Agent-based models (ABM) play a prominent role in guiding critical decision-making and supporting the development of effective policies for better urban resilience and response to the COVID-19 pandemic. However, many ABMs lack realistic representations of human mobility, a key process that leads to physical interaction and subsequent spread of disease. Therefore, we propose the application of Latent Dirichlet Allocation (LDA), a topic modeling technique, to foot-traffic data to develop a realistic model of human mobility in an ABM that simulates the spread of COVID-19. In our novel approach, LDA treats POIs as "words" and agent home census block groups (CBGs) as "documents" to extract "topics" of POIs that frequently appear together in CBG visits. These topics allow us to simulate agent mobility based on the LDA topic distribution of their home CBG. We compare the LDA based mobility model with competitor approaches including a naive mobility model that assumes visits to POIs are random. We find that the naive mobility model is unable to facilitate the spread of COVID-19 at all. Using the LDA informed mobility model, we simulate the spread of COVID-19 and test the effect of changes to the number of topics, various parameters, and public health interventions. By examining the simulated number of cases over time, we find that the number of topics does indeed impact disease spread dynamics, but only in terms of the outbreak's timing. Further analysis of simulation results is needed to better understand the impact of topics on simulated COVID-19 spread. This study contributes to strengthening human mobility representations in ABMs of disease spread.
Nucleosome DNA unwrapping and its disassembly into hexasomes and tetrasomes is necessary for genomic access and plays an important role in transcription regulation. Previous single-molecule mechanical nucleosome unwrapping revealed a low- and a high-force transitions, and force-FRET pulling experiments showed that DNA unwrapping is asymmetrical occurring always first from one side before the other. However, the assignment of DNA segments involved in these transitions remains controversial. Here, using high-resolution optical tweezers with simultaneous single-molecule FRET detection we show that the low-force transition corresponds to the undoing of the outer-wrap of one side of the nucleosome (~27 bp), a process that can occur either cooperatively or non-cooperatively, whereas the high-force transition corresponds to the simultaneous unwrapping of ~76 bp from both sides. This process may give rise stochastically to the disassembly of nucleosomes into hexasomes and tetrasomes whose unwrapping/rewrapping trajectories we establish. In contrast, nucleosome rewrapping does not exhibit asymmetry. To rationalize all previous nucleosome unwrapping experiments, it is necessary to invoke that mechanical unwrapping involves two nucleosome reorientations: one that contributes to the change in extension at the low-force transition, and another that coincides but does not contribute to the high-force transition.
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