| 1. |
- Bergström, Sara K., et al.
(author)
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Polyamine deactivation of integrated poly(dimethylsiloxane) structures investigated by radionuclide imaging and capillary electrophoresis experiments
- 2005
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In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 77:3, s. 938-942
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Journal article (peer-reviewed)abstract
- The poly(dimethylsiloxane) (PDMS) material provides a number of advantageous features, such as flexibility, elasticity, and transparency, making it useful in integrated analytical systems. Hard fused-silica capillary structures and soft PDMS channels can easily be combined by a tight fit, which offers many alternatives for structure combinations. PDMS and fused silica are in different ways prone to adsorption of low levels of organic compounds. The need for modification of the inner wall surface of PDMS channels may often be necessary, and in this paper, we describe an easy and effective method using the amine-containing polymer PolyE-323 to deactivate both fused-silica and PDMS surfaces. The adsorption of selected peptides to untreated surfaces was compared to PolyE-323-modified surfaces, using both radionuclide imaging and capillary electrophoresis experiments. The polyamine modification displayed a substantially reduced adsorption of three hydrophobic test peptides compared to the native PDMS surface. Filling and storage of aqueous solution were also possible in PolyE-323-modified PDMS channels. In addition, hybrid microstructures of fused silica and PDMS could simultaneously be deactivated in one simple coating procedure.
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| 2. |
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| 3. |
- Durgaryan, Andranik, et al.
(author)
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Identification of human chorionic gonadotropin hormone in illegally distributed products by MALDI-TOF mass spectrometry and double-injection capillary zone electrophoresis
- 2016
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In: Analytical Methods. - : Royal Society of Chemistry (RSC). - 1759-9660 .- 1759-9679. ; 8:21, s. 4188-4196
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Journal article (peer-reviewed)abstract
- This paper describes two complementary methods, based on peptide-mass fingerprinting (PMF) using MALDI-TOF mass spectrometry and double injection capillary zone electrophoresis for identification of human chorionic gonadotropin (hCG). The identification was performed by determining the amino acid composition and comparing measured mass spectra with those predicted in silico. Capillary zone electrophoresis in double injection mode (DICZE) was used to confirm the identity of the protein. In DICZE, the identification was performed by analyzing illegal samples together with the corresponding reference standard during a double injection capillary zone electrophoretic run. The identification was based on the closeness of agreement between the calculated migration time (t(mig(c))) and the observed migration time (tmig) of the reference standard. Furthermore, the DICZE method provides the possibility to compare the electrophoretic separation patterns of the native reference standard and the target analyte. The inner surface of the capillary was dynamically coated with putrescine, present in the BGE at 8.2 mM, to improve the separation. The CZE analyses revealed that the protein consisted of at least ten glycosylated isoforms.
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| 4. |
- Elks, Cathy E, et al.
(author)
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Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
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Journal article (peer-reviewed)abstract
- To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
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| 7. |
- Henning, Martin, et al.
(author)
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Strukturomvandling och automatisering : Konsekvenser på regionala arbetsmarknader
- 2016
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Reports (other academic/artistic)abstract
- Denna rapport handlar om den regionala ekonomiska strukturomvandling som ägt rum i Västra Götaland och Skåne sedan 1990-talet, och om den fortsatta automatiseringens framtida regionala avtryck på svenska lokala arbetsmarknader. Rapporten beskriver och gör en sammanfattning av den debatt som på senare år varit intensiv om automatiseringens framtida effekter på arbetsmarknaden. Med utgångspunkt i den internationella litteraturen, förs en diskussion om automatiseringens drivkrafter, hinder ocheffekter.Det finns ingen direkt orsakskedja mellan teknisk utveckling av nya automatiseringslösningar, och effekter på arbetsmarknaden. Många hinder och fördröjningseffekter finns också, som påverkar när och hur nya automatiseringslösningar får genomslag. Dessa kan exempelvis vara av institutionell, social, legal eller etisk art. Vi har mycket att lära av historien. Många faktorer känner vi igen från tidigare teknikskiften.
