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2022

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Black Capitalists In The Transatlantic Financial Industry, Rachel Laryea Oct 2022

Black Capitalists In The Transatlantic Financial Industry, Rachel Laryea

Yale Graduate School of Arts and Sciences Dissertations

This dissertation is a study on the motivations and practices of willful Black participation in capitalism in the contemporary moment. With two sites of inquiry, Wall Street in New York City and Accra, Ghana, this ethnographic study examines how, and to what effect Black Capitalists successfully navigate financial institutions shaped by structural racism and covert inequality. I also track and assess the afterlives of Black professionals who leave Wall Street with an entrepreneurial posture as they sojourn across the Atlantic to create financial institutions of their own in Ghana. This migratory phenomenon is shaped in part by Ghana’s pivotal 2019 …

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The Biogeochemical Legacy Of The Landscape Of Fear: Pumas, Vicuñas, And Nutrient Cycling In The High Andes, Julia Dina Monk Oct 2022

The Biogeochemical Legacy Of The Landscape Of Fear: Pumas, Vicuñas, And Nutrient Cycling In The High Andes, Julia Dina Monk

Yale Graduate School of Arts and Sciences Dissertations

Research on biogeochemical cycles has historically focused on plant and microbial activity; however, growing evidence suggests that animals play an important role in nutrient cycling. Predators may be especially important drivers of these ecosystem processes, as they influence the quantity, quality, and distribution of organic matter through their control of herbivore prey. The role of predators and their herbivore prey in cycling and transporting nutrients may be particularly important in arid ecosystems, where productivity is low and resources are scarce and spatially clustered. In these landscapes with high heterogeneity of resources and risk, large herbivores may transport and hasten the …

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Structural And Functional Analysis Of Long Rnas, Rafael De Cesaris Araujo Tavares Oct 2022

Structural And Functional Analysis Of Long Rnas, Rafael De Cesaris Araujo Tavares

Yale Graduate School of Arts and Sciences Dissertations

The relationship between RNA structure and function has challenged generations of scientists trying to unravel the ways that RNA functions in health and disease. RNA is known to adopt elaborate 2-D and 3-D folds that extend their regulatory possibilities way beyond those enabled by their primary sequence. The discovery, more than a decade ago, that most of our genome is pervasively transcribed has largely expanded the repertoire of known structured RNAs and their modes of action. Adding to the complexity of this picture, posttranscriptional RNA modifications chemically change the building blocks of RNA polymers and can also affect their structural …

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The Dynamics Of Early Steps In Transcription And Their Dysregulation In X-Linked Dystonia Parkinsonism, Josh Zimmer Oct 2022

The Dynamics Of Early Steps In Transcription And Their Dysregulation In X-Linked Dystonia Parkinsonism, Josh Zimmer

Yale Graduate School of Arts and Sciences Dissertations

The dynamic life cycle of an RNA begins with transcription initiation and concludes when the mature transcript is degraded to monomer nucleotides. The early steps of RNA polymerase II (RNAPII) transcription, initiation and promoter-proximal pausing in metazoans, are the most complex and tightly orchestrated steps. To synthesize a single mature transcript,dozens of individual proteins must be assembled around a promoter to initiate transcription. In a reliable fashion, the initiated polymerase is halted only 20 to 60 base pairs downstream of the transcription start site (TSS) in a phenomenon called promoter-proximal pausing. Pausing is induced by a small number of additional …

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Paleontological Insights Into The Marine Silica Cycle, Sophie Westacott Oct 2022

Paleontological Insights Into The Marine Silica Cycle, Sophie Westacott

Yale Graduate School of Arts and Sciences Dissertations

Silicon is the second most abundant element in Earth’s crust and yet its seawater concentrations are far below saturation for any silicate mineral due to the activity of silicifiers, or organisms that make their shells, tests or spicules out of amorphous silica. On geologic timescales, the marine silica cycle is inextricably tied to the carbon cycle and global climate via the silicate weathering feedback and other pathways, and the concentration of silica in the ocean can vary the strength of these feedbacks. Silicifiers, primarily consisting of sponges, diatoms (phytoplankton) and radiolarians (zooplankton), are in turn affected by silica availability, and …

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Symptoms Of Schizophrenia And Their Relationship With Pharmacology And Learning Processes Across Species, Leah Fleming Oct 2022

Symptoms Of Schizophrenia And Their Relationship With Pharmacology And Learning Processes Across Species, Leah Fleming

Yale Graduate School of Arts and Sciences Dissertations

Schizophrenia is a debilitating psychiatric illness affecting roughly 1 percent of the global population. Psychiatry classifies schizophrenia, along with several other diagnoses, as a psychotic illness because patients experience a loss of touch with reality (psychosis). The current diagnostic criteria involve broad domains of symptoms including: Hallucinations, delusions, disorganized speech, grossly disorganized or catatonic behavior and negative symptoms (defined broadly by a lack of mental functioning). If a person experiences symptoms in two or more of these domains, they can be diagnosed with schizophrenia. This expansive definition makes schizophrenia difficult to investigate and treat. When examining the cause of schizophrenia, …

