The use of opioid drugs for pain management in postoperative settings has been widespread since the 1860s. However, the risk factor for developing an opioid use disorder (OUD) has increased substantially with its continued use, with addiction rates of more than 10% for those taking opioids. An obstacle to abstinence in opioid addiction are the adverse side effects that occur during cessation of drug use once dependence has formed, including nausea, anxiety, vomiting, and depression. The Nucleus Accumbens (NAc) is part of the mesocorticolimbic reward pathway. Decades of pharmacological studies demonstrate that nearly all abused drugs evoke dopamine release within the NAc, thus altering innate systems for how reward is processed. The activity of NAc neurons is strongly regulated by efferent excitatory input from numerous brain regions. The paraventricular thalamus (PVT) a relatively understudied brain region, regulates behavioral responses to reward and aversive stimuli as well as to drugs of abuse such as morphine. Our preliminary data demonstrate that the activity of these projections is highly regulated by the Cannabinoid 1 Receptor (CB1), which mediates the primary psychoactive effect of cannabis. This is particularly relevant on account of recent clinical findings demonstrating that activation of CB1 can ameliorate the aversive effects of opiate withdrawal. Using fiber photometry (which uses fluorescence emission of the calcium sensitive fluorophore, GCaMP, as a proxy measurement for neural activity), I have shown that this circuit is activated by aversive stimuli and inhibited by rewarding stimuli. Furthermore, treatment with morphine can attenuate the pain-induced activation of this circuit. However, whether cannabinoids can influence this circuit's activity to reduce withdrawal symptoms remains untested. Our research will contribute to our understanding of the neurophysiological basis for opiate withdrawal and how cannabinoids could represent a novel class of therapeutics for the treatment of opiate use disorder.

Addiction is characterized by the compulsive use of substances despite adverse consequences, a process closely linked to dopamine-induced changes in the Nucleus Accumbens (NAc) and its role as the brain's "reward center." The NAc integrates information from various brain regions, including the Paraventricular Thalamus (PVT), to produce motivated behaviors. Recent studies have identified the PVT, especially its anterior segment (aPVT), as a critical hub in addiction neurocircuitry, but findings have been inconsistent, likely due to the PVT's heterogeneity and the specific neurochemical and anatomical properties of its connections to the NAc. Prior research has shown that aPVT neurons, identifiable by neurotensin expression, send excitatory projections to the NAc, which are modulated by endogenous cannabinoids (eCBs). These interactions suggest a complex regulatory mechanism. Preliminary experiments used techniques including transsynaptic viral tracing and in vivo calcium imaging, to study the activity dynamics of NAc neurons, particularly those expressing Proenkephalin (PENK) and receiving aPVT inputs, during reward-seeking tasks. I propose to extend these findings by employing a multidisciplinary approach that combines experimental neuroscience with sophisticated computational analysis. By applying dimensionality reduction techniques, clustering algorithms, and machine learning models to neural and behavioral data, I aim to map the functional connectivity within the NAc and elucidate the roles of specific neuronal ensembles in reward-seeking behavior. This comprehensive analysis will not only clarify the neurobiological underpinnings of addiction but also contribute to the development of targeted therapies for addiction and related disorders, leveraging the unique intersection of computational neuroscience and behavioral analysis.

