Browsing by Author "Zhang, Xu"
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Item Open Access Chemotherapeutic drug screening in 3D-Bioengineered human myobundles provides insight into taxane-induced myotoxicities.(iScience, 2022-10) Torres, Maria J; Zhang, Xu; Slentz, Dorothy H; Koves, Timothy R; Patel, Hailee; Truskey, George A; Muoio, Deborah MTwo prominent frontline breast cancer (BC) chemotherapies commonly used in combination, doxorubicin (DOX) and docetaxel (TAX), are associated with long-lasting cardiometabolic and musculoskeletal side effects. Whereas DOX has been linked to mitochondrial dysfunction, mechanisms underlying TAX-induced myotoxicities remain uncertain. Here, the metabolic and functional consequences of TAX ± DOX were investigated using a 3D-bioengineered model of adult human muscle and a drug dosing regimen designed to resemble in vivo pharmacokinetics. DOX potently reduced mitochondrial respiratory capacity, 3D-myobundle size, and contractile force, whereas TAX-induced acetylation and remodeling of the microtubule network led to perturbations in glucose uptake, mitochondrial respiratory sensitivity, and kinetics of fatigue, without compromising tetanic force generation. These findings suggest TAX-induced remodeling of the microtubule network disrupts glucose transport and respiratory control in skeletal muscle and thereby have important clinical implications related to the cardiometabolic health and quality of life of BC patients and survivors.Item Open Access Indirect Training Algorithms for Spiking Neural Networks based on Spiking Timing Dependent Plasticity and Their Applications(2017) Zhang, XuSpiking neural networks have been used to investigate the mechanisms of processing
in biological neural circuits or to propose hypotheses that can be tested in exper-
iments. Because of their biological plausibility and event-based information trans-
mission, Spiking Neural Networks (SNNs) have suggested as alternatives to Articial
Neural Networks for pattern recognition, classication and function approximation
problems with fewer neurons. In machine learning, SNNs has been shown to be able
to solve pattern and robotic control. For SNNs to be used for such problems, they
must incorporate some mechanism for learning. Current methods to train SNNs use
learning algorithms which adjust the synaptic weights according to an update rule.
In most cases the weights are modied directly. In potential applications such as
driving plasticity in neural culture (in-vitro) and training neuromorphic chips the
directly manipulation of synaptic weights is not possible. Therefore, indirect algo-
rithms, which cause the SNNs to learn based on some biological learning mechanisms
using stimulation of neurons oer signicant advantages over the existing algorithm
for these real world applications.
Indirect algorithms train the neural network by using external stimuli to modulate
the synaptic strengths of a neural network according to synapses intrinsic mechanisms
for plasticity. The training algorithms have been demonstrated in both Integrate and
Fire neurons and more biologically realistic neural networks. In this thesis, four indi-
rect methods to drive the synaptic weights to its desired value in a network through Spike Time Dependent Plasticity (STDP) are developed: Indirect Perturbation, In-
direct Stochastic Gradient, Indirect ReSuMe, and Indirect Training with Supervised
Teaching Signals. These algorithms are used to solve the temporal and spatial input-
output mapping problem using temporal coding. The other type of problem is to
mapping input output ring rates using rate coding.
To test the algorithms, SNNs are used to control both virtual and real world
robots. For the real world robots with SNNs, known and Neurorobots, two types
of robot localization techniques are used: Optitrack, using ceiling mounted cameras
and onboard markers, and embedded cameras. Both small and large SNNs with
biologically realistic neurons are used to drive the neurorobots are modeled with
input coming from Optitrack or the cameras with GPU accelerated SNN simulator.
