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MEMS 4110: Precise Water Distribution System
No full textGreenhouse research requires precise, repeatable watering to maintain consistent experimental conditions. As plant counts scale to 150–360 pots, manual watering becomes inefficient, inconsistent. This project aims to design an automated irrigation system that reliably delivers controlled water volumes to an initial set of 36 pots, operates under greenhouse conditions with minimal user intervention, and provides a scalable foundation for future expansion
MEMS 4110: ASME Challenge
No full textThe goal of this project was to design and assemble a remote controlled device for a competition that can maneuver through a course, collect trash units from 3D-printed trash bins, and bring them to a receptacle at the end of the course. Important factors to consider in the design involved ensuring it followed traffic laws through the course, making sure it could operate multiple times, and fit within price and space constraints. Prototypes were tested against the ability to deliver 75 percent of trash units within 5 minutes, 50 percent of trash units within 5 minutes without any traffic violations, and making sure the device could dump trash units into the receptacle without spilling 5 times consecutively
MEMS 4110: Science Museum Bernoulli\u27s Demo
No full textThis report outlines the design and prototyping process of the Science Museum Bernoulli’s Demo (SMBD), a capstone project for MEMS 4110 Senior Design Project at Washington University in St. Louis. The SMBD is a fun game for a children’s science museum designed to demonstrate how the exit velocity of water from a pipe changes based on the pipe diameter. The design intends to teach kids about Bernoulli’s principle by allowing them to choose from two different sized pipes to spray water at a target. The key aspect of the game is that the water flows more slowly out of the larger pipe, so they have to aim the two pipes differently to hit a target at a fixed distance. The initial prototype consisted of platform used to apply pressure to a container of water and then spray water out of two pipes. The f inal prototype stabilizes the platform, and constrains the container of water to a piston to increase pressure. The pipes were also downsized to allow for a higher exit velocity and a more entertaining demonstration. The Science Museum Bernoulli’s Demo is a great way to teach kids about the basic of Bernoulli’s principle
Investigating Metabolic Heterogeneity in Engineered Isogenic Microorganisms
No full textEngineered microorganisms play an increasingly important role in the sustainable production of fuels, bioplastics, and other valuable biomaterials. Successful industrial deployment depends on maximizing product titers and ensuring process robustness at large scale. However, one of the major obstacles is non-genetic cell-to-cell heterogeneity arising from stochastic intracellular processes. Such heterogeneity can result in subpopulations that divert substrates toward growth rather than product biosynthesis, ultimately reducing yield and contributing to batch-to-batch inconsistency. To better understand the mechanisms by which cell-to-cell variation emerges, propagates, and impacts bioproduction, this dissertation investigated how intracellular energetic dynamics and stochastic biosynthetic noise contributed to metabolic heterogeneity and impact bioproduction, and developed strategies to enhance titer, yield, and productivity in both model and industrially relevant bioconversion systems. In Aim 1, we revealed how intracellular ATP dynamics influence microbial bioproduction by using an ATP biosensor to monitor energy levels across growth phases and carbon sources in Escherichia coli and Pseudomonas putida. We observed transient ATP accumulation during the transition to stationary phase that coincided with increased fatty acid (FA) and polyhydroxyalkanoate (PHA) production. We identified acetate and oleate as carbon sources that elevate steady-state ATP and enhance FA and PHA titers. ATP dynamics also served as a diagnostic indicator of metabolic burden, revealing pathway bottlenecks limiting limonene production, thereby demonstrating ATP’s utility as both a mechanistic and engineering handle. In Aim 2, we used time-lapse fluorescent microscopy and stochastic modeling to characterize noise propagation in a heterologous betaxanthin pathway. We found that over half of initially high-producing cells transitioned to medium or low production states within two doublings, demonstrating rapid phenotypic diversification. Model predictions identified a genetic circuit featuring enzyme-feedback-to-growth selection as the most effective for enhancing titer and