Recent new experiments showed that wide-field imaging at millimeter scale is capable of recording hundreds of neurons in behaving mice brain. Monitoring hundreds of individual neurons at a high frame rate provides a promising tool for discovering spatiotemporal features of large neural networks. However, processing the massive data sets is impossible without automated procedures. Thus, this thesis aims at developing a new tool to automatically segment and track individual neuron cells. The new method used in this study employs two major ideas including feature extraction based on power spectral density of single neuron temporal activity and clustering tree to separate overlapping cells. To address issues associated with high-resolution imaging of a large recording area, focused areas and out-of-focus areas were analyzed separately. A static segmentation with a fixed PSD thresholding method is applied to within focus visual field. A dynamic segmentation by comparing maximum PSD with surrounding pixels is applied to out-of-focus area. Both approaches helped remove irrelevant pixels in the background. After detection of potential single cells, some of which appeared in groups due to overlapping cells in the image, a hierarchical clustering algorithm is applied to separate them. The hierarchical clustering uses correlation coefficient as a distance measurement to group similar pixels into single cells. As such, overlapping cells can be separated. We tested the entire algorithm using two real recordings with the respective truth carefully determined by manual inspections. The results show high accuracy on tested datasets while false positive error is controlled within an acceptable range. Furthermore, results indicate robustness of the algorithm when applied to different image sequences.

Mechanical properties of cells are important in maintaining physiological functions of biological systems. Quantitative measurement and analysis of mechanical properties can help understand cellular mechanics and its functional relevance and discover physical biomarkers for diseases monitoring and therapeutics.

This dissertation presents a work to develop optical methods for studying cell mechanics which encompasses four applications. Surface plasmon resonance microscopy based optical method has been applied to image intracellular motions and cell mechanical motion. This label-free technique enables ultrafast imaging with extremely high sensitivity in detecting cell deformation. The technique was first applied to study intracellular transportation. Organelle transportation process and displacement steps of motor protein can be tracked using this method. The second application is to study heterogeneous subcellular membrane displacement induced by membrane potential (de)polarization. The application can map the amplitude and direction of cell deformation. The electromechanical coupling of mammalian cells was also observed. The third application is for imaging electrical activity in single cells with sub-millisecond resolution. This technique can fast record actions potentials and also resolve the fast initiation and propagation of electromechanical signals within single neurons. Bright-field optical imaging approach has been applied to the mechanical wave visualization that associated with action potential in the fourth application. Neuron-to-neuron viability of membrane displacement was revealed and heterogeneous subcellular response was observed.

All these works shed light on the possibility of using optical approaches to study millisecond-scale and sub-nanometer-scale mechanical motions. These studies revealed ultrafast and ultra-small mechanical motions at the cellular level, including motor protein-driven motions and electromechanical coupled motions. The observations will help understand cell mechanics and its biological functions. These optical approaches will also become powerful tools for elucidating the interplay between biological and physical functions.

Brain-machine interfaces (BMIs) were first imagined as a technology that would allow subjects to have direct communication with prosthetics and external devices (e.g. control over a computer cursor or robotic arm movement). Operation of these devices was not automatic, and subjects needed calibration and training in order to master this control. In short, learning became a key component in controlling these systems. As a result, BMIs have become ideal tools to probe and explore brain activity, since they allow the isolation of neural inputs and systematic altering of the relationships between the neural signals and output. I have used BMIs to explore the process of brain adaptability in a motor-like task. To this end, I trained non-human primates to control a 3D cursor and adapt to two different perturbations: a visuomotor rotation, uniform across the neural ensemble, and a decorrelation task, which non-uniformly altered the relationship between the activity of particular neurons in an ensemble and movement output. I measured individual and population level changes in the neural ensemble as subjects honed their skills over the span of several days. I found some similarities in the adaptation process elicited by these two tasks. On one hand, individual neurons displayed tuning changes across the entire ensemble after task adaptation: most neurons displayed transient changes in their preferred directions, and most neuron pairs showed changes in their cross-correlations during the learning process. On the other hand, I also measured population level adaptation in the neural ensemble: the underlying neural manifolds that control these neural signals also had dynamic changes during adaptation. I have found that the neural circuits seem to apply an exploratory strategy when adapting to new tasks. Our results suggest that information and trajectories in the neural space increase after initially introducing the perturbations, and before the subject settles into workable solutions. These results provide new insights into both the underlying population level processes in motor learning, and the changes in neural coding which are necessary for subjects to learn to control neuroprosthetics. Understanding of these mechanisms can help us create better control algorithms, and design training paradigms that will take advantage of these processes.

