Computational Oral Absorption Simulation for Low‐Solubility Compounds

Bile micelles play an important role in oral absorption of low‐solubility compounds. Bile micelles can affect solubility, dissolution rate, and permeability. For the pH–solubility profile in bile micelles, the Henderson–Hasselbalch equation should be modified to take bile‐micelle partition into account. For the dissolution rate, in the Nernst–Brunner equation, the effective diffusion coefficient in bile‐micelle media should be used instead of the monomer diffusion coefficient. The diffusion coefficient of bile micelles is 8‐ to 18‐fold smaller than that of monomer molecules. For permeability, the effective diffusion coefficient in the unstirred water layer adjacent to the epithelial membrane, and the free fraction at the epithelial membrane surface should be taken into account. The importance of these aspects is demonstrated here using several in vivo and clinical oral‐absorption data of low‐solubility model compounds. Using the theoretical equations, the food effect on oral absorption is further discussed.     

Effect of soil water stress on soil respiration and its temperature sensitivity in an 18-year-old temperate Douglas-fir stand

We analyzed 17 months (August 2005 to December 2006) of continuous measurements of soil CO₂ efflux or soil respiration (R_S) in an 18‐year‐old west‐coast temperate Douglas‐fir stand that experienced somewhat greater than normal summertime water deficit. For soil water content at the 4 cm depth (θ) > 0.11 m³ m^?3 (corresponding to a soil water matric potential of ?2 MPa), R_S was positively correlated to soil temperature at the 2 cm depth (T_S). Below this value of θ, however, R_S was largely decoupled from T_S, and evapotranspiration, ecosystem respiration and gross primary productivity (GPP) began to decrease, dropping to about half of their maximum values when θ reached 0.07 m³ m^?3. Soil water deficit substantially reduced R_S sensitivity to temperature resulting in a Q₁₀ significantly < 2. The absolute temperature sensitivity of R_S (i.e. dR_S/dT_S) increased with θ up to 0.15 m³ m^?3, above which it slowly declined. The value of dR_S/dT_S was nearly 0 for θ < 0.08 m³ m^?3, thereby confirming that R_S was largely unaffected by temperature under soil water stress conditions. Despite the possible effects of seasonality of photosynthesis, root activity and litterfall on R_S, the observed decrease in its temperature sensitivity at low θ was consistent with the reduction in substrate availability due to a decrease in (a) microbial mobility, and diffusion of substrates and extracellular enzymes, and (b) the fraction of substrate that can react at high T_S, which is associated with low θ. We found that an exponential (van't Hoff type) model with Q₁₀ and R₁₀ dependent on only θ explained 92% of the variance in half‐hourly values of R_S, including the period with soil water stress conditions. We hypothesize that relating Q₁₀ and R₁₀ to θ not only accounted for the effects of T_S on R_S and its temperature sensitivity but also accounted for the seasonality of biotic (photosynthesis, root activity, and litterfall) and abiotic (soil moisture and temperature) controls and their interactions.     

SPECIATION AND FEATHER ORNAMENTATION IN BIRDS

The hypothesis that sexual selection promotes speciation has rarely been tested. We identified 70 evolutionarily independent events of feather ornaments in birds. For each focal species we noted the number of ornamented and nonornamented species belonging to its genus and its number of subspecies, as well as its mating system and the extent of its geographic range. For purposes of comparison, we randomly chose a second, nonornamented species for which we obtained information on the number of subspecies, and in cases in which the nonornamented species was in the same genus, we chose a third, nonornamented species in a related genus and obtained the same information. We then noted the number of species in each genus and the difference in numbers of species, or species richness, between paired genera. For the genera of the focal ornamented species, we regressed number of ornamented species on number of nonornamented species and found a positive relationship. As number of species per genus rose, number of ornamented species per genus rose more rapidly, indicating that more speciose genera have a higher proportion of ornamented species than less speciose genera. We then took the deviations from this regression, the residual number of species, and regressed them on the differences in species richness between the paired genera. This relationship was positive indicating that ornamented genera with more than the expected number of ornamented species were more speciose with respect to their paired genera than were genera with fewer than the expected number of ornamented species. Finally, we compared the deviations from this regression, the residual number of ornamented species, with species' mating system and found a greater residual number of ornamented species among species whose mating system is associated with greater skew in male mating success and thus more intense sexual selection. Ornamented species had more subspecies than nonornamented species, even when controlling for geographic range, suggesting an association between subspeciation and ornaments.     

The Effects of Misspecification of a Regression Model

The consequences of the misspecification of a regression model are considered. For small effects of covariates a proportional consistency theorem is derived. The consistent estimation of the covariance matrix of the estimates is discussed.     

A Generalization of the GMANOVA-Model

It is shown that in some experimental designs the MANOVA- and the GMANOVA-model are too restrictive either to yield all hypothesis tests of interest or to reflect all known features of the design. An extension of these models is derived by relating the response vectors with the unknown model parameters by linear equations which may be completely different for each of the p components of the response vector and for each of the n independent vectors. For situations, in which a Wishart-distributed estimator for the underlying common covariance matrix is attainable, a test for any s-dimensional linear hypothesis on the model parameters is derived.     

Modeling productivity of a salt marsh

A model of primary productivity in a salt marsh is developed and compared to a regression analysis study of data showing dependence of growth on growing season, mean tidal height, and average monthly temperatures for several grass species.     

Optimal Split-plot Designs for a Mixed Model

Exact tests are given, for the usual hypotheses on split-plot models with random blocks and fixed treatment effects, considering different numbers of blocks for each level of whole-plot treatment and assuming normally distributed observations. U- and D-optimal designs are considered with respect to the tests of main effects and interactions as well as to estimation of parameters.