| 1. |
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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Couch, Fergus J., et al.
(författare)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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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.
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| 4. |
- 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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| 5. |
- Hamdi, Yosr, et al.
(författare)
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Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3
- 2017
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 161:1, s. 117-134
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
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| 6. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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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.
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| 7. |
- Osorio, Ana, et al.
(författare)
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DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7×10-3) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8×10-3). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
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| 8. |
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| 9. |
- Womersley, Freya C., et al.
(författare)
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Identifying priority sites for whale shark ship collision management globally
- 2024
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Ingår i: SCIENCE OF THE TOTAL ENVIRONMENT. - 0048-9697 .- 1879-1026. ; 934
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Tidskriftsartikel (refereegranskat)abstract
- The expansion of the world 's merchant fleet poses a great threat to the ocean 's biodiversity. Collisions between ships and marine megafauna can have population-level consequences for vulnerable species. The Endangered whale shark ( Rhincodon typus ) shares a circumglobal distribution with this expanding fleet and tracking of movement pathways has shown that large vessel collisions pose a major threat to the species. However, it is not yet known whether they are also at risk within aggregation sites, where up to 400 individuals can gather to feed on seasonal bursts of planktonic productivity. These "constellation " sites are of significant ecological, socioeconomic and cultural value. Here, through expert elicitation, we gathered information from most known constellation sites for this species across the world ( >50 constellations and >13,000 individual whale sharks). We defined the spatial boundaries of these sites and their overlap with shipping traffic. Sites were then ranked based on relative levels of potential collision danger posed to whale sharks in the area. Our results showed that researchers and resource managers may underestimate the threat posed by large ship collisions due to a lack of direct evidence, such as injuries or witness accounts, which are available for other, sub-lethal threat categories. We found that constellations in the Arabian Sea and adjacent waters, the Gulf of Mexico, the Gulf of California, and Southeast and East Asia, had the greatest level of collision threat. We also identified 39 sites where peaks in shipping activity coincided with peak seasonal occurrences of whale sharks, sometimes across several months. Simulated collision mitigation options estimated potentially minimal impact to industry, as most whale shark core habitat areas were small. Given the threat posed by vessel collisions, a coordinated, multi-national approach to mitigation is needed within priority whale shark habitats to ensure collision protection for the species.
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| 10. |
- Borälv, Eva
(författare)
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Substorm Features in the High-Latitude Ionosphere and Magnetosphere : Multi-Instrument Observations
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The space around Earth, confined in the terrestrial magnetosphere, is to some extent shielded from the Sun's solar wind plasma and magnetic field. During certain conditions, however, strong interaction can occur between the solar wind and the magnetosphere, resulting in magnetospheric activity of several forms, among which substorms and storms are the most prominent. A general framework for how these processes work have been outlayed through the history of research, however, there still remain questions to be answered. The most striking example regards the onset of substorms, where both the onset cause and location in the magnetosphere/ionosphere are still debated. These are clearly not easily solved problems, since a substorm is a global process, ideally requiring simultaneous measurements in the magnetotail and ionosphere. Investigated in this work are temporal and spatial scales for substorm and convection processes in the Earth's magnetosphere and ionosphere. This is performed by combining observations from a number of both ground-based and spacecraft-borne instruments. The observations indicate that the magnetotail's cross-section is involved to a larger spatial extent than previously considered in the substorm process. Furthermore, convection changes result in topological changes of the magnetosphere on a fast time scale. The results show that the magnetosphere is, on a global magnetospheric scale, highly dynamic during convection changes and ensuing substorms.
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| 11. |
- Candido-dos-Reis, Francisco J, et al.
(författare)
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Germline mutation in BRCA1 or BRCA2 and ten-year survival for women diagnosed with epithelial ovarian cancer
- 2015
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 21:3, s. 7-652
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To analyze the effect of germline mutations in BRCA1 and BRCA2 on mortality in patients with ovarian cancer up to 10 years after diagnosis.EXPERIMENTAL DESIGN: We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analyzed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analyzed using Fine and Gray model.RESULTS: The combined 10-year overall survival rate was 30% [95% confidence interval (CI), 28%-31%] for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The HR for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the HR was 0.42 at time zero and increased over time (predicted to become greater than 1 at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors and to ovarian cancer-specific mortality.CONCLUSIONS: BRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/2 mutation carriers.
