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Topological and Optical Properties of Two-Dimensional Materials
No full textRecent advances in condensed matter physics have revealed a wide range of novel quantum phenomena in two-dimensional (2D) materials. The discovery of unique topological, magnetic, and optical properties in solids has greatly expanded our understanding of quantum phases in electronic structures. As more material systems are proposed theoretically and realized experimentally, our research focuses on uncovering and explaining these phenomena through effective models and first-principles calculations. First, we explore topological mosaic patterns in moiré superlattices—structures composed of periodic, spatially distinct domains, each with different topological properties. These domains give rise to periodic edge states along domain walls. We explore the interaction between these topological domains and predict a global topological phase transition at the charge neutrality point, driven by the size of the domain walls and the moiré period. A phase diagram is provided to illustrate how the twist angle and the geometry of the mosaic pattern influence the emergence of nontrivial topological phases. Second, we investigate the photogalvanic effect, a second-order nonlinear optical response, in multiferroic breathing kagome materials. Using monolayer NbI as a case study, we show that the shift current—linked to real-space electron–hole displacement—is predominantly unaffected by magnetic order. In contrast, the injection current, associated with the quantum metric dipole in momentum space,is closely related to valley polarization which can be tuned by magnetic field. Both types of photocurrent can be reversed by applying an out-of-plane electric field that modulates the breathing distortion of the lattice. These results suggest that breathing kagome structures are promising platforms for multifunctional optoelectronic devices and sensors. Lastly, we explore the optical properties of altermagnets, a recently proposed magnetic phase distinguished by its unique spin symmetry. Altermagnets exhibit spin-split electronic structures even in the absence of both net magnetization and spin–orbit coupling, setting them apart from conventional ferromagnets and antiferromagnets. Using first-principles many-body perturbation theory, we study valley-resolved optical and excitonic properties in monolayer MnWS, a 2D -wave altermagnet. We discover valley-selective linear dichroism arising from the interplay of spin symmetry and orbital character, along with a spin–valley-dependent optical selection rule that enables linearly polarized light to selectively excite spin-polarized excitons. Additionally, we show that uniaxial strain lifts the valley degeneracy and allows for selective excitation of excitons with highly anisotropic wavefunctions. These findings highlight the potential of altermagnets for next-generation spintronic and valleytronic applications
The Brownies\u27 Book: The First Black Children\u27s Literature Magazine
Get PDFThe Brownies\u27 Book is the first Black children\u27s literary magazine, published by DuBois and Dill Publisher between 1920 to 1921. W.E.B. Du Bois described the monthly periodical as “…a little magazine for children—for all children, but especially for ours.” This zine seeks to highlight the significance and impact of the periodical that established African American children’s literature.
Mendel Sato Research Award 2025, Graduate studen
Single-Cell Analysis of Clonal and Transcriptional Dynamics During Direct Reprogramming
Get PDFDirect lineage reprogramming converts one cell type into another, a process characterized by significant heterogeneity. Single-cell genomic techniques have been instrumental in dissecting this variability, yet they often fail to preserve lineage relationships. Here, I present CellTagging, a sequential, combinatorial indexing method that enables the reconstruction of clonal history and gene expression dynamics at single-cell resolution. This facilitates the construction of multi-level lineage trees, providing insights into cellular reprogramming trajectories. We applied CellTagging to investigate direct lineage reprogramming of mouse embryonic fibroblasts into induced endoderm progenitors. Our analysis revealed two distinct reprogramming trajectories: one leading to successful conversion and another resulting in a ‘dead-end’ state. Notably, the divergence of these trajectories occurs early in the reprogramming process. Additionally, we identified Mettl7a1, a putative RNA methyltransferase, as a pro-reprogramming factor that enhances reprogramming efficiency. These findings highlight the power of CellTagging in resolving the transcriptional and clonal dynamics of direct lineage reprogramming
Mechanisms of Protective Humoral Immunity and Pathogenesis in Alphavirus Infection
