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- Törnqvist, Gunnar, et al.
(författare)
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Forskare utan gränser
- 2015
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Ingår i: Samhällsvetenskapliga fakulteten i Lund - en vital 50-åring : En jubileumsskrift - En jubileumsskrift. - 9789176233597 ; , s. 593-611:3
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Bokkapitel (populärvet., debatt m.m.)
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2. |
- Carlsson, Henrik, 1987-
(författare)
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Development of an adductomic approach to identify electrophiles in vivo through their hemoglobin adducts
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Humans are exposed to electrophilically reactive compounds, both formed endogenously and from exogenous exposure. Such compounds could react and form stable reaction products, adducts, at nucleophilic sites in proteins and DNA. The formation of adducts constitutes a risk for effects, such as cancer and contact allergy, and plays a role in ageing processes. Adducts to proteins offer a possibility to measure electrophilic compounds in vivo.Adductomic approaches aim to study the totality of adducts, to specific biomolecules, by mass spectrometric screening. This thesis describes the development and application of an adductomic approach for the screening of unknown adducts to N-terminal valine (Val) in hemoglobin (Hb) by liquid chromatography tandem mass spectrometry (LC/MS/MS).The adductomic approach is based on the FIRE procedure, a modified Edman procedure for the analysis of adducts to N-terminal Val in Hb by LC/MS/MS. The adduct screening was performed by stepwise scanning of precursor ions in small mass increments and monitoring four fragments common for derivatives of detached Val adducts, in the multiple reaction monitoring mode. Samples from 12 smokers/nonsmokers were screened with the adductomic approach, and seven previously identified adducts and 19 unknown adducts were detected. A semiquantitative approach was applied for approximate quantification of adduct levels.A strategy for identifying unknown Hb adducts using adductome LC/MS/MS data was formulated and applied for the identification of unknown adducts. Identifications were based on the observed m/z of precursor ions and retention times combined with databases and Log P calculations. Hypothesized adducts were generated in vitro for comparison and matching with the corresponding unknown adducts. Five identified adducts correspond to the precursor electrophiles ethyl vinyl ketone (EVK), glyoxal, methylglyoxal, acrylic acid, and 1-octen-3-one. These adducts, except the adducts corresponding to glyoxal and methylglyoxal, have not been observed as protein adducts before. Probable exposure sources to these electrophiles are diet and/or endogenous formation. The observation of these adducts motivate further studies to evaluate possible contributions to health risks, as well as their potential as biomarkers of exposure.The adduct from EVK was quantitatively assessed through different experiments to estimate the daily internal dose (area under the concentration-time-curve, AUC). EVK is about 2 × 103 more reactive than the reference compound acrylamide. The EVK adduct was shown to be unstable, with a relatively short half-life. The daily AUC in humans of EVK was estimated to be about 20 times lower than the corresponding AUC of acrylamide from intake via food.To confirm the observation of the detected unknown adducts and obtain a statistical foundation, analysis of unknown adducts were performed in large sets of blood samples (n = 50–120) from human cohorts. The majority of the previously detected unknown adducts were found in all analyzed samples, and the levels of many adducts showed large variations between individuals. The cause and significance of these observed variations are not yet clarified, but are of importance for the directions of future studies.In conclusion, a new approach for identification of unknown human exposure to electrophiles was developed and successfully applied.
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4. |
- Duarte-Salles, Talita, et al.
(författare)
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Dietary Acrylamide Intake during Pregnancy and Fetal Growth-Results from the Norwegian Mother and Child Cohort Study (MoBa)
- 2013
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 121:3, s. 374-379
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Acrylamide has shown developmental and reproductive toxicity in animals, as well as neurotoxic effects in humans with occupational exposures. Because it is widespread in food and can pass through the human placenta, concerns have been raised about potential developmental effects of dietary exposures in humans. OBJECTIVES: We assessed associations of prenatal exposure to dietary acrylamide with small for gestational age (SGA) and birth weight. METHODS: This study included 50,651 women in the Norwegian Mother and Child Cohort Study (MoBa). Acrylamide exposure assessment was based on intake estimates obtained from a food frequency questionnaire (FFQ), which were compared with hemoglobin (Hb) adduct measurements reflecting acrylamide exposure in a subset of samples (n = 79). Data on infant birth weight and gestational age were obtained from the Medical Birth Registry of Norway. Multivariable regression was used to estimate associations between prenatal acrylamide and birth outcomes. RESULTS: Acrylamide intake during pregnancy was negatively associated with fetal growth. When women in the highest quartile of acrylamide intake were compared with women in the lowest quartile, the multivariable-adjusted odds ratio (OR) for SGA was 1.11 (95% CI: 1.02, 1.21) and the coefficient for birth weight was -25.7 g (95% CI: -35.9, -15.4). Results were similar after excluding mothers who smoked during pregnancy. Maternal acrylamide-and glycidamide-Hb adduct levels were correlated with estimated dietary acrylamide intakes (Spearman correlations = 0.24; 95% CI: 0.02, 0.44; and 0.48; 95% CI: 0.29, 0.63, respectively). CONCLUSIONS: Lowering dietary acrylamide intake during pregnancy may improve fetal growth.
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5. |
- Gunnarsson, Fredrik, et al.
(författare)
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Uplink Transmission Timing in WCDMA
- 2003
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Ingår i: Proceedings of the 58th IEEE Vehicular Technology Conference. - Linköping : Linköping University Electronic Press. - 0780379543 ; , s. 1688-1692 vol.3
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Konferensbidrag (refereegranskat)abstract
- In wireless network uplink communications, there is a trade off between transmission coordination to avoid overload situations, and distributed transmission decisions to adapt to fast channel variations. Here, uplink transmission timing (UTT) is proposed as a scheme to allow some load control support, while transmitting mainly when the channel is favorable. It utilizes channel state feedback in the form of power control commands, which already are available in the system. Simulations illustrate the transmission timing behavior, and also indicate that UTT is a power and intercell interference efficient scheme to transport data compared to traditional dedicated channels with continuous transmissions and to schemes where transmission decisions are random.
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9. |
- Karlsson, Ingemar, et al.
(författare)
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Territoriets gränser
- 1997
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Bok (övrigt vetenskapligt/konstnärligt)
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10. |
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