This dissertation concerns two aspects of Plutarch’s ethics that have received relatively little attention: the link between his metaphysics and ethics, and Plutarch’s use of diatribe, a rhetorical style primarily associated with Stoics and Cynics, as a means of targeting a wider audience of educated elite for his philosophy. I argue that Plutarch’s De virtute morali links his ethics with his understanding of Platonic metaphysics. De virtute morali also serves as model for Plutarch’s ethical treatises on specific topics. I analyze the following works: De curiositate, De garrulitate, De vitando aere alieno, De vitioso pudore, and De superstitione. In these, Plutarch identifies a vicious behavior (κρίσις) and suggests methods of self-training to eliminate the vicious behavior (ἄσκησις). Self-training always involves the subordination of emotions to reason (μετριοπάθεια), rather than the elimination of emotions (άπάθεια) advocated by the Stoics. Plutarch uses diatribe, in which the author adopts a conversational tone and addresses the reader in second person, both in κρίσις and ἄσκησις, as well as in his arguments against Stoic άπάθεια. Since Stoicism was the most popular philosophical adherence among educated elites during the time when Plutarch began to write, I argue that Plutarch adopts rhetoric associated with the Stoics as a means of promoting Platonism, and himself as its interpreter, in a culture where intellectuals required the patronage of the educated elite for their personal livelihood and the livelihood of their schools.

Fluoroquinolones, a class of type-II topoisomerase inhibitors, have successfully been used as antibiotics for the last several decades, beginning with the use of nalidixic acid in urinary tract infections. This led to the broad-spectrum activity of ciprofloxacin in the 1980s. Unfortunately, use of fluoroquinolones has led to the emergence of resistant bacteria. Recently, this has generated new bacteria such as multidrug-resistant and extensive-drug-resistant strains of M. tuberculosis that are also fluoroquinolone-resistant. Infections caused by these bacterial strains are widespread, with high mortality rate in immune-compromised populations such as the elderly, infants, and in AIDS or HIV-positive patients. Fluoroquinolone resistance is acquired through amino acid substitutions of key fluoroquinolone-binding residues of the type-II bacterial topoisomerases DNA Gyrase and Topoisomerase IV, the enzyme targets of fluoroquinolones. Amino acid substitutions that result in fluoroquinolone resistance are located on Helix-4 of these enzymes, which is the site of a magnesium (Mg)-water bridge that is a crucial binding interaction for fluoroquinolones. When certain substitutions to Helix-4 occur, the Mg-water bridge is compromised and no longer available to anchor fluoroquinolones into a ternary complex composed of topoisomerase, fluoroquinolone, and DNA. This results in drug resistance. Herein are described attempts to generate fluoroquinolones that are capable of overcoming this mechanism of resistance. In the first study, attempts were made to generate a series of novel tricyclic fluoroquinolones and diones designed to exploit intercalative or pi-stacking binding interactions with the bacterial DNA in the ternary complex in order to lessen the importance of the Mg-water bridge interaction. Despite numerous attempts, no complete synthetic pathway to these core structures was ever discovered. The second study investigated the utility of a C7-aminomethylpyrrolidine group on the fluoroquinolone structure. This was done in order to explore the mechanistic reasons why previously generated fluoroquinolones possessing this C7-aminomethylpyrrolidine group maintained activity against common Helix-4 mutants. A panel of fluoroquinolones with C7-aminomethylpyrrolidine groups and diverse core structures was synthesized and docking studies with the original C7-aminomethylpyrrolidine fluoroquinolone and other fluoroquinolones were performed. Target compounds were synthesized and evaluated for inhibition/poisoning purified enzyme and for the ability to inhibit growth with wild-type and fluoroquinolone-resistant cells. In a third study, fluoroquinolones possessing structural variations of the C7-aminomethylpyrrolidine were designed and synthesized to explore structural requirements of the aminomethylpyrrolidine group binding and overcoming fluoroquinolone-resistance caused by alterations of Helix-4. This led to further exploration of the binding space around the C7-position of the fluoroquinolones. In both the second and third studies, the new fluoroquinolones were evaluated for the ability to specifically target bacterial topoisomerases over human topoisomerase. The results of these studies have contributed new knowledge to the binding requirements of fluoroquinolones that maintain potency against fluoroquinolone-resistant type-II topoisomerases, and represent a step towards methodology to overcome bacteria resistant to fluoroquinolones.

