| 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. |
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| 3. |
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| 4. |
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| 5. |
- Tovesson, Fredrik, et al.
(författare)
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233Pa(n, f) cross section up to En=8.5 MeV
- 2004
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Ingår i: Nuclear Physics A. - : Elsevier BV. - 0375-9474 .- 1873-1554. ; 733:1-2, s. 3-19
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Tidskriftsartikel (refereegranskat)abstract
- The energy dependence of the neutron-induced fission cross section of 233Pa has been measured directly for the first time from the fission threshold up to En=8.5 MeV. This reaction plays an important role in the thorium-uranium fuel cycle, and is thus of interest for the design and modeling of advanced reactor and transmutation facilities. The existing information in the ENDF/B-VI and JENDL-3.3 evaluated nuclear data files differ by a factor of two for the 233Pa(n, f) cross section values and show different fission threshold energies. Our new experimental data give lower cross section values than both evaluations and resolves the question about the threshold energy. In addition to the experimental investigation, also a new theoretical calculation of the reaction cross section has been performed with the statistical model code STATIS, showing a good agreement with the experimental data.
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| 6. |
- Birgersson, E., et al.
(författare)
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Reduced two-dimensional one-phase model for analysis of the anode of a DMFC
- 2003
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Ingår i: Journal of the Electrochemical Society. - : The Electrochemical Society. - 0013-4651 .- 1945-7111. ; 150:10, s. A1368-A1376
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Tidskriftsartikel (refereegranskat)abstract
- An isothermal two-dimensional liquid phase model for the conservation of mass, momentum, and species in the anode of a direct methanol fuel cell (DMFC) is presented and analyzed. The inherent electrochemistry in the DMFC anode active layer is reduced to boundary conditions via parameter adaption. The model is developed for the case when the geometry aspect ratio is small, and it is shown that, under realistic operating conditions, a reduced model, which nonetheless describes all the essential physics of the full model, can be derived. The significant benefits of this approach are that physical trends become much more apparent than in the full model and that there is considerable reduction in the time required to compute numerical solutions, a fact especially useful for wide-ranging parameter studies. Such a study is then performed in terms of the three nondimensional parameters that emerge from the analysis, and we subsequently interpret our results in terms of the dimensional design and operating parameters. In particular, we highlight their effect on methanol mass transfer in the flow channel and on the current density. The results indicate the relative importance of mass-transfer resistance in both the flow channel and the adjacent porous backing.
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| 7. |
- Birgersson, K. E., et al.
(författare)
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Energy Solutions for a Sustainable World
- 2012
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Ingår i: Applied Energy. - : Elsevier BV. - 0306-2619 .- 1872-9118. ; 90:1, s. 1-2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 8. |
- Borg, K. I., et al.
(författare)
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Effects of non-linear kinetics on free convection in an electrochemical cell with a porous separator
- 2007
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Ingår i: Journal of Applied Electrochemistry. - : Springer Science and Business Media LLC. - 0021-891X .- 1572-8838. ; 37:11, s. 1287-1302
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Tidskriftsartikel (refereegranskat)abstract
- The spatial evolution of the ionic concentration of an electrolyte in an isothermal electrochemical cell with a porous separator between the electrodes was investigated for large values of Rayleigh number. The reaction kinetics were described by the Butler-Volmer equation. The full problem, involving the coupled partial differential equations describing the velocity field, the ionic concentration, and the electric potential, was reduced by means of regular and singular perturbation theory, to a simplified evolution equation, coupled with a transcendental function for the ionic concentration and electric potential; the solution was found to agree well with the numerical solution of the full problem. In the limit of large and small cell voltages, closed analytical solutions were secured for the concentration, potential, and overall current density.
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| 9. |
- Ek, Helene, 1976, et al.
