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Sökning: WFRF:(Wolffenbuttel R. F.)

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2.
  • Justice, A. E., et al. (författare)
  • Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
  • 2017
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
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3.
  • Berndt, Sonja I., et al. (författare)
  • Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
  • Tidskriftsartikel (refereegranskat)abstract
    • Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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4.
  • Do, Ron, et al. (författare)
  • Common variants associated with plasma triglycerides and risk for coronary artery disease
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
  • Tidskriftsartikel (refereegranskat)abstract
    • Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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5.
  • Lagou, Vasiliki, et al. (författare)
  • Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
  • 2021
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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6.
  • Willer, Cristen J., et al. (författare)
  • Discovery and refinement of loci associated with lipid levels
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
  • Tidskriftsartikel (refereegranskat)abstract
    • Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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7.
  • Kilpelainen, TO, et al. (författare)
  • Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
  • 2019
  • Ingår i: Nature communications. - London : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 376-
  • Tidskriftsartikel (refereegranskat)abstract
    • Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
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8.
  • Koettgen, Anna, et al. (författare)
  • Genome-wide association analyses identify 18 new loci associated with serum urate concentrations
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:2, s. 145-154
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SEMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
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  • Stolk, Lisette, et al. (författare)
  • Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
  • 2012
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:3, s. 260-268
  • Tidskriftsartikel (refereegranskat)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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12.
  • van der Harst, Pim, et al. (författare)
  • Seventy-five genetic loci influencing the human red blood cell
  • 2012
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
  • Tidskriftsartikel (refereegranskat)abstract
    • Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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13.
  • Kato, Norihiro, et al. (författare)
  • Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
  • 2015
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
  • 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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  • Wheeler, Eleanor, et al. (författare)
  • Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations : A transethnic genome-wide meta-analysis
  • 2017
  • Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 14:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.Methods & findings: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 x 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI0.55-0.74) of African American adults with T2Dto remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.Conclusions: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.
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  • van Vliet-Ostaptchouk, J. V., et al. (författare)
  • Pleiotropic effects of obesity-susceptibility loci on metabolic traits : a meta-analysis of up to 37,874 individuals
  • 2013
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 56:10, s. 2134-2146
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic pleiotropy may contribute to the clustering of obesity and metabolic conditions. We assessed whether genetic variants that are robustly associated with BMI and waist-to-hip ratio (WHR) also influence metabolic and cardiovascular traits, independently of obesity-related traits, in meta-analyses of up to 37,874 individuals from six European population-based studies. We examined associations of 32 BMI and 14 WHR loci, individually and combined in two genetic predisposition scores (GPSs), with glycaemic traits, blood lipids and BP, with and without adjusting for BMI and/or WHR. We observed significant associations of BMI-increasing alleles at five BMI loci with lower levels of 2 h glucose (RBJ [also known as DNAJC27], QPTCL: effect sizes -0.068 and -0.107 SD, respectively), HDL-cholesterol (SLC39A8: -0.065 SD, MTCH2: -0.039 SD), and diastolic BP (SLC39A8: -0.069 SD), and higher and lower levels of LDL- and total cholesterol (QPTCL: 0.041 and 0.042 SDs, respectively, FLJ35779 [also known as POC5]: -0.042 and -0.041 SDs, respectively) (all p < 2.4 x 10(-4)), independent of BMI. The WHR-increasing alleles at two WHR loci were significantly associated with higher proinsulin (GRB14: 0.069 SD) and lower fasting glucose levels (CPEB4: -0.049 SD), independent of BMI and WHR. A higher GPS-BMI was associated with lower systolic BP (-0.005 SD), diastolic BP (-0.006 SD) and 2 h glucose (-0.013 SD), while a higher GPS-WHR was associated with lower HDL-cholesterol (-0.015 SD) and higher triacylglycerol levels (0.014 SD) (all p < 2.9 x 10(-3)), independent of BMI and/or WHR. These pleiotropic effects of obesity-susceptibility loci provide novel insights into mechanisms that link obesity with metabolic abnormalities.
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23.
