COORDINATED TRAFFICKING OF HEME TRANSPORTERS BY CARGO SORTING COMPLEXES IS ESSENTIAL FOR ORGANISMAL HEME HOMEOSTASIS

Heme, an iron-containing organic ring, is a vital cofactor responsible for diverse biologicalfunctions and is the major source of bioavailable iron in the human diet. As a hydrophobic and cytotoxic cofactor, heme must be transported in a highly controlled manner through membranes via specific intra- and inter-cellular pathways. However, the genes and pathways responsible for heme trafficking remain poorly understood. Unlike other metazoans, Caenorhabditis elegans cannot synthesize heme but requires heme for sustenance. Thus, C. elegans is an ideal animal model to identify heme trafficking pathways as it permits organismal heme homeostasis to be directly manipulated by controlling environmental heme. Heme is imported apically into the intestine by HRG-1-related permeases and exported basolaterally by MRP-5/ABCC5 to extra- intestinal tissues. Loss of mrp-5 causes embryonic lethality that can be suppressed by dietary heme supplementation raising the possibility that MRP-5-independent heme export pathways must exist. Here we show, by performing a forward genetic screen in mrp-5 null mutants, that loss of the vesicular cargo sorting Adaptor Protein complexes (AP-3) fully rescues mrp-5 lethality and restores heme homeostasis. Remarkably, intestinal heme accumulation due to mrp-5-deficiency causes a concomitant deficit in the lysosomal heme importer HRG-1 abundance and localization. Loss of both MRP-5 and AP-3 subunits resurrects HRG-1 levels and localization, thus underscoring the crucial role of HRG-1 in dictating mrp-5 mutant phenotypes. In the absence of MRP-5, heme is exported by SLC49A3 homolog, a previously uncharacterized transporter. Live- cell imaging reveals vesicular coalescence that facilitates heme transfer between the importers and exporters at the interface of lysosomal-related organelle. These results define a mechanistic model for metazoan heme trafficking and identifies SLC49A3 as a promising candidate for heme export in mammals

Decreased Host-Cell ATP Levels Affects Bacteriophage Replication in Knockout E. coli Strains

Bacteriophages are viruses that use host cell metabolic resources for replication. Altering Escherichia coli's ATP production pathway can inhibit bacteriophage replication, offering a new approach to bacteriophage therapy.The atp genes encode ATP synthase subunits crucial for ATP generation in E. coli. Knockouts ΔatpA, B, D, E, and H, alongside the parent strain, were studied. Focus narrowed to ΔatpA and B due to significant deviations from the parent strain. It is hypothesized that these knockout strains reduce growth in E. coli and bacteriophage due to decreased ATP production, vital for metabolism and phage replication. Comparative growth assays of E. coli parent and ATP knockout strains were conducted in LB-rich media and M9 minimal media. T4 bacteriophage replication was measured through lysis curves, plaque assays, and two time-point phage titer experiments, chosen for consistent replication. Characterization of T4 bacteriophage replication revealed ΔatpA's crucial role, showing difficulties in growth and lysing. ΔatpA required 10-4 dilutions in phage titer experiments due to low PFU/mL, contrasting with 10-7 dilutions for other strains. ATP assay data showed significantly lower ATP concentration (319nM) in ΔatpB compared to the parent strain, also implying its crucial role in ATP synthesis.Future research will focus on characterizing phage replication in ATP synthase knockout strains using E. coli ATP synthase inhibitors to deepen understanding of phage-host interactions. Controlled bacteriophage manipulation can be studied further to have a better understanding of the application of bacteriophage therapy and to potentially improve its clinical efficacy

