VictorJuiz/thesis huggingface dataset:
Discrimination of Neural Sources using Spatiotemporal Signatures in Nerve Cuff Electrode Recordings

Recording and stimulating from the peripheral nervous system are becoming important components in new generations of bioelectronic systems. Neurostimulation has seen a long history of success in chronic application but robust neural recordings remain a challenge. Nerve cuff electrodes are an option that have demonstrated chronic viability in humans but lack the required recording selectivity. The objective of this thesis was to increase the recording selectivity achievable using multi-contact nerve cuff electrodes. Neural activity recorded from multi-contact nerve cuffs for a given neural pathway will have a distinct spatiotemporal signature. This signature is determined by the location of the bioelectric sources in the nerve combined with the type of fiber, which governs the propagation properties of the action potentials. Both the spatial and temporal information are needed to interpret the physiological meaning of the recorded activity, but have not been adequately combined in signal processing techniques to date. We investigated selective recording approaches based on spatiotemporal characterizations of neural pathways. First, we performed a simulation study to investigate the effects of the spatial and temporal information on recording selectivity. A matched filter approach was developed and results showed that neural pathways that had different fiber types were highly distinguishable, whereas neural pathways with similar fiber types showed varying distinguishability results depending on pathway locations. Next, we performed a validation study in vivo in a rat sciatic nerve model. We tested our matched filter approach and machine learning algorithms in distinguishing the neural pathways. The results of the matched filter approach were comparable to the simulation study, validating our simulations, and the machine learning algorithms showed improvements in recording selectivity. These results demonstrated classification of individual naturally evoked compound action potentials (nCAPs) for the first time. Lastly, we demonstrated that the use of a convolutional neural network (CNN) led to further improvements in recording selectivity. With the help of a recurrent neural network, joint angles could be tracked accurately based on the classified nCAPs. These findings suggest that nerve cuff electrodes can provide robust recordings and be beneficial in many neuroprosthetic and neuromodulation application.

Keywords: Machine Learning
Nerve Cuff Electrode
Peripheral Nerve Recordings
Rat Sciatic Nerve
Simulations
Spatiotemporal Signatures
Advisor: Zariffa, José
Nachman, Adrian I
Protein-protein Interactions Provide a Platform for G-protein-coupled Receptors to Exert Physiological and Pathological Functions in Central Nervous System: Therapeutic Potential?

In the central nervous system membrane receptors play an important role in neuronal communication. Since neurons mainly communicate through the release of neurotransmitters, membrane receptors are responsible for binding neurotransmitters and transducing their message into an intracellular response. In general, there are two types of membrane receptors: ionotropic and metabotropic. Ionotropic receptors are ligand-gated ion channels, which are responsible for mediating fast synaptic responses. On the other hand, metabotropic receptors act through their downstream signaling cascades to trigger intracellular responses. A prominent example of metabotropic receptors is the G-protein-coupled receptor (GPCR) superfamily. In the human body this receptor superfamily consists of approximately 799 receptors. Conventionally, these GPCRs are seven-transmembrane-domain receptors which act through their coupled G-proteins to elicit their physiological actions. There is also a growing body of evidence that these GPCRs can physically interact with each other as well as with other types of membrane receptors. This present study focuses on examining whether protein-protein interactions, other than coupled G-protein signaling cascades, are another platform for GPCRs to exert their effects or to regulate the functions of other proteins. We also investigate whether these protein-protein interactions involving GPCRs present any physiological or pathological implications.