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| 12. |
- Gusarova, Viktoria, et al.
(författare)
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Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85-0.92, p = 6.3 × 10-10), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49-0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D.
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| 13. |
- Holmström, Mats, et al.
(författare)
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Future opportunities in solar system plasma science through ESA's exploration programme
- 2024
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Ingår i: npj Microgravity. - : Springer Nature. - 2373-8065. ; 10:1
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Forskningsöversikt (refereegranskat)abstract
- The solar wind interacts with all solar system bodies, inducing different types of dynamics depending on their atmospheric and magnetic environments. We here outline some key open scientific questions related to this interaction, with a focus on the Moon and Mars, that may be addressed by future Mars and Moon missions by the European Space Agency's Human and Robotic Exploration programme. We describe possible studies of plasma interactions with bodies with and without an atmosphere, using multi-point and remote measurements, and energetic particle observations, as well as recommend some actions to take.
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| 14. |
- Kastinen, Daniel, et al.
(författare)
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Resolving the ambiguous direction of arrival of weak meteor radar trail echoes
- 2021
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 14:5, s. 3583-3596
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Tidskriftsartikel (refereegranskat)abstract
- Meteor phenomena cause ionized plasmas that can be roughly divided into two distinctly different regimes: a dense and transient plasma region co-moving with the ablating meteoroid and a trail of diffusing plasma left in the atmosphere and moving with the neutral wind. Interferometric radar systems are used to observe the meteor trails and determine their positions and drift velocities. Depending on the spatial configuration of the receiving antennas and their individual gain patterns, the voltage response can be the same for several different plane wave directions of arrival (DOAs), thereby making it impossible to determine the correct direction. A low signal-to-noise ratio (SNR) can create the same effect probabilistically even if the system contains no theoretical ambiguities. Such is the case for the standard meteor trail echo data products of the Sodankyl Geophysical Observatory SKiYMET all-sky interferometric meteor radar. Meteor trails drift slowly enough in the atmosphere and allow for temporal integration, while meteor head echo targets move too fast. Temporal integration is a common method to increase the SNR of radar signals. For meteor head echoes, we instead propose to use direct Monte Carlo (DMC) simulations to validate DOA measurements. We have implemented two separate temporal integration methods and applied them to 2222 events measured by the Sodankyl meteor radar to simultaneously test the usefulness of such DMC simulations on cases where temporal integration is possible, validate the temporal integration methods, and resolve the ambiguous SKiYMET data products. The two methods are the temporal integration of the signal spatial correlations and matchedfilter integration of the individual radar channel signals. The results are compared to Bayesian inference using the DMC simulations and the standard SkiYMET data products. In the examined data set, 13% of the events were indicated as ambiguous. Out of these, 13% contained anomalous signals. In 95% of all ambiguous cases with a nominal signal, the three methods found one and the same output DOA, which was also listed as one of the ambiguous possibilities in the SkiYMET analysis. In all unambiguous cases, the results from all methods concurred.
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| 15. |
- Lester, Mark, et al.
