| 1. |
- Ahearn, Thomas U., et al.
(författare)
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Common variants in breast cancer risk loci predispose to distinct tumor subtypes
- 2022
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Ingår i: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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| 2. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 3. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 4. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 5. |
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| 6. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 7. |
- Moosmann, Julian, et al.
(författare)
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A load frame for in situ tomography at PETRA III
- 2019
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Ingår i: Developments in X-Ray Tomography XII. - : SPIE. - 0277-786X .- 1996-756X. - 9781510629196 ; 11113
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- A load frame for in situ mechanical testing is developed for the microtomography end stations at the imaging beamline P05 and the high-energy material science beamline P07 of PETRA III at DESY, both operated by the Helmholtz- Zentrum Geesthacht. The load frame is fully integrated into the beamline control system and can be controlled via a feedback loop. All relevant parameters (load, displacement, temperature, etc.) are continuously logged. It can be operated in compression or tensile mode applying forces of up to 1 kN and is compatible with all contrast modalities available at IBL and HEMS i.e. conventional attenuation contrast, propagation based phase contrast and differential phase contrast using a grating interferometer. The modularity and flexibility of the load frame allows conducting a wide range of experiments. E.g. compression tests to understand the failure mechanisms in biodegradable implants in rat bone or to investigate the mechanics and kinematics of the tessellated cartilage skeleton of sharks and rays, or tensile tests to illuminate the structure-property relationship in poplar tension wood or to visualize the 3D deformation of the tendonbone insertion. We present recent results from the experiments described including machine-learning driven volume segmentation and digital volume correlation of load tomography sequences.
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| 8. |
- Moosmann, Julian, et al.
(författare)
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Biodegradable magnesium-based implants in bone studied by synchrotron radiation microtomography
- 2017
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Ingår i: Developments in X-Ray Tomography XI. - : SPIE - International Society for Optical Engineering. ; 10391
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Konferensbidrag (refereegranskat)abstract
- Permanent implants made of titanium or its alloys are the gold standard in many orthopedic and traumatological applications due to their good biocompatibility and mechanical properties. However, a second surgical intervention is required for this kind of implants as they have to be removed in the case of children that are still growing or on patient's demand. Therefore, magnesium-based implants are considered for medical applications as they are degraded under physiological conditions. The major challenge is tailoring the degradation in a manner that is suitable for a biological environment and such that stabilization of the bone is provided for a controlled period. In order to understand failure mechanisms of magnesium-based implants in orthopedic applications and, further, to better understand the osseointegration, screw implants in bone are studied under mechanical load by means of a push-out device installed at the imaging beamline P05 of PETRA III at DESY. Conventional absorption contrast microtomography and phasecontrast techniques are applied in order to monitor the bone-to-implant interface under increasing load conditions. In this proof-of-concept study, first results from an in situ push-out experiment are presented.
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| 9. |
- Peruzzi, Niccolò, et al.
(författare)
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Multimodal ex vivo methods reveal that Gd-rich corrosion byproducts remain at the implant site of biodegradable Mg-Gd screws
- 2021
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Ingår i: Acta Biomaterialia. - : Elsevier. - 1742-7061 .- 1878-7568. ; 136, s. 582-591
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Tidskriftsartikel (refereegranskat)abstract
- Extensive research is being conducted on magnesium (Mg) alloys for bone implant manufacturing, due to their biocompatibility, biodegradability and mechanical properties. Gadolinium (Gd) is among the most promising alloying elements for property control in Mg alloy implants; however, its toxicity is controversial. Investigating Gd behavior during implant corrosion is thus of utmost importance. In this study, we analyzed the degradation byproducts at the implant site of biodegradable Mg-5Gd and Mg-10Gd implants after 12 weeks healing time, using a combination of different imaging techniques: histology, energy-dispersive x-ray spectroscopy (EDX), x-ray microcomputed tomography (µCT) and neutron µCT. The main finding has been that, at the healing time in exam, the corrosion appears to have involved only the Mg component, which has been substituted by calcium and phosphorus, while the Gd remains localized at the implant site. This was observed in 2D by means of EDX maps and extended to 3D with a novel application of neutron tomography. X-ray fluorescence analysis of the main excretory organs also did not reveal any measurable accumulation of Gd, further reinforcing the conclusion that very limited or no removal at all of Gd-alloy happened during degradation.
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| 10. |
- Willumeit-Römer, Regine, et al.
(författare)
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Visualization of Implant Failure by Synchrotron Tomography
- 2018
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Ingår i: TMS 2018 147th Annual Meeting & Exhibition Supplemental Proceedings. - Cham : Springer. - 9783319725253 - 9783319725260 ; , s. 275-284
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Konferensbidrag (refereegranskat)abstract
- Magnesium (Mg) and its alloys degrade under physiological conditions. But how strong is the connection between the implant, the corrosion layer and the surrounding tissue, namely bone? Biomechanical tests like push-out tests have shown that a degraded Mg-pin is surprisingly well integrated with the bone “as reported by Castellani et al. (Acta Biomater 7(1):432–440, 2011) [1]”. High-resolution synchrotron tomography offers a deep look into the microstructure of the material as well as of the bone during deformation until fracture happens. Here we present first data from an in situ tomography experiment of a biodegradable Mg-based implant under compressive load showing how Mg implants are incorporated into bone.
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