Keywords: Animal Studies
GPCR
Peptide
Protein-Protein Interaction
Therapeutic
Advisor: Liu, Fang
The Investigation of Aerobic Interval Training in Women with Coronary Artery Disease in Cardiac Rehabilitation

The generalizability of the potential superiority of aerobic interval training (AIT) over moderate intensity continuous exercise (MICE) in improving aerobic exercise capacity (VO2peak) remains elusive in women with coronary artery disease (CAD), as they have been underrepresented in the majority of studies to date. The overarching aim of this doctoral thesis was to optimize exercise training modalities for outpatient, cardiac rehabilitation (CR) programs to maximize the potential gains in quality of life, and survival. The central hypothesis was that a six-month CR program of AIT would significantly improve VO2peak more than six-months of usual care CR involving MICE, in postmenopausal women with CAD. The first of three studies sought to retrospectively determine the effectiveness of progressive AIT in the form of walk/jog intervals in individuals with CAD. Treatment effect analysis revealed a 3.84 mL·kg -1·min -1 superior improvement in VO2peak in response to AIT compared to usual care MICE (p

Keywords: aerobic exercise capacity
cardiac rehabilitation
exercise
interval training
women
Advisor: Brooks, Dina
Predicting the Thermal Dependencies of Infectious Disease

Climate change is affecting infectious disease around the world. These effects can be complicated, as disease spread depends on characteristics of the host-parasite system in question, including host mortality rates, parasite contact rates, and how quickly the parasite kills its host. Importantly, these key parameters often vary with temperature. Combining mechanistic models of disease spread with thermal performance curves can be a powerful approach to predicting temperature’s effects on disease; however, most host-parasite systems are data poor and it is therefore difficult to parameterize their phenomenological thermal functions. The Metabolic Theory of Ecology (MTE) provides a potential solution to these data limitations. The MTE framework suggests that since metabolism scales with body mass and temperature, metabolic rate can be used to predict temperature’s effects on physiological rates, thereby generating models for the thermal dependencies of disease traits. Since MTE is predicated on first principles of chemistry and physics, it should be generalizable across biological systems and its functions may be parameterized a priori. Recent work has proposed combining MTE with host-parasite models, though we lack empirical tests of how well this approach can describe the thermal dependencies of disease across different host-parasite scales. Here, I use a Daphnia magna – microsporidian experimental host-parasite system to test this approach’s performance. In Chapter 1, I show that MTE is able to capture the thermal dependencies of within-host disease, including parameters that describe host aging and mortality, and parasite growth and equilibrium abundance. In Chapter 2, I provide evidence that MTE can accurately describe the rates that constitute disease transmission (contact and parasite infectivity) across temperature. Finally, in Chapter 3 I use the models described above to parameterize a population-level epidemiological model that predicts disease dynamics under warming or constant temperatures. I test the independent model predictions by driving experimental populations through constant or slowly warming conditions and show that MTE is able to accurately forecast warming-driven disease emergence. This thesis serves as a proof of principle that linking simple metabolic models with a mechanistic host–parasite framework can be used to predict temperature responses of within-host disease dynamics, disease transmission, and overall epidemics.

Keywords: daphnia
disease
experimental
metabolic theory
modeling
temperature
Advisor: Krkosek, Martin
Semi-infinite Cohomology, Quantum Group Cohomology, and the Kazhdan-Lusztig Equivalence

The Kazhdan-Lusztig tensor equivalence is a monoidal functor which sends modules over an affine Lie algebra at negative level to modules over the associated quantum group. A positive level Kazhdan-Lusztig functor is defined using Arkhipov-Gaitsgory's duality between positive and negative level affine Lie algebras. Our main result proves that under the positive level Kazhdan-Lusztig functor, the semi-infinite cohomology functor corresponds to the quantum group cohomology functor with respect to the positive part of Lusztig's quantum group. Monoidal structures of a category can be interpreted as factorization data on the associated global category. We describe a conjectural reformulation of the Kazhdan-Lusztig tensor equivalence in factorization terms. In this reformulation, the semi-infinite cohomology functor at positive level is naturally factorizable, and it is conjectured that the factorizable semi-infinite cohomology functor is essentially the positive level Kazhdan-Lusztig tensor functor modulo the Riemann-Hilbert correspondence. Our main result provides an important technical tool in a proposed approach to a proof of this conjecture.