productivity. We validated this prediction experimentally by coupling enzyme expression to nutrient availability, which enriched high-producing cells and increased overall betaxanthin titer by 4.4-fold. These results reveal how metabolic noise drives bioproduction heterogeneity and demonstrate that targeted circuit design can steer population dynamics toward improved production. In Aim 3, we examined the sources of heterogeneity in PHA production in P. putida by introducing a fluorescent reporter after additional copies of key enzymes phaC1 and phaJ4. Single-cell microscopy analysis revealed weak correlation between enzyme expression and PHA content in both genome-inserted strain and plasmid-bearing strain, suggesting other complex mechanisms behind cell-to-cell variation in PHA content. Based on the single-cell microscopy images, we speculated that the heterogeneity may stem from uneven PHA granule partitioning regulated by a family of proteins that are associated with the surface of intracellular PHA called phasin, identifying new regulatory targets for improving population-level uniformity. This dissertation establishes ATP dynamics, pathway-noise quantification, and growth-coupled circuit design as practical strategies to improve microbial production systems. By investigating and understanding sources of non-genetic cell-to-cell variation, these studies offer generalizable approaches to increase titer, yield, and batch consistency. The findings inform predictable strain engineering, identify new targets, and provide modeling and circuit-design frameworks adaptable to diverse industrial pathways
Essays in Financial Economics and Banking
No full textThis dissertation studies U.S. banks’ interest rate risk management, with a focus on how regulation, funding composition, and market conditions jointly shape maturity mismatch and hedging behavior. Across three chapters, I combine empirical evidence, theoretical modeling, and econometric methods to provide new insights into the evolution of risk exposure in the banking sector after the Global Financial Crisis. Chapter 1 uses publicly available data to document the evolution of banks’ maturity mismatch between 1997 and 2019. Before 2008, larger banks systematically carried greater maturity risk, while after 2008 this cross-sectional relationship vanishes, leading to a more homogeneous distribution of maturity profiles across banks. Estimating the effect of interest rate changes on banks’ equity, I show that this convergence also translates into more uniform equity exposure to policy shocks. These findings suggest that the standard Deposit Franchise Theory cannot fully explain observed risk-taking patterns. Complementary econometric evidence highlights correlations between maturity mismatch and equity ratios, funding composition, and interest rate spreads, motivating the need for a new framework. Chapter 2 develops a framework to explain the “Catching Up” phenomenon by embedding stan- dardized, asset-level capital requirements into a mean–variance portfolio model. Using panel IV local projections, I first document a structural break in the equity exposure of non-large banks after 2010, consistent with the implementation of Basel III. This motivates the introduction of capital requirements into the model, which shows that binding constraints reduce heterogeneity in optimal risk-taking and, under certain market conditions, can even increase aggregate exposure despite rising volatility. Finally, I test the model’s predictions with GARCH-based estimates of returns and variances and find that securities and non-mortgage loans uniquely met the conditions for increased exposure during 2008–2015, consistent with the empirical evidence. Chapter 3 decomposes banks’ interest rate risk into balance-sheet maturity mismatch, franchise value (FV) duration, and derivative positions. The main contribution is to show that FV duration is positive for most U.S. banks and increases systematically with bank size, reinforcing rather than offsetting balance-sheet exposures. This implies that large banks are structurally more exposed to interest rate risk through their FV, even though maturity mismatch has become more homogeneous across banks since 2008, as documented in Chapter 1. At the same time, I document that large banks extend duration further through long interest rate swap (IRS) positions, raising the question of why large banks add risk off the balance sheet. As an extension, I propose a bond–IRS substitution channel, in which large banks rely on cheaper bond financing to manage liquidity risk, while smaller banks hedge deposit volatility through swaps
Hydroclimate Dynamics from the North Atlantic to the Tropical Pacific: Water Isotope Perspectives from 850-2100 CE
