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- Barregård, Lars, 1948, et al.
(author)
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Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine
- 2013
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In: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 18:18, s. 2377-2391
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Journal article (peer-reviewed)abstract
- Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.
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- Danese, E., et al.
(author)
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Impact of the CYP4F2 p.V433M Polymorphism on Coumarin Dose Requirement: Systematic Review and Meta-Analysis
- 2012
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In: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 1532-6535 .- 0009-9236. ; 92:6, s. 746-756
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Research review (peer-reviewed)abstract
- A systematic review and a meta-analysis were performed to quantify the accumulated information from genetic association studies investigating the impact of the CYP4F2 rs2108622 (p.V433M) polymorphism on coumarin dose requirement. An additional aim was to explore the contribution of the CYP4F2 variant in comparison with, as well as after stratification for, the VKORC1 and CYP2C9 variants. Thirty studies involving 9,470 participants met prespecified inclusion criteria. As compared with CC-homozygotes, T-allele carriers required an 8.3% (95% confidence interval (CI): 5.6-11.1%; P < 0.0001) higher mean daily coumarin dose than CC homozygotes to reach a stable international normalized ratio (INR). There was no evidence of publication bias. Heterogeneity among studies was present (I-2 = 43%). Our results show that the CYP4F2 p.V433M polymorphism is associated with interindividual variability in response to coumarin drugs, but with a low effect size that is confirmed to be lower than those contributed by VKORC1 and CYP2C9 polymorphisms.
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4. |
- Gridneva, Lidia, et al.
(author)
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Experimental investigation of the spin reorientation of Co/Au based magnetic nanodot arrays
- 2008
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In: Physical Review B (Condensed Matter and Materials Physics). - 1098-0121 .- 1550-235X. ; 77:10
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Journal article (peer-reviewed)abstract
- (Co/Au) and (Au/ Co/ Au) nanomagnet arrays grown on nanostructured self-organized SiGe templates have been characterized by means of x-ray photoemission electron microscopy, x-ray magnetic circular dichroism, and by extended x-ray absorption spectroscopy using synchrotron radiation. In-plane magnetization is observed at room temperature for practically all Co thicknesses, a stable macroscopic perpendicular magnetic order only at low temperature. The spin reorientation transition in these dot arrays takes place for smaller Co thicknesses over a broader thickness range than in two-dimensional systems. This finding appears to be related with structural relaxation modifications, occurring within the local Co atom environment, which are not necessarily connected with the orbital moment variations. These variations appear in the form of a systematic increase, correlated with the existence of out-of-plane magnetization.
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5. |
- Hirn, Ulrich, et al.
(author)
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The Area of Molecular Contact in Fiber-Fiber Bonds
- 2013
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In: Advances in Pulp and Paper Reserach, Cambridge 2013. - 9780992616304 ; , s. 201-223
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Conference paper (peer-reviewed)abstract
- We are presenting a coherent theoretical concept as well as empirical evidence suggesting that there is a high degree of molecular contact in fiberfiber bonds, the surfaces might even be in full contact.Fundamental theoretical relations from contact mechanics governing the area in molecular contact between surfaces are reviewed and proposed for the quantitative analysis of the area in molecular contact in fiber-fiber bonds.The key parameters determining the degree of molecular contact according to the theory are indentation hardness and elastic modulus of the wet pulp fibers, surface roughness of the wet fibers and the pressure applied to the fiber bonds during bond formation.We provide results for fiber indentation hardness and effective elastic modulus from nanoindentation measurements of fiber surfaces at varying relative humidity and in water. The fiber surface properties have been determined with an atomic force microscopy technique specifically designed to measure soft, viscoelastic materials. Also, surface roughness has been measured in the wet and dry state.Experiments with individual fiber-fiber joints show that the breaking strength of these joints is independent from the pressure during bond formation indicating that the surfaces in fiber-fiber bonds are in a high degree of molecular contact, maybe even full contact. This is the case even if they are formed without external pressure. Computer simulations of the degree of mechanical contact of fiber surfaces during drying were performed indicating that capillary adhesion is pulling the fiber surfaces into a high degree of molecular contact. These findings are discussed with respect to the literature considering FRET microscopy and Transmission Electron Microscopy of fiber-fiber bonds.
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8. |
- Dieterich, Lothar C., et al.
(author)
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Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGFβ2 in vascular abnormalization
- 2012
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In: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 228:3, s. 378-390
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Journal article (peer-reviewed)abstract
- Glioblastoma are aggressive astrocytic brain tumours characterized by microvascular proliferation and an abnormal vasculature, giving rise to brain oedema and increased patient morbidity. Here, we have characterized the transcriptome of tumour-associated blood vessels and describe a gene signature clearly associated with pleomorphic, pathologically altered vessels in human glioblastoma (grade IV glioma). We identified 95 genes differentially expressed in glioblastoma vessels, while no significant differences in gene expression were detected between vessels in non-malignant brain and grade II glioma. Differential vascular expression of ANGPT2, CD93, ESM1, ELTD1, FILIP1L and TENC1 in human glioblastoma was validated by immunohistochemistry, using a tissue microarray. Through qPCR analysis of gene induction in primary endothelial cells, we provide evidence that increased VEGF-A and TGFβ2 signalling in the tumour microenvironment is sufficient to invoke many of the changes in gene expression noted in glioblastoma vessels. Notably, we found an enrichment of Smad target genes within the distinct gene signature of glioblastoma vessels and a significant increase of Smad signalling complexes in the vasculature of human glioblastoma in situ. This indicates a key role of TGFβ signalling in regulating vascular phenotype and suggests that, in addition to VEGF-A, TGFβ2 may represent a new target for vascular normalization therapy.
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9. |
- Krumme, B., et al.
(author)
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Element-specific electronic structure and magnetic properties of an epitaxial Ni51.6Mn32.9Sn15.5 thin film at the austenite-martensite transition
- 2015
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In: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 91:21
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Journal article (peer-reviewed)abstract
- An austenite-martensite transition was observed in a 100-nm-thick Ni51.6Mn32.9Sn15.5 film by temperature-dependent resistivity and magnetization measurements, revealing a martensite starting temperature of M-S approximate to 260 K. The influence of the structural phase transition on the electronic structure and the magnetic properties was studied element specifically employing temperature-dependent x-ray-absorption spectroscopy and x-ray magnetic circular dichroism. In addition, density functional theory calculations have been performed to study the electronic and magnetic properties of both phases. It is shown that off-stoichiometric Ni-Mn-Sn alloys can exhibit a substantial magnetocrystalline anisotropy energy in the martensite phase. For Mn a change of the electronic structure and a strong increase of the ratio of orbital to spin magnetic moment m(l)/m(S) can be observed, whereas for Ni nearly no changes occur. Applying an external magnetic field of B = 3 T reverses the change of the electronic structure of Mn and reduces the ratio of m(l)/m(S) from 13.5 to approximate to 1 % indicating a field-induced reverse martensitic transition.
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