Keywords: affine Lie algebra
BRST
chiral algebra
quantum algebra
vertex algebra
Advisor: Kamnitzer, Joel
Braverman, Alexander
The Intersection of Renewable Energy Finance and Governance: Solutions to the Multi-trillion Dollar Challenges

The International Finance Corporation (IFC) estimated in 2016 that the 2015 Paris Agreement could drive demand for tens of trillions of dollars of new climate-related investment between 2016 and 2030. Assessments suggest that at least some percentage of these funds will need to be mobilized from private investment sources. Renewable energy, the primary supply-side decarbonization tool, stands poised to capture a significant portion of this number, yet numerous technical, economic, and governance questions loom large in any discussion of renewable energy sector deployment. This thesis focuses on the question of financing all stages of renewables, as well as the ability of finance-linked entities to implement energy governance structures designed to drive a substantial level of renewables integration. We start by presenting case studies on both the United States and the Gulf Cooperation Council (GCC) countries. This study of contrasts is followed by a synthesis of insights on key renewable energy governance challenges from one perspective; specifically, the perspective of individuals with connections to the private finance sector that will be responsible for some of the financial flows for renewables deployment. Derived from extensive time in the field (including unstructured interviews, semi-structured interviews, and ethnographic work), this thesis critically examines the perspectives of leading renewable energy financiers (as well as academics and other knowledgeable market observers from around the world) on how best to improve the financial flows to, and governance of, renewable energy finance. Given the difficulty of offering definitive prescriptions in the inherently idiosyncratic political, economic, social, and environmental context guiding each nation, the thesis starts by offering region-specific prescriptions, followed by general directions. In the final substantial chapter, it draws on a geographically diverse set of key stakeholder interviews to tease out common lessons that can be shared across borders. These lessons include the importance of a carbon tax, the criticality of appropriate policy structure and market design, the urgency of pursuing low-cost options (such as applied research), and the need for encouraging new capital sources into the space. Further research on the role of private sector and public sector capital in the renewable energy space is encouraged.

Keywords: Climate change
Finance
GCC
Renewable energy
Advisor: Harvey, Danny
1H NMR-Based Metabolomics of Daphnia magna Sub-lethal Exposure to Organic Contaminants in the Absence and Presence of Dissolved Organic Matter

Ecotoxicity tests which monitor observable endpoints such as mortality, growth and reproduction do not assess the molecular mode of action of contaminants in target organisms. Also, aquatic toxicity tests often do not include dissolved organic matter (DOM), which is ubiquitously found in natural waters. Hydrophobic organic contaminants sorb to DOM which may alter the bioavailability and toxicity of these contaminants. To assess this hypothesis, proton (1H) nuclear magnetic resonance (NMR)-based metabolomics was used to analyze the metabolome of Daphnia magna after acute sub-lethal exposure to organic contaminants in the absence or presence of DOM. Triclosan, carbamazepine and ibuprofen exposure resulted in different metabolic responses in D. magna. DOM at 5 mg dissolved organic carbon/L (DOC/L) did not change the D. magna metabolome from carbamazepine, imidacloprid or tris(2-chloroethyl) phosphate exposure, perhaps because these weakly hydrophobic contaminants do not sorb to DOM. The metabolic response of D. magna from 17α-ethynylestradiol (EE2) exposure was suppressed by 1, 2, 3, 4 and 5 mg DOC/L, likely from decreased EE2 bioavailability with DOM. The metabolic response in D. magna from perfluorooctane sulfonate (PFOS) exposure was not altered with 1 mg DOC/L. However, PFOS exposure with 2, 3, 4 and 5 mg DOC/L resulted in a unique metabolic response in D. magna, which may be due to enhanced PFOS bioavailability or combined action of PFOS and DOM on the metabolome. The metabolic response of D. magna from tris(2-butoxyethyl) phosphate (TBOEP) exposure was unaltered with 5 mg DOC/L, perhaps from the high potency of TBOEP. D. magna exposure to triphenyl phosphate (TPhP) with 5 mg DOC/L resulted in a unique metabolic response compared to TPhP exposure, possibly from combined stress of TPhP and DOM on the metabolome or altered TPhP bioavailability. The mode of action of mixtures of the hydrophobic contaminants triclosan, TPhP and diazinon in D. magna was not altered by 1 and 5 mg DOC/L. Overall, DOM may enhance or suppress the metabolic perturbations in aquatic organisms that originate from sub-lethal exposure to organic contaminants. Therefore, DOM should be included when evaluating molecular-level responses from sub-lethal ecotoxicity tests and during risk assessment of environmental mixtures.