(författare)
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Fate and effects of 2,4,6-trinitrotoluene (TNT) from dumped ammunition in a field study with fish and invertebrates
- 2006
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Ingår i: Archives of Environmental Contamination and Toxicology. - : Springer Science and Business Media LLC. - 0090-4341 .- 1432-0703. ; 51:2, s. 244-252
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- 2,4,6-Trinitrotoluene (TNT) is the major explosive ingredient in ammunition dumped into lakes and sea after World War II. The aim of the present field study was to study the fate and effect of TNT and its degradation products from dumped ammunition. Artillery shells were cleaved longitudinally to expose TNT and placed in open boxes filled with sediment, and then placed at the sea bottom. Sediment samples were taken in each box at the start and after 3, 9, 13, 20, 24, 33, and 36 months, and the sediments were tested for toxicity with bioassays using Nitocra spinipes (96 h), Hyalella azteca (96 h), and Daphnia magna (24 and 48 h). The result from the bioassays showed no impact of dumped ammunition on the survival of H. azteca and mobility of D. magna. Bioassays with N. spinipes showed significant differences in toxicity between control boxes and boxes with shells after 9 months and thereafter. The mean mortality (+/- SD) of N. spinipes in boxes with shells was 63 +/- 22%, and the mortality in control boxes was 23 +/- 17%. No continuous increase in sediment toxicity over time was found. After 3 years, cages with European flounder (Platichtys flesus) and blue mussels (Mytilus edulis) were attached to the boxes. The fish were examined for biochemical and physiological effects 8 weeks later. Exposure to ammunition, which had rested on the sea bottom 3 years, caused no significant effects on body indices, hematological variables, and detoxification and antioxidant enzymes activities in the flounder. The sediment, bile, and blood plasma of exposed fish, and hepatopancreas of exposed mussels, contained no detectable levels of TNT and its metabolites. Only minor disappearance of TNT from the shells could be detected by visual inspection on site (by scuba divers). This study suggests that the survival of sensitive benthic organisms, e.g., N. spinipes, might be negatively affected at an ammunition dumping site.
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| 10. |
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| 11. |
- 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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| 12. |
- Luna, Fabio, et al.
(författare)
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Diffusion equation applied to isothermal drying of a multicomponent liquid film
- 2005
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Ingår i: Drying Technology. - : Informa UK Limited. - 0737-3937 .- 1532-2300. ; 23:11-sep, s. 1953-1975
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Tidskriftsartikel (refereegranskat)abstract
- Liquid-side-controlled drying by convection of a multicomponent liquid film is studied. Interactive diffusion in liquid phase is considered the main mechanism for mass transfer. Assuming an isothermal drying process and a constant matrix of multicomponent diffusion coefficients, an analytical solution of the diffusion equation is developed. The equations are decoupled by a similarity transformation and solved by the method of variable separation. The solution is applied to the drying of ternary mixtures, one of them containing a component of negligible volatility. The variation of diffusion coefficients along the process trajectory was taken into account by a piecewise application of the solution in time intervals with averaged coefficients from previous time steps. Despite the simplifications made, the analytical solution gives a god insight into the selectivity of the drying process and is computationally fast. The limitations of the analytical solution and the prospect of applying the solution to the description of a nonisothermal process are discussed. It would introduce an important computational economy since the rigorous treatment of multicomponent drying leads to partial differential equations with variable coefficients, which can only be solved by time-consuming iterative procedures.
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| 13. |
- Schiebe, Christian, et al.
(författare)
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Inducibility of chemical defenses in Norway spruce bark is correlated with unsuccessful mass attacks by the spruce bark beetle
- 2012
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Ingår i: Oecologia. - : Springer Science and Business Media LLC. - 0029-8549 .- 1432-1939. ; 170:1, s. 183-198
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Tidskriftsartikel (refereegranskat)abstract
- Secondary attraction to aggregation pheromones plays a central role in the host colonization behavior of the European spruce bark beetle Ips typographus. However, it is largely unknown how the beetles pioneering an attack locate suitable host trees, and eventually accept or reject them. To find possible biomarkers for host choice by I. typographus, we analyzed the chemistry of 58 Norway spruce (Picea abies) trees that were subsequently either (1) successfully attacked and killed, (2) unsuccessfully attacked, or (3) left unattacked. The trees were sampled before the main beetle flight in a natural Norway spruce-dominated forest. No pheromones were used to attract beetles to the experimental trees. To test the trees' defense potential, each tree was treated in a local area with the defense hormone methyl jasmonate (MeJ), and treated and untreated bark were analyzed for 66 different compounds, including terpenes, phenolics and alkaloids. The chemistry of MeJ-treated bark correlated strongly with the success of I. typographus attack, revealing major chemical differences between killed trees and unsuccessfully attacked trees. Surviving trees produced significantly higher amounts of most of the 39 analyzed mono-, sesqui-, and diterpenes and of 4 of 20 phenolics. Alkaloids showed no clear pattern. Differences in untreated bark were less pronounced, where only 1,8-cineole and (-)-limonene were significantly higher in unsuccessfully attacked trees. Our results show that the potential of individual P. abies trees for inducing defense compounds upon I. typographus attack may partly determine tree resistance to this bark beetle by inhibiting its mass attack.
