| 1. |
- Breitfeld, Jana, et al.
(författare)
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Genetic dissection of serum vaspin highlights its causal role in lipid metabolism
- 2023
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Ingår i: Obesity. - 1930-7381. ; 31:11, s. 2862-2874
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Vaspin (visceral adipose tissue derived serine protease inhibitor, SERPINA12) is associated with obesity-related metabolic traits, but its causative role is still elusive. The role of genetics in serum vaspin variability to establish its causal relationship with metabolically relevant traits was investigated. Methods: A meta-analysis of genome-wide association studies for serum vaspin from six independent cohorts (N = 7446) was conducted. Potential functional variants of vaspin were included in Mendelian randomization (MR) analyses to assess possible causal pathways between vaspin and homeostasis model assessment and lipid traits. To further validate the MR analyses, data from Genotype-Tissue Expression (GTEx) were analyzed, db/db mice were treated with vaspin, and serum lipids were measured. Results: A total of 468 genetic variants represented by five independent variants (rs7141073, rs1956709, rs4905216, rs61978267, rs73338689) within the vaspin locus were associated with serum vaspin (all p < 5×10−8, explained variance 16.8%). MR analyses revealed causal relationships between serum vaspin and triglycerides, low-density lipoprotein, and total cholesterol. Gene expression correlation analyses suggested that genes, highly correlated with vaspin expression in adipose tissue, are enriched in lipid metabolic processes. Finally, in vivo vaspin treatment reduced serum triglycerides in obese db/db mice. Conclusions: The data show that serum vaspin is strongly determined by genetic variants within vaspin, which further highlight vaspin's causal role in lipid metabolism.
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| 2. |
- Anton, Arthur Markus, et al.
(författare)
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Hydrogen bonding and charge transport in a protic polymerized ionic liquid
- 2020
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Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 16:26, s. 6091-6101
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Tidskriftsartikel (refereegranskat)abstract
- Hydrogen bonding and charge transport in the protic polymerized ionic liquid poly[tris(2-(2-methoxyethoxy)ethyl)ammoniumacryloxypropyl sulfonate] (PAAPS) are studied by combining Fourier transform infrared (FTIR) and broadband dielectric spectroscopy (BDS) in a wide temperature range from 170 to 300 K. While the former enables to determine precisely the formation of hydrogen bonds and other moiety-specific quantized vibrational states, the latter allows for recording the complex conductivity in a spectral range from 10(-2)to 10(+9) Hz. A pronounced thermal hysteresis is observed for the H-bond network formation in distinct contrast to the reversibility of the effective conductivity measured by BDS. On the basis of this finding and the fact that the conductivity changes with temperature by orders of magnitude, whereas the integrated absorbance of the N-H stretching vibration (being proportional to the number density of protons in the hydrogen bond network) changes only by a factor of 4, it is concluded that charge transport takes place predominantly due to hopping conduction assisted by glassy dynamics (dynamic glass transition assisted hopping) and is not significantly affected by the establishment of H-bonds.
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| 3. |
- Fehr, Andre, et al.
(författare)
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Mucoepidermoid carcinoma of the salivary glands revisited with special reference to histologic grading and CRTC1/3-MAML2 genotyping.
