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Mechanisms For High Light Tolerance In A Fast-Growing Cyanobacterium, Patricia Walker Dec 2022

Mechanisms For High Light Tolerance In A Fast-Growing Cyanobacterium, Patricia Walker

Arts & Sciences Graduate Student Theses and Dissertations

Through oxygenic photosynthesis, cyanobacteria, algae, and plants convert light into chemical energy. However, highly energetic light often damages the photosynthetic apparatus, which can lead to the decline of photosynthetic activity (photoinhibition), and prolonged photoinhibition can lead to cell death. Cyanobacteria enact various protective mechanisms to mitigate photodamage, many of which have been conserved in plants. Repair of PSII reaction centers, decreased light absorption, quenching of excess absorbed energy, and biosynthesis of antioxidants all work to mitigate damage during high light. Due to the adjustments to photosynthesis, acclimation to high light requires remodeling of cellular metabolism and physiology. Therefore, phototrophs have …


Tracking Reducing Equivalents Between Cellular Compartments To Understand The Metabolic Demands Of Proliferation, Yahui Wang Dec 2022

Tracking Reducing Equivalents Between Cellular Compartments To Understand The Metabolic Demands Of Proliferation, Yahui Wang

Arts & Sciences Graduate Student Theses and Dissertations

Proliferating cancer cells compartmentalize metabolic reactions, many of which require reducing equivalents. This compartmentalization is functionally important, but it is challenging to study with current technologies. As a consequence, our understanding of proliferating metabolism has been limited. Here, I developed an approach to track reducing equivalents between cellular compartments. By applying this method to a panel of different cell lines under various conditions, I investigated a dysregulated metabolic phenotype in proliferating cells known as “aerobic glycolysis”. Aerobic glycolysis is characterized by an elevated rate of glucose fermentation to lactate irrespective of oxygen availability. Using the NCI-60 cell lines, I first …


An Online Vignette Study To Examine The Outcomes Of A Preclinical Alzheimer Disease Diagnosis, Matthew John Wynn Dec 2022

An Online Vignette Study To Examine The Outcomes Of A Preclinical Alzheimer Disease Diagnosis, Matthew John Wynn

Arts & Sciences Graduate Student Theses and Dissertations

As Alzheimer disease research forges ahead, and new potential treatments are developed, a conceptualization is emerging of a presymptomatic disease stage. This stage, known as preclinical Alzheimer disease, is characterized by the buildup of amyloid beta and tau proteins in the brain to abnormal levels in a cognitively normal person. There are unknown potential risks and benefits of communicating biological marker risk information for Alzheimer disease using the preclinical Alzheimer disease diagnostic label. The current study uses a vignette methodology to measure older adults’ understanding of risk information when presented with information regarding their risk for developing Alzheimer dementia. Participants …


Understanding Gene Regulation With High-Throughput Genome-Integrated Reporter Assays, Clarice Hong Dec 2022

Understanding Gene Regulation With High-Throughput Genome-Integrated Reporter Assays, Clarice Hong

Arts & Sciences Graduate Student Theses and Dissertations

Proper spatiotemporal gene expression depends on specific interactions between cis-regulatory sequences (CRSs) and chromatin modifications at a genomic location. However, we do not yet understand the rules that determine how CRSs work together to influence gene expression. The goal of this thesis is to systematically assay and quantify how different genomic environments interact with CRSs to control gene expression output using a variety of genome-integrated massively parallel reporter assays (MPRAs). First, we tested the hypothesis that core promoters confer specificity by only responding to compatible enhancers and chromatin in specific genomic environments. We measured the activities of hundreds of core …


Quasiparticle And Excitonic Effects In Two-Dimensional Van Der Waals Materials, Linghan Zhu Dec 2022

Quasiparticle And Excitonic Effects In Two-Dimensional Van Der Waals Materials, Linghan Zhu

Arts & Sciences Graduate Student Theses and Dissertations

Since their discovery, low dimensional van der Waals materials have attracted increasing research interests. They serve as ideal platforms to study novel physics in reduced-dimensional systems, and are critical in nowadays’ nanotechnology applications. Due to the reduced dielectric screening in low dimensions, strong excited state properties dictate their electronic, transport and optical properties, the study of which calls for a description of the many-particle interactions beyond the traditional density functional theory. This is where the many-body perturbation theory comes into play. In this thesis, I will present a comprehensive study of the quasiparticle and excitonic properties of a variety of …