Two-dimensional (2D) materials are layered materials made up of either a single or very few atomic layers. The properties they exhibit are fundamentally different from those of three-dimensional crystals, and they provide us with high levels of control to design novel systems in order to study new physical phenomena. 2D dielectrics are used in electrostatic gating to control the displacement field and carrier doping being applied to a 2D sample, making the properties and performance of 2D dielectrics very important. In 2D heterostructure devices, the standard dielectric used is hexagonal boron nitride (hBN). However, a recently published paper  claims that the novel 2D dielectric Bi₂SeO₅ is readily exfoliated, transferrable, and has a dielectric constant of 15, significantly higher than that of hBN, which ranges between 3-4. In this project I aimed to determine the dielectric constant and breakdown characteristics of Bi₂SeO₅ in hopes of finding a more effective substitute for hBN. I successfully measured the dielectric constant of Bi₂SeO₅ by fabricating a 2D graphene heterostrcuture device and taking graphene transport measurements comparing hBN and Bi₂SeO₅. From the data obtained I found the dielectric constant to be 14.3, which agrees with literary values. I fabricated a Bi₂SeO₅ backgate using a dry transfer technique in order to perform characterize the breakdown characteristics of the dielectric. By applying a voltage to each contact, grounding the gates, and then floating all other contacts, I measured the current passing through the dielectric until we began to see an exponential trend in order to measure breakdown. This is of interest because if Bi₂SeO₅ is proven to be more effective than hBN, it would let us apply a higher displacement field and doping to samples which would let us access new, exotic phases in 2D materials such as WTe₂.

The Campanian stage of the Cretaceous (~84–72 million years [Ma]) was the zenith of dinosaur diversity. Western North America is highly fossiliferous and preserves Campanian-age rock units throughout the Western Interior Basin. Most studies that investigated dinosaur diversity from this interval used data obtained from macrosites (e.g., skeletons), whereas few have investigated vertebrate microfossil sites. Vertebrate microfossil sites are a rich source of data on biodiversity (e.g., taxon richness, relative abundance) and how it changes through time. The Judith River Formation of north-central Montana is rich in vertebrate microfossil sites, preserving 4 million years of the Campanian (~79–74 Ma). Here we aim to observe patterns of dinosaur diversity in the Judith River Formation by quantifying dinosaur taxon richness and relative abundances based on dinosaur teeth from two stratigraphically and temporally separated microfossil sites. These sites are the lower Makela-French 1 (~77 Ma) and the upper Clamfetti (~75 Ma). Presently, we have 300 specimens out of a planned 400. We hypothesize that changes in diversity and abudance occurred between these two sites. Our preliminary results reveal a change in dinosaur diversity between Makela-French 1 and Clamfetti. Hadrosaurs and ceratopsians are present and relatively abundance at both sites, whereas ankylosaurs decrease in abundance from Makela-French 1 to Clamfetti. Small herbivores like pachycephalosaurs and hypsilophodonts are rare at both sites. Theropods show similar patterns to the herbivore’s trends. Tyrannosaurs and dromaeosaurs are common at both sites, whereas troodontids are absent from Makela-French 1. These preliminary findings reflect diversity patterns that are not easily observable solely through the collection of dinosaur macrofossils. Our continued collection of fossils from Makela-French 1, Clamfetti, and additional sites will increase our sample size and provide better fine-scale resolution of dinosaur diversity patterns during this crucial interval in their evolution.

Physics concepts dealing with charges, particles, and electricity are difficult to conceptualize, yet foundational for students' scientific understanding. As an undergraduate researcher at the Novel Observations in Mixed Reality (NOMR) lab, I work on developing virtual reality applications for introductory physics lab courses at UW. To develop tools and scenarios for the labs, we use C# in Unity. One of the tools that I worked on developing was the Charge Tool, a tool that allows students to change particle charges and experiment with the relationship between charge and force according to Coulomb's Law. We conducted usability testing by taking participants with different levels of familiarity with VR, using the “think aloud” method. Through this, we identified user pain points for ease of use and ensuring an easier learning curve for students who are new to using VR. Based on key insights, we improved the particle colors to being more intuitive and color-blind friendly, as well as redesigned the tool to make it more functional and easier to use. I also work on a decay particle project that focuses on the principle of conservation of charge, momentum, and mass-energy, and a tutorial project which allows students to access instructions and lab manuals inside the VR lab scene. Since virtual reality is still pretty new in the field of education, research in it becomes important as it allows students to interact with physics concepts in a way that they never have before.

