| 1. |
- Couch, Fergus J., et al.
(författare)
-
Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
-
Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
-
Tidskriftsartikel (refereegranskat)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
|
|
| 2. |
- Friebel, Daniel, et al.
(författare)
-
In situ x-ray probing reveals the importance of surface platinum oxide formation in fuel cell catalysis
- 2011
-
Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 13:1, s. 262-266
-
Tidskriftsartikel (refereegranskat)abstract
- In situ X-ray absorption spectroscopy (XAS) at the Pt L3 edge is a useful probe for Pt–O interactions at polymer electrolyte membrane fuel cell (PEMFC) cathodes. We show that XAS using the high energy resolution fluorescence detection (HERFD) mode, applied to a well-defined monolayer Pt/Rh(111) sample where the bulk penetrating hard X-rays probe only surface Pt atoms, provides a unique sensitivity to structure and chemical bonding at the Pt-electrolyte interface. Ab initio multiple-scattering calculations using the FEFF code and complementary extended X-ray absorption fine structure (EXAFS) results indicate that the commonly observed large increase of the white-line at high electrochemical potentials on PEMFC cathodes originates from platinum oxide formation, whereas previously proposed chemisorbed oxygen-containing species merely give rise to subtle spectral changes.
|
|
| 3. |
- Hollestelle, Antoinette, et al.
(författare)
-
No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
-
Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
|
|
| 4. |
- Öberg, Henrik, et al.
(författare)
-
Stability of Pt-Modified Cu(111) in the Presence of Oxygen and Its Implication on the Overall Electronic Structure
- 2013
-
Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 117:32, s. 16371-16380
-
Tidskriftsartikel (refereegranskat)abstract
- The electronic structure and stability of Cu(111)-hosted Pt overlayers with and without the presence of atomic oxygen have been studied by means of core-level spectroscopy and density functional theory (DFT). Because of lattice mismatch, Pt(111) overlayers grown on Cu(111) are compressively strained, and hard X-ray photoelectron spectroscopy together with Pt L-3-edge X-ray absorption spectroscopy (XAS) reveals a pronounced downshift of the Pt d-band owing to the increased overlap of the d-orbitals, an effect also reproduced theoretically. Exposure to oxygen severely alters the surface composition; the O-Cu binding energy largely exceeds that of O-Pt, and DFT calculations predict surface segregation of Cu atoms. Comparing the adsorbate electronic structure for O on unstrained Pt(111) with that of O on Pt-modified Cu(111) using O K-edge XAS and X-ray emission spectroscopy salient differences are observed and calculations show that Cu-segregation to the topmost layer is required to reproduce the measured spectra. It is proposed that O is binding in a hollow site constituted by at least two Cu atoms and that up to 75% of the Pt atoms migrate below the surface.
|
|
| 5. |
- Eilert, André, et al.
(författare)
-
Formation of Copper Catalysts for CO2 Reduction with High Ethylene/Methane Product Ratio Investigated with In Situ X-ray Absorption Spectroscopy
- 2016
-
Ingår i: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 7:8, s. 1466-1470
-
Tidskriftsartikel (refereegranskat)abstract
- Nanostructured copper cathodes are among the most efficient and selective catalysts to date for making multicarbon products from the electrochemical carbon dioxide reduction reaction (CO2RR). We report an in situ X-ray absorption spectroscopy investigation of the formation of a copper nanocube CO2RR catalyst with high activity that highly favors ethylene over methane production. The results show that the precursor for the copper nanocube formation is copper(I)-oxide, not copper(I)-chloride as previously assumed. A second route to an electrochemically similar material via a copper(II)-carbonate/hydroxide is also reported. This study highlights the importance of using oxidized copper precursors for constructing selective CO2 reduction catalysts and shows the precursor oxidation state does not affect the electrocatalyst selectivity toward ethylene formation.
|
|
| 6. |
- Eilert, André, et al.
(författare)
-
Subsurface Oxygen in Oxide-Derived Copper Electrocatalysts for Carbon Dioxide Reduction
- 2017
-
Ingår i: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 8:1, s. 285-290
-
Tidskriftsartikel (refereegranskat)abstract
- Copper electrocatalysts derived from an oxide have shown extraordinary electrochemical properties for the carbon dioxide reduction reaction (CO2RR). Using in situ ambient pressure X-ray photoelectron spectroscopy and quasi in situ electron energy loss spectroscopy in a transmission electron microscope, we show that there is a substantial amount of residual oxygen in nanostructured, oxide-derived copper electrocatalysts but no residual copper oxide. On the basis of these findings in combination with density functional theory simulations, we propose that residual subsurface oxygen changes the electronic structure of the catalyst and creates sites with higher carbon monoxide binding energy. If such sites are stable under the strongly reducing conditions found in CO2RR, these findings would explain the high efficiencies of oxide-derived copper in reducing carbon dioxide to multicarbon compounds such as ethylene.
|
|
| 7. |
- Pedersen, Anders F., et al.
(författare)
-
Operando XAS Study of the Surface Oxidation State on a Monolayer IrOx, on RuOx and Ru Oxide Based Nanoparticles for Oxygen Evolution in Acidic Media
- 2018
-
Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 122:2, s. 878-887
-
Tidskriftsartikel (refereegranskat)abstract
- Herein we present surface sensitive operando XAS L-edge measurements on IrOx/RuO2 thin films as well as mass-selected RuOx and Ru nanoparticles. We observed shifts of the white line XAS peak toward higher energies with applied electrochemical potential. Apart from the case of the metallic Ru nanoparticles, the observed potential dependencies were purely core-level shifts caused by a change in oxidation state, which indicates no structural changes. These findings can be explained by different binding energies of oxygenated species on the surface of IrOx and RuOx. Simulated XAS spectra show that the average Ir oxidation state change is strongly affected by the coverage of atomic O. The observed shifts in oxidation state suggest that the surface has a high coverage of O at potentials just below the potential where oxygen evolution is exergonic in free energy. This observation is consistent with the notion that the metal-oxygen bond is stronger than ideal.
|
|
| 8. |
- Rebbeck, Timothy R., et al.
(författare)
-
Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women
- 2016
-
Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood. Methods: From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2. Results: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive (p = 0.010) or progesterone receptor (PR) positive (p = 0.013) than in SH1, but less likely to be ER positive (p < 0.001) or PR positive (p = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for BRCA1 or BRCA2 in either BC or OC. Conclusions: Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2.
|
|
