| 1. |
- Adcox, K, et al.
(författare)
-
PHENIX detector overview
- 2003
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 499:2-3, s. 469-479
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Tidskriftsartikel (refereegranskat)abstract
- The PHENIX detector is designed to perform a broad study of A-A, p-A, and p-p collisions to investigate nuclear matter under extreme conditions. A wide variety of probes, sensitive to all timescales, are used to study systematic variations with species and energy as well as to measure the spin structure of the nucleon. Designing for the needs of the heavy-ion and polarized-proton programs has produced a detector with unparalleled capabilities. PHENIX measures electron and muon pairs, photons, and hadrons with excellent energy and momentum resolution. The detector consists of a large number of subsystems that are discussed in other papers in this volume. The overall design parameters of the detector are presented. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 2. |
- Awes, T., et al.
(författare)
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Design and performance of a silicon–tungsten calorimeter prototype module and the associated readout
- 2021
-
Ingår i: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 988
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Tidskriftsartikel (refereegranskat)abstract
- We describe the details of a silicon–tungsten prototype electromagnetic calorimeter module and associated readout electronics. Detector performance for this prototype has been measured in test beam experiments at the CERN PS and SPS accelerator facilities in 2015/16. The results are compared to those in Monte Carlo Geant4 simulations. This is the first real-world demonstration of the performance of a custom ASIC designed for fast, lower-power, high-granularity applications.
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| 3. |
- Adler, SS, et al.
(författare)
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PHENIX on-line systems
- 2003
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 499:2-3, s. 560-592
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Tidskriftsartikel (refereegranskat)abstract
- The PHENIX On-Line system takes signals from the Front End Modules (FEM) on each detector subsystem for the purpose of generating events for physics analysis. Processing of event data begins when the Data Collection Modules (DCM) receive data via fiber-optic links from the FEMs. The DCMs format and zero suppress the data and generate data packets. These packets go to the Event Builders (EvB) that assemble the events in final form. The Level-1 trigger (LVL1) generates a decision for each beam crossing and eliminates uninteresting events. The FEMs carry out all detector processing of the data so that it is delivered to the DCMs using a standard format. The FEMs also provide buffering for LVL1 trigger processing and DCM data collection. This is carried out using an architecture that is pipelined and deadtimeless. All of this is controlled by the Master Timing System (MTS) that distributes the RHIC clocks. A Level-2 trigger (LVL2) gives additional discrimination. A description of the components and operation of the PHENIX On-Line system is given and the solution to a number of electronic infrastructure problems are discussed. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 4. |
- Alström, Per, et al.
(författare)
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Complete species-level phylogeny of the leaf warbler (Aves: Phylloscopidae) radiation
- 2018
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Ingår i: Molecular Phylogenetics and Evolution. - : Elsevier BV. - 1055-7903 .- 1095-9513. ; 126, s. 141-152
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Tidskriftsartikel (refereegranskat)abstract
- The leaf warbler radiation (Aves: Phylloscopidae) has undergone a c. 50% increase in the number of recognised species over the last three decades, mainly as a result of analyses of vocalisations and DNA. Using a multilocus dataset for all of the species in this family, and multispecies coalescent-based as well as concatenation methods, we provide the first complete species-level phylogeny for this important group, as well as an estimate of the timing of diversification. The most recent common ancestor for the family was dated at 11.7 million years ago (mya) (95% highest posterior density 9.8-13.7 mya), and divergence times between sister species ranged from 0.5 mya (0.3-0.8 mya) to 6.1 mya (4.8-7.5 mya). Based on our results, we support synonymising Seicercus with Phylloscopus, which results in a monogeneric Phylloscopidae. We discuss the pros and cons of this treatment, and we argue against proliferation of taxonomic names, and conclude that a large monogeneric Phylloscopidae leads to the fewest taxonomic changes compared to traditional classifications. We briefly discuss morphological evolution in the light of the phylogeny. The time calibrated phylogeny is a major improvement compared to previous studies based on a smaller number of species and loci and can provide a basis for future studies of other aspects of phylloscopid evolution.
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| 5. |
- Cros, Emilie, et al.
(författare)
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Fine‐scale barriers to connectivity across a fragmented South‐East Asian landscape in six songbird species
- 2020
-
Ingår i: Evolutionary Applications. - 1752-4571. ; 13:5, s. 1026-1036
-
Tidskriftsartikel (refereegranskat)abstract
- Habitat fragmentation is a major extinction driver. Despite dramatically increas-ing fragmentation across the globe, its specific impacts on population connectivityacross species with differing life histories remain difficult to characterize, let alonequantify. Here, we investigate patterns of population connectivity in six songbirdspecies from Singapore, a highly fragmented tropical rainforest island. Using massivepanels of genome-wide single nucleotide polymorphisms across dozens of samplesper species, we examined population genetic diversity, inbreeding, gene flow andconnectivity among species along a spectrum of ecological specificities. We found ahigher resilience to habitat fragmentation in edge-tolerant and forest-canopy speciesas compared to forest-dependent understorey insectivores. The latter exhibited lev-els of genetic diversity up to three times lower in Singapore than in populations fromcontiguous forest elsewhere. Using dense genomic and geographic sampling, weidentified individual barriers such as reservoirs that effectively minimize gene flowin sensitive understorey birds, revealing that terrestrial forest species may exhibitlevels of sensitivity to fragmentation far greater than previously expected. This studyprovides a blueprint for conservation genomics at small scales with a view to iden-tifying preferred locations for habitat corridors, flagging candidate populations forrestocking with translocated individuals and improving the design of future reserves.
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| 6. |
- Zuo, H., et al.
(författare)
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Vitamin B6 catabolism and lung cancer risk : Results from the Lung Cancer Cohort Consortium (LC3)
- 2019
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 30:3, s. 478-485
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Tidskriftsartikel (refereegranskat)abstract
- Background Increased vitamin B6 catabolism related to inflammation, as measured by the PAr index (the ratio of 4-pyridoxic acid over the sum of pyridoxal and pyridoxal-5'-phosphate), has been positively associated with lung cancer risk in two prospective European studies. However, the extent to which this association translates to more diverse populations is not known. Materials and methods For this study, we included 5323 incident lung cancer cases and 5323 controls individually matched by age, sex, and smoking status within each of 20 prospective cohorts from the Lung Cancer Cohort Consortium. Cohort-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PAr and lung cancer risk were calculated using conditional logistic regression and pooled using random-effects models. Results PAr was positively associated with lung cancer risk in a dose-response fashion. Comparing the fourth versus first quartiles of PAr resulted in an OR of 1.38 (95% CI: 1.19-1.59) for overall lung cancer risk. The association between PAr and lung cancer risk was most prominent in former smokers (OR: 1.69, 95% CI: 1.36-2.10), men (OR: 1.60, 95% CI: 1.28-2.00), and for cancers diagnosed within 3 years of blood draw (OR: 1.73, 95% CI: 1.34-2.23). Conclusion Based on pre-diagnostic data from 20 cohorts across 4 continents, this study confirms that increased vitamin B6 catabolism related to inflammation and immune activation is associated with a higher risk of developing lung cancer. Moreover, PAr may be a pre-diagnostic marker of lung cancer rather than a causal factor.