The Jacobson radical of a ring was first formally studied in 1945 by Nathan Jacobson and is an important object in modern abstract algebra. The analogous notion of the Jacobson radical for a module is referred to as the radical of a module. The radical of a module is the intersection of all its maximal submodules. In general, the radical of a module is simpler than the module itself and contains important information about the module. The study of the radical of a module often appears as an incidental to other investigations. This thesis represents work towards understanding the radical of a module extension. Given a ring $R$ and $R$-modules $A,B,X$ such that $X$ is an extension of $B$ by $A$ as in the short exact sequence $$0 rightarrow A rightarrow X rightarrow B rightarrow 0 ,$$ we seek to determine properties of the radical of $X$, denoted $rad{X}$. These properties are dependent on the ring $R$ and properties of the modules $A$ and $B$. In this thesis we examine several different types of extensions and discuss a phenomenon in which a non-zero radical implies a split sequence. We work in the context of rings and their ideals. Extensions of abelian groups provide motivation for the results we prove about injectivity of radicals of extensions involving divisible modules and torsion modules. We are able to prove such properties of the radical for extensions of modules over principal ideal domains and Dedekind domains. Expanding upon these cases, we explore a more general construction of an extension and use it to explain our motivating abelian group results. We use the theorems proven about this construction to remark on possible generalizations to other types of rings and modules. We conclude with plans to generalize our statements by translating into terms of infinite matrices and $h$-local rings.

Because few women were permitted to join professional orchestras before World War II, women’s orchestras developed in major American cities, including Boston, New York, Chicago, and Philadelphia, during the interwar period. The Orchestrette Classique, a women’s chamber orchestra, performed in New York City between 1933 and 1944 under the direction of conductor and violinist Frédérique Petrides. Over the course of its tenure, the ensemble became known for its unusual concert programs, which often juxtaposed contemporary compositions with more traditional classical repertoire. Using primary source documents from the Frédérique Petrides Papers collection at the New York Public Library and articles from New York newspapers, this thesis presents the ways in which Petrides promoted the members of her ensemble as serious musicians, despite gender bias and the economic difficulties of the Depression. By cultivating working relationships with contemporary composers such as Henry Cowell, David Diamond, and Paul Creston, Petrides gave female musicians a role in the development of American classical music.

Contact structures on 3-manifolds are 2-plane fields satisfying a set of conditions. The study of contact structures can be traced back for over two-hundred years, and has been of interest to mathematicians such as Hamilton, Jacobi, Cartan, and Darboux. In the late 1900's, the study of these structures gained momentum as the work of Eliashberg and Bennequin described subtleties in these structures that could be used to find new invariants. In particular, it was discovered that contact structures fell into two classes: tight and overtwisted. While overtwisted contact structures are relatively well understood, tight contact structures remain an area of active research. One area of active study, in particular, is the classification of tight contact structures on 3-manifolds. This began with Eliashberg, who showed that the standard contact structure in real three-dimensional space is unique, and it has been expanded on since. Some major advancements and new techniques were introduced by Kanda, Honda, Etnyre, Kazez, Matić, and others. Convex decomposition theory was one product of these explorations. This technique involves cutting a manifold along convex surfaces (i.e. surfaces arranged in a particular way in relation to the contact structure) and investigating a particular set on these cutting surfaces to say something about the original contact structure. In the cases where the cutting surfaces are fairly nice, in some sense, Honda established a correspondence between information on the cutting surfaces and the tight contact structures supported by the original manifold. In this thesis, convex surface theory is applied to the case of handlebodies with a restricted class of dividing sets. For some cases, classification is achieved, and for others, some interesting patterns arise and are investigated.

