| 1. |
- Arvidsson, Björn, et al.
(författare)
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Online capillary solid phase extraction and liquid chromatographic separation with quantitative tandem mass spectrometric detection (SPE-LC-MS/MS) of ximelagatran and its metabolites in a complex matrix.
- 2009
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Ingår i: Journal of chromatography. B. - : Elsevier BV. - 1570-0232 .- 1873-376X. ; 877:3, s. 291-297
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Tidskriftsartikel (refereegranskat)abstract
- This work presents the development and validation of a fully automated quantitative analysis method of melagatran, its prodrug ximelagatran, and its major metabolites for the study of drug behavior in biofluids. The method involves online sample clean-up and enrichment on a C4 capillary column followed by separation on a capillary C18 column. Electrospray ionization tandem mass spectrometric detection in positive ion mode was performed with multiple reactions monitoring of eight different transients, divided into two time segments with four transients each. The structural similarity, the complexity of the matrix (pig liver extract) and the formation of isobaric fragment ions, made efficient chromatographic separation necessary. The analysis method provides valid accuracy (<9%; RSD%), precision (<8%; RSD%), linearity (<1.2 nM–1 μM; R2 > 0.999), limit of quantitation (<3.6 nM), retention repeatability (<1.2%; RSD%), selectivity, as well as analyte and column stabilities over a wide concentration range.
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| 2. |
- Chen, Deliang, 1961, et al.
(författare)
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Summary of a workshop on extreme weather events in a warming world organized by the Royal Swedish Academy of Sciences
- 2020
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Ingår i: Tellus Series B-Chemical and Physical Meteorology. - : Stockholm University Press. - 1600-0889 .- 0280-6509. ; 72:1
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Tidskriftsartikel (refereegranskat)abstract
- Climate change is not only about changes in means of climatic variables such as temperature, precipitation and wind, but also their extreme values which are of critical importance to human society and ecosystems. To inspire the Swedish climate research community and to promote assessments of international research on past and future changes in extreme weather events against the global climate change background, the Earth Science Class of the Royal Swedish Academy of Sciences organized a workshop entitled 'Extreme weather events in a warming world' in 2019. This article summarizes and synthesizes the key points from the presentations and discussions of the workshop on changes in floods, droughts, heat waves, as well as on tropical cyclones and extratropical storms. In addition to reviewing past achievements in these research fields and identifying research gaps with a focus on Sweden, future challenges and opportunities for the Swedish climate research community are highlighted.
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| 3. |
- Sjögren, Erik, et al.
(författare)
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Hepatic disposition of ximelagatran and its metabolites in pig; prediction of the impact of membrane transporters through a simple disposition model
- 2010
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Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 27:4, s. 597-607
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The double prodrug ximelagatran is bioconverted, via the intermediates ethylmelagatran and N-hydroxymelagatran, to the direct thrombin inhibitor melagatran. The aims of this study were 1) to investigate the hepatic metabolism and disposition of ximelagatran and the intermediates in pig; and 2) to test a simple in vitro methodology for quantitative investigations of membrane transporters impact on the disposition of metabolized drugs. Methods: Porcine S1 (supernatant fraction obtained by centrifuging at 1000g for 10 min) liver fractions and hepatocytes were incubated in absence and presence of known membrane transporter inhibitors. The in vitro kinetics and disposition were determined by simultaneously fitting of the disappearance of ximelagatran and appearance of ethylmelagatran, N-hydroxymelagatran and melagatran. Results: In S1 liver fractions, the metabolism was significant inhibited by co-incubation of verapamil and ketoconazole but not by erythromycin, quinine and quinidine. The disposition of ximelagatran and the intermediate metabolites in hepatocytes were influenced, to various degrees, by carrier-mediated distribution processes. Conclusion: This work demonstrates that it is possible to obtain profound information of the general mechanisms important in the drug liver disposition with the combination of common in vitro systems and the simple disposition model proposed in this study.
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| 4. |
- Abend, Sven, et al.
(författare)
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Terrestrial very-long-baseline atom interferometry : Workshop summary
- 2024
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Ingår i: AVS Quantum Science. - : American Institute of Physics (AIP). - 2639-0213. ; 6:2
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Forskningsöversikt (refereegranskat)abstract
- This document presents a summary of the 2023 Terrestrial Very-Long-Baseline Atom Interferometry Workshop hosted by CERN. The workshop brought together experts from around the world to discuss the exciting developments in large-scale atom interferometer (AI) prototypes and their potential for detecting ultralight dark matter and gravitational waves. The primary objective of the workshop was to lay the groundwork for an international TVLBAI proto-collaboration. This collaboration aims to unite researchers from different institutions to strategize and secure funding for terrestrial large-scale AI projects. The ultimate goal is to create a roadmap detailing the design and technology choices for one or more kilometer--scale detectors, which will be operational in the mid-2030s. The key sections of this report present the physics case and technical challenges, together with a comprehensive overview of the discussions at the workshop together with the main conclusions.
