VictorJuiz/thesis huggingface dataset:
Ring-Opening Alkyne Metathesis Methods For Functional Conjugated Polymer Synthesis

Since its discovery in the mid 20th century, most applications of alkyne metathesis have relied on thermodynamics to control product distributions. Ring-opening alkyne metathe- sis polymerization (ROAMP), in contrast, requires the kinetic product of metathesis of a strained, cyclic alkyne monomer to give a living, chain-growth polymerization (Chapter 1, Introduction). This living polymerization of conjugated alkyne-containing monomers has the potential to access a wide range of functional poly(arylene ethynylene) materials with excep- tional control over length, dispersity, topology, and endgroups. To this end, we demonstrate the first ROAMP synthesis of conjugated poly(ortho-phenylene ethynylene) and elucidate a mechanistic description of the reaction to understand the enabling catalyst selectivity and unexpectely find that initiator sterics dictate endgroup fidelity and polymer topology (Chap- ter 2). To disentangle the role of steric and electronic factors in initiator performance, we describe a novel synthetic method that gives a series of isosteric benzylidyne catalysts which exhibit a strong, deterministic electronic effect on both ROAMP initiation rates and polymer endgroup fidelity (Chapter 3). Finally, we develop an extension of this methodology to lever- age the alkynes from these living polymers to template the synthesis of telechelic graphene nanoribbons (GNRs) (Chapter 4). This work has not only uncovered mechanistic insights and design principles to improve ROAMP catalysts and facilitate access to hybrid poly- mer materials, but also demonstrated the potential of ROAMP to access other conjugated materials via post-polymerization modification of precision polymer templates.

Advisor: Fischer, Felix R
Disciplining the Tongue: Speech and Emotion in Later Middle English Poetry

Late medieval English writers confronted what they saw as a crisis of false display. Across genres, the relationship between the inner self and the outer world was depicted as one prone to deception and hypocrisy. Speech was the privileged site for this concern. For religious writers, the solution was stringent verbal and emotional honesty. Poets, by contrast, exploited this perceived disjunction for the purposes of their art. But both drew on a vocabulary that linked speech and emotion, first developed in fourteenth-century instruction on the “sins of the tongue.” This lexicon included words like “scorn” and “shame” as well as those less recognizable today: “sclaundren,” for example, meant “to induce shame,” while “boistous” speech was honest, rude, and affectively harsh. As the first chapter of Discplining the Tongue shows, this vocabulary initially provided a devout reading public with a sense of belonging and a language for itself. “Boistous” texts fostered scorn, anger, and shame: emotions invariably identified with speech acts, each capable of binding a community of strangers together./nThis lexicon proved portable, and subsequent chapters turn to its place in foundational works of English poetry. William Langland’s Piers Plowman repeatedly invokes shame, but its shame does not create a sense of virtue or belonging, as contemporary religious writing would suggest. Instead, its scenes of misspeaking link shame with learning; as the poem repeats these scenes, the act of poetic making itself comes to seem a shameful but licit act of discovery. Chaucer makes mirth, comfort, and pleasure––words that elsewhere describe the act of prayer––the emotional norm that governs the telling of the Canterbury Tales: sacred pleasure becomes the pleasure of idle fiction. The fourth chapter turns from the lexis of medieval emotion to its physiology. In Mum and the Sothsegger and Thomas Hoccleve’s Series, cautionary images that depict affect swelling and bursting out as intemperate speech become self-reflexive figures for poetic making. These reinvented metaphors suggest how elements of truth-telling satire and religious instruction become incorporated into poetic self-presentation./nRather than offering a narrative of secularization, however, the project as a whole points to the common ground where literature and prescriptive religious writing meet. Antinomies of ethics and aesthetics resolve in a shared understanding of the speaking self, its inward feelings realized only in intersubjective exchange.