- 2021
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Ingår i: Virchows Archiv : an international journal of pathology. - : Springer Science and Business Media LLC. - 1432-2307. ; 479, s. 975-985
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Tidskriftsartikel (refereegranskat)abstract
- Mucoepidermoid carcinoma (MEC) is the most common carcinoma of the salivary glands. Here, we have used two large patient cohorts with MECs comprising 551 tumors to study clinical, histological, and molecular predictors of survival. One cohort (n=167), with known CRCT1/3-MAML2 fusion status, was derived from the Hamburg Reference Centre (HRC; graded with the AFIP and Brandwein systems) and the other (n=384) was derived from the population-based Cancer Registry of North Rhine-Westphalia (LKR-NRW; graded with the AFIP system). The reliability of both the AFIP and Brandwein grading systems was excellent (n=155). The weighted kappa for inter-rater agreement was 0.81 (95% CI 0.65-0.97) and 0.83 (95% CI 0.71-0.96) for the AFIP and Brandwein systems, respectively. The 5-year relative survival was 79.7% (95% CI 73.2-86.2%). Although the Brandwein system resulted in a higher rate of G3-MECs, survival in G3-tumors (AFIP or Brandwein grading) was markedly worse than in G1/G2-tumors. Survival in>T2 tumors was markedly worse than in those with lower T-stage. Also, fusion-negative MECs had a worse 5-year progression-free survival. The frequency of fusion-positive MECs in the HRC cohort was 78.4%, of which the majority (86.7%) was G1/G2-tumors. In conclusion, the AFIP and Brandwein systems are useful in estimating prognosis and to guide therapy for G3-MECs. However, their significance regarding young age (≤30years) and location-dependent heterogeneity of in particular G2-tumors is more questionable. We conclude that CRTC1/3-MAML2 testing is a useful adjunct to histologic scoring of MECs and for pinpointing tumors with poor prognosis with higher precision, thus avoiding overtreatment.
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| 4. |
- Fichte, Johannes K., et al.
(författare)
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Structure-Aware Lower Bounds and Broadening the Horizon of Tractability for QBF
- 2023
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Ingår i: 2023 38TH ANNUAL ACM/IEEE SYMPOSIUM ON LOGIC IN COMPUTER SCIENCE, LICS. - : IEEE. - 9798350335873 - 9798350335880
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Konferensbidrag (refereegranskat)abstract
- The QSAT problem, which asks to evaluate a quantified Boolean formula (QBF), is of fundamental interest in approximation, counting, decision, and probabilistic complexity and is also considered the prototypical PSPACE-complete problem. As such, it has previously been studied under various structural restrictions (parameters), most notably parameterizations of the primal graph representation of instances. Indeed, it is known that QSAT remains PSPACE-complete even when restricted to instances with constant treewidth of the primal graph, but the problem admits a double-exponential fixed-parameter algorithm parameterized by the vertex cover number (primal graph). However, prior works have left a gap in our understanding of the complexity of QSAT when viewed from the perspective of other natural representations of instances, most notably via incidence graphs. In this paper, we develop structure-aware reductions which allow us to obtain essentially tight lower bounds for highly restricted instances of QSAT, including instances whose incidence graphs have bounded treedepth or feedback vertex number. We complement these lower bounds with novel algorithms for QSAT which establish a nearly-complete picture of the problems complexity under standard graph-theoretic parameterizations. We also show implications for other natural graph representations, and obtain novel upper as well as lower bounds for QSAT under more fine-grained parameterizations of the primal graph.
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| 5. |
- Olstam, Johan, et al.
(författare)
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An Approach for Handling Uncertainties Related to Behaviour and Vehicle Mixes in Traffic Simulation Experiments with Automated Vehicles
- 2020
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Ingår i: Journal of Advanced Transportation. - : WILEY-HINDAWI. - 0197-6729 .- 2042-3195. ; 2020
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of automated vehicles is expected to affect traffic performance. Microscopic traffic simulation offers good possibilities to investigate the potential effects of the introduction of automated vehicles. However, current microscopic traffic simulation models are designed for modelling human-driven vehicles. Thus, modelling the behaviour of automated vehicles requires further development. There are several possible ways to extend the models, but independent of approach a large problem is that the information available on how automated vehicles will behave is limited to todays partly automated vehicles. How future generations of automated vehicles will behave will be unknown for some time. There are also large uncertainties related to what automation functions are technically feasible, allowed, and actually activated by the users, for different road environments and at different stages of the transition from 0 to 100% of automated vehicles. This article presents an approach for handling several of these uncertainties by introducing conceptual descriptions of four different types of driving behaviour of automated vehicles (Rail-safe, Cautious, Normal, and All-knowing) and presents how these driving logics can be implemented in a commonly used traffic simulation program. The driving logics are also linked to assumptions on which logic that could operate in which environment at which part of the transition period. Simulation results for four different types of road facilities are also presented to illustrate potential effects on traffic performance of the driving logics. The simulation results show large variations in throughput, from large decreases to large increases, depending on driving logic and penetration rate.
