Generation and Classification of Activity Sequences for Spatiotemporal Modeling of Human Populations.

Human activity encompasses a series of complex spatiotemporal processes that are difficult to model but represent an essential component of human exposure assessment. A significant empirical data source, like the American Time Use Survey (ATUS), can be leveraged to model human activity. However, tractable models require a better stratification of activity data to inform about different, but classifiable groups of individuals, that exhibit similar activity sequences and mobility patterns. Using machine learning algorithms, we developed an unsupervised classification and sequence generation method that is capable of generating coherent and stochastic sequences of activity from the ATUS data. This classification, when combined with any spatiotemporal exposure profile, allows the development of stochastic models of exposure patterns and records for groups of individuals exhibiting similar activity behaviors.

STHAM: an agent based model for simulating human exposure across high resolution spatiotemporal domains.

Human exposure to particulate matter and other environmental species is difficult to estimate in large populations. Individuals can encounter significant and acute variations in exposure over small spatiotemporal scales. Exposure is strongly tied to both the environmental and activity contexts that individuals experience. Here we present the development of an agent-based model to simulate human exposure at high spatiotemporal resolutions. The model is based on simulated activity and location trajectories on a per-person basis for large geographical areas. We demonstrate that the model can successfully estimate trajectories and that activity patterns have been validated against traffic patterns and that can be integrated with exposure-agent geographical distributions to estimate total human exposure.

Report on the sixth blind test of organic crystal structure prediction methods.

The sixth blind test of organic crystal structure prediction (CSP) methods has been held, with five target systems: a small nearly rigid molecule, a polymorphic former drug candidate, a chloride salt hydrate, a co-crystal and a bulky flexible molecule. This blind test has seen substantial growth in the number of participants, with the broad range of prediction methods giving a unique insight into the state of the art in the field. Significant progress has been seen in treating flexible molecules, usage of hierarchical approaches to ranking structures, the application of density-functional approximations, and the establishment of new workflows and `best practices' for performing CSP calculations. All of the targets, apart from a single potentially disordered Z' = 2 polymorph of the drug candidate, were predicted by at least one submission. Despite many remaining challenges, it is clear that CSP methods are becoming more applicable to a wider range of real systems, including salts, hydrates and larger flexible molecules. The results also highlight the potential for CSP calculations to complement and augment experimental studies of organic solid forms.

Molecular dynamics simulations in drug delivery research: Calcium chelation of G3.5 PAMAM dendrimers.

Poly(amido amine) (PAMAM) dendrimers have been considered as possible delivery systems for anticancer drugs. One potential advantage of these carriers would be their use in oral formulations, which will require absorption in the intestinal lumen. This may require the opening of tight junctions which may be enabled by reducing the Ca2+ concentration in the intestinal lumen, which has been shown as an absorption mechanism for EDTA (ethylenediaminetetraacetic acid). Using molecular dynamics simulations, we show that the G3.5 PAMAM dendrimers are able to chelate Ca2+ at similar proportions to EDTA, providing support to the hypothesis that oral formulations of PAMAM dendrimers could use this high chelating efficiency as a potential mechanism for permeating the tight junctions of the intestines if other formulation barriers could be overcome.

Crystal Structure Prediction from First Principles: The Crystal Structures of Glycine.

Here we present the results of our unbiased searches of glycine polymorphs obtained using the Genetic Algorithms search implemented in Modified Genetic Algorithm for Crystals coupled with the local optimization and energy evaluation provided by Quantum Espresso. We demonstrate that it is possible to predict the crystal structures of a biomedical molecule using solely first principles calculations. We were able to find all the ambient pressure stable glycine polymorphs, which are found in the same energetic ordering as observed experimentally and the agreement between the experimental and predicted structures is of such accuracy that the two are visually almost indistinguishable.