Neelesh A. Patankar - US grants

Abstract
CTS-0134546
N. Patankar, Northwestern University

The PI is proposing to develop a broad range of simulation techniques to address several difficult and important problems in the area of modeling nanoscale systems such as MEMS devices, including Brownian motion of complex shape microstructures, motion of charged particles and motion of flexible molecules.

The PI is also proposing to develop a hybrid continuum/atomistic simulation for systems that span a broad range of length scales. All of the techniques are either novel or are building off of state of the art work in the literature.

In the education plan, the PI proposes to develop two undergraduate courses and one graduate course in the area of computational methods for MEMS devices. The two undergraduate courses will deal with fluid simulations associated with these devices and the graduate course will incorporate the more novel numerical techniques described in the research plan.

NER: Particle Light Valves
PI. Rod Ruoff, Northwestern University

Abstract. This project concerns fabrication of identical disc-shaped particles in the ~300 to 1000 nm diameter size range and of small and uniform thickness (ranging from 10 to 50 nm, approximately), and study of their light scattering when immersed in a liquid and oriented by an AC electric field. Our team includes an expert in particle fabrication and properties measurements (Ruoff), and in electrodynamics and fluid dynamics modeling (Schatz and Patankar, respectively).
The fluid mechanics, electrodynamics, and light scattering studies of this effort are forefront science, and fabrication of the particle size and type in sufficient quantity is a challenging nano-engineering problem. This work will lead to understanding of the electrokinetics of the interaction of an AC field and particles of appropriate size to well scatter visible light, and the interaction of light with such particles. The understanding that will be generated should be of immense interest to the colloid, fluid dynamics, particle fabrication, and light scattering communities.

CBET-0828749
Patankar

The physical principles underlying the extraordinary mobility of swimming and flying animals have been the subject of years of effort and there is still much that is not understood. This study develops an efficient numerical method for fully resolved simulation of self-propulsion of organisms called Fully Resolved Momentum Redistribution for self Propulsion (FuRMoRP). It will be used to study swimming fish; however, it is sufficiently general to function for small flying animals as well. The motivation to develop such a tool is two-fold: first, to develop a high resolution efficient fluid simulation technology that is transformational by its potential to significantly impact many interdisciplinary areas; second, to gain insight into a number of fundamental problems in aquatic locomotion which will also lead to insights into the design of a novel, highly-maneuverable underwater vehicle being developed through a separate project in the Co-PI's lab. The maneuverability and efficiency of fish is inspiring new styles of propulsion and maneuvering in underwater vehicles for applications such as undersea exploration and environmental monitoring. The development of such vehicles will depend on the resolution of open issues in aquatic locomotion which will be studied here using FuRMoRP applied to three important swimming modes and fish morphologies. The PIs hope to answer specific questions: What is the most efficient deformation kinematics three given fish types? How do they compare with experimentally observed gaits? What are their comparative efficiencies? The education plan involves developing new graduate and undergraduate courses, fluid animations for explanation of biofluid-dynamic principles, a book project, and international outreach. For outreach, the PIs will work with the world renowned Shedd Aquarium in Chicago to help develop a more educational display of the electric eels. The display will provide real-time acoustic and visual cues to the visitors to help them appreciate some of the fluid dynamical science and beauty of the electric eels.

In the traditional view, the nervous system performs the computational "heavy lifting" in an organism. This view neglects, however, the critical role of biomaterials, passive mechanical physics, and other pre-neuronal or non-neuronal systems. Given that neurons consume forty times more energy per unit mass than structural materials such as bone, it is better, when possible, that biological systems employ relatively inexpensive structural materials rather than relying on more costly neuronal control. In this "bone-brain continuum" view, animal intelligence and behavioral control systems can only be understood using integrative modeling approaches that expose the computational roles of both neural and non-neural substrates and their close coupling in behavioral output. To this end, a group of researchers from Northwestern University, The Johns Hopkins University, and Harvard University propose to create a unique high fidelity neuromechanical model of a vertebrate. The effort is divided between the development of a general purpose computational tool set for neuromechanics research and application of these tools to an ideally suited model system, weakly electric knifefish.

The research will lead to breakthroughs in fundamental problems of how nervous systems work together with biomechanics to generate adaptive behavior. The final goal of the research is to construct an integrated neuromechanical model of a unique biological system - weakly electric knifefish - that places biomechanics and neural control on equal footing. Prior such neuromechanical models have used highly simplified models of mechanics and highly abstracted neuronal control approaches. This research advances the state of the art by incorporating high-fidelity mechanics with neuronal mechanisms motivated by direct neurophysiological evidence. Ultimately, this computational approach will help elucidate how animals distribute computations between brain and bone.

