| 1. |
- Caporale, N., et al.
(författare)
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From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375:6582
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Tidskriftsartikel (refereegranskat)abstract
- Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio, as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay. © 2022 American Association for the Advancement of Science. All rights reserved.
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| 2. |
- Birgersson, Sofia, 1976, et al.
(författare)
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Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum malaria in Burkina Faso: An open label trial [version 2; peer review: 2 approved]
- 2020
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Ingår i: Wellcome Open Research. - : F1000 Research Ltd. - 2398-502X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Malaria during pregnancy is a major health risk for both the mother and the foetus. Pregnancy has been shown to influence the pharmacokinetics of a number of different antimalarial drugs. This might lead to an under-exposure in these patients which could increase the risk of treatment failure and the development of drug resistance. The study aim was to evaluate the pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant patients using a population modelling approach. Methods: Twenty-four women in their second and third trimester of pregnancy and twenty-four paired non-pregnant women, all with uncomplicated P. falciparum malaria, were enrolled in this study. Treatment was a fixed-dose combination of oral artesunate and mefloquine once daily for three days. Frequent blood samples were collected and concentration-time data for artesunate and dihydroartemisinin were analysed simultaneously using nonlinear mixed-effects modelling. Results: Artesunate pharmacokinetics was best described by a transit-compartment absorption model followed by a one-compartment disposition model under the assumption of complete in vivo conversion of artesunate into dihydroartemisinin. Dihydroartemisinin pharmacokinetics was best described by a one-compartment disposition model with first-order elimination. Pregnant women had a 21% higher elimination clearance of dihydroartemisinin, compared to non-pregnant women resulting in proportionally lower drug exposure. In addition, initial parasitaemia and liver enzyme levels (alanine aminotransferase) were found to affect the relative bioavailability of artesunate. Conclusions: Results presented here show a substantially lower drug exposure to the antimalarial drug dihydroartemisinin during pregnancy after standard oral treatment of artesunate and mefloquine. This might result in an increased risk of treatment failure and drug resistance development especially in low transmission settings where relative immunity is lower. Trial registration: ClinicalTrials.gov NCT00701961 (19/06/2008). © 2020 Birgersson S et al.
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| 3. |
- Goodrich, H. R., et al.
(författare)
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Understanding the gastrointestinal physiology and responses to feeding in air-breathing Anabantiform fishes
- 2020
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Ingår i: Journal of Fish Biology. - : Wiley. - 0022-1112 .- 1095-8649. ; 96:4, s. 986-1003
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Tidskriftsartikel (refereegranskat)abstract
- The Mekong Delta is host to a large number of freshwater species, including a unique group of facultative air-breathing Anabantiforms. Of these, the striped snakehead (Channa striata), the climbing perch (Anabas testudineus), the giant gourami (Osphronemus goramy) and the snakeskin gourami (Trichogaster pectoralis) are major contributors to aquaculture production in Vietnam. The gastrointestinal responses to feeding in these four species are detailed here. Relative intestinal length was lowest in the snakehead, indicating carnivory, and 5.5-fold greater in the snakeskin, indicating herbivory; climbing perch and giant gourami were intermediate, indicating omnivory. N-waste excretion (ammonia-N + urea-N) was greatest in the carnivorous snakehead and least in the herbivorous snakeskin, whereas the opposite trend was observed for net K+ excretion. Similarly, the more carnivorous species had a greater stomach acidity than the more herbivorous species. Measurements of acid-base flux to water indicated that the greatest postprandial alkaline tide occurred in the snakehead and a potential acidic tide in the snakeskin. Additional findings of interest were high levels of both PCO2 (up to 40 mmHg) and HCO3- (up to 33 mM) in the intestinal chyme of all four of these air-breathing species. Using in vitro gut sac preparations of the climbing perch, it was shown that the intestinal net absorption of fluid, Na+ and HCO3- was upregulated by feeding but not net Cl- uptake, glucose uptake or K+ secretion. Upregulated net absorption of HCO3- suggests that the high chyme (HCO3-) does not result from secretion by the intestinal epithelium. The possibility of ventilatory control of PCO2 to regulate postprandial acid-base balance in these air-breathing fish is discussed.
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| 4. |
- Schlyter, F, et al.
(författare)
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A model for peak and width of signaling windows: Ips duplicatus and Chilo partellus pheromone component proportions - Does response have a wider window than production?