Mechanisms Regulating Photoreceptor Subtype Specification And Chromophore Utilization In Zebrafish, Leo Volkov Dec 2022

Mechanisms Regulating Photoreceptor Subtype Specification And Chromophore Utilization In Zebrafish, Leo Volkov

Arts & Sciences Graduate Student Theses and Dissertations

The first step in vision is the detection of light by a photoreceptor cell. The spectral sensitivity of a photoreceptor, in turn, is determined by the composition of its visual pigment, which consists of an opsin protein and a covalently bound chromophore derived from either vitamin A1 or vitamin A2. In the course of evolution, opsin gene duplication and functional divergence led to the emergence of four distinctive cone opsins, maximally sensitive to ultraviolet (UV), blue, green, or red light, as well as the rod opsin. Subsequently, the expression of these functionally distinct opsins was segregated into distinct cell types …


The Effect Of Ionization Density In Applications Of Radiation Detection, Dosimetry, And Therapy, Daniel Mulrow Dec 2022

The Effect Of Ionization Density In Applications Of Radiation Detection, Dosimetry, And Therapy, Daniel Mulrow

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation covers a wide range of topics but is linked by the common theme of radiation interacting with materials and studying the result of those interactions. The introduction describes the fundamentals of how radiation interacts with material and how we are able to detect that radiation and the application of how we use those interactions in radiation oncology. The thesis starts with a chapter detailing the temperature dependence of the photophysics in two organic scintillators. This chapter is the foundation for a future study that will look the degree to which these scintillators can distinguish between gammas and neutrons …


Poverty, Child Maltreatment And Adverse Childhood Experiences – Just Comorbidities?, Darejan Dvalishvili Dec 2022

Poverty, Child Maltreatment And Adverse Childhood Experiences – Just Comorbidities?, Darejan Dvalishvili

Brown School Graduate Student Theses and Dissertations

Both child abuse and neglect (hereafter maltreatment) and poverty are serious social and public health problems that are related to numerous negative and costly outcomes as well as being related to other so-called adverse childhood experiences (ACES). A significant, yet recent, body of work suggests a strong, perhaps causal, relationship between poverty and maltreatment. Much remains unknown about how they are associated and whether or not a true causal relationship exists while controlling for other potential risks in the ecology. This dissertation conducted a secondary analysis of the Panel Study of Income Dynamics (PSID) to help address this gap. First, …


Effectiveness Of Community Development Organizations In The St. Louis Metropolitan Area, Kyle Pitzer Dec 2022

Effectiveness Of Community Development Organizations In The St. Louis Metropolitan Area, Kyle Pitzer

Brown School Graduate Student Theses and Dissertations

Concentrated poverty has been a core issue in urban America for close to half of a century. The consequences of living in these neighborhoods are also dire. These "neighborhood effects" are defined as the effects of living in concentrated poverty over and above individual circumstances, which have been tied to a number of important life outcomes. One approach to addressing these issues is community development, and perhaps the most salient vehicle of community development is the community development corporation (CDC). This current study sought to address three aims: 1), understand the effects of CDCs on population-level outcomes; 2), understand the …


Tissue Resident Macrophages Drive Fibrosis During Pancreas Inflammatory Injury And Pancreatic Ductal Adenocarcinoma, John Baer Dec 2022

Tissue Resident Macrophages Drive Fibrosis During Pancreas Inflammatory Injury And Pancreatic Ductal Adenocarcinoma, John Baer

Arts & Sciences Graduate Student Theses and Dissertations

The immune system, and especially macrophages, are central in responding to infections, as well as providing a wide array of functions in other pathologies, especially in responding to inflammation. It is established that macrophages will accumulate within tissues during inflammation, many times secreting cytokines and chemokines central to the inflammatory response. This is particularly true during pancreatitis, or inflammation of the pancreas, where it has been shown that macrophages and monocytes accumulate in the pancreas to have various roles in further promoting inflammation. It is not well established, however, whether there are divergent roles for the distinct macrophage subsets that …


Toward Enhancing The Synthesis Of Renewable Polymers: Feedstock Conversions And Functionalizable Copolymers, Tedd Casey Wiessner Dec 2022

