116964 research outputs found
Sort by
De novo gene birth in experimental and natural bacterial populations
Get PDFThe question of the origin of new genes has been one of perennial significance to evolutionary biologists. While the birth of new genes from “scratch” – i.e., non-coding sequences – has been widely investigated in eukaryotes, this mode of gene evolution remains virtually unexplored in bacteria. In this work, I investigate this question across different time-scales and phases of gene birth in bacterial populations. I first identify incipient proto-genes – hypothesized precursors of new genes – in an experimental evolutionary context, and demonstrate that they can rapidly arise through the recruitment of existing regulatory sequences in the genome (Chapter 1). I then look to natural bacterial populations to investigate the frequency and evolutionary potential of these proto-genes (Chapter 2), and discover that the process shows taxon-specific trends: proto-genes frequently emerge in Mycobacterium tuberculosis and show potential of maturing into de novo genes, while the same pattern is not seen in the case of E. coli. I then expand the scope of my investigation to the entire pangenome of E. coli to attempt to identify mature forms of these genes, and demonstrate that such elements are either exceedingly rare in this taxon, or the method of detection has limited applicability to bacterial genomes subject to frequent gene transfer (Chapter 3). Finally, I survey the existing work done to explain the abundance of taxonomically restricted (“orphan”) genes in bacteria to identify pitfalls in extant approaches and describe fruitful avenues for research (Chapter 4).Cellular and Molecular Biolog
Doctoral thesis recital, flute (lecture)
No full textLecture: Diversifying flute repertoire as performers and educators -- Performances of 3 works, including: On a painting by Henry Ossawa Tanner : The thankful poor / Shawn E. Okpebholo.MusicName of supervisor not provide
Roles of sex and gonadal hormones in the modulation of risk-based decision making
Get PDFThis dissertation investigates neurobiological and hormonal mechanisms underlying sex differences in risk-based decision making using behavioral approaches. My research comprises three specific Aims, each addressed in their respective chapter. First, I characterized cognitive mechanisms underlying decision making, revealing distinct behavioral profiles of performance in males and females. Consistent with prior work, females were more risk averse than males. Risk aversion in females was associated with greater working memory performance whereas greater risk taking was associated with better cognitive flexibility in males. In my second Aim, I employed optogenetic techniques to elucidate the neurobiological substrates of risky decision making. By selectively inhibiting projections from the basolateral amygdala to the nucleus accumbens (BLA → NAc) or cells that selectively express dopamine D2 receptors (D2Rs) in the NAc, I determined how these neural pathways influence risk taking at distinct decision-making stages. Specifically, I found that the BLA → NAc pathway promotes risk aversion during distinct phases of decision making and does so in a sex-dependent manner. Additionally, my data show that D2R-expressing neurons in the NAc are similarly necessary for promoting risk aversion, but only prior to making a choice. This set of experiments advances our understanding of the neurobiological mechanisms that may mediate sex differences in risk taking. Finally, in my third Aim, I investigated the role of ovarian hormones in mediating female risk aversion. In these experiments, I tested whether exogenous administration of estrogen, progesterone and estrogen receptor agonists were able to restore risk aversion in ovariectomized females. I demonstrated that estradiol significantly decreases risk taking in female rats through action at ER [alpha] while progesterone does not play a role in this behavior. These findings indicate that estradiol is necessary for phenotypical female risk aversion through its action at ER [alpha]. Future studies are necessary to identify the critical locus of estradiol’s action in the brain for female risk-based decision making. I explore implications of these results and propose a conceptual model exploring how estradiol modulates D2R’s ability to promote risk aversion. Overall, this dissertation research advances our understanding of the mechanisms by which sex and gonadal hormones influence risk-based decision making.Neuroscienc
Benefits of traffic-following on order of autonomous airspace operations
Get PDFIn this thesis, we explore the dynamic emergence of traffic order within a distributed multi-agent system, focusing on minimizing inefficiencies stemming from unnecessary impositions of structural rules. We leverage a methodology for creating a dynamically updating traffic pattern map of the airspace. This map utilizes information about the consistency and frequency of flow directions used by current as well as preceding traffic. Informed by this map, an agent may adjust the degree of traffic-following behavior it exhibits. We show that at low densities, traffic following behavior results in a decrease in entropy of the airspace with low penalties in terms of travel times. As the density of an airspace increases, substantial gains in both airspace entropy and travel times are seen as the degree of traffic following behavior increases. Ultimately, the methods and metrics presented in this work can be used to optimally and dynamically adjust an agent's traffic-following behavior based on the density of traffic within an airspace.Aerospace Engineerin