Advisor: Nolan, Maura
Evolution in Times of Revolution: Darwinism, Nature, and Society in the Soviet Union

Darwinism, the Soviet Union claimed, had found its second home in revolutionary Russia. While the Tsarist government viewed Darwinism with trepidation and suspected it of being linked to atheism and revolution, the Bolshevik revolutionaries embraced it for these very reasons. Despite this accepted narrative, the story of evolutionary theory in Russia and the Soviet Union is more complex. First, not all supporters of Darwin in pre-revolutionary Russia were materialists. Second, Darwinism posed vexing problems to Bolsheviks: although they considered Darwinism a cornerstone of their materialistic, scientific, and revolutionary worldview, this dissertation argues that Soviet scientists and ideologues struggled to reconcile Darwin’s gradualist theory of evolution that decentered humankind with their Marxist theory of revolution. This tension between evolution and revolution is apparent from the history of the Moscow State Darwin Museum, an educational and research institution founded in late Imperial Russia in 1907, which is the setting of this dissertation./nBased on archival research conducted in Russia, Germany, and the US, this study analyzes the conflicted history of Darwinism in twentieth-century Russia and the Soviet Union, spanning both sides of the revolutionary divide of 1917. The Darwin Museum as a hub of Darwin-inspired research and dedicated to popularizing evolutionary theory both shaped and reflected the engagement with the British naturalist and his theory in Imperial and Soviet Russia. Its history underscores how much richer the Soviet reception of Darwin was than the well-studied case of Lysenko’s “creative Darwinism.” From comparative psychology to cryptozoological research on the Yeti, the scientists, environmentalists, artists, and popularizers of science linked to the museum puzzled over the conundrum evolutionary theory posed in the political and ideological context of revolutionary Russia. In the end, researchers invoked Darwin but diverged from key aspects of his theory. They criticized the notion that evolution develops gradually, rather than in leaps or revolutions, and they argued that homo sapiens as a species capable of wielding tools and transforming the environment is qualitatively different from other beings. Yet culture in the Soviet Union was not monolithic. Parallel to advancing an anthropocentric worldview during Stalinism that aligned with the Bolsheviks’ aspirations of mastering nature, the Darwin Museum was a center of environmental activism. As seen through the research conducted under the aegis of the Darwin Museum, this dissertation argues for the complexity of the Soviet scientific and theoretical debate on the relationship between humanity and the natural world, which informed the interaction with the environment. In sum, the Darwin Museum with its long history functioned as a key site for research, for shaping future generations of biologists and nature protectionists, and for negotiating the close but conflicted relationship between evolutionary theory and Bolshevik revolutionary ideology.

Advisor: Slezkine, Yuri
Cumulative and Persistent Changes in the Brain in Response to Stress and Aging

The brain has a remarkable capacity for plasticity: it physically encodes lived experiences within itself, and so is constantly sculpted and shaped by the environment. On short time scales, specific experiences and events are embedded as structural changes at the level of the synapse – in other words, memory. Over longer time scales, other forms of plasticity are involved in causing cumulative and persistent structural changes that do not necessarily represent specific information or experiences per say, but rather influence the overall behavioral mode of the organism. Such changes are not limited to the synapse, but rather may involve broad changes in the cellular composition and structure of the brain. This work seeks to characterize such mechanisms of long-lasting plasticity, focusing on two major areas. Firstly, we investigate how chronic stress affects the cell fate of neural stem cells in the adult hippocampus to cause an increase in the production oligodendrocytes and a decrease in neurons. By changing the cellular composition of the hippocampus, this shift towards oligodendrogenesis may provide a structural basis for long-lasting changes in mood and behavior that can occur after stressful experiences. Secondly, we investigate biological changes in the aging brain, seeking to uncover mechanisms that are involved in cognitive decline. We find that aging involves a loss of integrity of the vascular blood-brain barrier, which allows molecules from the blood to enter into the brain. In turn, this triggers an inflammatory response the causes neural dysfunction and induces cognitive decline. Together, these studies seek to broaden the time scales on which we observe and characterize brain plasticity. By understanding persistent changes that accumulate in the brain over months or years, we may provide new insights into complex neurological diseases that manifest slowly in response to lifestyle risk factors, and ultimately develop new, more effective treatments.