Through spectral analysis, synthesis, and manipulation, I incorporate the transient and resonant sounds of tap dance into an acoustic piece, Aperture Assonance, for chamber orchestra. By means of abstraction, I explore the idioms of tap dance through distortions, common to practices of spectral composition. The title, metaphorically, refers to the small opening through which light travels (an aperture) and the manipulation of that light to create a resemblance of like-sounds (assonance). Instead of light, however, I treat sound as the source that travels through the, metaphorical, aperture. The pitch and rhythmic material were derived from the analysis of me dancing. The frequencies discovered were approximated to the nearest quarter-tone (24-tone equal temperament). These approximations served as a reservoir of pitch material to be explored throughout Aperture Assonance. Formally, the piece unfolds through explorations of the transient (the attack that instigates a sound) and resonant (the sustain that occurs after the instigation) properties of my tap dance recordings. By separating the transience from the resonance, I am able to isolate or rearrange each element to create new, musical gestures. For example, the transience and resonance may be reversed where the resonance instigates the gesture and the transient ends it. In a fractal manner, many gestures from the motivic, cellular level were rhythmically augmented to serve on the phrasal, mid-level form or become part of a larger texture. The macro level of the piece is divided into three sections: Transience, Resonance, and Transience Through Resonance. The abstraction of this material allows for differing, sonic interpretations. Because of the unique sounds created through tap dance, Aperture Assonance serves as a model for further transient and resonant exploration through the investigation of non-musical sounds.

How asexual reproduction affects genome evolution, and how organisms that are ancestrally sexual alter their reproductive machinery upon becoming asexual are both central unanswered questions in evolutionary biology. While these questions have been addressed to some extent in organisms such as asexual clams, rotifers, ostracods, arthropods, and fungi, the most powerful and direct tests of how sex and its absence influence evolution requires direct comparisons between closely related and otherwise similar sexual and asexual taxa. Here, I quantify the rates and patterns of molecular evolution in the meiosis-specific genes Msh4, Msh5, and Spo11 in multiple sexual and asexual lineages of Potamopyrgus antipodarum, a New Zealand freshwater snail. Because asexual P. antipodarum reproduce apomictically (without recombination), genes used only for meiosis should be under relaxed selection relative to meiosis-specific genes in sexual P. antipodarum, allowing me to directly study how asexuality affects the evolution of meiosis-specific genes. Contrary to expectations under relaxed selection, I found no evidence that these meiosis-specific genes are degrading in asexual P. antipodarum; instead they display molecular patterns consistent with purifying selection. The presence of intact meiosis-specific genes in asexual P. antipodarum hints that the asexuals may maintain the ability to perform meiosis despite reproducing apomictically. Asexual meiotic capability suggests that some meiotic components may persist or acquire a new role in these asexuals.