Keywords: Daphnia magna
Metabolomics
NMR spectroscopy
Organic contaminants
Advisor: Simpson, Myrna J
Chemistry in Action: Making Molecular Movies with Ultrafast Electron Diffraction and Data Science

A long-held thought experiment of science is the direct observation of the motions of atoms and molecules as they undergo chemical reactions and phase transitions. The advent of microscopy and diffraction beyond the visible spectrum of light ⁠— using X-rays, electrons, and neutrons ⁠— has since enabled such atomic-level elucidation of the structure of matter in the steady state. Recently, time-resolved techniques have finally enabled the making of the titular `molecular movie' on the time scale of chemical physics. In this thesis, I report on my works which further this quest by using ultrafast electron diffraction and data science to fully resolve the photoinduced structural dynamics of five large, low-symmetry, and weakly scattering molecular systems: two Bechgaard-Fabre salts of 4,5-ethylenedioxy-tetrathiafulvalene, a ring-closing diarylethene derivative, and two iron(II)-based spin-crossover complexes. Leveraging the ultrabright femtosecond electron source presently available, large overdetermining time-series maps of reciprocal space were measured and structurally refined to track the individual atomic motions that lead to each photoproduct: two transient metallic phases, a ring-closed isomer, and two expanded high-spin states. In all cases, a dramatic and heretofore unknown reduction in dimensionality was found, whereby the photoinduced structural dynamics is governed by key reaction modes that are much fewer in number than the degrees of freedom expected of the respective molecular systems. This insight — along with the experiments and methods presented herein — should find application in uncovering the physics of reduced dimensionality as a solution to the problem of how chemistry scales with complexity.This work lays the foundation to recast chemistry in terms of reduced reaction modes, unifying structure and dynamics as a new conceptual basis for chemistry.

Keywords: Crystallography
Data science
Femtochemistry
Spin crossover
Structural dynamics
Ultrafast electron diffraction
Advisor: Miller, R. J. Dwayne
The Ecological Validity of Traditional Pen-and-paper, Ecologically Oriented, and Virtual Reality Neuropsychological Test Measures to Cognitive Impairment and Real-World Function after Mild Traumatic Brain Injury

A growing concern in neuropsychology is whether neuropsychological test measures (NTMs) can predict functional outcome (i.e., ecological validity). Ecological validity can be understood in two ways: veridicality (i.e., prediction of functional outcome is independent of how the test reflects the outcome being measured) and verisimilitude (i.e., tests resemble the functional outcome they are predicting). Historically, the veridicality approach has been utilized (i.e., by way of traditional, pen-and-paper NTMs), but there has been a movement to employ verisimilitude approaches (e.g., Behavioural Assessment for Dysexecutive Syndrome; BADS). These approaches were examined in patients experiencing ongoing cognitive complaints in the post-acute period of recovery (> 3 months) following a mild traumatic brain injury (mTBI). This was the principal inclusion criteria for the studies described here. A meta-analytic study was conducted and found that traditional NTMs were not sensitive to persistent cognitive complaints in this population across all domains. Studies 2 and 3 utilized archival data to determine whether NTMs could predict return to work (RTW) status. The BADS predicted employment status by way of medium-to-large effects, while traditional NTMs did not. Overall, these findings suggest the verisimilitude approach is more ecologically valid than the veridicality approach. As such, two virtual reality tests (VRTs) evaluating attention and executive function were developed to investigate their ability to predict RTW. Tests of attention (VR and traditional tests) significantly predicted group membership at 82% accuracy, with 82.6% sensitivity and 81.5% specificity. The attention shift trial of the VRT and to a lesser degree the total speed score of the Ruff 2 7 were predictive of employment status. Overall, this research provides empirical evidence for the verisimilitude approach when evaluating RTW status in patients who are in the post-acute period of recovery following mTBI. Moreover, it provides initial evidence for the clinical utility of VRTs to evaluate real-world functioning.