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| 8. |
- Lavén, Martin, et al.
(author)
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Analysis of microsomal metabolic stability using high-flow-rate extraction coupled to capillary liquid chromatography-mass spectrometry
- 2004
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In: Journal of Chromatography B. ; :806, s. 119-126
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Journal article (peer-reviewed)abstract
- A method described for on-line high-speed extraction of microsomal samples and analysis by capillary liquid chromatography - mass spectrometry (LC-MS) for the determination of metabolic stability in connection with the development of positron emission tomography (PET) tracers. the method allowed direct injections of large sample volumes at a fast extraction rate, providing a gain in both sensitivity and sample preparation time. The calibration curve of the test compound flumazenil (Ro 15-1788) was linear in the concentration range of 1-150 nM, with a correlation coefficient exceeding 0.999. The accuracy of the method ranged from 98 to 101%. A high precision was obtained, with mean intra-assay and inter-assay relative standard deviations of at most 1.4 and 1.5%, respectively, for quality control (QC) samples. The extraction efficiency was determined to be 99.4%, the total recovery 96% and the carryover to <0.23%. Extractions were performed in a concentration interval of 30-300 nM without any sign of column overload. The method was successfully used for determining the microsomal metabolic stability of flumazenil. As a result, the described analysis system is currently used for metabolic screening of PET tracer candidates in our laboratory.
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| 9. |
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| 10. |
- Lavén, Martin, et al.
(author)
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Determination of flumazenil in human plasma by liquid chromatography - electrospray ionisation tandem mass spectrometry
- 2004
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In: Journal of Chromatography B. ; :808, s. 221-227
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Journal article (peer-reviewed)abstract
- A liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS/MS) method was developed to determine unlabelled flumazenil (Ro 15-1788) in human plasma in (11 C)flumazenil positron emission tomagraphy (PET) studies.N-Methyl tri-deuterated flumazenil was used as an internal standard. The analyte and internal standard were extracted from plasma samples using solid-phase extraction, with a recovery of 78%. This was determined through the convenience of radioactivity measurements of 11 C-labelled flumazenil. The evaporated and reconstituted eluate was analysed by LC-ESI-MS/MS. The calibration curve was linear over the tested concentration range of 0.05-0.5 nM (15-150 pg/ml) with a correlation coefficient, R 2, of 0.998 +- 0.001. A high precision was achieved, with mean intra-assay and inter-assay relative standard deviations of at most 6 and 7%, respectively. The accuracy of the method ranged from 95 to 104%. As a proof of concept, the validated method was applied in the determination of flumazenil in plasma from two healthy volunteers participating in a PET study with three repeated investigations. A bolus-infusion protocol was used to achieve a constant concentration level of flumazenil. The average plasma concentrations ranged from 0.11 and 0.19 nM and all measurements were within the calibration standard range. The flumazenil concentrations were relatively constant within each scan and the average intra-scan precision was 15%.
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| 11. |
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| 14. |
- Lavén, Martin, et al.
(author)
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Imaging of peptide adsorption to microfluidic channels in a plastic compact disc using a positron emitting radionuclide
- 2005
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In: Lab Chip. ; :5, s. 756-763
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Journal article (peer-reviewed)abstract
- A method for studying peptide-surface interactions within microfluidic channels by radionuclide imaging is described. With the high surface area-to-volume ratio of channels in miniaturised devices, combined with low amunts of analyte, non-specific peptide adsorption is a critical issue. The objective of the study was therefore to develop a method capable of direct detection of adsorbed peptide within microfluidic channels. A micro-device consisting of channels moulded in a plastic compact disc was chosen for the study, together with two selected peptides of different lengths and isolelectric point (pI) values. A bifunctional chelator, DOTA, was attached to the peptide by conjugation and labelled with the short-lived positron emitting radionuclide 68Ga. Quantitative images of radiotracer distribution within the microfluidic channels were obtained using a PhosphorImager system. The power of the method was demonstrated by the ability to clearly measure changes in adsorption when varying a number of parameters that typically affect peptide adsorption. These included surface modifications, analyte concentration, pH, and ionic strength. Additionally, two quantification methods were developed and compared. Radionuclide imaging also permitted visualisation of adsorption and release processes in microchannel chromatographic columns. The results suggest that radionuclide imaging is a suitable tool not only for the study of peptide adsorption to the microchannels presented in this study but also as a versatile tool to measure peptide-surface interactions in a wide variety of miniaturised structures and devices.
