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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
In a Man’s World: Jacqueline Kennedy, Cultural Diplomacy, and Gender in the Kennedy Administration, 1961-1963
No full textDuring the Kennedy administration (1961-1963), Jacqueline Kennedy functioned as a cultural diplomat, helping convey the administration’s political messaging. Specifically, she aided in the presentation of the US as the new Western, modern superpower, whose material and cultural prosperity was a result of its democratic and capitalist system. To communicate this effectively, Mrs. Kennedy played into the expectations of Cold War American femininity, presenting herself as the ideal American woman whose life revolved around the domestic sphere. In her diplomatic endeavors, she underscored the image of the United States as a leader on scale with its European peers, yet one who was sympathetic to developing countries. Although often thought of as mostly apolitical, examining her work on the White House Tour and Restoration, state dinners and official international trips reveals Jacqueline’s role as an essential part of the Kennedy administration’s diplomacy during the escalating Cold War
Long-term control of synthetic microbial consortia
No full textSynthetic microbial consortia are communities of engineered microbes living in a shared environment. These communities are composed of multiple strains or species, each engineered for some particular function. They tend to be more robust and efficient when compared with their single-strain counterparts due to the inherent diversity and redundancy present in communities. Their use remains quite limited in the broader field, however. This is largely because diversity also brings complexity, making synthetic microbial consortia much more difficult to control than simpler systems.
One of the largest problems with controlling these communities for longer periods of time is maintaining the presence of each member of the community. Small growth rate differences can result in enormous population imbalances. Many applications allow for individual members to die out entirely, but even applications without turnover can be vulnerable to these imbalances. This problem is made especially difficult because it is only a precursor to achieving any other desired function. Any solution cannot overly tax the community without risking the functionality the community is being engineered towards.
In this thesis, I present my work studying a ratio control mechanism which uses cross-feeding auxotrophs. These cells lack the ability to make a key nutrient, and so must rely on another community member to provide that nutrient. This cross-feeding precisely regulates the growth rate of the constituent members, tightly controlling the population ratios over many days of growth. I first show the effectiveness of this control strategy, establishing its stability in a continuous culture environment that allows for population loss. I show that it is tunable via the supplementation of the cross-fed metabolites, expanding its usefulness beyond population maintenance. I also discuss the work my collaborators did to show that this tunability is predictable through mathematical modeling. I then go on to discuss my work expanding and combining this tool with other population behaviors. I first demonstrate the ability for this tool to control larger communities and to be dynamically controlled via transcriptional regulation. I then focus on cell-cell adhesion, as this is another consortia-level behavior with a wide range of uses. I demonstrate that both behaviors function when present in the same community. I also go on to show that composing these "multicellular" behaviors together cannot be done without care. In particular, I show that cell-cell adhesion enhances the growth rate of the entire community, implying an increase to the cross-feeding of each population. I also show that altering the ratio biases the cell-cell adhesion patterning towards larger aggregates, compared to the paired doublets typically seen in 1:1 ratio regimes. Together, these results demonstrate the power of this tool as a ratio control mechanism, as it is stable, tunable, and modular, making it a useful tool for researchers seeking to engineer microbial consortia
Lightweight Physical-Layer Security Primitives for 5G-and-Beyond Wireless Communications
No full textThe development of 5G-and-beyond wireless communication represents a major transition toward faster, more intelligent, and more flexible connectivity. Compared with previous generations, 5G-and-beyond systems are designed not only for higher data rates and larger capacity, but also for lower latency, enhanced intelligence, and broader applicability. These capabilities enable a wide range of mission-critical applications, such as immersive AR/VR, intelligent transportation, remote robotic surgery, and drone-assisted communication, where communication quality is tightly coupled with safety, efficiency, or privacy. However, the open nature of wireless propagation also introduces significant security concerns. In particular, as wireless transceivers become more mobile, autonomous, and distributed, it becomes increasingly difficult to verify their identity and prevent eavesdropping. These concerns raise new requirements for the transmitter (TX), which must be able to identify itself as a legitimate source and prevent sensitive information from leaking to unintended receivers.