Keywords: assessment
ecological validity
mild traumatic brain injury
neuropsychology
return to work
virtual reality
Advisor: Zakzanis, Konstantine K
Low-frequency Piezoelectric Energy Harvesting

In this work, a novel approach to reduce the resonant frequency of current piezoelectric energy harvesters is proposed to harness energy from low-frequency vibrations. The approach is to embed revolute joint mechanism(s) into the structure of harvesters. This approach is applied onto two typical configurations. The modeling, simulation and experimental results demonstrate that joints can effectively lower linear stiffness of the structures and further decrease the resonant frequencies of the harvesters. Besides, additional advantageous influences are found in widened operating bandwidth and higher voltage outputs. The voltage output enhancement results in a power output with matched impedance 440% or 730% as high as those of the two counterpart cases. As the joint mechanism embedment does not lead to increase in volume or mass of the harvesters, the power density is enhanced by the same magnitude. Also a truss-based compressive-mode piezoelectric energy harvester is proposed for ultra-low-frequency vibrations. Several techniques are employed: separated piezoelectric transduction element from the mechanically-excited system so that the resonant frequency is designed to be ultra-low; the truss mechanism for force amplification; an amplitude limiter causing impacts between the mass and limiter for frequency up conversion. Experimental results indicate that an open-circuit voltage reaches 83.3 V and a peak-peak power of 32 mW is generated with matched impedance. The harvester also demonstrates excellent charging performance to capacitors with a rapid charging rate and high saturation voltages. The harvester is able to charge a 47μF capacitor to over 2V in 50s, which powered a thermometer for 10s. Also two hybridization schemes with triboelectric and electromagnetic transductions are proposed. Both schemes demonstrate output power improvement. In the latter scheme, the harvester can generate a 1/3W peak power under excitation of 0.7g at resonance. A self-powered sensing system and a battery-free systems were developed so that not only can the sensor and electronic device be powered real-time, but also when excitation stops, residual charges can power them for a 20.38 and 8.33 minutes, respectively. This work can be greatly significant for high-performance energy harvesting and for development of self-power sensing and battery-free electronic systems.

Keywords: battery-free electronics
energy conversion
low-frequency
piezoelectric energy harvesting
self-powered sensing system
vibration
Advisor: Naguib, Hani E.
Working Together: Indigenous Knowledges, Urban Youth, and Mental Health for Career Development

Indigenous people in Canada have endured and survived many traumas as a result of the legacy of colonization, which have negatively impacted their social determinants of health. Employment, especially for Indigenous youth, has been identified as an area in need of urgent attention. Despite the fact that Indigenous youth are the fast growing population in Canada, they continue to be underemployed despite programs that were designed to increase Indigenous youth employment rates. This study explores the intersections of employment policies and practices, traditional and cultural knowledges, and mental health by interviewing ten Indigenous key community informants and five Indigenous Elders/Traditional Knowledge keepers in the Greater Toronto Area. The results revealed that decolonizing and Indigenizing current employment policies and practices and is integral to supporting Indigenous youth employment. The results of this study highlight the importance of modifying services so that they emphasize the strengths of Indigenous knowledges and cultures to promote healing and mental wellness. Implications were identified that policies, practices, and vocational psychology models can be enhanced in their application with Indigenous youth by integrating Indigenous worldviews related to health and wellness to promote healing from trauma and mental health.

Keywords: Employment solutions
Indigenous
Indigenous youth
Mental Health
Traditional Knowledges
Advisor: Stewart, Suzanne