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| 7. |
- Ahmad, Shafqat, et al.
(författare)
-
Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry. : combined analysis of 111,421 individuals of European ancestry
- 2013
-
Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 9:7, s. 1003607-1003607
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Tidskriftsartikel (refereegranskat)abstract
- Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS × physical activity interaction effect estimate (Pinteraction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, Pinteraction = 0.014 vs. n = 71,611, Pinteraction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (Pinteraction = 0.003) and the SEC16B rs10913469 (Pinteraction = 0.025) variants showed evidence of SNP × physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.
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| 8. |
- Ahmad, Shafqat, et al.
(författare)
-
Gene x physical activity interactions in obesity : combined analysis of 111,421 individuals of European ancestry
- 2013
-
Ingår i: PLOS Genetics. - : Public Library of Science. - 1553-7390 .- 1553-7404. ; 9:7, s. e1003607-
-
Tidskriftsartikel (refereegranskat)abstract
- Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS x physical activity interaction effect estimate (P-interaction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, P-interaction = 0.014 vs. n = 71,611, P-interaction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (P-interaction = 0.003) and the SEC16B rs10913469 (P-interaction = 0.025) variants showed evidence of SNP x physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.
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| 9. |
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| 10. |
- Anderson, Leif G, 1951, et al.
(författare)
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Export of calcium carbonate corrosive waters from the East Siberian Sea
- 2017
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 14:7, s. 1811-1823
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Tidskriftsartikel (refereegranskat)abstract
- The Siberian shelf seas are areas of extensive biogeochemical transformation of organic matter, both of marine and terrestrial origin. This in combination with brine production from sea ice formation results in a cold bottom water of relative high salinity and partial pressure of carbon dioxide (pCO(2)). Data from the SWERUS-C3 expedition compiled on the icebreaker Oden in July to September 2014 show the distribution of such waters at the outer shelf, as well as their export into the deep central Arctic basins. Very high pCO(2) water, up to similar to 1000 mu atm, was observed associated with high nutrients and low oxygen concentrations. Consequently, this water had low saturation state with respect to calcium carbonate down to less than 0.8 for calcite and 0.5 for aragonite. Waters undersaturated in aragonite were also observed in the surface in waters at equilibrium with atmospheric CO2; however, at these conditions the cause of undersaturation was low salinity from river runoff and/or sea ice melt. The calcium carbonate corrosive water was observed all along the continental margin and well out into the deep Makarov and Canada basins at a depth from about 50 m depth in the west to about 150 m in the east. These waters of low aragonite saturation state are traced in historic data to the Canada Basin and in the waters flowing out of the Arctic Ocean north of Greenland and in the western Fram Strait, thus potentially impacting the marine life in the North Atlantic Ocean.
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| 11. |
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| 12. |
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| 13. |
- Batalha-Filho, Henrique, et al.
(författare)
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Molecular systematics and evolution of the Synallaxis ruficapilla complex (Aves : Furnariidae) in the Atlantic Forest.
- 2013
-
Ingår i: Molecular Phylogenetics and Evolution. - : Elsevier BV. - 1055-7903 .- 1095-9513. ; 67:1, s. 86-94
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Tidskriftsartikel (refereegranskat)abstract
- The Neotropical Synallaxis ruficapilla complex is endemic to the Atlantic Forest and is comprised of three species: S. ruficapilla, S. whitneyi, and S. infuscata. This group is closely related to the Synallaxis moesta complex that occurs in the Andes, Tepuis, and Guianan shield. Here we used mitochondrial and nuclear gene sequences to infer the phylogeny and the time of diversification of the S. ruficapilla and S. moesta complexes. We also included samples of an undescribed population of Synallaxis that resembles other populations of the S. ruficapilla complex. Our results showed that different geographical lineages within the S. ruficapilla complex are reciprocally monophyletic, but the northern form (S. infuscata) grouped with an Andean taxon. This suggests that at least two lineages of this group independently colonized the Atlantic Forest. Specimens of the undescribed population formed a monophyletic clade with deep divergence. Estimated diversification dates were within the late Pliocene to Pleistocene (2.75-0.16 million of years ago). This suggests that at this time there was a higher connectivity between habitats in the rugged landscapes of the circum-Amazonian bioregions. The observed Pleistocene diversification within the Atlantic Forest is congruent in space and time with studies of other co-distributed organisms, and may be associated with climate changes and tectonic activity during this period.
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| 14. |
- Batalha-Filho, Henrique, et al.
(författare)
-
Phylogeny and historical biogeography of gnateaters (Passeriformes, Conopophagidae) in the South America forests.
- 2014
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Ingår i: Molecular Phylogenetics and Evolution. - : Elsevier BV. - 1055-7903 .- 1095-9513. ; 79, s. 422-432
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Tidskriftsartikel (refereegranskat)abstract
- We inferred the phylogenetic relationships, divergence time and biogeography of Conopophagidae (gnateaters) based on sequence data of mitochondrial genes (ND2, ND3 and cytb) and nuclear introns (TGFB2 and G3PDH) from 45 tissue samples (43 Conopophaga and 2 Pittasoma) representing all currently recognized species of the family and the majority of subspecies. Phylogenetic relationships were estimated by maximum likelihood and Bayesian inference. Divergence time estimates were obtained based on a Bayesian relaxed clock model. These chronograms were used to calculate diversification rates and reconstruct ancestral areas of the genus Conopophaga. The phylogenetic analyses support the reciprocal monophyly of the two genera, Conopophaga and Pittasoma. All species were monophyletic with the exception of C. lineata, as C. lineata cearae did not cluster with the other two C. lineata subspecies. Divergence time estimates for Conopophagidae suggested that diversification took place during the Neogene, and that the diversification rate within Conopophaga clade was highest in the late Miocene, followed by a slower diversification rate, suggesting a diversity-dependent pattern. Our analyses of the diversification of family Conopophagidae provided a scenario for evolution in Terra Firme forest across tropical South America. The spatio-temporal pattern suggests that Conopophaga originated in the Brazilian Shield and that a complex sequence of events possibly related to the Andean uplift and infilling of former sedimentation basins and erosion cycles shaped the current distribution and diversity of this genus.
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| 15. |
- Bestas, Burcu, et al.
(författare)
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A Type II-B Cas9 nuclease with minimized off-targets and reduced chromosomal translocations in vivo
- 2023
-
Ingår i: NATURE COMMUNICATIONS. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes Cas9 (SpCas9) and derived enzymes are widely used as genome editors, but their promiscuous nuclease activity often induces undesired mutations and chromosomal rearrangements. Several strategies for mapping off-target effects have emerged, but they suffer from limited sensitivity. To increase the detection sensitivity, we develop an off-target assessment workflow that uses Duplex Sequencing. The strategy increases sensitivity by one order of magnitude, identifying previously unknown SpCas9's off-target mutations in the humanized PCSK9 mouse model. To reduce off-target risks, we perform a bioinformatic search and identify a high-fidelity Cas9 variant of the II-B subfamily from Parasutterella secunda (PsCas9). PsCas9 shows improved specificity as compared to SpCas9 across multiple tested sites, both in vitro and in vivo, including the PCSK9 site. In the future, while PsCas9 will offer an alternative to SpCas9 for research and clinical use, the Duplex Sequencing workflow will enable a more sensitive assessment of Cas9 editing outcomes. SpCas9 unintended editing is a major concern. Here the authors report an off-target method using Duplex Sequencing with increased sensitivity for Cas9 mutation detection; they also identify a Cas9 variant of the II-B subfamily with intrinsic high fidelity (PsCas9) and see improved specificity.