Get PDFAlphaviruses are enveloped, mosquito-transmitted, positive-sense RNA viruses of the Togaviridae family classified into Old and New World groups based on endemic regions and human disease characteristics. Old World alphaviruses, including chikungunya virus preferentially cause arthritogenic disease, whereas New World viruses like Venezuelan equine encephalitis virus (VEEV), Eastern equine encephalitis virus (EEEV), and Western equine encephalitis virus (WEEV) can cause neurological disease. Since the 1920s, VEEV has been responsible for major periodic outbreaks affecting hundreds of thousands of humans and equines in South and Central America. Expansion of mosquito vectors raises concern for possible VEEV reemergence. In addition, VEEV is a bioterrorism threat and was weaponized in the 1960s and 1970s for possible aerosol dissemination. Thus, alphaviruses, including VEEV, have been responsible for numerous worldwide epidemic outbreaks in the past century and yet, approved vaccines or treatments still do not exist. Here we investigate mechanisms of antibody-mediated protection against alphaviruses and how understanding alphavirus-host interactions leading to pathogenesis is critical for mitigating disease through antiviral therapeutic design. We describe the molecular basis of neutralization by murine and human monoclonal antibodies (mAbs) targeting several envelope protein epitopes. These mAbs inhibited multiple steps in the viral replication cycle including viral attachment, fusion to host membranes, and egress. Epitope mapping identified antigenically distinct sites on the VEEV E2 protein targeted by mAbs. Cryo-electron microscopy (cryo-EM) analysis of a potently neutralizing human mAb bound to VEEV defined a critical binding site within domain B of the E2 protein. Anti-VEEV mAbs targeting each antigenic site conferred robust protection and post-exposure therapeutic efficacy in mice challenged with aerosolized VEEV, highlighting targets for potential therapeutic development and vaccine immunogen design. Our studies link epitopes recognized by inhibitory anti-VEEV mAbs elicited after immunization with mechanisms of neutralization and thus further define the structural and functional components that contribute to protective efficacy against aerosolized VEEV infection. While neutralizing antibodies that inhibit individual alphaviruses have been described, broadly reactive antibodies that protect against both arthritogenic and encephalitic alphaviruses had not been reported. We screened and identified several candidate anti-WEEV cross-reactive mAbs and then developed an immunization and B cell sorting strategy to generate pan-alphavirus cross-reactive mAbs. Biosafety level 2 mouse models of EEEV, WEEV, and VEEV were developed for use in lethality and virological endpoints as a tool for screening these mAbs. Ultimately, two pan-protective yet poorly neutralizing human mAbs were identified, which bind to viral antigen on the surface of alphavirus-infected cells. These mAbs engage a conserved epitope in the E1 protein. Treatment with these mAbs protected against arthritogenic and encephalitic alphaviruses through various mechanisms including inhibition of viral egress and monocyte-dependent Fc effector functions. To better understand mechanisms of protective humoral immunity that might inform anti-alphavirus therapeutic development, we also defined key alphavirus receptors critical for pathogenesis in vivo. A VEEV-specific entry receptor, low-density lipoprotein receptor class A domain containing 3 (LDLRAD3), was identified using a loss-of-infection-based CRISPR-Cas9 genome-wide screen. LDLRAD3 is a highly conserved type I membrane protein of the LDL receptor superfamily and has been reported to regulate amyloid processing and auto-ubiquitination in neurons, although its endogenous ligand(s) are unknown. The most membrane-distal domain 1 (D1) of the three extracellular domains of LDLRAD3 was shown to be necessary and sufficient for VEEV infection, and a cryo-EM structure showed that LDLRAD3 D1 binds in a cleft formed between adjacent VEEV E2 and E1 proteins on the virion surface. We investigated the role of the entry receptor LDLRAD3 in VEEV pathogenesis using newly generated LDLRAD3-deficient mice. We found consistently lower levels of VEEV infection in all target tissues of LDLRAD3-deficient mice after subcutaneous inoculation, as early as 6 hours post-infection and at every timepoint tested thereafter. While VEEV entry into the brain occurred in the absence of LDLRAD3 expression, spread was delayed, infection accumulated at substantially lower levels, and animals did not sustain weight loss or lethality. Bone marrow chimera studies established that VEEV pathogenesis was largely dependent on LDLRAD3 expression in radioresistant stromal cells. Direct inoculation of VEEV into the brain via intracranial or intranasal inoculation resulted in uniform lethality in wild-type mice, whereas in LDLRAD3-deficient mice, animals lost weight but survived infection. This phenotype was associated with reduced central nervous system (CNS) viral burdens in LDLRAD3-deficient mice. Using in situ hybridization and immunohistochemistry, the absence of LDLRAD3 was associated with marked decreases in infection of neurons in adult mouse brains and in mixed primary neuron cultures isolated from embryos. Overall, we establish a key role for LDLRAD3 in the infection, dissemination, and pathogenesis of VEEV in peripheral and CNS tissues
AI-assisted Model-guided Image Reconstruction Methods for Photoacoustic and Ultrasound Computed Tomography
