| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
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| 3. |
- Menden, MP, et al.
(författare)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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| 4. |
- Cruz, Raquel, et al.
(författare)
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Novel genes and sex differences in COVID-19 severity
- 2022
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
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Tidskriftsartikel (refereegranskat)abstract
- Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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| 6. |
- Simancas, J.F., et al.
(författare)
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The seismic crustal structure of the Ossa-Morena Zone and its geological interpretation
- 2004
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Ingår i: Journal of Iberian Geology. - 1698-6180 .- 1886-7995. ; 30, s. 133-142
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Tidskriftsartikel (refereegranskat)abstract
- The IBERSEIS deep reflection seismic experiment has provided a crustal image of the Variscan orogen of southwest Iberia. A brief presentation of the entire seismic profile is given, and then the Ossa-Morena Zone (OMZ) and its boundaries are considered. The crust of the OMZ is shown to be divided into an upper crust, characterized by dominantly NE-dipping reflectivity, and a poorly reflective lower crust. The reflectivity of the upper crust has good correlation with the geological cross-section constructed from surface mapping. In the seismic image, the upper crustal geological structures are seen to merge in the middle crust. Nevertheless, the OMZ middle crust is not a mere detachment level, as it shows very unusual features: it appears as a band of strong reflectivity and irregular thickness (the Iberian Reflective Body, IRB) that we interpret as a great sill-like intrusion of basic rocks. The boundaries of the OMZ are considered sutures of the orogen, and their geometrical features, as deduced from geological mapping and the seismic image, are in accordance with the transpressional character of the Variscan collision recorded in SW Iberia. The present Moho is flat, obliterating the root of the orogen.
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| 9. |
- Miliucci, M., et al.
(författare)
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Kaonic Deuterium Precision Measurement at DA Φ NE : The SIDDHARTA-2 Experiment
- 2020
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Ingår i: Recent Progress in Few-Body Physics : Proceedings of the 22nd International Conference on Few-Body Problems in Physics, FB22 2018 - Proceedings of the 22nd International Conference on Few-Body Problems in Physics, FB22 2018. - Cham : Springer International Publishing. - 0930-8989 .- 1867-4941. - 9783030323578 - 9783030323561 ; 238, s. 965-969
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Bokkapitel (refereegranskat)abstract
- Light kaonic atoms spectroscopy offers the unique opportunity to perform experiments equivalent to scattering at vanishing relative energies. This allows the determination of the antikaon-nucleus interaction at threshold, without the need of extrapolation to zero energy, as in the case of scattering experiments. In this framework, the SIDDHARTA-2 collaboration aims to perform the first measurement of kaonic deuterium transition to the fundamental level, which is mandatory to extract the isospin dependent antikaon—nucleon scattering lengths. The experiment will be carried out at the DA(formula presented)NE collider of LNF-INFN in 2019–2020.
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| 10. |
- Carbonell, R., et al.
(författare)
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Geophysical Evidence of a Mantle Plume Derived Intrusion Complex
- 2004
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 31, s. L11601-
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Deep seismic reflection data acquired as part of the SW-Iberia EUROPROBE project across the transpressional Variscan orogen sample three tectonic terranes: the South Portuguese Zone, the Ossa-Morena Zone, and the Central Iberian Zone. The seismic data reveal the existence of a mid-crustal reflective body 140 km long and of variable thickness (up to 5 km), the Iberian Reflective body. The conductivity image provided by coincident MT soundings, the amplitude characteristics of the seismics, mineralization studies related to magmatic ore deposits, and the surface geology suggest that the IRB is a mantle-derived mafic intrusion. The geophysical, geological and petrological data suggest that the IRB is most probably an Early Carboniferous (approximately at 350–340 Ma) mantle-derived intrusion possibly linked to plume activity that took place in Europe in the Carboniferous and Permian.
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