The results show that the indirect perturbation and indirect stochastic gradient
algorithms can train an SNN to control the robot to nd targets and avoid obstacles
even in the presence of sensor noise. The results also show that indirect training with
supervised training signals algorithm can train a feedforward network with 1000s of
neurons to process and output the correct movement commands to localize a target
using from real time images captured from an embedded camera. Finally. an indirect
version of the Remote Supervised Method (ReSuMe) algorithm was developed using
a more biologically realistic form of Spike-Timing Dependent Plasticity to produce a
specic temporal pattern of spiking from a group of neurons. The indirect algorithms
developed in this thesis may eventually allow the ability to train in vitro and in
vivo biological circuits to perform specic tasks using patterns of electrical or light
stimulation.
Item Open Access Indirect Training Algorithms for Spiking Neural Networks Controlled Virtual Insect Navigation(2015) Zhang, XuEven though Articial Neural Networks have been shown capable of solving many problems such as pattern recognition, classication, function approximation, clinics, robotics, they suers intrinsic limitations, mainly for processing large amounts of data or for fast adaptation to a changing environment. Several characteristics, such as iterative learning algorithms or articially designed neuron model and network architecture, are strongly restrictive compared with biological processing in natural neural networks. Spiking neural networks as the newest generation of neural models can overcome the weaknesses of ANNs. Because of the biologically realistic properties, the electrophysiological recordings of neural circuits can be compared to the outputs of the corresponding spiking neural network simulated on the computer, determining the plausibility of the starting hypothesis. Comparing with ANN, it is known that any function that can be computed by a sigmoidal neural network can also be computed by a small network of spiking neurons. In addition, for processing a large amount of data, SNNs can transmit and receive a large amount of data through the timing of the spikes and remarkably decrease the interactions load between neurons. This makes possible for very ecient parallel implementations.
Many training algorithms have been proposed for SNN training mainly based on the direct update of the synaptic plasticities or weights. However, the weights can not be changed directly and, instead, can be changed by the interactions of pre- and postsynaptic neural activities in many potential applications of adaptive spiking neural networks, including neuroprosthetic devices and CMOS/memristor nanoscale neuromorphic chips. The eciency of the bio-inspired, neuromorphic processing exposes the shortcomings of digital computing. After trained, the simulated neuromorphic model can be applied to speaker recognition, looming detection and temporal pattern matching. The properties of the neuromorphic chip enable it to solve the same problem while using fewer energies comparing with other hardware. The neuromorphic chips need applicable training methods that do not require direct manipulations of the connection strength.
Nowadays, thanks to fast improvements in hardware for neural stimulation and recording technologies, neurons in vivo and vitro can be controlled to re precisely in milliseconds. These improvements enable the study on the link between synaptic level and functional-level plasticity in the brain. However, existing training methods rely on learning rules for manipulating synaptic weights and on detailed knowledge of the network connectivity and synaptic strengths. New training algorithms that do not require the knowledge of the synaptic weights or connections are needed while they cannot require direct manipulations of the synaptic strength.
This thesis presents indirect training methods to train spiking neural networks,
which can both modeling neuromorphic chips and biological neural networks in vivo, via extra stimulus without the knowledge of synaptic strengths and connections. The algorithms are based on the spike timing-dependent plasticity rule by controlling input spike trains. One of the algorithms minimizes the error between the synaptic weight and the optimal weight, by stimulating the input neuron with an adaptive pulse training determined by the gradient of the error function. Another algorithm uses numerical gradient of the output error with respect to the weight change to control the training stimulus, which are injected to the neural network for controlling a virtual insect for navigating and nding target in an unknown terrain. Finally, the newest algorithm uses indirect perturbation of the temporal dierences between the extra stimulus in order to train a large spiking neural network. The trained spiking neural network can control both a unicycle modeled virtual insect and a virtual insect
moving in a tripod gait. The results show that these indirect training algorithms can train SNNs for solving control problems. In the thesis, the trained insect can and its target while avoiding obstacles in an unknown terrain. Future studies will focus on improving the insect's movement to using more complex locomotion model. The training algorithms will also be applied to biological neural networks and CMOS memristors. The trained neural networks will also be used for controlling flying microrobots.