Quantile regression estimates of animal population trends

Ecologists often estimate population trends of animals in time series of counts using linear regression to estimate parameters in a linear transformation of multiplicative growth models, where logarithms of rates of change in counts in time intervals are used as response variables. We present quantile regression estimates for the median (0.50) and interquartile (0.25, 0.75) relationships as an alternative to mean regression estimates for common density-dependent and density-independent population growth models. We demonstrate that the quantile regression estimates are more robust to outliers and require fewer distributional assumptions than conventional mean regression estimates and can provide information on heterogeneous rates of change ignored by mean regression. We provide quantile regression trend estimates for 2 populations of greater sage-grouse (Centrocercus urophasianus) in Wyoming, USA, and for the Crawford population of Gunnison sage-grouse (Centrocercus minimus) in southwestern Colorado, USA. Our selected Gompertz models of density dependence for both populations of greater sage-grouse had smaller negative estimates of density-dependence terms and less variation in corresponding predicted growth rates (λ) for quantile than mean regression models. In contrast, our selected Gompertz models of density dependence with piecewise linear effects of years for the Crawford population of Gunnison sage-grouse had predicted changes in λ across years from quantile regressions that varied more than those from mean regression because of heterogeneity in estimated λs that were both less and greater than mean estimates. Our results add to literature establishing that quantile regression provides better behaved estimates than mean regression when there are outlying growth rates, including those induced by adjustments for zeros in the time series of counts. The 0.25 and 0.75 quantiles bracketing the median provide robust estimates of population changes (λ) for the central 50% of time series data and provide a 50% prediction interval for a single new prediction without making parametric distributional assumptions or assuming homogeneous λs. Compared to mean estimates, our quantile regression trend estimates for greater sage-grouse indicated less variation in density-dependent λs by minimizing sensitivity to outlying values, and for Gunnison sage-grouse indicated greater variation in density-dependent λs associated with heterogeneity among quantiles.     

Mapping the binding sites of challenging drug targets

An increasing number of medically important proteins are challenging drug targets because their binding sites are too shallow or too polar, are cryptic and thus not detectable without a bound ligand or located in a protein–protein interface. While such proteins may not bind druglike small molecules with sufficiently high affinity, they are frequently druggable using novel therapeutic modalities. The need for such modalities can be determined by experimental or computational fragment based methods. Computational mapping by mixed solvent molecular dynamics simulations or the FTMap server can be used to determine binding hot spots. The strength and location of the hot spots provide very useful information for selecting potentially successful approaches to drug discovery.     

Evaluation of 2-indolcarbohydrazones as potent α-glucosidase inhibitors,in silico studies and DFT based stereochemical predictions

2-Indolcarbohydrazones 1–28 were synthesized and evaluated for their α-glucosidase inhibitory potential. A varying degree of inhibitory potential with IC₅₀ values in the range of 2.3 ± 0.11–226.4 ± 6.8 μM was observed while comparing these outcomes with the standard acarbose (IC₅₀ = 906.0 ± 6.3 μM). The stereochemistry of ten (10) randomly selected compounds (1, 3, 6, 8, 12, 18, 19, 23, 25 and 28) was predicted by Density Functional Theory (DFT). The stability of E isomer was deduced by comparing the calculated and experimental vibration modes of ν_CO, ν_NC and ν_CH (CH in NCH-R). It was observed that except compound 18, all other compounds were deduced to have E configuration while molecular modeling studies revealed the key interactions between enzyme and synthesized compounds.