1066575
Patankar

Summary description: Deciphering the logic behind how neural circuits generate behavior is a fundamental question in neuroscience. Locomotion offers a unique opportunity to probe issues of neuronal organization because motor circuitry generates a measurable product ? movement. Thus, studies of neural circuits for movement can not only help understand how the nervous system functions in general, but can also help to repair the motor circuitry after it has been disrupted, either by injury or disease. To fully grasp how to address the clinical challenges of overcoming neuronal disease or injury, it is informative to look for solutions in natural processes. This proposal is focused on the fundamental science underlying this transformational vision. The NU team will concentrate on discovering and understanding the function of spinal motor circuitry of a model system: the zebrafish.

Intellectual merit: A major drawback of modern computational models is considered to be that the patterns of connectivity among spinal neurons are largely assumed. With a large parameter space, the assumed neural circuitry in the computational models, that mimic natural behavior, may not be the actual circuitry in organisms. The NU team has designed a research approach based on the hypothesis that information about the required muscle forcing for movement can be used to discover the actual neural circuitry. Hence, instead of assuming any neural circuitry, they propose a novel inverse paradigm in which they will first identify the muscle forcing required to produce the observed swimming kinematics. Second, they will construct possible neural circuits that could lead to the predicted muscle forcing. Finally, they will use transgenic zebrafish lines to hunt for classes of neurons predicted by the modeling, but as yet unidentified.
Transformational impact: This project will lead to the discovery of new classes of neurons and the related circuitry, and to a fundamental understanding of how neuronal activation leads to a sequence of events in which the muscle energy is focused and transformed into the translational kinetic energy of movement. These fundamental discoveries and insights will not be restricted to the zebrafish model system but will conceptually apply in general to vertebrates whose movements range from swimming to limbed locomotion.

Broader impact: The PIs will develop new interdisciplinary courses. The work done in this proposal will be a crucial application example that will be introduced in a book on computational methods that the PI is writing. The PI is also developing a novel approach based on computer animation to teach the fundamental principles in his research field. These educational videos will be broadly distributed through the internet by using YouTube.

The rodent vibrissal-trigeminal system is one of the most important models in neuroscience for the study of sensorimotor integration. To date, however, research has focused exclusively on direct tactile sensation. Recent results from the Hartmann and Gopal laboratories have demonstrated that rat vibrissae have a robust and repeatable mechanical response to airflow. In addition, neurons in the vibrissal-trigeminal system are known to respond to air puffs. These results suggest that the rat may use its vibrissae to detect air currents and determine wind direction. The Northwestern-Elmhurst team will perform mechanical, behavioral, and computational studies to characterize the role of vibrissae in wind-following behaviors, and the vibrissal-related neural response to air currents. These will constitute some of the first investigations of the underlying mechanisms that permit terrestrial mammals to sense and follow the wind. The team will specifically identify the morphological features of vibrissae and their orientation on the mystacial pad that enable flow sensing behaviors. They will investigate the broad hypothesis that differential mechanical deformations of the vibrissae across the mystacial pad can encode a variety of flow parameters. Finally, behavioral experiments will be performed to determine the extent to which the rat uses its vibrissae to sense airflow, and to quantify the movement strategies used during anemotaxis in the behaving animal. The partnership between Northwestern and Elmhurst will provide significant research opportunities for undergraduates; in addition, videos will be developed to teach the fundamental principles of fluid dynamics and biological sensing that underlie this research. The proposed work has potentially large implications for olfactory localization and the structure of the olfactory system, and is likely to lead to the development of novel flow-sensing technologies.

Over the last decade there has been rapid progress in the manufacturing and design of materials and devices that employ small-scale active particles to produce novel physical behaviours such as self-organizing flows (e.g., active colloidal suspensions), or to perform specific tasks such as cargo transport (e.g., targeted drug delivery). While much progress has been made experimentally, theoretical and computational modelling lags behind, due to the difficulty in designing suitable numerical algorithms and the lack of public-domain codes capable of capturing the complex multi-physics of active propulsion. In this work we develop novel computational methods for simulating active-particles suspended in fluid, and implement the developed techniques in the public-domain code IBAMR, therefore making them available to applied researchers in physics and engineering. A specific distinguishing aspect of the work is the consistent inclusion of the random Brownian motion necessarily present when dealing with small-scale flows due to the small numbers of molecules involved in the process. Such stochastic effects are important in flows at micro and nano scales typical of nano- and micro-fluidic and microelectromechanical devices, novel materials such as nanofluids, and biological systems such as lipid membranes, Brownian molecular motors, and nanopores. We therefore expect the work to have a broad range of applications in science and engineering, beyond the specific research goals detailed below. The scientific component of this project will be supplemented by an educational and outreach component, including the development and enrichment of new graduate courses, such as Coarse Grained Modeling of Materials, which will include training in statistical mechanics, applied stochastic analysis, fluid dynamics, and high-performance computing.