Toward Enhancing The Synthesis Of Renewable Polymers: Feedstock Conversions And Functionalizable Copolymers, Tedd Casey Wiessner

Arts & Sciences Graduate Student Theses and Dissertations

This thesis describes research under the rubric of the Center for Sustainable Polymers that is aimed at two separate goals. The goal of the first project (Chapters 1 and 2) was to develop a deeper mechanistic understanding of a method for the synthesis of linear α-olefins, while the second aimed at synthesizing statistical copolymers that incorporate olefin-containing monomers through ring-opening transesterification polymerization and showing that these copolymers could be functionalized. In Chapter 1, published methods for the conversion of fatty acids to linear α-olefins are reviewed to provide context for the mechanistic work we accomplished (Chapter 2). In Chapter 2 …


Behavioral, Neural, And Psychiatric Correlates Of Responses To Social Feedback, Brent Rappaport Dec 2022

Behavioral, Neural, And Psychiatric Correlates Of Responses To Social Feedback, Brent Rappaport

Arts & Sciences Graduate Student Theses and Dissertations

Problems responding to peer feedback and disrupted interpersonal relationships arise in numerous psychiatric disorders; yet heterogeneity and homogeneity across disorders suggests both common and unique mechanisms of impaired social function. Identifying brain correlates of these disruptions could help explain diagnostic comorbidities as well as unique pathways, thus informing more individualized treatments. However, studies seeking to understand the link between psychological and neural mechanisms often have to rely on reverse inference assumptions to match psychological processes to brain activity. One hypothesis is that social feedback is processed similar to other forms of feedback (e.g., monetary). Thus, we aimed to test such …


Perceptual Experience, Representation, And The Environment, James Gulledge Dec 2022

Perceptual Experience, Representation, And The Environment, James Gulledge

Arts & Sciences Graduate Student Theses and Dissertations

Recent cognitive science suggests that the system responsible for perceptual experience is flexible, can learn, and is robustly affected by information stored in subjects’ minds. My dissertation is about the account of the mind and subjective awareness that emerges if this picture of perceptual experience is true. Whether perceptual experience is affected by stored information is usually tied to discussions of so-called ‘cognitive penetration’ (what I call cognitive ‘permeation’). I consider the focus on cognitive permeation largely as a red herring, instead holding that we should view the relevant epistemic issue more broadly: as that of whether changing stores of …


The Enemy Within: An Investigation Of The Intracellular Bacteria In Urinary Tract Infections, Jennie Elizabeth Hazen Dec 2022

The Enemy Within: An Investigation Of The Intracellular Bacteria In Urinary Tract Infections, Jennie Elizabeth Hazen

Arts & Sciences Graduate Student Theses and Dissertations

Urinary tract infections (UTIs) are common diseases that are associated with significant morbidities. Multiple studies have indicated that multiple species of uropathogenesis bacteria invade and persist within bladder epithelial cells as a necessary step of uropathogenesis. Interestingly, many of these species are not canonically associated with intracellular infections. Although the first study describing bacteria within the urothelium was published two decades ago, this critical step of uropathogenesis remains relatively understudied.I established a murine model of community-acquired A. baumannii UTI, a previously unstudied manifestation of the disease. While immunocompetent mice resolved their infections quickly, immunocompromised mice displayed high bacterial burdens throughout …


Cooperation And Conflict In The Social Amoeba Dictyostelium Discoideum And Its Paraburkholderia Endosymbionts, James Medina Dec 2022

Cooperation And Conflict In The Social Amoeba Dictyostelium Discoideum And Its Paraburkholderia Endosymbionts, James Medina

Arts & Sciences Graduate Student Theses and Dissertations

A big question in biology is how organisms compete in an environment of competitors for scarce resources. Part of the answer lies in distinguishing friend from foe and in forging cooperative bonds in the face of cheaters. The social amoeba – bacteria system I have studied here is an excellent place to explore these tensions. The first part of my thesis research involves a review of cooperation and conflict in the social amoeba Dictyostelium discoideum and a study of the limits on obligate social cheating in this species. The second part focuses on the benefits of associating with D. discoideum …