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| 16. |
- Björnsdotter, Maria, 1989-, et al.
(författare)
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Challenges in the analytical determination of ultra-short-chain perfluoroalkyl acids and implications for environmental and human health
- 2020
-
Ingår i: Analytical and Bioanalytical Chemistry. - : Springer. - 1618-2642 .- 1618-2650. ; 412, s. 4785-4796
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Forskningsöversikt (refereegranskat)abstract
- Ultra-short-chain perfluoroalkyl acids have recently gained attention due to increasing environmental concentrations being observed. The most well-known ultra-short-chain perfluoroalkyl acid is trifluoroacetic acid (TFA) which has been studied since the 1990s. Potential sources and the fate of ultra-short-chain perfluoroalkyl acids other than TFA are not well studied and data reporting their environmental occurrence is scarce. The analytical determination of ultra-short-chain perfluoroalkyl acids is challenging due to their high polarity resulting in low retention using reversed-phase liquid chromatography. Furthermore, recent studies have reported varying extraction recoveries in water samples depending on the water matrix and different methods have been suggested to increase the extraction recovery. The present review gives an overview of the currently used analytical methods and summarizes the findings regarding potential analytical challenges. In addition, the current state of knowledge regarding TFA and other ultra-short-chain perfluoroalkyl acids, namely perfluoropropanoic acid, trifluoromethane sulfonic acid, perfluoroethane sulfonic acid, and perfluoropropane sulfonic acid‚ are reviewed. Both known and potential sources as well as environmental concentrations are summarized and discussed together with their fate and the environmental and human implications.
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| 17. |
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| 18. |
- Björnsdotter, Maria, 1989-, et al.
(författare)
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Levels and Seasonal Trends of C1-C4 Perfluoroalkyl Acids and the Discovery of Trifluoromethane Sulfonic Acid in Surface Snow in the Arctic
- 2021
-
Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 55:23, s. 15853-15861
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Tidskriftsartikel (refereegranskat)abstract
- C1-C4 perfluoroalkyl acids (PFAAs) are highly persistent chemicals that have been found in the environment. To date, much uncertainty still exists about their sources and fate. The importance of the atmospheric degradation of volatile precursors to C1-C4 PFAAs were investigated by studying their distribution and seasonal variation in remote Arctic locations. C1-C4 PFAAs were measured in surface snow on the island of Spitsbergen in the Norwegian Arctic during January-August 2019. Trifluoroacetic acid (TFA), perfluoropropanoic acid (PFPrA), perfluorobutanoic acid (PFBA), and trifluoromethane sulfonic acid (TFMS) were detected in most samples, including samples collected at locations presumably receiving PFAA input solely from long-range processes. The flux of TFA, PFPrA, PFBA, and TFMS per precipitation event was in the ranges of 22-1800, 0.79-16, 0.19-170, and 1.5-57 ng/m2, respectively. A positive correlation between the flux of TFA, PFPrA, and PFBA with downward short-wave solar radiation was observed. No correlation was observed between the flux of TFMS and solar radiation. These findings suggest that atmospheric transport of volatile precursors and their subsequent degradation plays a major role in the global distribution of C2-C4 perfluoroalkyl carboxylic acids and their consequential deposition in Arctic environments. The discovery of TFMS in surface snow at these remote Arctic locations suggests that TFMS is globally distributed. However, the transport mechanism to the Arctic environment remains unknown.
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| 19. |
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| 20. |
- Björnsdotter, Maria, 1989-, et al.
(författare)
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Mass Balance of Perfluoroalkyl Acids, Including Trifluoroacetic Acid, in a Freshwater Lake
- 2022
-
Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 56:1, s. 251-259
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Tidskriftsartikel (refereegranskat)abstract
- Perfluoroalkyl acids (PFAAs) are highly persistent chemicals that are ubiquitously found in the environment. The atmospheric degradation of precursor compounds has been identified as a source of PFAAs and might be an important pathway for contamination. Lake Vättern is one of Sweden's largest lakes and is an important source for drinking water. In addition to contamination via atmospheric deposition, the lake is subject to several potential contamination sources via surface water inflow. The relevance of different sources is not well understood. A mass balance of selected PFAAs was assembled based on measured concentrations in atmospheric deposition, surface water from streams that constitute the main inflow and outflow, and surface water in the lake. The largest input was seen for trifluoroacetic acid (150 kg/year), perfluoropropanoic acid (1.6 kg/year), perfluorobutanoic acid (4.0 kg/year), and perfluoro-octanoic acid (1.5 kg/year). Both atmospheric deposition and surface water inflow was found to be important input pathways. There was a positive correlation between the input of most perfluoroalkyl carboxylic acids via atmospheric deposition and global radiation and between the input via surface water inflow and catchment area. These findings highlight the importance of atmospheric oxidation of volatile precursor compounds for contamination in surface waters.
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| 21. |
- Björnsdotter, Maria, 1989-
(författare)
-
Ultra-short-chain perfluoroalkyl acids : Environmental occurrence, sources and distribution
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ultra-short-chain perfluoroalkyl acids (PFAAs) is a group of highly fluorinated and very stable chemicals. Their small molecular structure in combination with the acidic functional group result in highly polar compounds and concern has been raised as these substances may threaten our drinking water supplies.The aim with this thesis was to study and assess the occurrence, sources, and distribution of ultra-short-chain PFAAs in the environment. The main objectives were to analyze ultra-short-chain PFAAs in surface water with different anthropogenic impact, in atmospheric deposition and surface snow at local and remote locations, and to examine the relevance of local and diffuse input pathways to Lake Vättern, Sweden.The results revealed that ultra-short-chain PFAAs are released to the environment from various sources such as firefighting training sites, landfills, and hazardous waste management facilities. Trifluoroacetic acid (TFA) and perfluoropropanoic acid (PFPrA) were detected in all atmospheric deposition samples and surface snow samples, including those collected at remote sites in the Arctic. Atmospheric oxidation of volatile precursors was found to play a major role in the global distribution of these as well as being the main input pathway to Lake Vättern. A total annual flux of 120–170 kg and 1.3–2.0 kg was observed for TFA and PFPrA, respectively.Trifluoromethane sulfonic acid (TFMS) was detected in most samples and was reported for the first time in atmospheric deposition and surface snow at local as well as remote locations. The discovery of TFMS at remote locations suggests that TFMS is globally distributed. Neither atmospheric degradation of volatile precursors, nor the long-range oceanic transport seem to be main sources of TFMS to the Arctic environment, and local sources seem to be of higher importance for TFMS input to Lake Vättern.
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| 22. |
- Björnsdotter, Maria, 1989-, et al.
