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Directed evolution of an orthogonal transcription engine for programmable gene expression in eukaryotes
No full textT7 RNA polymerase (RNAP) has enabled orthogonal control of gene expression and recombinant protein production across diverse prokaryotic host chassis organisms for decades. However, the absence of 5′ methyl guanosine caps on T7 RNAP-derived transcripts has severely limited its utility and widespread adoption in eukaryotic systems. To address this shortcoming, we evolved a fusion enzyme combining T7 RNAP with the single subunit capping enzyme from African swine fever virus using Saccharomyces cerevisiae. We isolated highly active variants of this fusion enzyme, which exhibited roughly two orders of magnitude higher protein expression compared to the wild-type enzyme. We demonstrate the programmable control of gene expression using T7 RNAP-based genetic circuits in yeast and validate enhanced performance of these engineered variants in mammalian cells. This study presents a robust, orthogonal gene regulatory system applicable across diverse eukaryotic hosts, enhancing the versatility and efficiency of synthetic biology applications
Components of the Emerton-Gee Moduli Stack of Galois Representations for GL2 and A Graph-Theoretic Approach to Computing Selmer Groups of Elliptic Curves over Q(i)
Get PDFLet K be a finite unramified extension of Q_p with p ≥ 5. In the first part of this thesis, we study the local geometry of the irreducible components in the reduced part of the Emerton–Gee stack for GL_2, which serves as a moduli space for two-dimensional mod p representations of Gal(K/K). We determine precisely which irreducible components are smooth, which are normal, and which have Gorenstein normalizations. We prove that the normalizations of these components admit smooth–local covers by Cohen-Macaulay and resolution-rational varieties, which are generally not Gorenstein. Finally, we determine the singular loci in the components, providing insights which up- date expectations about the conjectural categorical p–adic Langlands correspondence.
In the second part of this thesis, we introduce a graph-theoretic algorithm to compute the φ-Selmer group of the elliptic curve E_b : y^2 = x^3 + bx defined over Q(i), where b ∈ Z[i] and φ is a degree 2 isogeny of E_b. We begin by associating a weighted graph G_b to each curve E_b, whose vertices correspond to the odd Gaussian primes dividing b. The weights on the edges connecting these vertices are determined by the quartic residue symbols between these primes. We then establish a bijection between the elements of the φ-Selmer group of E_b and certain partitions of the graph G_b. This correspondence provides a linear-algebraic interpretation of the φ-Selmer group through the Laplacian matrix of G_b.
Using our algorithm, we explicitly construct several subfamilies of elliptic curves E_b over Q(i) with trivial Mordell–Weil rank. Furthermore, by combining our method with Tao’s Constellation Theorem for Gaussian primes, we prove the existence of infinitely many elliptic curves E_b over Q(i) with rank exactly 2. Additionally, we show that for each pair of rational twin primes (p, q), the curve E_{pq} considered over Q(i) has rank either 2 or 4, with the rank exactly 2 when p ≡ 5 mod 8. Lastly, we show that for each rational prime of the form p = a^2 + c^4 (of which there are infinitely many), the elliptic curve E_{-p} over Q(i) has rank either 2 or 4, with rank exactly 2 if p ≡ 5 or 9 mod 16
Parental Perspectives and Experiences from HISD’s Parent University
Get PDFParental involvement in children's education significantly improves attendance, behavior, grades, and social skills, all of which are crucial for long-term success. To increase parental engagement and advocacy from parents, the Houston Independent School District (HISD) established the Parent University program in the 2018-19 school year. While the program has continuously evolved since its inception, the overall goal has remained the same: to connect parents with district-provided resources and information through a series of courses on topics that include parents’ dreams and aspirations for their children, the inner workings of HISD, challenges to equity and quality education, parental advocacy and volunteerism, and the pathway to college. Given this wide range of content and the resource-intensive nature of the intervention, the Kinder Institute for Urban Research’s Houston Education Research Consortium (HERC) has partnered with HISD to better understand which elements of Parent University have been the most effective in promoting parental engagement and advocacy. Information from this study will be used by program administrators to streamline and improve the content provided to future Parent University cohorts
Continuities and Divergences in Baroque Twelve-Mode Theory
No full textTwelve-mode theory, which originated in the theoretical writings of Heinrich Glarean (Dodecachordon, 1547) and Gioseffo Zarlino (Le istitutioni harmoniche, 1558), was widely disseminated in Italian and German theoretical and pedagogical sources until about 1800, which raises the question: what relevance did a theory that originated in plainchant and later adapted to vocal polyphony have for a musical culture increasingly dominated by concertato idioms and the newer genres of opera, oratorio, sonata, and concerto? Any answer to this question is complicated by the fact that twelve-mode theorists rarely addressed the relevance of their theory to newer music in explicit and unequivocal terms. As a result, previous scholarship has offered an array of views on the practical relevance of Baroque-era modal theory, ranging from outright skepticism, on the one hand, to its whole-sale adoption as a means of analyzing tonal style, on the other.