(författare)
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The Impact of Energetic Particles on the Martian Ionosphere During a Full Solar Cycle of Radar Observations: Radar Blackouts
- 2022
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Ingår i: Journal of Geophysical Research - Space Physics. - : John Wiley & Sons. - 2169-9380 .- 2169-9402. ; 127:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the first long-term characterization of ionization layers in the lower ionosphere of Mars (below ∼90 km), a region inaccessible to orbital in-situ observations, based on an analysis of radar echo blackouts observed on Mars Express and the Mars Reconnaissance Orbiter from 2006 to 2017. A blackout occurs when the expected surface reflection is partly or totally attenuated for portions of an observation. Enhanced ionization at altitudes of 60–90 km, below the main ionospheric electron density peak, leads to increased absorption of the radar signal, resulting in the blackouts. We find that (a) MARSIS, operating at frequencies between 1.8 and 5 MHz, suffered more blackouts than SHARAD, which has a higher carrier frequency (20 MHz), (b) there is a clear correlation of blackout occurrence with solar cycle, (c) there is no apparent relationship between blackout occurrence and crustal magnetic fields, and (d) blackouts occur during both nightside and dayside observations, although the peak occurrence is deep on the nightside. Analysis of Mars Atmosphere and Volatile EvolutioN Solar Energetic Particle electron counts between 20 and 200 keV demonstrates that these electrons are likely responsible for attenuating the radar signals. We investigate the minimum SEP electron fluxes required to ionize the lower atmosphere and produce measurable attenuation. When both radars experience a blackout, the SEP electron fluxes are at their highest. Based on several case studies, we find that the average SEP spectrum responsible for a blackout is particularly enhanced at its higher energy end, that is, above 70 keV.
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| 16. |
- 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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| 17. |
- Lindblad-Toh, Kerstin, et al.
(författare)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Tidskriftsartikel (refereegranskat)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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| 18. |
- Liu, William, et al.
(författare)
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Scientific challenges and instrumentation for the International Meridian Circle Program
- 2021
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Ingår i: Science China. Earth Sciences. - : Springer. - 1674-7313 .- 1869-1897. ; 64:12, s. 2090-2097
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Tidskriftsartikel (refereegranskat)abstract
- Earth’s ecosystems and human activities are threatened by a broad spectrum of hazards of major importance for the safety of ground infrastructures, space systems and space flight: solar activity, earthquakes, atmospheric and climatic disturbances, changes in the geomagnetic field, fluctuations of the global electric circuit. Monitoring and understanding these major hazards to better predict and mitigate their effects is one of the greatest scientific and operational challenges of the 21st century. Though diverse, these hazards share one feature in common: they all leave their characteristic imprints on a critical layer of the Earth’s environment: its ionosphere, middle and upper atmosphere (IMUA). The objective of the International Meridian Circle Program (IMCP), a major international program led by the Chines Academy of Sciences (CAS), is to deploy, integrate and operate a global network of research and monitoring instruments to use the IMUA as a screen on which to detect these imprints. In this article, we first show that the geometry required for the IMCP global observation system leads to a deployment of instruments in priority along the 120°E–60°W great meridian circle, which will cover in an optimal way both the dominant geographic and geomagnetic latitude variations, possibly complemented by a second Great Circle along the 30°E–150°W meridians to capture longitude variations. Then, starting from the Chinese Meridian Project (CMP) network and using it as a template, we give a preliminary and promising description of the instruments to be integrated and deployed along the 120°E–60° W great circle running across China, Australia and the Americas.
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| 19. |
- Opgenoorth, Hermann J., et al.
(författare)
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Assessment and recommendations for a consolidated European approach to space weather - as part of a global space weather effort
- 2019
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Ingår i: Journal of Space Weather and Space Climate. - : EDP Sciences. - 2115-7251. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Over the last 10-20 years there has been an ever-increasing international awareness of risks to modern society from adverse and potentially harmful - and in extreme cases even disastrous - space weather events. Many individual countries and even international organisations like the United Nations (UN) have begun to increase their activities in preparing for and mitigating effects of adverse space weather. As in the rest of the world there is also in Europe an urgent need for coordination of Space Weather efforts in individual countries as well as in and among European organisations such as the European Space Agency (ESA) and the European Union (EU). This coordination should not only improve our ability to meet space weather risks, but also enable Europe to contribute to on-going global space weather efforts. While space weather is a global threat, which needs a global response, it also requires tailored regional and trans-regional responses that require coordination at all levels. Commissioned by the European Space Science Committee (ESSC) of the European Science Foundation, the authors - together with ex-officio advice from ESA and the EU - have over two years assessed European activities in the realm of space weather and formulated a set of recommendations to ESA, the EU and their respective member states, about how to prepare Europe for the increasing impact of adverse space weather effects on man-made infrastructure and our society as a whole. We have also analysed parallel international activities worldwide, and we give advice how Europe could incorporate its future activities into a global scheme.