(författare)
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Ultra-Short-Chain Perfluoroalkyl Acids Including Trifluoromethane Sulfonic Acid in Water Connected to Known and Suspected Point Sources in Sweden
- 2019
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 53:19, s. 11093-11101
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Tidskriftsartikel (refereegranskat)abstract
- Data presenting the environmental occurrence of ultra-short-chain perfluoroalkyl acids (PFAAs) are scarce and little is known about the potential sources. In this study, ultra-short-chain PFAAs were analyzed in water connected to potential point sources using supercritical fluid chromatography coupled with tandem mass spectrometry. Samples (n = 34) were collected in connection with firefighting training sites, landfills, and a hazardous waste management facility. Ultra-short-chain PFAAs were detected in all samples at concentrations up to 84 000 ng/L (∑C1-C3), representing up to 69% of the concentration of 29 per- and polyfluoroalkyl substances (PFASs). Trifluoroacetic acid (TFA), perfluoropropanoic acid (PFPrA), trifluoromethane sulfonic acid (TFMS), perfluoroethane sulfonic acid (PFEtS), and perfluoropropane sulfonic acid (PFPrS) were detected at concentrations up to 14 000, 53 000, 940, 1700, and 15 000 ng/L, respectively. Principal component analysis suggests that TFA is associated with landfills. PFPrS was associated with samples collected close to the source at all types of sites included in this study. These findings reveal the presence of high concentrations of ultra-short-chain PFAAs released into the environment from various sources and emphasize the large fraction of ultra-short-chain PFAAs to the total concentration of PFASs in water.
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| 23. |
- Brabant, G, et al.
(författare)
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E-cadherin: a differentiation marker in thyroid malignancies.
- 1993
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Ingår i: Cancer research. - 0008-5472. ; 53:20, s. 4987-93
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Tidskriftsartikel (refereegranskat)abstract
- Loss of E-cadherin (uvomorulin), a Ca(2+)-dependent cell adhesion molecule required for normal epithelial function, has been attributed a pathogenetic role in tumor invasion. The expression of E-cadherin was studied in normal and neoplastic follicular epithelium of the human thyroid by Northern blot analysis and immunofluorescence on frozen tissue sections. In the normal thyroid (n = 10) and in benign thyroid disorders (n = 21; toxic diffuse goitre; multinodular goitre; follicular adenomas), E-cadherin mRNA levels were equally high and the follicles were generally stained, mainly along the lateral surface of the epithelial cells, by the anti-E-cadherin monoclonal antibody. In anaplastic thyroid carcinomas (n = 6) E-cadherin expression was very low or lacking. In papillary carcinomas (n = 23), E-cadherin mRNA levels varied from nearly normal to highly reduced, which roughly correlated with the overall immunofluorescence intensity. However, the immunostaining also revealed a heterogeneous "all-or-nothing" expression of E-cadherin among adjacent cells in the same tumor. In the follicular carcinomas (n = 9), E-cadherin mRNA levels were in general rather high but the immunostaining varied considerably. A few papillary and follicular tumors lacked immunoreactive E-cadherin in spite of high mRNA levels. In oxyphilic (Hürthle) cell tumors, comprising both adenomas (n = 4) and carcinomas (n = 2), E-cadherin immunoreactivity was reduced and distributed intracellularly rather than at the cell surface. The expression of E-cadherin in relapsing thyroid carcinomas and in tumors with metastatic spreading was, irrespective of the histiotype, low or lacking. Sequential Northern analysis revealed a close correlation between the expression levels of E-cadherin and the thyrotropin receptor. Together, the data suggest that in human thyroid malignancies both gene expression and posttranscriptional control of E-cadherin may be impaired.
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| 24. |
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| 25. |
- Carreras, A., et al.
(författare)
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In vivo genome and base editing of a human PCSK9 knock-in hypercholesterolemic mouse model
- 2019
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Ingår i: Bmc Biology. - : Springer Science and Business Media LLC. - 1741-7007. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background Plasma concentration of low-density lipoprotein (LDL) cholesterol is a well-established risk factor for cardiovascular disease. Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), which regulates cholesterol homeostasis, has recently emerged as an approach to reduce cholesterol levels. The development of humanized animal models is an important step to validate and study human drug targets, and use of genome and base editing has been proposed as a mean to target disease alleles.ResultsTo address the lack of validated models to test the safety and efficacy of techniques to target human PCSK9, we generated a liver-specific human PCSK9 knock-in mouse model (hPCSK9-KI). We showed that plasma concentrations of total cholesterol were higher in hPCSK9-KI than in wildtype mice and increased with age. Treatment with evolocumab, a monoclonal antibody that targets human PCSK9, reduced cholesterol levels in hPCSK9-KI but not in wildtype mice, showing that the hypercholesterolemic phenotype was driven by overexpression of human PCSK9. CRISPR-Cas9-mediated genome editing of human PCSK9 reduced plasma levels of human and not mouse PCSK9, and in parallel reduced plasma concentrations of total cholesterol; genome editing of mouse Pcsk9 did not reduce cholesterol levels. Base editing using a guide RNA that targeted human and mouse PCSK9 reduced plasma levels of human and mouse PCSK9 and total cholesterol. In our mouse model, base editing was more precise than genome editing, and no off-target editing nor chromosomal translocations were identified.ConclusionsHere, we describe a humanized mouse model with liver-specific expression of human PCSK9 and a human-like hypercholesterolemia phenotype, and demonstrate that this mouse can be used to evaluate antibody and gene editing-based (genome and base editing) therapies to modulate the expression of human PCSK9 and reduce cholesterol levels. We predict that this mouse model will be used in the future to understand the efficacy and safety of novel therapeutic approaches for hypercholesterolemia.
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| 26. |
- de Batlle, J., et al.
(författare)
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Dietary Folate Intake and Breast Cancer Risk: European Prospective Investigation Into Cancer and Nutrition
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 107:1, s. 367-367
-
Tidskriftsartikel (refereegranskat)abstract
- There is limited evidence on the association between dietary folate intake and the risk of breast cancer (BC) by hormone receptor expression in the tumors. We investigated the relationship between dietary folate and BC risk using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 367993 women age 35 to 70 years were recruited in 10 European countries. During a median follow-up of 11.5 years, 11575 women with BC were identified. Dietary folate intake was estimated from country-specific dietary questionnaires. Cox proportional hazards regression models were used to quantify the association between dietary variables and BC risk. BC tumors were classified by receptor status. Subgroup analyses were performed by menopausal status and alcohol intake. Intake of other B vitamins was considered. All statistical tests were two-sided. A borderline inverse association was observed between dietary folate and BC risk (hazard ratio comparing top vs bottom quintile [HRQ5-Q1] = 0.92, 95% CI = 0.83 to 1.01, P (trend) = .037). In premenopausal women, we observed a statistically significant trend towards lower risk in estrogen receptor-negative BC (HRQ5-Q1 = 0.66, 95% CI = 0.45 to 0.96, P (trend) = .042) and progesterone receptor-negative BC (HRQ5-Q1 = 0.70, 95% CI = 0.51 to 0.97, P (trend) = .021). No associations were found in postmenopausal women. A 14% reduction in BC risk was observed when comparing the highest with the lowest dietary folate tertiles in women having a high (> 12 alcoholic drinks/week) alcohol intake (HRT3-T1 = 0.86, 95% CI = 0.75 to 0.98, P (interaction) = .035). Higher dietary folate intake may be associated with a lower risk of sex hormone receptor-negative BC in premenopausal women.
