Pa center dot s asthenosphere viscosity), but not the gravity data. Based on 2-D modelling, the gravity data favour a low-viscosity plume in the form of a cylinder of 80 km radius and 10(17) to 10(18) Pa center dot s viscosity below a 6 km-thick elastic lid, embedded in a layered PREM-type earth, although the elevation data are less well explained by this model. Strain-porosity-hydrology effects are likely to enhance the magnitude of the gravity changes, but need verification by drilling. More accurate data may resolve the discrepancies or suggest improved models.
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| 5. |
- Lever, Fabiano, et al.
(författare)
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Core-level spectroscopy of 2-thiouracil at the sulfur L1 and L2,3-edges utilizing a sase free-electron laser
- 2021
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Ingår i: Molecules. - : MDPI AG. - 1420-3049. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we report X-ray absorption and core-level electron spectra of the nucleobase derivative 2-thiouracil at the sulfur L1-and L2,3-edges. We used soft X-rays from the free-electron laser FLASH2 for the excitation of isolated molecules and dispersed the outgoing electrons with a magnetic bottle spectrometer. We identified photoelectrons from the 2p core orbital, accompanied by an electron correlation satellite, as well as resonant and non-resonant Coster–Kronig and Auger– Meitner emission at the L1-and L2,3-edges, respectively. We used the electron yield to construct X-ray absorption spectra at the two edges. The experimental data obtained are put in the context of the literature currently available on sulfur core-level and 2-thiouracil spectroscopy.
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| 6. |
- Puschnig, Johannes, et al.
(författare)
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Correcting sky-quality-meter measurements for ageing effects using twilight as calibrator
- 2021
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 502:1, s. 1095-1103
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Tidskriftsartikel (refereegranskat)abstract
- In the last decade, numerous sky quality meters (SQMs) have been installed around the world, aiming to assess the temporal change of the night sky brightness, and thus the change in light pollution. However, it has become clear that SQM readings may be affected by ageing effects such as degradation of the sensor sensitivity and/or loss of transmissivity of optical components (filter, housing window). To date, the magnitude of the darkening has not been assessed in a systematic way. We report for the first time on the quantification of the SQM ageing effect and describe the applied method. We combine long-term SQM measurements obtained between 2011 and 2019 in Potsdam-Babelsberg (23 km to the south-west of the centre of Berlin), Vienna and Stockholm with a readily available empirical twilight model, which serves as a calibrator. Twilight SQM observations, calibrated for changing Sun altitudes, reveal a linear degradation of the measurement systems (SQM + housing window) with the following slopes: 34 +/- 4, 46 +/- 2 and 53 +/- 2 mmag(SQM) arcsec(-2) yr(-1) for Stockholm, Potsdam-Babelsberg and Vienna, respectively. With the highest slope found in Vienna (latitude similar to 48 degrees) and the lowest one found in Stockholm (latitude similar to 59 degrees), we find an indication for the dependence of the trend on solar irradiance (which is a function of geographic latitude).
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| 7. |
- Puschnig, Johannes, et al.
(författare)
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Long-term trends of light pollution assessed from SQM measurements and an empirical atmospheric model(dagger)
- 2022
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 518:3, s. 4449-4465
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Tidskriftsartikel (refereegranskat)abstract
- We present long-term (4–10 yr) trends of light pollution observed at 26 locations, covering rural, intermediate, and urban sites, including the three major European metropolitan areas of Stockholm, Berlin, and Vienna. Our analysis is based on (i) night sky brightness (NSB) measurements obtained with sky quality metres (SQMs) and (ii) a rich set of atmospheric data products. We describe the SQM data reduction routine in which we filter for moon- and clear-sky data and correct for the SQM ‘aging’ effect using an updated version of the twilight method of Puschnig et al. (2021). Our clear-sky, aging-corrected data reveal short- and long-term (seasonal) variations due to atmospheric changes. To assess long-term anthropogenic NSB trends, we establish an empirical atmospheric model via multivariate penalized linear regression. Our modelling approach allows to quantitatively investigate the importance of different atmospheric parameters, revealing that surface albedo and vegetation have by far the largest impact on zenithal NSB. Additionally, the NSB is sensitive to black carbon and organic matter aerosols at urban and rural sites, respectively. Snow depth was found to be important for some sites, while the total column of ozone leaves impact on some rural places. The average increase in light pollution at our 11 rural sites is 1.7 per cent per year. At our nine urban sites, we measure an increase of 1.8 per cent per year and for the remaining six intermediate sites we find an average increase of 3.7 per cent per year. These numbers correspond to doubling times of 41, 39, and 19 yr. We estimate that our method is capable of detecting trend slopes shallower/steeper than ±1.5 per cent per year.
