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The Role of Reactive Oxygen Species in Response to Chronic Ischemia and Exercise Training Within the Coronary Microcirculation of Swine
No full textThe overall goal of this thesis was to explore adaptations in the contribution of reactive oxygen species (ROS) to coronary microvascular function in response to chronic ischemia and exercise training. The main hypothesis of this study was that superoxide and NADPH oxidase (NOX)-derived ROS would contribute to vasodilation of coronary arterioles and that the contributions of these ROS would be impaired by chronic ischemia and ameliorated with exercise training. These studies utilized a swine model of chronic ischemia via occlusion of the proximal portion of the left circumflex artery with an ameroid occluder while exercise adaptations were examined via the completion of a 14-week progressive (5 days/week) treadmill regimen. Functional pressure myography experiments were performed on isolated arterioles from occluded and nonoccluded regions of sedentary and exercise-trained swine. Additionally, microvascular endothelial cells and arterioles were isolated for high performance liquid chromatography (HPLC) to examine superoxide anion levels and immunoblot to evaluate protein levels of superoxide dismutase (SOD), p22phox, and NOX isoforms.
Functional microvascular studies demonstrated that exercise training produced a rightward shift in vasodilation to the endothelium-dependent agonist, bradykinin, when scavenging superoxide with tempol, independent of occlusive treatment. Further experiments with the NOX1/4 inhibitor, GKT136901, revealed attenuated dilation after exercise training plus occlusion, but not with either exercise or occlusion alone. HPLC revealed that there were no differences in the basal or bradykinin-stimulated production of superoxide anion, regardless of occlusion or exercise. Furthermore, immunoblot analyses revealed decreased NOX2 protein after exercise with no differences found in NOX1, NOX4, p22phox, or SOD protein levels.
Together, these studies demonstrate that exercise-training stimulates independent contributions of both superoxide and NOX1/4-derived ROS to endothelium-dependent, bradykinin-mediated dilation of swine coronary arterioles. It is evident that exercise training produces cellular adaptations within the coronary microcirculation resulting in the contribution of ROS to vasodilation, and subsequently, increases in coronary blood flow. While we determined that ROS play a role in exercise-induced adaptations in the coronary microcirculation, additional study of specific sources and downstream effectors of these ROS are warranted
Electric Powertrain Models for Small UAS Conceptual Design
No full textSmall, battery powered unmanned aerial systems (SUAS) have become indispensable tools for researchers, civilians, and warfighters. However, conceptual designers do not have rigorous tools to design and analyze their electric powertrains which consist of brushless DC motors; therefore, lid-state motor controllers, and lithium polymer batteries. Literature models to analyze the components��� efficiencies rely on detailed information that a vehicle designer cannot practically acquire at the early design stage, such as empirical test data. Therefore, engineers must rely on inaccurate constant powertrain efficiency assumptions which lead to subpar designs. Moreover, existing models ignore the influence of a component���s thermal dynamics on size and performance; therefore, these models could lead to designs that are significantly over or undersized depending on the thermal conditions in which the existing models��� underlying data was collected. Consequently, the resulting designs can overheat or add too much weight penalty in the final vehicle. We have developed a set of efficiency, thermal, and sizing models to address this literature gap in the design and analysis of electric powertrains. We validated these models using wind tunnel tests, motor teardowns, and flight tests. Individually, the models can predict a motor���s efficiency, heat transfer, mass, and electrical constants given high-level inputs which a user can easily find at the conceptual design stage. The models capture the coupled dynamics of a motor���s size, performance, and thermal response. The nuanced results enable users to size the optimal motor for a desired application and given thermal conditions. We also developed efficiency models for the motor controller and battery which rely on fewer inputs than similar literature models, and we validated them with parametric experimental tests. Finally, we developed an instrumentation system that measured and recorded a quadcopter���s propeller torque, propeller speed, and electrical power during flight. We used the flight data to validate an integrated powertrain model that combined the motor, motor controller, and battery efficiency models. The integrated model predicted the vehicle���s battery discharge within 5% of flight data for a six-minute flight. The integrated model enables a user to evaluate different powertrain configurations for an entire mission using readily available inputs
Spectroscopic Studies of Stars and Black Holes Across Cosmic Time
No full textIn this work, I present my spectroscopic studies of galaxy evolution across a large majority of cosmic time (0 ��� z ��� 9). My career to this point has two distinct phases: pre-JWST, when I utilized spectroscopy from HST to study star formation, dust attenuation, and accreting black holes out to the peak of cosmic star formation rate and active supermassive black hole density (cosmic noon; z ��� 2), and post-JWST, where my focus shifted to this new observatory to push the study of galaxy evolution to some of the earliest known galaxies at z ��� 8.