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| 6. |
- Reiter, Manuel, et al.
(författare)
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Tuning the glass transition of siloxane-based poly(ionic liquid)s towards high ion conductivity
- 2021
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Ingår i: Journal of Polymer Science. - : Wiley. - 2642-4150 .- 2642-4169. ; 59:14, s. 1518-1527
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Tidskriftsartikel (refereegranskat)abstract
- Herein, we report a simple and versatile synthetic approach towards siloxane-based poly(ionic liquid)s (PILs) with unusually low glass transition temperatures (Tg) down to −73°C, and thus “liquid-like” behavior at room temperature. We designed a polydimethylsiloxane-derived copolymer carrying dialkylimidazolium moieties, and by careful selection of the side-chain length and the type of anions we were able to manipulate its Tg over a wide range and reach high ionic conductivities (σDC) up to 4.8 × 10−5 S/cm at 300 K. The ionized species make up only a minor fraction (<25 mol%) of the overall repeating units and are supposedly randomly distributed: Yet our results indicate dramatic effects on the thermal properties due to repulsive interactions between ionic and non-ionic segments.
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| 7. |
- Strelnikov, Boris, et al.
(författare)
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Sounding rocket project PMWE for investigation of polar mesosphere winter echoes
- 2021
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Ingår i: Journal of Atmospheric and Solar-Terrestrial Physics. - : Elsevier BV. - 1364-6826 .- 1879-1824. ; 218
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Tidskriftsartikel (refereegranskat)abstract
- A first sounding rocket campaign dedicated to investigate the creation mechanism of Polar Mesosphere Winter Echoes (PMWE) was conducted in April 2018 from the north Norwegian Andøya Space Center (69 °N, 16 °E). Two instrumented sounding rockets were launched on 13th and 18th of April under PMWE and non-PMWE conditions, respectively. In this paper we give an overview of the PMWE sounding rocket mission. We describe and discuss some results of combined in situ and ground-based measurements which allow to verify existing PMWE theories. Our measurements ultimately show that: a) polar winter mesosphere is abounded with meteor smoke particles (MSP) and intermittent turbulent layers, b) all PMWE observed during this campaign can be explained by neutral air turbulence, c) turbulence creates small-scale structures in all D-region constituents, including free electrons; d) MSP ultimately influence the radar volume reflectivity by distorting the turbulence spectrum of electrons, e) the influence of MSP and of background electron density is just to increase SNR.
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| 8. |
- Szabo, Paul S., et al.
(författare)
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Dynamic Potential Sputtering of Lunar Analog Material by Solar Wind Ions
- 2020
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Ingår i: Astrophysical Journal. - : IOP PUBLISHING LTD. - 0004-637X .- 1538-4357. ; 891:1
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Tidskriftsartikel (refereegranskat)abstract
- Pyroxenes ((Ca, Mg, Fe, Mn)(2)Si2O6) belong to the most abundant rock forming minerals that make up the surface of rocky planets and moons. Therefore, sputtering of pyroxenes by solar wind ions has to be considered as a very important process for modifying the surface of planetary bodies. This is increased due to potential sputtering by multiply charged ions; to quantify this effect, sputtering of wollastonite (CaSiO3) by He2+ ions was investigated. Thin films of CaSiO3 deposited on a quartz crystal microbalance were irradiated, allowing precise, in situ, real time sputtering yield measurements. Experimental results were compared with SDTrimSP simulations, which were improved by adapting the used input parameters. On freshly prepared surfaces, He2+ ions show a significant increase in sputtering, as compared to equally fast He+ ions. However, the yield decreases exponentially with fluence, reaching a lower steady state after sputtering of the first few monolayers. Experiments using Ar8+ ions show a similar behavior, which is qualitatively explained by a preferential depletion of surface oxygen due to potential sputtering. A corresponding quantitative model is applied, and the observed potential sputtering behaviors of both He and Ar are reproduced very well. The results of these calculations support the assumption that mainly O atoms are affected by potential sputtering. Based on our findings, we discuss the importance of potential sputtering for the solar wind eroding the lunar surface. Estimated concentration changes and sputtering yields are both in line with previous modeling for other materials, allowing a consistent perspective on the effects of solar wind potential sputtering.