In this paper, I argue that twelve-mode theory was never a widespread and coherently disseminated technique; rather, it remained a theoretical construct that, over its long history, underwent diverse, even incompatible interpretations. To illustrate this, I will trace the divergent paths of German and Italian modal theory, examining their distinct technical and stylistic orientations in three chapters. In Chapter 1, I examine two early eighteenth-century theoretical writings by Benedetto Marcello (Lettera famigliare, c. 1716) and Johann Joseph Fux (Gradus ad Parnassum, 1725) to demonstrate that the continued appeal of modal theory in the late Baroque lay in nuances absent from major-minor keys. In Chapter 2, I will compare early seventeenth-century theorists Girolamo Diruta (Seconda parte del Transilvano, 1609) and Seth Calvisius (Exercitationes musicae duae, 1600) along with early nineteenth-century theorists Giacomo Tritto (Scuola di Contrappunto, 1816) and Georg Joseph Vogler (Choral-System, 1800) to demonstrate that German and Italian twelve-mode theories diverged in two ways: first, while Italians largely adhered to traditional modal-polyphonic precepts as a stylistic topos, German theorists sought a more flexible application of the modes as a theory of tonal organization; and second, Italian theoretical sources and modally-designated compositions document a strong association between the modes and fugal technique, whereas German theoretical sources testify to a consistent association between the twelve modes and Lutheran chorales. In Chapter 3, to further substantiate these divergences, I will compare two early eighteenth-century twelve-mode collections by Azzolino Bernardino della Ciaja (Saggi per Organo, 1727) and Georg Philipp Telemann (XX kleine Fugen, 1731).
The broader significance of twelve-mode theory’s continued survival lies in the many kinds and purposes of music theory in the early modern era: as I will demonstrate, twelve-mode theorists aimed, not at music analysis in the modern sense, but variously to engage in rational and humanist speculation, demonstrate authority and erudition, provide prescriptions for composers, and negotiate between newly composed and liturgical music
Adaptive Reuse: Abandoned Navy Base New Orleans
No full textAdaptive Reuse of abandoned army/navy base constructed in 1919. Focused on one of three identical concrete buildings, building 601, to explore what is possible with massive regular structures to adapt to new programs and a wide range of use over time
The roles of WNT ligands in early human embryogenesis
No full textDevelopmental biology seeks to understand how a single cell gives rise to a complete organism through growth and morphogenesis, processes regulated by diffusible signaling molecules called morphogens. Wnt signaling, a key pathway controlling cell fate and tissue patterning, is well studied in model organisms, but its roles in human development are less understood.
This thesis investigates the spatial and functional diversity of Wnt ligands during early human differentiation, focusing on their roles in gastrulation and neurulation. Using inducible WNT overexpression hESC lines, we show that WNT3, WNT3A, and WNT8A activate WNT signaling through TCF/LEF1 transcription factors and posteriorize the anterior neural ectoderm, albeit with different strengths. In contrast, WNT6 does not use LEF1 for signaling and cannot induce posterior markers.
To further explore the functional roles of Wnt ligands, we generated knockout hESC lines for WNT3, WNT6, WNT8A, and WNT5B. Our findings show that WNT3 is essential for early gastrulation, consistent with observations in mice. WNT8A supports mesodermal formation and maintains ectodermal fates, while WNT6 is specifically required for the anterior ectoderm. In contrast, WNT5B does not play a critical role in these key morphogenetic events.
Additionally, we introduce a novel tool for visualizing Wnt dynamics in live cells, the WNT3::sYFP2 knock-in (KI) cell line, which enables real-time tracking of Wnt3 expression and activity during key stages of differentiation. Despite needing further optimization, this tool allows for unprecedented insights into the context-dependent regulation of Wnt signaling and provides a valuable resource for future studies on developmental signaling pathways.
By combining functional analysis with advanced imaging techniques, this thesis enhances our understanding of WNT ligands in human development and offers potential applications in regenerative medicine and developmental disorders
TIDE: A Trace-Informed Depth-First Exploration for Planning with Temporally Extended Goals
No full textTask planning with temporally extended goals (TEGs) is a critical challenge in AI and robotics, enabling agents to achieve complex sequences of objectives over time rather than addressing isolated, immediate tasks. Linear Temporal Logic on finite traces (LTL) provides a robust formalism for encoding these temporal goals. Traditional LTL task planning approaches often transform the temporal planning problem into a classical planning problem with reachability goals, which are then solved using off-the-shelf planners. However, these methods often lack informed heuristics to provide a guided search for temporal goals.