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| 20. |
- Rebbeck, Timothy R., et al.
(författare)
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Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women
- 2016
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18:1
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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.
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| 21. |
- 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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| 22. |
- 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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| 23. |
- Sanchez-Cano, Beatriz, et al.
(författare)
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Origin of the Extended Mars Radar Blackout of September 2017
- 2019
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Ingår i: Journal of Geophysical Research - Space Physics. - : AMER GEOPHYSICAL UNION. - 2169-9380 .- 2169-9402. ; 124:6, s. 4556-4568
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Tidskriftsartikel (refereegranskat)abstract
- The Mars Advanced Radar for Subsurface and Ionosphere Sounding (MARSIS) onboard Mars Express, which operates between 0.1 and 5.5 MHz, suffered from a complete blackout for 10 days in September 2017 when observing on the nightside (a rare occurrence). Moreover, the Shallow Radar (SHARAD) onboard the Mars Reconnaissance Orbiter, which operates at 20 MHz, also suffered a blackout for three days when operating on both dayside and nightside. We propose that these blackouts are caused by solar energetic particles of few tens of keV and above associated with an extreme space weather event between 10 and 22 September 2017, as recorded by the Mars Atmosphere and Volatile EvolutioN (MAVEN) mission. Numerical simulations of energetic electron precipitation predict that a lower O-2(+) nighttime ionospheric layer of magnitude similar to 10(10) m(-3) peaking at similar to 90-km altitude is produced. Consequently, such a layer would absorb radar signals at high frequencies and explain the blackouts. The peak absorption level is found to be at 70-km altitude. Plain Language Summary Several instrument operations, as well as communication systems with rovers at the surface, depend on radio signals that propagate throughout the atmosphere of Mars. This is the case also for two radars that are currently working in Mars' orbit, sounding the ionosphere, surface, and subsurface of the planet. In mid-September 2017, a powerful solar storm hit Mars, producing a large amount of energetic particle precipitation over a 10-day period. We have found that high-energy electrons ionized the atmosphere of Mars, creating a dense layer of ions and electrons at similar to 90 km on the Martian nightside. This layer attenuated radar signals continuously for 10 days, stopping the radars to receive any signal from the planetary surface. In this work, we assess the properties of this layer in order to understand the implications of this kind of phenomenon for radar performance and communications.
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| 24. |
- Sánchez-Cano, Beatriz, et al.
(författare)
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Solar Energetic Particle Events Detected in the Housekeeping Data of the European Space Agency's Spacecraft Flotilla in the Solar System
- 2023
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Ingår i: Space Weather. - : American Geophysical Union (AGU). - 1542-7390. ; 21:8
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Tidskriftsartikel (refereegranskat)abstract
- Despite the growing importance of planetary Space Weather forecasting and radiation protection for science and robotic exploration and the need for accurate Space Weather monitoring and predictions, only a limited number of spacecraft have dedicated instrumentation for this purpose. However, every spacecraft (planetary or astronomical) has hundreds of housekeeping sensors distributed across the spacecraft, some of which can be useful to detect radiation hazards produced by solar particle events. In particular, energetic particles that impact detectors and subsystems on a spacecraft can be identified by certain housekeeping sensors, such as the Error Detection and Correction (EDAC) memory counters, and their effects can be assessed. These counters typically have a sudden large increase in a short time in their error counts that generally match the arrival of energetic particles to the spacecraft. We investigate these engineering datasets for scientific purposes and perform a feasibility study of solar energetic particle event detections using EDAC counters from seven European Space Agency Solar System missions: Venus Express, Mars Express, ExoMars-Trace Gas Orbiter, Rosetta, BepiColombo, Solar Orbiter, and Gaia. Six cases studies, in which the same event was observed by different missions at different locations in the inner Solar System are analyzed. The results of this study show how engineering sensors, for example, EDAC counters, can be used to infer information about the solar particle environment at each spacecraft location. Therefore, we demonstrate the potential of the various EDAC to provide a network of solar particle detections at locations where no scientific observations of this kind are available.
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| 25. |
- 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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