Recent developments of superhydrophobic surfaces (SHSs) have attracted much attention because of the possibility of achieving substantial skin-friction drag reduction at high Reynolds number turbulent flows. An SHS, consisting of a hydrophobic surface combined with micro- or nano-scaled topological features, can yield an effective slip length on the order of several hundred microns. In this numerical study, direct numerical simulations of turbulent channel flows and turbulent boundary layers (TBLs) developing over SHSs were performed. An SHS was modeled through the shear-free boundary condition, assuming the sustainable gas-liquid interface remained as a flat surface. For the considered Reynolds number ranges and SHS geometries, it was found that the effective slip length normalized by viscous wall units was the key parameter and the effective slip length should be on the order of the buffer layer in order to have the maximum benefit of drag reduction. The effective surface slip length can be interpreted as a depth of influence into which SHSs affect the flow in the wall-normal direction. This result demonstrates that an SHS achieves its drag reduction by affecting the turbulence structures within the buffer layer of wall-bounded turbulent flow. It was also found that the width of an SHS, relative to the spanwise width of near-wall turbulence structures, was also a key parameter to the total amount of drag reduction. Significant suppression of near-wall turbulence structures were observed, which resulted in large skin-friction drag reduction due to the lack of the shear over SHSs. A comparison between TBLs and turbulent channel flows over SHSs were also examined. In contrast to fully developed turbulent channel flows, the effective slip velocity and hence the effective slip length varied in the streamwise direction of TBL, implying that total drag reduction of TBL would depend on the streamwise length of a given SHS. The present numerical study was compared with recent experimental results and showed good agreement. In addition to flow and SHS geometry conditions, the streamwise length of SHSs was also a key factor to understand the underlying physics of wall-bounded shear flows. Finally, it was found that the amount of drag reduction was theoretically estimated as a function of the effective slip length normalized by viscous wall units.

The spliceosome is a dynamic eukaryotic macromolecular complex responsible for catalysis of pre-mRNA splicing. High quality processing of a pre-mRNA by removal of non-coding introns and ligation of exons is essential to preserve the accuracy of a mature RNA transcript that will undergo eventual translation into a functional protein. Given the irresolute nature of the spliceosome, much of the machinery underlying the structural rearrangements that occur throughout the splice cycle have yet to be fully characterized. Thus far, biochemical characteristics of spliceosome assembly in humans have been studied by complexes purified by in-vitro reconstitution with HeLa nuclear extract and a transcribed radiolabeled pre-mRNA substrate. While in-vitro reconstitution has been a standard for purification of both human and yeast spliceosomes, studies in yeast have also been able to utilize endogenous protein tags to study the physical nature of spliceosome intra-interactions. Here we have re-purposed a RMCE protocol from Khandelia et al. to endogenously express V5-tagged snRPB2, a core component of the U2 snRNP, in HeLa cells. Our tagged construct was integrated into the HeLa cell genome by Cre-Lox recombination and construct expression is regulated by a TET-ON system. Selected HeLa cells were then induced to express V5-tagged snRPB2 for eventual purification of the tagged protein and its endogenous interactions by co-immunoprecipitation (Co-IP). Mass spectrometry data revealed the Co-IP eluent contains all the components of an endogenously assembled U2snRNP from active HeLa nuclear extract. Altogether, these preliminary results open the door for a pipeline to study biochemical characteristics of mammalian spliceosomal complexes purified via endogenously tagged proteins.

Schwann cells play a vital role in maintaining homeostasis of the nerve and in recovery when an injury occurs in the peripheral nervous system. An improperly healed nerve or impaired Schwann cells can lead to the development of neuropathic pain. Most treatments for neuropathic pain treat the symptom but not the underlying cause. By developing drugs that can activate Schwann cells to become a recovery phenotype can be a method of treating neuropathic pain. The binding of the hemopexin domain of MMP9 to the LRP1 receptor of Schwann cells was previously found to cause the same signaling pathways that can activate these cells to differentiate into a recovery phenotype. Thus, developing small peptides of MMP9 to bind to LRP1 and cause the same signaling response, would be a viable option for developing a treatment for neuropathic pain.

