| 1. |
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| 2. |
- Bellenguez, C, et al.
(författare)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Tidskriftsartikel (refereegranskat)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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| 7. |
- Lambert, J-C, et al.
(författare)
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Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease
- 2013
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 18:4, s. 461-470
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Tidskriftsartikel (refereegranskat)abstract
- Recently, several genome-wide association studies (GWASs) have led to the discovery of nine new loci of genetic susceptibility in Alzheimer's disease (AD). However, the landscape of the AD genetic susceptibility is far away to be complete and in addition to single-SNP (single-nucleotide polymorphism) analyses as performed in conventional GWAS, complementary strategies need to be applied to overcome limitations inherent to this type of approaches. We performed a genome-wide haplotype association (GWHA) study in the EADI1 study (n = 2025 AD cases and 5328 controls) by applying a sliding-windows approach. After exclusion of loci already known to be involved in AD (APOE, BIN1 and CR1), 91 regions with suggestive haplotype effects were identified. In a second step, we attempted to replicate the best suggestive haplotype associations in the GERAD1 consortium (2820 AD cases and 6356 controls) and observed that 9 of them showed nominal association. In a third step, we tested relevant haplotype associations in a combined analysis of five additional case-control studies (5093 AD cases and 4061 controls). We consistently replicated the association of a haplotype within FRMD4A on Chr.10p13 in all the data set analyzed (OR: 1.68; 95% CI: (1.43-1.96); P=1.1 x 10(-10)). We finally searched for association between SNPs within the FRMD4A locus and A beta plasma concentrations in three independent non-demented populations (n = 2579). We reported that polymorphisms were associated with plasma A beta 42/A beta 40 ratio (best signal, P=5.4 x 10(-7)). In conclusion, combining both GWHA study and a conservative three-stage replication approach, we characterised FRMD4A as a new genetic risk factor of AD.
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| 8. |
- Wang, Li-San, et al.
(författare)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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| 9. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 10. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 11. |
- Zhu, L Y, et al.
(författare)
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Cross section measurements of charged pion photoproduction in hydrogen and deuterium from 1.1 to 5.5 GeV
- 2005
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 71:4
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Tidskriftsartikel (refereegranskat)abstract
- The differential cross sections for the gamma n ->pi(-)p and the gamma p ->pi(+)n processes were measured at Jefferson Lab. The photon energies ranged from 1.1 to 5.5 GeV, corresponding to center-of-mass energies from 1.7 to 3.4 GeV. The pion center-of-mass angles varied from 50(degrees) to 110(degrees). The pi(-) and pi(+) photoproduction data both exhibit a global scaling behavior at high energies and high transverse momenta, consistent with the constituent counting rule prediction and the existing pi(+) data. The data suggest possible substructure of the scaling behavior, which might be oscillations around the scaling value. The data show an enhancement in the scaled cross section at center-of-mass energy near 2.2 GeV. The differential cross section ratios [d sigma/dt(gamma n ->pi(-)p)/d sigma/dt(gamma p ->pi(+)n)] at high energies and high transverse momenta can be described by calculations based on one-hard-gluon-exchange diagrams.
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| 12. |
- Alcorn, J, et al.
(författare)
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Basic instrumentation for Hall A at Jefferson Lab
- 2004
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 522:3, s. 294-346
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Tidskriftsartikel (refereegranskat)abstract
- The instrumentation in Hall A at the Thomas Jefferson National Accelerator Facility was designed to study electro-and photo-induced reactions at very high luminosity and good momentum and angular resolution for at least one of the reaction products. The central components of Hall A are two identical high resolution spectrometers, which allow the vertical drift chambers in the focal plane to provide a momentum resolution of better than 2 x 10(-4). A variety of Cherenkov counters, scintillators and lead-glass calorimeters provide excellent particle identification. The facility has been operated successfully at a luminosity well in excess of 10(38) CM-2 s(-1). The research program is aimed at a variety of subjects, including nucleon structure functions, nucleon form factors and properties of the nuclear medium. (C) 2003 Elsevier B.V. All rights reserved.
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| 13. |
- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 15. |
- Casolino, M., et al.