Traditionally, wireless security is achieved through digital cryptography. Although effective in many scenarios, cryptographic methods face four limitations when applied to future systems: (1) the added power and latency overhead becomes problematic for real-time bit-wise encryption, (2) key management becomes complex and power-hungry, and (3) physical signal leakage itself is not protected by encryption. To address these issues, physical-layer security (PLS) has gained increasing attention. By embedding security directly into the physical behavior of the TX, such as frequency, phase, amplitude, or time, PLS enables protection without relying on high-level cryptographic protocols. These techniques can be implemented with minimal latency, power, and area overhead, making them suitable for 5G-and-beyond systems where both performance and security are critical.
This thesis focuses on low-overhead, TX-based physical-layer security techniques that address two major security requirements: (1) identification of TX to the receiver, and (2) prevention of wireless eavesdropping. Three system-level designs are proposed, each implemented with custom application-specific integrated circuit (ASIC) TXs and modules, and demonstrated through measurement.
The first TX design addresses the identification problem. We propose a physical-layer identification TX that incorporates a digital physically unclonable function (PUF) to control its spectral regrowth. This creates a unique RF fingerprint (RFF) for each TX, beyond what is achievable with intrinsic process variation alone. A 2.4-GHz prototype is implemented in GlobalFoundries 45-nm CMOS SOI process with 4.7 dBm output power and 36% efficiency. Measurement results show significant improvement in RFF stability, uniqueness, and dynamic range compared to prior work.
On top of it, we further enhance the identification performance with feature extraction and identification model. We develop a lightweight neural network that extracts PSD features from TX signals and performs device identification. The model is optimized for low-power implementation and works seamlessly with the proposed hardware. In measurement, 240 devices are identified with over 99% accuracy, and 40 devices at unseen distance achieve over 95%, demonstrating strong generalization and robustness under various conditions.
The second TX design focuses on preventing sidelobe eavesdropping. We present a mm-Wave antenna subset modulation (ASM) TX operating at 28 GHz. By randomly selecting antenna subsets at the symbol rate, the transmitted I/Q symbols are scrambled outside the main direction, preventing eavesdropping without degrading performance in the desired direction. The ASIC is integrated with on-board antennas and includes a high-speed on-chip true random number generator (TRNG) for secure and unpredictable antenna selection. The system supports 1.2-Gb/s 64-QAM communication with ±2° information beamwidth and maintains high EVM performance. This work highlights the great potential and practicality of integrating ASM technology into future radios.
In summary, this thesis proposes and demonstrates three low-overhead PLS techniques at the transmitter level, targeting future communication systems with tight constraints on power, latency, and security. These methods provide a practical and efficient way to enhance wireless security without relying on complicated cryptographic operations, and can serve as a complementary layer of protection in 5G-and-beyond wireless networks
Leveraged ETFs: The Key to Early Retirement?
Get PDFIn modern day retirement planning, many people manage their investments themselves, investing in index funds that track broad market indices such as the S&P 500. This project investigates whether investing in leveraged Exchange-Traded Funds (ETFs) can provide a viable strategy for retirement investing. The study evaluates different leverage strategies to determine the optimal ratio to balance risk and reward. In order to measure portfolio performance, backtesting, bootstrapping, and Monte Carlo simulations will be done on historical stock price data from 1965 to 2024). This project aims to determine if leveraged ETFs can amplify returns without excessive risk, offering insights into their potential role in retirement portfolios. The results from this project show that highly-leveraged portfolios are risky for the average investor, but if one has a longer investment timeframe, slightly leveraging up an investment portfolio would give increased returns with limited risk
Development of large-channel-count, high-density recording and stimulating flexible neural probes
No full textFlexible neural probes represent a revolutionary approach for establishing stable, glial scar-free neuronal interfaces by leveraging biocompatible materials and compact designs. Their bidirectional functionality enables the recording of brain signals and precise stimulation with sub-millisecond temporal resolution. However, these probes currently lack the electrode count and density compared to state-of-the-art silicon-based neural probes, limiting the number of neurons that can be recorded within the same implantable depth.