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| 27. |
- Deschasaux, M., et al.
(författare)
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Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe: Results from the EPIC prospective cohort study
- 2018
-
Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- Background Helping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods with high/low FSAm-NPS relates to cancer risk has been studied in national/regional cohorts but has not been characterized in diverse European populations. This prospective analysis included 471,495 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC, 1992-2014, median follow-up: 15.3 y), among whom there were 49,794 incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745; colon-rectum, n = 5,806). Usual food intakes were assessed with standardized country-specific diet assessment methods. The FSAm-NPS was calculated for each food/beverage using their 100-g content in energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores of all food items usually consumed by a participant were averaged to obtain the individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower nutritional quality of the food consumed, was associated with a higher risk of total cancer (HRQ5 versus (Q1) = 1.07; 95% CI 1.03-1.10, P-trend < 0.001). Absolute cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI scores were specifically associated with higher risks of cancers of the colon-rectum, upper aerodigestive tract and stomach, lung for men, and liver and postmenopausal breast for women (all P < 0.05). The main study limitation is that it was based on an observational cohort using self-reported dietary data obtained through a single baseline food frequency questionnaire; thus, exposure misclassification and residual confounding cannot be ruled out. In this large multinational European cohort, the consumption of food products with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher risk of cancer. This supports the relevance of the FSAm-NPS as underlying nutrient profiling system for front-of-pack nutrition labels, as well as for other public health nutritional measures.
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| 28. |
- Ericson Jogsten, Ingrid, 1980-, et al.
(författare)
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Analysis of ultra-short chain perfluoroalkyl substances in Swedish environmental waters
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this study was to investigate the environmental occurrence of ultra-short chain perfluoroalkyl substances (PFASs) in Swedish water samples. So far established protocols have focused on measuring PFASs with a carbon chain length of four or more carbons. In this study, perfluoroalkyl sulfonates of chain lengths of two, perfluoroethane sulfonate (PFEtS), and three, perfluoropropane sulfonate (PFPrS), carbons have been measured using a newly established instrumental method employing supercritical fluid separation (SFC) coupled to tandem mass spectrometry detection.A total of 26 samples were analysed, including ground water, surface water, rain water and snow. The sample locations included military and civilian airports, a former hard chromium plating facility, the vicinity of a hazardous waste management facility and background areas (lake surface water, rain and snow). Results show that both PFPrS and PFEtS could be detected in environmental samples using SFC separation coupled to triple quadrupole detection. Out of the 26 samples analysed, the ultra-short-chain PFPrS could be detected and quantified in 22 samples. The concentrations for PFPrS in all the samples ranged between 0.93 ng/l to 39 000 ng/l. The ultra-short-chain PFPEtS could be quantified in all of the 26 samples, with a concentration range between 0.07 and 5 700 ng/l. The highest concentrations represents highly contaminated ground water samples collected from a military airport. In the samples, PFPrS had a relative contribution to total PFAS concentration of 6 and 10 %, indicating the importance of measuring these compounds in environmental samples.
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| 29. |
- Ericson, Y, et al.
(författare)
-
Faktablad från Integrerad kustfiskövervakning: Fjällbacka (Västerhavet) 1989-2015
- 2016
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Ingår i: Faktablad 2016 från Inst för Akvatiska resurser, SLU. ; :2016:1
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Faktabladet presenterar resultat och bedömningar från den integrerade kustfiskövervakningen i Fjällbacka-området 1989-2015. Övervakningen visar att situationen för tånglake i Fjällbacka är ansträngd. En återhämtning kan dock skönjas de allra sista åren. Tidigare vikande fångster och en försämring av tånglakens hälsotillstånd samt yngelstatus antyder att arten påverkas negativt av omgivningsfaktorer såsom den ökande vattentemperaturen, syrenivåer och exponering för kemikalier.
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| 30. |
- Ericson, Y, et al.
(författare)
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Faktablad från Integrerad kustfiskövervakning: Holmön (Bottniska viken) 1989-2015.
- 2016
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Ingår i: Faktablad 2016 från Inst för Akvatiska Resurser, SLU. ; :2016: 2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Faktabladet presenterar resultat och bedömningar från den integrerade kustfiskövervakningen vid Holmön under tidsperioden 1989-2015. Övervakningen visar för varje år ett alltmer påverkat hälsotillstånd hos abborre trots att de flesta analyserade metaller och organiska miljögifter visar nedåtgående trender eller oförändrade halter. Den tydliga och successiva påverkan som ses på hälsotillståndet på individnivå har ännu inte resulterat i några påtagliga förändringar på bestånds- och samhällsnivå.
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| 31. |
- Ericson, Y, et al.
(författare)
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Faktablad från Integrerad kustfiskövervakning: Kvädöfjärden (Egentliga Östersjön) 1989-2015.
- 2016
-
Ingår i: Faktablad 2016 från Inst för Akvatiska Resurser, SLU. ; :2016:3
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Faktabladet presenterar resultat och bedömningar från den integrerade kustfiskövervakningen i Kvädöfjärden under tidsperioden 1989-2015. Kustfiskövervakningen visar på minskande karpfiskbestånd, minskad totalfångst av fisk och ett påverkat hälsotillstånd hos abborre och tånglake, samtidigt som de flesta analyserade miljögifter visar nedåtgående trender eller oförändrade halter.
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| 32. |
- Ericson, Y, et al.
(författare)
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Faktablad från Integrerad kustfiskövervakning: Torhamn (södra Egentliga Östersjön) 2002-2015
- 2016
-
Ingår i: Faktablad 2016 från Inst för Akvatiska resurser, SLU. ; :2016:4
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Faktabladet presenterar resultat och bedömningar från den integrerade kustfiskövervakningen i Torhamnsområdet under tidsperioden 2002-2015. Resultaten från tretton års undersökningar visar en alltmer tydlig påverkan på hälsotillståndet hos abborre liknande den som observeras hos abborre och tånglake i andra kustreferensområden. Denna tydliga och successiva påverkan som ses på abborrens hälsa på individnivå har ännu inte resulterat i några påtagliga förändringar på bestånds- eller samhällsnivå.
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| 33. |
- Gilbert, M. Thomas P., et al.
(författare)
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Intraspecific phylogenetic analysis of Siberian woolly mammoths using complete mitochondrial genomes
- 2008
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 105:24, s. 8327-8332
-
Tidskriftsartikel (refereegranskat)abstract
- We report five new complete mitochondrial DNA (mtDNA) genomes of Siberian woolly mammoth (Mammuthus primigenius), sequenced with up to 73-fold coverage from DNA extracted from hair shaft material. Three of the sequences present the first complete mtDNA genomes of mammoth clade II. Analysis of these and 13 recently published mtDNA genomes demonstrates the existence of two apparently sympatric mtDNA clades that exhibit high interclade divergence. The analytical power afforded by the analysis of the complete mtDNA genomes reveals a surprisingly ancient coalescence age of the two clades, approximate to 1-2 million years, depending on the calibration technique. Furthermore, statistical analysis of the temporal distribution of the C-14 ages of these and previously identified members of the two mammoth clades suggests that clade II went extinct before clade I. Modeling of protein structures failed to indicate any important functional difference between genomes belonging to the two clades, suggesting that the loss of clade II more likely is due to genetic drift than a selective sweep.