  • Ayerden, N.P., et al. (författare)
  • Design, fabrication and characterization of LVOF-based IR microspectrometers
  • 2014
  • Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. - 9781628410785 ; 9130
  • Konferensbidrag (refereegranskat)abstract
    • This paper presents the design, fabrication and characterization of a linear variable optical filter (LVOF) that operates in the infrared (IR) spectral range. An LVOF-based microspectrometer is a tapered-cavity Fabry-Perot optical filter placed on top of a linear array of detectors. The filter transforms the optical spectrum into a lateral intensity profile, which is recorded by the detectors. The IR LVOF has been fabricated in an IC-compatible process flow using a resist reflow and is followed by the transfer etching of this resist pattern into the optical resonator layer. This technique provides the possibility to fabricate a small, robust and high-resolution micro-spectrometer in the IR spectral range directly on a detector chip. In these designs, the LVOF uses thin-film layers of sputtered Si and SiO 2 as the high and low refractive index materials respectively. By tuning the deposition conditions and analyzing the optical properties with a commercial ellipsometer, the refractive index for Si and SiO2 thin-films was measured and optimized for the intended spectral range. Two LVOF microspectrometers, one operating in the 1.8-2.8 μm, and the other in the 3.0-4.5 μm wavelength range, have been designed and fabricated on a silicon wafer. The filters consist of a Fabry-Perot structure combined with a band-pass filter to block the out-of-band transmission. Finally, the filters were fully characterized with an FTIR spectrometer and the transmission curve widening was investigated. The measured transmittance curves were in agreement with theory. The characterization shows a spectral resolution of 35-60 nm for the short wavelength range LVOF and 70 nm for the long wavelength range LVOF, which can be further improved using signal processing algorithms.
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25.
  • Schlosser, P, et al. (författare)
  • Meta-analyses identify DNA methylation associated with kidney function and damage
  • 2021
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7174-
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.
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26.
  • Silva, M. F., et al. (författare)
  • Magnesium fluoride as low-refractive index material for near-ultraviolet filters applied to optical sensors
  • 2020
  • Ingår i: Vacuum. - : Elsevier BV. - 0042-207X. ; 181
  • Tidskriftsartikel (refereegranskat)abstract
    • This article describes the fabrication of MgF2 and MgO thin-film-based optical filters and compares the optical transmission of the filters over UV. The MgF2 thin-films were deposited by use of an e-beam technique and their optical properties were characterised by ellipsometry. The effect of substrate temperature on the optical properties was studied. The MgF2 optimum refractive indices were obtained with a substrate temperature between 200 °C and 300 °C. Optical simulations were performed to compare the performance of MgF2 and MgO in the fabrication of near-UV narrow bandpass optical filters. While MgO-based optical filters result in a higher transmittance peak intensity, especially at 350 nm, the MgF2 optical filters are narrower, present lower values of FWHM, a mean value of 20 nm. This feature could be especially relevant for specific applications on fluorescent optical sensors. Finally, a Fabry-Perot based on a MgF2/TiO2 optical filter was deposited, using an e-beam technique for the MgF2 thin-films and RF-sputtering technique for the TiO2 thin-films. The MgF2/TiO2 optical filter peak transmittance is approximately 70% close to 400 nm, as expected. The results are discussed with focus on applications in fluorescent optical sensors for peaks at 350, 370, 380 and 400 nm, respectively.
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27.
  • Tin, A, et al. (författare)
  • Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus
  • 2021
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7173-
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E–7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.
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28.
  • Ayerden, N.P., et al. (författare)
  • A highly miniaturized NDIR methane sensor
  • 2016
  • Ingår i: Micro-Optics 2016, Brussels, 4-5 Apr.; (SPIE Proceedings vol. 9888). - : SPIE. - 0277-786X. - 9781510601338 ; 9888, s. art. no. UNSP 98880D-
  • Konferensbidrag (refereegranskat)abstract
    • The increasing demand for handheld systems for absorption spectroscopy has triggered the development of microspectrometers at various wavelength ranges. Several MEMS implementations of the light source, interferometer/optical filter, and detector have already been reported in the literature. However, the size of microspectrometers is still limited by the required absorption path length in the sample gas cell. This paper presents a compact MEMS linear-variable optical filter (LVOF) where the resonator cavity of the filter is also used as a sample gas cell to measure the absorption of methane at 3392nm wavelength. The physical resonator cavity length is elongated 62.2-fold, using multiple reflections from highly reflective Bragg mirrors to achieve a sufficiently long effective optical absorption path. Although the LVOF would in principle enable operation as a robust portable microspectrometer, here it is used in a miniaturized NDIR methane sensor for wavelength selection and calibration.
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29.