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| 15. |
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| 16. |
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| 17. |
- Lavén, Martin, 1971-
(author)
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Liquid Chromatography – Mass Spectrometry Analysis of Short-lived Tracers in Biological Matrices : Exploration of Radiotracer Chemistry as an Analytical Tool
- 2005
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Doctoral thesis (other academic/artistic)abstract
- Liquid chromatography – mass spectrometry (LC-MS) methods were developed for the analysis of positron emission tomography (PET) radiotracers in biological matrices. Additionally, radiotracer chemistry was explored as an analytical tool for supporting LC-MS method development and imaging molecular interactions in miniaturised chemical analysis systems.Conventional radiodetection methods can offer high sensitivity in the analysis of radiotracers in biological matrices, although with the short half-life of PET tracers, this mass sensitivity decreases rapidly with time. This limits the time frame for analysis, and may compromise the precision and accuracy of the later measurements. Performing LC-MS analysis of the dominant stable isotope form of the tracer removes such time restrictions.An LC-MS/MS method was developed for determination of the tracer flumazenil in human plasma, with high inter-assay precision (RSD < 7%) and accuracy (95 – 104%). The method was applied in a multiple scan PET study where the plasma concentration spanned from 0.07 to 0.21 nM. The method removed the time restrictions associated with radiodetection methods and thus provided the opportunity of analysing a greater number of samples than would have been possible with radioanalysis.Furthermore, an LC-MS/MS method was developed that provided an efficient metabolic screening tool of potential PET tracers, whereby the substrates could be collected directly from 11C-labelling batches. This permitted repeated incubation experiments without the need of repeated labelling syntheses. A para-methoxy-benzamide analogue of the radiotracer WAY-100635 was thus identified as a potential tracer with improved metabolic stability. Additionally, a capillary LC-MS method was developed with rapid (0.75 min) and efficient (> 99%) on-line high flow-rate extraction for determination of metabolic stability of PET radiotracers.Finally, the concept of radionuclide imaging of miniaturised chemical analysis systems was demonstrated with the direct study of interactions within capillary extraction columns and microchannels moulded in a plastic CD and poly(dimethylsiloxane).
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| 18. |
- Lavén, Martin, et al.
(author)
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Radionuclide Imaging of Miniaturized Chemical Analysis Systems
- 2004
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In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 76:23, s. 7102-7108
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Journal article (peer-reviewed)abstract
- We propose radionuclide imaging as a valuable tool for the study of molecular interactions in miniaturized systems for chemical analysis. Sensitive and quantitative imaging can be performed with compounds labeled with short-lived positron-emitting radionuclides, such as C-11 and Ga-68, within selected parts of the system. Radionuclide imaging is not restricted to transparent materials since the relatively energetic positrons can penetrate high optical density materials. Experimentally, a radiotracer is introduced into the object of study, which is subsequently placed on a phosphor storage plate. After exposure, the plate is scanned with a laser and a digital, quantitative image can be reconstituted. To demonstrate the concept, three types of microstructures suited for integration in chemical analysis systems were imaged with C-11- and Ga-68-labeled tracers. The influence of factors such as geometry of the object and type of radionuclide on resolution and sensitivity was investigated. The resolution ranged from 0.9 to 2.7 mm (fwhm). Measuring low amounts of radioactivity in the three structures, 2-20 Bq could be detected, which corresponded to 2.3-500 amol or 2.4-110 pM tracer. The imaging approach was applied to study analyte concentration and sample dilution effects on the performance of a capillary extraction column integrated in an automated LC-ESI-MS system. The utility of the technique was further illustrated by imaging of microchannels in a zeonor plastic compact disk and in a poly(dimethylsiloxane) material for the study of nonspecific peptide adsorption.
