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  • 1
    Keywords: POPULATION ; RISK ; IMPACT ; BREAST-CANCER ; PATTERNS ; HYPOMETHYLATION ; GENOMIC DNA METHYLATION ; colorectal adenoma ; BLOOD-CELLS ; LEUKOCYTE DNA
    Abstract: Reproductive factors have been linked to both breast cancer and DNA methylation, suggesting methylation as an important mechanism by which reproductive factors impact on disease risk. However, few studies have investigated the link between reproductive factors and DNA methylation in humans. Genome-wide methylation in peripheral blood lymphocytes of 376 healthy women from the prospective EPIC study was investigated using LUminometric Methylation Assay (LUMA). Also, methylation of 458877 CpG sites was additionally investigated in an independent group of 332 participants of the EPIC-Italy sub-cohort, using the Infinium HumanMethylation 450 BeadChip. Multivariate logistic regression and linear models were used to investigate the association between reproductive risk factors and genome wide and CpG-specific DNA methylation, respectively. Menarcheal age was inversely associated with global DNA methylation as measured with LUMA. For each yearly increase in age at menarche, the risk of having genome wide methylation below median level was increased by 32% (OR: 1.32, 95% CI: 1.14-1.53). When age at menarche was treated as a categorical variable, there was an inverse dose-response relationship with LUMA methylation levels (OR12-14vs.〈= 11 yrs: 1.78, 95% CI: 1.01-3.17 and OR 〉= 15vs.〈= 11 yrs: 4.59, 95% CI: 2.04-10.33; P for trend〈0.0001). However, average levels of global methylation as measured by the Illumina technology were not significantly associated with menarcheal age. In locus by locus comparative analyses, only one CpG site had significantly different methylation depending on the menarcheal age category examined, but this finding was not replicated by pyrosequencing in an independent data set. This study suggests a link between age at menarche and genome wide DNA methylation, and the difference in results between the two arrays suggests that repetitive element methylation has a role in the association. Epigenetic changes may be modulated by menarcheal age, or the association may be a mirror of other important changes in early life that have a detectable effect on both methylation levels and menarcheal age.
    Type of Publication: Journal article published
    PubMed ID: 24278132
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  • 2
    Keywords: GENE ; ASSOCIATION ; COLORECTAL-CANCER ; BLADDER-CANCER ; HYPERMETHYLATION ; HYPOMETHYLATION ; leukocytes ; methylome ; IGF2 ; BRCA1 PROMOTER METHYLATION
    Abstract: Few studies have evaluated the association between DNA methylation in white blood cells (WBC) and the risk of breast cancer. The evaluation of WBC DNA methylation as a biomarker of cancer risk is of particular importance as peripheral blood is often available in prospective cohorts and easier to obtain than tumor or normal tissues. Here, we used prediagnostic blood samples from three studies to analyze WBC DNA methylation of two ATM intragenic loci (ATMmvp2a and ATMmvp2b) and genome-wide DNA methylation in long interspersed nuclear element-1 (LINE1) repetitive elements. Samples were from a case-control study derived from a cohort of high-risk breast cancer families (KConFab) and nested case-control studies in two prospective cohorts: Breakthrough Generations Study (BGS) and European Prospective Investigation into Cancer and Nutrition (EPIC). Bisulfite pyrosequencing was used to quantify methylation from 640 incident cases of invasive breast cancer and 741 controls. Quintile analyses for ATMmvp2a showed an increased risk of breast cancer limited to women in the highest quintile [OR, 1.89; 95% confidence interval (CI), 1.36-2.64; P = 1.64 x 10(-4)]. We found no significant differences in estimates across studies or in analyses stratified by family history or menopausal status. However, a more consistent association was observed in younger than in older women and individually significant in KConFab and BGS, but not EPIC. We observed no differences in LINE1 or ATMmvp2b methylation between cases and controls. Together, our findings indicate that WBC DNA methylation levels at ATM could be a marker of breast cancer risk and further support the pursuit of epigenome-wide association studies of peripheral blood DNA methylation.
