Uncertainty quantification analysis and optimization for proton therapy beam lines.

Since many years proton therapy is an effective treatment solution against deep-seated tumors. A precise quantification of sources of uncertainty in each proton therapy aspect (e.g. accelerator, beam lines, patient positioning, treatment planning) is of profound importance to increase the accuracy of the dose delivered to the patient. Together with Monte Carlo techniques, a new research field called Uncertainty Quantification (UQ) has been recently introduced to verify the robustness of the treatment planning. In this work we present the first application of UQ as a method to identify typical errors in the transport lines of a cyclotron-based proton therapy facility and analyze their impact on the properties of the therapeutic beams. We also demonstrate the potential of UQ methods in developing optimized beam optics solutions for high-dimensional problems. Sensitivity analysis and surrogate models offer a fast way to exclude unimportant parameters frcomplex optimization problems such as the design of a superconducting gantry performed at Paul Scherrer Institute in Switzerland.

Proposal for an electron antineutrino disappearance search using high-rate 8Li production and decay.

This paper introduces an experimental probe of the sterile neutrino with a novel, high-intensity source of electron antineutrinos from the production and subsequent decay of 8Li. When paired with an existing ∼1 kton scintillator-based detector, this = 6.4 MeV source opens a wide range of possible searches for beyond standard model physics via studies of the inverse beta decay interaction ν(e) + p → e+ + n. In particular, the experimental design described here has unprecedented sensitivity to ν(e) disappearance at Δm2 ∼ 1 eV2 and features the ability to distinguish between the existence of zero, one, and two sterile neutrinos.

Multi-gene/allele control of Mlsb of CBA/H.

Festenstein originally described the Mls locus as a single dominant autosomal gene with four alleles which mapped in the 13th linkage group of chromosome 1. We subsequently presented evidence indicating that the mixed leukocyte reaction (MLR) stimulatory products of DBA/2 and CBA/J were controlled by two independently segregating Mls loci and that Mls of C3H was in fact a composite of three independently segregating loci. Recently, Mlsd of CBA/J was shown to be composed of Mlsa of AKR and a product on C3H, which was presumed to be Mlsc. Based on strain distributions, this product cannot be encoded by the Mlsc originally defined by Festenstein. In the present report, three Mls specificities of CBA/H (Mlsb) are defined. Based on the strain distribution, we postulate that these specificities are controlled by three loci, three alleles/locus, or by some combination of the preceding two possibilities.

Genetic complexity of Mls.

For almost 20 years, little new has been described for Mls or the products it encodes. In the present report, data is presented which indicate that either the number of loci or the number of alleles per locus that control Mls-like products is much larger than the two-locus model or five allele-model presently envisaged.

Multigene control of Mlsc.

Festenstein originally described the Mls locus as a single dominant autosomal gene with four alleles which mapped in the 13th linkage group of chromosome 1. We subsequently presented evidence which indicated that the mixed leukocyte reaction stimulatory products of DBA/2 and CBA/J were controlled by two independently segregating Mls loci. Recently, Mlsd of CBA/J was shown to be composed of Mlsa of AKR and Mlsc of C3H. In the present report, classic segregation data is presented which indicates that Mlsc of C3H is controlled by three independently segregating loci. As defined by stimulatory patterns of numerous cell lines, we postulate the following: either one of the loci is shared with BALB.K, CE, C58, and partially with MA/MyJ, one is shared with CBA/H and CBA/J, and one is shared with BALB.K, CBA/J, and partially with CE; or the groups of shared determinants are controlled by different alleles of unique loci (or locus). In any event, Mlsc appears to be composed of at least three independently segregating loci; the number of alleles/locus is being investigated. In addition, C3H was stimulated by BALB.K (both were recently postulated to be Mlsc); this epitope was shared with CBA/J, CBA/H, AKR/Cum, Ma/MyJ, and C58/J.

Metabolite profile in milk of lactating rats after treatment with a carcinogen, N-2-fluorenylacetamide.

Metabolites were determined in milk and urine of lactating rats 4 to 5 hr after each of 3 to 6 ip injections of N-2-fluorenylacetamide (2-FAA) at 0.2 mmol/kg of body weight. Milk contained 2-FAA as the major free compound, variable amounts of N-2-fluorenamine (2-FA) and phenols (7- greater than 5- greater than 3-hydroxy-2-FAA) chiefly as glucuronides, and very small amounts of the glucuronide of N-hydroxy-2-FAA. Urine contained large amounts of the phenols and N-hydroxy-2-FAA as free and conjugated compounds, but in contrast to milk, only small amounts of 2-FAA and no 2-FA. Pretreatment of rats with beta-napthoflavone, an inducer of microsomal C- and N-hydroxylations of 2-FAA, increased the amounts of 3- and 5-hydroxy-2-FAA in milk and of 3-hydroxy-2-FAA in urine. However, the total amounts of the compounds excreted in 1 ml of milk or urine, i.e. 0.05 to 0.13% or 0.6% of the dose of 2-FAA, respectively, were similar in the uninduced and induced groups. Protein hydrolysates of milk of 2-FAA-treated rats and of milk interacted with 2-nitrosofluorene (2-NOF) in vitro both contained 2-FA and 9-oxo-2-FA. This suggested formation of 2-NOF in vivo possibly by peroxidative metabolism of N-OH-2-FAA. Since 2-NOF has been reported to form adducts with unsaturated lipids, the effect of treatment of lactating rats with 2-FAA on the fatty acid composition of milk lipids was examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Nonresponsiveness to Mlsd in F1 hybrid mice carrying Mlsa and Mlsc genes.

Neither the biological function nor a basic understanding of the enigmatic chromosome 1-encoded Mls locus of the mouse has yet been uncovered despite extensive investigations. The present report is a continuation of our genetic analyses of the Mls locus in an attempt to better define the system. Data presented here indicate that in contrast to cells of mice expressing either the Mlsa or Mlsc allele which respond in mixed leukocyte reactions to cells expressing the Mlsd allelic products, cells from (Mlsa X Mlsc)F1-hybrid mice do not. In addition, the nonresponder phenotype appears to segregate as a single autosomal genetic system in backcross animals. These findings fail to support two recently advanced hypotheses: first, that the Mls locus is nonpolymorphic, or second, that the Mls locus controls differential expression of Ia antigenic determinants. Although the mechanism by which a (responder X responder) converts to a nonresponder remains unknown, three models involving gene complementation are discussed.

Immune responses in vitro. XIII. MLR detectability of Mlsa-, Mlsb-, Mlsc-, and Mlsd-encoded products.

The Mls locus was originally defined to have four alleles; all controlled products that were detectable in MLR except b, which was described as being null. More recent evidence led other investigators to postulate that the Mls locus is nonpolymorphic, being composed of only the b null allele and a singly expressed allele previously ascribed to be the a and d alleles. Our results indicate that Mlsa and Mlsd control products that are antigenically distinct and, therefore, the products cannot be controlled by the same allele. In addition, the product of Mlsb was easily detectable by Mlsa and Mlsd responding cells and cannot be considered null. Alternative explanations are considered for these conflicting results.