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While accurate inference of U is not a primary aim of our method, a rough approximation can be calculated using the result that in a Wright Fisher model, the probability of a mutant with selection coefficient σ reaching frequency 1/σ is 2σ [see e.g. Desai and Fisher (2007)], giving (7) where n m is the number of inferred mutations and T is the simulation time in generations.
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In an otherwise isogenic population of size N, a mutant haplotype with selection coefficient σ (denoting the fitness difference between the mutant and the wild-type population; σ= f a − fwildtype) is affected more by selection than drift above a frequency of ~ 1/ Nσ (Rouzine et al., 2001).
Therefore, segregation of the observed phenotype of a mutant with the selection marker has to be evaluated for several progeny.
For both positions of the selected mutant, we simulated with selection coefficients of 0.1, 0.05, 0.01 and 0.005.
This effect is likely to underlie the increased mean inferred selection coefficient called for mutants with constant selection coefficient 0.2, described above.
More recently, a collection of mutant strains tagged with selection markers in the entire S. japonicus genome and a cosmid library were generated (Furuya et al. 2012).
Therefore, legionellosis patients might have been infected with a complex L. pneumophila population containing low abundance of gyrA83 mutants, with subsequent selection of this population in patients #2 and #4 under fluoroquinolone therapy.
For example, induction of auxotrophies by mutagenesis in industrial strains unable to sporulate (and thus unfit for use in sexual hybridization experiments) can provide mutants with appropriate selection markers for rare mating or protoplast fusion experiments.
The single mutant with the highest selection coefficient was S83F (MLE s ^ = +.013 ) and the double S83F-D87N mutant displayed the highest selection coefficient of all tested strains (MLE s ^ = +.074 ).
The increased incidence of a second episode within 14, 21 and 28 days of a CQ treatment from 1995 to 1999 correlating with increasing of the 76T Pfcrt mutant frequency is consistent with selection of parasites (be they recrudescence or re-infection) during the post-treatment period.
All mutant stocks have been maintained with selection in favour of the mutant phenotype and, when necessary to avoid inbreeding depression, were outcrossed to the laboratory outbred WT stock.
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