Mycobacterium abscessus are non-motile bacilli that cause soft-tissue and pulmonary infections, commonly in healthcare settings or patients with cystic fibrosis. Though it is considered an opportunistic pathogen, its many virulence factors signal its potential for evolution into a true pathogen. Upon infection, the bacilli are internalized by macrophages, forming granulomas to contain the infection. Macrophages can harbor bacilli during infection stages and induce drug resistance by expelling toxins through ABC transporters. Treatment is often challenging as M. abscessus is intrinsically resistant to many antibiotics. Current treatment uses a combination of two or more intravenous drugs and one or more oral antibiotics over several months. Treatment success is challenged by patient adherence and may also be impacted by drug efflux by macrophage ABC transporters. Transporters identify certain drugs as toxic to the body and try to flush them out of the cell. Since Mycobacteria infect macrophages, these channels pose a significant disadvantage to treatment since the cell will actively efflux the drug, preventing the drug's intracellular concentration from increasing to an effective level against the bacilli inside. Certain drugs are known to inhibit ABC transporters, and the addition of these inhibitors in treatment could increase bacteriocidal activity and reduce the development of drug tolerance. First, we will determine the drug's minimum inhibitory concentrations to each inhibitor to see if there is an intrinsic activity on M. abscessus. Next, we will use the Human THP-1 cell line infect with Mycobacterium abscessus and treat with known ABC transport inhibitors in concert with a current therapeutic drug, Clarithromycin. They will then be plated at various time points to determine the colony-forming units. If efflux by macrophage transporters reduces the efficacy of Clarithromycin, bacteriocidal activity will increase between the combination therapy and the clarithromycin-only treatment. These results may improve the current treatment regimens for M. abscessus.

The nucleolus is an essential subnuclear organelle that performs central regulatory roles in cellular metabolism, epigenetic programming, and stress signaling. In mammals, nucleoli are disassembled and rebuilt de novo with each cell division, through an elaborate assembly mechanism that has long eluded molecular characterization. This assembly process is spatiotemporally controlled by a long noncoding RNA termed the 47S pre-ribosomal RNA (47S pre-rRNA), which initiates nucleolar assembly at the site of its transcription, and for which continued expression is required to maintain nucleolar integrity. Yet, while the 47S’ roles in nucleating and scaffolding nucleolar architecture are well established cytologically (they were first observed nearly a century ago), the structural elements on the 47S that enable these architectural functions remain unknown. I hypothesize that an RNA domain within the 47S, termed the 5´–External Transcribed Spacer (5´–ETS), harbors the long-sought structural scaffolds of the nucleolus. To test this, I am implementing a live-cell reporter assay that will monitor, in real time, if transcripts derived from the 5´–ETS drive nucleolar localization and architecture. My approach leverages recent advancements in artificial gene synthesis and live-cell RNA imaging. A novel drug-inducible promoter will enable me to temporally control expression of 5´–ETS sequence variants in live cells. I will monitor the kinetics and efficiency with which these transcripts localize into the nucleolus by two-color live cell imaging, using the newly discovered fluorescent RNA aptamer RhoBAST, and a fluorescently tagged nucleolar marker protein. To design our negative controls, I implemented a bioinformatic pipeline that generates scrambles of long, low-complexity RNA sequences—ablating primary structure but preserving dinucleotide content. This allows us to investigate whether nucleotide composition or sequence affects nucleolar formation. We anticipate that this powerful system will set the stage for detailed molecular characterization studies, revealing the long-elusive molecular interactions that control nucleolar architecture in health and disease.

