| 1. |
- Heinze, Karolin, et al.
(author)
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Validated biomarker assays confirm ARID1A loss is confounded with MMR deficiency, CD8 TIL infiltration, and provides no independent prognostic value in endometriosis-associated ovarian carcinomas.
- 2021
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In: The Journal of pathology. - : Wiley. - 1096-9896 .- 0022-3417. ; 256:4, s. 388-401
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Journal article (peer-reviewed)abstract
- ARID1A (BAF250a) is a component of the SWI/SNF chromatin modifying complex, plays an important tumour suppressor role, and is considered prognostic in several malignancies. However, in ovarian carcinomas there are contradictory reports on its relationship to outcome, immune response, and correlation with clinicopathological features. We assembled a series of 1,623 endometriosis-associated ovarian carcinomas, including 1,078 endometrioid (ENOC) and 545 clear cell (CCOC) ovarian carcinomas through combining resources of the Ovarian Tumor Tissue Analysis (OTTA) Consortium, the Canadian Ovarian Unified Experimental Resource (COEUR), local, and collaborative networks. Validated immunohistochemical surrogate assays for ARID1A mutations were applied to all samples. We investigated associations between ARID1A loss/mutation, clinical features, outcome, CD8+ tumour-infiltrating lymphocytes (CD8+ TIL), and DNA mismatch repair deficiency (MMRd). ARID1A loss was observed in 42% of CCOC and 25% of ENOC. We found no associations between ARID1A loss and outcomes, stage, age, or CD8+ TIL status in CCOC. Similarly, we found no association with outcome or stage in endometrioid cases. In ENOC, ARID1A loss was more prevalent in younger patients (p=0.012), and associated with MMRd (p<0.001), and presence of CD8+ TIL (p=0.008). Consistent with MMRd being causative of ARID1A mutations, in a subset of ENOC we also observed an association between ARID1A loss-of-function mutation as a result of small indels (p=0.035, versus single nucleotide variants). In ENOC, the association between ARID1A loss, CD8+ TIL, and age, appears confounded by MMRd status. Although this observation does not explicitly rule out a role for ARID1A influence on CD8+ TIL infiltration in ENOC, given current knowledge regarding MMRd, it seems more likely that effects are dominated by the hypermutation phenotype. This large dataset with consistently applied biomarker assessment now provides a benchmark for the prevalence of ARID1A loss-of-function mutations in endometriosis-associated ovarian cancers and brings clarity to the prognostic significance. This article is protected by copyright. All rights reserved.
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| 2. |
- Yang, Yaohua, et al.
(author)
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Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk
- 2019
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In: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 79:3, s. 505-517
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Journal article (peer-reviewed)abstract
- DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P < 7.94 x 10(-7). Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. Significance: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.
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| 3. |
- Doherty, Walter J, et al.
(author)
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Electrochemical copolymerization and spectroelectrochemical characterization of 3,4-ethylenedioxythiophene and 3,4-ethylenedioxythiophene-methanol copolymers on indium-tin oxide
- 2006
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In: Macromolecules. - : American Chemical Society (ACS). - 0024-9297 .- 1520-5835. ; 39:13, s. 4418-4424
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Journal article (peer-reviewed)abstract
- This work describes the electrochemical copolymerization and spectroelectrochemical characterization of 3,4-ethylenedioxythiophene (EDOT) with a commonly used EDOT derivative: 2,3-dihydrothieno[3,4b]-l,4-dioxyn-2-yl methanol (EDTM), on indium-tin oxide (ITO) electrodes, as a function of the EDTM/EDOT comonomer feed ratio. The potential of initial polymerization and the degree of optical contrast between reduced and oxidized states increased steadily with increasing proportions of EDTM. Reactivity ratios were determined by spectroscopic characterization of the copolymer film and by monitoring the depletion of monomer from the starting solution by liquid chromatography, following the formation of relatively thick PEDOT/PEDTM films. Average reactivity ratios of 1.5 ±0.2 and 0.4 ±0.3 were obtained for EDOT and EDTM, respectively, demonstrating preferential deposition of EDOT on ITO electrode surfaces. Significant differences were noted at low and high degrees of conversion, indicating changes in copolymer composition with film thickness. These results have real significance for the characterization of electron-transfer rates for the first monolayer of PEDOT/ PEDTM on ITO, determined by a new mode of potential-modulated attenuated total reflectance spectroelectrochemistry. © 2006 American Chemical Society.
