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Biology subjects

Ashok, M.

Publications and source records attributed to Ashok, M..

3 recordsLinked to original sources

The Trajectory Statistics of Biological Exploratory Dynamics

Biological processes, from molecules diffusing to their regulatory destinations to whales pursuing food or mates, are widely exploratory. Such behaviors are effective when some verifiable functional state or outcome can be reached regardless of initial conditions. In these cases, systems repeatedly undergo distinct and abortive trajectories; the process only ends when the system finds 'right' outcomes. This dominance of the terminal condition (and indifference to the initial state) provokes a very different perspective than the conventional 'dynamical systems' framework that has been a centerpiece of the quantitative sciences for centuries. We hypothesize that many of these problems defy the initial-condition driven or gradients on landscapes so useful in problems ranging from mechanics to electrodynamics to chemical kinetics to mass and heat transport. We examine several mathematical frameworks that capture and unify key aspects of exploratory dynamics. One powerful way of thinking of such processes is the geometric distribution, where repeated failures are punctuated by a successful trajectory. We develop intuitions for how random walks with resets accelerate search processes. We highlight fresh and surprising behaviors of search under drift, cues, and checkpoints. Last, appreciating the probability of trajectories conditioned on satisfying macroscopic final outcomes reveals a language for the potency of variation sculpted by selection in their broadest forms. This can give the fictitious appearance of the future making itself known in the present, but we view this as conceptually similar to the way 'fictitious forces' arise in non-inertial reference frames. These approaches stress unity, open questions, and applications across a range of biological phenomena.

biophysics↗

Energetic gradients emerge in developing motor-microtubule structures

Living matter produces a variety of beautiful spatiotemporal structures and patterns that are not enduringly present in their nonliving counterparts. These ordered, non-equilibrium steady states are often sustained through the consumption of energy. Here, we investigate the energetic cost of assembling an ordered aster from an initially disordered, uniform mixture of cytoskeletal microtubules and kinesin motors. Using a calibrated fluorescent ATP reporter, we measure reproducible radial ATP gradients on scales of tens of microns that establish within, and persist over, tens of minutes, alongside coupled spatial gradients in motor density. These appreciable gradients are predicted by a reaction-diffusion model that acknowledges the localization of ATP consumption to regions where both molecular motors and microtubules are sufficiently abundant to encourage consumption, as confirmed by finite element modeling. With our results, we compare the power per volume required by our cytoskeletal networks with the known power per volume expenditure in cells. Comparison of our measured results with estimates of the dissipative processes available to motor-microtubule mixtures leads to the hypothesis that maintaining spatial motor gradients dominates the energetic demand in this system. Our direct quantification of energetic fluxes across space unlocks future explorations of what steady states are accessible to cells, and how the cytoskeleton drives broad spatial organization. SignificanceHow much energy do organisms pay to form and maintain their organizing biochemical patterns? Existing measurements of cellular metabolism and energy expenditures largely resolve net or supply-side biochemical fluxes, without spatial information, impeding the study of this basic question. Here, we develop an experimental approach to directly measure the distributions of biochemical energy that respond to power expenditures of cytoskeletal motor-microtubule networks as they form aster structures, reminiscent of those found in the mitotic spindle. As these structures self-assemble, calibrated readouts in real molecular units register large, reproducible, and long-lived gradients of ATP. We interpret these measurements by developing theory to account for the functional destinies of energy expenditure. These advances clarify outstanding questions of energy in living matter.

biophysics↗

Deep Multi-State Dynamic Recurrent Neural Networks Operating on Wavelet Based Neural Features for Robust Brain Machine Interfaces

We present a new deep multi-state Dynamic Recurrent Neural Network (DRNN) architecture for Brain Machine Interface (BMI) applications. Our DRNN is used to predict Cartesian representation of a computer cursor movement kinematics from open-loop neural data recorded from the posterior parietal cortex (PPC) of a human subject in a BMI system. We design the algorithm to achieve a reasonable trade-off between performance and robustness, and we constrain memory usage in favor of future hardware implementation. We feed the predictions of the network back to the input to improve prediction performance and robustness. We apply a scheduled sampling approach to the model in order to solve a statistical distribution mismatch between the ground truth and predictions. Additionally, we configure a small DRNN to operate with a short history of input, reducing the required buffering of input data and number of memory accesses. This configuration lowers the expected power consumption in a neural network accelerator. Operating on wavelet-based neural features, we show that the average performance of DRNN surpasses other state-of-the-art methods in the literature on both single- and multi-day data recorded over 43 days. Results show that multi-state DRNN has the potential to model the nonlinear relationships between the neural data and kinematics for robust BMIs.

neuroscience↗