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| 3. |
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| 4. |
- Teumer, A, et al.
(författare)
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Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4130-
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Tidskriftsartikel (refereegranskat)abstract
- Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.
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| 5. |
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| 6. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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| 7. |
- Gorski, Mathias, et al.
(författare)
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Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
- 2022
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639
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Tidskriftsartikel (refereegranskat)abstract
- Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
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| 8. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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| 9. |
- Pashchenko, V. P., et al.
(författare)
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Structural and magnetic inhomogeneity and the NMR of Mn-55 and La-139 in the magnetoresistive ceramics La0.7Ba0.3-xSnxMnO3 -> La0.7-xBa0.3-xMnO3+0.5xLa(2)Sn(2)O(7)
- 2003
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Ingår i: Low temperature physics (Woodbury, N.Y., Print). - : AIP Publishing. - 1063-777X .- 1090-6517. ; 29:11, s. 910-916
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Tidskriftsartikel (refereegranskat)abstract
- The effects of substitution of barium by tin on the phase composition, structural imperfection, and properties of lanthanum manganite perovskites La0.7Ba0.3-xSnxMnO3 (X=0, 0.1, 0.15, 0.2, 0.3) are established by comprehensive studies done by x-ray diffraction, resistive, and magnetic (including NMR on Mn-55 and La-139) methods. It is shown that the introduction of Sn leads to the formation of a pyrochloric phase La2Sn2O7, to an increase in the density of lattice defects of the manganese-enriched main lanthanum manganite phase, and to a substantial decrease of the magnetoresistive effect. The smearing of the metal-semiconductor phase transition temperature is explained by an increase in the inhomogeneity and imperfection of the perovskite structure. The low activation energy is confirmed by a high degree of inhomogeneity and imperfection of the crystal lattice of the samples studied. The broad, asymmetric NMR spectra of Mn-55 and La-139 attest to high-frequency electron exchange between Mn3+ and Mn4+ and nonequivalence of the environment of those ions and La3+ due both to heterovalent ions and to vacancies and clusters.
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| 10. |
- Schaap, M., et al.
(författare)
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Standardized evaluation methodology and reference database for evaluating coronary artery centerline extraction algorithms
- 2009
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Ingår i: Medical Image Analysis. - : Elsevier. - 1361-8415 .- 1361-8423. ; 13:5, s. 701-714
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Tidskriftsartikel (refereegranskat)abstract
- Efficiently obtaining a reliable coronary artery centerline from computed tomography angiography data is relevant in clinical practice. Whereas numerous methods have been presented for this purpose, up to now no standardized evaluation methodology has been published to reliably evaluate and compare the performance of the existing or newly developed coronary artery centerline extraction algorithms. This paper describes a standardized evaluation methodology and reference database for the quantitative evaluation of coronary artery centerline extraction algorithms. The contribution of this work is fourfold: (1) a method is described to create a consensus centerline with multiple observers, (2) well-defined measures are presented for the evaluation of coronary artery centerline extraction algorithms, (3) a database containing 32 cardiac CTA datasets with corresponding reference standard is described and made available, and (4) 13 coronary artery centerline extraction algorithms, implemented by different research groups, are quantitatively evaluated and compared. The presented evaluation framework is made available to the medical imaging community for benchmarking existing or newly developed coronary centerline extraction algorithms.
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| 11. |
- Gorski, Mathias, et al.
(författare)
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Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
- 2021
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 99:4, s. 926-939
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Tidskriftsartikel (refereegranskat)abstract
- Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
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| 12. |
- Wang, J., et al.
(författare)
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Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:11, s. 1396-1406
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Tidskriftsartikel (refereegranskat)abstract
- Human gut microbiota is an important determinant for health and disease, and recent studies emphasize the numerous factors shaping its diversity. Here we performed a genome-wide association study (GWAS) of the gut microbiota using two cohorts from northern Germany totaling 1,812 individuals. Comprehensively controlling for diet and non-genetic parameters, we identify genome-wide significant associations for overall microbial variation and individual taxa at multiple genetic loci, including the VDR gene (encoding vitamin D receptor). We observe significant shifts in the microbiota of Vdr(-/-) mice relative to control mice and correlations between the microbiota and serum measurements of selected bile and fatty acids in humans, including known ligands and downstream metabolites of VDR. Genome-wide significant (P < 5 x 10(-8)) associations at multiple additional loci identify other important points of host-microbe intersection, notably several disease susceptibility genes and sterol metabolism pathway components. Non-genetic and genetic factors each account for approximately 10% of the variation in gut microbiota, whereby individual effects are relatively small.
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| 13. |
- Wosinski, T., et al.