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| 14. |
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| 15. |
- Sharma, A. K., et al.
(författare)
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The quasi-steady state of all-vanadium redox flow batteries : A scale analysis
- 2014
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Ingår i: Electrochimica Acta. - : Elsevier BV. - 0013-4686 .- 1873-3859. ; 147, s. 657-662
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Tidskriftsartikel (refereegranskat)abstract
- In general, mathematical models for all-vanadium redox flow batteries(VRFB) that seek to capture the transport phenomena are transient in nature. In this paper, we carry out scale analysis of VRFB operation and derive the conditions when it can be assumed to be quasi-steady state in nature, i.e., time-dependence only through a boundary condition. We find that it is true for typical tank volume and flow rate employed for VRFBs. The proposed analysisis generic and can also be employed for other types of redox flow batteries. (C) 2014 Elsevier Ltd. All rights reserved.
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| 16. |
- Sharma, A. K., et al.
(författare)
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Verified reduction of dimensionality for an all-vanadium redox flow battery model
- 2015
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Ingår i: Journal of Power Sources. - : Elsevier BV. - 0378-7753 .- 1873-2755. ; 279, s. 345-350
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Tidskriftsartikel (refereegranskat)abstract
- The computational cost for all-vanadium redox flow batteries (VRFB) models that seek to capture the transport phenomena usually increases with the number of spatial dimensions considered. In this context, we carry out scale analysis to derive a reduced zero-dimensional model. Two nondimensional numbers and their limits to support the model reduction are identified. We verify the reduced model by comparing its charge discharge curve predictions with that of a full two-dimensional model. The proposed analysis leading to reduction in dimensionality is generic and can be employed for other types of redox flow batteries.
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| 17. |
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| 18. |
- Sundell, Jesper, et al.
(författare)
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Effects of Enzyme Induction and Polymorphism on the Pharmacokinetics of Isoniazid and Rifampin in Tuberculosis/HIV Patients
- 2022
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 66:10
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Tidskriftsartikel (refereegranskat)abstract
- Tuberculosis is the most common cause of death in HIV-infected individuals. Rifampin and isoniazid are the backbones of the current first-line antitubercular therapy. The aim of the present study was to describe the time-dependent pharmacokinetics and pharmacogenetics of rifampin and isoniazid and to quantitatively evaluate the drug-drug interaction between rifampin and isoniazid in patients coinfected with HIV. Plasma concentrations of isoniazid, acetyl-isoniazid, isonicotinic acid, rifampin, and 25-desacetylrifampin from 40 HIV therapy-naive patients were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after the first dose and at steady state of antitubercular therapy. Patients were genotyped for determination of acetylator status and CYP2C19 phenotype. Nonlinear mixed-effects models were developed to describe the pharmacokinetic data. The model estimated an autoinduction of both rifampin bioavailability (0.5-fold) and clearance (2.3-fold). 25-Desacetylrifampin clearance was 2.1-fold higher at steady state than after the first dose. Additionally, ultrarapid CYP2C19 metabolizers had a 2-fold-higher rifampin clearance at steady state than intermediate or extensive metabolizers. An induction of isonicotinic acid formation from isoniazid dependent on total rifampin dose was estimated. Simulations indicated a 30% lower isoniazid exposure at steady state during administration of standard rifampin doses than isoniazid exposure in noninduced individuals. Rifampin exposure was correlated with CYP2C19 polymorphism, and rifampin administration may increase exposure to toxic metabolites by isoniazid in patients. Both findings may influence the risk of treatment failure, resistance development, and toxicity and require further investigation, especially with regard to ongoing high-dose rifampin trials.