  • Emadi, A., et al. (författare)
  • An UV linear variable optical filter-based micro-spectrometer
  • 2010
  • Ingår i: Procedia Engineering, Proc. Eurosensors XXIV, September 5-8, 2010, Linz, Austria. - : Elsevier BV. - 1877-7058. ; 5, s. 416-419
  • Konferensbidrag (refereegranskat)abstract
    • This paper presents the design, fabrication and spectral measurements of an Ultra-Violet (UV) Linear Variable Optical Filter (LVOF)-based micro-spectrometer operating in the 300 nm - 400 nm wavelength range. The UV LVOF has been fabricated in an IC-Compatible process using resist reflow. Characterization by passing monochromatic light through the LVOF, shows high linearity of the profile. It is expected that using signal processing, spectral resolution better than 0.5 nm can be achieved with this UV LVOF. The filter provides the possibility to have a robust high-resolution micro-spectrometer in the UV on a CMOS chip.
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31.
  • Emadi, A., et al. (författare)
  • Design, fabrication and measurements with a UV Linear-Variable Optical Filter microspectrometer
  • 2012
  • Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. - 9780819491312 ; 8439, s. Art. no. 84390V-
  • Konferensbidrag (refereegranskat)abstract
    • An IC-Compatible Linear-Variable Optical Filter (LVOF) for application in the UV spectral range between 310 nm and 400 nm has been fabricated using resist reflow and an optimized dry-etching. The LVOF is mounted on the top of a commercially available CMOS camera to result in a UV microspectrometer. A special calibration technique has been employed that is based on an initial spectral measurement on a Xenon lamp. The image recorded on the camera during calibration is used in a signal processing algorithm to reconstruct the spectrum of the Mercury lamp and the calibration data is subsequently used in UV spectral measurements. Experiments on fabricated LVOF-based microspectrometer with this calibration approach implemented reveal a spectral resolution of 0.5 nm.
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32.
  • Emadi, A., et al. (författare)
  • Fabrication and characterization of IC-Compatible Linear Variable Optical Filters with application in a micro-spectrometer
  • 2010
  • Ingår i: Sensors and Actuators, A: Physical. - : Elsevier BV. - 0924-4247. ; 162:2; Sp. Iss. SI, s. 400-405
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper reports on an IC-Compatible process for the fabrication of Linear Variable Optical Filter (LVOF). The LVOF is integrated with a detector array to result in a micro-spectrometer. The technological challenge in fabrication of an LVOF is fabrication of a well-controlled tapered cavity layer. Very small taper angles, ranging from 0.001 degrees to 0.1 degrees. are fabricated in a resist layer by just one lithography step and a subsequent reflow process. The 3D pattern of resist structures is subsequently transferred into SiO2 by an appropriate etching. Complete LVOF fabrication involves CMOS-compatible deposition of a lower dielectric mirror using a stack of dielectrics on the wafer, tapered layer formation and the deposition of the top dielectric mirror. The design principle, IC-Compatible processing and the characterization results on fabricated LVOFs are presented. (C) 2010 Elsevier B.V. All rights reserved.
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33.
  • Emadi, A., et al. (författare)
  • Linear variable optical filter-based ultraviolet microspectrometer
  • 2012
  • Ingår i: Applied Optics. - 1559-128X .- 2155-3165. ; 51:19, s. 4308-4315
  • Tidskriftsartikel (refereegranskat)abstract
    • An IC-compatible linear variable optical filter (LVOF) for application in the UV spectral range between 310 and 400 nm has been fabricated using resist reflow and an optimized dry-etching. The LVOF is mounted on the top of a commercially available CMOS camera to result in a UV microspectrometer. A special calibration technique has been employed that is based on an initial spectral measurement on a xenon lamp. The image recorded on the camera during calibration is used in a signal processing algorithm to reconstruct the spectrum of the mercury lamp and the calibration data is subsequently used in UV spectral measurements. Experiments on a fabricated LVOF-based microspectrometer with this calibration approach implemented reveal a spectral resolution of 0.5 nm.
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34.