Measurement of phonon angular momentum via the Einstein-de Haas effect, fiber-optic interferometry, and a high-Q oscillator
Get PDFIn this study, I report the measurement of the temperature dependent macroscopic phonon angular momentum using a fiber-optic-interferometer and mechanical oscillator system. An oscillating magnetic field is applied to an insulating ferromagnet attached to a single-crystal high-Q double torsional oscillator. By the Einstein-de Haas effect, oscillator displacement measurements between low temperatures and those closer to the Debye temperature allow observation of the changing phonon angular momentum. A force change on the order of 60 nN was detected between 77 K and 300 K for a 3 mm³ MgZn ferrite sample, in fair agreement with theoretical predictions. Our oscillator, with resonances at 1.3, 2.1, 9.4, and 12.4 kHz has a thermal noise limit on the order of 10⁻¹² N/√Hz, allowing the possibility of high-accuracy detection. Competing effects were minimized; for example, induced eddy current momentum can overwhelm the phonon effect for metallic ferromagnets, and careful temperature-dependent force calibrations were required.Physic
Experimentally characterizing the spark discharge process and electrode erosion mechanisms
No full textSpark ignition has long served a foundational role in initiating the combustion process for engines of varietal applications. Throughout the past 50 years, regulations of the combustion engine have exponentially increased, pushing for lower fuel consumption and reduced emissions with the goal of addressing environmental concerns. This has driven research into advanced understanding of the spark ignition process for guidance towards improved combustion efficiency. Many solutions require more extreme in-cylinder conditions such as increased pressure, air-fuel ratio, or exhaust gas recirculation, which may all inhibit the performance of the engine spark plugs. This work aids to address these concerns by providing experimental data used for improved spark plug designs and computational simulations under ever-intensifying conditions. The first part of this research focused on characterizing the electrical, thermal, and physical details of the spark discharge for varying experimental conditions. The goal of these experiments was to gather data for experimental conditions not previously studied, such as varied parameters at elevated pressure. Experiments were designed and fabricated to collect voltage and current data, as well as pressure and thermal energy deposition to the ambient gas. Breakdown voltage was investigated for the effects of pressure, temperature, electrode gap distance, gas composition, electrode geometry, and crossflow velocity. Equally important, thermal energy deposition from the plasma to the ambient gas was studied for similarly varying parameters, albeit without temperature or crossflow velocity. A spark calorimeter was employed to measure the small pressure rises from the spark, which were converted to energy quantifications and compared with overall energy delivered to the spark plug by the ignition system. Finally, a high-speed camera captured arc movement from the spark plug electrodes subjected to varying crossflow velocities. An analysis program was written to process images from the video files and quantify the stretched arc characteristics. The second half of the research focused on the cathode erosion for spark plug applications. Extended duration and short-term (down to single-spark) studies were conducted for quantifying erosion rates of various electrode materials under various sparking conditions. Imaging techniques utilizing scanning electron microscopy (SEM), energy dispersive x-ray spectroscopy (EDX), focus ion beam (FIB), and optical profilometry were employed for a qualitative study of electrode deformation characteristics. Erosion rates were found for both raw electrode materials and commercially available spark plugs using durability testing practices. Air and nitrogen environments are studied for the effects of oxidation on electrode wear, and at elevated temperatures and pressures.Mechanical Engineerin
Elucidating the molecular architecture of precision glycopolymers for improved lectin binding
Get PDFIn both plants and animals, many biological processes arise from the multivalent recognition of carbohydrates by lectins. As an approach to manipulate these processes, polymer chemists have begun developing synthetic glycopolymers that leverage multimeric glycan presentation toward specific lectins. However, much work has to be done on how polymer design influences their specificity toward lectins hosted by different biological kingdoms. In this work, we developed precision glycopolymers (PGPs) with precisely defined local chemical composition and well-controlled global architecture. These materials were designed as tools to systematically investigate how structural variations within glycopolymers influence their binding properties to both plant and animal lectins. To this end, we prepared a series of galactose-containing