A Universal Mechanism Of G Protein Inhibition, Tyson Daniel Todd Dec 2022

A Universal Mechanism Of G Protein Inhibition, Tyson Daniel Todd

Arts & Sciences Graduate Student Theses and Dissertations

G protein coupled receptors transduce a truly staggering number of diverse extracellular signals including chemical messengers, physical force, and even photons into specific cellular responses through their coupling to heterotrimeric G proteins. G proteins amplify the originating signal through their binding to downstream effectors, activating a complex network of overlapping responses that allow the cell to respond perfectly to that specific stimulus. It is critical to the cell that this process is carried out faithfully in order to respond to the myriad environmental cues and avoid injury, exhaustion, and death for the individual cell or the development of pathology if …


Non-Canonical Beta-Lactam Antibiotics, Brett Wesley Virgin-Downey Dec 2022

Non-Canonical Beta-Lactam Antibiotics, Brett Wesley Virgin-Downey

Arts & Sciences Graduate Student Theses and Dissertations

In canonical β-Lactam antibiotics, such as penicillin, the strained nature of the β-Lactam ring leads to acylation of the catalytic serine in the active site of transpeptidases. In 2018, our lab reported a novel mechanism for monocyclic β-lactam antibiotics in the inhibition of glutamine synthetase (GS) by a natural product, tabtoxinine-β-lactam (TβL) using a 3-hydroxy-β-lactam pharmacophore. This work aims to generalize the β-lactam scaffold from TβL to act as a warhead against ATP-dependent carboxylate-amine ligase enzymes, with dihydrofolate synthetase (DHFS) as the test case. A pure 3-hydroxy-β-lactam warhead was synthesized and ligated both chemically and chemoenzymatically to different pteridine mimics. …


Cultivating Life: Skill, Sovereignty, And The Nature Of Knowledge, Bradley Jones Dec 2022

Cultivating Life: Skill, Sovereignty, And The Nature Of Knowledge, Bradley Jones

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation examines the cultivation of knowledge, nature, and farmers in U.S. alternative agriculture. Based on ethnographic fieldwork in the Hudson Valley of New York and Central Appalachia, I trace the movement of knowledge across prominent training guides, educational workshops, and apprenticeship programs designed to train the next generation of sustainable farmers. I argue that the knowledge communities of alternative agriculture (strive to) transmit not only technical capacity—the ability to productively farm sustainability—but also holistic ways of understanding the natural world and the human place in it. In doing so practitioners of alternative agriculture gain autonomy from the political-economic and …


Making Emotions Trustworthy, Xiaoyu Ke Dec 2022

Making Emotions Trustworthy, Xiaoyu Ke

Arts & Sciences Graduate Student Theses and Dissertations

I investigate ways by which agents can make their emotions more trustworthy from a perspective that’s informed by recent psychological research on the nature of emotion regulation. This dissertation is a collection of three articles, each addressing one type of cases of untrustworthy emotions in a particular context. Chapter one (Developing Appropriate Emotions) concerns emotions that are untrustworthy because they are irrelevant to the moral or epistemic judgements at hand. By situating the problem in the context of a situationist challenge to neo-Aristotelian virtue ethics, I argue that we can address this problem by developing ameliorative abilities such as emotion …


Interpersonal Emotion Regulation In Current And Remitted Major Depressive Disorder: An Experience Sampling Study, Yunjing Liu Dec 2022

Interpersonal Emotion Regulation In Current And Remitted Major Depressive Disorder: An Experience Sampling Study, Yunjing Liu

Arts & Sciences Graduate Student Theses and Dissertations

Individuals with major depressive disorder (MDD) have difficulties regulating emotion on their own. As people also turn to others for help with emotion regulation (i.e., interpersonal emotion regulation [IER]), we examined whether these difficulties extend to IER in current and remitted MDD. We generally expected individuals with current MDD (and remitted MDD to a lesser extent) to utilize IER in distinct ways compared to those with no history of psychiatric disorders (i.e., controls) due to differences in emotional, cognitive, and interpersonal functioning. Using experience sampling, adults with current MDD (n=48), remitted MDD (n=80), and controls (n=87) reported on how frequently …


Sik3 & Wnk Signals Through Fray To Regulate Glial K+ Buffering And Seizure Susceptibility In Drosophila Models Of Hyperexcitability, Lorenzo Laronn Lones Dec 2022