This collaborative project focuses on computational methods for problems involving Brownian rigid and semi-rigid structures immersed in a fluid. Examples include colloidal particles, polymer chains, and macromolecules in a solvent. We aim to develop novel methods for fluid-structure coupling at small Reynolds numbers that consistently include the effects of thermal fluctuations. At small scales, the motion of immersed structures is driven by thermal fluctuations, giving rise to Brownian motion strongly affected by hydrodynamic effects. We plan to develop methods that couple an immersed-boundary Lagrangian representation of rigid bodies to a fluctuating finite-volume fluid solver. Unlike commonly-used methods based on Green's functions, we rely on an explicit-fluid fluctuating hydrodynamics formulation in which we add a stochastic stress tensor to the usual viscous stress tensor. We will handle complex rigid (e.g., synthetic nanorods) and semi-rigid (e.g., short DNA segments) bodies by composing each structure from a collection of spherical particles constrained to move (semi)rigidly. The underlying fluctuating hydrodynamics formulation automatically ensures the correct translational and rotational Brownian motion. The novel methods developed in this project will build upon prior work by the PIs and enable simulations of the long-time diffusive (Brownian) dynamics of the immersed structures. In particular, we will develop, implement, and apply computational methods that: (1) do not employ time splitting and are thus suitable for the steady Stokes (viscous-dominated or low Reynolds number) regime; (2) strictly enforce the rigidity constraint; and, (3) ensure fluctuation-dissipation balance in the overdamped limit even in the presence of nontrivial boundary conditions.

The decision to approach or avoid is a fundamental aspect of animal behavior. How this decision is made by networks of motor neurons that are located in the brainstem and spinal cord, and which trigger muscle cell contraction, is still unclear. This project will investigate the neural and mechanical basis of innate decision-making in vertebrates. Studies will be carried out using zebrafish larvae because they undergo a change in their innate decision-making ability during the first few days after hatching. Immediately after hatching, zebrafish larvae have the ability to generate escape behavior in response to threats. Three days later, they add the ability to not only avoid, but to approach and attack small objects. The goal of this project will be to determine how the neural circuitry supporting the decision to escape or approach visually detected objects is organized during development. Graduate students will be trained in the use of cutting-edge electrophysiological, imaging, computational and behavioral techniques uniquely applied in the zebrafish model system. In addition, an outreach program will be designed and implemented to introduce local high school students to basic neurobiological concepts addressed in this project. The program will involve intuitive and interactive experiments using simple robots with circuits that can be modified to create the approach or avoidance behaviors observed in fish.

The investigators will pursue several hypotheses regarding the development of approach and avoidance behaviors in larval zebrafish. Aim 1 will use high-speed videography and automated body tracking to evaluate the hypothesis that the circuitry for approach is not in place until later on in development. The expectation is that only the older larvae will be able to generate kinematically-distinct responses to attractive visual stimuli. Aim 2 will distinguish between two leading possibilities for how reticular circuitry mediates approach and avoidance, either via the addition of new components or the modification of pre-existing ones. In vivo dye labeling combined with functional calcium imaging approaches will assess changes in the morphologies and responses to visual stimuli of readily identifiable reticular neurons during development. In vivo patch clamp recordings will also be used to confirm outputs to spinal circuitry. Aim 3 will examine the likelihood that newly developed approach circuitry in the spinal cord is either overpowered or shut off by reticulospinal drive during avoidance maneuvers. The predictable read-outs of either scenario will be assessed using electrophysiological recordings of motor output, advanced computational fluids and body modeling, and targeted laser ablations followed by kinematic analysis.

