| 1. |
- Ballarini, F., et al.
(author)
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The physics of the FLUKA code : Recent developments
- 2007
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In: Advances in Space Research. - Elsevier : Elsevier BV. - 0273-1177 .- 1879-1948. ; 40:9, s. 1339-1349
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Journal article (peer-reviewed)abstract
- FLUKA is a Monte-Carlo code able to simulate interaction and transport of hadrons, heavy ions and electromagnetic particles from few keV (or thermal neutron) to cosmic ray energies in whichever material. The highest priority in the design and development of the code has always been the implementation and improvement of sound and modern physical models. A summary of the FLUKA physical models is given, while recent developments are described in detail: among the others, extensions of the intermediate energy hadronic interaction generator, refinements in photon cross sections and interaction models, analytical on-line evolution of radio-activation and remnant dose. In particular, new developments in the nucleus-nucleus interaction models are discussed. Comparisons with experimental data and examples of applications of relevance for space radiation are also provided.
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| 2. |
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| 3. |
- Geoerger, B., et al.
(author)
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Enasidenib treatment in two individuals with D-2-hydroxyglutaric aciduria carrying a germline IDH2 mutation
- 2023
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In: Nature Medicine. - 1078-8956. ; 29:6
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Journal article (peer-reviewed)abstract
- D-2-hydroxyglutaric aciduria type II (D2HGA2) is a severe inborn disorder of metabolism caused by heterozygous R140 mutations in the IDH2 (isocitrate dehydrogenase 2) gene. Here we report the results of treatment of two children with D2HGA2, one of whom exhibited severe dilated cardiomyopathy, with the selective mutant IDH2 enzyme inhibitor enasidenib. In both children, enasidenib treatment led to normalization of D-2-hydroxyglutarate (D-2-HG) concentrations in body fluids. At doses of 50 mg and 60 mg per day, no side effects were observed, except for asymptomatic hyperbilirubinemia. For the child with cardiomyopathy, chronic D-2-HG inhibition was associated with improved cardiac function, and for both children, therapy was associated with improved daily functioning, global motility and social interactions. Treatment of the child with cardiomyopathy led to therapy-coordinated changes in serum phospholipid levels, which were partly recapitulated in cultured fibroblasts, associated with complex effects on lipid and redox-related gene pathways. These findings indicate that targeted inhibition of a mutant enzyme can partly reverse the pathology of a chronic neurometabolic genetic disorder. In a study of two children with the metabolic condition D-2-hydroxyglutaric aciduria type II, the drug enasidenib, developed as a selective mutant IDH2 inhibitor for treatment of acute myeloid leukemia, had beneficial effects on cardiac and neurodevelopmental abnormalities, indicating the potential for the repurposing of this drug for this hereditary condition.
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| 4. |
- Kreuzer, M., et al.
(author)
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Multidisciplinary European Low Dose Initiative (MELODI) : strategic research agenda for low dose radiation risk research
- 2018
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In: Radiation and Environmental Biophysics. - : Springer Science and Business Media LLC. - 0301-634X .- 1432-2099. ; 57:1, s. 5-15
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Research review (peer-reviewed)abstract
- MELODI (Multidisciplinary European Low Dose Initiative) is a European radiation protection research platform with focus on research on health risks after exposure to low-dose ionising radiation. It was founded in 2010 and currently includes 44 members from 18 countries. A major activity of MELODI is the continuous development of a long-term European Strategic Research Agenda (SRA) on low-dose risk for radiation protection. The SRA is intended to identify priorities for national and European radiation protection research programs as a basis for the preparation of competitive calls at the European level. Among those key priorities is the improvement of health risk estimates for exposures close to the dose limits for workers and to reference levels for the population in emergency situations. Another activity of MELODI is to ensure the availability of European key infrastructures for research activities, and the long-term maintenance of competences in radiation research via an integrated European approach for training and education. The MELODI SRA identifies three key research topics in low dose or low dose-rate radiation risk research: (1) dose and dose rate dependence of cancer risk, (2) radiation-induced non-cancer effects and (3) individual radiation sensitivity. The research required to improve the evidence base for each of the three key topics relates to three research lines: (1) research to improve understanding of the mechanisms contributing to radiogenic diseases, (2) epidemiological research to improve health risk evaluation of radiation exposure and (3) research to address the effects and risks associated with internal exposures, differing radiation qualities and inhomogeneous exposures. The full SRA and associated documents can be downloaded from the MELODI website (http://www.melodi-online.eu/sra.html).
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