Solar energy is a promising form of renewable energy that will play a major role in reducing carbon emissions. Perovskite-based solar cells have attracted significant attention due to their high power conversion efficiency (PCE), which reached 26.1% this year, surpassing commercial silicon’s (23.3%). High PCE, low cost of materials, and ability to be solution processed make perovskite solar cells a prime candidate to replace silicon. However, efficiencies are still below the theoretical limit and these materials suffer from limited operational stability. To tackle these problems, scientists have focused on minimizing active layer and interfacial defects which act as barriers for charge extraction in a solar cell, lowering the device efficiencies. Defects also electronically dope the perovskite layer, changing the recombination kinetics in the sample. The goal of this project is to quantify how the electronic doping and defect concentration of the perovskite sample is affected by surface passivation treatements via fluence dependent photoluminescence (PL) and time resolved photoluminescence (TRPL) spectroscopy. By solving the kinetic equations at the basis of charge recombination, we can extract the rate constants that correspond to different charge recombination pathways. We pioneer a global fitting analysis to simultaneously fit TRPL and PL measurements for robust determination of these kinetic constants that are subsequently used to determine the doping density of films before and after passivation. We show that the electronic doping density is higher than previously reported in literature, and that this doping is reduced with a surface passivation treatment. We collaborate with the University of Arizona to correlate our measured electronic doping density to electrochemically measured defect densities on the same samples. This work will provide an implementable tool to quantitatively assess electronic doping and defect density values for various perovskite compositions which will be useful for optimizing future solar cell devices.

Multiple Particle Tracking (MPT) is a powerful technique for studying the behavior of microscopic particles, such as viruses and nanoparticles, by tracking individual displacement and movement. One application of MPT is to measure microstructural changes in the brain extracellular environment (ECM) in development and aging, and in response to disease onset and progression. MPT of nanoparticle probes results in the generation of thousands of individual nanoparticle trajectories, from which geometric features, diffusion coefficients, and viscosities can be extracted. The vast array of trajectories contained within our dataset presents a good opportunity for integration into deep learning models that contains self-supervised learning, equivariant graph neural network, and Equivariant transformer. However, to enable MPT data to be trainable and predictable by deep learning models, we need to curate the data to be readable and useable by these models. To enable this, I have created a database and developed a data architecture that would allow MPT data to be passed into Deep learning models that use various techniques such as transformers. I am currently working on utilizing the data architecture on a Deep Learning model that uses transformers and self-supervised learning to predict trajectories of MPT particles. From this model, my expected accuracy of prediction of the trajectories for the MPT data is around 85%. This can allow us to learn complex features directly from raw MPT trajectory data, improve our predictions, and extract biological insights. The python package with our data architecture, the various SQL scripts, and the model will be provided as an open-source resource, allowing other researchers to expand upon my code and apply their unique modifications based on their own data and trajectories.

Current concentrations of carbon dioxide are 420 ppm, a 50% increase since the industrial revolution. Nitrous oxide (N₂O) concentration has increased by 18% since the industrial revolution and is currently 319 ppb. This slight increase may not appear alarming, but since nitrous oxide traps 300 times more heat than carbon dioxide, lowering emissions of this greenhouse gas will help stabilize the climate. One major source and sink of N₂O is production and reduction by microbes, respectively, which have been perturbed by anthropogenic increases of nitrogen. Novel microbes found in low pH (3-6) subsurface sites in Tennessee have been shown to respire N₂O, reducing it to N₂ using both Clade I or II nitrous oxide reductases. Microbes that can reduce N₂O at such low pHs (below 5) are rare but could be beneficial as a sink for nitrous oxide. One such strain is a novel Bacteroidetes that encodes a Clade II nitrous oxide reductase and was provisionally named strain S13. In my experiment, I aim to better understand the metabolic processes of this strain and identify the optimal temperature for growth, using xylose, a 5-carbon sugar, as the carbon source. S13 was then grown in an electron acceptor (N₂O) limiting environment, electron donor (xylose) limiting environment, and fermentative conditions. After the microbes completed their growth, the gas and metabolite concentrations were measured using Gas Chromatography and High-Performance Liquid Chromatography. When grown on xylose, the products produced were hydrogen gas, succinate, and acetate. Optical density of these tubes was measured over the course of their growth to determine growth rates and maximum yield (optical density). This was done at 6 temperatures: 15°C, 20°C, 25°C, 30°C, 35°C, and 40°C. These data indicated that S13’s optimal temperature for growth was 25°C. This information could be utilized in future bioremediation and nitrous oxide control efforts.

