Myocardial infarctions (heart attacks) are the most common cause of cardiac damage globally, leading to the significant health consequences and even death. Biomaterials, such as hydrogels, can serve as a better method to manage cardiac damage. However, an exploration of the current biomaterial and microneedle solutions shows a lack of directed drug delivery capabilities or conductivity. Given the density and conductivity of human cardiac tissue, these aspects are critical in improving the effectiveness of any biomaterial solution. Introduced in this thesis is the combination of both elements into a conductive hydrogel-based microneedle patch. We utilized a new, naturally derived biomaterial, tannic acid:PEDOT (poly(3,4-ethylenedioxythiophene), also known as TADOT. We then combined this with gelatin methacryoyl (GelMA) hydrogel to develop a biomaterial-based microneedle platform aimed to solve both issues. The formation of a tannic acid complex with PEDOT to form TADOT allows the hydrogel to be conductive, while the GelMA provided sufficient mechanical strength. With the anti-inflammatory characteristics of tannic acid, and the biocompatible nature of gelatin, the material is designed for better contribution to cardiac healing. We were able to engineer a microneedle patch based on TADOT-GelMA into microneedles which could penetrate porcine cardiac tissue, proving the potential for this biomaterial as a platform for cardiac repair applications. The conductive and mechanical characteristics of the TADOT-GelMA microneedles can allow it to serve as a delivery platform to be combined with other cardiac repair solutions.

In recent years, neural networks have contributed significantly to the advancement of machine learning, achieving state-of-the-art over a broad range of challenging tasks. The world right now is seeing a global artificial intelligence (AI) revolution involving academic and industry alike: tech giants like Google and Microsoft are applying machine learning in their commercial products, while professors from every discipline- computer science, engineering, mathematics, biology, transportation - scrambling to apply these methods to advance their research. Stock analysts are using AI to analyze and predict stock prices, medical experts to diagnose and develop new drugs, while game developers create sophisticated, human-like behavior in characters. At the national level, both NSF and DARPA have identified AI as one of the major national research directions. Our research targets the advancement of next-generation AI from three vertical aspects along the computing hierarchy: At the algorithm level, we propose the use of application-specific, bio-inspired neural networks for information processing. We develop models of specialized audio and visual neurons that are compatible with existing algorithms; and optimize neural architectures containing these neurons to understand their role in creating an efficient network. At the hardware level, we address the memory bottleneck in AI accelerators. We propose two schemes to overcome limitations caused by variation in critical path and fabrication processes. At the single device level, we recognize the significant performance gain from devices that compose AI computation via physical mechanisms. We propose two spintronic structures capable of computing convolutions that achieve orders of magnitude higher efficiency than state-of-the-art technology. These innovations provide the foundation for higher performance and more efficient AI at different temporal points throughout the coming decade: in the short term, algorithms that can be implemented immediately; in the mid-term, hardware designs that can be realized in a few years; and in the long term, new device technologies to be adopted as the fabric of AI computation.

“[W]omen are…believers in muscular manhood. These lank, scrawny limbs…he was more like a woman than a man.”–1870

“What other men visit salons to get, the Asian gene pool provides for free…ladyboy fingers: soft and long.”–2004

Despite a difference of over a century in publication dates, these excerpts from popular periodicals evince remarkably similar imaginings of the Asian male body. This correspondence is indicative of the ways in which contemporary non-normative constructions of Asian American masculinity suggest a historical linearity rooted in early American conceptions of Asian immigrant men.

As the first group of Asian immigrants to warrant social visibility, an exploration of the social figuration of early Chinese immigrant laborers can serve as a basis for understanding this popularization of emasculation. Specifically, to the extent that this group also formed the foundational basis for a seemingly extant legacy of deviance today, an examination of how these pioneer Chinese men were descriptively bounded within popular spaces can expose both the parallels and points of departure from which we can more fully understand contemporary Asian American masculinity.

This paper analyzes the textual imagery of Chinese immigrant laborers as captured in popular periodicals and print media between 1850 and 1924. In exploring perceptions of Chinese masculinity during this period, the projection of deviance is examined through three lenses of Chinese male non-normative constitution: the diasporic attribution of otherness as non-White aliens, queer domesticity as defined by family and occupation, and most visibly within the perceived and material deficit of agency.

Ubiquitination is a process used by cells to tightly control signaling pathways by covalently attaching a ubiquitin molecule to a target substrate. This process is reversible by the activity of deubiquitinating enzymes. Otubain 1 (Otub1) is a novel deubiquitinating enzyme whose physiologic relevance in an in vivo setting had not been described. In this dissertation, we describe two novel functions of Otub1, discovered after creating and analyzing Otub1-deficient (Otub1-/-) mice.

We first found that Otub1-/- mice die during late embryonic development. To examine whether Otub1 plays a role in the functioning of immune cells, we reconstituted irradiated recipients with Otub1-/- fetal livers to create chimera. At baseline in the absence of overt stimulation, Otub1-/- chimera had more memory-phenotype CD8+ T cells than wildtype and T cell homeostasis was disrupted in a cell-intrinsic manner. Otub1-/- T cells also hyperrespond to homeostatic signals, particularly IL7 stimulation.

While studying Otub1's role in T cell homeostasis, we also discovered it had a role in regulating programmed cell death. Using mouse embryonic fibroblasts (MEFs) and a human cell line, we found that Otub1-deficiency or Otub1 knockdown sensitizes the cell to undergo more TNF-induced apoptosis and necroptosis. Specifically, Otub1-deficiency led to increased formation of the necrosome, the Rip3-containing complex that drives necroptosis. This function may in part be driven by an accelerated loss of cellular inhibitor of apoptosis protein-1 (c-IAP1) in Otub1-/- cells as compared to wildtype. Together, we have shown that Otub1 has important in vivo roles in regulating T cell homeostasis and programmed cell death. Along with other studies, this work establishes Otub1 as a critical regulator of diverse signaling pathways and opens up several future avenues of investigation.

Signaling reactions often originate at the membrane, where competing membrane reactions decide if and how the signal will be passed on to downstream signaling cascades. In some cases, membrane reactions can even lead to polarization of signaling molecules that convey spatial information to downstream pathways. Due to the microscopic size of cellular structures, reactions at the membrane are confined and limited to low molecular copy numbers. Signaling decisions are therefore subject to strong stochastic effects. Understanding how membrane reactions can be influenced by stochastic effects is an imperative step toward deciphering the molecular logic of cellular signaling. However, the space of possibilities remains sparsely mapped. In this dissertation, I aim to expand our understanding of this topic by studying two-dimensional confinement effects on phosphatidylinositol signaling and small GTPase signaling reactions, both of which are ubiquitous membrane signaling mediators. Reducing the size of the membrane can lead to two distinct types of stochastic effects: size-dependent reaction speed and stochastic bistability. The underlying physical mechanism is intrinsically stochastic and cannot be predicted by classical deterministic kinetics. The biochemical requirements and potential cellular regulation of these stochastic effects are further discussed. In membranes with asymmetric shapes, the difference in local stochastic effects that the reaction experiences could emerge as stochastic polarization. This stochastic polarization has no analog in continuum reaction-diffusion systems and exhibits a striking ability to polarize in a consistent direction when constrained to cellular shapes. The requirements of size-dependent reaction speed, stochastic bistability, and stochastic polarization are very basic, and largely met in cellular environments, such that many membrane signaling reactions may be subject to these effects. Overall, the discussions here provide a basis to understand how the size and shape of the membrane can be a regulating factor of biochemical reactions and further influence living phenomena.