A regression analysis using simple descriptors for multiple dermal datasets: Going from individual membranes to the full skin.

In silico methods to estimate and/or quantify skin absorption of chemicals as a function of chemistry are needed to realistically predict pharmacological, occupational, and environmental exposures. The Potts-Guy equation is a well-established approach, using multi-linear regression analysis describing skin permeability (Kp) in terms of the octanol/water partition coefficient (logP) and molecular weight (MW). In this work, we obtained regression equations for different human datasets relevant to environmental and cosmetic chemicals. Since the Potts-Guy equation was published in 1992, we explored recent datasets that include different skin layers, such as dermatomed (including dermis to a defined thickness) and full skin. Our work was consistent with others who have observed that fits to the Potts-Guy equation are stronger for experiments focused on the epidermis. Permeability estimates for dermatomed skin and full skin resulted in low regression coefficients when compared to epidermis datasets. An updated regression equation uses a combination of fitted permeability values obtained with a published 2D compartmental model previously evaluated. The resulting regression equation was: logKp = -2.55 + 0.65logP - 0.0085MW, R2 = 0.91 (applicability domain for all datasets: MW ranges from 18 to >584 g/mol and -4 to >5 for logP). This approach demonstrates the advantage of combining mechanistic with structural activity relationships in a single modeling approach. This combination approach results in an improved regression fit when compared to permeability estimates obtained using the Potts-Guy approach alone. The analysis presented in this work assumes a one-compartment skin absorption route; future modeling work will consider adding multiple compartments.

Estimation of probability distributions of parameters using aggregate population data: analysis of a CAR T-cell cancer model.

In this effort we explain fundamental formulations for aggregate data inverse problems requiring estimation of probability distribution parameters. We use as a motivating example a class of CAR T-call cancer models in mice. After ascertaining results on model stability and sensitivity with respect to parameters, we carry out first elementary computations on the question how much data is needed for successful estimation of probability distributions.

Population model for the decline of Homalodisca vitripennis (Hemiptera: Cicadellidae) over a ten-year period.

The glassy-winged sharpshooter, Homalodisca vitripennis (Germar), is an invasive pest which presents a major economic threat to grape industries in California, because it spreads a disease-causing bacterium, Xylella fastidiosa. In this note we develop a time and temperature dependent mathematical model to analyze aggregate population data for H. vitripennis from a 10-year study consisting of biweekly monitoring of H. vitripennis populations on unsprayed citrus, during which H. vitripennis decreased significantly. This model was fitted to the aggregate H. vitripennis time series data using iterative reweighted weighted least squares (IRWLS) with assumed probability distributions for certain parameter values. Results indicate that the H. vitripennis model fits the phenological and temperature data reasonably well, but the observed population decrease may possibly be attributed to factors other than the abiotic effect of temperature. A key factor responsible for this decline but not analyzed here could be biotic, for example, potentially parasitism of H. vitripennis eggs by Cosmocomoidea ashmeadi. A biological control program targeting H. vitripennis utilizing the mymarid egg parasitoid Cosmocomoidea (formerly Gonatocerus) ashmeadi (Girault) is described.