In the pre-JWST era, I used HST grism spectroscopy to study star formation rates and histories as well as dust attenuation by using the near-IR Paschen lines of hydrogen. Emission from Paschen lines indicates near-instantaneous star formation, while probing regions inaccessible to UV or optical star formation tracers due to dust attenuation.
I also used HST grism spectroscopy to probe galaxies around cosmic noon which exhibit the extremely-high-ionization [Ne V] line. This spectral feature is a strong tracer of an ionizing spectrum powered by an accreting black hole, at least in this epoch of cosmic time.
These studies serve as optimal pilot campaigns for the JWST era, where JWST spectroscopy can probe these features out to much earlier epochs of cosmic time. I discuss the implications of JWST studies of Paschen-line star formation rates and dust attenuation out to cosmic noon, and studies of high-ionization emission lines in the epoch of Reionization.
Using early JWST spectroscopy in conjunction with HST spectroscopy and photoionization models, I develop a novel diagnostic to trace ionization from different sources at all epochs of cosmic time. This is designed specifically with elusive objects in the early Universe in mind, including Population III stars and accreting intermediate-mass black holes, in an effort to study the earliest stages of star formation and black hole growth.
We stand at the beginning of a new era in the study of galaxy evolution. With the incredible capabilities of JWST, we can study the physical mechanisms governing galaxies across cosmic time like never before
The Hepatic Biotransformation Capability and Occurrence of Emerging Contaminants in American Alligators (Alligator Mississippiensis)
No full textRecently, emerging contaminants (ECs) have been drawing more attention due to health concerns in exposed organisms. Pharmaceuticals and per- and polyfluorinated substances (PFAS) are representative ECs that are ubiquitous and persistent in aquatic environments. American alligators (Alligator mississippiensis) are often considered a sentinel species in coastal aquatic ecosystems along the Gulf of Mexico as they are susceptible to the bioaccumulation of contaminants due to their high trophic position and longevity. However, the biotransformation capability of alligators for ECs and EC exposure impact in wild alligators are yet to be understood. Therefore, this study aimed to address these knowledge gaps.
