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UC Santa Cruz Electronic Theses and Dissertations

Cover page of Essays on Influence of Information and Innovation in Digital Markets

Essays on Influence of Information and Innovation in Digital Markets

(2024)

This dissertation presents three experimental studies with an emphasis on the influence of information and innovation on digital markets including financial exchanges and online marketplaces. The first chapter focuses on the experimental evaluation of a new financial market design. The second and third chapters focus on how access to information affects people's behavior in the online marketplaces.

The first chapter provides a laboratory study of a newly proposed Flow Market format as a response to the design weaknesses of the continuous double auction used in most financial markets worldwide.We designed and deployed a laboratory experiment that compares the Flow Market and the CDA using several fundamental metrics. We find evidence that the flow market changes traders’ behavior relative to CDA, allowing them to shred orders more effectively: compared to the CDA, the Flow market exhibits fewer and larger orders. We also find both formats perform similarly in terms of price and allocative efficiency. However, the Flow Market leads to lower price volatility. Interestingly, the total traded volume is lower under the Flow Market than under CDA. Still, this difference decreases with traders’ experience, i.e., as they learn the mechanics of the Flow format. Our findings provide initial insights regarding the feasibility of the Flow trade format and its potential to promote financial market stability and fairness.

The second chapter modifies the traditional sequential search models to consider the ex post uncertainty in which the uncertainty cannot be fully eliminated by the search. We derived players' optimal search strategy given their risk attitudes. We also test our theory in a laboratory experiment with a search game to track subjects' behavior and use a multiple price list and a bomb risk elicitation task to elicit subjects' risk preferences. We find that, in this scenario, risk-averse players tend to increase their reservation value and extend their search duration.

The last chapter investigates the informational barrier problem in the online marketplaces. We design a sequential game to study how informational barrier is formed due to the reputation system and propose a fractional searching mechanism to enable the entry by reliable firms. The model predicts the optimal behaviors of the firms and shows that the fractional searching enables cost-effective firms with no reputation to enter the market more easily. Additionally, we test our theory in a laboratory experiment using an interactive market game to track subjects' behaviors with a simplified reputation system. The experimental results indicate that fractional searching effectively alleviates the entry problem of new firms with superior quality.

Cover page of Investigating the Underlying Causes of Cancer Using Sequencing

Investigating the Underlying Causes of Cancer Using Sequencing

(2024)

Cancer is a genetic disease. All cancers are caused by and dependent on mutations. The widespread adoption of NGS in cancer research has revolutionized the field by allowing us to catalog the variants within and across cancer types. This knowledge was used to create a new taxonomy of cancers, where many tumors are classified by genetic alterations in addition to tissue of origin. Despite the role of NGS in identifying the mutations behind these new classifications, pre-genomic methods such as ISH and IHC are still commonly used in the clinic to identify relevant genetic alterations in tumors.About 20% of tumors worldwide are caused by viruses such as HPV, Epstein-Barr virus and Hepatitis B and C viruses. The virus may act as a mutagen by causing prolonged inflammation or by integration into the host genome. Viral infection can therefore be considered another type of genetic alteration used for the classification of tumors, and indeed some tumors are now classified by their causal viral infections. Epimutations are a type of genetic alteration affects epigenetic marks such as DNA methylation rather than the DNA sequence. Epimutations are the genetic lesions behind several disorders including cancer predisposition syndromes. Here I present my work developing an app that integrates with the UCSF 500 pipeline to detect known oncogenic viral sequences in DNA samples from tumors (Chapter 2). I also present my work analyzing long-read sequencing and methylation data of a patient with bilateral Wilms tumor to identify the epimutation causing their cancer predisposition syndrome previously missed by other technologies (Chapter 3). My work reflects the utility of adapting state-of-the-art sequencing technologies for diagnostic use in the clinic. H3K27M gliomas have a mutation in the genes encoding histone H3 that interferes with the deposition of the repressive epigenetic mark H3K27me3. This mark is important in regulating cell type development and EMT. In Chapter 4 I present my work using gene expression analysis to identify the role of EMT in the development and oncogenesis of H3K27M gliomas. Aberrant EMT may serve as a key dependency of these tumors.