Get PDFPhotoacoustic computed tomography (PACT) and ultrasound computed tomography (USCT) are two emerging medical modalities that hold great promise for both pre-clinical and clinical imaging applications, including cancer diagnosis and management. PACT is a hybrid imaging modality that combines benefits from both optical and acoustic imaging to provide high contrast images of biological absorbers. USCT is an ultrasound imaging modality that provides high-resolution quantitative images of acoustic properties utilizing accurate physics models. Both PACT and USCT can be applied for monitoring or diagnosis of cancer and are non-invasive and radiation free. However, both imaging modalities are in the early stages of development and suffer fundamental difficulties that prevent their widespread adoption. To further develop PACT and USCT, this dissertation pursues three specific aims: 1) Enable high-resolution 4D PACT with scalable neural field representations; 2) Demonstrate in-vivo estimation of tumor perfusion rates using 5D DCE-PACT; 3) Accelerate USCT reconstruction with learned and hybrid FWI methods. Achieving these aims will result in computationally efficient image reconstruction methods for PACT and USCT and allow them to transfer into medical applications. Widespread use of PACT and USCT will then provide important tools for medical experts to monitor the progression of cancer and its response to treatments
Essays on International and Development Economics
No full textThis dissertation explores key issues in international and development economics, focusing on trade liberalization, foreign exchange intervention, and the interaction between fiscal and monetary policies. The first chapter investigates the optimal timing of trade liberalization for low-income countries. It develops a three-sector model incorporating productivity spillovers and organizational capital accumulation to assess how early or delayed trade liberalization affects long-term economic development. The results show that premature liberalization can inhibit manufacturing growth, whereas strategic delay can enhance overall welfare. The second chapter examines the redistributive effects of foreign exchange intervention (FXI) in a two-country model where all international trade is conducted in a dominant foreign currency. It finds that while FXI increases export quantity, the primary burden falls on the domestic sector of the intervening country rather than on foreign exporters. This challenges the conventional belief that FXI benefits domestic producers at the expense of foreign competitors. The calibration results suggest that an increase in foreign reserves leads to a measurable loss of wealth for the domestic sector. The third chapter investigates how different fiscal policies affect monetary policy efficiency, particularly in economies with state-owned businesses (SOBs). Using a cash-in-advance framework, the study compares the effectiveness of lump-sum taxes, labor taxes, output taxes, and SOB profits as sources of government revenue. The findings indicate that while the Friedman Rule suggests deflationary policies are optimal under lump-sum taxation, alternative tax schemes create distortions, making deflation suboptimal. Among non-lump-sum revenue sources, output taxation is the least distortionary in a positive inflation regime. These insights underscore the importance of fiscal constraints in the formation in optimal monetary policy. Together, these chapters contribute to our understanding of trade policy, foreign currency intervention, and monetary-fiscal interactions, providing policy-relevant insights for developing and emerging economies
Role of the small intestinal microbiota in the pathogenesis of environmental enteric dysfunction in undernourished children and mothers
No full textUndernutrition in women and its propagation in their children remains a major global health challenge. Worldwide, one in five children under five years of age manifests undernutrition as impaired linear growth, or stunting. Stunting, defined as having a length-for-age z-score (LAZ) \u3c-2, is associated with poor developmental outcomes, including impaired neurodevelopment and immune responses. Furthermore, stunting and its long-term sequelae persist across generations, contributing to an intergenerational cycle of undernutrition. Existing nutritional interventions fail to substantially improve stunting, highlighting the need to (i) better understand other factors contributing to stunting and (ii) focus clinical efforts towards treating maternal undernutrition. Environmental enteric dysfunction (EED) is a subclinical inflammatory enteropathy of the small intestine proposed to contribute to stunting. EED is diagnosed histologically by blunted intestinal villi, epithelial barrier disruption and an immunoinflammatory infiltrate in the lamina propria. However, the pathophysiology of EED remains poorly defined. Furthermore, the small intestinal microbiota remains understudied due to difficulties in sampling. Evidence that the small intestinal microbiota contributes to EED pathogenesis comes in part from our collaborative work with colleagues at icddr,b (the International Centre for Diarrhoeal Disease Research, Bangladesh) who oversaw the Bangladesh EED (BEED) study. In this study children, aged 12-18 months residing in an urban slum in the Mirpur district of Dhaka who failed a nutritional intervention for their stunting, underwent esophago-gastroduodenoscopy (EGD) to obtain duodenal mucosal biopsies, aspirates of duodenal luminal fluid and plasma samples. A set of 14 