No full textHydroclimate variability plays a central role in shaping ecosystems, agricultural productivity, and water security, yet its response to anthropogenic forcing remains uncertain. Facing growing risks from floods, droughts, and shifts in circulation patterns, our ability to anticipate and diagnose hydroclimate change has become a critical scientific priority. However, the instrumental record is too short to capture the full range of natural variability, and models often diverge in their projections of water cycle change in many regions of the world. Observations, proxies, and modeling of stable O and H isotope ratios in water (hereafter, “water isotopes”) offer a unique opportunity to address these gaps, as they integrate signals of temperature, precipitation, circulation, and moisture transport at local to global scales, and geologic archives preserve these signals on timescales that extend beyond the instrumental period. This dissertation employs novel approaches to intercomparing water isotope proxy data and isotope-enabled climate model simulations to examine hydroclimate variability from the start of the Last Millennium (1000 C.E.) through the industrial era, and into the future. First, I perform a synthesis of isotope-based proxy records to evaluate the far-reaching hydroclimate impacts of major features of the climate system like the North Atlantic Oscillation (NAO) and compare these results with model simulations. I find stronger multidecadal variability in the NAO than is captured by models, highlighting that models may not capture the full range of low-frequency dynamics in future projections. I then use a novel approach to detecting change points in spatiotemporally incomplete time series to identify the timing of industrial-era hydroclimate transitions which are often obscured by natural variability. This analysis of globally distributed proxy records is the first systematic evaluation of the timing of global hydroclimate shifts across the industrial transition. Tropical and monsoon-sensitive records identify a reorganization of hydroclimate around the onset of industrial forcing but preceding the onset of global mean warming. The spatial pattern of these changes implicates reorganizations of tropical circulation as drivers of globally coherent isotopic trends. These results indicate that tropical ocean-atmosphere interactions play a central role in mediating the sensitivity of the water cycle to anthropogenic forcing. Finally, I explore the combined impacts of anthropogenic warming and large-scale atmospheric dynamics on the hydrologic cycle in experiments of future warming. I use an isotope-enabled projection of 21st century climate under high greenhouse gas forcing to demonstrate that, despite a weakening of the Pacific and Indian Ocean Walker Circulation, thermodynamic changes in atmospheric water vapor drive a greater reliance on remote moisture sources across the tropical oceans. By bridging proxy evidence, modern observations, and isotope-enabled modeling, this dissertation advances understanding of the mechanisms governing hydroclimate variability across inter-annual to centennial timescales. The findings highlight the value of applying novel methodological approaches to leveraging the information contained in water isotope proxy and observational data, applying these lessons to improve the fidelity of climate models, sharpen estimates of regional rainfall change, and inform water resource planning and risk assessment in a warming world
RAGE Directed Control of the Bone Matrix and Mechanical Modifications in Type 2 Diabetes
No full textType 2 Diabetes (T2D) is an increasingly prevalent disease which can be detrimental to a person’s quality of life, especially when combined with comorbidities. Some of the most significant comorbidities occur in the musculoskeletal system where skeletal fragility, osteoarthritis, and low back pain. Vertebral fractures specifically are 3.1xs more likely to occur in post-menopausal women with T2D, a fact that is counterintuitive to T2D patient’s presenting with an increase in bone mineral density (BMD). This disparity between vertebral bone mass and fragility fracture incidence suggests that there are mechanisms contributing to vertebral fracture independent of bone mass. This highlights the importance of studying alterations to the bone matrix material properties and the activity of bone cells responsible for maintaining that matrix in T2D. The hyperglycemic state in T2D contributes to the formation and accumulation of advanced glycation end-products (AGEs). The accumulation of AGEs impairs bone biomechanics via increasing collagen cross-linking and is a potential mechanism contributing to T2D skeletal fragility. AGEs not only directly alter the bone