  • Ghaderi, M., et al. (författare)
  • Design, fabrication and characterization of infrared LVOFs for measuring gas composition
  • 2014
  • Ingår i: Journal of Micromechanics and Microengineering. - : IOP Publishing. - 1361-6439 .- 0960-1317. ; 24:8, s. Art. no. 084001-
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper presents the design, fabrication and characterization of a linear-variable optical-filter (LVOF) that will be used in a micro-spectrometer operating in infrared (IR) for natural gas composition measurement. An LVOF is placed on top of an array of detectors and transforms the optical spectrum into a lateral intensity profile, which is recorded by the detectors. The IR LVOF was fabricated in an IC-compatible process using a photoresist reflow technique, followed by transfer etching of the photoresist into the optical resonator layer. The spectral range between 3 to 5 mu m contains the absorption peaks for hydrocarbons, carbon-monoxide and carbon-dioxide. The resulting optical absorption is utilized to measure the gas concentrations in a sample volume. Two LVOF structures were designed and fabricated on silicon wafers using alternate layers of sputtered silicon and silicon-dioxide as the high- and low- refractive index materials. These filters consist of a Fabry-Perot resonator combined with a band-pass filter designed to block out-of-band transmissions. Finally, the filters were fully characterized with an FTIR spectrometer and showed satisfactory agreement with the optical thin-film simulations. The characterization showed a spectral resolution of 100 nm, which can be further improved with signal processing algorithms. This method makes it possible to fabricate small and robust LVOFs with high resolving power in the IR spectral range directly on the detector array chip.
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35.
  • Kappelle, Paul J. W. H., et al. (författare)
  • Plasma apolipoprotein M responses to statin and fibrate administration in type 2 diabetes mellitus
  • 2010
  • Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 213:1, s. 247-250
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Plasma apolipoprotein M (apoM) is potentially anti-atherogenic, and has been found to be associated positively with plasma total, LDL and HDL cholesterol in humans. ApoM may, therefore, be intricately related to cholesterol metabolism. Here, we determined whether plasma apoM is affected by statin or fibrate administration in patients with diabetes mellitus. Methods: Fourteen type 2 diabetic patients participated in a placebo-controlled crossover study which included three 8-week treatment periods with simvastatin (40 mg daily), bezafibrate (400 mg daily), and their combination. Results: ApoM was decreased by 7% in response to simvastatin (P < 0.05 from baseline and placebo), and remained unchanged during bezafibrate and combined simvastatin + bezafibrate administration. Plasma apoM concentrations correlated positively with apoB-containing lipoprotein measures at baseline and during placebo (P < 0.02 to P < 0.001), but these relationships were lost during all lipid lowering treatment periods. Conclusions: This study suggests that, even though plasma apoM is lowered by statins, apoM metabolism is to a considerable extent independent of statin-and fibrate-affected pathways involved in cholesterol homeostasis. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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36.
  • Middelburg, Luke, et al. (författare)
  • Combining impedance spectroscopy with optical absorption spectroscopy in the UV for biofuel composition measurement
  • 2017
  • Ingår i: I2MTC 2017 - 2017 IEEE International Instrumentation and Measurement Technology Conference, Proceedings. - 9781509035960
  • Konferensbidrag (refereegranskat)abstract
    • A capacitive probe is generally used in a flex-fuel engine for measuring the ethanol content in biofuel. However, the water content in biofuel of high ethanol content cannot be disregarded or considered constant and the full composition measurement of ethanol, gasoline and water in biofuel is required. Electrical impedance spectroscopy with a customized capacitive probe operating in the 10 kHz to 1 MHz frequency range is combined with optical absorption spectroscopy in the UV spectral range between 230 and 300 nm for a full composition measurement. This approach is experimentally validated using actual fuels and the results demonstrate that electrical impedance spectroscopy when supplemented with optical impedance spectroscopy can be used to fully determine the composition of the biofuel and applied for a more effective engine management. A concept for a low-cost combined measurement system in the fuel line is presented.
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37.
  • Surakka, Ida, et al. (författare)
  • A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol
  • 2011
  • Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:10, s. e1002333-
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain similar to 25% of the heritability of the phenotypes. To date, no unbiased screen for gene-environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). We collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on total cholesterol (TC) with a combined P-value of 4.79 x 10(-9). There were two potential candidate genes in the region, PCDH7 and CCKAR, with differential expression levels for rs6448771 genotypes in adipose tissue. The effect of WHR on TC was strongest for individuals carrying two copies of G allele, for whom a one standard deviation (sd) difference in WHR corresponds to 0.19 sd difference in TC concentration, while for A allele homozygous the difference was 0.12 sd. Our findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. However, more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus.
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