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| 9. |
- Treydte, Kerstin, et al.
(författare)
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Recent human-induced atmospheric drying across Europe unprecedented in the last 400 years
- 2024
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Ingår i: NATURE GEOSCIENCE. - 1752-0894 .- 1752-0908. ; 17, s. 58-65
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Tidskriftsartikel (refereegranskat)abstract
- The vapor pressure deficit reflects the difference between how much moisture the atmosphere could and actually does hold, a factor that fundamentally affects evapotranspiration, ecosystem functioning, and vegetation carbon uptake. Its spatial variability and long-term trends under natural versus human-influenced climate are poorly known despite being essential for predicting future effects on natural ecosystems and human societies such as crop yield, wildfires, and health. Here we combine regionally distinct reconstructions of pre-industrial summer vapor pressure deficit variability from Europe's largest oxygen-isotope network of tree-ring cellulose with observational records and Earth system model simulations with and without human forcing included. We demonstrate that an intensification of atmospheric drying during the recent decades across different European target regions is unprecedented in a pre-industrial context and that it is attributed to human influence with more than 98% probability. The magnitude of this trend is largest in Western and Central Europe, the Alps and Pyrenees region, and the smallest in southern Fennoscandia. In view of the extreme drought and compound events of the recent years, further atmospheric drying poses an enhanced risk to vegetation, specifically in the densely populated areas of the European temperate lowlands. The atmosphere has dried across most regions of Europe in recent decades, a trend that can be attributed primarily to human impacts, according to tree ring records spanning 400 years and Earth system model simulations.
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| 10. |
- Waltenberger, Johannes, et al.
(författare)
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Five-Year Results of the Bioflow-III Registry : Real-World Experience with a Biodegradable Polymer Sirolimus-Eluting Stent
- 2020
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Ingår i: Cardiovascular Revascularization Medicine. - : Elsevier. - 1553-8389 .- 1878-0938. ; 21:1, s. 63-69
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We aimed to assess long-term safety and performance of the Orsiro sirolimus-eluting coronary stent with biodegradable polymer in a large unselected population and in pre-specified subgroups.Methods: BIOFLOW-III is a prospective, multicenter, international, observational registry with follow-up visits scheduled at 6 and 12 months, and at 3 and 5 years (NCT01553526).Results: 1356 patients with 1738 lesions were enrolled. Of those, 392 (28.9%) declined to participate in the study extension from 18 months to 5 years, 37 (2.7%) withdrew consent, and 89 (6.6%) were lost to follow-up. At 5-years, Kaplan-Meier estimates of target lesion failure, defined as a composite of cardiac death, target-vessel myocardial infarction, coronary artery bypass grafting and clinically driven target lesion revascularization was 10.0% [95% confidence interval (CI): 8.4; 12.0] in the overall population, and 14.0% [95% CI: 10.5; 18.6], 10.3% [95% CI: 7.8; 13.5], 1.8% [95% CI: 0.3; 12.0], and 11.3% [95% CI: 8.5; 15.1] in the pre-defined risk groups of patients with diabetes mellitus, small vessels <= 2.75 mm, chronic total occlusion, and acute myocardial infarction. Definite stent thrombosis was observed in 0.3% [95% CI: 0.1; 0.9] of patients.Conclusion: These long-term outcomes provide further evidence on the safety and performance of a sirolimus-eluting biodegradable polymer stent within daily clinical practice. The very lowdefinite stent thrombosis rate affirms biodegradable polymer safety and performance.
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