Abstract: Empirical knowledge of the fitness effects of mutations is important for understanding many evolutionary processes, yet this knowledge is often hampered by several sources of measurement error and bias. Most of these problems can be solved using site-directed mutagenesis to engineer single mutations, an approach particularly suited for viruses due to their small genomes. Here, we used this technique to measure the fitness effect of 100 single-nucleotide substitutions in the bacteriophage f1, a filamentous single-strand DNA virus. We found that approximately one-fifth of all mutations are lethal. Viable ones reduced fitness by 11% on average and were accurately described by a log-normal distribution. More than 90% of synonymous substitutions were selectively neutral, while those affecting intergenic regions reduced fitness by 14% on average. Mutations leading to amino acid substitutions had an overall mean deleterious effect of 37%, which increased to 45% for those changing the amino acid polarity. Interestingly, mutations affecting early steps of the infection cycle tended to be more deleterious than those affecting late steps. Finally, we observed at least two beneficial mutations. Our results confirm that high mutational sensitivity is a general property of viruses with small genomes, including RNA and single-strand DNA viruses infecting animals, plants, and bacteria.

Abstract: Recent BaBar data on the pion transition form factor, whose Q(2)-dependence is much steeper then predicted by asymptotic Quantum Chromodynamics (QCD), have caused a renewed interest in its theoretical description. We present here a formalism based on a model-independent description for low photon virtuality and a high photon virtuality description based on QCD, which match at a scale Q(0). The high photon virtuality description incorporates a flat pion distribution amplitude, phi(x) = 1, at the matching scale Q(0) and QCD evolution from Q(0) to Q > Q(0). The flat pion distribution is connected, through soft pion theorems and chiral symmetry, to the pion valence parton distribution at the same low scale Q(0). The procedure leads to a good description of the data, and by incorporating additional twist-three effects, to an excellent description of the data.

Abstract: Random coincidences ('randoms') are one of the main sources of image degradation in PET imaging. In order to correct for this effect, an accurate method to estimate the contribution of random events is necessary. This aspect becomes especially relevant for high-resolution PET scanners where the highest image quality is sought and accurate quantitative analysis is undertaken. One common approach to estimate randoms is the so-called singles rate method (SR) widely used because of its good statistical properties. SR is based on the measurement of the singles rate in each detector element. However, recent studies suggest that SR systematically overestimates the correct random rate. This overestimation can be particularly marked for low energy thresholds, below 250 keV used in some applications and could entail a significant image degradation. In this work, we investigate the performance of SR as a function of the activity, geometry of the source and energy acceptance window used. We also investigate the performance of an alternative method, which we call 'singles trues' (ST) that improves SR by properly modeling the presence of true coincidences in the sample. Nevertheless, in any real data acquisition the knowledge of which singles are members of a true coincidence is lost. Therefore, we propose an iterative method, STi, that provides an estimation based on ST but which only requires the knowledge of measurable quantities: prompts and singles. Due to inter-crystal scatter, for wide energy windows ST only partially corrects SR overestimations. While SR deviations are in the range 86-300% (depending on the source geometry), the ST deviations are systematically smaller and contained in the range 4-60%. STi fails to reproduce the ST results, although for not too high activities the deviation with respect to ST is only a few percent. For conventional energy windows, i.e. those without inter-crystal scatter, the ST method corrects the SR overestimations, and deviations from the true random rate are of the order of 1% or less. In addition, in the case of conventional energy window STi results reproduce ST results and therefore the former can be used to obtain the true random rate.