Advisor: Kaufer, Daniela
The Present Impasse: Hemispheric American Modernism and the Poetics of History

My dissertation, “The Present Impasse: Hemispheric American Modernism and the Poetics of History,” shows how U.S., Caribbean, and Latin American authors innovated with narrative to conceptualize the course of history as U.S. expansionism threatened to replace, rather than rout, French, Spanish, and British empires. Alejo Carpentier, John Rechy, and Zora Neale Hurston, I argue, experimented with temporal elements of narrative emplotment, such as order, duration, and frequency, to align the passage of time with the unfolding of history. In doing so, they mediated the collision of repeating and overlapping empires in the hemispheric American South: an experience rendered cyclical in narrative discourse and, as such, one that contests the linear progress most commonly associated with modernity. Their work, therefore, presents a new modernist understanding of historical time: one in which the expectation of social change collapses back onto the experience of the past and promises not a divergent future but rather an eternal return of the same. In this way, cyclical time marks an impasse in narrative chronology that parallels the “present impasse” from which history is perceived to encounter the antinomies of colonial Enlightenment and reproduce the racialized social relations of empire. In response to this impasse, each work introduces the need for an alternative temporality of “the untimely,” i.e., an iteration of the premodern past or the unmodern present that nonetheless highlights the conditions of possibility with which modernity may be reconstituted in the future./nBeyond my first chapter, which details the advent of U.S. intervention and expansion in what Édouard Glissant termed “the Other America,” my second chapter focuses on Carpentier’s The Kingdom of This World (1949) to showcase the untimely dimension of the marvelous real, or lo real maravilloso: a transatlantic aesthetic and philosophical treatise that introduced a “historical counterpoint” to U.S. empire in Cuba and Haiti. My second chapter shifts from the Caribbean to the U.S.-Mexico borderlands to examine how Rechy’s City of Night (1963) responds to successive waves of internal colonialism by fashioning an untimely temporality that attempts to envision a reparative experience beyond racial and sexual intersectionality. My fourth chapter demonstrates how Hurston’s Their Eyes Were Watching God (1937) approaches the reemergence of empire with an affirmative concept of history that proposes a philosophy of self-determination and calls for decolonial change in the hemispheric South. This chapter is followed by a brief comparative coda that demonstrates how each author contributed to the emergence of what we could call, if only heuristically, a hemispheric American modernism: one that distinguishes itself from European and Anglo-American modernism and illuminates the neo-imperial challenges against which the next generation of authors, amid U.S. Civil Rights and “Third-World” independence movements, would have to face.

Advisor: Gonzalez, Marcial
Jones, Donna V.
The Lyric Forms of the Literati Mind: Yosa Buson, Ema Saikō, Masaoka Shiki and Natsume Sōseki

This dissertation examines the transformation of lyric thinking in Japanese literati (bunjin) culture from the eighteenth century to the early twentieth century. I examine four poet-painters associated with the Japanese literati tradition in the Edo (1603-1867) and Meiji (1867-1912) periods: Yosa Buson (1716-83), Ema Saikō (1787-1861), Masaoka Shiki (1867-1902) and Natsume Sōseki (1867-1916). Each artist fashions a lyric subjectivity constituted by the kinds of blending found in literati painting and poetry. I argue that each artist’s thoughts and feelings emerge in the tensions generated in the process of blending forms, genres, and the ideas (aesthetic, philosophical, social, cultural, and historical) that they carry with them. As poet-painters, Buson, Saikō, Shiki, and Sōseki blended these constitutive elements of literature like strokes of paint on a canvas. Through examinations of blending, I show the movement of thought and feeling, the dynamism of lyric thinking, in poetic form./nThrough such blending each artist evoked a heightened consciousness of the senses—sight, sound, smell, and touch. I examine how each artist thinks through sensual embodiment in poetic form, and show how the boundaries of lyric thinking expand by the Meiji period as traditional genres of poetry begin to overlap and blend with modern prose. Between the late eighteenth century and the Meiji period, new genres of writing emerge, yielding more possibilities for sensual embodiment in poetic form. Traditional genres such as haikai and kanshi also endure as antiquated and autonomous forms, and in vernacular prose as compounded forms that place ideas of the past and the present in dialectical motion. This dialectical motion appears in modern prose as constitutive elements of lyric thinking, and as obstructions to the linear movement of thought in narrative prose./nThe chapters are organized chronologically. In Chapter 1, I show how lyric thinking manifests as tensions in the perception of time and space in Buson’s haikai. In Chapter 2, I examine Saikō’s kanshi, and show how her lyric thinking manifests in a dialectical and ironic relationship with genre. In Chapter 3, I show how Shiki’s lyric thinking manifests as contradictions of thought in his artistic practice called shasei, or “representing life.” In Chapter 4, I examine lyric thinking in Sōseki’s modern prose. I show how his lyrical novel Kusamakura and prose-poem Omoidasu koto nado give form to grief through contradiction and irony./nThe dissertation shows what the lyric writings of Buson, Saikō, Shiki, and Sōseki can tell us about lyric thinking, subjectivity, and the philosophy of poetic form.