    Type of Publication: Journal article published
    PubMed ID: 22374981
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  • 3
    Keywords: EXPRESSION ; Germany ; MODEL ; MODELS ; liver ; NEW-YORK ; GENE ; GENE-EXPRESSION ; PROTEIN ; MICE ; PATIENT ; ASSOCIATION ; DELETION ; MOUSE ; gene expression ; ESCHERICHIA-COLI ; MUTATION ; LINE ; WILD-TYPE ; HEREDITARY ; MUTATIONS ; MHC CLASS-I ; PROTEIN LEVELS ; protein expression ; BRUSH-BORDER ; TRANSFERRIN RECEPTOR ; DIVALENT METAL TRANSPORTER ; duodenal cytochrome b,DMT1,hemochromatosis,hepcidin,HFE,Ireg1 ; HEMOCHROMATOSIS PROTEIN HFE ; HEPCIDIN EXPRESSION ; HEREDITARY HEMOCHROMATOSIS ; KNOCKOUT MOUSE
    Abstract: Patients suffering from hereditary hemochromatosis (HH) show progressive iron overload as a consequence of increased duodenal iron absorption. It has been hypothesized that mutations in the HH gene HFE cause misprogramming of the duodenal enterocytes towards a paradoxical iron-deficient state, resulting in increased iron transporter expression. Previous reports concerning gene expression levels of the duodenal iron transporters DMT1 and IREG1 in HH patients and animal models are controversial, however, and in many cases only mRNA expression levels were investigated. To analyze the duodenal expression of DMT1, Ireg1, Dcytb, and hephaestin and the association with iron overload in adult Hfe(-/-) mice, an Hfe(-/-) mouse line was generated. Duodenal DMTI and Treg1 protein levels, duodenal DMT1, Ireg1, Dcytb, hephaestin, and TfR1 mRNA levels, and hepatic hepcidin mRNA levels were quantified and the correlation to liver iron contents was calculated. We report that duodenal DMT1 and Ireg1 mRNA levels and DMT1 and Ireg1 protein levels remained unaffected by the Hfe deletion. Furthermore, duodenal hephaestin and TJR1 mRNA expression and hepatic hepcidin mRNA expression remained unaltered, while the duodenal mRNA expression of the brush border ferric reductase Dcytb was significantly increased in Hfe(-/-) mice. We found no correlation between the expression level of any of the analyzed transcripts and the liver iron content. In conclusion, the lack of correlation between DMT1 and Ireg1 protein expression and the liver iron content suggests that elevated duodenal iron transporter expression is not required for high liver iron overload. Hfe(-/-) mice do not necessarily display features of iron deficiency in the duodenum, indicated by an increase in mRNA and protein levels of DMT1 and Ireg1. Rather, the duodenal ferric reductase Dcytb may act as a possible mediator of iron overload in Hfe deficiency
    Type of Publication: Journal article published
    PubMed ID: 14618243
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  • 4
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 85 (1999), S. 2719-2721 
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: This paper presents a numerical study of two planar photodetector device designs, a heterojunction lateral p-i-n and a buried layer lateral p-i-n. The devices are planar structures comprised of interdigitated p+ and n+ wells containing either a heterojunction or buried charge sheet. Numerical simulation reveals that when pulsed with an 827 nm optical source at 0.68 mW/cm2, these two devices exhibited vastly superior frequency performance and responsivity compared to a heterostructure metal–semiconductor–metal photodetector formed with identical finger spacing and geometry. The calculated dark currents are similar in magnitude while the capacitances vary among the devices.© 1999 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 53 (1988), S. 2047-2049 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The quantitative analogies that have been established between electron wave propagation in semiconductors and optical wave propagation in dielectrics are used to demonstrate that high-resolution energy filters in semiconductors are possible. An example filter consisting of electron quarter-wavelength layers of GaAs and Ga0.55Al0.45As and a half-wavelength layer of GaAs is presented and theoretically analyzed. The pass electron energy is 0.139 eV and the passband is only 0.003 eV (2.2% of pass energy). Such a filter could be incorporated into semiconductor devices (e.g., as a hot-electron emitter in a ballistic transistor) or used to control free-space electron beams (e.g., in electron beam lithography).