Cover page of Data-Efficient Representation Learning for Gaze Estimation

Data-Efficient Representation Learning for Gaze Estimation

(2024)

The human gaze serves as a potential non-verbal cue that enhances human-computer interfaces, enabling users to engage with devices through eye movements. The ability to accurately measure and interpret gaze direction plays a critical role in various domains, including social interactions, assistive technologies, augmented reality, and psychological research to examine cognitive state.

Over the past decade, gaze estimation has emerged as a prominent area of interest within the research community. Conventional gaze estimation methods rely on specialized hardware, including high-resolution cameras, infrared light sources, and image processing units, to detect eye features like the pupil center and iris boundary. While these devices offer greater accuracy and precision, their practical use is limited by factors such as high costs, restricted head movements, and limited range of allowable distances between user and device. As an alternative to dedicated gaze-tracking hardware, several techniques have been developed to infer gaze direction directly from eye images captured by standard cameras on personal devices such as laptops, tablets, and phones.

The recent emergence of deep learning techniques has enhanced learning-based gaze estimation approaches. These appearance-based gaze estimation methods directly map eye images to gaze targets without the need for explicit detection of eye features and, therefore, have a strong capability to work in unconstrained environments. However, the effectiveness of these approaches greatly depends on having access to extensive training datasets that include a variety of eye appearances, gaze directions, head poses, lighting conditions, and other variables. In this thesis, we focus on improving the adaptability and effectiveness of webcam-based gaze estimation techniques through the application of generative modeling and representation learning.

First, we propose an easy approach for calibrating a laptop camera with a commercial gaze tracker, streamlining the process of collecting labeled gaze data to make it readily accessible for all users. This dataset can then be utilized to enhance the accuracy of appearance-based gaze estimation methods for new users and different domains.

Second, we introduce a generative redirection framework designed to manipulate gaze direction and head pose orientation in synthesized images. This framework is used to generate augmented, gaze-labeled datasets, thereby enhancing the performance of gaze estimation methods.

Third, we explore self-supervised contrastive learning to acquire equivariant gaze representations through an unlabeled multiview dataset. These gaze-specific representations are utilized for few-shot gaze estimation, enhancing the efficacy of user-specific models.

Finally, we present a spatiotemporal model for video-based gaze estimation, incorporating attention modules to enhance understanding of both local spatial and global temporal dynamics. Furthermore, we improve the performance of this model using person-specific few-shot learning through Gaussian processes.

Maintenance and Regulation of the pYV Virulence Plasmid Encoding the Type III Secretion system in Pathogenic Yersinia

(2024)