In this dissertation, I argue for a set of interpretations regarding the relationship between moral obligation and reasons for acting in the theories of Hobbes, Hutcheson, and Hume. Several commentators have noted affinities between these naturalist moral theories and contemporary ethical internalism. I argue that attempts to locate internalist theses in these figures are not entirely successful in any clear way. I follow Stephen Darwall's suggestion that addressing the question “why be moral?” is one of the fundamental problems of modern moral philosophy. Since, as some have argued, there is a tension between accepting internalism and providing an adequate response to the “why be moral” question, I argue that each figure maintains a distinctive response to this question given the sort of internalism, if any, he would accept. In the introduction, I provide the key distinctions that arise from contemporary discussions of ethical internalism, and I motivate my project of looking for insight into the relationship between internalism and amoralism in the British Moralists. Chapters 1 and 2 focus on the moral theory Hobbes who, I argue, would accept a version of constitutive existence internalism because he holds that there is a necessary connection between one's being contractually obligated and one's being in certain rationally motivating states. I then present the fool's objection as an objection to the assumption of a relevant similarity between divine obligation and contractual obligation. I argue that, irrespective of this dissimilarity, the fool has some rational motive to keep his covenants in virtue of the fact that making covenants changes one's decision situation in such a way that it becomes reasonable to treat covenants as if they imposed categorical constraints on behavior. I claim that Hobbes's response to the fool is, at least in part, that the fool fails to understand what moral obligation consists in. In the remainder of the dissertation I turn my attention to two classical sentimentalist moral theories. I examine the theories of Hutcheson and Hume because it is not clear what resources moral sentimentalism has available to it in order to address questions about the reasonableness of moral action. In chapters 3 and 4, I develop an interpretation of Hutcheson who, because he distinguishes between exciting and justifying reasons, is able to say there is some non-derivative sense in which moral actions are reasonable. I argue that he develops a theory whereby moral obligation is to be understood in terms of the non-motivating states of approval of moral spectators, and I do not think, contrary to Darwall, that there is anything puzzling about his doing so. I argue that Hutcheson does not accept a version of motive internalism, but that he shares much in common with internalist views: he claims that there is a very strong, if contingent, connection between our states of approval and our motivational states. I offer an explanation of how Hutcheson could respond to the amoalist, which holds that we ought to be moral because, in part, we all already have the motives for and the interests in doing the sorts of things of which moral spectators approve. In chapters 5 and 6, I turn my attention to Hume who, because he makes no distinction between motivating and justifying reasons, does not seem to have anything to say about the non-derivative reasonableness of moral action. I argue that a textually grounded interpretation of Hume's theory of the passions provides us with more reason to favor an (appraiser motive) internalist reading over an externalist reading of his moral theory. Much of my argument depends on an interpretation of Hume's claim that it is possible for agents to be moved to act from a sense of duty alone. When we ask what Hume can say to the question “why be moral,” some of the options that Hutcheson pursues are initially open to him. However, I argue that Hume thinks philosophical theorizing must give way to the operations of psychological mechanisms that are causally responsible for inspiring agents to act morally by giving rise in them to particular kinds of affections. I conclude with some general remarks about the problems surrounding Darwall's interpretation of Hume's theory of justice, and use this discussion to lend further support to the claim that the actual theories of Hobbes, Hutcheson, and Hume do not neatly fit into the taxonomies that Darwall seems to think they do.

Multiple myeloma is a plasma cell cancer that affects the bones, immune system, and kidneys. In this thesis, we focus on the impact on the bone, specifically routine bone remodeling. The bone remodeling process is governed by chemical signaling between several cell populations. In multiple myeloma patients, this process is out of balance. Bone destruction outpaces bone replacement, leaving patients with bone lesions. We describe the cell-signaling network that regulates bone remodeling and explain how it is impacted by multiple myeloma. We then present a series of mathematical models describing the bone remodeling process. We lay a thorough mathematical foundation, starting with the derivation of Savageau's power law approximations. Next, we introduce a novel one-dimensional moving-boundary partial differential equation model of this biological system. Our model improves upon models from the literature by including new cell populations, specifically osteoclast precursors, stromal cells, and tumor cells. We also discuss the model's computational results and their significance. We then discuss image processing techniques that can be used on bone marrow biopsies to gather data on the growth of a multiple myeloma tumor. By analyzing these medical images, we can extract tumor cell counts. In particular, we give the results of such an analysis for one patient using color unmixing. Image processing techniques, such as the ones presented here, could be used for validation of the models we present. The long-term goal of this project is the creation of a diagnostic tool that will aid oncologists in selecting the best treatment plan for their patients with multiple myeloma.

The purpose of my thesis project, A View of Affect has been two fold: to engage closely with an early modern book, and to experiment with the idea that self-examination as a legitimate way to gain knowledge about the body. Working with Robert Burton's Anatomy of Melancholy, (1621) has opened to view the extensive constellation of ideas that were part of the philosophical universe of the time. I engaged with the Anatomy of Melancholy by immersing myself in the prose, responding to Burton's writing with my own writing. I also studied and made drawings from early modern anatomical illustrations, and I drew shapes found in nature that seemed analogous to shapes in the body. All the while, I relied firmly on my own observations. The shapes found in nature, and the line quality in the early modern prints influenced my drawings, but I only drew what I saw. A View of Affect is not a historical model, but I did fully embrace Burton's belief in the importance of direct observation. The purpose of my treatise on the how emotions exist and function in the body is not to specify what is there for others, but to encourage readers to look carefully at their own internal life.