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- Okada, Yukinori, et al.
(author)
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Genetics of rheumatoid arthritis contributes to biology and drug discovery
- 2014
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 506:7488, s. 376-381
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Journal article (peer-reviewed)abstract
- A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)(1). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating similar to 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2-4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation(5), cis-acting expression quantitative trait loci(6) and pathway analyses(7-9)-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
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- Sato, T., et al.
(author)
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Overview of Particle and Heavy Ion Transport Code System PHITS
- 2014
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In: Sna + Mc 2013 - Joint International Conference on Supercomputing in Nuclear Applications + Monte Carlo. - Les Ulis, France : EDP Sciences. ; , s. article no 06018-
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Conference paper (peer-reviewed)abstract
- A general purpose Monte Carlo Particle and Heavy Ion Transport code System, PHITS, is being developed through the collaboration of several institutes in Japan and Europe. The Japan Atomic Energy Agency is responsible for managing the entire project. PHITS can deal with the transport of nearly all particles, including neutrons, protons, heavy ions, photons, and electrons, over wide energy ranges using various nuclear reaction models and data libraries. It is written in Fortran language and can be executed on almost all computers. All components of PHITS such as its source, executable and data-library files are assembled in one package and then distributed to many countries via the Research organization for Information Science and Technology, the Data Bank of the Organization for Economic Co-operation and Development's Nuclear Energy Agency, and the Radiation Safety Information Computational Center. More than 1,000 researchers have been registered as PHITS users, and they apply the code to various research and development fields such as nuclear technology, accelerator design, medical physics, and cosmic-ray research. This paper briefly summarizes the physics models implemented in PHITS, and introduces some important functions useful for specific applications, such as an event generator mode and beam transport functions.
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- Sato, T., et al.
(author)
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Particle and Heavy Ion Transport code System, PHITS, version 2.52
- 2013
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In: Journal of Nuclear Science and Technology. - : Informa UK Limited. - 0022-3131 .- 1881-1248. ; 50:9, s. 913-923
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Journal article (peer-reviewed)abstract
- An upgraded version of the Particle and Heavy Ion Transport code System, PHITS2.52, was developed and released to the public. The new version has been greatly improved from the previously released version, PHITS2.24, in terms of not only the code itself but also the contents of its package, such as the attached data libraries. In the new version, a higher accuracy of simulation was achieved by implementing several latest nuclear reaction models. The reliability of the simulation was improved by modifying both the algorithms for the electron-, positron-, and photon-transport simulations and the procedure for calculating the statistical uncertainties of the tally results. Estimation of the time evolution of radioactivity became feasible by incorporating the activation calculation program DCHAIN-SP into the new package. The efficiency of the simulation was also improved as a result of the implementation of shared-memory parallelization and the optimization of several time-consuming algorithms. Furthermore, a number of new user-support tools and functions that help users to intuitively and effectively perform PHITS simulations were developed and incorporated. Due to these improvements, PHITS is now a more powerful tool for particle transport simulation applicable to various research and development fields, such as nuclear technology, accelerator design, medical physics, and cosmic-ray research.
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- Srikulnath, K., et al.
(author)
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Identification of the linkage group of the Z sex chromosomes of the sand lizard (Lacerta agilis, Lacertidae) and elucidation of karyotype evolution in lacertid lizards
- 2014
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In: Chromosoma. - : Springer Science and Business Media LLC. - 0009-5915 .- 1432-0886. ; 123:6, s. 563-575
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Journal article (peer-reviewed)abstract
- The sand lizard (Lacerta agilis, Lacertidae) has a chromosome number of 2n = 38, with 17 pairs of acrocentric chromosomes, one pair of microchromosomes, a large acrocentric Z chromosome, and a micro-W chromosome. To investigate the process of karyotype evolution in L. agilis, we performed chromosome banding and fluorescent in situ hybridization for gene mapping and constructed a cytogenetic map with 86 functional genes. Chromosome banding revealed that the Z chromosome is the fifth largest chromosome. The cytogenetic map revealed homology of the L. agilis Z chromosome with chicken chromosomes 6 and 9. Comparison of the L. agilis cytogenetic map with those of four Toxicofera species with many microchromosomes (Elaphe quadrivirgata, Varanus salvator macromaculatus, Leiolepis reevesii rubritaeniata, and Anolis carolinensis) showed highly conserved linkage homology of L. agilis chromosomes (LAG) 1, 2, 3, 4, 5(Z), 7, 8, 9, and 10 with macrochromosomes and/or macrochromosome segments of the four Toxicofera species. Most of the genes located on the microchromosomes of Toxicofera were localized to LAG6, small acrocentric chromosomes (LAG11-18), and a microchromosome (LAG19) in L. agilis. These results suggest that the L. agilis karyotype resulted from frequent fusions of microchromosomes, which occurred in the ancestral karyotype of Toxicofera and led to the disappearance of microchromosomes and the appearance of many small macrochromosomes.
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- Titarenko, Yu E., et al.
(author)
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Measurement and simulation of the cross sections for nuclide production in Fe-56 and Cr-nat targets irradiated with 0.04- to 2.6-GeV protons
- 2011
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In: Physics of Atomic Nuclei. - 1063-7788 .- 1562-692X. ; 74:4, s. 523-536
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Journal article (peer-reviewed)abstract
- The cross sections for nuclide production in thin Fe-56 and Cr-nat targets irradiated by 0.04-2.6-GeV protons are measured by direct gamma spectrometry using two gamma spectrometers with the resolutions of 1.8 and 1.7 keV for the Co-60 1332-keV gamma line. As a result, 649 yields of radioactive residual product nuclei have been obtained. The Al-27(p, x)Na-22 reaction has been used as a monitor reaction. The experimental data are compared with the MCNPX (BERTINI, ISABEL), CEM03.02, INCL4.2, INCL4.5, PHITS, and CASCADE07 calculations.
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