(författare)
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The altcriss project on board the International Space Station
- 2007
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Ingår i: Advances in Space Research. - : Elsevier BV. - 1879-1948 .- 0273-1177. ; 40:11, s. 1746-1753
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Tidskriftsartikel (refereegranskat)abstract
- The Alteriss project aims to perform a long term survey of the radiation environment on board the International Space Station. Measurements are being performed with active and passive devices in different locations and orientations of the Russian segment of the station. The goal is to perform a detailed evaluation of the differences in particle fluence and nuclear composition due to different shielding material and attitude of the station. The Sileye-3/Alteino detector is used to identify nuclei up to Iron in the energy range above similar or equal to 60 MeV/n. Several passive dosimeters (TLDs, CR39) are also placed in the same location of Sileye-3 detector. Polyethylene shielding is periodically interposed in front of the detectors to evaluate the effectiveness of shielding on the nuclear component of the cosmic radiation. The project was submitted to ESA in reply to the AO in the Life and Physical Science of 2004 and data taking began in December 2005. Dosimeters and data cards are rotated every 6 months: up to now three launches of dosimeters and data cards have been performed and have been returned with the end of expedition 12 and 13. (C) 2007 Published by Elsevier Ltd on behalf of COSPAR.
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| 16. |
- Dutta, D, et al.
(författare)
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Nuclear transparency with the gamma n ->pi(-)p process in He-4
- 2003
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 68:2: 021001
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Tidskriftsartikel (refereegranskat)abstract
- We have measured the nuclear transparency of the fundamental process gamman-->pi(-)p in He-4. These measurements were performed at Jefferson Lab in the photon energy range of 1.6-4.5 GeV and at theta(cm)(pi)=70degrees and 90degrees. These measurements are the first of their kind in the study of nuclear transparency in photoreactions. They also provide a benchmark test of Glauber calculations based on traditional models of nuclear physics. The transparency results suggest deviations from the traditional nuclear physics picture. The momentum transfer dependence of the measured nuclear transparency is consistent with Glauber calculations that include the quantum chromodynamics phenomenon of color transparency.
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| 17. |
- La Tessa, C., et al.
(författare)
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Out-of-field dose studies with an anthropomorphic phantom : Comparison of X-rays and particle therapy treatments
- 2012
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 105:1, s. 133-138
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Characterization of the out-of-field dose profile following irradiation of the target with a 3D treatment plan delivered with modern techniques. Methods: An anthropomorphic RANDO phantom was irradiated with a treatment plan designed for a simulated 5×2×5cm 3 tumor volume located in the center of the head. The experiment was repeated with all most common radiation treatment types (photons, protons and carbon ions) and delivery techniques (Intensity Modulated Radiation Therapy, passive modulation and spot scanning). The measurements were performed with active diamond detector and passive thermoluminescence (TLD) detectors to investigate the out-of-field dose both inside and outside the phantom. Results: The highest out-of-field dose values both on the surface and inside the phantom were measured during the treatment with 25 MV photons. In the proximity of the Planned Target Volume (PTV), the lowest lateral dose profile was observed for passively modulated protons mainly because of the presence of the collimator in combination with the chosen volume shape. In the far out-of-field region (above 100 mm from the PTV), passively modulated ions were characterized by a less pronounced dose fall-off in comparison with scanned beams. Overall, the treatment with scanned carbon ions delivered the lowest dose outside the target volume. Conclusions: For the selected PTV, the use of the collimator in proton therapy drastically reduced the dose deposited by ions or photons nearby the tumor. Scanning modulation represents the optimal technique for achieving the highest dose reduction far-out-of-field.
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| 18. |
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| 19. |
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| 20. |
- Zhu, LY, et al.
(författare)
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Cross-section measurement of charged-pion photoproduction from hydrogen and deuterium
- 2003
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Ingår i: Physical Review Letters. - 1079-7114. ; 91:2: 022003
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Tidskriftsartikel (refereegranskat)abstract
- We have measured the differential cross section for the gamman-->pi(-)p and gammap-->pi(+)n reactions at theta(c.m.)=90degrees in the photon energy range from 1.1 to 5.5 GeV at Jefferson Lab (JLab). The data at E(gamma)greater than or similar to3.3 GeV exhibit a global scaling behavior for both pi(-) and pi(+) photoproduction, consistent with the constituent counting rule and the existing pi(+) photoproduction data. Possible oscillations around the scaling value are suggested by these new data. The data show enhancement in the scaled cross section at a center-of-mass energy near 2.2 GeV. The cross section ratio of exclusive pi(-) to pi(+) photoproduction at high energy is consistent with the prediction based on one-hard-gluon-exchange diagrams.
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| 21. |
- Bergin, Michael J., et al.
(författare)
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Fuel Injection and Mean Swirl Effects on Combustion and Soot Formation in Heavy Duty Diesel Engines
- 2007
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Ingår i: SAE, Session: Compression Ignition Combustion Processes (Part 2of 2)..