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| 19. |
- Lundström, Elin, et al.
(author)
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Characterization of additional sewage treatment technologies : Ecotoxicological effects and levels of selected pharmaceuticals, hormones and endocrine disruptors
- 2010
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In: Ecotoxicology and Environmental Safety. - : Elsevier BV. - 0147-6513 .- 1090-2414. ; 73:7, s. 1612-1619
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Journal article (peer-reviewed)abstract
- In the present study, two conventional (with and without sand filter) and four additional (moving bed biofilm reactor, ozone, moving bed biofilm reactor combined with ozone and a membrane bio reactor) treatment technologies were operated in small-scale at Hammarby Sjostad sewage treatment plant, Stockholm, Sweden. The effluents were tested with five short-term ( <= 7 days exposure) ecotoxicological tests, and analyzed for a number of target analytes, comprising pharmaceuticals, natural hormones and industrial chemicals. Overall, the tested effluents generated few adverse effects at lower concentrations ( < 50% sewage effluent), and no major differences were observed between any of the treatments. The effluent treated with the moving bed biofilm reactor resulted in the lowest effects in the ecotoxicological tests. The most efficient treatment technology with regard to the pharmaceutical residues was the ozone treatment, which however caused negative effects in some of the ecotoxicological tests.
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| 20. |
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| 21. |
- Schumacher, Martin C., et al.
(author)
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A comparative study of tissue omega-6 and omega-3 polyunsaturated fatty acids (PUFA) in benign and malignant pathologic stage pT2a radical prostatectomy specimens
- 2013
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In: Urologic Oncology. - : Elsevier BV. - 1078-1439 .- 1873-2496. ; 31:3, s. 318-324
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Journal article (peer-reviewed)abstract
- Objective: To analyze different polyunsaturated fatty acid (PUPA) tissue levels in malignant compared with benign prostatic tissue from the same prostate specimens. Materials and methods: Fresh frozen benign and malignant prostatic tissue was obtained from radical prostatectomy specimens in 49 men with pathologic stage pT2a prostate cancer. Histopathologic examination confirmed that all tissues from each prostate being analyzed were either completely benign or almost totally malignant. The PUFA composition in these tissues was determined by gas-liquid chromatography on a capillary column. The relative amount of each PUFA (% of total fatty acids) was quantified by integrating the area under the peak and dividing the result by the total area of all fatty acids. Results: Tissue levels of dihomo-gamma-linolenic acid, (C20:3w6), an omega-6 PUFA and a major precursor of omega-6 PUFA metabolites, were significantly higher in malignant compared with benign tissues (P = 0.002). Tissue levels of the downstream omega-6 metabolites, arachidonic acid (AA) (20:4 omega 6), and adrenic acid, (22:4 omega 6), were significantly lower in cancer tissues, (P < 0.0001 and P = 0.013, respectively). Overall, the total levels of omega-6 PUPA were lower in cancer (P = 0.001). Conclusion: We found that the omega-6 PUPA AA and adrenic acid are decreased in malignant prostatic tissues compared with benign tissues from the same prostates. These findings provide additional evidence that dietary fat is associated with prostatic carcinogenesis.
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| 22. |
- Stolk, Lisette, et al.
(author)
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Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
- 2012
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:3, s. 260-268
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Journal article (peer-reviewed)abstract
- To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.
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