| 1. |
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| 2. |
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| 3. |
- Ramdas, S., et al.
(författare)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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| 4. |
- Adcox, K, et al.
(författare)
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PHENIX detector overview
- 2003
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 499:2-3, s. 469-479
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Tidskriftsartikel (refereegranskat)abstract
- The PHENIX detector is designed to perform a broad study of A-A, p-A, and p-p collisions to investigate nuclear matter under extreme conditions. A wide variety of probes, sensitive to all timescales, are used to study systematic variations with species and energy as well as to measure the spin structure of the nucleon. Designing for the needs of the heavy-ion and polarized-proton programs has produced a detector with unparalleled capabilities. PHENIX measures electron and muon pairs, photons, and hadrons with excellent energy and momentum resolution. The detector consists of a large number of subsystems that are discussed in other papers in this volume. The overall design parameters of the detector are presented. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 5. |
- Bouyoucef, S E, et al.
(författare)
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Poster Session 2 : Monday 4 May 2015, 08
- 2015
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Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
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Tidskriftsartikel (refereegranskat)
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| 6. |
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| 7. |
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| 8. |
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 13. |
- Sugita, S., et al.
(författare)
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The geomorphology, color, and thermal properties of Ryugu: Implications for parent-body processes
- 2019
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Ingår i: Science. - : AAAS. - 0036-8075 .- 1095-9203. ; 364:6437
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Tidskriftsartikel (refereegranskat)abstract
- Asteroids fall to Earth in the form of meteorites, but these provide little information about their origins. The Japanese mission Hayabusa2 is designed to collect samples directly from the surface of an asteroid and return them to Earth for laboratory analysis. Three papers in this issue describe the Hayabusa2 team's study of the near-Earth carbonaceous asteroid 162173 Ryugu, at which the spacecraft arrived in June 2018 (see the Perspective by Wurm). Watanabeet al.measured the asteroid's mass, shape, and density, showing that it is a “rubble pile” of loose rocks, formed into a spinning-top shape during a prior period of rapid spin. They also identified suitable landing sites for sample collection. Kitazatoet al.used near-infrared spectroscopy to find ubiquitous hydrated minerals on the surface and compared Ryugu with known types of carbonaceous meteorite. Sugitaet al.describe Ryugu's geological features and surface colors and combined results from all three papers to constrain the asteroid's formation process. Ryugu probably formed by reaccumulation of rubble ejected by impact from a larger asteroid. These results provide necessary context to understand the samples collected by Hayabusa2, which are expected to arrive on Earth in December 2020.Science, this issue p.268, p.272, p.eaaw0422; see also p.230
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| 14. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 15. |
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| 16. |
- Sakatani, N., et al.
(författare)
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Anomalously porous boulders on (162173) Ryugu as primordial materials from its parent body
- 2021
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Ingår i: Nature Astronomy. - : Springer Nature. - 2397-3366. ; 5:8, s. 766-774
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Tidskriftsartikel (refereegranskat)abstract
- Planetesimals—the initial stage of the planetary formation process—are considered to be initially very porous aggregates of dusts1,2, and subsequent thermal and compaction processes reduce their porosity3. The Hayabusa2 spacecraft found that boulders on the surface of asteroid (162173) Ryugu have an average porosity of 30–50% (refs. 4,5,6), higher than meteorites but lower than cometary nuclei7, which are considered to be remnants of the original planetesimals8. Here, using high-resolution thermal and optical imaging of Ryugu’s surface, we discovered, on the floor of fresh small craters (<20 m in diameter), boulders with reflectance (~0.015) lower than the Ryugu average6 and porosity >70%, which is as high as in cometary bodies. The artificial crater formed by Hayabusa2’s impact experiment9 is similar to these craters in size but does not have such high-porosity boulders. Thus, we argue that the observed high porosity is intrinsic and not created by subsequent impact comminution and/or cracking. We propose that these boulders are the least processed material on Ryugu and represent remnants of porous planetesimals that did not undergo a high degree of heating and compaction3. Our multi-instrumental analysis suggests that fragments of the highly porous boulders are mixed within the surface regolith globally, implying that they might be captured within collected samples by touch-down operations10,11.
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| 17. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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| 18. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 19. |
- Fadanelli, S., et al.
