| 1. |
- Dracheva, Elena, et al.
(författare)
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In Silico Identification of Potential Thyroid Hormone System Disruptors among Chemicals in Human Serum and Chemicals with a High Exposure Index
- 2022
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 56:12, s. 8363-8372
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Tidskriftsartikel (refereegranskat)abstract
- Data on toxic effects are at large missing the prevailing understanding of the risks of industrial chemicals. Thyroid hormone (TH) system disruption includes interferences of the life cycle of the thyroid hormones and may occur in various organs. In the current study, high-throughput screening data available for 14 putative molecular initiating events of adverse outcome pathways, related to disruption of the TH system, were used to develop 19 in silico models for identification of potential thyroid hormone system-disrupting chemicals. The conformal prediction framework with the underlying Random Forest was used as a wrapper for the models allowing for setting the desired confidence level and controlling the error rate of predictions. The trained models were then applied to two different databases: (i) an in-house database comprising xenobiotics identified in human blood and ii) currently used chemicals registered in the Swedish Product Register, which have been predicted to have a high exposure index to consumers. The application of these models showed that among currently used chemicals, fewer were overall predicted as active compared to chemicals identified in human blood. Chemicals of specific concern for TH disruption were identified from both databases based on their predicted activity.
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| 2. |
- Rodriguez, Alvaro, et al.
(författare)
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ToxTrac : a fast and robust software for tracking organisms
- 2018
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Ingår i: Methods in Ecology and Evolution. - : British Ecological Society. - 2041-210X. ; 9:3, s. 460-464
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Tidskriftsartikel (refereegranskat)abstract
- 1. Behavioral analysis based on video recording is becoming increasingly popular within research fields such as; ecology, medicine, ecotoxicology, and toxicology. However, the programs available to analyze the data, which are; free of cost, user-friendly, versatile, robust, fast and provide reliable statistics for different organisms (invertebrates, vertebrates and mammals) are significantly limited.2. We present an automated open-source executable software (ToxTrac) for image-based tracking that can simultaneously handle several organisms monitored in a laboratory environment. We compare the performance of ToxTrac with current accessible programs on the web.3. The main advantages of ToxTrac are: i) no specific knowledge of the geometry of the tracked bodies is needed; ii) processing speed, ToxTrac can operate at a rate >25 frames per second in HD videos using modern computers; iii) simultaneous tracking of multiple organisms in multiple arenas; iv) integrated distortion correction and camera calibration; v) robust against false positives; vi) preservation of individual identification; vii) useful statistics and heat maps in real scale are exported in image, text and excel formats.4. ToxTrac can be used for high speed tracking of insects, fish, rodents or other species, and provides useful locomotor information in animal behavior experiments. Download ToxTrac here: https://toxtrac.sourceforge.io (Current version v2.61).
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| 3. |
- Larsson, Malin, et al.
(författare)
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Identification of potential aryl hydrocarbon receptor ligands by virtual screening of industrial chemicals
- 2018
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Ingår i: Environmental Science and Pollution Research. - : Springer. - 0944-1344 .- 1614-7499. ; 25:3, s. 2436-2449
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Tidskriftsartikel (refereegranskat)abstract
- We have developed a virtual screening procedure to identify potential ligands to the aryl hydrocarbon receptor (AhR) among a set of industrial chemicals. AhR is a key target for dioxin-like compounds, which is related to these compounds’ potential to induce cancer and a wide range of endocrine and immune system related effects. The virtual screening procedure included an initial filtration aiming at identifying chemicals with structural similarities to 66 known AhR binders, followed by three enrichment methods run in parallel. These include two ligand-based methods (structural fingerprints and nearest neighbor analysis) and one structure-based method using an AhR homology model. A set of 6,445 commonly used industrial chemicals was processed, and each step identified unique potential ligands. Seven compounds were identified by all three enrichment methods, and these compounds included known activators and suppressors of AhR. Only approximately 0.7% (41 compounds) of the studied industrial compounds was identified as potential AhR ligands and among these, 28 compounds have to our knowledge not been tested for AhR-mediated effects or have been screened with low purity. We suggest assessment of AhR-related activities of these compounds and in particular 2-chlorotrityl chloride, 3-p-hydroxyanilino-carbazole, and 3-(2-chloro-4-nitrophenyl)-5-(1,1-dimethylethyl)-1,3,4-oxadiazol-2(3H)-one.
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| 4. |
- Rodriguez, Alvaro, et al.