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| 8. |
- Wallner, Barbara, et al.
(författare)
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Y Chromosome Uncovers the Recent Oriental Origin of Modern Stallions
- 2017
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Ingår i: Current Biology. - : CELL PRESS. - 0960-9822 .- 1879-0445. ; 27:13, s. 2029-2035
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Tidskriftsartikel (refereegranskat)abstract
- The Y chromosome directly reflects male genealogies, but the extremely low Y chromosome sequence diversity in horses has prevented the reconstruction of stallion genealogies [1, 2]. Here, weresolve the first Y chromosomegenealogy of modern horses by screening 1.46 Mb of the male-specific region of the Y chromosome (MSY) in 52 horses from 21 breeds. Based on highly accurate pedigree data, we estimated the de novo mutation rate of the horse MSY and showed that various modern horse Y chromosome lineages split much later than the domestication of the species. Apart from few private northern European haplotypes, all modern horse breeds clustered together in a roughly 700-year-old haplogroup that was transmitted to Europe by the import of Oriental stallions. The Oriental horse group consisted of two major subclades: the Original Arabian lineage and the Turkoman horse lineage. We show that the English Thoroughbred MSY was derived from the Turkoman lineage and that English Thoroughbred sires are largely responsible for the predominance of this haplotype in modern horses.
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| 9. |
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| 10. |
- Wallner, Stefan, et al.
(författare)
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The reliability of satellite-based lighttrends for dark sky areas in Austria
- 2023
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Ingår i: Journal of Quantitative Spectroscopy and Radiative Transfer. - : Elsevier. - 0022-4073 .- 1879-1352. ; 311
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Tidskriftsartikel (refereegranskat)abstract
- Globally, light pollution is a phenomenon rising in its appearance and threatening human health and natural habitats for flora and fauna. Consequently, there is a great interest in interdisciplinary communities to keep an eye on its occurrence and development. One possibility to obtain meaningful data are satellite-based observations, coming mainly from the Visible Infrared Imaging Radiometer Suite (VIIRS) capturing top-of-the -atmosphere radiance levels originating from Earth's surface. Tools designed to easily inspect monthly averaged data of this instrument are web applications. In this work, we focus on dark sky areas in Austria, namely 47 nature parks, and investigate collected data from such application and their reliability in making statements about the development of artificial light at night on the ground. Including atmospheric variations and other limitations, our results lead to a detection limit in radiance change by a minimum of +/- 10%. Below this value, detected changes in surface brightness must not be traced back to changes of ground-based artificial light according to a specified statistical significance of three sigma. In total, 38 of 47 nature parks are examinable, showing an increase in radiance by similar to 42 percent over ten years in average, more than double compared to the entire national territory. As a conclusion, satellite data as analysed must be available for large periods, in order to decrease detection thresholds and make accurate statements about the development of light pollution. However, for detailed analytical research, it is highly recommended that especially dark areas globally establish ground-based light monitoring networks in their areas.
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| 11. |
- Zhang, Si Min, et al.
(författare)
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Development of a chemical probe against NUDT15
- 2020
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Ingår i: Nature Chemical Biology. - : Springer Science and Business Media LLC. - 1552-4450 .- 1552-4469. ; 16:10, s. 1120-1128
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Tidskriftsartikel (refereegranskat)abstract
- The NUDIX hydrolase NUDT15 was originally implicated in sanitizing oxidized nucleotides, but was later shown to hydrolyze the active thiopurine metabolites, 6-thio-(d)GTP, thereby dictating the clinical response of this standard-of-care treatment for leukemia and inflammatory diseases. Nonetheless, its physiological roles remain elusive. Here, we sought to develop small-molecule NUDT15 inhibitors to elucidate its biological functions and potentially to improve NUDT15-dependent chemotherapeutics. Lead compound TH1760 demonstrated low-nanomolar biochemical potency through direct and specific binding into the NUDT15 catalytic pocket and engaged cellular NUDT15 in the low-micromolar range. We also employed thiopurine potentiation as a proxy functional readout and demonstrated that TH1760 sensitized cells to 6-thioguanine through enhanced accumulation of 6-thio-(d)GTP in nucleic acids. A biochemically validated, inactive structural analog, TH7285, confirmed that increased thiopurine toxicity takes place via direct NUDT15 inhibition. In conclusion, TH1760 represents the first chemical probe for interrogating NUDT15 biology and potential therapeutic avenues.
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