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| 34. |
- Hanson, Niklas, 1976, et al.
(författare)
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Bottendjuren påverkar fiskens hälsa
- 2016
-
Ingår i: HAVET. ; , s. 86-89
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Under 2000-talet har kustfiskens hälsostatus förändrats kraftigt. Det gäller framför allt en mycket tydlig uppgång i aktiviteten av ett avgiftningssystem i levern hos abborre, följt av en lika kraftig nedgång. Förändringen var så stor att den är svår att förklara med något annat än ett förändrat upptag av miljögifter. Djupare analyser visar ett starkt samband med förekomsten av bottenlevande djur. Det är möjligt att dessa bidrar till att återföra miljögifter från bottensediment till ekosystemet.
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| 35. |
- Hartz, William F., et al.
(författare)
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Levels and distribution profiles of Per- and Polyfluoroalkyl Substances (PFAS) in a high Arctic Svalbard ice core
- 2023
-
Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 871
-
Tidskriftsartikel (refereegranskat)abstract
- Per- and polyfluoroalkyl substances (PFAS) are a group of persistent organic contaminants of which some are toxic and bioaccumulative. Several PFAS can be formed from the atmospheric degradation of precursors such as fluorotelomer alcohols (FTOHs) as well as hydrochlorofluorocarbons (HFCs) and other ozone-depleting chlorofluorocarbon (CFC) replacement compounds. Svalbard ice cores have been shown to provide a valuable record of long-range atmospheric transport of contaminants to the Arctic. This study uses a 12.3 m ice core from the remote Lomonosovfonna ice cap on Svalbard to understand the atmospheric deposition of PFAS in the Arctic. A total of 45 PFAS were targeted, of which 26 were detected, using supercritical fluid chromatography (SFC) tandem mass spectrometry (MS/MS) and ultra-performance liquid chromatography (UPLC) MS/MS. C2 to C11 perfluoroalkyl carboxylic acids (PFCAs) were detected continuously in the ice core and their fluxes ranged from 2.5 to 8200 ng m-2 yr-1 (9.51-16,500 pg L-1). Trifluoroacetic acid (TFA) represented 71 % of the total mass of C2 - C11 PFCAs in the ice core and had increasing temporal trends in deposition. The distribution profile of PFCAs suggested that FTOHs were likely the atmospheric precursor to C8 - C11 PFCAs, whereas C2 - C6 PFCAs had alternative sources, such as HFCs and other CFC replacement compounds. Perfluorooctanesulfonic acid (PFOS) was also widely detected in 82 % of ice core subsections, and its isomer profile (81 % linear) indicated an electrochemical fluorination manufacturing source. Comparisons of PFAS concentrations with a marine aerosol proxy showed that marine aerosols were insignificant for the deposition of PFAS on Lomonosovfonna. Comparisons with a melt proxy showed that TFA and PFOS were mobile during meltwater percolation. This indicates that seasonal snowmelt and runoff from post-industrial accumulation on glaciers could be a significant seasonal source of PFAS to ecosystems in Arctic fjords.
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| 36. |
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| 37. |
- Huang, Tao, et al.
(författare)
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Dairy Consumption and Body Mass Index Among Adults : Mendelian Randomization Analysis of 184802 Individuals from 25 Studies
- 2018
-
Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 64:1, s. 183-191
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies, and the causal relationship remains ill defined.METHODS: We performed Mendelian randomization (MR) analysis using an established dairy intake-associated genetic polymorphism located upstream of the lactase gene (LCT-13910 C/T, rs4988235) as an instrumental variable (IV). Linear regression models were fitted to analyze associations between (a) dairy intake and BMI, (b) rs4988235 and dairy intake, and (c) rs4988235 and BMI in each study. The causal effect of dairy intake on BMI was quantified by IV estimators among 184802 participants from 25 studies.RESULTS: Higher dairy intake was associated with higher BMI (β = 0.03 kg/m2 per serving/day; 95% CI, 0.00–0.06; P = 0.04), whereas the LCT genotype with 1 or 2 T allele was significantly associated with 0.20 (95% CI, 0.14–0.25) serving/day higher dairy intake (P = 3.15 × 10−12) and 0.12 (95% CI, 0.06–0.17) kg/m2 higher BMI (P = 2.11 × 10−5). MR analysis showed that the genetically determined higher dairy intake was significantly associated with higher BMI (β = 0.60 kg/m2 per serving/day; 95% CI, 0.27–0.92; P = 3.0 × 10−4).CONCLUSIONS: The present study provides strong evidence to support a causal effect of higher dairy intake on increased BMI among adults.
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| 38. |
- Ibsen, Daniel B, et al.
(författare)
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Replacement of Red and Processed Meat With Other Food Sources of Protein and the Risk of Type 2 Diabetes in European Populations : The EPIC-InterAct Study
- 2020
-
Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 43:11, s. 2660-2667
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: There is sparse evidence for the association of suitable food substitutions for red and processed meat on the risk of type 2 diabetes. We modeled the association between replacing red and processed meat with other protein sources and the risk of type 2 diabetes and estimated its population impact.RESEARCH DESIGN AND METHODS: The European Prospective Investigation into Cancer (EPIC)-InterAct case cohort included 11,741 individuals with type 2 diabetes and a subcohort of 15,450 participants in eight countries. We modeled the replacement of self-reported red and processed meat with poultry, fish, eggs, legumes, cheese, cereals, yogurt, milk, and nuts. Country-specific hazard ratios (HRs) for incident type 2 diabetes were estimated by Prentice-weighted Cox regression and pooled using random-effects meta-analysis.RESULTS: There was a lower hazard for type 2 diabetes for the modeled replacement of red and processed meat `(50 g/day) with cheese (HR 0.90, 95% CI 0.83-0.97) (30 g/day), yogurt (0.90, 0.86-0.95) (70 g/day), nuts (0.90, 0.84-0.96) (10 g/day), or cereals (0.92, 0.88-0.96) (30 g/day) but not for replacements with poultry, fish, eggs, legumes, or milk. If a causal association is assumed, replacing red and processed meat with cheese, yogurt, or nuts could prevent 8.8%, 8.3%, or 7.5%, respectively, of new cases of type 2 diabetes.CONCLUSIONS: Replacement of red and processed meat with cheese, yogurt, nuts, or cereals was associated with a lower rate of type 2 diabetes. Substituting red and processed meat by other protein sources may contribute to the prevention of incident type 2 diabetes in European populations.
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| 39. |
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| 40. |
- Keita, Åsa V, et al.