(författare)
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Refining particle positions using circular symmetry
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Particle and object tracking is gaining attention in industrial applications and is commonly applied in: colloidal, biophysical, ecological, and micro-fluidic research. Reliable tracking information is heavily dependent on the system under study and algorithms that correctly determine particle position between images. However, in a real environmental context with the presence of noise including particular or dissolved matter in water, and low and fluctuating light conditions, many algorithms fail to obtain reliable information. We propose a new algorithm, the Circular Symmetry algorithm (C-Sym), for detecting the position of a circular particle with high accuracy and precision in noisy conditions. The algorithm takes advantage of the spatial symmetry of the particle allowing for subpixel accuracy. We compare the proposed algorithm with four different methods using both synthetic and experimental datasets. The results show that C-Sym is the most accurate and precise algorithm when tracking micro-particles in all tested conditions and it has the potential for use in applications including tracking biota in their environment.
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| 5. |
- Tang, Zheng, et al.
(författare)
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Interlayer for Modified Cathode in Highly Efficient Inverted ITO-Free Organic Solar Cells
- 2012
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Ingår i: Advanced Materials. - : Wiley. - 0935-9648 .- 1521-4095. ; 24:4, s. 554-
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Tidskriftsartikel (refereegranskat)abstract
- Inverted polymer solar cells with a bottom metal cathode modified by a conjugated polymer interlayer show considerable improvement of photocurrent and fill factor, which is due to hole blocking at the interlayer, and a modified surface energy which affects the nanostructure in the TQ1/[70]PCBM blend.
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| 6. |
- Andersson, Patrik, 1981-
(författare)
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Four applications of stochastic processes : Contagious disease, credit risk, gambling and bond portfolios
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis consists of four papers on applications of stochastic processes. In Paper I we study an open population SIS (Susceptible - Infective - Susceptible) stochastic epidemic model from the time of introduction of the disease, through a possible outbreak and to extinction. The analysis uses coupling arguments and diffusion approximations. In Paper II we propose a model describing an economy where companies may default due to contagion. The features of the model are analyzed using diffusion approximations. We show that the model can reproduce oscillations in the default rates similar to what has been observed empirically. In Paper III we consider the problem of finding an optimal betting strategy for a house-banked casino card game that is played for several coups before reshuffling. A limit result for the return process is found and the optimal card counting strategy is derived. This continuous time strategy is shown to be a natural generalization of the discrete time strategy where the so called effects of removals are replaced by the infinitesimal generator of the card process. In Paper IV we study interest rate models where the term structure is given by an affine relation and in particular where the driving stochastic processes are so-called generalised Ornstein-Uhlenbeck processes. We show that the return and variance of a portfolio of bonds which are continuously rolled over, also called rolling horizon bonds, can be expressed using the cumulant generating functions of the background driving Lévy processes associated with the OU processes. We also show that if the short rate, in a risk-neutral setting, is given by a linear combination of generalised OU processes, the implied term structure can be expressed in terms of the cumulant generating functions.
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| 7. |
- Bergknut, Magnus, et al.
(författare)
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Identification of potentially toxic compounds in complex extracts of environmental samples using gas chromatography-mass spectrometry and multivariate data analysis
- 2007
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Ingår i: Environmental Toxicology and Chemistry. - New York : Pergamon. - 0730-7268 .- 1552-8618. ; 26:2, s. 208-217
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we examined 31 samples of varying chemical composition, including samples of soils from gasworks, coke production sites, and sites where wood preservatives were heavily used; ash and soot from municipal solid waste incinerators; antiskid sand; and dust from areas with heavy road traffic. The samples were comprehensively chemically characterized, especially their polycyclic aromatic compound contents, using gas chromatography-time-of-flight mass spectrometry, whereas their biological effects were assessed using dehydrogenase activity, root growth (Hordeum vulgare), reproduction of springtails (Folsomia candida), algal growth (Desmodesmus subspicatus), germinability (Sinapis alba), Vibrio fischeri, DR-CALUX, and Ames Salmonella assays. The number of compounds detected in the samples ranged from 123 to 527. Using the multivariate regression technique of partial-least-squares projections to latent structures, it was possible to find individual compounds that exhibited strong correlations with the different biological responses. Some of the results, however, indicate that a broader chemical characterization may be needed to identify all the compounds that may cause the measured biological responses.