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| 5. |
- Allard, Christina, et al.
(författare)
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Rasbiologiskt språkbruk i statens rättsprocess mot sameby : DN Debatt 2015-06-11
- 2015
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Annan publikation (populärvet., debatt m.m.)abstract
- Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
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| 6. |
- Allard, Erik, et al.
(författare)
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Comparing capillary electrophoresis : mass spectrometry fingerprints of urine samples obtained after intake of coffee, tea, or water.
- 2008
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 80:23, s. 8946-8955
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Tidskriftsartikel (refereegranskat)abstract
- Metabolomic fingerprinting is a growing strategy for characterizing complex biological samples without detailed prior knowledge about the metabolic system. A two-way analysis system with liquid separation and mass spectrometric detection provides detail-rich data suitable for such fingerprints. As a model study, human urine samples, obtained after intake of coffee, tea, or water, were analyzed with capillary electrophoresis electrospray ionization time-of-flight mass spectrometry (CE−ESI-TOF-MS). In-house-developed software (in Matlab) was utilized to manage and explore the large amount of data acquired (230 CE−MS runs, each with 50−100 million nonzero data points). After baseline and noise reduction, followed by suitable binning in time and m/z, the data sets comprised 9 and 14 million data points in negative and positive ESI mode, respectively. Finally, a signal threshold was applied, further reducing the number to about 100 000 data points per data set. A set of interactive exploratory tools, utilizing principal component analysis (PCA) and analysis of variance (ANOVA) results based on a general linear model, facilitated visual interpretation with score plots (for group assessment) and differential fingerprints (for “hot spot” detection). In the model study highly significant differences due to beverage intake were obtained among the 10 first principal components (p < 10−6 for two of the components in both ESI modes). Especially, the contrasts between “coffee” and “tea or water” indicated several “hot spots” with highly elevated intensities (e.g., for uncharged masses 93, 94, 109, 119, 123, 132, 148, 169, 178, 187, 190, and 193) suitable for further analysis, for example, with tandem MS.
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| 7. |
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| 8. |
- Allard, Erik, 1976-
(författare)
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Metabolic Studies with Liquid Separation Coupled to Mass Spectrometry
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Metabolism is the sum of all chemical processes with the purpose to maintain life, as well as enable reproduction, in a living organism. Through the study of metabolism, increased understanding of pharmacological mechanisms and diseases can be achieved. This thesis describes several ways of doing so, including targeted analysis of selected metabolites and investigations of systematic metabolic differences between selected groups through pattern recognition. A method for exploring metabolic patterns in urine samples after intake of coffee or tea was developed. The methodology was later used with the aim to find biomarkers for prostate cancer and urinary bladder cancer. Furthermore, a fully automated quantitative method was developed for concentration measurements of the double prodrug ximelagatran and its metabolites in pig liver. The method was then used to study the roll of active transporters in pig liver cells. Moreover, a fundamental study was conducted to investigate how monitoring of small, doubly charged analytes can improve the limit of detection and precision in a quantitative method. The techniques used for the experiments were liquid separation coupled to electrospray mass spectrometry. Extra efforts were made to make the separation and the ionization as compatible as possible to each other for increased quality of the collected data.
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| 9. |
- Allard, Erik, 1976-, et al.
(författare)
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Quantitative aspects of analyzing small molecules - monitoring singly or doubly charged ions? : A case study of ximelagatran.
- 2010
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Ingår i: Rapid Communications in Mass Spectrometry. - : Wiley. - 0951-4198 .- 1097-0231. ; 24:4, s. 429-435
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Tidskriftsartikel (refereegranskat)abstract
- Precision, reproducibility and lower limit of quantitation (LLOQ) are important characteristics of a quantitative method. We have investigated these properties for Ximelagatran (Xi), which has a high tendency to form doubly charged ions in electrospray ionization (ESI), by studying the percentage of doubly charged species formed when varying the formic acid (FA) concentration, analyte concentration, amount of organic modifier and flow rate. It was found that the percentage of [Xi + 2H]2+ can be controlled to be more than 90% or less than 10% by varying the amount of FA present, and that the change between these values is dramatic. Furthermore, the percentage of [Xi + 2H]2+ formed decreases with increased analyte concentration and increased flow rate. No apparent relationship with the amount of organic modifier was found. The results have the implication that, by carefully controlling the selected parameters, the LLOQ, precision and reproducibility can be improved. We have compared the fragmentation of the singly and doubly charged species and concluded that the [Xi + 2H]2+ ion is more inclined to undergo fragmentation than [Xi + H]+. As a consequence, unusual instrumental settings had to be used for the experiments. The fragmentation patterns are to a great extent similar, but the doubly charged species is more inclined to generate low-mass product ions.
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| 10. |
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