(författare)
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Characterization of antigen and bacterial transport in the follicle-associated epithelium of human ileum
- 2006
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Ingår i: Laboratory investigation. - : Elsevier BV. - 0023-6837 .- 1530-0307. ; 86:5, s. 504-516
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Tidskriftsartikel (refereegranskat)abstract
- The follicle-associated epithelium (FAE), covering Peyer's patches, provides a route of entry for antigens and microorganisms. Animal studies showed enhanced antigen and bacterial uptake in FAE, but no study on barrier function of human FAE has been reported. Our aim was to characterize the normal barrier properties of human FAE. Specimens of normal ileum were taken from 30 patients with noninflammatory colonic disease. Villus epithelium (VE) and FAE were identified and mounted in Ussing chambers. Permeability to 51Cr-EDTA, transmucosal flux of the protein antigen, horseradish peroxidase (HRP), and transport of fluorescent Escherichia coli (chemically killed K-12 and live HB101) were measured. Uptake mechanisms were studied by confocal- and transmission electron microscopy, and by using pharmacological inhibitors in an in vitro coculture model of FAE and in human ileal FAE. HRP flux was substantially higher in FAE than in VE, and was reduced by an amiloride analog. Electron microscopy showed HRP-containing endosomes. Transport of E. coli K-12 and HB101 was also augmented in FAE and was confirmed by confocal microscopy. In vitro coculture experiments and electron microscopy revealed actin-dependent, mainly transcellular, uptake of E. coli K-12 into FAE. 51Cr-EDTA permeability was equal in FAE and VE. Augmented HRP flux and bacterial uptake but similar paracellular permeability, suggest functional variations of transcellular transport in the FAE. We show for the first time that FAE of human ileum is functionally distinct from regular VE, rendering the FAE more prone to bacterial–epithelial cell interactions and delivery of antigens to the mucosal immune system.
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| 41. |
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| 42. |
- Kvist, Malin, et al.
(författare)
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Detection of ultra-short chain perfluoroalkyl substances in Swedish environmental waters
- 2017
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The ubiquitous distribution of perfluoroalkyl substances (PFASs) has been documented worldwide in different environmental samples including humans. In Sweden, severe PFAS contamination in drinking water has resulted in elevated blood PFAS concentrations in residents living in contaminated areas. In many cases, the use of aqueous film forming-foams (AFFFs) at both civil and military airports has resulted in this contamination, as PFASs are one of the active ingredients in AFFFs. According to a nationwide survey, it was estimated that 30 % of the Swedish population has their closest drinking water source contaminated with these substances. A guideline value for safe use of drinking water set by the Swedish Food Agencyis the sum of eleven PFASs including perfluoroalkylated sulfonates (PFSAs; C4, C6, C8), perfluoroalkylated carboxylates (PFCAs; C4-C10) and 6:2 fluorotelomer sulfonate.This is set to 90 ng/L, while the health based limit, based on the tolerable daily intake,is set to 900 ng/L. In the US, Barzen-Hansen et al.showed the presence of ultra-short chain PFASs, perfluoropropanesulfonate (PFPrS) and perfluoroethanesulfonate (PFEtS), in five AFFFs. In ground water samples from eleven US military bases, PFEtS was detected in eight out of eleven samples ranging from 11-7500 ng/L, while PFPrS was detected in all samples, ranging from 19-63000 ng/L). Conventional reversed-phase LC using C18 column is not suitable to chromatograph these ultra-short chain PFAS, because they are highly polar; ion-exchange column has been demonstrated useful for separating these ultra-short chain PFAS. In this study a new analytical approach employing supercritical fluid chromatography (SFC) was developed for chromatographic separation of these ultra-short chain PFASs. Environmental water samples (surface water, ground water, rain water, snow and sediment) from various locations with suspected PFAS contamination were analyzed to investigate the potential occurrence of these ultra-short chain compounds in the Swedish environment. Solid phase extraction according to ISO method was used to concentrate water samples prior to instrumental analyses using both UPLC-MS/MS and UPC2-MS/MS.Results show that both PFPrS and PFEtS could be detected in environmental samples from Sweden using SFC separation coupled to triple quadrupole detection. Out of the 26 samples analysed,the ultra-short-chain PFPrS could be detected and quantified in 22 samples. The concentrations for PFPrS in all the samples ranged between 0.93 ng/l to 390 μg/l. The ultra-short-chain PFPEtS could be quantified in 24 out of the 26 samples, with a concentration range between 0.07-5 680 ng/l. The highest concentrations represents highly contaminated ground water samples collected from a military airport.
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| 43. |
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| 44. |
- Laine, Jessica E., et al.
(författare)
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Co-benefits from sustainable dietary shifts for population and environmental health : an assessment from a large European cohort study
- 2021
-
Ingår i: The Lancet Planetary Health. - 2542-5196. ; 5:11, s. 786-796
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Unhealthy diets, the rise of non-communicable diseases, and the declining health of the planet are highly intertwined, where food production and consumption are major drivers of increases in greenhouse gas emissions, substantial land use, and adverse health such as cancer and mortality. To assess the potential co-benefits from shifting to more sustainable diets, we aimed to investigate the associations of dietary greenhouse gas emissions and land use with all-cause and cause-specific mortality and cancer incidence rates. Methods: Using data from 443 991 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a multicentre prospective cohort, we estimated associations between dietary contributions to greenhouse gas emissions and land use and all-cause and cause-specific mortality and incident cancers using Cox proportional hazards regression models. The main exposures were modelled as quartiles. Co-benefits, encompassing the potential effects of alternative diets on all-cause mortality and cancer and potential reductions in greenhouse gas emissions and land use, were estimated with counterfactual attributable fraction intervention models, simulating potential effects of dietary shifts based on the EAT–Lancet reference diet. Findings: In the pooled analysis, there was an association between levels of dietary greenhouse gas emissions and all-cause mortality (adjusted hazard ratio [HR] 1·13 [95% CI 1·10–1·16]) and between land use and all-cause mortality (1·18 [1·15–1·21]) when comparing the fourth quartile to the first quartile. Similar associations were observed for cause-specific mortality. Associations were also observed between all-cause cancer incidence rates and greenhouse gas emissions, when comparing the fourth quartile to the first quartile (adjusted HR 1·11 [95% CI 1·09–1·14]) and between all-cause cancer incidence rates and land use (1·13 [1·10–1·15]); however, estimates differed by cancer type. Through counterfactual attributable fraction modelling of shifts in levels of adherence to the EAT–Lancet diet, we estimated that up to 19–63% of deaths and up to 10–39% of cancers could be prevented, in a 20-year risk period, by different levels of adherence to the EAT–Lancet reference diet. Additionally, switching from lower adherence to the EAT–Lancet reference diet to higher adherence could potentially reduce food-associated greenhouse gas emissions up to 50% and land use up to 62%. Interpretation: Our results indicate that shifts towards universally sustainable diets could lead to co-benefits, such as minimising diet-related greenhouse gas emissions and land use, reducing the environmental footprint, aiding in climate change mitigation, and improving population health. Funding: European Commission (DG-SANCO), the International Agency for Research on Cancer (IARC), MRC Early Career Fellowship (MR/M501669/1).
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| 45. |
- Merino, Jordi, et al.