Since their introduction to clean energy applications, organic-inorganic lead halide perovskites have received great attention for their potential to create highly efficient, manufacturable and cheap solar cell devices. To make effective perovskite solar cells, charge transport layers are used to remove electrons and holes from the bulk perovskite semiconductor, increasing current, voltage and power conversion efficiency. Phosphonic acid self-assembled monolayers (SAMs) are a common hole transport layer. The phosphonic acid binds to the transparent conductive oxide electrode while an organic head group forms the SAM/perovskite interface. This head group is key for charge transfer and voltage characteristics, but the structure-function relationship is still poorly understood. My project investigates the role that deposition techniques and electronic structure play in the optimization of this SAM/perovskite interface. Expanding from the standard two step spincoating SAM/perovskite deposition method, I explored whether the codeposition of the two layers or the addition of a SAM solvent wash step produced an improved interface. I also fabricated films using several different SAM compositions to test for performance trends and improvements compared to the current field standard SAM, Me-4PACz. I collected photoluminescence lifetimes, quantum yields and solar simulation measurements to evaluate film performance. Preliminary data shows that neither the washing step nor codeposition add any performance benefit, but the single step codeposition achieves a more streamlined manufacturing method. Two of the new experimental SAMs performed comparably to Me-4PACz. These results encourage codeposition of the SAM/perovskite interface as the most efficient method to create high quality devices and show promising alternatives to the industry standard Me-4PACz SAM.

PIONEER is a rare-pion decay experiment, which aims to test Lepton Flavor Universality (LFU), a consequence of the Standard Model (SM) of particle physics. The SM is very successful but is known to be incomplete as it cannot describe gravity, dark matter, and other observed phenomena. PIONEER will test LFU by measuring the relative frequency of the two primary decays of a subatomic particle known as a pion. The ratio of the rates of pion decay to muon and pion decay to electron is predicted extremely precisely by the SM and is sensitive to physics beyond the SM. Therefore, this ratio is extremely important to measure. Muons quickly decay to electrons, so the final product of both decays is an electron, but their energies can distinguish the decay path. Thus, this measurement requires an extremely sensitive calorimeter to measure the energies of the resulting electrons. One candidate for this calorimeter is a large array of LYSO crystals. LYSO is a fast, dense, high-light-yield scintillator whose intrinsic properties suggest it would be a natural candidate for the experiment. Despite its advantages, a large, LYSO-based calorimeter has never been developed. We wish to measure certain properties of large LYSO crystals, such as energy resolution and uniformity, to determine if they meet the requirements necessary for use in the PIONEER calorimeter. Bench tests conducted thus far have displayed impressive single-crystal resolution and uniformity at low energies when crystals are wrapped in a well-fitted specular reflector. Energy resolution tests were conducted on an array of 10 LYSO crystals, using 17.6 MeV gamma rays produced by the Van der Graff accelerator at the Center for Experimental Nuclear Physics and Astrophysics (CENPA) here at UW. LYSO crystal performance and energy resolution have been shown in preliminary tests to be within the specifications for the PIONEER calorimeter.