- 2001
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Ingår i: Journal of Chemical Ecology. - 1573-1561. ; 27:7, s. 1481-1511
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Tidskriftsartikel (refereegranskat)abstract
- Pheromone communication systems have a reliable signal with a restricted window of amounts and ratios released and perceived. We propose a model based on a Gaussian response profile that allows a quantification of the response peak (location of optimum) and a measure of the peak width (response window). Interpreting the Gaussian curve, fitted by nonlinear regression (NLR), as a standard normal distribution, the peak location equals the mean (mu) and the window width equals 2x the standard deviation (2 sigma). The NLR procedure can provide an objective measure for both peak location and width for a wide range of data sets. Four empirical data sets as well as 10 literature data sets were analyzed. The double-spined spruce engraver, fps duplicatus, was field tested in four populations to find the optimum proportion for attraction to the two male aggregation pheromone components. ipsdienol (Id) and (E)-myrcenol (EM), ranging from 0 to 100% of Id. Tests in Norway and the Czech Republic confirmed the preference of western populations for a blend between 50 and 90% Id. A population in Inner Mongolia showed a preference for traps with the 10 and 50% Id baits. The NLR fitted values for response peak and width (mu; 2 sigma) were: Norway 0.64,0.73 Czech Republic 0.53, 0.73; NE China 0.77,0.29; and Inner Mongolia 0.33, 0.50. The signal produced by Norwegian field-collected males had a narrower window width (2 sigma = 0.12). Males of the maize stem borer, Chilo partellus, were tested in a flight tunnel for their response to variation in the two major female sex pheromone gland components, (Z)-11-hexadecenal and the corresponding alcohol (OH). Variation of the alcohol in seven levels from 2 to 29% OH showed the highest male response for 17% OH. For all behavioral steps, the peak of male response was near mu = 0.14, while the window width fell from 2 sigma = 0.5 to 0.2 for eight sequential behavioral steps from take-off to copulation. Female production had a similar peak location (mu = 0.13) but a narrower width, 2 sigma = 0.14. Literature data from other moth species showed similar patterns, with a wider male response relative to the female production windows. Literature data on response to enantiomer ratios in a hymenopteran and to pheromone amounts in a dipteran were also described by our model. In a bark beetle population (Ips pini), with two hybridizing enantiomeric strains, the production peaks were narrower (0.1) than the response peaks (0.5). Thus, it in general, seems that in the pheromone systems analyzed. the width of the response window (2 sigma = 0.1 to 0.9) is larger than that of the production window (2 sigma = 0.03 to 0.14), irrespective of the sex of the sender.
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| 5. |
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| 6. |
- Agrell, J., et al.
(författare)
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Production of hydrogen from methanol over Cu/ZnO catalysts promoted by ZrO2 and Al2O3
- 2003
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Ingår i: Journal of Catalysis. - : Elsevier BV. - 0021-9517 .- 1090-2694. ; 219:2, s. 389-403
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Tidskriftsartikel (refereegranskat)abstract
- Production of H-2 from methanol by steam reforming, partial oxidation, or a combination thereof was studied over Cu/ZnO-based catalysts. The catalysts were characterized by a variety of techniques, including N2O chemisorption, X-ray photoelectron spectroscopy, X-ray diffraction, and temperature-programmed reduction/oxidation. The influence of feed composition, reaction temperature, and catalyst formulation on H-2 production rate, product distribution, and catalyst lifetime was investigated. Distinct differences between the processes were observed with respect to catalyst behavior. ZrO2-containing catalysts, especially Cu/ZnO/ZrO2/Al2O3, exhibit the best performance in the steam reforming reaction. During partial oxidation, however, a binary Cu/ZnO catalyst exhibits the lowest light-off temperature and the lowest level of CO by-product. The redox properties of the catalyst appear to play a key role in determining the pathway for H-2 production. In particular. the extent of methanol and/or H-2 combustion at differential O-2 conversion is strongly dependent on the ease of copper oxidation in the catalyst.
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| 7. |
- Anderbrant, Olle, et al.
