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AZD9291 (Osimertinib) is highly effective in treating EGFR-mutated non-small-cell lung cancers (NSCLCs) with T790M-mediated drug resistance. Despite the remarkable success of AZD9291, its binding pose with EGFR T790M remains unclear. Here, we report unbiased, atomic-level molecular dynamics (MD) simulations in which spontaneous association of AZD9291 with EGFR kinases having WT and T790M mutant gatekeepers was observed. Simulation-generated structural models suggest that the binding pose of AZD9291 with T790M differs from its binding pose with the WT, and that AZD9291 interacts extensively with the gatekeeper residue (Met 790) in T790M but not with Thr 790 in the WT, which explains why AZD9291 binds T790M with higher affinity. The MD simulation-generated models were confirmed by experimentally determined EGFR/T790M complex crystal structures. This work may facilitate the rational design of drugs that can overcome resistance mutations to AZD9291, and more generally it suggests the potential of using unbiased MD simulation to elucidate small-molecule binding poses.

Tooth agenesis is a type of dental anomaly in which individuals are missing teeth due to developmental failure as a result of genetic or environmental factors. With approximately one fourth of the population missing ≥1 third molar, tooth agenesis is considered a common dental anomaly. However, the severity of tooth agenesis can range from a missing single tooth to multiple teeth. When suffering from severe tooth agenesis, the patient's health and social relationships are often affected. The patient in this report congenitally lost 11 teeth and suffered from compromised esthetics and impaired chewing function. In such a severe tooth agenesis case, interdisciplinary treatments involving orthodontics, periodontics, and prosthodontics were engaged to reconstruct the ideal biology, function, and esthetics for the patient. With an interdisciplinary approach, the periodontist played an important role in the rehabilitation of the edentulous regions with implants in combination with various hard and soft tissue augmentation procedures. In addition, the patient with severe tooth agenesis presented with additional dental anomalies. The periodontist, therefore, had to collaborate with other specialists to provide early detection and intervention to avoid future complications, such as the management of infraoccluded ankylosed deciduous molars and aberrant frenum. The patient at the end of treatment had a good occlusion with improved function and esthetics. This case report describes the interdisciplinary treatment approach used and points out the role of periodontists in the treatment of a patient with severe tooth agenesis.

Diffusion coefficient measurements are important for many biological and material investigations, such as studies of particle dynamics and kinetics, and size determinations. Among current measurement methods, single particle tracking (SPT) offers the unique ability to simultaneously obtain location and diffusion information about a molecule while using only femtomoles of sample. However, the temporal resolution of SPT is limited to seconds for single-color-labeled samples. By directly imaging three-dimensional diffusing fluorescent proteins and studying the widths of their intensity profiles, we were able to determine the proteins' diffusion coefficients using single protein images of submillisecond exposure times. This simple method improves the temporal resolution of diffusion coefficient measurements to submilliseconds, and can be readily applied to a range of particle sizes in SPT investigations and applications in which diffusion coefficient measurements are needed, such as reaction kinetics and particle size determinations.

We probe the bending characteristics of functionalized graphene sheets with the tip of an atomic force microscope. Individual sheets are transformed from a flat into a folded configuration. Sheets can be reversibly folded and unfolded multiple times, and the folding always occurs at the same location. This observation suggests that the folding and bending behavior of the sheets is dominated by pre-existing kink (or even fault) lines consisting of defects and/or functional groups.

The cycle-life analysis of lithium ion batteries (LIBs) is generally performed from their brand-new state and under fixed charge/discharge (C/D) cycling conditions, especially under a constant cycle temperature. This, however, is not an adequate analysis since in real situations, an LIB is usually not in a fresh state and is cycled at an ambient temperature different from its past operating environment. To predict the remaining capacity of an aged LIB, we develop a four-parameter incremental fading model which introduces two quantities (K, Δ) related to the capacity loss rate and the increase of SEI thickness. The four parameters are constant in different temperatures and can be easily determined from a relatively small amount of cycle-life experimental data. We construct the temperature-independent K− Δ curve, which can capture the characteristic fading feature of a cycled LIB, called the fading trajectory in this study. From this curve, one can identify the current state of an aged LIB and its subsequent time evolution. This model accompanied by a simple experiment reveals that the nonlinear cycle fading of an aged LIB not only depends on its future cycling conditions, but it is also correlated with its past cycling history.

Existing methods for predicting the capacity fade of lithium ion batteries (LIBs) are typically limited to the description of cells under fixed charge/discharge (C/D) cycling conditions. The prediction requires a large amount of experimental data for various cycling environments to construct empirical equations or to obtain parameters in physical-based models. Based on the porous electrode theory, a semi-empirical model with three constant parameters is developed here. It is found that fading data at various temperatures collapse into a single curve on a newly proposed plot. This finding enables us to use a much smaller amount of cycle-life data to determine the values of these parameters, which sufficiently characterize the fading response under a broad range of cycling conditions. The prediction yielded from the model is confirmed by several scenarios with varying cycling conditions, such as temperature, depth of discharge, and C/D rate. A further prediction shows that different average C/D rates, which give rise to different cell-temperature histories, have a strong influence on the capacity degradation of an LIB. By introducing the average C/D rate, we analyze the capacity loss after 1500 cycles with the use of two types of charging protocols, from which two operational treatments are suggested.