Alpine areas are host to diverse plant communities that support ecosystems with their structure and floral resources and existing through specialized adaptations to harsh high-elevation conditions. An ongoing question in these plant communities is whether composition is shaped by stochastic processes (e.g., dispersal limitations) or by deterministic processes (e.g., climate) and if those processes select for common phylogenetic clades across space. This study evaluates the drivers of dissimilarity in vascular plant communities of alpine areas of 32 peaks in the Cascade Mountain Range of Washington State and the effects of incorporating phylogenetic relatedness to these conclusions. Observing an average of 54 species per peak, an inventory of 315 vascular total plant taxa were compiled to construct a phylogenetic tree relating each taxa to one another. We used multivariate techniques to quantify the phylogenetic and taxonomic differences between alpine plant communities and to relate those differences to each peak’s climate, geology, and topography. Our models indicate that each peak’s elevation, geologic parent material, and precipitation seasonality had the largest role in shaping alpine plant communities relative to the baseline effects of distance between peaks. Despite phylogeny contributing to lower overall dissimilarity, it conforms to the same trends between peaks and does not change the relationships to space, geology, and climate seen in taxonomic distance at the mountain-range scale. These results support the existence of deterministic spatial patterns of geology and climate driving community composition but fail to explain any evolutionary processes influencing colonization and survival in alpine environments.

Bacteria face a variety of threats, including antagonistic killing by other bacteria in competition for space and resources. In response to this antagonism, many bacteria have evolved specific defense systems. One pertinent example is the Pseudomonas aeruginosa Response to Antagonism (PARA) in P. aeruginosa, which provides defense against various antagonists by activating a suite of genes, mediated by two-component pathway Gac/Rsm, in response to kin cell lysis. The Gac/Rsm machinery is conserved across the Pseudomonas genus, but its function in defense has not been studied outside of P. aeruginosa. Here, we investigate whether two divergent Pseudomonas species, P. putida (KT2440) and P. protegens (Pf-5), similarly use Gac/Rsm in defense. To do this, we performed competitive growth assays against an antagonistic competitor, Enterobacter cloacae, comparing Gac/Rsm deletion mutants against wild-type, and quantified relative survival as an indicator of competitive fitness. Preliminary data indicate that the deletion of the core Gac/Rsm gene gacS results in dramatically decreased competitive fitness for Pf-5, but not for KT2440. This indicates that Pf-5 uses the Gac/Rsm system in a similar manner to P. aeruginosa and that, while Gac/Rsm is conserved, it may differ in function between species. To identify additional specific genes involved in defense systems, we set up a genome-wide screen. The screen indicated that genes related to the flagellum and lipopolysaccharide biosynthesis may be involved in defense against antagonism, which was surprising because these well-characterized structures have never before been implicated in defense. Work is currently underway to validate these genes as true defense factors and determine the mechanism by which they confer survival. Our findings advance the understanding of defense systems among Pseudomonas species by shedding light on their conservation and complexity, thus providing a foundation for future work on defense systems across bacterial phyla.

Climate change caused by CO2 emissions creates a need for greater energy efficiency, as energy production produces CO2. One area of improvement is in chemical separations, which consume roughly half of all industrial energy use. Most of these processes could be made ten times more efficient by switching from energy-intensive distillation and absorption processes to membrane separations. Mixed Matrix Membranes (MMMs) are a particularly promising option for use in gas separations. These MMMs incorporate Metal Organic Framework (MOF) crystallites within polymer membranes to balance the benefits of both. However, the parameters that determine the growth of some MOFs, like ZIF-8, are still unknown. Here, we explore the growth conditions of ZIF-8 to enable the production of these MMMs on an industrial scale. By exposing zinc oxide (ZnO) coated silicon wafers to 2-methylimidazole (HmIm) in a tube furnace, I measure ZIF-8 crystal formation at varying temperatures, temperature gradients, and anneal times. Crystal thickness is measured using ellipsometry to observe successful crystal formation. Using COMSOL software, we explore models of the HmIm concentration to determine what experimental variables could have the largest effect on ZnO to ZIF-8 conversion. Preliminary experimental results suggest a specific temperature profile is needed, as well as a required minimum anneal time for successful ZnO to ZIF-8 conversion. Furthermore, temperature gradients appear to impact HmIm concentration, which affects crystal growth. These findings may enable industrial-scale production methods for MMMs with ZIF-8, and may also prove useful when producing MMMs with other MOFs.