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 51 (1987), S. 276-278 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: A new device structure useful in detecting long-wavelength radiation which uses a variably spaced superlattice both to inject photogenerated electrons into a wider band-gap semiconductor and to promote efficient impact ionization and gain at low bias voltages is proposed. Both of these properties result directly from the unique property of the superlattice structure to create a near monoenergetic stream of electrons and inject them at high energy into an adjacent semiconducting layer. Thus for the first time it should be possible to obtain long-wavelength sensors with high gain (∼103), ultralow noise, and high detectivity.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1442-9993
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: The bird faunas of the adjacent Wessel and English Company island chains were sampled at two scales (0.25 ha quadrats and entire islands). Ninety-six species were recorded from 226 quadrats, with the most frequently recorded species being mistletoebird Dicaeum hirundinaceum, brown honeyeater Lichmera indistincta, silver-crowned friarbird Philemon argenticeps, bar-shouldered dove Geopelia humeralis, northern fantail Rhipidura rufiventris and yellow white-eye Zosterops lutea. At the quadrat scale, vegetation type was a major determinant of the abundance of individual species (and hence species composition), species richness and total bird abundance. Bird species composition and richness at the quadrat scale was also significantly affected by island isolation (particularly the amount of land within 20 km of the island perimeter). Island size had no effect on quadrat-scale richness or total abundance. However, the abundance of 10 of the 38 most frequently recorded individual species was significantly related to island size, in most cases even when the comparison was restricted to similar habitats. The most striking cases were rufous fantail Rhipidura rufifrons, mangrove golden whistler Pachycephala melanura, brown honeyeater and yellow white-eye, which were all significantly more abundant on smaller islands. One hundred and seventy-one species were recorded from the 62 islands sampled. There was a very tight relationship between island size and the number of terrestrial species (73% of deviance explained) and of all species (84% of deviance explained). This relationship was improved (marginally) when isolation was included in the model. Ordination of islands by their terrestrial bird species composition was related to island size and isolation, and suggested an erratic species composition on small islands.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Impedance transformers for ballistic (collisionless) electron waves traveling between dissimilar energy-gap semiconductors are designed as a series of quarter (electron) wavelength layers in the form of a compositional superlattice. The quantitative analogies that have been previously established [J. Appl. Phys. 65, 814 (1989)] between electron-wave propagation in semiconductors and electromagnetic-wave propagation in dielectrics are used. For the design energy, the electron wave would be totally transmitted and the structure is analogous to an antireflection coating in electromagnetic optics. Practical constraints on the impedance transformer layers are (1) their compositions must be within the usable compositional range and (2) their thicknesses must be integer multiples of a monolayer thickness. These constraints are included in the design process. Procedures for designing narrow-band, maximally flat (Butterworth), and equal-ripple (Chebyshev) impedance transformers of arbitrary spectral bandwidth are presented. Example practical single-layer and three-layer transformers for connecting GaAs and Ga0.8Al0.2As are presented.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 66 (1989), S. 1842-1848 
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: A quantum well in a semiconductor can act as a slab waveguide for electron waves in a manner analogous to the way a layered dielectric can act as a slab waveguide for electromagnetic waves (e.g., as commonly employed in integrated optics). In this work, the case of a general electron asymmetric slab waveguide (a quantum well comprised of three materials each with a different potential energy and a different effective mass) is analyzed and the conditions for electron waveguiding are quantified. Electron waveguide modes exist for electron energies in the well and for electron energies above one or both of the potential energy barriers. Furthermore, due to dispersion, each electron waveguide mode has an upper-energy cutoff as well as a lower-energy cutoff. This is in contrast to electromagnetic guided modes which typically have only lower-energy (low-frequency) cutoffs. At the upper-energy cutoff the electron wave is refracted into the substrate and/or cover. An example quantum well waveguide consisting of Ga0.80 Al0.20 As (substrate), GaAs (film), Ga0.55 Al0.45 As (cover) is analyzed. This structure is a single-mode electron waveguide for GaAs thicknesses of from 5 (1.413 nm) to 26 monolayers (7.349 nm).
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 72 (1998), S. 1641-1643 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: We present a numerical study of a high speed GaAs lateral p-i-n (LPIN) photodiode. The LPIN is a planar structure composed of interdigitated p+ and n+ wells. A metal–semiconductor–metal (MSM) photodiode with identical finger spacing and geometry is simulated for comparison. When pulsed with an 827 nm optical source at 0.68 mW/cm2, the lateral p-i-n exhibited improved frequency performance and responsivity compared to the MSM. The dark current and capacitance are similar in magnitude between the two devices. Based on these results, it is concluded that a lateral p-i-n can be an attractive alternative to standard MSM photodetectors. © 1998 American Institute of Physics.
    Type of Medium: Electronic Resource
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