Sik3 & Wnk Signals Through Fray To Regulate Glial K+ Buffering And Seizure Susceptibility In Drosophila Models Of Hyperexcitability, Lorenzo Laronn Lones

Arts & Sciences Graduate Student Theses and Dissertations

K+ homeostasis is important for maintaining healthy, physiological levels of neuronal activity. Glial cells play a central role in maintaining homeostatic ion gradients. In previous work from our lab, we unravel a glial K+ buffering program that is centered on a key kinase, salt-inducible kinase 3 (SIK3). SIK3-HDAC4 signaling in glial regulates the transcription of channels and transporters involved in water and ion transport. Defects in this pathway lead to peripheral nerve edema, neuronal hyperactivity, and seizure sensitivity. In an hyperexcitability mutant, eag Shaker, we show this pathway is downregulated and genetic activation suppresses seizure behavior. In this thesis, I …


A War Of Compassion: Challenging The Species Barrier In The Works Of Céline And Léautaud, Dawn Mohrmann Dec 2022

A War Of Compassion: Challenging The Species Barrier In The Works Of Céline And Léautaud, Dawn Mohrmann

Arts & Sciences Graduate Student Theses and Dissertations

Jacques Derrida, when affirming the undeniability of animal suffering in L’Animal que donc je suis, states that there is “une guerre en cours … entre d’une part, ceux qui violent non seulement la vie animale mais jusqu’à ce sentiment de compassion et d’autre part, ceux qui en appellent au témoignage irrécusable de cette pitié” (50). This study investigates the nature of this ongoing war to which Derrida referred. I investigate both the nature of human cruelty and its counterpoint, empathy, which I propose as the response to the anthropocentrism that allows this struggle to continue. Through investigating theories of empathy, …


Dealing With Dimensionality: Problems And Techniques In High-Dimensional Statistics, Cezareo Rodriguez Dec 2022

Dealing With Dimensionality: Problems And Techniques In High-Dimensional Statistics, Cezareo Rodriguez

Arts & Sciences Graduate Student Theses and Dissertations

In modern data analysis, problems involving high dimensional data with more variables than subjects is increasingly common. Two such cases are mediation analysis and distributed optimization. In Chapter 2 we start with an overview of high dimensional statistics and mediation analysis. In Chapter 3 we motivate and prove properties for a new marginal screening procedure for performing high dimensional mediation analysis. This screening procedure is shown via simulation to perform better than benchmark approaches and is applied to a DNA methylation study. In Chapter 4 we construct a cryptosystem that accurately performs distributed penalized quantile regression in the high-dimensional setting …


Systems Level Analysis Of Organelle Biogenesis In Saccharomyces Cerevisiae, Kiandokht Panjtan Amiri Dec 2022

Systems Level Analysis Of Organelle Biogenesis In Saccharomyces Cerevisiae, Kiandokht Panjtan Amiri

Arts & Sciences Graduate Student Theses and Dissertations

Eukaryotic cells contain hundreds of subcellular structures that serve different functions to maintain cellular homeostasis. A hallmark of Eukaryotic cells is its compartmentalization into membrane-bound organelles. One of the grand challenges in quantitative cell biology is understanding the precision with which cells assemble and maintain subcellular organelles. Despite identification of numerous molecular factors that regulate organelle sizes we lack insight into the quantitative principles underlying organelle size control. We examine organelle sizes from Saccharomyces cerevisiae and human iPS cells with mathematical theory to show that cells can robustly control average fluctuations in organelle size. By demonstrating that organelle sizes obey …


Politics During And After Democratic Backsliding, Benjamin Rieth Schneider Dec 2022

Politics During And After Democratic Backsliding, Benjamin Rieth Schneider

Arts & Sciences Graduate Student Theses and Dissertations

Why do voters support backsliding incumbents? Under what conditions are voters more permissive to backsliding? In recent years, scholars have been interested in what leads to voters to support backsliding incumbents where we should expect them to be sanctioned and generally these answers have been focused on partisanship and polarization. I build on this literature by arguing that societal threat reduces the negative evaluation of backsliding actions and highlights the need for competent leaders to protect against future crisis. I develop an original formal model that considers the different strategies available to backsliding incumbents and shows that societal threat benefits …


