Spatiotemporal trends of illegal activities from ranger-collected data in a Ugandan national park.

Within protected areas, biodiversity loss is often a consequence of illegal resource use. Understanding the patterns and extent of illegal activities is therefore essential for effective law enforcement and prevention of biodiversity declines. We used extensive data, commonly collected by ranger patrols in many protected areas, and Bayesian hierarchical models to identify drivers, trends, and distribution of multiple illegal activities within the Queen Elizabeth Conservation Area (QECA), Uganda. Encroachment (e.g., by pastoralists with cattle) and poaching of noncommercial animals (e.g., snaring bushmeat) were the most prevalent illegal activities within the QECA. Illegal activities occurred in different areas of the QECA. Poaching of noncommercial animals was most widely distributed within the national park. Overall, ecological covariates, although significant, were not useful predictors for occurrence of illegal activities. Instead, the location of illegal activities in previous years was more important. There were significant increases in encroachment and noncommercial plant harvesting (nontimber products) during the study period (1999-2012). We also found significant spatiotemporal variation in the occurrence of all activities. Our results show the need to explicitly model ranger patrol effort to reduce biases from existing uncorrected or capture per unit effort analyses. Prioritization of ranger patrol strategies is needed to target illegal activities; these strategies are determined by protected area managers, and therefore changes at a site-level can be implemented quickly. These strategies should also be informed by the location of past occurrences of illegal activity: the most useful predictor of future events. However, because spatial and temporal changes in illegal activities occurred, regular patrols throughout the protected area, even in areas of low occurrence, are also required.

Beyond mere diversity: tailoring combinatorial libraries for drug discovery.

Combinatorial library design attempts to choose the best set of substituents for a combinatorial synthetic scheme to maximize the chances of finding a useful compound, such as a drug lead. Initial efforts were focused primarily on maximizing diversity, perhaps allowing some bias by the inclusion of a small, fixed set of pharmacophoric substituents. However, many factors besides diversity impact good library design for drug discovery. A library can be better "tailored" by assigning the candidate substituents to categories such as polar, pharmacophoric, rigid, low molecular weight, and expensive. Stratified sampling by successive steps of D-optimal design generates diverse designs which are also consistent with desirable profiles of these properties. Comparing the diversity scores among design profiles reveals the tradeoffs between diversity, physical property distributions, synthetic difficulty, expense, and pharmacophoric bias. The diversity scores can be calibrated by scoring the best designs from subsets of the candidates made either from specific classes of substituents or by randomly eliminating candidates. This procedure shows how poor random designs are compared even to highly biased optimal designs. Library design requires a synergistic effort between computational and synthetic medicinal chemists, so specialized interactive software has been developed to integrate substructure searching, display, and statistical experimental design to facilitate this interaction for the effective design of well-tailored libraries.

Navigator: tools for informal structure-activity relationship discovery.

Navigator is a molecular database visualization system, designed to support exploratory data analysis and informal structure-activity relationship studies. In addition to the operations commonly found in chemical database systems, it provides new tools that facilitate substituent analysis and help elucidate the relationships among similar molecules and between related assays. Navigator's capabilities include two ways of displaying the relationships between analogs, mouse-sensitive charts of sets of molecules, mouse-sensitive plots of assay relationships, and access to a system for three-dimensional quantitative structure-activity relationship discovery. Navigator's mouse-based user interface provides a one-object/one-window paradigm that makes data manipulation easy even for inexperienced users. Navigator runs on Silicon Graphics workstations.

A shape-based machine learning tool for drug design.

Building predictive models for iterative drug design in the absence of a known target protein structure is an important challenge. We present a novel technique, Compass, that removes a major obstacle to accurate prediction by automatically selecting conformations and alignments of molecules without the benefit of a characterized active site. The technique combines explicit representation of molecular shape with neural network learning methods to produce highly predictive models, even across chemically distinct classes of molecules. We apply the method to predicting human perception of musk odor and show how the resulting models can provide graphical guidance for chemical modifications.