This thesis addresses the challenges and approaches of increasing channel count and electrode density in flexible neural probes. First, I utilized electron-beam lithography to pattern thinner interconnect traces, achieving a denser electrode layout with 128 channels per shank—representing a fourfold increase in channel count compared to photolithography-made flexible probes. These oversampling electrodes enable the isolation of highly clustered single units locally and across brain regions over extended periods (up to one year in mice and four months in rats), facilitating population-level neuronal tracking. Intracortical microstimulation (ICMS) delivered via microelectrodes allows precise modulation of neural circuitry and large-scale neural activity.
Second, I developed and demonstrated an ultra-high channel count neural probe integrated with a custom application-specific integrated circuit (ASIC), capable of recording from 5,376 individual channels simultaneously. This surface electrocorticography (ECoG) array achieves a density of up to 70 microelectrodes per mm², enabling high-resolution, large-scale cortical mapping and the capture of fine-temporal neural responses to stimuli.
Finally, I designed an electrode array as a visual prosthetic for non-human primates. The array, comprising 1,024 sparsely distributed electrodes, targets the primary visual cortex to restore rudimentary vision through the generation of phosphenes via electrical stimulation.
In summary, the techniques developed in this thesis for large-scale brain mapping and modulation provide valuable tools for neural dynamics sensing, disease monitoring, neuropathology studies, and brain-machine interface applications
INSTILL: Instructor Network to Support Teaching Innovation and eLevate Learning, 2024-2025
No full textINSTILL mini-grants provided an opportunity for faculty to do the logistics planning and organizational work necessary to implement a concrete improvement in one of their courses. This portfolio contains summaries of 2024-2025 INSTILL projects and explanatory handouts for several of the course changes
6.5 Public Engagement
Get PDFThis entreaty was created as part of The Spirit of Asilomar and the Future of Biotechnology summit (February 23-26, 2025) in Pacific Grove, CA
5.5 The Future of Biotechnology: A Show of Good Faith
Get PDFThis entreaty emerged from conversations during the 'History, Culture, Religion, and our Framing of Biotechnology’s Future' session.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.Religion and biotechnology are often seen as being in conflict, but this narrow view can deepen divisions and alienate communities. Building biotechnology’s future requires learning from the past and understanding its cultural and religious contexts. We urge scientists to engage with other disciplines to grasp broader social issues and improve communication across divides. Envisioning responsible innovation means honoring history, fostering dialogue, and recognizing the diverse traditions that shape how biotechnology is received and applied
Desire and Moral Virtue in Aristotle's Ethics
No full textAccording to a standard reading of the Nicomachean Ethics, Aristotle’s account of the moral virtues in Books III-IV—qualities like courage, magnanimity, temperance, and so on—is a kind of grab-bag, an unsystematic list of virtues. At best, commentators say, Aristotle fails to offer us principles that explain his selection of the virtues. At worst, the list is merely the result of Aristotle’s intuitions, perniciously conditioned by his elite Athenian cultural context. In this dissertation I argue that this standard reading is false.
My account has two major aspects. First, I look at what, in Aristotle’s view, are the two basic sources of non-rational desire: appetite (epithumia) and spirit (thumos), themselves neglected topics of study. These desire-types are non-rational in that we share them with other animals, even if we experience them in distinctively human form. Appetitive desire is for food, drink, or sexual activity and, more broadly, for those things necessary to keep the individual and the species alive. Spirited desires aim to affirm our place in a rank relative to some group or avoid what denies our ranking; in humans, spirit manifests itself in a broad range of phenomena that includes anger, shame, affection, and a desire for honor. Appetitive and spirited motivations largely determine the relevant spheres of the moral virtues: honor, anger, tactile pleasure, money and so on. These conclusions begin to show the systematicity in Aristotle’s theory and the structural role played by non-rational desire in books III-IV.
The second aspect concerns the way those appetitive and spirited motivations must be shaped in order to be virtuous. This is largely determined, I argue, by Aristotle’s account of the way relationships within a community (koinônia) generate norms of justice. These relationships are wide-ranging: parents and children, spouses, intimate friends, political associates, citizens, and beyond. Appetitive and spirited motivations must be shaped so as to conform to these norms.
To the extent that Aristotle’s account is driven by a philosophical psychology and the norms of justice that arise out of communities, it turns out to be not parochial, but systematic and a rich source for further reflection