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| 2. |
- Jiang, X., et al.
(författare)
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Shared heritability and functional enrichment across six solid cancers
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
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| 3. |
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| 4. |
- Stergiopoulou, Katerina, et al.
(författare)
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Mars Express Observations of Cold Plasma Structures in the Martian Magnetotail
- 2020
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Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 125:10
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Tidskriftsartikel (refereegranskat)abstract
- We present observations from five Mars Express (MEX) orbits in September 2016 while the spacecraft passed through the Martian induced magnetotail at altitudes up to 3,500 km. On these orbits, the Mars Advanced Radar for Subsurface and Ionosphere Sounding (MARSIS) instrument was operated in Active Ionospheric Sounding (AIS) mode at much higher altitude than normal, acting as a local sounder and detecting cold plasma structures in this region. In this paper we combine MARSIS tail measurements with solar wind data from the Solar Wind Ion Analyzer (SWIA) instrument and the Magnetometer (MAG) from Mars Atmosphere and Volatile EvolutioN (MAVEN) in order to investigate possible factors affecting plasma transport from the dayside and through the terminator. MARSIS observed structured cold ionospheric plasma along its trajectory, at all altitudes and solar zenith angles (SZAs). Isolated regions of cold plasma were also observed on each orbit as the spacecraft crossed the terminator, even at high altitudes. We conclude that the variability of plasma seen in the tail results from a multifactorial transport process, the development of which cannot be attributed to a sole parameter influencing it, despite the availability of simultaneous high quality solar wind measurements.
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| 5. |
- Vigorito, Elena, et al.
(författare)
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Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95% CI: 0.68 to 0.79, p-value 2x 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95% CI: 0.59 to 0.80, p-value 1.0 x 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.
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| 6. |
- Sanchez-Cano, Beatriz, et al.
(författare)
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Mars' Ionospheric Interaction With Comet C/2013 A1 Siding Spring's Coma at Their Closest Approach as Seen by Mars Express
- 2020
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Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 125:1
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Tidskriftsartikel (refereegranskat)abstract
- On 19 October 2014, Mars experienced a close encounter with Comet C/2013 A1 Siding Spring. Using data from the Mars Advanced Radar for Subsurface and Ionosphere Sounding (MARSIS) on board Mars Express (MEX), we assess the interaction of the Martian ionosphere with the comet's coma and possibly magnetic tail during the orbit of their closest approach. The topside ionospheric electron density profile is evaluated from the altitude of the peak density of the ionosphere up to the MEX altitude. We find complex and rapid variability in the ionospheric profile along the MEX orbit, not seen even after the impact of a large coronal mass ejection. Before closest approach, large electron density reductions predominate, which could be caused either by comet water damping or comet magnetic field interactions. After closest approach, a substantial electron density rise predominates. Moreover, several extra topside layers are visible along the whole orbit at different altitudes, which could be related to different processes as we discuss.
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| 7. |
- Lillis, Robert J., et al.
(författare)
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MOSAIC: A satellite constellation to enable groundbreaking mars climate system science and prepare for human exploration
- 2021
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Ingår i: Planetary Science Journal. - : Institute of Physics (IOP). - 2632-3338. ; 2:5
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Tidskriftsartikel (refereegranskat)abstract
- The Martian climate system has been revealed to rival the complexity of Earth's. Over the last 20 yr, a fragmented and incomplete picture has emerged of its structure and variability; we remain largely ignorant of many of the physical processes driving matter and energy flow between and within Mars' diverse climate domains. Mars Orbiters for Surface, Atmosphere, and Ionosphere Connections (MOSAIC) is a constellation of ten platforms focused on understanding these climate connections, with orbits and instruments tailored to observe the Martian climate system from three complementary perspectives. First, low-circular near-polar Sun-synchronous orbits (a large mothership and three smallsats spaced in local time) enable vertical profiling of wind, aerosols, water, and temperature, as well as mapping of surface and subsurface ice. Second, elliptical orbits sampling all of Mars' plasma regions enable multipoint measurements necessary to understand mass/energy transport and ion-driven escape, also enabling, with the polar orbiters, dense radio occultation coverage. Last, longitudinally spaced areostationary orbits enable synoptic views of the lower atmosphere necessary to understand global and mesoscale dynamics, global views of the hydrogen and oxygen exospheres, and upstream measurements of space weather conditions. MOSAIC will characterize climate system variability diurnally and seasonally, on meso-, regional, and global scales, targeting the shallow subsurface all the way out to the solar wind, making many first-of-their-kind measurements. Importantly, these measurements will also prepare for human exploration and habitation of Mars by providing water resource prospecting, operational forecasting of dust and radiation hazards, and ionospheric communication/positioning disruptions.
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| 8. |
- Sánchez-Cano, Beatriz, et al.