Advisor: Tansman, Alan
Nucleic acid-guided genome defense systems from bacteria and archaea

Bacterial and archaeal genomes are under constant threat by genetic invaders. The need to maintain genomic and cellular integrity has driven the evolution of numerous and diverse genome defense systems. A common theme in prokaryotic defense strategies is interference of foreign DNA and RNA on the sequence level. Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems confer adaptive immunity to previously encountered genetic invaders. Guided by short RNAs, the main effectors of CRISPR-Cas systems are sequence specific nucleases that catalyze degradation of exogenous nucleic acids. At the center of a similar method of genome defense to CRISPR-Cas systems, but operating through non-homologous proteins and pathways, prokaryotic Argonaute proteins (pAgos) have been proposed as sequence specific defense systems. However, our mechanistic knowledge of both CRISPR-Cas and pAgo systems stems from a small subset of the total genetic diversity of these systems. Here, we address this limited understanding through analysis of new CRISPR-Cas and pAgo systems, as well as describe novel activity for previously identified members./nCRISPR-Cas9 has rapidly been adopted as a programmable platform for sequence-specific DNA targeting with endless applications in gene editing, genome-wide screening, and transcriptional control. Current applications draw upon the biochemical activities of a few common Cas9 enzymes. The study of diverse homologs has potential to yield novel Cas9 proteins with desired traits such as increased efficiency or specificity. Surveying a vast metagenomic database, we report the first Cas9 from archaea, expanding the occurrence of CRISPR-Cas9 systems to a new domain of life./nDNA targeting is a hallmark of CRISPR-Cas9 systems. Engineering SpyCas9 to bind and target RNA has been difficult and suffers from reduced efficiency. We sought to identify Cas9 homologs with a natural ability to target RNA molecules. Using in vitro purification and biochemical assays, we discovered Cas9 enzymes that efficiently cleave RNA. Furthermore, we show that this activity can be harnessed to reduce phage infection and mediate gene repression in vivo, expanding the toolkit of CRISPR-Cas nucleases./nAnalogous to CRISPR-Cas systems, Argonaute proteins are well known, RNA-guided nucleases that operate in eukaryotic RNA-interference. Motivated by initial observations that Argonaute homologs in prokaryotes constitute a nucleic acid-guided genome defense system, we studied the physiological role and biochemical activities of a novel clade of pAgos. We offer the first experimental evidence of complex formation between natural, two-piece Argonaute proteins. Preliminary in vivo observations implicate this split-pAgo in maintaining motility under conditions induced by introduction of an exogenous plasmid. Together with our studies on CRISPR-Cas systems, our work highlights unexpected functional diversity across divergent nucleic acid-guided genome defense systems.