The current rate of acquired antibiotic resistance (AR) in bacterial pathogens is projected to cause 10 million deaths per year and result in a global cost of up to 100 trillion USD by 2050. It is therefore urgent that we develop new therapies that target pathogen-specific virulence factors (i.e.-microbial genes required to cause disease). However, our limited understanding of how these virulence factors are regulated is a major obstacle in the field, and studies exploring how these pathogens coordinate expression of virulence genes are desperately needed in general. Many Gram negative pathogens harbor large extrachromosomal plasmids encoding genes important for virulence and/or antimicrobial resistance, many of which belong to the IncF family of plasmids. Understanding how these plasmids are regulated and maintained is critical for addressing the threat posed by AR pathogens, and yet the underlying biology regulating many of these plasmids remains poorly understood. Using the Gram negative enteric pathogen Y. pseudotuberculosis as a model organism, the aim of this research is to broaden our understanding of how facultative pathogens like Yersinia regulate virulence gene expression at the level of virulence plasmid copy number (PCN) and plasmid maintenance. Y. pseudotuberculosis is closely related to Y. pestis, the causative agent of the plague. Both Y. pseudotuberculosis and Y. pestis harbor an IncFII, ~70kb virulence plasmid known as pYV that encodes a major Yersinia virulence factor known as the type III secretion system (T3SS). The T3SS is a specialized injectisome used by many species of Gram negative pathogens to inject effector proteins into the host cell cytosol, interfering with host innate immunity signaling pathways and ultimately dampening host defense mechanisms. Despite being critical for Yersinia virulence, expression of the T3SS is energetically costly and must be tightly controlled to achieve optimal fitness, and so expression and activity of the T3SS is restricted to host temperatures of 37°C where it is needed for virulence. It was recently discovered that expression and activity of the T3SS is dynamically regulated via changes in PCN, or the number of pYV plasmids per Y. pseudotuberculosis cell. At environmental temperatures of 26°C, where the T3SS is not needed, pYV PCN is kept low to about one copy per cell. However, upon entering the mammalian host (37°C), pYV PCN is quickly and specifically increased to 5-12 copies per cell. This increase in pYV PCN is required for Y. pseudotuberculosis virulence in mice, and yet the mechanism by which pYV PCN is kept low at 26°C and rapidly increased at 37°C is completely unknown. The first chapter of this dissertation reviews how the Yersinia T3SS has served as a tool for discovering and elucidating host immune pathways that have evolved through extensive host-pathogen interactions with T3SS-utilizing bacteria. The rest of this work focuses on the discovery of two factors that impact pYV PCN and/or maintenance in Y. pseudotuberculosis. In chapter 2, we demonstrate that a transposon (Tn) insertion in a previously unannotated locus near the pYV IncF replicon drives abnormally high pYV PCN at environmental temperatures of 26°C, resulting in a hyperactive T3SS phenotype at 37°C and a severe growth defect under T3SS-inducing conditions. This locus, which we will call plasmid copy number inhibitory locus or pil, encodes a predicted ORF that is conserved in some other species of Gram negative bacteria. By taking advantage of the serve growth defect of this strain, we further demonstrate that pil insertion mutants can be used as genetic tools for identifying novel factors affecting pYV PCN, T3SS activity, and Yersinia growth in a suppressor screen. A pilot suppressor screen identified specific residues in factors that impacts pYV PCN and T3SS activity in various ways, and we propose that pil insertion mutants will serve as a powerful tool for identifying additional factors in future studies. Chapter 3 of this dissertation focuses on one of the hits arising from the pil suppressor screen, which identified the pcnB gene encoding the polyadenylase poly (A) polymerase I (PAP I) as a novel regulator of pYV maintenance in pathogenic Yersinia. We show that PAP I is essential for normal pYV PCN, T3SS activity, and Yersinia virulence in a mouse infection model. In addition, we report that PAP I is required for Y. pseudotuberculosis maintenance of sRNA-regulated plasmids that harbor AR genes in general, suggesting that PAP I is important for the maintenance of both virulence and AR plasmids by pathogenic bacteria. PAP I homologs are widespread in bacteria but have only been studied in a small handful of species to date. Importantly, this is the first time PAP I has been linked to regulation of a virulence plasmid in the natural pathogenic host for that plasmid. To our knowledge, this is also the first direct evidence that a bacterial polyadenylase impacts virulence of a bacterial pathogen. Overall, this work broadens our understanding of how IncF plasmids are regulated to balance virulence and bacterial fitness by pathogens like Y. pseudotuberculosis. Given that PAP I homologs are widespread and many AR plasmids and nearly all virulence plasmids belong to the IncF family, this work likely applies to other species of Gram negative pathogens as well. Finally, this work highlights that there are many additional levels of gene expression regulation to consider when it comes to addressing the threat posed by bacterial pathogens, including changes in gene dosage via changes in PCN of extrachromosomal plasmids and the potential contribution of polyadenylation to regulation of virulence gene expression.

Exploring Planetary Atmospheres In The JWST Era: Pluto's Emission And Sub-Neptune's Transmission

(2024)

Planets both inside and beyond the solar system have different atmospheres, making them display various phenomena. With the increasing number of exoplanets detected, in particular with detailed observations taken by the advanced JWST nowadays, more samples are available to widen such diversity. One of the key challenges is to understand their atmospheric components and physical properties via remote sensing (like images, spectra, and lightcurves) rather than in-situ detection of probes, especially for these distant objects. So applying physical models could offer additional assistance in explaining currently limited data, as well as give some guidance for conducting future observations. Moreover, the Bayesian retrieval approach makes it possible to seek the most probable solutions in a high-dimension parameter space efficiently.