For the evaluation of biotransformation capability, a novel in situ liver perfusion system was developed using juvenile alligators. The operativity of perfused livers was tested with normoxic and hypoxic treatments. Under normoxia, the aspartate transferase (AST) and lactate/pyruvate ratio in effluent perfusate remained stable for 6 hours whereas hypoxia significantly increased the lactate/pyruvate ratio after 2 hours. The elevation of lactate suggests the induction of anaerobic metabolism indicating the viability of the organ. With the establishment of operable perfused livers, alligator biotransformation capability for carbamazepine (CBZ) and nicotine (NCT) was investigated by measuring the formation of their primary metabolites. Additionally, the in vitro S9 assay was performed to compare its metabolic potential with perfused livers. For CBZ, perfused livers exhibited only 30% intrinsic formation clearance (CLf,int) relative to the S9 assay. The NCT metabolism was only observed in perfused livers. Compared to the corresponding rat models (S9 or perfused livers), alligators��� CLf,int was 20-60% for CBZ and 50% for NCT of rats. Lastly, wild alligator plasma was analyzed for select ECs and biochemistry parameters. The detected ECs included amphetamine, atenolol, ketoprofen, naproxen, nicotine, and perfluorooctane sulfonic acid. Statistical analyses showed positive correlations between the plasma EC levels and biochemistry indicating potential physiological stress associated with organ injury and endocrine disruption. While this study provides invaluable insight into the metabolic capability and vulnerability to EC exposure in alligators, the methods developed in this study can also serve as an effective toolbox for future studies to protect this ecologically important species
A Primate Model for Studying the Importance of Environment and Family Lineage on Development, Health, and Aging
No full textThe Cayo Santiago rhesus macaques are one of the most intensely studied primate colonies in the world. They are associated with a rare skeletal collection that is contextualized with known sex, age, and familial information. The purpose of this dissertation is to elucidate environmental and genetic contributions of bone health, evolution, and development. In doing so, this will become a translational resource for human disease and variation. This study departs from previous endeavors by extracting almost all development and pathological data from the derived skeletal collection and stratifying it with known life-history and demographic information to produce reliable biomedical models of health. The backbone of the proposed model is derived from the skeletal collections housed at the Caribbean Primate Research Center University of Puerto Rico, Medical Sciences Campus and New York University, Department of Anthropology. Statistical analysis such as relative risk ratios, and multivariate regression were employed to test for the relative roles of environment and genetics on bone health in the population. The Cayo Santiago population were found to exhibit secular trends in congruence with ecogeographic rules. Specifically, body weights declined, and limb dimensions became slenderer, increasing surface area/volume ratios of individuals and heightening heat expenditure in a more homogeneously warm climate than the one they were adapted to over evolutionary timescales. In contrast to the gradual impacts of climate, major hurricane events precipitated increased levels of systemic disease, bone mineral density (BMD) reductions, and delayed dental eruption timings. Greater rheumatic disease, lower BMD, and delayed dental eruption are believed to relate to immune dysregulation, low grade chronic inflammation, and early-adversity. Further analysis indicated that disease is also patterned across families indicating that a genetic susceptibility to disease can be observed within the matrilines of the Cayo population. Lastly, the neurosurgical landmark, the pterion, exhibited strong support for inheritance of pattern. This work suggests craniotomies using the pterional approach may benefit from taking or making use of family history of pterion type and subsequently benefit from aspects of its variatio
Unveiling the Myth Within: The Role of Narrative Perspective in C.S. Lewis' "Till We Have Faces"
No full textThis thesis explores the embodiment and performance of myth through the first-person viewpoint in C.S. Lewis��� Till We Have Faces (Faces). In this novel, Lewis moves away from his previous rationalist approach and uses myth and a first-person narrator to write an intimate story unlike what he had accomplished before. It is a shift in narrative methodology that signifies a corresponding evolution in Lewis��� theology. I study the potential cause of this shift through a study of Lewis��� Christian conversion and an impactful philosophical debate. The result is a particular and unique utilization of myth as a vehicle of conflict, as the protagonist, Orual, is shrouded from reality and must reckon with her own mythology to gain an accurate interpretation of herself and of the divine. I compare the original myth of Cupid and Psyche in The Golden Asse with Faces in order to understand Lewis��� purposes in changing the original story and glimpse the result. Ultimately, he seeks to reveal the importance of coming ���face to face��� with one���s self and holding on to one���s identity. I investigate the theme of identity, as highlighted by the first-person perspective, through the embodiment and performance of myth to argue how Faces is unique among Lewis��� literature