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Konferensbidrag (refereegranskat)abstract
- High-speed video imaging in a swirl-supported (Rs = 1.7), direct-injection heavy-duty diesel engine operated with moderate-to-high EGR rates reveals a distinct correlation between the spatial distribution of luminous soot and mean flow vorticity in the horizontal plane. The temporal behavior of the experimental images, as well as the results of multi-dimensional numerical simulations, show that this soot-vorticity correlation is caused by the presence of a greater amount of soot on the windward side of the jet. The simulations indicate that while flow swirl can influence pre-ignition mixing processes as well as post-combustion soot oxidation processes, interactions between the swirl and the heat release can also influence mixing processes. Without swirl, combustion-generated gas flows influence mixing on both sides of the jet equally. In the presence of swirl, the heat release occurs on the leeward side of the fuel sprays. Asymmetric combustion-induced flows alter the vorticity on the leeward side of the jet and lead to better entrainment and fuel-air mixing during the period of peak heat release. This leads to lower local equivalence ratio and lower soot production rates with swirl.
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| 23. |
- Graf, Alexander, et al.
(författare)
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Joint optimization of land carbon uptake and albedo can help achieve moderate instantaneous and long-term cooling effects
- 2023
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Ingår i: Communications Earth and Environment. - 2662-4435. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Both carbon dioxide uptake and albedo of the land surface affect global climate. However, climate change mitigation by increasing carbon uptake can cause a warming trade-off by decreasing albedo, with most research focusing on afforestation and its interaction with snow. Here, we present carbon uptake and albedo observations from 176 globally distributed flux stations. We demonstrate a gradual decline in maximum achievable annual albedo as carbon uptake increases, even within subgroups of non-forest and snow-free ecosystems. Based on a paired-site permutation approach, we quantify the likely impact of land use on carbon uptake and albedo. Shifting to the maximum attainable carbon uptake at each site would likely cause moderate net global warming for the first approximately 20 years, followed by a strong cooling effect. A balanced policy co-optimizing carbon uptake and albedo is possible that avoids warming on any timescale, but results in a weaker long-term cooling effect.
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| 24. |
- Gustafsson, Katarina, 1980, et al.
(författare)
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PHITS simulations of the Matroshka experiment
- 2010
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Ingår i: Advances in Space Research. - : Elsevier BV. - 1879-1948 .- 0273-1177. ; 46:10, s. 1266-1272
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Tidskriftsartikel (refereegranskat)abstract
- The radiation environment in space is very different from the one encountered on Earth. In addition to the sparsely ionizing radiation, there are particles of different Z with energies ranging from keV up to hundreds of GeV which can cause severe damage to both electronics and humans. It is therefore important to understand the interactions of these highly ionizing particles with different materials such as the hull of space vehicles, human organs and electronics. We have used the Particle and Heavy-Ion Transport code System (PHITS), which is a three-dimensional Monte Carlo code able to calculate interactions and transport of particles and heavy ions with energies up to 100 GeV/nucleon in most matter. PHITS is developed and maintained by a collaboration between RIST (Research Organization for Information Science & Technology), JAEA (Japan Atomic Energy Agency), KEK (High Energy Accelerator Research Organization), Japan and Chalmers University of Technology, Sweden. For the purpose of examining the applicability of PHITS to the shielding design we have simulated the ESA facility Matroshka (MTR) designed and lead by the German Aerospace Center (DLR). Preliminary results are presented and discussed in this paper.
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| 25. |
- Kim, Myung-Hee Y., et al.
(författare)
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Comparison of Martian surface ionizing radiation measurements from MSL-RAD with Badhwar-O'Neill 2011/HZETRN model calculations
- 2014
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Ingår i: Journal of Geophysical Research - Planets. - 2169-9097 .- 2169-9100. ; 119:6, s. 1311-1321
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Tidskriftsartikel (refereegranskat)abstract
- Dose rate measurements from Mars Science Laboratory-radiation assessment detector (MSL-RAD) for 300 sols on Mars are compared to simulation results using the Badhwar-O'Neill 2011 galactic cosmic ray (GCR) environment model and the high-charge and energy transport (HZETRN) code. For the nuclear interactions of primary GCR through Mars atmosphere and Curiosity rover, the quantum multiple scattering theory of nuclear fragmentation is used. Daily atmospheric pressure is measured at Gale Crater by the MSL Rover Environmental Monitoring Station. Particles impinging on top of the Martian atmosphere reach RAD after traversing varying depths of atmosphere that depend on the slant angles, and the model accounts for shielding of the RAD “E” detector (used for dosimetry) by the rest of the instrument. Simulation of average dose rate is in good agreement with RAD measurements for the first 200 sols and reproduces the observed variation of surface dose rate with changing heliospheric conditions and atmospheric pressure. Model results agree less well between sols 200 and 300 due to subtleties in the changing heliospheric conditions. It also suggests that the average contributions of albedo particles (charge number Z < 3) from Martian regolith comprise about 10% and 42% of the average daily point dose and dose equivalent, respectively. Neutron contributions to tissue-averaged effective doses will be reduced compared to point dose equivalent estimates because a large portion of the neutron point dose is due to low-energy neutrons with energies.
