- ItemOpen AccessIntegrating discrete stochastic models with single-cell and single-molecule experiments(Colorado State University. Libraries, 2019) Fox, Zachary R., author; Munsky, Brian, advisor; Stargell, Laurie, committee member; Wilson, Jesse, committee member; Prasad, Ashok, committee memberModern biological experiments can capture the behaviors of single biomolecules within single cells. Much like Robert Brown looking at pollen grains in water, experimentalists have noticed that individual cells that are genetically identical behave seemingly randomly in the way they carry out their most basic functions. The field of stochastic single-cell biology has been focused developing mathematical and computational tools to understand how cells try to buffer or even make use of such fluctuations, and the technologies to measure such fluctuations has vastly improved in recent years. This dissertation is focused on developing new methods to analyze modern single-cell and single-molecule biological data with discrete stochastic models of the underlying processes, such as stochastic gene expression and single-mRNA translation. The methods developed here emphasize a strong link between model and experiment to help understand, design, and eventually control biological systems at the single-cell level.
- ItemOpen AccessA comparison of tri-polar concentric ring electrodes to disc electrodes for decoding real and imaginary finger movements(Colorado State University. Libraries, 2019) Alzahrani, Saleh Ibrahim, author; Anderson, Charles W., advisor; Vigh, Jozsef, committee member; Rojas, Don, committee member; Abdel-Ghany, Salah, committee memberThe electroencephalogram (EEG) is broadly used for diagnosis of brain diseases and research of brain activities. Although the EEG provides a good temporal resolution, it suffers from poor spatial resolution due to the blurring effects of volume conduction and signal-to-noise ratio. Many efforts have been devoted to the development of novel methods that can increase the EEG spatial resolution. The surface Laplacian, which is the second derivative of the surface potential, has been applied to EEG to improve the spatial resolution. Tri-polar concentric ring electrodes (TCREs) have been shown to estimate the surface Laplacian automatically with better spatial resolution than conventional disc electrodes. The aim of this research is to study how well the TCREs can be used to acquire EEG signals to decode real and imaginary finger movements. These EEG signals will be then translated into finger movements commands. We also compare the feasibility of discriminating finger movements from one hand using EEG recorded from TCREs and conventional disc electrodes. Furthermore, we evaluated two movement-related features, temporal EEG data and spectral features, in discriminating individual finger from one hand using non-invasive EEG. To do so, movement-related potentials (MRPs) are measured and analyzed from four TCREs and conventional disc electrodes while 13 subjects performed either motor execution or motor imagery of individual finger movements. The tri-polar-EEG (tEEG) and conventional EEG (cEEG) were recorded from electrodes placed according to the 10-20 International Electrode Positioning System over the motor cortex. Our results show that the TCREs achieved higher spatial resolution than conventional disc electrodes. Moreover, the results show that signals from TCREs generated higher decoding accuracy compared to signals from conventional disc electrodes. The average decoding accuracy of five-class classification for all subjects was of 70.04 ± 7.68% when we used temporal EEG data as feature and classified it using Artificial Neural Networks (ANNs) classifier. In addition, the results show that the TCRE EEG (tEEG) provides approximately a four times enhancement in the signal-to-noise ratio (SNR) compared to disc electrode signals. We also evaluated the interdependency level between neighboring electrodes from tri-polar, disc, and disc with Hjorth's Laplacian method in time and frequency domains by calculating the mutual information (MI) and coherence. The MRP signals recorded with the TCRE system have significantly less mutual information (MI) between electrodes than the conventional disc electrode system and disc electrodes with Hjorth's Laplacian method. Also, the results show that the mean coherence between neighboring tri-polar electrodes was found to be significantly smaller than disc electrode and disc electrode with Hjorth's method, especially at higher frequencies. This lower coherence in the high frequency band between neighboring tri polar electrodes suggests that the TCREs may record a more localized neuronal activity. The successful decoding of finger movements can provide extra degrees of freedom to drive brain computer interface (BCI) applications, especially for neurorehabilitation.
- ItemOpen AccessForce spectroscopy and dynamics in biological systems(Colorado State University. Libraries, 2019) Schroder, Bryce William, author; Krapf, Diego, advisor; Bark, David, committee member; Popat, Ketul, committee member; DeLuca, Jennifer, committee memberCommunication is key to any process involving the transmission of information or some sort of signal. For communication to occur, a signal must be created that can be detected. Cells communicate through cues transmitted in the forms of chemical and mechanical signals. The most fundamental means for transmitting chemical cues is through the process of diffusion. A single particle undergoing diffusion is considered to undergo Brownian motion, which can be modelled as a random walk. The random walk behavior is characteristic of both the particles properties and the fields in which it is occurring. An unbiased walk will be completely random without outside influence. A biased walk will be random within the confines of a potential influencing its direction. Both are Stochastic processes characterized through probabilistic models with known solutions. The work herein presents the development of single molecule experiments and the associated particle tracking tools targeting particles undergoing biased random walks within a trapping potential on or near a cellular membrane. In the first set of experiments, the trapping potential, an optical tweezers setup, has been developed and employed in measuring cellular membrane biophysical properties as well as blebbing forces. The optical trap was also used to directly measure flow driven forces in live embryonic zebrafish, the first known measurements of this kind. In the second set of experiments, synthetic lipid bilayers provided a trapping potential in a single dimension for protein binding experiments leading to exchanges between free, 3-dimensional diffusion and bound, or biased, 2-dimensional diffusion. In all cases, stochastic models have been used in conjunction with image-based particle tracking tools to better characterize the biophysical properties and forces associated with the cellular membrane and its means of signal transduction. These measurements are key to understanding both the chemical and mechanical signaling means by which the cellular membrane transduces an external signal into an internal response.