(författare)
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Pheromone of the elm bark beetle Scolytus laevis (Coleoptera Scolytidae) : stereoisomers of 4-methyl-3-heptanol reduce interspecific competition
- 2010
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Ingår i: Chemoecology. - : Springer Science and Business Media LLC. - 0937-7409 .- 1423-0445. ; 20:3, s. 179-187
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Tidskriftsartikel (refereegranskat)abstract
- Stereoisomers of 4-methyl-3-heptanol (MH) are pheromone components of several Scolytus bark beetles. The elm bark beetle Scolytus laevis (Coleoptera: Scolytidae) has in previous studies been caught in traps baited with commercial MH containing all four stereoisomers, but the lure has been considered a weak attractant. In this study, we addressed the question whether stereospecific responses by S. laevis to stereoisomers of MH might contribute to its niche separation from other sympatric Scolytus species. Using GC-MS, we analyzed extracts of hindguts and abdomens from male and female S. laevis and the sympatric S. triarmatus. We also tested all four MH-stereoisomers individually and in combinations in the field to determine their role for S. laevis. All four stereoisomers were synthesized via a boronic ester method with 1,2-dicyclohexylethanediol as chiral director. In addition, the (3S,4R)-stereoisomer of MH was prepared through enantioselective, lipase-mediated transesterification of a mixture of the four stereoisomers of MH. Females of both species contained small amounts of syn-MH, and males contained trace amounts of anti-MH. The anti stereoisomer (3R,4S)-MH was attractive to male and female S. laevis, whereas the syn stereoisomer (3S,4S)-MH acted as an inhibitor or deterrent and reduced the catch when added to the attractive isomer. The syn isomer is the main aggregation pheromone component of the larger and sympatric S. scolytus and possibly also of S. triarmatus. The avoidance response of S. laevis to the (3S,4S)-stereoisomer may reduce interspecific competition for host trees.
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| 8. |
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| 9. |
- Ayoglu, Burcu, et al.
(författare)
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Multiplexed protein profiling by sequential affinity capture
- 2016
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Ingår i: Proteomics. - : Wiley-Blackwell. - 1615-9853 .- 1615-9861. ; 16:8, s. 1251-1256
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Tidskriftsartikel (refereegranskat)abstract
- Antibody microarrays enable parallelized and miniaturized analysis of clinical samples, and have proven to provide novel insights for the analysis of different proteomes. However, there are concerns that the performance of such direct labeling and single antibody assays are prone to off-target binding due to the sample context. To improve selectivity and sensitivity while maintaining the possibility to conduct multiplexed protein profiling, we developed a multiplexed and semi-automated sequential capture assay. This novel bead-based procedure encompasses a first antigen capture, labeling of captured protein targets on magnetic particles, combinatorial target elution and a read-out by a secondary capture bead array. We demonstrate in a proof-of-concept setting that target detection via two sequential affinity interactions reduced off-target contribution, while lowered background and noise levels, improved correlation to clinical values compared to single binder assays. We also compared sensitivity levels with single binder and classical sandwich assays, explored the possibility for DNA-based signal amplification, and demonstrate the applicability of the dual capture bead-based antibody microarray for biomarker analysis. Hence, the described concept enhances the possibilities for antibody array assays to be utilized for protein profiling in body fluids and beyond.
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| 10. |
- Birgersson, Erik, et al.
(författare)
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Analysis of a two-phase non-isothermal model for a PEFC
- 2005
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Ingår i: Journal of the Electrochemical Society. - : The Electrochemical Society. - 0013-4651 .- 1945-7111. ; 152:5, s. A1021-A1034
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Tidskriftsartikel (refereegranskat)abstract
- A non-isothermal, two-phase model for a polymer electrolyte fuel cell (PEFC) is presented, analyzed, and solved numerically under three different thermal, and two hydrodynamic, modeling assumptions; the consequences of these are then discussed in terms of thermal and water management and cell performance. The study is motivated by recent experimental results that suggest the presence of previously unreported, and thus unmodeled, thermal contact resistances between the components of PEFCs and the discrepancy in the value for the capillary pressure that is used by different authors when modeling the two-phase flow in PEFCs. For the three different thermal assumptions (assuming effective heat conductivities, isothermal flow, and interfacial and bulk conductivites), liquid saturations of around 10% are obtained at the cathode active layer for 1000 mA cm(-2) and a cell voltage of 0.6 V. When lowering the capillary pressure (hydrodynamic assumption), liquid saturations of almost 30% and locally up to 100% are observed at the active layer of the cathode. At this current density and voltage, temperature differences across the cell of around 9 degrees C are predicted. In addition, the effect of varying clamping pressure within the framework of the model is touched upon. The benefits of the scaling analysis conducted here, to predict correctly, prior to numerical computations, important characteristic cell performance quantities such as current density and temperature drop are also highlighted.
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