Chapter One describes two possible scenarios of Pluto's atmospheric haze, directly based on the temperature-pressure profile acquired by the New Horizons spacecraft. A radiative-conductive-conductive model was used to examine the energy balance of gases and haze individually, suggesting that an additional mechanism of eddy heat transport is essential in Pluto's lower atmosphere. An icy haze, 20 times smaller than Titan's tholins in opacity, is also proposed and will be determined by infrared observations of JWST.

Chapter Two further studies Pluto's haze by rotational emission lightcurves indirectly. The total outgoing thermal emission comes from not only Pluto's and Charon's surfaces as previously believed, but also Pluto's atmospheric haze as learned in Chapter One. A two-dimensional surface model of heat conduction is developed to estimate the surface parameters and flux contribution more accurately. After removing surfaces, the remaining total flux should come from Pluto's haze, which is significant in the mid-infrared but may be neglected in the far-infrared. Predictions at other mid-infrared wavelengths are then given in view of current haze knowledge. JWST MIRI works at these wavelengths to prove or constrain such haze.

Chapter Three jumps out of the solar system and pays attention to the sub-Neptune planets that are intermediate in size between Earth and Neptune. Helium enrichment due to preferential hydrogen escape is suggested for their thin atmospheric envelopes, which requires a method to obtain its helium amount correctly. Transmission spectra featured by the mechanism of collision-induced absorption are applied to retrievals for assessing how accurate it can be when future JWST data arrive. The results are optimistic in the helium-enhanced situation with 30 ppm errors.

In summary, this dissertation thesis consists of three projects exploring the physics of planetary atmospheres, two of which are constraining Pluto's haze opacity but from different aspects. The other one is loosely related to icy planets (like Pluto) and is mainly focused on the helium abundances in sub-Neptune's atmosphere. These projects cover the flux calculations of emission and transmission, along with the time or wavelength sequences, from the surface or atmosphere. The physical modeling method is applied as a bridge between the physical understanding of atmospheric components and current or future observations, in the era of JWST.

Aspects of Emersonianism in American Fiction & At Interminable Oceans (A Novel)

(2024)

This creative-critical project is a trying out of Emersonian transcendental reconceptions of aesthetic experience. I have written a “draught of a draught” of a novel with a sequence of events and a main character, Darshan Kehama, based loosely on the struggle Ralph Waldo Emerson describes in his great essay, “Experience,” to “realize” the “self” by recovering indigenous feelings of serenity native to the self as Emerson comes to terms with the loss of his son. I take the title of my Emersonian novel - At Interminable Oceans – from a crucial Emersonian passage in the essay to refer to homes found within and on the shores of seas and oceans, the metaphorical and literal setting for the Kehama family. The panoramic view of the Arabian Sea and Pacific Ocean and their horizons from Indian and American homes on the Bombay and Carmel, California coasts is a reminder of the inexhaustible oceanic powers the Kehamas draw from, as they find their “true romance” in Emersonian moments of calm in the face of incalculable grief. This irenic mood enacted in a serene pitch of third person narration and description crucial to conjure up the “tone” of family life in this lost Indian American world is one way to envision that Emersonian slogan of transforming loss into “practical power.” Wai Chee Dimock’s reading of a crucial passage on ownership in Emerson’s moving essay, “Experience,” inspire my modified notion of “aesthetic ownership” as I attempt to dramatize this struggle of transformation in this “draught of a draught” of a novel. I could only express what I found in Ralph Waldo Emerson’s account of having, getting, and keeping irenic feelings, his essential story of self-renewal offered in that indispensable essay, in novelistic form. I draw inspiration for my Emersonian novel from my first attempt to read aspects of Emersonianism I find in Emerson’s “Experience” in the great American novels by Herman Melville, Henry James, and Frank Norris.