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| 26. |
- Larsson, Oscar, et al.
(författare)
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Measurements of heavy-ion anisotropy and dose rates in the Russian section of the International Space Station with the Sileye-3/Alteino detector
- 2015
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 42:2, s. 025002-
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Tidskriftsartikel (refereegranskat)abstract
- In this work we present data on linear energy transfer (LET), dose and dose equivalent rates from different locations of the Russian part of the International Space Station (ISS) measured by the Sileye-3/Alteino detector. Data were taken as part of the ESA ALTCRISS project from late 2005 through 2007. The LET rate data shows a heavy-ion (LET > 50 keV/mu m) anisotropy. From the heavy-ion LET rate in the Zvezda service module we find ISS (y) over cap (Starboard) and (z) over cap (Nadir) to be about 10-15 times higher than in (x) over cap (Forward). The situation is similar for dose and dose equivalent rates, ranging from 25-40 mu Gy d(-1) in (x) over cap to about 75 mu Gy d(-1) in (z) over cap, whereas for the dose equivalent the rate peaks in (y) over cap with around 470 mu Sv d(-1). The heavy-ion anisotropy confirms what has been reported by the ALTEA collaboration. Measurements using two sets of passive detectors, DLR-TLDs and PADLES (TLD+CR-39), have also been performed in conjunction with Alteino measurements, both shielded and unshielded. The passive detectors register a dose rate about 3-5 times as high as Alteino, 260-280 mu Gy d(-1) for PADLES and 200-260 mu Gy d(-1) for DLR-TLDs. For the dose equivalent PADLES measurements ranges from 560-740 mu Sv d(-1).
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| 27. |
- Puchalska, Monika, 1977, et al.
(författare)
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NUNDO: a numerical model of a human torso phantom and its application to effective dose equivalent calculations for astronauts at the ISS
- 2014
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Ingår i: Radiation and Environmental Biophysics. - : Springer Science and Business Media LLC. - 1432-2099 .- 0301-634X. ; 53:4, s. 719-727
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Tidskriftsartikel (refereegranskat)abstract
- The health effects of cosmic radiation on astronauts need to be precisely quantified and controlled. This task is important not only in perspective of the increasing human presence at the International Space Station (ISS), but also for the preparation of safe human missions beyond low earth orbit. From a radiation protection point of view, the baseline quantity for radiation risk assessment in space is the effective dose equivalent. The present work reports the first successful attempt of the experimental determination of the effective dose equivalent in space, both for extra-vehicular activity (EVA) and intra-vehicular activity (IVA). This was achieved using the anthropomorphic torso phantom RANDO(A (R)) equipped with more than 6,000 passive thermoluminescent detectors and plastic nuclear track detectors, which have been exposed to cosmic radiation inside the European Space Agency MATROSHKA facility both outside and inside the ISS. In order to calculate the effective dose equivalent, a numerical model of the RANDO(A (R)) phantom, based on computer tomography scans of the actual phantom, was developed. It was found that the effective dose equivalent rate during an EVA approaches 700 mu Sv/d, while during an IVA about 20 % lower values were observed. It is shown that the individual dose based on a personal dosimeter reading for an astronaut during IVA results in an overestimate of the effective dose equivalent of about 15 %, whereas under an EVA conditions the overestimate is more than 200 %. A personal dosemeter can therefore deliver quite good exposure records during IVA, but may overestimate the effective dose equivalent received during an EVA considerably.
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| 28. |
- Rafkin, Scot C.R., et al.
(författare)
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Diurnal variations of energetic particle radiation at the surface of Mars as observed by the Mars Science Laboratory Radiation Assessment Detector
- 2014
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Ingår i: Journal of Geophysical Research - Planets. - 2169-9097 .- 2169-9100. ; 119:6, s. 1345-1358
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Tidskriftsartikel (refereegranskat)abstract
- The Radiation Assessment Detector onboard the Mars Science Laboratory rover Curiosity is detecting the energetic particle radiation at the surface of Mars. Data collected over the first 350 Martian days of the nominal surface mission show a pronounced diurnal cycle in both the total dose rate and the neutral particle count rate. The diurnal variations detected by the Radiation Assessment Detector were neither anticipated nor previously considered in the literature. These cyclic variations in dose rate and count rate are shown to be the result of changes in atmospheric column mass driven by the atmospheric thermal tide that is characterized through pressure measurements obtained by the Rover Environmental Monitoring Station, also onboard the rover. In addition to bulk changes in the radiation environment, changes in atmospheric shielding forced by the thermal tide are shown to disproportionately affect heavy ions compared to H and He nuclei.
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