Toward the ambitious long-term goal of a fleet of cooperating Flexible Autonomous Machines operating in an uncertain Environment (FAME), this thesis addresses several

critical modeling, design and control objectives for ground vehicles. One central objective was to show how off-the-shelf (low-cost) remote-control (RC) “toy” vehicles can be converted into intelligent multi-capability robotic-platforms for conducting FAME research. This is shown for two vehicle classes: (1) six differential-drive (DD) RC vehicles called Thunder Tumbler (DDTT) and (2) one rear-wheel drive (RWD) RC car called Ford F-150 (1:14 scale). Each DDTT-vehicle was augmented to provide a substantive suite of capabilities as summarized below (It should be noted, however, that only one DDTT-vehicle was augmented with an inertial measurement unit (IMU) and 2.4 GHz RC capability): (1) magnetic wheel-encoders/IMU for(dead-reckoning-based) inner-loop speed-control and outer-loop position-directional-control, (2) Arduino Uno microcontroller-board for encoder-based inner-loop speed-control and encoder-IMU-ultrasound-based outer-loop cruise-position-directional-separation-control, (3) Arduino motor-shield for inner-loop motor-speed-control, (4)Raspberry Pi II computer-board for demanding outer-loop vision-based cruise- position-directional-control, (5) Raspberry Pi 5MP camera for outer-loop cruise-position-directional-control (exploiting WiFi to send video back to laptop), (6) forward-pointing ultrasonic distance/rangefinder sensor for outer-loop separation-control, and (7) 2.4 GHz spread-spectrum RC capability to replace original 27/49 MHz RC. Each “enhanced”/ augmented DDTT-vehicle costs less than 􀀀175 but offers the capability of commercially available vehicles costing over 􀀀500. Both the Arduino and Raspberry are low-cost, well-supported (software wise) and easy-to-use. For the vehicle classes considered (i.e. DD, RWD), both kinematic and dynamical (planar xy) models are examined. Suitable nonlinear/linear-models are used to develop inner/outer-loopcontrol laws.

All demonstrations presented involve enhanced DDTT-vehicles; one the F-150; one a quadrotor. The following summarizes key hardware demonstrations: (1) cruise-control along line, (2) position-control along line (3) position-control along curve (4) planar (xy) Cartesian stabilization, (5) cruise-control along jagged line/curve, (6) vehicle-target spacing-control, (7) multi-robot spacing-control along line/curve, (8) tracking slowly-moving remote-controlled quadrotor, (9) avoiding obstacle while moving toward target, (10) RC F-150 followed by DDTT-vehicle. Hardware data/video is compared with, and corroborated by, model-based simulations. In short, many capabilities that are critical for reaching the longer-term FAME goal are demonstrated.

This thesis addresses control design for fixed-wing air-breathing aircraft. Four aircraft with distinct dynamical properties are considered: a scram-jet powered hypersonic (100foot long, X-43 like, wedge shaped) aircraft with flexible modes operating near Mach 8, 85k ft, a NASA HiMAT (Highly Maneuverable Aircraft Technology) F-18 aircraft,

a McDonnell Douglas AV-8A Harrier aircraft, and a Vought F-8 Crusader aircraft. A two-input two-output (TITO) longitudinal LTI (linear time invariant) dynamical model is used for each aircraft. Control design trade studies are conducted for each of the aircraft. Emphasis is placed on the hypersonic vehicle because of its complex nonlinear (unstable, non-minimum phase, flexible) dynamics and uncertainty associated with hypersonic flight (Mach $>$ 5, shocks and high temperatures on leading edges). Two plume models are used for the hypersonic vehicle – an old plume model and a new plume model. The old plume model is simple and assumes a typical decaying pressure distribution for aft nozzle. The new plume model uses Newtonian impact theory and a nonlinear solver to compute the aft nozzle pressure distribution. Multivariable controllers were generated using standard weighted $H_{\inf}$ mixed-sensitivity optimization as well as a new input disturbance weighted mixed-sensitivity framework that attempts to achieve good multivariable properties at both the controls (plant inputs) as well as the errors (plant outputs). Classical inner-outer (PD-PI) structures (partially centralized and decentralized) were also used. It is shown that while these classical (sometimes partially centralized PD-PI) structures could be used to generate comparable results to the multivariable controllers (e.g. for the hypersonic vehicle, Harrier, F-8), considerable tuning (iterative optimization) is often essential. This is especially true for the highly coupled hypersonic vehicle – thus justifying the need for a good multivariable control design tool. Fundamental control design tradeoffs for each aircraft are presented – comprehensively for the hypersonic aircraft. In short, the thesis attempts to shed light on when complex controllers are essential and when simple structures are sufficient for achieving control designs with good multivariable loop properties at both the errors (plant outputs) and the controls (plant inputs).