In “Aesthetic ownership as Self-Renewal,” I read Emerson’s “Experience,” taking into account one recent reappraisal of experience that gives a prominent place to Emersonian concepts of “ownership” and “property.” Since Wai Chee Dimock’s idea of ownership grounds an interpretation that goes against contemporary materialistic definitions or restatements of Emersonianism it is worth foregrounding a model of self-renewal consistent with an Emersonian idealism and dualism that is more in sync with the transcendentalism of 1842-44. Dimock, in an unforgettable and overlooked reading of this essay, posits a self, “sovereign within itself,” as a consequence of “division” between an “inner locale” of experience with its own measures of “scarcity, sufficiency, superfluity” “separate and apart” from “objective reality” with its economic measures of what is or is not sufficient. The inner aesthetic economy Dimock describes rests on a specific claim about ownership that equates property with poverty. The self that is a consequence of this surprising “commoditization” of poverty or scarcity is in a mode of “aesthetic ownership,” a cooler register of subjective experience shorn of intensities. The ghost-like, soporific, illusory glow, the stunned depleted quality of experience Emerson complains about in the first half of the essay, I argue, also brings its shine and is claimed as a virtue in the second part of “Experience.” This wisdom found in the closing of Emerson’s essay is brought about by a shift from observation conducive to scientific scrutiny of paltry empiricism to Emersonian moments of seeing crucial to renewing awareness of the self’s constitutional indigence or emptiness. The emptiness or poverty claimed in this inner aesthetic mode of ownership is also a first step in reclaiming the recuperative powers of surprise/wonder in the Emersonian self.

In Chapter 1, “Transcendental Resistance: Emersonian Irenic Thinking and the Passage to India in Herman Melville’s Moby-Dick,” I argue that members of the crew in the Pequod, as they struggle to move away from the rising forces of capitalism sweeping the eastern shores of America, also offer transcendental resistance to the possessive/pillaging drive of the whaling business they have unwittingly committed themselves to. The resistance of the Pequod crew is a reminder of how indigenous thinking [the nature of it] of William Apess, a nineteenth century religious figure from the Peqout tribe, resists the paradoxes/hypocrisies in the political/religious arena in colonial America. In Apess’s words: “the pious fathers wrestled hard and long with their God, in prayer, that he would prosper their arms and deliver their enemies into their hands.” This hypocrisy, according to Apess, the “foundation” of “all the slavery and degradation" in the American colonies, was also the basis of the laws for Indian Removal. Even when openly legal crimes were being passed off as part of God's great design, Apess suggests cleaving to what is nobler, and finding ways to resist, not react, to the lower moral orbit of hypocrisy. The parallel between the great Pequot’s example of indigenous thinking, an early precursor to Emersonian irenic thinking, and the hypocrisies/paradoxes of imperialism/racism it uncovers in colonial America and what Melville’s voyage discovers in the role played by Queequeg, Pip, Fedallah, Tashtego, suggests that an Emersonian aesthetic ownership is being offered in this novel to allow the duplicitous nature of this full scale slaughter on the high seas to become clearly visible. When the Pequod’s eastward movement across the oceans orients the ship towards America’s western shores this whale hunt transforms to a quest romance, an obvious reversal of the Columbian voyage and its aspirations. Melville finds a passage to India not to claim the material wealth of the Indies but to reclaim the worth of dispossession, an austere mode of aesthetic ownership, modeled on ancient worship in India’s Elephanta Caves, where Melville’s narrator claims the oldest known portrait of a whale can be found on one of its cave walls. This invocation of a more serene relationship to the non-human world makes starker the tragic fall/lapse in perception that underlies the brutal slaughter/business of whales. Blood flows freely in this oceanic hunt but the brief passage to India offers another renunciatory space, after Apess’s example, to help transcend the grasping tendencies of this business on the oceans.

