Modeling, Simulating, and Parameter Fitting of Biochemical Kinetic Experiments

In many chemical and biological applications, systems of differential equations containing unknown parameters are used to explain empirical observations and experimental data. The DEs are typically nonlinear and difficult to analyze, requiring numerical methods to approximate the solutions. Compounding this difficulty are the unknown parameters in the DE system, which must be given specific numerical values in order for simulations to be run. Estrogen receptor protein dimerization is used as an example to demonstrate model construction, reduction, simulation, and parameter estimation. Mathematical, computational, and statistical methods are applied to empirical data to deduce kinetic parameter estimates and guide decisions regarding future experiments and modeling. The process demonstrated serves as a pedagogical example of quantitative methods being used to extract parameter values from biochemical data models.Comment: 23 pages, 9 figures, to be published in SIAM Revie

Outcome of dyadic conflict in male green swordtail fish, Xiphophorus helleri: effects of body size and prior dominance

The relative contribution of prior experience and of size asymmetries to the determination of dyadic dominance between unfamiliar individuals was examined using pairs of green swordtail fish, Xiphophorus helleri. Three experiments were conducted to assess the extent to which superiority in size could override potential handicaps resulting from prior experience. These results indicated that prior experience accounted for dyadic dominance when the size advantage of a previously subordinate over a previously dominant opponent was less than 25 mm2. However, as the lateral surface of the subordinate fish increased, neither previous experience nor size differences clearly accounted for the outcome of dyadic conflict. Even when the size advantage of subordinate opponents was in the 126-150 mm2 range, size differences did not adequately explain the outcome. In conflicts between large previously subordinate and smaller dominant fish, there was evidence for an inverse linear relation between the effects of size and the likelihood of establishing dyadic dominance. In general, males with prior experience as subordinates had to be at least 40% larger than a previously dominant fish to win a significant proportion of conflicts. These results indicate that prior agonistic experience and body size effects can be additive when at the advantage of one opponent. These factors can also cancel each other out when in opposition, at least when size differences are not extreme. The results also confirm the main effect of both factors as well as their interaction in the determination of conflict outcomes for X. helleri

The effects of a chemosterilant (Mestranol) on population and behavior in the Richardson's ground squirrel (Spermophilus richardsonii) in Alberta

A chemosterilant, mestranol, was administered to three populations of Richardson's ground squirrel in southeastern Alberta. Mestranol was given to all squirrels in one plot, to only 50 percent in another plot, while a third plot remained as control. In all plots social behavior and population dynamics were followed over two seasons by live trapping and visual observations. Mestranol sterilized all females who received the drug shortly before or in early pregnancy; accordingly the birth rates were reduced. Levels of total aggression were also reduced but increased survival and immigration rates nullified the effects of the treatment during the first season. During the second season, low birth rates due to repeated treatment in one plot and to adult emigration and unknown causes in the other, were not compensated for by immigration. As a result of the repeated mestranol treatment and in one case also of adult emigration, the numbers of squirrels were reduced in the vicinity, thus limiting potential immigration in the treated plots. As a consequence, both treated populations crashed, demonstrating the effectiveness of mestranol

A Comparative Life Cycle Assessment between a Metered Dose Inhaler and Electric Nebulizer

Life cycle assessment (LCA) evaluates the environmental impact of a product based on the materials and processes used to manufacture the item as well as the item’s use and disposal. The objective of this LCA was to evaluate and compare the environmental impact of a metered dose inhaler, specifically the Proventil® HFA inhaler (Merk & Co., Inc., Kenilworth, NJ, USA), and an electric nebulizer, specifically the DeVilbiss Pulmo-Aide® nebulizer (DeVilbiss, Port Washington, NY, USA). GaBi LCA software was used to model the global warming potential (GWP) of each product by using substantiated data and well-justified assumptions for the components, manufacturing, assembly, and use of both devices. The functional unit used to model each device was one dose of the active drug, albuterol sulfate. The inhaler’s GWP, 0.0972 kg CO2-eq, was greater than the nebulizer’s even when uncertain parameters were varied ±100x. During the use phase ofa the inhaler, which accounted for approximately 96% of the inhaler’s total GWP, HFA 134a is used as a propellant to deliver the drug. The total GWP for the electric nebulizer was 0.0294 kg CO2-eq assuming that the mouthpiece was cleaned in a dishwasher, while it was 0.0477 kg CO2-eq when the nebulizer mouthpiece was hand washed between uses. The GWP breakeven scenario between dishwashing and hand washing occurred when the mouthpiece accounted for 10% of the dishwasher load

Inversion of initial dominance relationships following the interchange of roles of resident and intruder within pairs of male swordtail fish (Xiphophorus helleri)

This experiment consisted of 75 different pairs composed of two male adults Xiphophorus helleri meeting each other twice. On the first occasion, one of the fish was familiarized with the meeting place for 3h (resident) while its opponent was familiarized with another aquarium (intruder). Upon dominance of one individual over the other, the pair members were separated and returned to their respective home groups for 168 hours (7 days). After this period of separation, the same pair members were reunited and met while roles had been reversed: the initial resident became the intruder, and the initial intruder was given prior-residency. Individuals in the initial resident role defeated the initial intruder in a significant majority of cases (76%). On their second meeting, the newly established dominance relationship was noted in favour of the new resident in a significant majority of cases (82%), and in a reversed direction as compared to the initially established dominance order. This shows that prior-residence is a powerful determinant of dyadic dominance outcome in Xiphophorus males when fish show minimal size differences