Using the crystal structure of MMP9 hemopexin domain as a template, 4 peptides were designed from the hydrophilic regions of the protein. These peptides were subjected to in vitro cell signaling studies, in situ pull downs assays and in vivo nerve crush assays to assess their biological similarity and relevance compared to the parent MMP9 hemopexin domain. Of the 4 peptides, peptide 2 with the sequence “SGRGKMLLFSGRRLWRFDVKAQ,” was seen to have similar activity to the parent MMP9 hemopexin domain.

To observe if the peptide would be capable of alleviating neuropathic pain, a drug delivery system needed to be developed to locally delivery the peptide to a PNL rat model. Alginate hydrogels were first used with a PNL injury model and seen to have no behavioral changes. However, due to high levels of inflammation seen in the immunohistochemistry and immunoblots, a PEG derived system was used to locally deliver the peptide to the nerve. Using the PEG system, peptide 2 was seen to alleviate pain 10 days post PNL operation compared to the controls. Although there are still many questions that need to be answered about the mechanism of action of peptide 2 and how it can alleviate neuropathic pain, this dissertation served as a starting point to this project.

Microfluidics enables high-throughput protein measurements and holds great promise in unraveling the mechanisms underlying complex biological systems, such as the estrogen receptor signaling pathways in breast cancer. However, implementation of protein cytometry for precision oncology is stymied by insufficient classification and insight of protein isoforms, high sample losses during handling, and lack of standards that evaluate device performance. In my dissertation, I address each of these challenges by applying chemistry and physics to develop and optimize single-cell electrophoretic protein assays.

Lab-on-a-disc platform for sparse sample handling: To minimize cell handling losses in sparse samples from both clinical and experimental settings, we designed and developed a multi-stage assay using a lab-on-a-disc that integrates cell handling and subsequent single-cell western blotting. As the two-layer microfluidic device rotates, the induced centrifugal force directs dissociated cells to dams, which in turn localize the cells over microwells. Taking into account cell losses from loading, centrifugation, and lysis-buffer exchange, our lab-on-a-disc device handles cell samples with as few as 200 cells with 75% cell settling efficiencies. By integrating the lab-on-a-disc cell preparation and the single-cell western blot, our platform measures proteins from sparse cell samples at single-cell resolution.

\textbf{Microparticle-delivered standards for protein sizing:} To identify different protein species (i.e. isoforms) and complexes that are spatially resolved in the separation lanes of single-cell western blot, protein sizing standards are needed for thousands of separation lane to accurately measure the protein masses. Here, we developed a technique to deliver magnetic microparticles with protein sizing standards into microwells and integrate with the single-cell western blot workflow. Using nickel-histidine chemistry, we demonstrated that 80% of protein standards are released from microparticles within a time scale of in-situ cell lysis. After characterizing release and electrophoresis of protein sizing standards in hundreds of single-cell separation lanes, we successfully analyzed lane-to-lane and chip-to-chip technical variability and extracted mass sizes of cellular endogenous proteins from individual cells.

Single-cell western blotting for refining estrogen receptor taxonomy: Estrogen receptor (ER-alpha) is a key regulator of cancer growth, and different ER-alpha isoforms have been shown to affect hormone therapy response in breast cancer (BCa). Conventional immunoassays cannot selectively measure ER-alpha isoforms, given the high amino-acid sequence overlap between all isoforms of ER-alpha. To address this challenge, we demonstrate a high-selectivity, single-cell western blot, that distinguishes full-length ER-alpha66 from truncated ER-alpha46 in single cells by prepending an electrophoretic separation of proteins to a subsequent immunoassay. Employing this assay, we measured abundance and frequency of ER-alpha isoforms in ER-alpha+/- BCa and identified a < 10% subpopulation of BCa cells with truncated ER-alpha46. Then, by treating cells with estradiol and tamoxifen, we discovered distinctive activations of ER-alpha signaling pathways from different BCa subtypes. Our single-cell quantitation of downstream ER-alpha and downstream signaling proteins have a potential to bring new therapeutic regimes for hormone-resistant cancers.

