Fluorescence recovery after photobleaching (FRAP) is a well-established experimental technique to study binding and diffusion of molecules in cells. Although a large number of analytical and numerical models have been developed to extract binding and diffusion rates from FRAP recovery curves, active transport of molecules is typically not included in the existing models that are used to estimate these rates. Here we present a validated numerical method for estimating diffusion, binding/unbinding rates, and active transport velocities using FRAP data that captures intracellular dynamics through partial differential equation models. We apply these methods to transport and localization of mRNA molecules in Xenopus laevis oocytes, where active transport processes are essential to generate developmental polarity. By providing estimates of the effective velocities and diffusion, as well as expected run times and lengths, this approach can help quantify dynamical properties of localizing and nonlocalizing RNA. Our results confirm the distinct transport dynamics in different regions of the cytoplasm, and suggest that RNA movement in both the animal and vegetal directions may influence the timescale of RNA localization in Xenopus oocytes. We also show that model initial conditions extracted from FRAP postbleach intensities prevent underestimation of diffusion, which can arise from the instantaneous bleaching assumption. The numerical and modeling approach presented here to estimate parameters using FRAP recovery data is a broadly applicable tool for systems where intracellular transport is a key molecular mechanism.
In the Unites States, the public has a constitutional right to access criminal trial proceedings. In practice, it can be difficult or impossible for the public to exercise this right. We present JUSTFAIR: Judicial System Transparency through Federal Archive Inferred Records, a database of criminal sentencing decisions made in federal district courts. We have compiled this data set from public sources including the United States Sentencing Commission, the Federal Judicial Center, the Public Access to Court Electronic Records system, and Wikipedia. With nearly 600,000 records from the years 2001 - 2018, JUSTFAIR is the first large scale, free, public database that links information about defendants and their demographic characteristics with information about their federal crimes, their sentences, and, crucially, the identity of the sentencing judge.
Localization of messenger RNA (mRNA) at the vegetal cortex plays an important role in the early development of Xenopus laevis oocytes. While it is known that molecular motors are responsible for the transport of mRNA cargo along microtubules to the cortex, the mechanisms of localization remain unclear. We model cargo transport along microtubules using partial differential equations with spatially dependent rates. A theoretical analysis of reduced versions of our model predicts effective velocity and diffusion rates for the cargo and shows that randomness of microtubule networks enhances effective transport. A more complex model using parameters estimated from fluorescence microscopy data reproduces the time and spatial scales of mRNA localization observed in Xenopus oocytes, corroborates experimental hypotheses that anchoring may be necessary to achieve complete localization, and shows that anchoring of mRNA complexes actively transported to the cortex is most effective in achieving robust accumulation at the cortex.
In a complex system, the interactions between individual agents often lead to emergent collective behavior like spontaneous synchronization, swarming, and pattern formation. The topology of the network of interactions can have a dramatic influence over those dynamics. In many studies, researchers start with a specific model for both the intrinsic dynamics of each agent and the interaction network, and attempt to learn about the dynamics that can be observed in the model. Here we consider the inverse problem: given the dynamics of a system, can one learn about the underlying network? We investigate arbitrary networks of coupled phase-oscillators whose dynamics are characterized by synchronization. We demonstrate that, given sufficient observational data on the transient evolution of each oscillator, one can use machine learning methods to reconstruct the interaction network and simultaneously identify the parameters of a model for the intrinsic dynamics of the oscillators and their coupling.
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