(författare)
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Quality of dietary fat and genetic risk of type 2 diabetes : individual participant data meta-analysis
- 2019
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Ingår i: BMJ. British Medical Journal. - : BMJ Publishing Group Ltd. - 0959-8146 .- 0959-535X. ; 366
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To investigate whether the genetic burden of type 2 diabetes modifies the association between the quality of dietary fat and the incidence of type 2 diabetes.DESIGN Individual participant data meta-analysis.DATA SOURCES Eligible prospective cohort studies were systematically sourced from studies published between January 1970 and February 2017 through electronic searches in major medical databases (Medline, Embase, and Scopus) and discussion with investigators.REVIEW METHODS Data from cohort studies or multicohort consortia with available genome-wide genetic data and information about the quality of dietary fat and the incidence of type 2 diabetes in participants of European descent was sought. Prospective cohorts that had accrued five or more years of follow-up were included. The type 2 diabetes genetic risk profile was characterized by a 68-variant polygenic risk score weighted by published effect sizes. Diet was recorded by using validated cohort-specific dietary assessment tools. Outcome measures were summary adjusted hazard ratios of incident type 2 diabetes for polygenic risk score, isocaloric replacement of carbohydrate (refined starch and sugars) with types of fat, and the interaction of types of fat with polygenic risk score.RESULTS Of 102 305 participants from 15 prospective cohort studies, 20 015 type 2 diabetes cases were documented after a median follow-up of 12 years (interquartile range 9.4-14.2). The hazard ratio of type 2 diabetes per increment of 10 risk alleles in the polygenic risk score was 1.64 (95% confidence interval 1.54 to 1.75, I-2 = 7.1%, tau(2) = 0.003). The increase of polyunsaturated fat and total omega 6 polyunsaturated fat intake in place of carbohydrate was associated with a lower risk of type 2 diabetes, with hazard ratios of 0.90 (0.82 to 0.98, I-2 = 18.0%, tau(2) = 0.006; per 5% of energy) and 0.99 (0.97 to 1.00, I-2 = 58.8%, tau(2) = 0.001; per increment of 1 g/d), respectively. Increasing monounsaturated fat in place of carbohydrate was associated with a higher risk of type 2 diabetes (hazard ratio 1.10, 95% confidence interval 1.01 to 1.19, I-2 = 25.9%, tau(2) = 0.006; per 5% of energy). Evidence of small study effects was detected for the overall association of polyunsaturated fat with the risk of type 2 diabetes, but not for the omega 6 polyunsaturated fat and monounsaturated fat associations. Significant interactions between dietary fat and polygenic risk score on the risk of type 2 diabetes (P>0.05 for interaction) were not observed.CONCLUSIONS These data indicate that genetic burden and the quality of dietary fat are each associated with the incidence of type 2 diabetes. The findings do not support tailoring recommendations on the quality of dietary fat to individual type 2 diabetes genetic risk profiles for the primary prevention of type 2 diabetes, and suggest that dietary fat is associated with the risk of type 2 diabetes across the spectrum of type 2 diabetes genetic risk.
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| 46. |
- Mullin, Lauren Gayle, 1984-
(författare)
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Advances in Mass Spectrometry for the Analysis of Emerging Persistent Organic Pollutants
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mass spectrometry (MS) is a technique widely implemented for the measurement of environmental pollutants. A critical tool for the analysis of persistent organic pollutants (POPs) over several decades, MS as coupled with liquid and gas chromatography (LC and GC) techniques enables the analysis of emerging POPs. The aim of this thesis was to investigate the use of alternative MS-based techniques to assist specific analytical challenges including separation of stereoisomers using supercritical fluid chromatography (SFC), reduced ionization competition with appropriate mobile phase additives, and applied rotationally averaged collision-cross section (CCS) of ions via ion mobility measurements of emerging POPs.Chromatographic efficiency improvements for the brominated flame retardant, hexabromocyclododecane (HBCDD), were implemented through the development of two supercritical fluid chromatography (SFC) methods. Based on the inherent qualities of supercritical fluids, separation of both predominant diastereomers and respective enantiomers was performed in a shorter time with wider chromatographic resolution using SFC than existing LC methods.Turning next to MS ionization considerations, the emerging perfluoroalkyl substance hexafluoropropylene oxide-dimer acid (HFPO-DA) was investigated. Following a survey of analytical methodologies for HFPO-DA, the challenge of extreme dimer formation, in-source fragmentation and very low [M-H]- production was described. Method development using alternative mobile phase additives in currently used LC-MS acquisition techniques was deployed.Finally, ion mobility spectrometry (IMS) was implemented in a non-targeted acquisition study of indoor dust samples. This study used IMS coupled with quadrupole time-of-flight MS to identify a wide range of contaminant classes, including emerging POPs. Identification confidence is a challenge currently facing non-targeted studies, and the use of prediction mechanisms of analyte IMS gas-phase separations was explored.Through applying diverse alternative techniques, increased method performance was explored for emerging POPs analyses.
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| 47. |
- Mullin, Lauren Gayle, 1984-, et al.
(författare)
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Analysis of hexafluoropropylene oxide-dimer acid (HFPO-DA) by liquid chromatography-mass spectrometry (LC-MS) : Review of current approaches and environmental levels
- 2019
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Ingår i: TrAC. Trends in analytical chemistry. - : Elsevier. - 0165-9936 .- 1879-3142. ; 118, s. 828-839
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Forskningsöversikt (refereegranskat)abstract
- Emerging per- and polyfluorinated compounds (PFAS) compounds are of increasing interest for environmental monitoring, one being hexafluoropropylene oxide-dimer acid (HFPO-DA), commonly referred to as GenX. The following review describes existing liquid chromatography-mass spectrometry (LC-MS) methods used to analyse HFPO-DA, including sample preparation and method sensitivity relative to other PFAS. Analytical challenges are also described, in particular the significant formation of in-source fragmentation, dimer and dimer adducts which detract from [M-H](-) signal. Lastly, detected levels of HFPO-DA in environmental and biological samples are compared across the limited number of available field exposure studies, which found several mu g/L concentrations in water samples taken near fluorochemical plant discharges.
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| 48. |
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| 49. |
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| 50. |
- Mullin, L., et al.
(författare)
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Liquid chromatography-ion mobility-high resolution mass spectrometry for analysis of pollutants in indoor dust : Identification and predictive capabilities
- 2020
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Ingår i: Analytica Chimica Acta. - : Elsevier. - 0003-2670 .- 1873-4324. ; 1125, s. 29-40
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Tidskriftsartikel (refereegranskat)abstract
- Dust analysis provides a means to assess the degree of exposure of humans in an indoor environment to various contaminant classes such as flame retardants, pesticides and others. There is increasing interest in non-targeted acquisitions using high resolution mass spectrometry (HRMS) to better capture the contaminant profile. However, these studies are confronted with the challenge of assessing confidence in proposed identifications, particularly when authentic standards are not available. Here, we demonstrate the analysis of dust extracts representing various indoor environments (industrial e-waste processing and domestic) for high-abundance environmental contaminants using a data-independent LC-HRMS approach, incorporating ion mobility spectrometry (IMS) to provide additional characterization capability for the complex samples. Twenty-nine xenobiotic compound identifications were made based on both targeted and non-targeted processing approaches using accurate mass precursor and product ion measurement combined with an ion mobility derived collision-cross section (TWCCSN2) determination. Characterization of the repeatability of TWCCSN2 value measurements and their average relative error to compared authentic standards of 0.38% were consistent with various published studies and represent a robust measurement property. TWCCSN2 values were particularly useful in cases where confirmation after the initial dust analysis was performed using a different chromatographic method, due to the gas-phase measurement being unaffected by such changes. Observed compound TWCCSN2 values were then compared to predicted CCSN2 values obtained using two different machine-learning based predictive techniques. Results from one of the predictive programs indicates a promising avenue for use of these models for supporting compound identification in non-targeted analyses.
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