Mathematical modeling of population structure in bioreactors seeded with light-controllable microbial stem cells.

Industrial bioreactors use microbial organisms as living factories to produce a wide range of commercial products. For most applications, yields eventually become limited by the proliferation of "escape mutants" that acquire a growth advantage by losing the ability to make product. The goal of this work is to use mathematical models to determine whether this problem could be addressed in continuous flow bioreactors that include a "stem cell" population that multiplies rapidly and could be used to compete against the emergence of cheater mutants. In this system, external stimuli can be used to induce stem cell multiplication through symmetric cell division, or to limit stem cell multiplication and induce higher production through an asymmetric cell division that produces one stem cell and one new product-producing "factory cell". Our results show product yields from bioreactors with microbial stem cells can be increased by 18% to 127% over conventional methods, and sensitivity analysis shows that yields could be improved over a broad range of parameter space.

Multiple Dose Pharmacokinetic Models Predict Bioavailability of Toxins in Vertebrate Herbivores.

In this paper, compartmental pharmacokinetic models are built to predict the concentration of toxic phytochemical in the gastrointestinal tract and blood following oral intake by an individual vertebrate herbivore. The existing single and multiple dose pharmacokinetic models are extended by inclusion of impulsive differential equations which account for an excretion factor whereby unchanged toxins are excreted in the feces due to gastrointestinal mobility. An index α is defined to measure the fraction of bioavailability attributed to the excretion factor of gastrointestinal motility. Sensitivity analysis was conducted and suggests, for any toxin, the bioavailability index α depends mostly on absorption rate of toxin from gastrointestinal tract into the blood, frequency of elimination due to gastrointestinal motility, and the frequency of toxin intake, under the model assumptions.