(författare)
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Domain-wall contribution to magnetoresistance of a ferromagnetic (Ga,Mn)As layer
- 2007
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Ingår i: Physica Status Solidi. A, Applied Research. - : Wiley. - 0031-8965. ; 204:2, s. 472-476
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Tidskriftsartikel (refereegranskat)abstract
- Low-temperature charge-carrier transport in simple magnetoresistive nanodevices, consisted of narrow constrictions of submicron width in the epitaxial layer of a ferromagnetic (Ga,Mn)As semiconductor, has been investigated and correlated with magnetic properties of the layer. The devices containing constrictions; revealed abrupt jumps of a reduced resistance that appeared when the sweeping magnetic field crossed the regions of the coercive field of the layer magnetization. In contrast, the non-constricted reference device displayed abrupt jumps of an enhanced resistance at the same values of magnetic field. We interpret the both features, whose positions on the magnetic-field scale reflect the hysteresis loop of magnetization, as manifestation of domain wall contribution to the (Ga,Mn)As layer resistance. The negative contribution of a domain wall to the resistance in the constricted device results most likely from the suppression of the weak localization effects by a domain wall located at the constriction.
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| 14. |
- Wosinski, T., et al.
(författare)
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Magnetoresistive memory in ferromagnetic (Ga,Mn)As nanostructures
- 2008
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Ingår i: Materials Sceince - Poland. - 0137-1339 .- 2083-134X. ; 26:4, s. 1097-1104
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Konferensbidrag (refereegranskat)abstract
- Magneto-resistive nanostructures have been investigated. The structures were fabricated by electron beam lithography patterning and chemical etching from thin epitaxial layers of the ferromagnetic semiconductor (Ga,Mn)As, in shape of three nanowires joined in one point and forming three-terminal devices, in which an electric current can be driven through any of the three pairs of nanowires. In these devices, a novel magneto-resistive memory effect has been demonstrated, related to a rearrangement of magnetic domain walls between different pairs of nanowires in the device consisting in that its zero-field resistance depends on the direction of previously applied magnetic field. The nanostructures can thus work as two-state devices providing basic elements of nonvolatile memory cells.
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| 15. |
- Babonas, G. J., et al.
(författare)
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Optical properties of Fe-doped silica films on Si
- 2006
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Ingår i: Applied Surface Science. - : Elsevier BV. - 0169-4332 .- 1873-5584. ; 252:15, s. 5391-5394
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Tidskriftsartikel (refereegranskat)abstract
- Optical properties of Fe-doped silica films on Si were investigated by ellipsometric technique in the region 1-5 eV. Samples were produced by sol-gel method. Precursors were prepared by mixing tetraethoxysilane (TEOS) solution in ethanol and water with aqueous solution of Fe-chloride or Fe-acetate. The coating solution was deposited on Si substrates by spin on technique. The size of Fe-containing nanometric-sized particles depended on technology and varied from 20 to 100 nm. Optical response of complex hybrid samples SiO2:Fe/Si was interpreted in a multi-layer model. In the inverse problem, the Maxwell equations were solved by transfer matrix technique. Dielectric function of Fe-doped silica layers was calculated in the model of effective media. Analysis of optical data has shown that various Fe-oxides formed. Experimental data for films obtained from precursors with Fe-acetate and annealed in hydrogen were well described by the model calculations taking into account a small contribution 1-5% of metal Fe imbedded in silica. The Fe/Fe-O contribution to optical response increased for samples grown from FeCl3-precursor. Ellipsometric data for Fe-doped silica films on Si were interpreted taking into account the structural AFM studies as well as the results of magnetic measurements.
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| 16. |
- Bortz, Robert H., et al.
(författare)
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Single-Dilution COVID-19 Antibody Test with Qualitative and Quantitative Readouts
- 2021
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Ingår i: mSphere. - : American Society for Microbiology. - 2379-5042. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- The coronavirus disease 2019 (COVID-19) global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to place an immense burden on societies and health care systems. A key component of COVID-19 control efforts is serological testing to determine the community prevalence of SARS-CoV-2 exposure and quantify individual immune responses to prior SARS-CoV-2 infection or vaccination. Here, we describe a laboratory-developed antibody test that uses readily available research-grade reagents to detect SARS-CoV-2 exposure in patient blood samples with high sensitivity and specificity. We further show that this sensitive test affords the estimation of viral spike-specific IgG titers from a single sample measurement, thereby providing a simple and scalable method to measure the strength of an individual's immune response. The accuracy, adaptability, and cost-effectiveness of this test make it an excellent option for clinical deployment in the ongoing COVID-19 pandemic.IMPORTANCE Serological surveillance has become an important public health tool during the COVID-19 pandemic. Detection of protective antibodies and seroconversion after SARS-CoV-2 infection or vaccination can help guide patient care plans and public health policies. Serology tests can detect antibodies against past infections; consequently, they can help overcome the shortcomings of molecular tests, which can detect only active infections. This is important, especially when considering that many COVID-19 patients are asymptomatic. In this study, we describe an enzyme-linked immunosorbent assay (ELISA)-based qualitative and quantitative serology test developed to measure IgG and IgA antibodies against the SARS-CoV-2 spike glycoprotein. The test can be deployed using commonly available laboratory reagents and equipment and displays high specificity and sensitivity. Furthermore, we demonstrate that IgG titers in patient samples can be estimated from a single measurement, enabling the assay's use in high-throughput clinical environments.
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| 17. |
- Dai, Lu, et al.