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| 4. |
- Doherty, Walter J, et al.
(author)
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Potential-modulated, attenuated total reflectance spectroscopy of poly(3,4-ethylenedioxythiophene) and poly(3,4-ethylenedioxythiophene methanol) copolymer films on indium-tin oxide
- 2006
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In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 110:10, s. 4900-4907
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Journal article (peer-reviewed)abstract
- We report the first application of a potential-modulated spectroelectrochemical ATR (PM-ATR) instrument utilizing multiple internal reflections at an optically transparent electrode to study the charge-transfer kinetics and electrochromic response of adsorbed films. A sinusoidally modulated potential waveform was applied to an indium-tin oxide (ITO) electrode while simultaneously monitoring the optical reflectivity of thin (2-6 equivalent monolayers) copolymer films of poly(3,4-ethylenedioxythiophene) (PEDOT) and poly(3,4ethylenedioxythiophene methanol) (PEDTM), previously characterized in our laboratory.1 At high modulation frequencies the measured response of the polymer film is selective toward the fastest electrochromic processes in the film, presumably those occurring within the first adsorbed monolayer. Quantitative determination of the electrochromic switching rate, derived from the frequency response of the attenuated reflectivity, shows a linear decrease in the rate, from 11 × 103 s-1 to × 103 s -1, with increasing proportions of PEDTM in the copolymer, suggesting that interactions between the methanol substituent on EDTM and the ITO surface slow the switching process by limiting the rate of conformational change in the polymer film. © 2006 American Chemical Society.
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| 5. |
- Doherty, Walter J, et al.
(author)
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Conducting polymer growth in porous sol-gel thin films : Formation of nanoelectrode arrays and mediated electron transfer to sequestered macromolecules
- 2005
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In: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 17:14, s. 3652-3660
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Journal article (peer-reviewed)abstract
- The templated electrochemical growth of poly(3,4-ethylenedioxythiophene) (PEDOT) into porous sol-gel (PSG) films and PEDOT-mediated electron transfer to ferrocene-modified dendrimers encapsulated within these sol-gel matrices, were analyzed. The conditions needed to optimize PEDOT electropolymerization within the PSG films such that barely emergent PEDOT features protrude from a PSG thin film surface, were also described. It was observed that oxidation/reduction of the encapsulated Fc-PAMAM units could be voltammetrically detected after PEDOT growth into the sol-gel film. The results show that up to ca. 20% of these Fc-PAMAM units became electrochemically active, with high rates of electron transfer, when EDTM was conjugated to the Fc-PAMAM dendrimer.
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| 6. |
- Doherty, Walter J, et al.
(author)
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Electronic structure of Li-intercalated oligopyridines : A comparative study by photoelectron spectroscopy
- 2007
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In: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 126:9
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Journal article (peer-reviewed)abstract
- The role of nitrogen in the charge transfer and storage capacity of lithium-intercalated heterocyclic oligophenylenes was investigated using photoelectron spectroscopy. The development of new occupied states at low binding energies in the valence band region, as well as core level chemical shifts at both carbon and nitrogen sites, demonstrates partial charge transfer from lithium atoms to the organic component during formation of the intercalated compound. In small compounds, i.e., biphenyl and bipyridine derivatives, the position of the nitrogen heteroatom significantly affects the spacing between gap states in the Li-intercalated film, yet it has minimal effects on the charge storage capacity. In larger, branched systems, the presence of nitrogen in the aromatic system significantly enhances the charge storage capacity while the Li-N bond strength at high intercalation levels is significantly weakened relative to the nitrogen-free derivative. These observations have strong implications towards improved deintercalation processes in organic electrodes in lithium-ion batteries. © 2007 American Institute of Physics.
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| 7. |
- Doherty, Walter J, et al.
(author)
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Layer-by-layer deposition of copper phthalocyanine from aqueous solution : Molecular orientation, ordering parameters, and electronic structure
- 2007
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In: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 111:6, s. 2724-2729
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Journal article (peer-reviewed)abstract
- Highly ordered, multilayer films composed of alternating, oppositely charged, polyionic copper phthalocyanines were prepared on HOPG [0001] substrates via layer-by-layer deposition from aqueous solution and characterized by scanning force microscopy and photoelectron spectroscopies. In films of up to four layers, individual layers alternate. Angle-resolved ultraviolet photoelectron spectra are consistent with a molecular orientation parallel to the substrate surface and indicate that structural order is reduced with film thickness © 2007 American Chemical Society.