Magnetic and Toroidal Symmetry of Lithium Transition Metal Orthophosphates

LiCoPO4 is the foremost candidate material for a novel type of ferroic ordering calledferrotoroidicity. In this work, the synthesis of polycrystalline sample of LiCoPO4 is discussed, along with the structural analog LiMnPO4. Their magnetic susceptibility and magnetic structure were determined and analyzed and found to be consistent with previous reports on single crystal materials. This work also provides a thorough introduction to ferrotoroidicity, a history of its theoretical development, and a summary of the most studied candidate materials. The work then presents a detailed methodology for determining the toroidal structure which would result for the magnetic structure in candidate ferrotoroidal materials. The model provides a method for determining how many toroidal moments would be present, where they would be located within the unit cell, and along which crystallographic direction they would be oriented. Detailed examples for determining the magnetic structure are provided for LiCoPO4 and analogous structures with the olivine structure type, as well as several structures with the pyroxene structure type. The results demonstrate a method for understanding ferrotoroidal arrangements, anti-ferrotoroidal arrangements and non-toroidal structures

Essays on Information and Non-Bayesian Beliefs

In this dissertation, I present a comprehensive discussion of a class of biases within the realm of probabilistic reasoning, namely confirmation bias (encompassing or closely related to commonly seen terms in the literature such as motivated reasoning and wishful thinking). The dissertation consists of three main chapters. In Chapter 1, I propose a new and improved belief updating model that can accommodate both motivated and unmotivated confirmation bias. The model improves upon existing models in its ability to explain data better, and its applicability to settings beyond binary-state spaces. I characterize the model with three intuitive axioms. In two extended applications, I show that the model establishes a link between confirmation bias and several well-known phenomena, such as the significance of first impressions, the polarization of beliefs, and the perseverance of inaccurate beliefs. In Chapter 2, I turn to the experimental elicitation of motivated and unmotivated confirmation bias. Previous experiments have provided evidence for motivated and unmotivated confirmation bias individually, but never discussed the possibility that the two can occur together in depth. This chapter presents one of the first experiments that examines both forms of confirmation bias together. Subjects were asked to update their beliefs regarding both politically contextualized questions and neutral questions. Subjects exhibited both motivated and unmotivated confirmation bias, but there was also significant heterogeneity among them. Notably, motivated confirmation bias is significantly stronger in later rounds of the experimental tasks, which may be correlated with the shorter response times in the later rounds. In Chapter 3, which is joint work with Emel Filiz-Ozbay, we discuss wishful thinking (motivated confirmation bias) within a major application. In a rational inattention setting where consumers acquire information on the good’s quality before making purchasing decisions, we examine the implications of the presence of consumers with wishful thinking. These biased consumers are unaware of their bias, and weigh any good news about the product quality more heavily than a Bayesian consumer. The firm, which aims to increase the volume of sales, can strategically constrain the accuracy of the information that consumers can acquire. We show that in the presence of biased consumers, a firm would find it profitable to constrain information acquisition unless the prior belief on the quality of the product is too low. We characterize the conditions under which the entry of a competitor firm can effectively alleviate this type of exploitation. Our findings shed light on the incentives of review platforms for bombarding wishful consumers with low quality product reviews and limit consumers’ ability to identify to reviews with informative contents

ESSAYS ON THE ECONOMICS OF EDUCATION

In this dissertation, I examine various factors shaping students’ trajectories and opportunitieslater in life. In Chapter 1, I explore the role of grade retention policies. Grade retention as a remedial policy is controversial because the benefits of extra instruction time may not outweigh its costs. Previous research has primarily examined retention for specific grades. By exploiting plausibly exogenous variation in retention generated by a nationwide promotion policy in Chile, I demonstrate that retention timing is critical in determining its effect on academic performance and access to higher education. Being held back only reduces the probability of future grade retention for young primary students. Additionally, older primary students are less likely to return to school the following academic year or graduate from high school. High school grade-retained students are the most affected, with a 10-20 percentage point reduction in their likelihood of high school graduation, and many switch to adult education in response to retention. Interestingly, even though high school students who are held back are just as likely to take the college admission test, they show a positive 0.1 SD increase in Spanish and math performance. Then, in Chapter 2, I focus on the impact of massive and sudden school closures followingthe 2011 nationwide student strike in Chile on teenage pregnancy. We observe an average increase of 2.7% in teenage pregnancies in response to temporary high school shutdowns, equal to 1.9 additional pregnancies per lost school day. The effect diminishes after three quarters since the strike’s onset. The effects are predominantly driven by first-time mothers aligned with highschool absenteeism periods and are unrelated to the typical seasonality of teenage fertility or pregnancies in other age groups. Additionally, we document that the strike had a larger disruptive role by affecting students’ educational trajectories, evidenced by a persistent increase in dropout rates and a reduction in college admission test take-up for both female and male students. Lastly, in Chapter 3, I explore inequalities in performance associated with the school typestudents attend, particularly the contribution of teachers to student performance in Chile’s college admission test (PSU). Our analysis is based on a unique teacher-student matched dataset and decomposition methods. The findings suggest that teachers’ performance on the PSU and the characteristics of their educational degrees are significant predictors of students’ success. When controlling for students’ and predetermined school characteristics, the gap between voucher and public schools reduces. Productivity differences emerge as key factors driving the disparities across school types. The analysis underscores the crucial role of teacher-student interactions in shaping student outcomes