(författare)
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Four-Spacecraft Measurements of the Shape and Dimensionality of Magnetic Structures in the Near-Earth Plasma Environment
- 2019
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Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 124:8, s. 6850-6868
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Tidskriftsartikel (refereegranskat)abstract
- We present a new method for determining the main relevant features of the local magnetic field configuration, based entirely on the knowledge of the magnetic field gradient four‐spacecraft measurements. The method, named “magnetic configuration analysis” (MCA), estimates the spatial scales on which the magnetic field varies locally. While it directly derives from the well‐known magnetic directional derivative and magnetic rotational analysis procedures (Shi et al., 2005, htpps://doi.org/10.1029/2005GL022454; Shen et al., 2007, https://doi.org/10.1029/2005JA011584), MCA was specifically designed to address the actual magnetic field geometry. By applying MCA to multispacecraft data from the Magnetospheric Multiscale (MMS) satellites, we perform both case and statistical analyses of local magnetic field shape and dimensionality at very high cadence and small scales. We apply this technique to different near‐Earth environments and define a classification scheme for the type of configuration observed. While our case studies allow us to benchmark the method with those used in past works, our statistical analysis unveils the typical shape of magnetic configurations and their statistical distributions. We show that small‐scale magnetic configurations are generally elongated, displaying forms of cigar and blade shapes, but occasionally being planar in shape like thin pancakes (mostly inside current sheets). Magnetic configurations, however, rarely show isotropy in their magnetic variance. The planar nature of magnetic configurations and, most importantly, their scale lengths strongly depend on the plasma β parameter. Finally, the most invariant direction is statistically aligned with the electric current, reminiscent of the importance of electromagnetic forces in shaping the local magnetic configuration.
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| 20. |
- Kitamura, N., et al.
(författare)
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Energy Transfer Between Hot Protons and Electromagnetic Ion Cyclotron Waves in Compressional Pc5 Ultra-low Frequency Waves
- 2021
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Ingår i: Journal of Geophysical Research - Space Physics. - : AMER GEOPHYSICAL UNION. - 2169-9380 .- 2169-9402. ; 126:5
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Tidskriftsartikel (refereegranskat)abstract
- The Magnetospheric Multiscale (MMS) spacecraft observed many enhancements of electromagnetic ion cyclotron (EMIC) waves in an event in the late afternoon outer magnetosphere. These enhancements occurred mainly in the troughs of magnetic field intensity associated with a compressional ultralow frequency (ULF) wave. The ULF wave had a period of similar to 2-5 min (Pc5 frequency range) and was almost static in the plasma rest frame. The magnetic and ion pressures were in antiphase. They are consistent with mirror-mode type structures. We apply the Wave-Particle Interaction Analyzer method, which can quantitatively investigate the energy transfer between hot anisotropic protons and EMIC waves, to burst-mode data obtained by the four MMS spacecraft. The energy transfer near the cyclotron resonance velocity was identified in the vicinity of the center of troughs of magnetic field intensity, which corresponds to the maxima of ion pressure in the compressional ULF wave. This result is consistent with the idea that the EMIC wave generation is modulated by ULF waves, and preferential locations for the cyclotron resonant energy transfer are the troughs of magnetic field intensity. In these troughs, relatively low resonance velocity due to the lower magnetic field intensity and the enhanced hot proton flux likely contribute to the enhanced energy transfer from hot protons to the EMIC waves by cyclotron resonance. Due to the compressional ULF wave, regions of the cyclotron resonant energy transfer can be narrow (only a few times of the gyroradii of hot resonant protons) in magnetic local time.
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| 21. |
- Kitamura, N., et al.
(författare)
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Observations of the Source Region of Whistler Mode Waves in Magnetosheath Mirror Structures
- 2020
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Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 125:5
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Tidskriftsartikel (refereegranskat)abstract
- In the magnetosheath, intense whistler mode waves, called "Lion roars," are often detected in troughs of magnetic field intensity in mirror mode structures. Using data obtained by the four Magnetospheric Multiscale (MMS) spacecraft, we show that reversals of gradient of magnetic field intensity along the magnetic field correspond to reversals of the field-aligned component of Poynting flux of whistler mode waves in the troughs. Such a characteristic is consistent with the idea that the whistler mode waves are effectively generated near the local minima of magnetic field intensity because of the smallest cyclotron resonance velocity and propagate toward regions of larger magnetic field intensity along the magnetic field lines on both sides. We use the reversal of the Poynting flux as an indicator of wave source regions. In these regions, we find that pancake or an outer edge of butterfly electron distributions above similar to 100 eV are good candidates for wave generation. Unclear correlations of phase difference and amplitude variations of whistler mode waves in cases of similar to 40 km spacecraft separation indicate that a simple plane wave approximation with a constant amplitude is not valid at this spatial scale that is much smaller than the ion gyroradius. The whistler mode waves consist of small coherent wave packets from multiple sources with spatial scales smaller than tens of electron gyroradii transverse to the background magnetic field in a mirror mode structure.
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| 22. |
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| 23. |
- Milz, Mathias, et al.