(författare)
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Mars’ plasma system. Scientific potential of coordinated multipoint missions : "The next generation"
- 2022
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Ingår i: Experimental astronomy. - : Springer. - 0922-6435 .- 1572-9508. ; 54, s. 641-676
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this White Paper, submitted to ESA’s Voyage 2050 call, is to get a more holistic knowledge of the dynamics of the Martian plasma system, from its surface up to the undisturbed solar wind outside of the induced magnetosphere. This can only be achieved with coordinated multi-point observations with high temporal resolution as they have the scientific potential to track the whole dynamics of the system (from small to large scales), and they constitute the next generation of the exploration of Mars analogous to what happened at Earth a few decades ago. This White Paper discusses the key science questions that are still open at Mars and how they could be addressed with coordinated multipoint missions. The main science questions are: (i) How does solar wind driving impact the dynamics of the magnetosphere and ionosphere? (ii) What is the structure and nature of the tail of Mars’ magnetosphere at all scales? (iii) How does the lower atmosphere couple to the upper atmosphere? (iv) Why should we have a permanent in-situ Space Weather monitor at Mars? Each science question is devoted to a specific plasma region, and includes several specific scientific objectives to study in the coming decades. In addition, two mission concepts are also proposed based on coordinated multi-point science from a constellation of orbiting and ground-based platforms, which focus on understanding and solving the current science gaps.
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| 9. |
- Schillings, Audrey, et al.
(författare)
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Signatures of wedgelets over Fennoscandia during the St Patrick s Day Storm 2015
- 2023
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Ingår i: Journal of Space Weather and Space Climate. - : EDP Sciences. - 2115-7251. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- During the long main phase of the St Patrick's Day storm on March 17, 2015, we found three separate enhancements of the westward electrojet. These enhancements are observed in the ionospheric equivalent currents computed using geomagnetic data over Fennoscandia. Using data from the IMAGE magnetometer network, we identified localised field-aligned current (FAC) systems superimposed on the pre-existing ionospheric current system. We suggest that these localised current systems are wedgelets and that they can potentially contribute to a larger-scale structure of a substorm current wedge (SCW). Each wedgelet is associated with a negative BX spike. Each spike is recorded at a higher latitude than the former one and all three are very localised over Fennoscandia. The first spike occurred at 17:34 UT and was observed at Lycksele, R rvik and Nurmij rvi, the second spike was recorded at 17:41 UT and located at Lycksele and R rvik, whereas the last spike occurred at 17:47 UT and was observed at Kevo and Abisko. Simultaneous optical auroral data and electron injections at the geosynchronous orbit indicate that one or more substorms took place in the polar ionosphere at the time of the wedgelets. This study demonstrates the occurrence of small and short-lived structures such as wedgelets at different locations over a short time scale, 15 min in this case.
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| 10. |
- Coronado, Liani, et al.
(författare)
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Positive selection pressure on E2 protein of classical swine fever virus drives variations in virulence, pathogenesis and antigenicity : implication for epidemiological surveillance in endemic areas
- 2019
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Ingår i: Transboundary and Emerging Diseases. - : Blackwell Verlag. - 1865-1674 .- 1865-1682. ; 66:6, s. 2362-2382
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Tidskriftsartikel (refereegranskat)abstract
- Classical swine fever (CSF), caused by CSF virus (CSFV), is considered one of the most important infectious diseases with devasting consequences for the pig industry. Recent reports describe the emergence of new CSFV-strains resulting from the action of positive selection pressure, due mainly to the bottleneck effect generated by ineffective vaccination. Even though a decrease in the genetic diversity of the positive selected CSFV-strains has been observed by several research groups, there is little information about the effect of this selective force on the virulence degree, antigenicity and pathogenicity of this type of strains. Hence, the aim of the current study was to determine the effect of the positive selection pressure on these three parameters of CSFV-strains, emerged as result of the bottleneck effects induced by unproper vaccination in a CSF-endemic area. Moreover, the effect of the positive selected strains on the epidemiological surveillance system was assessed. By the combination of in vitro, in vivo and immunoinformatic approaches we revealed that the action of the positive selection pressure induces a decrease in virulence and alteration in pathogenicity and antigenicity. However, we also noted that the evolutionary process of CSFV, especially in segregated microenvironments, could contribute to the gain-fitness event, restoring the highly virulent pattern of the circulating strains. Besides, we denoted that the presence of low virulent strains selected by bottleneck effect after inefficient vaccination can lead to a relevant challenge for the epidemiological surveillance of CSF, contributing to under-reports of the disease, favoring the perpetuation of the virus in the field. In this study B-cell and CTL epitopes on the E2 3D-structure model were also identified. Thus, the current study provides novel and significant insights into variation in virulence, pathogenesis and antigenicity experienced by CSFV strains after the positive selection pressure effect.
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