In Chapter 2, Austere Aestheticism and Emersonian Renunciation in Henry James’s The Portrait of a Lady, I begin with a quick overview, following Jonathan Freedman, of the motivations of the British aestheticism movement. Freedman discusses British aestheticism in the late nineteenth century as the historical context for introducing an aspect of Emersonianism I call austere aestheticism, which brings back Stuart Sherman’s reading of Henry James’s aesthetic idealism and his overlooked essay on Emerson as another way to look at the late nineteenth and early twentieth century revival of aestheticism, a carry over of the American version of the aesthetic project to mark out a special sphere, “a locus of value and a guarantee of authority” to “Art.” I argue that this motivation to allot art its autonomy is derived from an aspect of Emersonianism where aesthetic ownership’s idealistic registers counterbalance the materialist registers of Paterian aesthetic experience. Aesthetic ownership, first shown/described in the “transparent eyeball” passage and its afterlife in moments of seeing in the Emersonian literary tradition, as THE master metaphor for the impersonal/irenic aesthetic dimension of ownership, contrasts with the charged intensity of aesthetic experience defined by Walter Pater in his conclusion to The Renaissance: Studies in Art and Poetry. The calmer, more detached, mode of aesthetic ownership in Henry James’s austere aestheticism achieves the ambition of “Art” (the source of the autonomy and authority that marks the special sphere of “Art” - uppercase “A” as Richard Poirier and F.O. Matthiessen explain this difference) by introducing “ascesis” as the basis of the American writer’s implicit critique and fulfillment of what the British aesthetes attempted to but could not quite achieve in art. I argue that this austere aspect of aestheticism is born out of an overlap between Pater’s ascesis and Emerson’s renunciatory ideals. This conception of life/experience in that defining Emerson essay, “Experience,” is brought about by a beautiful balance in aesthetic ownership and aesthetic experience, the vantage of austere aestheticism that makes renewal possible.

In Chapter 3, “Emersonianism West: Aesthetic Experience and Aesthetic Ownership,” in Frank Norris’s novel, McTeague: A Story of San Francisco, I begin by noting how the use and exchange value of things remain the most obvious measures of worth in the novel. But these values ascribed to possessing things only superficially account for McTeague’s obsessive attachment to what he owns and refuses to part with. I argue that the aspect of aesthetic experience most called for in the novel goes beyond what Gavin Jones has called “the embarrassment of naturalism,” or the feeling of being “stuck” that has come to dominate McTeague’s lived experience in Polk Street. Emersonian compensatory consolations of aesthetic ownership in reimagined property relations take the place of lost material conditions of ownership when McTeague is forced to dispossess his most valued things. This displacement radically transforms McTeague’s longing and the sense of the novel’s unusual ending. A hidden, more dominant, measure of worth reveals itself in these renunciatory moments giving McTeague’s possessive drives an expansive scale. I present a Norris we have not yet fully appreciated, a naturalist working within the tradition of Emersonian aestheticism that was first conceived in Richard Poirier’s A World Elsewhere: The Place of Style in American Literature and that has recently found new articulation in Wai Chee Dimock’s Emerson.

Visceral Landscapes: Recuperating Migrant Narratives in Contemporary Photography of the U.S.-Mexico Border

(2024)

From its conception as a nation, the U.S. pushed from east to west and north to south expanding and establishing new borders, a process reinforced by nineteenth and twentieth century U.S. landscape photography. By contrast, twentieth and twenty-first century Chicanx and Latinx artists addressed the border as a site of political turmoil, violence, and resistance as well as a metaphorical and transportable space of identity formation. My dissertation draws upon these two fields, landscape studies and Chicanx/Latinx visual culture, to addresses contemporary landscape photography at the U.S.-Mexico border. In doing so, I established a comparative analysis of nineteenth and twentieth century landscapes against the decolonizing potential of the contemporary works that expose, subvert, and expand traditional landscape vernaculars. My dissertation examines closely David Taylor and Marcos Ramirez ERRE’s DeLIMITations (2014), the Border Film Project (2005-2007), Richard Misrach and Guillermo Galindo’s Border Cantos (2016), and Delilah Montoya’s Sed: Trail of Thirst (2004-2008). Each of these projects delve into a critical set of questions around what is happening at the border and why, but also how the border crisis impacts migrants and migrant communities. To address these questions, I approach the photographs in search of narratives that are often omitted from history, art history, and contemporary discourse on the U.S.-Mexico border. I then use visual clues in the images to generate new narratives about who has existed in the border landscape, who is currently attempting to cross, and what these experiences might be like. I argue that their work transgresses old forms and pushes against the limiting nature of the border itself. In doing so they bring attention to the double erasure of Indigenous and migrant memory, history, and bodies from the landscape; expose the lasting colonial legacy of earlier landscape practices that contributed to the making of the border; and explore the possibility for innovative visions that deviate from those of territorial mastery, and instead attend to migrant subjectivities.