Kinetic binding measurement assay: Traditional biochemical assays suffer from low reproducibility and lengthy sample handling time to prepare a large set of samples. By using a microfluidic platform, serial preparation steps are reduced by exploiting a laminar flow and channel design to create spatial gradient and uniform concentration of proteins. Using a polyacrylamide gel as an size exclusion zone, the amount of bounded molecules over a different range of initial molecule concentrations are captured. The result of bounded fraction are plotted to find a dissociation constant rate of a receptor protein and its binding molecule.

Taken together, these advancements for robust protein measurement will provide a potential to apply microfluidic protein tools for precision oncology.

Since the mid-1990s, Korean American writers have written novels to double-voice Korean/Asian American issues by a detour through the Japanese Imperial Army’s sexual slavery (the ‘comfort women’ issue) during World War II. Unfortunately, their double-voicing forgets the U.S. Cold War involvement in the issue, leading to American nationalist representations of it. Such discursive acts metonymically reinforce Korean/Asian American national subjecthood. The following chapters are divided into three parts to embody this gradual amnesia and the resultant increase in their Korean/Asian “American” legibility through the disappearing slash in the parts’ titles. Part I, “Claiming Korea(n)/America,” consists of Chapter 1, “Anticommunist Nationalizing ‘Comfort Women’ through Multiracial Democracy in Therese Park’s A Gift of the Emperor.” I examine why the novel’s critical representation of Japan’s colonial rule of Korea, the U.S. detention and mobilization of Japanese Americans, and Syngman Rhee’s anticommunism rather indicates its assimilation into a U.S. anticommunist foreign policy called multiracial democracy that intended to propagandize the U.S.-led panethnic anticommunist collectivity in Asia. Part II, “Claiming Korean America,” has two chapters. In Chapter 2, “Americanizing ‘Comfort Women’ through the Homogenization of Nationalisms in Chang-rae Lee’s A Gesture Life,” I critique the novel’s homogenization, whose American imperialist logic starts to forget the U.S. involvement in the continuity between the ‘comfort women’ issue and U.S. military-centered prostitution while remembering the Cold War origin of the model minority myth. Chapter 3, “Korean/Americanizing ‘Comfort Women’ through Transparent Translation in Nora Okja Keller’s Comfort Woman,” debunks the novel’s attribution of the shared gender and ethnic affinities as the reason for a transparent translation, which dialectically Orientalizes both a comfort woman and Korean American woman due to their sharing of Asianness. The last chapter, “Cold War Nationalizing ‘Comfort Women’ through the Universalization of Women’s Oppression in Mary Lynn Bracht’s White Chrysanthemum,” is located in Part III, “Claiming Korea.” I investigate the novel’s discursive link between Japan’s military sexual slavery and the Jeju 4.3 (April 3) Incident, whose gender-essentialist emphasis on women’s economic and thus sexual empowerment against universal patriarchy in the domestic realm is metaphorically reminiscent of a U.S. anticommunist policy called domestic containment.

My dissertation is focused on one question from different cultural and historical sites: what is a perpetual state of emergency and how is it used to enact state violence? Generally, I hope for this dissertation to stage an intervention in, and to open questions and investigations around, violence, condemnation, ethics, and the law. More specifically, through this project I seek to read explicit legal state violence in post-Revolutionary Iran to elucidate more implicit legal state violence in the contemporary U.S. In the Islamic Republic of Iran, the state does not conceal that it functions as what Édouard Glissant calls a “root model” with hierarchical and fixed moral parameters determining the laws of the country; in fact, the government publicly touts its widespread deployment of violence in order to deter individuals—condemned as enemies—who may try to deviate from, or challenge, the laws. In the U.S., the state rhetorically reinvents seemingly new crises—such as the War on Drugs—to sustain the notion of an enemy warranting the state’s use of violence. While I investigate published texts that pertain to the U.S. system, I have chosen to examine Iranian cinema—rather than published texts—as a venue for critical discourse addressing the issue of state violence. Ultimately, this project proposes the following inquiries: how can a reading of state violence—legal, juridical, rhetorical, and physical—in post-Revolutionary Iran elucidate concealed state violence in the contemporary U.S.? What is at stake when one compares U.S. legal and juridical systems with those of the Islamic Republic of Iran? How can our relation to law be critically and creatively re-imagined?

The effects of surface roughness on compressible turbulent flow have not been studied as closely as the effects of surface roughness on incompressible flow.