(författare)
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Validation of water vapour profiles (version 13) retrieved by the IMK/IAA scientific retrieval processor based on full resolution spectra measured by MIPAS on board Envisat
- 2009
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 2:2, s. 379-399
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Tidskriftsartikel (refereegranskat)abstract
- Vertical profiles of stratospheric water vapour measured by the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) with the full resolution mode between September 2002 and March 2004 and retrieved with the IMK/IAA scientific retrieval processor were compared to a number of independent measurements in order to estimate the bias and to validate the existing precision estimates of the MIPAS data. The estimated precision for MIPAS is 5 to 10% in the stratosphere, depending on altitude, latitude, and season. The independent instruments were: the Halogen Occultation Experiment (HALOE), the Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS), the Improved Limb Atmospheric Spectrometer-II (ILAS-II), the Polar Ozone and Aerosol Measurement (POAM III) instrument, the Middle Atmospheric Water Vapour Radiometer (MIAWARA), the Michelson Interferometer for Passive Atmospheric Sounding, balloon-borne version (MIPAS-B), the Airborne Microwave Stratospheric Observing System(AMSOS), the Fluorescent Stratospheric Hygrometer for Balloon (FLASH-B), the NOAA frostpoint hygrometer, and the Fast In Situ Hygrometer (FISH). For the in-situ measurements and the ground based, air- and balloon borne remote sensing instruments, the measurements are restricted to central and northern Europe. The comparisons to satellite-borne instruments are predominantly at mid- to high latitudes on both hemispheres. In the stratosphere there is no clear indicationof a bias in MIPAS data, because the independent measurements in some cases are drier and in some cases are moister than the MIPAS measurements. Compared to the infrared measurements of MIPAS, measurements in the ultraviolet and visible have a tendency to be high, whereas microwave measurements have a tendency to be low. Theresults of chi2-based precision validation are somewhat controversial among the comparison estimates. However, for comparison instruments whose error budget also includes errors due to uncertainties in spectrally interfering species and where good coincidences were found, the chi2 values found are in the expected range or even below. This suggests that there is no evidence of systematically underestimated MIPAS random errors.
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| 24. |
- Rojo, M., et al.
(författare)
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Structure and dynamics of the Hermean magnetosphere revealed by electron observations from the Mercury electron analyzer after the first three Mercury flybys of BepiColombo
- 2024
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 687
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Tidskriftsartikel (refereegranskat)abstract
- Context: The Mercury electron analyzer (MEA) obtained new electron observations during the first three Mercury flybys by BepiColombo on October 1, 2021 (MFB1), June 23 , 2022 (MFB2), and June 19, 2023 (MFB3). BepiColombo entered the dusk side magnetotail from the flank magnetosheath in the northern hemisphere, crossed the Mercury solar orbital equator around midnight in the magnetotail, traveled from midnight to dawn in the southern hemisphere near the closest approach, and exited from the post-dawn magnetosphere into the dayside magnetosheath.Aims: We aim to identify the magnetospheric boundaries and describe the structure and dynamics of the electron populations observed in the various regions explored along the flyby trajectories.Methods: We derive 4s time resolution electron densities and temperatures from MEA observations. We compare and contrast our new BepiColombo electron observations with those obtained from the Mariner 10 scanning electron spectrometer (SES) 49 yr ago.Results: A comparison to the averaged magnetospheric boundary crossings of MESSENGER indicates that the magnetosphere of Mercury was compressed during MFB1, close to its average state during MFB2, and highly compressed during MFB3. Our new MEA observations reveal the presence of a wake effect very close behind Mercury when BepiColombo entered the shadow region, a significant dusk-dawn asymmetry in electron fluxes in the nightside magnetosphere, and strongly fluctuating electrons with energies above 100s eV in the dawnside magnetosphere. Magnetospheric electron densities and temperatures are in the range of 10-30 cm-3 and above a few 100s eV in the pre-midnight-sector, and in the range of 1-100 cm-3 and well below 100 eV in the post-midnight sector, respectively.Conclusions: The MEA electron observations of different solar wind properties encountered during the first three Mercury flybys reveal the highly dynamic response and variability of the solar wind-magnetosphere interactions at Mercury. A good match is found between the electron plasma parameters derived by MEA in the various regions of the Hermean environment and similar ones derived in a few cases from other instruments on board BepiColombo.
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| 25. |
- Takahashi, H., et al.
(författare)
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A thermal-neutron detector with a phoswich system of LiCaAlF6 and BGO crystal scintillators onboard PoGOLite
- 2010
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Ingår i: 2010 IEEE Nuclear Science Symposium, Medical Imaging Conference, NSS/MIC 2010 and 17th International Workshop on Room-Temperature Semiconductor X-ray and Gamma-ray Detectors, RTSD 2010. ; , s. 32-37
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Konferensbidrag (refereegranskat)abstract
- To measure the flux of atmospheric neutrons and study the neutron contribution to the background of the main detector of the PoGOLite (Polarized Gamma-ray Observer) balloon-borne experiment, a thermal-neutron detector with a phoswich system of LiCaAlF6 (Eu) and BGO crystal scintillators is developed. The performance to separate thermal-neutron events from those of gamma-rays and charged particles is validated with 252Cf on ground. The detector is attached to the PoGOLite instrument and is launched in 2011 from the Esrange facility in the North of Sweden. Although the emission wavelength of the LiCaAlF6 (Ce) is 300 nm and overlaps with the absorption wavelength of the BGO, the phoswich capability of the LiCaAlF6 (Ce) with the BGO is also confirmed with installing a waveform shifter.
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