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  • 1
    Keywords: TUMORS ; mechanisms ; ASSOCIATION ; SUSCEPTIBILITY ; ABERRATIONS ; MUTATIONS ; CHRONIC LYMPHOCYTIC-LEUKEMIA ; ANEUPLOIDY ; GENOMIC IMBALANCES ; MAFFUCCI SYNDROME ; OLLIER DISEASE
    Abstract: In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of 〉 2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 x 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 x 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases
    Type of Publication: Journal article published
    PubMed ID: 22561519
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  • 2
    Keywords: CANCER ; COHORT ; RISK ; ASSOCIATION ; SUSCEPTIBILITY ; HEALTH ; DESIGN ; WOMEN ; MEN ; cancer risk ; NETHERLANDS ; UNITED-STATES ; TOBACCO ; ALCOHOL ; ALCOHOL-CONSUMPTION ; CONSUMPTION ; pancreatic cancer ; NESTED CASE-CONTROL ; LIFE-STYLE FACTORS ; ONCOLOGY ; case-control study ; REGRESSION ; ASSOCIATIONS ; PANCREATIC-CANCER ; pooled analysis ; CANCER-RISK ; BASE-LINE CHARACTERISTICS ; nested case-control study ; GENOME-WIDE ASSOCIATION ; WOMENS HEALTH ; COFFEE CONSUMPTION ; Type ; nested case control study
    Abstract: The literature has consistently reported no association between low to moderate alcohol consumption and pancreatic cancer; however, a few studies have shown that high levels of intake may increase risk. Most single studies have limited power to detect associations even in the highest alcohol intake categories or to examine associations by alcohol type. We analyzed these associations using 1,530 pancreatic cancer cases and 1,530 controls from the Pancreatic Cancer Cohort Consortium (PanScan) nested case-control study. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression, adjusting for potential confounders. We observed no significant overall association between total alcohol (ethanol) intake and pancreatic cancer risk (OR = 1.38, 95% CI = 0.86-2.23, for 60 or more g/day vs. 〉 0 to 〈 5 g/day). A statistically significant increase in risk was observed among men consuming 45 or more grams of alcohol from liquor per day (OR = 2.23, 95% CI = 1.02-4.87, compared to 0 g/day of alcohol from liquor, P-trend = 0.12), but not among women (OR = 1.35, 95% CI = 0.63-2.87, for 30 or more g/day of alcohol from liquor, compared to none). No associations were noted for wine or beer intake. Overall, no significant increase in risk was observed, but a small effect among heavy drinkers cannot be ruled out
    Type of Publication: Journal article published
    PubMed ID: 20373013
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  • 3
    Keywords: liver ; RISK ; METABOLISM ; SIGNALING PATHWAYS ; MUTATIONS ; C-REACTIVE PROTEIN ; GLUCOSE ; NUCLEAR FACTOR 1-ALPHA ; LOGIC REGRESSION ; MICE LEADS
    Abstract: Four loci have been associated with pancreatic cancer through genome-wide association studies (GWAS). Pathway-based analysis of GWAS data is a complementary approach to identify groups of genes or biological pathways enriched with disease-associated single-nucleotide polymorphisms (SNPs) whose individual effect sizes may be too small to be detected by standard single-locus methods. We used the adaptive rank truncated product method in a pathway-based analysis of GWAS data from 3851 pancreatic cancer cases and 3934 control participants pooled from 12 cohort studies and 8 case-control studies (PanScan). We compiled 23 biological pathways hypothesized to be relevant to pancreatic cancer and observed a nominal association between pancreatic cancer and five pathways (P 〈 0.05), i.e. pancreatic development, Helicobacter pylori lacto/neolacto, hedgehog, Th1/Th2 immune response and apoptosis (P = 2.0 x 10(-6), 1.6 x 10(-5), 0.0019, 0.019 and 0.023, respectively). After excluding previously identified genes from the original GWAS in three pathways (NR5A2, ABO and SHH), the pancreatic development pathway remained significant (P = 8.3 x 10(-5)), whereas the others did not. The most significant genes (P 〈 0.01) in the five pathways were NR5A2, HNF1A, HNF4G and PDX1 for pancreatic development; ABO for H.pylori lacto/neolacto; SHH for hedgehog; TGFBR2 and CCL18 for Th1/Th2 immune response and MAPK8 and BCL2L11 for apoptosis. Our results provide a link between inherited variation in genes important for pancreatic development and cancer and show that pathway-based approaches to analysis of GWAS data can yield important insights into the collective role of genetic risk variants in cancer.
