In this article the Tomographic Iterative GPU-based Reconstruction (TIGRE) Toolbox, a MATLAB/ CUDA toolbox for fast and accurate 3D x-ray image reconstruction, is presented. One of the key features is the implementation of a wide variety of iterative algorithms as well as FDK, including a range of algorithms in the SART family, the Krylov subspace family and a range of methods using total variation regularization. Additionally, the toolbox has GPU-accelerated projection and back projection using the latest techniques and it has a modular design that facilitates the implementation of new algorithms. We present an overview of the structure and techniques used in the creation of the toolbox, together with two usage examples. The TIGRE Toolbox is released under an open source licence, encouraging people to contribute.

As carbon ions, at therapeutic energies, penetrate tissue, they undergo inelastic nuclear reactions and give rise to significant yields of secondary fragment fluences. Therefore, an accurate prediction of these fluences resulting from the primary carbon interactions is necessary in the patient's body in order to precisely simulate the spatial dose distribution and the resulting biological effect. In this paper, the performance of nuclear fragmentation models of the Monte Carlo transport codes, FLUKA and GEANT4, in tissue-like media and for an energy regime relevant for therapeutic carbon ions is investigated. The ability of these Monte Carlo codes to reproduce experimental data of charge-changing cross sections and integral and differential yields of secondary charged fragments is evaluated. For the fragment yields, the main focus is on the consideration of experimental approximations and uncertainties such as the energy measurement by time-of-flight. For GEANT4, the hadronic models G4BinaryLightIonReaction and G4QMD are benchmarked together with some recently enhanced de-excitation models. For non-differential quantities, discrepancies of some tens of percent are found for both codes. For differential quantities, even larger deviations are found. Implications of these findings for the therapeutic use of carbon ions are discussed.

0(-Methylguanine (m6G) was incorporated site-specifically into two 25-base oligonucleotides differing only in the nucleotide on the 3' side of the modified base. Templates were primed with oligonucleotides terminating one or two bases prior to the site at which incorporation kinetics were to be investigated. Escherichia coli DNA polymerase I (Klenow fragment) was used to determine the apparent Km and relative V,,x of incorporation of either dCTP or dTTP opposite m6G or G.These data were used to calculate the relative frequency of incorporation opposite the m6G or the unmodified G. When the sequence was 3'-Cm6G-5', there was a 6-to 7-fold preference for formation of a m6G-T pair compared with m6G-C. The m6G-T frequency, based on Vmix/Km, was at least 50-fold greater than that of a G-T pair at the same site. Changing the sequence to 3'-Tm6G-5' had a marked effect on both Km and V.,, of pairs containing m6G and on the incorporation frequency of T opposite m6G, which was then only slightly favored over m6G-C. When replication was started directly opposite m6G, the kinetics appeared unaffected. These data indicate that the frequency of incorporation of C or T opposite m6G in a DNA template is dependent on the flanking neighbors and that a change of even a single base at the 3' position can have a major effect on mutagenic efficiency. Replication using Drosophila Pol a gave the same values for relative frequencies. Pairing of either C or T with m'G on the primer terminus did not significantly inhibit extension of the next normal base pair, in contrast to terminal mismatches of unmodified bases. It is concluded that, in the absence of repair, m6G can exhibit widely differing mutation frequencies which, in these experiments, can be as high as 85% of the replicated base. This variation in frequency of changed pairing could contribute to the occurrence of mutational "hot spots" after replication of damaged DNA.The likely role of 06-alkylguanines as a major factor in mutagenesis by certain alkylating agents was recognized by Loveless about 20 years ago (1). In an attempt to resolve contradictions in the literature, he suggested that O6-methylguanine (m6G) might pair with thymine (T) during replication and thus cause the G-C -* A-T transitions found as the major genetic change after reaction with certain carcinogenic alkylating agents. Further studies in a number of laboratories established that the occurrence, and in particular the persistence of this alkylated base, often correlated with the biological endpoints of mutagenesis and carcinogenesis (2). In accord with the proposed mechanism of mutagenesis, m6G can pair with T both in vitro (3) and in vivo (4), when presented to a polymerase either in the template or as a precursor to DNA synthesis. This model of mutagenesis occurring by base pairing between m6G and T during replication has long been assumed, but only recently has it begun to be tested rigorously [reviewed by Basu and Essigmann (5)]. When an m6G-containing dodecamer was annealed with a series of anal...

We have previously reported that human cels and tissues contain a 1,N-ethenoadenine (EA) binding protein, which, tuh glycosylase activity, releases both 3-ethyladine (m3A) and eA from DNA treated with methylating agents or the vinyl chloride metabolite chloroacetaldehyde, respectively. We now find that both the partially purified human eA-binding pren and cell-free extracts contaiing the cloned human m3A-DNA glycosylase release all four cyclic etheno adducts-namely eA, 3,N4-ethenoCyte (eC), N2,3-ethen aine (N2,3-eG), and l,N2-ethenoguanine (1,N2-eG). Base