ARE CANADA’S NET-ZERO PLANS ACHIEVABLE, PRUDENT, AND DURABLE?

Canada is a major oil- and gas-producing country that has committed into law the goal of achieving net-zero greenhouse gas (GHG) emissions economy-wide by 2050. Yet the prospect of reduced Canadian oil production has major domestic political and economic implications. Climate change mitigation requires sustained policy engagement, and so policymakers must endeavor to make climate policy that is politically durable. Scenario analysis is a vital decision-support tool for understanding these transition dynamics associated with pursuit of net zero. The first paper in this dissertation explores transition dynamics for Canada across several scenarios with detailed policy representation for achieving net-zero GHG emissions by 2050 using the Global Change Analysis Model (GCAM), an open-source multi-sector dynamics model. The results highlight the importance of effective policy implementation and the variation in transition dynamics attributable to socioeconomic and technological assumptions, carbon dioxide removal scalability, and non-CO2 mitigation. The second paper in this dissertation uses GCAM to examine the sensitivity of Canadian oil production to several external forces in pursuit of net zero. The results show that forces outside of Canada’s control are highly determinative of future oil production levels in Canada. But if Canada moves toward net-zero GHG emissions on its announced timeline, it can reduce the magnitude of the additional declines in Canadian oil production attributable to external forces. Such a move would give Canada greater autonomy to shape transition outcomes in a way that best balances domestic societal priorities. The alternative would be for external forces to thrust a transition upon Canada without regard for such domestic concerns. The third paper in this dissertation examines how these domestic political forces impact Canada’s pursuit of net zero using archival analysis followed by scenario analysis in GCAM. The results of the qualitative policy analysis highlight that a little more than one third (9 of 26) of the modeled policies are less likely to be politically durable, because they fail tests of pan-political acceptability or pan-regional acceptability or both. Reductions in net GHG emissions are significantly smaller in modeled current-policy scenarios where these nine policies are rolled back after 2025. Accordingly, the policies identified as less likely to be politically durable demand greater focus to build stronger cross-party and cross-regional support

BIOMATERIAL BASED STRATEGIES FOR VIRAL AEROSOL CAPTURE AND PREVENTION OF RESPIRATORY INFECTIONS

In the 2022-2023 flu season, the Center for Disease Control (CDC) estimated 21,000 deaths and 31 million symptomatic illnesses in the United States. Current FDA approved antivirals for influenza are grouped into three categories, matrix protein 2 (M2) inhibitors, neuraminidase inhibitors (NAI) and polymerase acidic protein cap-dependent endonuclease (CEN) inhibitors. However, limitations of these treatments have been evident. For example, NAI inhibitors require early treatment to be efficacious and some influenza strains can develop resistance to both NAI and CEN inhibitors. Thus, there is a need for new classes of antivirals as well as better understanding of influenza transmission and monitoring of influenza to inform development of efficacious interventions. In chapter 2 we describe how we design biomaterials inspired by the physiological characteristics of mucus to capture and trap pathogens. We performed studies to establish this material as a suitable substrate for viral capture and release after collection using advanced aerosol capture technology. In chapter 3, we formulate an antiviral based around polyinosinic polycytidylylic acid (polyIC). PolyIC is commonly used in research as an adjuvant in vaccine delivery through its targeting of Toll like receptor 3 (TLR3). This pathway also results in type 1 and 3 interferon production, which in turn stimulate a range of antiviral mechanisms. Because of this, it has also been investigated as a prophylactic or treatment to various viruses, including hepatitis B virus, human immunodeficiency virus and rhinovirus. However, due to stability and toxicity concerns, it has not been implemented as an inhaled treatment to induce local immunity in the lungs at the site of infection. Towards this end, we used polyethylene imine-polyethylene glycol (PEI-PEG) copolymer to condense PolyIC into nanoparticles to enhance their bioavailability in target cells. By combining the two, we can utilize the antiviral capabilities of Poly(IC) while minimizing the dosage concentration to therapeutic levels