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| 8. |
- Golosovskaia, Elena, 1993-
(författare)
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Development of in silico methods to aid chemical risk assessment : focusing on kinetic interactions in mixtures
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The environment and biota are constantly exposed to numerous chemicals through contaminated food, soil, water, and air. These chemicals can be taken up and distributed to reach sensitive tissues where they may cause various effects. Many of these chemicals lack data on their environmental and human health effects. Traditional toxicological tests relying on animal experiments are today being phased out in favor of cell-based and computational methods for early hazard detection and exposure assessment. This thesis focuses on developing computational tools for various stages of chemical risk assessment with a particular focus on bisphenols and per- and polyfluoroalkyl substances (PFAS). In Paper I, quantitative structure-activity relationship (QSAR) models covering molecular targets of the thyroid hormone (TH) system were developed and applied to two data sets to prioritize chemicals of concern for detailed toxicological studies. In Papers II and III, experimental and computational approaches were combined to study toxicokinetics and maternal transfer in zebrafish. Our main focus was to study potential mixture effects on administration, distribution, metabolism, and elimination (ADME) processes, i.e., to reveal if co-exposed chemicals impact each other’s ADME. Physiologically based kinetic (PBK) mixture models were developed to allow translation of external exposure concentrations into tissue concentrations and modelling plausible mechanisms of chemical interactions in a mixture.Main findings of this thesis are summarized as follows:• Application of QSAR models (Paper I) to two chemical inventories revealed that chemicals found in human blood could induce a large iirange of pathways in the TH system whereas chemicals used in Sweden with predicted high exposure index to consumers showed a lower likelihood to induce TH pathways.• Two zebrafish experiments (Paper II and Paper III) did not reveal statistically significant mixture effects on ADME of chemicals.• In Paper II, a PBK mixture model for PFAS accounting for competitive plasma protein binding was developed. The model demonstrated good predictive performance. Competitive plasma protein binding did not affect the predicted internal concentrations.• In Paper III we developed a binary PBK model parametrized for two bisphenols and PFOS showing that competitive plasma protein binding has an effect on ADME of bisphenols at PFOS concentrations at μg/L levels. At these levels internal concentrations of bisphenols were shown to decrease, implying that PFOS outcompeted bisphenols from studied plasma proteins resulting in higher excretion rates.Developed QSAR models showed good predictive power and the ability to identify and prioritize chemicals of concern with confidence. Additionally, PBK models aid in hypotheses testing and predicting exposure concentrations at which co-exposed chemicals could potentially influence each other’s ADME properties. These tools will provide overall early tier data on exposure and effects using non-testing methods in assessment of risks of chemicals.
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| 9. |
- Hedberg, P. A. Mikael, et al.
(författare)
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Measurements and Simulations of the Flow Distribution in a Down-Scaled Multiple Outlet Spillway with Complex Channel
- 2024
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Ingår i: Water. - : Multidisciplinary Digital Publishing Institute (MDPI). - 2073-4441. ; 16:6
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of mass flow through a three-outlet spillway modeled after a scaled-down spillway were conducted. The inlet and channel leading up to the outlets were placed to lead the water toward the outlet at an angle. With this, measurements of the water level at three locations were recorded by magnetostrictive sensors. The volumetric flow rates for each individual outlet were recorded separately to study the differences between them. Additionally, Acoustic Doppler Velocimetry was used to measure water velocities close to the outlets. The conditions changed were the inlet volume flow rate and the flow distribution was measured at 90, 100, 110, and 200 L per second. Differences between the outlets were mostly within the error margin of the instruments used in the experiments with larger differences shown for the 200 L test. The results produced together with a CAD model of the setup can be used for verification of CFD methods. A simulation with the k-epsilon turbulence model is included and compared to earlier experiments and the new experimental results. Larger differences are seen in the new experiments. Differing inlet conditions are assumed as the principal cause for the differences seen.
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| 10. |
- Persson, Mats, 1987-, et al.
(författare)
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Upper limits of the photon fluence rate on CT detectors : case study on a commercial scanner
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: The highest photon fluence rate that a CT detector must be able to measure is animportant parameter. We calculate the maximum transmitted fluence rate in a commercial CT scanner as a function of patient size for standard head, chest and abdomen protocols.Method: We scanned an anthropomorphic phantom (Kyoto Kagaku PBU-60) with the reference CT protocols provided by AAPM on a GE LightSpeed VCT scanner and noted the tube currentapplied with the tube current modulation (TCM) system. By rescaling this tube current usingpublished measurements on the tube current modulation of a GE scanner we could estimate the tube current that these protocols would have resulted in for other patient sizes. An ECG gatedchest protocol was also simulated. Using measured dose rate profiles along the bowtie filters, wesimulated imaging of anonymized patient images with a range of sizes on a GE VCT scanner andcalculated the maximum transmitted fluence rate. In addition, the 99th and the 95th percentilesof the transmitted fluence rate distribution behind the patient are calculated and the effect of omitting projection lines passing just below the skin line is investigated.Results: The highest transmitted fluence rates on the detector for the AAPM reference protocolswith centered patients are found for head and chest images of small patients, with a maximumof 7.1 · 107 mm−2 s−1 for head and 9.6 · 107 mm−2 s−1 for chest. Miscentering the head by 50 mm downwards increases the maximum transmitted fluence rate to 3.9 · 108 mm−2 s−1 . The ECG gatedchest protocol gives fluence rates up to 2.3 · 108 − 2.4 · 108 mm−2 s−1 depending on miscentering.Conclusion: The fluence rate on a CT detector reaches 1 · 108 − 4 · 108 mm−2 s−1 in standardimaging protocols, with the highest rates occurring for ECG gated chest and miscentered headscans. These results will be useful to developers of CT detectors, in particular photon countingdetectors.
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