Metaphysical Biases in the Discourse of Artificial Intelligence

(2024)

This text examines implicit metaphysical assumptions that influence the discourse of artificial intelligence by shaping key underlying concepts such as intelligence, agency, rationality, thought, mechanism, process and number. I consider the impact of these assumptions on the frameworks and methods of the field, as well as their relevance to debates concerning the ethics of research in AI. In this context, I evaluate the consequences of Jacques Derrida’s critique of metaphysics, examining its implications for conceptual models of artificial intelligence that continue to depend on the foundational ideas his critique puts into question.The first part, “Mind Against Mechanism,” deals generally with the idea of intelligence and the figure of the thinking machine. I argue that Beneficial AI, a prominent research program within machine ethics, relies on a misguided theory of intelligence that combines misconceptions about evolutionary biology with inappropriate analogies to nuclear energy, and mobilizes longstanding anxieties about the viability of traditional beliefs regarding individual autonomy and agency. My analysis corroborates Timnit Gebru’s call for a holistic approach to Ethical AI that incorporates a more diverse group of scientists into the design process. I add to this that scientists are not enough—serious engagement is needed with a wider range of scholarly work beyond the sciences. The second part of this manuscript, “Number Beyond the Algorithm,” considers the provenance of premises that inform the way we conceive of the limits of computation. I show that the adoption of the set as the founding element of the real number system follows from a concept of number that elevates presence over process (i.e., cardinality over sequence). This preference for presence aligns with the culturally- specific beliefs of a small group of European mathematicians, particularly with regard to the nature of number and infinity. Yet, the resulting definitions continue to inform contemporary characterizations of the relationship between mathematics and computa- tion by contributing to the conviction that the objects of mathematics (and the world they correspond to) vastly exceed what machines can compute.

Teaching Beyond the Basics in Kindergarten Mathematics: An Analysis of the 2011 Early Childhood Longitudinal Study

(2024)

State and federal departments of education, the Common Core State Standards for Mathematics (CCSS-M), the National Association of Educators of Young Children (NAEYC), and the National Council of Teachers of Mathematics (NCTM) agree that high-quality mathematics instruction (a) challenges learners; (b) focuses on conceptual understanding; (c) makes connections to children’s lived experiences; and (d) provides opportunities for multimodal, collaborative, and dialogic learning. Despite widespread understanding that mathematics is a crucial, foundational component of the curriculum in early childhood (EC) (Claessens et al., 2009; Duncan et al., 2007), research has shown that mathematics teachers in United States kindergarten classrooms overwhelmingly focus on covering basic content and skills (Engel et al., 2016), rarely employing the type of beyond-the-basics instructional practices advocated above. Instead of focusing on the apparent deficits of kindergarten mathematics instruction, this study explores what characteristics predict teachers’ allocation of instructional time to beyond-the-basics mathematics practices. One avenue of investigation into these high-quality teaching practices is to examine teachers who have experience in working with diverse student populations (i.e. bilingual EC teachers and EC teachers who have completed formal training in best practices for working with multilingual learners[ML]), who seem to exhibit more progressive, effective, and linguistically-responsive instructional practices than their counterparts (Hopkins, 2013; López et al., 2013).

Using data from the Early Childhood Longitudinal Survey (ECLS-K: 2011), this quantitative study investigates whether kindergarten teachers’ educational preparation and classroom language contexts are correlated with the frequency at which they report using beyond-the-basics mathematics instruction (i.e. instruction that is cognitively demanding, conceptually-focused, uses real-life examples, and is collaborative and dialogic), and whether these relationships vary across sociodemographic contexts. Results of multiple regression analysis and supplementary t-tests revealed that teaching in a bilingual classroom, completion of at least one ML methods course, and completion of at least one EC methods course were positively associated with time spent on beyond-the-basics mathematics instruction, along with total time spent teaching mathematics overall. Schools’ sociodemographic characteristics (proportion of students eligible for free/reduced lunch and proportion of students designated English learners) were not found to be significant influences on these particular components of mathematics instruction. This study provides educational administrators, university teacher education programs, and agencies of teacher credentialing with valuable information on the types of experiences and environments that result in teachers employing the types of high quality, beyond-the-basics mathematics instruction that have been shown to increase student learning.

