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Narayanan, H.

Publications and source records attributed to Narayanan, H..

4 recordsLinked to original sources

Extracellular vesicles aid in the transfer of long-term associative memory between Caenorhabditis elegans

Memory formation is necessary for the survival of animals across phyla. Here, we elucidate the mechanism underlying the formation of long-term associative memory (LTAM) formed by treating Caenorhabditis elegans with a volatile chemoattractant and heat. Previous work has shown that training animals with a paradigm involving heat and isoamyl alcohol (IAA) simultaneously, causes C. elegans to lose their attraction to IAA. In this study, we elaborate on the mechanism behind this LTAM formation and suggest that during training with heat and IAA, C. elegans release extracellular vesicles (EVs) that upon being taken up by the same trained animals or their untrained counterparts causes the organism to lose attraction to IAA. Our data suggests that the vesicles are highly specific to the training paradigms used and differ with differing cues. Finally, we show that this mechanism of transfer of LTAM appears to be conserved between C. elegans and C. briggsae allowing for both intra and interspecies transfer of memory.

neuroscience↗

Accelerating Cell Culture Media Development Using Bayesian Optimization-Based Iterative Experimental Design

Optimizing operational conditions for complex biological systems used in life sciences research and biotechnology is an arduous task. Here, we have applied a Bayesian Optimization-based iterative framework for experimental design to accelerate cell culture media development for two applications. First, we show this approach yields new compositions of media with cytokine supplementation to maintain the viability and distribution of PBMCs in culture. Second, we applied this framework to optimize the production of three recombinant proteins in K.phaffii cultivations. For both applications, we identified conditions with improved outcomes compared to the initial standard media using 3 to 30 times fewer experiments than other methods such as the Design of Experiments. Subsequently, we also demonstrated the extensibility of our approach to efficiently account for additional design factors through transfer learning. These examples demonstrate how coupling data collection, modeling, and optimization in this iterative paradigm, while using an exploration-exploitation tradeoff in each iteration, can reduce the time and resources for these types of optimizations.

bioengineering↗

Hybrid Gaussian Process Models for continuous time series in bolus fed-batch cultures

Hybrid modeling, meaning the integration of data-driven and knowledge-based methods, is quickly gaining popularity among many research fields, including bioprocess engineering and development. Recently, the data-driven part of hybrid methods have been largely extended with machine learning algorithms (e.g., artificial neural network, support vector regression), while the mechanistic part is typically using differential equations to describe the dynamics of the process based on its current state. In this work we present an alternative hybrid model formulation that merges the advantages of Gaussian Process State Space Models and the numerical approximation of differential equation systems through full discretization. The use of Gaussian Process Models to describe complex bioprocesses in batch, fed-batch, has been reported in several applications. Nevertheless, handling the dynamics of the states of the system, known to have a continuous time-dependent evolution governed by implicit dynamics, has proven to be a major challenge. Discretization of the process on the sampling steps is a source of several complications, as are: 1) not being able to handle multi-rate date sets, 2) the step-size of the derivative approximation is defined by the sampling frequency, and 3) a high sensitivity to sampling and addition errors. We present a coupling of polynomial regression with Gaussian Process Models as representation of the right-hand side of the ordinary differential equation system and demonstrate the advantages in a typical fed-batch cultivation for monoclonal antibody production.

bioengineering↗

Functional-Hybrid Modeling through automated adaptive symbolic regression for interpretable mathematical expressions

Mathematical models used for the representation of (bio)-chemical processes can be grouped into two broad paradigms: white-box or mechanistic models, completely based on knowledge or black-box data-driven models based on patterns observed in data. However, in the past two-decade, hybrid modeling that explores the synergy between the two paradigms has emerged as a pragmatic compromise. The data-driven part of these have been largely based on conventional machine learning algorithm (e.g., artificial neural network, support vector regression), which prevents interpretability of the finally learnt model by the domain-experts. In this work we present a novel hybrid modeling framework, the Functional-Hybrid model, that uses the ranked domain-specific functional beliefs together with symbolic regression to develop dynamic models. We demonstrate the successful implementation of these hybrid models for four benchmark systems and a microbial fermentation reactor, all of which are systems of (bio)chemical relevance. We also demonstrate that compared to a similar implementation with the conventional ANN, the performance of Functional-Hybrid model is at least two times better in interpolation and extrapolation. Additionally, the proposed framework can learn the dynamics in 50% lower number of experiments. This improved performance can be attributed to the structure imposed by the functional transformations introduced in the Functional-Hybrid model.

bioengineering↗