New approaches are presented to infer plasma densities and satellite floating potentials from currents collected with fixed-bias multi-needle Langmuir probes (m-NLP). Using synthetic data obtained from kinetic simulations, comparisons are made with inference techniques developed in previous studies and, in each case, model skills are assessed by comparing their predictions with known values in the synthetic data set. The new approaches presented rely on a combination of an approximate analytic scaling law for the current collected as a function of bias voltage, and multivariate regression. Radial basis function regression (RBF) is also applied to Jacobsen et al's procedure (2010 Meas. Sci. Technol. 21 085902) to infer plasma density, and shown to improve its accuracy. The direct use of RBF to infer plasma density is found to provide the best accuracy, while a combination of analytic scaling laws with RBF is found to give the best predictions of a satellite floating potential. In addition, a proof-of-concept experimental study has been conducted using m-NLP data, collected from the Visions-2 sounding rocket mission, to infer electron densities through a direct application of RBF. It is shown that RBF is not only a viable option to infer electron densities, but has the potential to provide results that are more accurate than current methods, providing a path towards the further use of regression-based techniques to infer space plasma parameters.
Rising rates of resistance to antimicrobial drugs threaten the effective treatment of infections across the globe. Drug resistance has been established to emerge from non-genetic mechanisms as well as from genetic mechanisms. However, it is still unclear how non-genetic resistance affects the evolution of genetic drug resistance. We develop deterministic and stochastic population models that incorporate resource competition to quantitatively investigate the transition from non-genetic to genetic resistance during the exposure to static and cidal drugs. We find that non-genetic resistance facilitates the survival of cell populations during drug treatment while hindering the development of genetic resistance due to competition between the non-genetically and genetically resistant subpopulations. Non-genetic resistance in the presence of subpopulation competition increases the fixation times of drug resistance mutations, while increasing the probability of mutation before population extinction during cidal drug treatment. Intense intraspecific competition during drug treatment leads to extinction of susceptible and non-genetically resistant subpopulations. Alternating between drug and no drug conditions results in oscillatory population dynamics, increased resistance mutation fixation timescales, and reduced population survival. These findings advance our fundamental understanding of the evolution of resistance and may guide novel treatment strategies for patients with drug-resistant infections.
Rising rates of resistance to antimicrobial drugs threatens the effective treatment of infections across the globe. Recently, it has been shown that drug resistance can emerge from non-genetic mechanisms, such as fluctuations in gene expression, as well as from genetic mutations. However, it is unclear how non-genetic drug resistance affects the evolution of genetic drug resistance. We develop deterministic and stochastic population models to quantitatively investigate the transition from non-genetic to genetic resistance during the exposure to static and cidal drugs. We find that non-genetic resistance facilitates the survival of cell populations during drug treatment, but that it hinders the development of genetic resistance due to competition between the non-genetically and genetically resistant subpopulations. The presence of non-genetic drug resistance is found to increase the first-appearance, establishment, and fixation times of drug resistance mutations, while increasing the probability of mutation before population extinction during cidal drug treatment. These findings advance our fundamental understanding of the evolution of drug resistance and may guide novel treatment strategies for patients with drug resistant infections.
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