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| 19. |
- Sundell, Jesper, et al.
(författare)
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Model-Based Assessment of Variability in Isoniazid Pharmacokinetics and Metabolism in Patients Co-Infected With Tuberculosis and HIV: Implications for a Novel Dosing Strategy
- 2020
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Ingår i: Clinical Pharmacology & Therapeutics. - : Wiley. - 0009-9236 .- 1532-6535. ; 108:1, s. 73-80
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Tidskriftsartikel (refereegranskat)abstract
- Tuberculosis is the most common cause of death in HIV-infected patients. Isoniazid is used as a first-line drug to treat tuberculosis infection. However, variability in isoniazid pharmacokinetics can result in hepatotoxicity or treatment failure. Determination of clinical factors affecting isoniazid pharmacokinetics and metabolic pathways in HIV co-infected patients is therefore critical. Plasma levels of isoniazid, acetyl-isoniazid, and isonicotinic acid from 63 patients co-infected with tuberculosis and HIV were analyzed by liquid chromatography with tandem mass spectrometry followed by nonlinear mixed-effects modeling. Patients were genotyped to determine acetylator status. Patients were either on concomitant efavirenz-based antiretroviral therapy or HIV treatment naive. Clearances of isoniazid were 1.3-fold and 2.3-fold higher in intermediate and rapid acetylators, respectively, compared with slow acetylators. Patients on concomitant efavirenz-based antiretroviral therapy had 64% and 80% higher population predicted clearances of acetyl-isoniazid and isonicotinic acid, respectively, compared with patients who were HIV treatment naive. Both sex and CD4 cell count affected the bioavailability of isoniazid. Variability in isoniazid exposure could be reduced by dose adaptions based on acetylator type and sex in addition to the currently used weight bands. A novel dosing strategy that has the potential to reduce isoniazid-related toxicity and treatment failure is presented.
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| 20. |
- Sundell, Jesper, et al.
(författare)
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Population Pharmacokinetics and Pharmacogenetics of Ethambutol in Adult Patients Coinfected with Tuberculosis and HIV
- 2020
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 64:2
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to characterize the population pharmacokinetics and pharmacogenetics of ethambutol in tuberculosis-HIV-coinfected adult patients. Ethambutol plasma concentrations, determined by liquid chromatography-tandem mass spectrometry, in 63 patients receiving ethambutol as part of rifampin-based fixed-dose combination therapy for tuberculosis were analyzed using nonlinear mixed-effects modeling. A one-compartment disposition model with first-order elimination and four transit compartments prior to first-order absorption was found to adequately describe the concentration-time profiles of ethambutol in plasma. Body weight was implemented as an allometric function on the clearance and volume parameters. Estimates of oral clearance and volume of distribution were 77.4 liters/h and 76.2 liters, respectively. A G/A mutation with regard to CYP1A2 2159 G>A was associated with a 50% reduction in relative bioavailability. Simulations revealed that doses of 30 mg/kg of body weight and 50 mg/kg for G/G and G/A carriers, respectively, would result in clinically adequate exposure. The results presented here suggest that CYP1A2 polymorphism affects ethambutol exposure in this population and that current treatment guidelines may result in underexposure in patients coinfected with tuberculosis and HIV. Based on simulations, a dose increase from 15 to 20 mg/kg to 30 mg/kg is suggested. However, the 50-mg/kg dose required to reach therapeutic exposure in G/A carriers may be inappropriate due to the dose-dependent toxicity of ethambutol. Additional studies are required to further investigate CYP450 polymorphism effects on ethambutol pharmacokinetics.
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| 21. |
- Sundell, Jesper, et al.