matrix, but they can have a negative effect on bone cells by activating the receptor for advanced glycation end-products (RAGE) which upregulates inflammatory pathways. The role of RAGE signaling in bone homeostasis and the control of bone strength remains relatively unknown. RAGE signaling and AGE accumulation may disrupt bone homeostasis and impair bone mechanics by altering bone cell function. Our hypothesis is that targeting RAGE may be a viable approach to restore bone cell function and rescue mechanical deficits in bone observed in AGEs-enriched pathologies like T2D. This dissertation aims to elucidate the role of RAGE signaling in bone homeostasis and matrix mechanics under type 2 diabetic conditions. This was addressed by the completion of three specific aims. First, evaluated whole bone mechanics, morphology, and AGE concentration in a mouse model of T2D and determined how those factors would be altered when we ablate RAGE signaling. As expected, with T2D bone had increased AGE concentration and impaired mechanical properties, some of these impairments were improved with the ablation of RAGE signaling. The second aim of this dissertation focuses on the cancellous bone matrix and characterizes bone cell activity, osteocyte density, and bone material properties in T2D mice with and without RAGE signaling. Here we showed that RAGE ablation improved matrix mechanics in T2D bone and osteocyte lacunar density. Finally, the third aim hopes to translate the prior results to a clinically relevant model. Here we determined whether or not a RAGE inhibition therapy could recapitulate the changes to the bone cell activity and matrix mechanics from the genetic model of RAGE ablation. RAGE inhibition resulted in similar matrix mechanical alterations to the genetic RAGE ablation model and there were improvements in longitudinal bone homeostasis. With the completion of these aims we have uncovered that bone matrix mechanics in T2D is at least partially controlled by RAGE signaling and warrants further research as a therapeutic approach for T2D bone fragility
Integrating Physics and Deep Learning for Transmission-less Attenuation Compensation in Clinical SPECT
Get PDFAttenuation compensation (AC) is beneficial for visual interpretation and serves as a prerequisite for quantification tasks in single-photon emission computed tomography (SPECT) imaging. However, conventional AC methods typically rely on a separate X-ray CT component, leading to multiple challenges. In this context, studies have shown that scatter-window projection data contains information to estimate the attenuation distribution. Furthermore, large amounts of SPECT emission data in both photopeak and scatter-energy windows and corresponding CT scans are available. The ability of deep learning (DL) to model complex relationships by leveraging large datasets motivates its use for transmission-less AC in SPECT. Building upon the idea of integrating physical and DL techniques, this dissertation proposes scatter-window projection and DL-based AC methods for SPECT: CTLESS for myocardial perfusion SPECT and DaT-CTLESS for dopamine transporter SPECT. The proposed CTLESS method was evaluated on the clinical task of cardiac perfusion defect detection. This task-specific evaluation was motivated by another study conducted in this dissertation demonstrating that evaluating using visual fidelity metrics may not correlate with performance on clinical tasks. We evaluated the CTLESS method on the clinical task in both an anthropomorphic model study and a multi-reader multi-case human observer study involving physician readers with expertise in detecting cardiac defects in myocardial perfusion SPECT images. The CTLESS method yielded similar receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) compared to the standard-of-care CT-based AC method (CTAC) and demonstrated statistical non-inferiority to CTAC. Moreover, CTLESS significantly outperformed a method without AC (NAC). These findings were consistent across stratified analyses by sex and defect types. Additionally, CTLESS demonstrated strong generalizability on the clinical task across different SPECT scanners. The proposed DaT-CTLESS method was evaluated in an \textit{in silico} imaging trial that simulated patient variability and SPECT system physics. DaT-CTLESS yielded a similar performance to CTAC and significantly outperformed an AC method that uses uniform attenuation maps (UAC) on the task of regional uptake quantification. Furthermore, DaT-CTLESS significantly outperformed UAC in distinguishing patients with normal versus reduced putamen-specific binding ratios. These findings demonstrate the capability of CTLESS and DaT-CTLESS for transmission-less AC in SPECT and provide evidence for the potential clinical translation