Advisor: Doudna, Jennifer A
A Haunting Conviction: Frege on Truth and Logic

Many of us think that truth is prior to science: though it belongs to the nature of science to pursue truth, the nature of truth does not involve science. Frege denies this. He thinks that to be true is to play a role in the characteristic goals of science, such as explanation./n/nFor Frege and the Neo-Kantian philosophers in his philosophical milieu, the point of this view is that no truth is trivial: every one makes a contribution to a deep understanding of the world. This allows them to maintain that truth is a value, whose significance is rivalled only by that of the Good and the Beautiful. This view leads Frege to a normative conception of logic, on which the logical laws are the ones that tell us how we ought to judge if we are to achieve our highest scientific goals. Since the nature of truth itself is to be found in such goals, these laws tell us about truth itself./nThis makes possible an epistemology for logical axioms that has frustrated readers by its apparent inconsistency: Frege seems both/nto rule out arguing for logical axioms, and himself to offer arguments for them. But he only means to rule out arguments that derive the axioms from other truths that we are already justified in accepting. His own arguments, by contrast, derive them from a goal: they show us that the axioms must be true if that goal is to be reached. The goal in question is the construction of a logical system; but because such a system is needed in every science, the goal is none other than truth itself./nFrege's discussions of truth and logic are conducted independently of any claims about language, which sits badly with his reputation as the herald of the ``linguistic turn,'' who proclaims the philosophy of language to be the foundation of all philosophy. This calls for a re-evaluation of the role of language in Frege's philosophy. I argue that Frege's philosophy of language is a grand technological project in linguistic engineering: he does not aim to describe language, but to change it so that we can reach the truth more effectively. Reading Frege this way helps us understand the most puzzling passages in his early work, and, I hope, points us to a resolution of the outstanding puzzles in his later philosophy of language as well.

Advisor: MacFarlane, John
Campbell, John
Utilizing Chemoproteomics Platforms to Discover Novel Anti-Cancer Ligand and Target Pairs

Cancer is the second leading cause of death in the world and it is estimated that 600,000 people will die of cancer in 2018 1. Mortality from cancer is almost always attributed to metastatic spread of the disease, and unfortunately, chemotherapy fails to eradicate many forms of aggressive cancer. As research has evolved, certain forms of aggressive cancers have been uncovered such as triple negative breast cancers (TNBCs) that are devoid of estrogen/progesterone/human epidermal growth factor receptor 2 (ER/PR/HER2) and pancreatic ductal adenocarcinomas (PDAs) that show poor prognosis and resistance to various chemotherapies. Currently there are no targeted therapies for curing TNBCs and PDAs, as well as other cancer subtypes, which forces many patients to resort to nonspecific treatments such as radiation. Developing drugs for these cancer subtypes is crucial for eliminating these aggressive forms of cancer and reducing cancer-related mortalities./nThe sequencing of the human genome led to the discovery of many proteins implicated in cancer that do not have altered expression or activity. Developing drugs for these proteins could serve as a method for treating cancer, but finding small-molecules to target these proteins is a remaining challenge because the majority of these proteins are “undruggable.” Covalent ligand discovery is a promising strategy to develop small-molecule effectors against therapeutic targets. This method couples chemical genetics screening of covalent ligands with chemoproteomic platforms for target identification. In this dissertation, I present examples of utilizing this technology to discover small molecules that impair both TNBC and PDA cancer survival and proliferation and determine the protein targets of these small molecules. These examples show that discovering novel cancer targets and developing small-molecule ligands for these proteins can enable the development of targeted therapies for these lethal and poorly treated cancers.

Advisor: Nomura, Daniel K
Locally Volume Collapsed 4-Manifolds with Respect to a Lower Sectional Curvature Bound

Perelman stated without proof that a 3-dimensional compact Riemannian manifold which is locally volume collapsed, with respect to a lower curvature bound, is a graph manifold. The theorem was used to complete his Ricci flow proof of Thurston’s geometrization conjecture. Kleiner and Lott gave a proof of the theorem as a part of their presentation of Perelman’s proof./nIn this dissertation, we generalize Kleiner and Lott’s version of Perelman’s theorem to 4-dimensional closed Riemannian manifolds. We show that under some regularity assumptions, if a 4-dimensional closed Riemannian manifold is locally volume collapsed then it admits an F-structure or a metric of nonnegative sectional curvature.

Advisor: Lott, John