    Type of Publication: Journal article published
    PubMed ID: 22523087
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  • 4
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Systematic studies have been carried out on the transition from the amorphous to the microcrystalline phase in intrinsic Si:H as a function of the accumulated film thickness and the effect of this transition on p–i–n solar cell performance [J. Koh, Y. Lee, H. Fujiwara, C. R. Wronski, and R. W. Collins, Appl. Phys. Lett. 73, 1526 (1998)]. Guided by a deposition phase diagram obtained from real-time spectroscopic ellipsometry, cell structures having i layers deposited with different H2-dilution levels and thicknesses were investigated. For these structures, the fill factors are controlled by the bulk i layers. From the systematic changes in the fill factors, specifically their initial and degraded steady-state values and their degradation kinetics, the effects of the transition from the amorphous to the microcrystalline phase within the Si:H layers are identified, and insights are obtained into the properties of these structurally graded materials. © 1999 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The uncertainties inherent in the normalization of subgap photoconductivity spectra to the optical absorption spectra α(hv) in a-Si:H based films have been addressed. An analysis is presented which is based on optical transitions of constant dipole matrix element between parabolic distributions of extended states and exponential distributions of localized tail states. This analysis has been used to normalize the two sets of results accurately, as verified by photothermal deflection spectroscopy measurements, and is shown to be useful in the commonly encountered cases, in which the two spectra do not overlap over an extended region. Improved quantitative fits of α(hv), for photon energy from ∼1.5 to 2.4 eV, obtained on different a-Si:H based films indicate that the localized exponential band tail regions extend ∼60–70 meV above the optical gap. © 1998 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-093X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract An overview of the whole process of reconstructing the coronal magnetic field from boundary data measured at the photosphere is presented. We discuss the errors and uncertainties in the data and in the data reduction process. The problems include noise in the magnetograph measurements, uncertainties in the interpretation of polarization signals, the 180° ambiguity in the transverse field, and the fact that the photosphere is not force-free. Methods for computing the three-dimensional structure of coronal active region magnetic fields, under the force-free assumption, from these boundary data, are then discussed. The methods fall into three classes: the ‘extrapolation’ technique, which seeks to integrate upwards from the photosphere using only local values at the boundary; the ‘current-field iteration’ technique, which propagates currents measured at the boundary along field lines, then iteratively recomputes the magnetic field due to this current distribution; and the ‘evolutionary’ technique, which simulates the evolution of the coronal field, under quasi-physical resistive magnetohydrodynamic equations, as currents injected at the boundary are driven towards the observed values. The extrapolation method is mathematically ill-posed, and must be heavily smoothed to avoid exponential divergence. It may be useful for tracing low-lying field lines, but appears incapable of reconstructing the magnetic field higher in the corona. The original formulation of the current-field iteration method had problems achieving convergence, but a recent reformulation appears promising. Evolutionary methods have been applied to several real datasets, with apparent success.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0039-6028
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 8
    Publication Date: 2018-11-10
    Description: The impact of nonmagnetic and magnetic impurities on topological insulators is a central focus concerning their fundamental physics and possible spintronics and quantum computing applications. Combining scanning tunneling spectroscopy with transport measurements, we investigate, both locally and globally, the effect of nonmagnetic and magnetic substituents in SmB 6 , a predicted topological Kondo insulator. Around the so-introduced substitutents and in accord with theoretical predictions, the surface states are locally suppressed with different length scales depending on the substituent’s magnetic properties. For sufficiently high substituent concentrations, these states are globally destroyed. Similarly, using a magnetic tip in tunneling spectroscopy also resulted in largely suppressed surface states. Hence, a destruction of the surface states is always observed close to atoms with substantial magnetic moment. This points to the topological nature of the surface states in SmB 6 and illustrates how magnetic impurities destroy the surface states from microscopic to macroscopic length scales.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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