Voting Under the Federal Constitution
Get PDFThere is no explicit, affirmative right to vote in the federal Constitution. At the Founding, States had total discretion to choose their electorate. Although that electorate was the most democratic in history, the franchise was largely limited to property-owning White men. Over the course of two centuries, the United States democratized, albeit in fits and starts. The right to vote was often expanded in response to wartime service and mobilization.A series of constitutional amendments prohibited discrimination in voting on account of race (Fifteenth), sex (Nineteenth), inability to pay a poll tax (Twenty-Fourth), and age (Twenty-Sixth). These amendments were worded as anti-discrimination provisions with nearly identical language. Although they vastly expanded who was eligible to vote, these constitutional amendments’ negative framing permits States to disenfranchise voters through facially neutral requirements, such as felon disenfranchisement laws.Starting in the 1960s, the Supreme Court relied on the Equal Protection Clause—rather than the voting rights amendments themselves—to protect the “fundamental” right to vote, applying strict scrutiny to voting qualifications. This line of cases comes closest to recognizing an affirmative right to vote that receives protection even absent an invidious facial classification. These decisions, combined with the Voting Rights Act of 1965 (VRA) and the civil rights movement, helped eradicate Jim Crow.This chapter charts how the United States democratized, and its focus is on voting qualifications under the federal Constitution. As this chapter demonstrates, democratization has been accomplished through federal constitutional amendments, state-law changes, judicial decisions, and popular support during or shortly after wartime
Fiber-Based Speckle Contrast Optical Tomography in Humans
No full textCerebral blood flow (CBF) is an important biomarker for indicating many brain diseases, such as stroke and traumatic brain injury. Therefore, the development of real-time CBF measures in the clinic is desired, and many techniques have been developed to measure CBF. However, the current standard techniques, including positron emission tomography (PET), arterial spin labeling magnetic resonance imaging (ASL-MRI), and computed tomography (CT) perfusion are limited to the high instrument cost, massive size, and the requirement of ionizing radiation, and thus are not able to map CBF at the bedside. Furthermore, these techniques offer only snapshots due to scanner logistics. An alternative optical modality is diffuse correlation spectroscopy (DCS); however, DCS requires a sensor with very high temporal resolution and has a lower signal-to-noise ratio (SNR) because it measures only one speckle at a time. Speckle contrast optical tomography (SCOT) is an attractive optical technique that can address the challenges in current CBF measurement techniques. SCOT offers a cost-efficient, radiation-free, and portable optical method for continuously mapping CBF. It also overcomes the SNR limitation in DCS by simultaneously aggregating many speckles. The current free-space design of SCOT has been shown to have similar results as in fMRI in phantoms and rodents. However, this design is difficult for imaging CBF in humans due to the focus challenge through a large region of the brain and the signal attenuation caused by hairs. Thus, this research focuses on developing a fiber-based SCOT to overcome these challenges. A fiber-based design can adapt to the complex shape of a head and can comb through the hairs to obtain a good signal. To investigate the unknown performance of a fiber-based SCOT in humans, we developed a computational modeling method to simulate the measurement and images of a fiber-based SCOT. In addition, to address to limitation of the current models that use only the homogeneous model and do not include system noise, we developed a reconstruction method based on an anatomical head model from MRI with five tissue layers and an array with 24 sources and 28 detectors with multiple noise models. Results show that including longer source-detector distances reduces the localization error of the SCOT reconstruction. Moreover, even though SCOT signals are smaller with increased exposure time, the SNR increases by 1000X by extending exposure time from 10 µs to 10 ms. In experimental results, we demonstrate that cost-efficient multi-mode fiber (MMF) bundles can be used to relay flow. Furthermore, speckle statistics can be used to distinguish speckle signals and noise. Finally, we demonstrate the feasibility of measuring pulsatile blood flow in humans through MMFs and show that they can be used to develop a SCOT system