Generation, Characterization, And Treatment Of Functional Zebrafish Models For Musculoskeletal Disorders, Julia Nicole Whittle Dec 2022

Generation, Characterization, And Treatment Of Functional Zebrafish Models For Musculoskeletal Disorders, Julia Nicole Whittle

Arts & Sciences Graduate Student Theses and Dissertations

Musculoskeletal disorders in humans present with a broad range of phenotypes that vary in severity, onset, and genetic cause. The musculoskeletal system is comprised of complex and diverse tissues that make up the majority of total body mass. Thus, mutations in many different genes with differing structure and function can produce phenotypically similar developmental and morphological defects in the muscle and skeleton. In addition, the muscular and skeletal systems develop non-autonomously, wherein development and function of each will affect development of the other. Thus, mutations in genes responsible for development of this complex system have the potential to influence morphogenesis …


Analysis Of Regulatory Element Variation In Autism Spectrum Disorder, Evin Mitchel Padhi Dec 2022

Analysis Of Regulatory Element Variation In Autism Spectrum Disorder, Evin Mitchel Padhi

Arts & Sciences Graduate Student Theses and Dissertations

Autism Spectrum Disorder (ASD) is a highly prevalent neurodevelopmental disorder that affects over 2% of the population. Studies of this disorder have demonstrated that genetics plays a strong role in the underlying etiology and over the past decade, substantial progress has been made in elucidating the genetic architecture. Large-scale studies have now been conducted to identify the genes involved in the genetic architecture by analyzing data from over 40,000 probands. However, the identification and characterization of regulatory elements involved have remained non-trivial for many reasons. Generally, studies that have analyzed whole genome sequencing (WGS) have demonstrated enrichment of de novo …


The Effects Of Nmda Antagonism On Neuronal Activity And Neurovascular Coupling In Non-Human Primate Cortex, Benjamin Thomas Acland Dec 2022

The Effects Of Nmda Antagonism On Neuronal Activity And Neurovascular Coupling In Non-Human Primate Cortex, Benjamin Thomas Acland

Arts & Sciences Graduate Student Theses and Dissertations

The N-methyl-D-aspartate receptor (NMDAR) plays a variety of important roles in the development and function of primate central nervous systems. This thesis describes three nonhuman primate studies that, together, demonstrate that pharmacologically reducing NMDAR activity not only causes dramatic changes in neural activity in cortex, but also changes the relationship between that activity and a key signal often used as its proxy in human studies, the blood-oxygen-level-dependent (BOLD) signal. The first study reveals that NMDA antagonism is sufficient to induce powerful low-frequency modulation of spiking activity and extracellular local field potential (LFP) and discusses the implications of this finding for …


Fructose Promotes The Growth Of Tumors Through Metabolite Exchange With Non-Malignant Tissues, Ronald Joseph Fowle-Grider Dec 2022

Fructose Promotes The Growth Of Tumors Through Metabolite Exchange With Non-Malignant Tissues, Ronald Joseph Fowle-Grider

Arts & Sciences Graduate Student Theses and Dissertations

The amount of dietary fructose consumed in the United States has increased considerably over the past five decades, largely due to the widespread use of high fructose corn syrup as a sweetener. The potential link between this elevated fructose intake and the development of cancer remains incompletely understood. Here we show that, even though cervical cancer cells themselves cannot directly utilize fructose carbon, diets high in fructose enhance the growth of cervical tumors by nearly threefold in mice. We demonstrate that efficient utilization of fructose carbon requires ketohexokinase-C, which was not expressed in ~100 cervical tumors that we examined from …


The Isotropic And Anisotropic Structure Of Antarctica From Seismic Inversion, Zhengyang Zhou Dec 2022

The Isotropic And Anisotropic Structure Of Antarctica From Seismic Inversion, Zhengyang Zhou

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation utilizes multiple techniques of earthquake tomography to investigate the seismic structure of the crust and mantle beneath Antarctica. The isotropic structure of the Antarctic crust and upper mantle is now constrained by several seismic studies, but until now few studies have investigated the anisotropic structure. Therefore, in this study, I focus on the anisotropic structure, which is crucial information to understanding current or historic deformation and flow patterns, as well as the organic process of Antarctica. I use the data from the seismic stations deployed on the Antarctica continent during the past 20 years, as well as other …