Many biological and biomedical systems involve the interaction of a flexible structure and a fluid. These systems range from the writhing and coiling of DNA, to the beating and pumping of cilia and flagella, to the flow of blood in the body, to the locomotion of fish, insects, and birds. This project aims to develop advanced software infrastructure for performing dynamic computer simulations of such biological and biomedical systems. To facilitate the deployment of this software in a range of scientific and engineering applications, this project will develop new software capabilities in concert with new computer models that use the software. Specific application domains to be advanced in this project include models of aquatic locomotion that can be used to understand the neural control of movement and ultimately to develop new treatments for neurological pathologies such as spinal cord injuries, and models that simulate the interaction between the electrophysiology of the heart and the contractions of the heart that pump blood throughout the body, which could lead to improved approaches to treating heart disease. The software to be developed within the project is freely available online and is used by a number of independent research groups in a variety of scientific and engineering domains. It is being actively used in projects that model different aspects of cardiovascular dynamics, such as platelet aggregation and the dynamics of natural and prosthetic heart valves, and in projects that study other biological problems, including cancer dynamics, insect flight, aquatic locomotion, and the dynamics of phytoplankton. The software is also being applied to non-biological problems, including nanoscale models of colloidal suspensions and models of active particles. The improved methods and software to be developed in this project will thereby have a broad and sustained impact on a large number of ongoing research efforts in the biological and biomedical sciences and other scientific and engineering disciplines.

The immersed boundary (IB) method is a broadly applicable framework for modeling and simulating fluid-structure interaction (FSI). The IB method was introduced to model the fluid dynamics of heart valves, and subsequent development initially focused on simulating cardiac fluid dynamics. This methodology is broadly useful, however, and has been applied to a variety of problems in which a fluid flow interacts with immersed structures, including elastic bodies, bodies with known or prescribed deformational kinematics, and rigid bodies. Extensions of the IB method have also been developed to model electrophysiological systems and systems with chemically active structures. To improve the efficiency of the IB method, the PI has developed adaptive versions of the IB method that employ structured adaptive mesh refinement (AMR) to deploy high spatial resolution only where needed. These methods have been implemented within the IBAMR software framework, which provides parallel implementations of the IB method and its extensions that leverage high-quality computational libraries including SAMRAI, PETSc, and libMesh. This project will further extend the IBAMR software by implementing modeling and discretization technologies required by the research applications of current and prospective users of the software, by developing improved solver infrastructure facilitated by the implementation of native support for structured AMR discretizations in the PETSc library, and by integrating with existing high-quality software tools for model development, deployment, and analysis. IBAMR is freely distributed online and is used within a number of independent research groups both to the further development of the IB method and also to its application to simulate diverse problems in fluid dynamics and FSI. By enhancing IBAMR, this project will also enhance the ability of these and other researchers to construct detailed models without requiring those researchers to develop the significant software infrastructure needed to perform such simulations. This project will also develop general-purpose support for AMR discretizations in PETSc, a software library with thousands of active users, ~400 downloads per month, and numerous applications. The work of this project will help to grow the IBAMR user community of students and researchers by developing UI tools for building models, running simulations, and analyzing results. Students will be actively engaged in all aspects of the project, including code, method, and model development.

CORE SUMMARY The Biophysiologic Modeling Core will have the following primary components: 1) Biophysiologic Data Warehouse (BDW), 2) Biophysiologic Modeling Center (BMC), and 3) Mechanistic Data Warehouse (MDW). The Biophysiologic Data Warehouse will be a database and file repository that provides high-level physiological data coupled with clinical and research data, and will serve as the central data hub for the PPG. The Biophysiologic Modeling Center will contain computational hardware for desktop and high-fidelity parallel computing, and computational software for physics-based computations of esophageal physiology under normal and abnormal conditions. The center will al so house physics-based software for novel in-vivo/in-silico hybrid diagnostic tools based on FLIP and manometry. The primary development work of these mathematical modeling tools will be done in this CORE. In addition, user support to apply these tools to tasks in Project 3 will be provided in this CORE. The goal is the translation of computational biophysics models into clinical practice. To that end, BMC will provide technical support for the following activities: i) software development, ii) fundamental research of organ/system physiology, iii) patient specific analysis and diagnostics, and iv) design and development of next generation diagnostic tools (e. g. FLIP, manometry). Esophageal physiology simulations, performed using the software, will generate data providing insights into the mechanism underlying the normal and abnormal function of the esophagus. These will be termed Mechanistic Data, which will be housed within the MDW. These data will be coupled to physiological and clinical data from the BDW. The mechanistic data will be mapped onto The Chicago Classification of esophageal motility disorders. These data will be important to the development of the Virtual Disease Landscape (VDL) in Project 3.