Effects of Plastic Bag Regulations on the Chesapeake Bay

Microplastic pollution in waterways poses a critical environmental challenge worldwide by having long lasting effects on wildlife, human health, and ecological balance. To address this issue, many local governments have implemented plastic bag bans as a mitigation measure. This research investigates the effectiveness of such policies in reducing microplastic levels within the Chesapeake Bay Watershed by drawing data from the USGS Water and Chesapeake Bay Data Hub. After merging plastic ban status from each county’s website with water quality data, we examined changes in particulate inorganic carbon and total organic nitrogen levels across various locations surrounding the Chesapeake Bay. Previous research reveals that higher levels of microplastics in water typically increases the amount of organic nitrogen present in the water and decreases the amount of inorganic carbon found in the water. Since our current data contains water quality up until 2021, Harford county is the only county with an effective plastic ban. Because of this, we do not yet have conclusive evidence regarding the effectiveness of plastic bans on microplastic pollution levels. Despite inconclusive findings, this study underscores the importance of addressing microplastic pollution for environmental sustainability and underscores the need for further investigation to inform policy-making and conservation efforts

Fine Tuning Sol-gel Synthesis and Further Applications

Sol-gel synthesis consists of the hydrolysis and polycondensation of alkoxide precursors to result in a glass-like material. Within these sol-gels, properties of the bulk liquids can be regulated by pore size of the sol-gels. Previous research has suggested that the mechanical stresses are predominant during the drying process of the sol-gel synthesis because the constrained sol-gels must shrink and debond from the substrate. Although the sol-gels may not fracture during this stage, increased stress may cause cracking as they are subject to higher temperatures during the firing process. This experiment involves modifying the procedure to assist in separating the gel from the substrate and reducing the effect of higher temperatures during the firing process. Major results to date have centered around optimization of the sol-gel synthesis process and production of gels with good optical quality. Through calculated edits to the procedure such as troubleshooting the amount of stir time, temperature, and adding new reagents such as RainX in the polyethylene tubes, yield has increased by 84% from our first to most recent batches prior to firing. After successful synthesis, the sol-gels can be used to study the behavior of monomers and confined liquids through optical spectroscopy. Future projects include immersion in a monomer with rhodamine 6G dye to create fluorescent nanoparticles controlled by the pores of the gel

Cool Diffusion Flames and Their Applications on Earth

Cool diffusion flames are a type of diffusion flame that burns at a much lower temperature (~700 K) than a traditional hot flame. Discovered in 2012 on the ISS, these flames have been a growing research topic for the last decade. These flames are observed at UMD through a dual hot plate setup in which a pool of a liquid hydrocarbon is heated. An intensified camera and color camera were used to view the movement of the flames and take pictures of the flames, respectively. Thermocouples attached to the apparatus output temperatures of both plates as well as the flame temperature. An anemometer was used to measure flow in the vent above the apparatus, and a formaldehyde sensor was used to track formaldehyde yield of the flames. The fuel that created the most stable flame, n-heptane, was found to work best at a lower heater temperature of 105-110 degrees Celsius and an upper heater temperature of 400-420 degrees Celsius. The peak temperatures of these flames rested between 420-440 degrees Celsius (693-713 K). It is possible that cool flames could be applicable to increasing efficiency in gasoline engines by using them to ignite the hot flame. Results from these experiments could help to improve the accuracy of models that can simulate these technologies