(författare)
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Simultaneous quantification of four first line antitubercular drugs and metabolites in human plasma by hydrophilic interaction chromatography and tandem mass spectrometry
- 2019
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Ingår i: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences. - : Elsevier BV. - 1570-0232. ; 1105, s. 129-135
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Tidskriftsartikel (refereegranskat)abstract
- Co-infection of tuberculosis in HIV-patients is a major health concern worldwide and especially so in Sub-Saharan Africa. To enhance the study of potential drug-drug interactions when simultaneously treating the two infections, a liquid chromatography tandem mass spectrometry method was developed for the quantitation of the four first line anti-tuberculosis drugs isoniazid, rifampicin, pyrazinamide, ethambutol and four of their major metabolites in human plasma. Analytes were extracted from 200 μL of plasma using a sequential liquid-liquid extraction with ethyl acetate at neutral and acidic pH. The combined extracts were analyzed by liquid chromatography with mass spectrometric detection in a multiple reaction monitoring mode. The chromatographic separation was performed on a hydrophilic interaction column using a stepwise gradient with two mobile phases consisting of water with 0.3% formic acid and methanol with 0.3% formic acid, respectively. The total run time of each analysis was 4 min. The lower limit of quantification applied was 40 ng/mL for ethambutol, acetylisoniazid and 25-desacetylrifampicin, 60 ng/mL for 5-hydroxypyrazinamide, 80 ng/mL for isoniazid and isonicotinic acid, 200 ng/mL for rifampicin and 320 ng/mL for pyrazinamide. The method was validated according to US Food and Drug Administration guidance. The method exhibited adequate accuracy (87.1–114.9%), precision (CV < 12.8%) and specificity. Recovery and matrix effect were consistent (CV < 11.9%). The extracted samples were stable in the autosampler at 8 °C for up to 24 h as well as after three freeze-thaw cycles (recovery > 86.3%). The method has been shown to be robust for the analysis of the stated drugs and metabolites in human plasma obtained from 73 patients receiving these four first line anti-tuberculosis drugs. © 2018 Elsevier B.V.
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| 22. |
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| 23. |
- Zhang, Qing H.E., et al.
(författare)
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Leaf volatiles from nonhost deciduous trees : Variation by tree species, season and temperature, and electrophysiological activity in Ips typographus
- 1999
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Ingår i: Journal of Chemical Ecology. - 0098-0331. ; 25:8, s. 1923-1943
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Tidskriftsartikel (refereegranskat)abstract
- The leaf volatiles emitted from four nonhost tree species of lps typographus, i.e. Betula pendula, B. pubescens, Populus tremula, and Sambucus nigra, were collected outdoors by headspace sampling in situ and analyzed by GC-MS. Three major classes of compounds, aliphatics [mainly green-leaf volatiles (GLVs)], monoterpenes, and sesquiterpenes, existed in all the deciduous tree species investigated. In June, when the bark beetles are searching in flight for host trees, GLVs mainly consisting of (Z)-3-hexenyl acetate and (Z)-3-hexen-1-ol were the dominant constituents in B. pendula and S. nigra. In B. pubescens and P. tremula, sesquiterpenes (and their derivatives) and monoterpenes made up the major part of whole volatile blends, respectively. Surprisingly, sesquiterpene alcohols and other oxides released from B. pubescens in considerable amounts were not found in the closely related species, B. pendula. By August, both the total volatiles and individual compounds significantly decreased, mainly due to the maturation of leaves, since the light intensity and temperatures during sampling were the same as in June. There were almost no volatiles detected from P. tremula and S. nigra leaves in August. The total emissions from these deciduous species were significantly different among the species, with B. pubescens releasing 5-10 times more than other species. Under the conditions of constant light intensity and humidity, emissions of both total volatiles and most individual components of severed B. pendula and S. nigra branches (with fresh leaves) increased according to a saturation curve from 16°C to 40°C. Ips typographus antennae responded strongly to green leaf alcohols: (Z)-3-hexen- 1-ol, 1-hexanol, and (E)-2-hexen-1-ol, but not to aldehydes or acetates in GC-EAD analyses of B. pendula and B. pubescens leaf volatiles. No antennal responses to monoterpenes, sesquiterpenes, or sesquiterpene oxides were found. These three antennally active GLVs emitted from nonhost tree leaves might be indicators of a wrong habitat in the host selection of conifer bark beetles.
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