bacteria taxa (defined by 16S rRNA amplicon sequencing) were identified in the duodenal microbiota of \u3e80% of children with EED. Moreover, the absolute abundances of these ‘core taxa’ were positively correlated with duodenal mucosal and systemic inflammation in study participants and negatively correlated with linear growth. Our lab showed that introduction of a consortium of bacteria cultured from these duodenal aspirates, including these core taxa, produced small intestinal inflammation in young adult gnotobiotic, providing initial preclinical evidence for a causal role for the duodenal microbiota in a small intestinal enteropathy. Additionally, the BEED study revealed that EED is very prevalent in malnourished (low-BMI) women of reproductive age living in Mirpur. Building upon this work, my thesis aimed to elucidate the mechanisms by which the pattern of intergenerational undernutrition manifests through the transmission of the small intestinal microbiota from mother to child. Here, I present a novel gnotobiotic mouse model of EED involving intergenerational transmission of two different consortia of bacterial strains cultured from duodenal aspirates of children in the BEED study with histopathologic evidence of EED – one that did, and one did not, produce intestinal and systemic inflammation. Histological analyses, protein biomarkers, bulk tissue RNA-Seq and flow cytometry were used to define host pathology in postnatal day 37 (P37) offspring of gnotobiotic female mice colonized with one or the other consortium prior to pregnancy; inflammation was characterized along the length of the intestine, as well as systemically, including in the immune-privileged brain. Single nucleus RNA-Seq (snRNA-Seq) of small intestinal tissue segments further defined alterations in expression of signaling pathways related to intestinal epithelial regeneration, epithelial barrier integrity and immune function, while snRNA-Seq of the cerebral cortex revealed perturbed glial- and endothelial-neuronal intercellular signaling involved in neuronal development, angiogenesis and inflammation. Together, these results provide evidence of a causal role of the small intestinal microbiota in the intestinal and systemic pathology that is manifested in EED. To nominate microbial mediators of the enteropathy, I pursued a series of follow-up gnotobiotic mouse experiments combined with multi-omic analyses. Cohousing young adult mice colonized 9 days earlier with one or the other consortium, revealed the dominance of the inflammatory EED donor-derived consortium compared to the non-inflammatory consortium, reflected by induced inflammation in cohoused mice originally colonized with the non-inflammatory consortium. Metagenome-assembled genomes (MAGs) defined the composition of bacterial communities along the length of the gut; three MAGs were found to be consistently associated with host pathology in both the cohousing and intergenerational transmission models; they represent organisms that are commonly found in the oral microbiota. Genome annotations and microbial RNA-Seq provided context for predicted microbial functions contributing to fitness and pathogenicity of these MAGs. Finally, the addition of cultured bacterial isolates representing these MAGs into mice harboring the non-inflammatory consortium was sufficient to induce features of the enteropathy – most notably in the colon. These findings support the concept that ‘decompartmentalization’, where members of the oral microbiota are established in the intestinal microbiota, is a contributor to EED. In summary, this thesis illustrates an approach for elucidating structure-function relationships in the human small intestinal microbiota - a poorly explored community due to difficulties in obtaining samples. These types of preclinical models should help guide subsequent efforts to better understand the role of the small intestinal microbiota in the pathogenesis of EED, identify candidate therapeutic targets and validate candidate therapeutic agents for treating EED in children (and their mothers)
Exploring the Thermal Physiology Evolution Across Mountain Slopes
No full textI investigated whether critical thermal limits to low and high temperatures exhibit patterns of thermal tolerance specialization across altitudes, both between and within species, in the complex terrain of the Neotropical mountains. In these mountains, species have found different ways to adapt and diversify to their various elevational and climatic gradients (Chapter 2). I used climatic and distribution data to assess patterns and test for changes in the evolution rates of highland specialization across the entire anole phylogeny. Few animal groups have been able to adapt and thrive in several different mountain ranges (Chapter 3). I tested whether those biogeographical shifts from low elevation to high elevation have led to an increase in diversification and speciation rates (Chapter 4). Finally, I tested whether water loss is influenced more by the intrinsic physiology of the lizards or by the climatic niche they inhabit. I also investigated to what extent these two factors affect water loss in lizards (Chapter 5). I found that understanding the evolution of highland specialization and climatic niche evolution is particularly complex. Different clades have converged in their critical thermal