This thesis addresses the design and control of three phase inverters. Such inverters are

used to produce three-phase sinusoidal voltages and currents from a DC source. They

are critical for injecting power from renewable energy sources into the grid. This is

especially true since many of these sources of energy are DC sources (e.g. solar

photovoltaic) or need to be stored in DC batteries because they are intermittent (e.g. wind

and solar). Two classes of inverters are examined in this thesis. A control-centric design

procedure is presented for each class. The first class of inverters is simple in that they

consist of three decoupled subsystems. Such inverters are characterized by no mutual

inductance between the three phases. As such, no multivariable coupling is present and

decentralized single-input single-output (SISO) control theory suffices to generate

acceptable control designs. For this class of inverters several families of controllers are

addressed in order to examine command following as well as input disturbance and noise

attenuation specifications. The goal here is to illuminate fundamental tradeoffs. Such

tradeoffs include an improvement in the in-band command following and output

disturbance attenuation versus a deterioration in out-of-band noise attenuation.

A fundamental deficiency associated with such inverters is their large size. This can be

remedied by designing a smaller core. This naturally leads to the second class of inverters

considered in this work. These inverters are characterized by significant mutual

inductances and multivariable coupling. As such, SISO control theory is generally not

adequate and multiple-input multiple-output (MIMO) theory becomes essential for

controlling these inverters.

Gas turbine engine for aircraft propulsion represents one of the most physics-complex and safety-critical systems in the world. Its failure diagnostic is challenging due to the complexity of the model system, difficulty involved in practical testing and the infeasibility of creating homogeneous diagnostic performance evaluation criteria for the diverse engine makes.

NASA has designed and publicized a standard benchmark problem for propulsion engine gas path diagnostic that enables comparisons among different engine diagnostic approaches. Some traditional model-based approaches and novel purely data-driven approaches such as machine learning, have been applied to this problem.

This study focuses on a different machine learning approach to the diagnostic problem. Some most common machine learning techniques, such as support vector machine, multi-layer perceptron, and self-organizing map are used to help gain insight into the different engine failure modes from the perspective of big data. They are organically integrated to achieve good performance based on a good understanding of the complex dataset.

The study presents a new hierarchical machine learning structure to enhance classification accuracy in NASA's engine diagnostic benchmark problem. The designed hierarchical structure produces an average diagnostic accuracy of 73.6%, which outperforms comparable studies that were most recently published.

Control engineering offers a systematic and efficient approach to optimizing the effectiveness of individually tailored treatment and prevention policies, also known as adaptive or ``just-in-time'' behavioral interventions. These types of interventions represent promising strategies for addressing many significant public health concerns. This dissertation explores the development of decision algorithms for adaptive sequential behavioral interventions using dynamical systems modeling, control engineering principles and formal optimization methods. A novel gestational weight gain (GWG) intervention involving multiple intervention components and featuring a pre-defined, clinically relevant set of sequence rules serves as an excellent example of a sequential behavioral intervention; it is examined in detail in this research.

 

A comprehensive dynamical systems model for the GWG behavioral interventions is developed, which demonstrates how to integrate a mechanistic energy balance model with dynamical formulations of behavioral models, such as the Theory of Planned Behavior and self-regulation. Self-regulation is further improved with different advanced controller formulations. These model-based controller approaches enable the user to have significant flexibility in describing a participant's self-regulatory behavior through the tuning of controller adjustable parameters. The dynamic simulation model demonstrates proof of concept for how self-regulation and adaptive interventions influence GWG, how intra-individual and inter-individual variability play a critical role in determining intervention outcomes, and the evaluation of decision rules.

 

Furthermore, a novel intervention decision paradigm using Hybrid Model Predictive Control framework is developed to generate sequential decision policies in the closed-loop. Clinical considerations are systematically taken into account through a user-specified dosage sequence table corresponding to the sequence rules, constraints enforcing the adjustment of one input at a time, and a switching time strategy accounting for the difference in frequency between intervention decision points and sampling intervals. Simulation studies illustrate the potential usefulness of the intervention framework.

The final part of the dissertation presents a model scheduling strategy relying on gain-scheduling to address nonlinearities in the model, and a cascade filter design for dual-rate control system is introduced to address scenarios with variable sampling rates. These extensions are important for addressing real-life scenarios in the GWG intervention.

To uncover the neural correlates to go-directed behavior, single unit action potentials are considered fundamental computing units and have been examined by different analytical methodologies under a broad set of hypotheses. Using a behaving rat performing a directional choice learning task, we aim to study changes in rat's cortical neural patterns while he improved his task performance accuracy from chance to 80% or higher. Specifically, simultaneous multi-channel single unit neural recordings from the rat's agranular medial (AGm) and Agranular lateral (AGl) cortices were analyzed using joint peristimulus time histogram (JPSTHs), which effectively unveils firing coincidences in neural action potentials. My results based on data from six rats revealed that coincidences of pair-wise neural action potentials are higher when rats were performing the task than they were not at the learning stage, and this trend abated after the rats learned the task. Another finding is that the coincidences at the learning stage are stronger than that when the rats learned the task especially when they were performing the task. Therefore, this coincidence measure is the highest when the rats were performing the task at the learning stage. This may suggest that neural coincidences play a role in the coordination and communication among populations of neurons engaged in a purposeful act. Additionally, attention and working memory may have contributed to the modulation of neural coincidences during the designed task.