- ItemOpen AccessHemocompatibility of hyaluronan enhanced linear low-density polyethylene for heart valve leaflet applications(Colorado State University. Libraries, 2018) Simon-Walker, Rachael, author; Popat, Ketul C., advisor; Reynolds, Melissa, committee member; Orton, Christopher, committee member; Chicco, Adam, committee memberHeart valve disease is a major concern in both developed countries with advanced ageing populations and undeveloped countries which experience a high incidence of rheumatism leading to valvular disease. To reduce mortality and improve quality of life, heart valve implantations have been widely used to assist in improving function of the native cardiovascular system. While mechanical heart valves and tissue-based heart valves have been successfully used to improve quality of life compared to untreated valvular disease, draw-backs are inherent. Mechanical heart valves are prone to thrombosis and require life-long supplemental anti-coagulation therapy. Tissue-based valves are more hemocompatible, but lack the durability required for long-term implantation. To address these issues, polymeric heart valves have been highly sought after due to polymers' abilities to enhance durability and be manufactured to be similar to the native heart valve leaflet. In addition, their surfaces can be modified to increase hemocompatibility. In this work we explore the hemocompatibility and immune response to a novel polymer for use in heart valve leaflet applications; hyaluronan enhanced linear low-density polyethylene. It is proposed that the combination of linear low-density polyethylene with hyaluronan will create a highly durable material that will reduce thrombosis and inflammation due to the anionic and hydrophilic nature of the glycosaminoglycan.
- ItemOpen AccessSpinal cord and meningeal mechanics: viscoelastic characterization and computational modeling(Colorado State University. Libraries, 2018) Ramo, Nicole Lauren, author; Puttlitz, Christian M., advisor; Troyer, Kevin L., advisor; Heyliger, Paul, committee member; James, Susan, committee memberSuffering a spinal cord injury (SCI) can be physically, emotionally, and financially devastating. With the complex loading environment typically seen in SCI events, finite element (FE) computational models provide an important economical and ethical option for investigating the mechanical etiology of SCI, evaluating prevention techniques, and assessing clinical treatments. To this end, numerous research groups have developed FE models of the spinal cord using various degrees of material and structural sophistication. However, the level of model complexity that is necessary to achieve accurate predictions of SCI has not been explicitly investigated as few studies have reported applicable tissue behavior. What are reported in the literature as "spinal cord mechanical properties" are most commonly based on ex-vivo tests of the spinal-cord-pia-arachnoid construct (SCPC). The pia and arachnoid maters are fibrous meningeal tissues that closely envelope the spinal cord, and together are referred to as the pia-arachnoid-complex (PAC). Currently available data demonstrate the PAC's importance in the overall SCPC stiffness and shape restoration following compression. However, only one previous study has reported mechanical properties of isolated spinal PAC, and therefore, conclusions about its contribution to SCPC mechanics are largely unknown. Additionally, it has been shown that SCPC material properties begin to degrade within 90 minutes of death. Considering the experimental difficulties and ethical concerns associated with in-vivo mechanical testing of the SCPC, determining the relationship between in-vivo and ex-vivo viscoelastic properties would allow researchers to more accurately analyze existing ex-vivo data. Therefore, the overarching goal of this work is to address the current gaps in knowledge regarding spinal cord and meningeal tissue mechanics and incorporate the developed material models into a FE model. Comparisons of ex-vivo and in-vivo porcine SCPC non-linear viscoelastic behavior revealed significantly different acute behaviors where the ex-vivo condition exhibited a higher stress response but also relaxed quicker and to a greater extent than the in-vivo condition. Although it only made up less than 6% of the ovine SCPC volume, the PAC was found to significantly affect the non-linear viscoelastic behavior of the SCPC which supports the conclusion that it plays an important protective mechanical role. Examining the fitting and predictive accuracy of linear, quasi-linear, and non-linear viscoelastic formulations to SCPC, cord, and PAC stress-strain data, non-linear formulations are recommended to model the SCPC and cord response to arbitrary loading conditions while the QLV is recommended for the PAC. This work provides researchers with novel insights into the complex mechanical behavior of the spinal cord and PAC. The experimental results represent an important addition to the limited literature on in-vivo versus ex-vivo neural tissue viscoelastic properties; they are also the first to quantify the non-linear elastic behavior of spinal PAC and the non-linear viscoelastic properties of the isolated spinal cord. Finally, the computational portion of this work provides a detailed report of the effects of viscoelastic formulation complexity on FE model prediction accuracy and computational time allowing researchers interested in modeling SCI to make informed decisions about the balance of accuracy and efficiency necessary for their specific modeling efforts.