limits, where the critical thermal minimum and maximum decrease as elevation increases (Chapter 2). This convergence suggests that high-elevation environments exert strong selective pressures that shape the thermal tolerances of species. Additionally, cold adaptation has evolved several times in similar ways when analyzed within an elevational and cold temperature framework (Chapter 3). This repeated pattern of adaptation highlights the predictability of evolutionary responses to similar environmental challenges. However, I observed distinct evolutionary trajectories between highland and lowland species, likely shaped by climatic heterogeneity and ecological specialization across elevation gradients (Chapter 4). Factors such as the temporal scale of analysis, the specific environmental variables considered, the phylogenetic context, and the climatic heterogeneity all play crucial roles in shaping our understanding of climatic niche evolution. Lastly, I discovered that water loss is intricately associated with climatic conditions, particularly temperature and precipitation (Chapter 5). The relationship between water loss and climate suggests that species have evolved mechanisms to cope with varying levels of humidity, precipitation and temperature. This adaptation is critical for maintaining hydration and overall physiological function in desertic regions
Leveraging AI for Marketing Decisions: Algorithmic Targeting and Healthcare Applications
Get PDFIn this dissertation, I leverage artificial intelligence (AI) for making effective marketing decisions, specifically on how to measure the causal effects of targeting promotions and detecting suspicious retail buyers of opioids. In the first chapter, we propose a novel approach in measuring the true causal effects of targeting promotions. Targeting promotions on online platforms are often determined by AI algorithms, which utilize extensive customer and seller information to generate various algorithmic scores for targeting. Effective targeting, however, will lead to selection bias when evaluating the causal effects of promotions. we analyzed 2,294 promotion experiments on a major online retail platform and found that traditional methods, such as propensity score matching and double machine learning, cannot accurately recover the true effects using readily available data. To overcome this challenge, we propose an approach that logs and utilizes the algorithmic scores to match treated and untreated customers, effectively mitigating the selection bias and addressing the curse of dimensionality in matching. We validate this approach by analyzing the same set of experiments and demonstrate that the estimates from the proposed matching approach, based on algorithmic scores, closely align with the promotion effects estimated from the separately run randomized field experiments. This approach can assist platforms and sellers in accurately evaluating the value of targeted promotions. Additionally, it can be implemented easily and at a low cost since algorithmic scores are easy to store. In the second chapter, we propose an anomaly detection algorithm to effectively detect suspicious opioid retail buyers. The opioid epidemic adversely affects thousands of communities across the US. The objective in this research is to examine how a US drug distributor can leverage cutting-edge analytics to monitor opioid diversion and stop opioid shipments from reaching those at risk. In doing so, the firm can lead with purpose and create maximum social impact through CSR. The authors propose an anomaly detection algorithm that can be used to identify suspicious retail buyers of opioids. The authors implement the proposed algorithm on the ARCOS database -- which tracks all opioid drug shipments across the US from 2006 to 2012. The proposed algorithm effectively identifies suspicious retail pharmacies and practitioners involved in drug diversion. It achieves 100 % precision and 100 % sensitivity, resulting in 100 % F-1 score for retail pharmacies. By applying the proposed algorithm, the drug distributor gains a powerful tool for promptly detecting suspicious retail buyers. By reporting suspicious opioid orders as they occur to the DEA, the distributor can safeguard vulnerable communities and save lives. Putting societal purpose before short-term profit will build sustained competitive advantage for the drug distributor in the long run
Controlled-Airflow Sensor Enclosure (CASE) Design Document
Get PDFThe purpose of this document is to organize the theory, industry practices, and research related to designing a device that pulls air through a pipe, containing an environmental sensor, at a rate controlled by a computer fan. Using such a device to regulate the airflow over a sensor can improve the accuracy of field readings, as sensors are often unintentionally sensitive to multiple external conditions. Changes in wind direction and speed or heating due to solar radiation, for example, can cause errors in gas concentration and temperature readings, warranting the need to correct for these factors without decoupling these sensors from their environment.
In short, this document provides a foundation in fluid dynamics, HVAC, wind tunnels, computer cooling, compressed air systems, and sensor shielding—crafted specifically for the MEMS 3120 Controlled-Airflow Sensor Enclosure (CASE)