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| 8. |
- Doherty, Walter J, et al.
(author)
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Molecular ordering in monolayers of an alkyl-Substituted perylene-bisimide dye by attenuated total reflectance ultraviolet-visible spectroscopy
- 2005
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In: Applied Spectroscopy. - : SAGE Publications. - 0003-7028 .- 1943-3530. ; 59:10, s. 1248-1256
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Journal article (peer-reviewed)abstract
- Surface-relative orientational parameters were determined for monolayer films of N, N'-ditridecylperylenetetracarboxylic dianhydridediimide (C 13-PTCDI) in terms of the relative electronic transition dipole strengths, providing a three-dimensional view of the absorption dipole distribution. In order to obtain a macroscopically ordered film, C 13-PTCDI was deposited by (1) horizontal Langmuir-Blodgett (LB) transfer onto methyl- and phenyl-silanized glass, and (2) vapor deposition onto oriented films of poly(tetrafluoroethylene) (PTFE) on glass. Films of LB-deposited C13-PTCDI were found to be completely Isotropic prior to annealing. After annealing, these films remained isotropic in the plane of the substrate while the out-of-plane anisotropy was significantly enhanced. In contrast, films of C13-PTCDI vapor deposited onto oriented poly(tetrafluoroethylene) (PTFE)-modified substrates yielded films with a high degree of both in- and out-of-plane anisotropy. Atomic force microscopy (AFM) images of both the LB- and vapor-deposited films show substantial differences in film morphology and long-range order. These results demonstrate that molecular orientation in C13-PTCDI films can be controlled by varying substrate surface chemistry and post-deposition processing. © 2005 Society for Applied Spectroscopy.
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| 9. |
- Gorgoi, M, et al.
(author)
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The high kinetic energy photoelectron spectroscopy facility at BESSY progress and first results
- 2009
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 601:1-2, s. 48-53
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Journal article (peer-reviewed)abstract
- Photoelectron spectroscopy at high kinetic energy is a research field that receives an increasing interest due to the possibility of studying bulk properties of materials and deeply buried interfaces. Recently the high kinetic energy electron (HIKE) spectroscopy facility at BESSY in Berlin has become operative at the bending magnet beamline KMC-1. The first results show very good performance. Electron spectra have been recorded using X-ray energies from 2 keV up to 12 keV. Using back-scattering conditions in the crystal monochromator, very high-resolution has been achieved for photon energies around 2, 6 and 8 keV. In the latter case, spectra with a resolving power from the monochromator of >= 80 000 have been achieved and it has been possible to perform electron spectroscopy with resolving power of >= 60 000, yielding a total instrument resolution of about 150 meV as determined directly from spectra. This paper describes the facility and reports some of the first results. (C) 2009 Elsevier B.V. All rights reserved.
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| 10. |
- J Doherty, Walter, et al.
(author)
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Selective hydrogen bond disruption in adenine monolayer films by reaction with water
- 2009
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In: Journal of Electron Spectroscopy and Related Phenomena. - : Elsevier BV. - 0368-2048. ; 174:1-3, s. 107-109
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Journal article (peer-reviewed)abstract
- High-resolution X-ray photoelectron spectroscopy of two-dimensional films of adenine on a highly oriented pyrolitic graphite [0 0 0 1] surface reveal bonding changes induced by exposure to water. The hydrogen-bond interactions between adenine molecules were replaced by adenine-water hydrogen bonds in a stepwise pattern. This reaction destroyed the film network and changed the chemical state of the nitrogen sites. The reaction with water molecules affected both the donor and acceptor states of the oxygen atoms, as compared to those in water. (C) 2009 Elsevier B.V. All rights reserved.
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| 11. |
- Yim, Keng-Hoong, et al.
(author)
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Phase-Separated Thin Film Structures for Efficient Polymer Blend Light-Emitting Diodes
- 2010
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In: NANO LETTERS. - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 10:2, s. 385-392
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Journal article (peer-reviewed)abstract
- We report laterally and vertically phase-separated thin film structures in conjugated polymer blends created by polymer molecular weight variation. We find that micrometer-scale lateral phase separation is critical in achieving high initial device efficiency of light-emitting diodes, whereas improved balance of charge carrier mobilities and film thickness uniformity are important in maintaining high efficiency at high voltages. The optoelectronic properties of these blend thin films and devices are strongly influenced by the polymer chain order/disorder and the interface state formed at polymer/polymer heterojunctions.
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