(författare)
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The association between TMAO, CMPF, and clinical outcomes in advanced chronic kidney disease : results from the European QUALity (EQUAL) Study
- 2022
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 116:6, s. 1842-1851
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Tidskriftsartikel (refereegranskat)abstract
- Background: Trimethylamine N-oxide (TMAO), a metabolite from red meat and fish consumption, plays a role in promoting cardiovascular events. However, data regarding TMAO and its impact on clinical outcomes are inconclusive, possibly due to its undetermined dietary source.Objectives: We hypothesized that circulating TMAO derived from fish intake might cause less harm compared with red meat sources by examining the concomitant level of 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), a known biomarker of fish intake, and investigated the association between TMAO, CMPF, and outcomes.Methods: Patients were recruited from the European QUALity (EQUAL) Study on treatment in advanced chronic kidney disease among individuals aged ≥65 y whose estimated glomerular filtration rate (eGFR) had dropped for the first time to ≤20 mL/min per 1.73 m2 during the last 6 mo. The association between TMAO, CMPF, and outcomes including all-cause mortality and kidney replacement therapy (KRT) was assessed among 737 patients. Patients were further stratified by median cutoffs of TMAO and CMPF, suggesting high/low red meat and fish intake.Results: During a median of 39 mo of follow-up, 232 patients died. Higher TMAO was independently associated with an increased risk of all-cause mortality (multivariable HR: 1.46; 95% CI: 1.17, 1.83). Higher CMPF was associated with a reduced risk of both all-cause mortality (HR: 0.79; 95% CI: 0.71, 0.89) and KRT (HR: 0.80; 95% CI: 0.71, 0.90), independently of TMAO and other clinically relevant confounders. In comparison to patients with low TMAO and CMPF, patients with low TMAO and high CMPF had reduced risk of all-cause mortality (adjusted HR: 0.49; 95% CI: 0.31, 0.73), whereas those with high TMAO and high CMPF showed no association across adjusted models.Conclusions: High CMPF conferred an independent role in health benefits and might even counteract the unfavorable association between TMAO and outcomes. Whether higher circulating CMPF concentrations are due to fish consumption, and/or if CMPF is a protective factor, remains to be verified.
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| 18. |
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| 19. |
- Dyakonov, V., et al.
(författare)
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Spin-wave resonance in the La0.7Mn1.3O3-delta film
- 2000
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Ingår i: Physics Letters A. - 0375-9601 .- 1873-2429. ; 268:3, s. 202-207
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Tidskriftsartikel (refereegranskat)abstract
- The spin-wave resonance (SWR) spectra have been observed in the (001) oriented La0.7Mn1.3O3-delta epitaxial films. The spectra consist of a series of well-resolved spin-wave modes clearly seen in the: perpendicular external field configuration. It is shown that the spins are completely pinned on both sides of the film surface. Based on a study of the SWR spectra the value of the spin-wave exchange constant, D, is found to be 150 meV Angstrom(2). This value of. D correlates well with this one determined for all known until now manganites.
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| 20. |
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| 21. |
- Yastrubchak, O., et al.
(författare)
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Influence of Ion Implantation on Magnetic, Structural and Optical Properties of (Ga,Mn)As Epitaxial Films
- 2008
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Ingår i: ACTA PHYSICA POLONICA A. - 0587-4246. ; 114:5, s. 1445-1450
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Konferensbidrag (refereegranskat)abstract
- We performed implantation experiments; applying both the chemically active oxygen ions and inactive ions of neon noble gas, to thin epitaxial films of (Ga,Mn)As ferromagnetic semiconductor. Inspection of their magnetic properties by means of a superconducting quantum interference device magnetometer revealed that the implantation with a low dose of either O or Ne ions completely suppressed ferromagnetism in the films. Both the high resolution X-ray diffraction technique and the Raman spectroscopy showed significant changes in the structural and optical properties of the films caused by oxygen and neon implantation.
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| 22. |
- Yastrubchak, O., et al.
(författare)
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Ion-Implantation Control of Ferromagnetism in (Ga,Mn)As Epitaxial Layers
- 2010
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Ingår i: Journal Of Electronic Materials. - : Springer Science and Business Media LLC. - 0361-5235 .- 1543-186X. ; 39:6, s. 794-798
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Konferensbidrag (refereegranskat)abstract
- Epitaxial layers of (Ga,Mn)As ferromagnetic semiconductor have been subjected to low-energy ion implantation by applying a very low fluence of either chemically active, oxygen ions or inactive ions of neon noble gas. Several complementary characterization techniques have been used with the aim of studying the effect of ion implantation on the layer properties. Investigation of their electrical and magnetic properties revealed that implantation with either O or Ne ions completely suppressed both the conductivity and ferromagnetism in the layers. On the other hand, Raman spectroscopy measurements evidenced that O ion implantation influenced optical properties of the layers noticeably stronger than did Ne ion implantation. Moreover, structural modifications of the layers caused by ion implantation were investigated using high-resolution x-ray diffraction technique. A mechanism responsible for ion-implantation-induced suppression of the conductivity and ferromagnetism in (Ga,Mn)As layers, which could be applied as a method for tailoring nanostructures in the layers, is discussed in terms of defects created in the layers by the two implanted elements.
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