precision glycopolymers (PGPs) using graft-through ring-opening metathesis polymerization (ROMP). This library was systematically varied to explore the effects of polymer length, linker length, backbone composition, glycan density, and glycan identity on the binding interactions with galectin-3 (Gal-3, a mammalian lectin) and peanut agglutinin (PNA, a plant lectin). Our findings demonstrate that while all structural parameters influence the binding of PGPs to lectins, glycan density emerges as the most critical factor. Polymers with less than 50% grafting density show markedly higher dissociation constants (KD), resulting in decreased interactions with both Gal-3 and PNA To connect these binding properties to biological function, we evaluated the activity of Gal-PGPs in vitro, where they significantly decreased both cellular viability and migration in 4T1 triple-negative breast cancer cells. Together, these findings highlight how macromolecular considerations for polymeric carbohydrate presentation governs their binding to both plant and animal lectins, laying the groundwork for the development for the design of more specific glycopolymers targeting galectins.Chemistr
An exploration of reversable covalent systems including the thiol-Michael addition and EVA depletant study
Get PDFHydrogels offer many uses in the medical field because their hydrophilicity makes them compatible with the human body. However, challenges in the application of hydrogels occur due to the rigid nature of covalent bonding. These barriers restrict hydrogels’ capacity to exhibit tunable system designs, offering self-healing structural properties, or value in the release of slow acting drug molecules. Interestingly, a solution to these challenges proposes synthetically incorporating dynamic covalent bonding pairs in these materials systems. With the implementation of dynamic covalent chemistry, material systems can be modulated to introduce reversible binding and then dispersion upon the introduction of an experimentally controlled stimulus. This thesis describes an investigation into the properties of the dynamic covalent binding pair of a thiol moiety with a conjugate acceptor via a thiol-Michael addition. A controlled molecular assembly offers a simplified system in which the role of substituent effects can be fully investigated and understood, with limited interference of variables introduced by material assemblies. In the first study, a library of conjugate acceptors was studied to develop a Hammet plot to elucidate the influence of substituent effects on the thiol-Michael addition. It was discovered that electron withdrawing groups react extremely fast and can form stable intermediates with water if not carefully controlled. The second study lays the foundation to probe depletant effects of a dynamic compound, known as EVA, and a conjugate acceptor by modulating the molecular weight of groups attached to EVA. As such, this research into the dynamic covalent chemistry of the thiol-Michael addition provides the understanding and groundwork needed for future implementation into materials systems, specifically hydrogels. Adapting this chemistry in hydrogels provides the potential for more tunable properties that are directly modulated by the relationship between the identity of the substituent and the equilibrium of the reaction. Such tunable material assemblies allow for the exploration of systems capable of achieving chemically modulated out-of-equilibrium states that are fundamental to our understanding of life.Chemistr
Attribution theory in medicine : a review of the current literature
Get PDFAttribution theory is a field of inquiry in motivation research regarding the perception of the causes of an outcome and how the attributed causes may shape future decision making. Attributions are classified by three causal dimensions of stability, controllability, and locus of control. Attribution theory has been applied across several disciplines, including the healthcare field. Medical applications of attribution theory are aimed at understanding social stigma that contributes to causal antecedents, understanding patient and provider causal beliefs, and evaluating the physical and psychological impact of shifting between attributional domains as a patient. Attribution theory has been primarily studied in the context of highly stigmatized, chronic diseases with multifactorial etiologies such as obesity, type II diabetes, and substance use disorder. The reviewed literature suggests that providing uncontrollable and/or external attributions such as genetics and environmental factors can decrease self-blame among patients and therefore improve psychological well-being. However, this must be balanced by internal, controllable attributions that allow for a sense of agency as patients move forward in the treatment process. Further research is required to better understand how providers can best utilize attribution theory to improve counseling practices and patient outcomes.Educational Psycholog
DOPE : a work for wind band
Get PDFDOPE is an extensive look at the musical genres of black cultures such as hiphop, jazz, soul, and others through the lens of the western wind ensemble setting. With the use of several harmonic tropes and motifs influenced by great black artists, DOPE create sonic blend of past triumphs with hints of the future of fusion.Musi