Temporal Regulation of Nematode Development from a Biochemical, Circadian Perspective

(2024)

Timing mechanisms are utilized by organisms in a variety of biological functions. From circadian rhythms to nematode development, the genetic networks that underly the keeping of time are complex and thoroughly regulated. Circadian rhythms allow organisms to anticipate daily environmental changes and thus confer an adaptive advantage and the genetic network that governs them is well-established. While much is still to be gleaned about the molecular basis of circadian timekeeping, a model of a rewired developmental timer based on conserved circadian clock orthologs C. elegans, is beginning to emerge. In this dissertation, I discuss the conservation of specific factors and provide new insights that highlight the biochemical mechanisms that regulate C. elegans development. C. elegans are a widely studied model organism, yet little is known about the molecular basis for its temporal control of development. Two intricately linked timers, the molting cycle and heterochronic pathway, coordinate cuticle regeneration and growth with stage-specific cellular events. Several circadian orthologs have established roles in regulating these processes. Chapter 2 describes the homology between nuclear hormone receptors (NHRs), retinoic acid-related nuclear receptor (RORα/β/γ) and NHR-23, transcription factors that activate the expression of a core clock component and drives the transcriptional network that governs nematode molting, respectively. We lay the groundwork for a conserved mode of ligand-binding, as well as identify a separate class of small molecules that bind to NHR-23. The interaction between PERIOD (PER) proteins and its cognate kinase, Casein Kinase 1 and ε (CK1), is integral to determining the phase and timing of circadian rhythms. PER is a stoichiometrically limiting factor in the repressive complex that provides the inhibition of circadian transcription. Stable anchoring of CK1 to PER2 mediates phosphorylation of PER that regulates its stability and abundance in the cell. This interaction is also required for CK1-dependent displacement of the core clock transcription factor from DNA. Chapter 3 demonstrates the C. elegans homologs to PER and CK1, LIN-42 and KIN-20, respectively, interact in a similar mode to regulate C. elegans development. We show that two kinase-binding motifs within the CK1-binding domain (CK1BD; CK1BD-A and CK1BD-B) are conserved enough in LIN-42 to mediate binding to CK1 in vitro. We determine that the expression of LIN-42 and KIN-20 temporally and spatially overlaps and that the CK1BD as well as KIN-20 kinase activity are required from proper molting timing. We further show that phosphorylation of LIN-42 by CK1 leads to kinase inhibition, suggesting a conserved mode of product inhibition whereby phosphoserine(s) anchor into conserved anion binding sites along the kinase active site. In chapter 4, we discuss our recent work to identify a novel regulator of the C. elegans molt cycle. Through in vivo techniques, we show that KIN-20 and a previously uncharacterized ankyrin repeat domain-containing protein (ANKRD49), are similarly expressed temporally and spatially, and interact. We show that C. elegans ANKRD49 binds to human CK1 with nanomolar affinity in vitro, and that this interaction influences kinase activity on LIN-42. An AlphaFold binding model of the complex predicts that stable binding is mediated through the ANKRD49 structured C-terminus and a flexible CK1 helix near the active site that is important for substrate recognition and processing. This model also predicts that the interaction is enhanced via binding of the ANKRD49 unstructured N-terminus to the CK1 substrate binding cleft. We show that deletion of the ANKRD49 unstructured N-terminus as well as mutations near and on the flexible CK1 helix that alter circadian period in mammals, reduce the C. elegans ANKRD49/human CK1 affinity >10-fold. Depletion of ANKRD49 in vivo leads to asynchronous and delayed molting similar to kin-20(null) phenotypes. Given the high conservation of CK1 across organisms as well as several proteome-scale studies that also identify a human ANKRD49/CK1 interaction, this work potentially has broader implications for understanding circadian rhythms and temporal regulation in diverse organisms. In summary, throughout this dissertation I have used an interdisciplinary approach of utilizing biochemistry and in vivo C. elegans genetics, to describe the molecular basis for circadian homolog function in C. elegans development. In addition to the findings discussed herein, this work provides a framework elucidating the molecular underpinnings of nematode timing mechanisms as well as an additional insight into evolutionary conservation of timekeeping mechanisms.