Compositional Path Design for Graded Alloys Using Reinforcement Learning
No full textCompositionally Graded Alloys belongs to the category of Functionally Graded Materials (FGMs), distinguished by their varying spatial composition within the structure that results in material alloys of superior properties over traditional alloys. In the recent years, these compositionally graded alloys have gained significant recognition, primarily because of the advancements in the additive manufacturing techniques like Directed Energy Deposition (DED) which make the production of these alloys feasible. However, a linear gradient path of these alloys result in the inclusion of deleterious phases within the alloys micro-structure that can adversely affect the final alloy properties which may result in cracks & in the work done by Kirk et al [1] an innovative gradient path planning algorithm inspired by the state-of-the-art robotic route planning algorithms was adopted and a successful gradient path was designed in Fe-Ni-Cr material system which avoided the deleterious phases that was impacting alloy gradient when printed from 316L stainless steel to pure Cr. One significant drawback of this technique is that it limits the flexibility of material space exploration that could be done by the designer, any new composition exploration can only occur after re-configuring the path planner to compute the feasible gradient throughout the material domain and this limitation leaves designers with few alternatives. Q-Learning is a model-free Reinforcement Learning algorithm was used to solve this design space exploration problem in the ternary materials environment. An innovative method of encoding absolute position of the agent in barycentric coordinates along with the relative heading state to goal was formulated to model the system thus enabling design space exploration. The effectiveness of the proposed method was measured in a holdout dataset which produced a validation accuracy of 97%
Search for New Resonances Produced by Bottom Fermion Fusion in Dimuon Final State with Run 2 CMS Data
No full textA search is presented for a new neutrally-charged boson Z��� decaying into two muons associated with one or two jets and at least one b tag among them. The analysis is performed using data corresponding to an integrated luminosity of 137.58 f b^���1 collected in 2016-2018 with the CMS detector in proton-proton collisions at ��� s = 13 TeVand sets limits upon Z��� masses between 125 and 350 GeV. No significant deviation from the expected background is observed, setting 95% confidence level upper limits on the production cross section times branching ratio times acceptance (�� �� Br(Z ��� ��� ����)�� A) ranging between 3-10 f b. Acceptances for a variety of final states are also provided, allowing for the interpretation of these results to a variety of models
BATF3 and IRF4 Control iTreg Cell Fate Decisions
No full textFOXP3 is the lineage-defining transcription factor for Tregs, a cell type critical to immune tolerance, but the mechanisms that control FOXP3 expression in Tregs remain incompletely defined- particularly as it relates to signals downstream of TCR and CD28 signaling. In this dissertation, I studied the role of IRF4 and BATF3, two transcription factors upregulated upon T cell activation, to the conversion of conventional CD4+ T cells to FOXP3+ T cells (iTregs) in vitro. I found that BATF3 is a potent inhibitor of FOXP3 expression and iTreg differentiation but is dependent on interactions with IRF4 to mediate this inhibition. BATF3 allows IRF4 to bind an upstream regulatory region within the Foxp3 super enhancer. I further demonstrate that interactions of these transcription factors are necessary for glycolytic reprogramming of activated T cells that is antagonistic to FOXP3 expression and stability. However, I also show that BATF3 and IRF4 play critical roles to iTreg function, demonstrating unique roles for these transcription factors in FOXP3 induction vs. in differentiated iTregs. Thus, my findings highlight how BATF3/IRF4 interactions contribute to the complex interplay between TCR signaling, FOXP3 expression and stability, and iTreg function while providing important insights to cellular mechanisms that govern expression of the Foxp3 locus
Developing the Texas A&M Smart and Connected Homes Testbed
No full textThe Texas A&M Smart and Connected Homes Testbed has been developed to support residential HVAC research. The flexible testbed enables the windows and walls to be replaced, the floorplan to be reconfigured, provides two separate duct networks, and incorporates on-site renewable energy. Heavy instrumentation is done at the testbed to capture information on local weather conditions, building envelope performance, occupant comfort, HVAC equipment performance, and the power consumption of all household end-uses. A smart thermostat is also incorporated to provide HVAC control capabilities. Occupants are simulated inside the home to mimic actual operation and internal loads. A Modelica model has been created for the building envelope and split system HVAC at the testbed. Using data from the experimental testbed, the model is tuned to ensure accurate implementation. Researchers can use these models to bridge the gap between simulation-based studies and their real-world application