We introduce TIDE (Trace-Informed Depth-first Exploration), a novel approach that addresses this limitation by decomposing a temporal problem into a sequence of smaller, manageable reach-avoid subproblems, each solvable using an off-the-shelf planner. TIDE identifies and prioritizes promising automaton traces within the domain graph, using cost-driven heuristics to guide exploration. Its adaptive backtracking mechanism systematically recovers from failed plans by recalculating costs and penalizing infeasible transitions, ensuring completeness and efficiency. Experimental results demonstrate that TIDE achieves promising performance and is a valuable addition to the portfolio of planning methods for temporally extended goals
Vaisselle Odyssey
No full text“Vaisselle Odyssey” is an illustrated epic poem narrated through the persona of a non-human, architectural agent, resonating with profoundly human emotions and embodied conditions related to foreignness—particularly the othered’s unsettling experiences of being perceived as foreign, whether foreign or not.
World-built in the mythical spaces of Paris and its banlieue, the epic follows the metamorphosis and conflicted loyalties of a mobile vessel for communal cooking, REMI, as it journeys in a quest from margin to center. REMI is accompanied by seven similar commensality machines, each being a formal allegory representing one of peripheral Paris’s oft-misconceived and -stigmatized "grands ensembles" (mass housing projects built between the 1950s and the 1980s in response to an influx of foreign migrants, and deemed unfitting for the city’s curated image). Carrying the weight of belonging denied from the dominant social and national imaginaries, the vessels grapple with the fear of exclusion, the yearning for rootedness, and the right to permanence even amid the inevitability of change.
Always dismissed as transient, ephemeral, and disposable presences, REMI and its companions insist to mend these irremediable schisms that cause them pain. Wherever they go, the vessels underscore the power of food for solidarity and cultural care, turning urban spaces into communal places for collective cooking, commensality, cross-cultural conversations, and identity reclamation. Their visitors are invited to reimagine belonging and consider how containing multitudes and including pluralistic layers of identity can enrich the meanings and social representations of nationhood.
Throughout this epic, the vessel transitions from the scale of a vehicle on the move, to that of a temporary festival installation, to that of a fantastical monument. Each transition captures the complicated essence of evolving worldviews: from idealism, to radical imaginations, to questioning and self-awareness. The emotional cores about finding one’s place transcend any single identity label and can resonate universally despite all the discordances of the world. The vessel explores the human condition by freezing aside identity categories. Precisely because the vessel is a non-human agent, it invites readers to insert their own humanity and subjectivity into their reading of this odyssey
4.4 Risks from Mirror Life
Get PDFThis document emerged and evolved in discussions at the "Bioweapons and Pathogens" + "Synthetic Cell" recombination event at the "Spirit of Asilomar and the Future of Biotechnology" summit on the morning February 25, 2025. The wording was further discussed in the “mirror life” workshop that afternoon and iteratively refined in the following months with feedback from numerous summit participants.This entreaty was created as part of The Spirit of Asilomar and the Future of Biotechnology summit (February 23-26, 2025) in Pacific Grove, CA
Trust in an Age of Uncertainty: Evangelical Christian Attitudes Towards Science and Medicine
No full textIn this dissertation I examine how religion shapes trust in science and medicine among evangelical Christians. Specifically, I focus on the role of religion in shaping perspectives on the intersecting authority of religious, scientific, and political institutions. To explore this topic, I draw from interviews with a racially diverse sample of 74 evangelical Christian leaders and congregants located in Houston, Texas conducted between March 2021 and May 2024. While researchers have identified mechanisms that explain the relationship between religion, science, and medicine, (such as religious understandings of conflict or collaboration with science, anti-institutionalism, and responses to scientific racism), I posit trust is a central factor that helps us to understand these disparate influences. Through this work I discuss evangelical Christian perceptions and trust of scientists, beliefs about authority on the topic of climate change, and trust in medicine and medical professionals. I find that when religious communities engage with scientific topics it often results in greater trust in scientific expertise but when churches frame science as being too political, distrust and misinformation are more prominent. This is important because evangelical Christians play an influential role in American political life, influencing decisions such as the repeal of Roe v. Wade or loosening climate restrictions. It is also important because many evangelicals are members of marginalized racial populations and their religious views can bolster or hinder their trust in science and medicine which has implications for addressing health and education disparities. More broadly, I argue for the importance of considering trust as a major influence on outcomes such as political attitudes, health, and educational attainment