To date, our knowledge of fully-rough high-speed turbulent flows comes from experiments, large eddy simulations, or direct numerical simulations of rough-wall channel flows.

This dissertation seeks to extend our understanding of rough-wall boundary layers by examining the effect of the freestream Mach number.

A previously-verified fifth-order hybrid weighted essentially non-oscillatory scheme with geometries imposed by a third-order cut-stencil method was modified to handle turbulent inflow boundary conditions and spanwise periodicity. The turbulence capabilities of the code were then validated against published results of a Mach 2.5 smooth-wall turbulent boundary layer.

Two direct numerical simulations of different freestream Mach numbers, 2.5 and 5.0, were conducted.

The results show that scaling the root mean square (RMS) of velocity and vorticity fluctuations with the local density accounts for the difference in magnitude.

Scaling the RMS of non-dimensionalized temperature fluctuations by the ratio of wall temperature and freestream temperature, provides reasonable collapse between both simulations.

Similarly, scaling by the ratio of wall density and freestream density offers reasonable collapse for the RMS of density fluctuations.

Both of these scalings offer good collapse regardless of the surface topology.

The Favre-averaged Reynolds shear stresses exhibit increased magnitude in regions with local compression.

Conversely the Favre-averaged Reynolds shear stresses decreased in regions with increased expansion.

A similar trend was observed for the wall-normal Favre-averaged Reynolds stress, but is not as pronounced.

The location of the expansion and compression waves from the edges of the roughness is directly affected by the local Mach angle.

For the \mf case, the Mach angles varied much more resulting in regions of decreased dilatation.

The freestream Mach number plays an indirect role in setting the shift in the log-layer.

The compressible results from both Mach numbers do not compare well to incompressible results.

This could be due to the different topologies.

As our nation continues to transition into the Next Generation Science Standards, it will be important to take a closer look at teacher preparation programs. In particular, the language demands of the NGSS will require that teachers integrate approaches to open up opportunities for student to engage in productive, student-centered discourse. This study follows ten teachers into their first year of teaching to observe the impacts of a secondary science methods course focused on opening up student discourse through the a model-based pedagogical framework. Findings illustrate first-year teachers’ perspectives on the goal of student talk, as well as their perspectives on how models and modeling activities support student talk. The findings from this study offers recommendations on how teachers preparation programs might revise their programs to better align to the language demands of the Next Generation Science Standards.

Through the cultural lens of California’s Inland Empire, India, and Italy, this dissertation explores how creditor-debtor relationships translate into literature, film, media, and space. Raising key questions about the moral and monetary values that shape creditor-debtor relationships, I discuss in detail the histories and processes that shape and inform both creditors and debtors. I argue that from the emphasis on the debtor’s guilt and punishment in previous scholarly investigations of the creditor-debtor relationship, debtors have taken on the burden of unethical credit schemes manufactured on behalf of the free market’s health. Divided into five chapters, this project addresses different aspects of the creditor-debtor relationship. With an analysis of student debt the preface and the introduction illustrate how the creditor-debtor relationship is shaped by the sovereignty of the economy such that the health of the economy becomes more significant than the well-being of people and the environment. The introduction also exposes the creditor’s fear of the potential capitalist and the limitations that the industrial-complex imposes on the creditor-debtor relationship. ‘Geographies of Debt’ focuses on California’s prison industrial complex in order to examine how the capitalist’s debt that develops from surplus-value is negated through prison labor and the southern trope. “Dancing to Debt” investigates how Bollywood’s investment in making Pakistanis the guilty and punishable subject has developed alongside various modes of accumulation by dispossession that seemingly favor a Hindu nationalist political agenda, but have, in turn, made all brown bodies vulnerable to the terrorist trope and the military industrial complex. “Protesting Moral Debt” illustrates how the farmer suicides that have plagued India’s agrarian community for the last two decades are indicative of their moral debts to the land, the perennial creditor, and not, as popular media suggests, their monetary debts to various moneylenders, which debunks the authority of market fundamentalist discourse. Lastly, through an analysis of Italian neorealist cinema, “The Pleasure of Debt” reveals the effects of the pleasure creditor’s take in imposing suffering on the debtor and, likewise, the pleasure poor communities take in witnessing the decadence of elite culture.