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The Optics Of Hatred: Visualizing The Vietnamese Other In Cambodia, Ngoc Tram Luong Oct 2022

The Optics Of Hatred: Visualizing The Vietnamese Other In Cambodia, Ngoc Tram Luong

Yale Graduate School of Arts and Sciences Dissertations

Informed by scholarship on the phenomenon of anti-Vietnamese violence and discrimination in Cambodia, this dissertation probes the construction of Vietnamese Otherness throughout Cambodian history and its imprints upon the lived reality of an eclectic population colloquially dubbed Yuon. It investigates the ways diverse groups of people identified as Vietnamese, either by themselves or others, can be construed within a Khmer ethno-nationalist discourse as the source of sociopolitical troubles—enemies from within, invaders of Cambodian land, strangers in our midst—that threaten the stability and survival of the Cambodian nation. This multilayered way of seeing has inspired waves of genocidal violence against the …

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Understanding Crystal Nucleation Using Molecular Simulations And Path Sampling Techniques: From Method Development To Atmospheric Contact Freezing, Sarwar Hussain Oct 2022

Understanding Crystal Nucleation Using Molecular Simulations And Path Sampling Techniques: From Method Development To Atmospheric Contact Freezing, Sarwar Hussain

Yale Graduate School of Arts and Sciences Dissertations

Crystal nucleation occurs during the initial stages of crystallization and constitutes the emergence of sufficiently large crystalline regions– known as critical nuclei– within the metastable liquid or the supersaturated solution. Nucleation plays an important role in a wide variety of areas such as cloud microphysics, semiconductor and solar cell manufacturing and the production of pharmaceuticals. In the absence of any external impurity, nucleation proceeds via homogeneous nucleation. Heterogeneous nucleation over an external surface, however, is the predominant mode of nucleation on the planet due to the abundance of a wide variety of impurities or crystal nucle- ation agents (CNA’s). Despite …

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Biophysical Signatures In Cancer And Sickle Cell Disease, Xingjian Zhang Oct 2022

Biophysical Signatures In Cancer And Sickle Cell Disease, Xingjian Zhang

Yale Graduate School of Arts and Sciences Dissertations

Physical cues are ubiquitous in biological systems, from the formation of molecules to the activities of living organisms. While bioprocessing requires functional and efficient biophysics, anomalies in biophysics also present medical challenges. My research integrated biophysical phenotyping and bioinformatics to investigate the physical cues in cancer and sickle cell disease. Cancer is one disease with a wide range of physical challenges. Numerous internal and environmental factors contribute to the heterogeneity of the tumor population. The development of tumor results in numerous physical stresses, which compress tumor cells. In addition, some aggressive tumor cells can migrate through the dense pores in …

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Rational Design Of Mixed-Graft Block Copolymers For Hierarchical Nanostructure Fabrication, Ruiqi Liang Oct 2022

Rational Design Of Mixed-Graft Block Copolymers For Hierarchical Nanostructure Fabrication, Ruiqi Liang

Yale Graduate School of Arts and Sciences Dissertations

Bottom-up fabrication of hierarchically structured materials with precisely controlled molecular arrangements is desirable for numerous advanced applications, ranging from separations, microelectronics, photonics, to energy storage. However, the inability to synthesize hierarchical structures with independently tunable lattices across multiple length scales limits the discovery of next-generation multifunctional materials. This thesis aims to develop a molecular self-assembly strategy based on multicomponent mixed-graft block copolymers (mGBCPs) to fabricate nanostructured materials with a variety of phase-in-phase hierarchical morphologies that combine nano- and mesoscale features. In this thesis, mGBCPs containing sequence-defined side chains can phase-separate to form ordered hierarchical structures with intramolecularly defined interfaces and …

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A Comparison Of Object Representations In The Primate Visual System And Convolutional Neural Networks, Viola Mocz Oct 2022

A Comparison Of Object Representations In The Primate Visual System And Convolutional Neural Networks, Viola Mocz

Yale Graduate School of Arts and Sciences Dissertations

Convolutional neural networks (CNNs) are the state-of-the-art artificial vision models for object recognition tasks. Their architecture is inspired by the organization of the ventral visual system of the brain, and although the way they are trained is not constrained by neural responses, the activations of artificial neural networks nevertheless show some similarities to activations of primate visual regions. Here, across three different studies, I compare the representation of objects in CNNs with that of the primate visual system in two different ways: (1) examining the relationship between object identity and non-identity information and (2) examining the representation of multiple objects. …

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Croup: Observation Time Post Racemic Epinephrine Dosing In Children With Croup, Children's Mercy Kansas City Oct 2022

Croup: Observation Time Post Racemic Epinephrine Dosing In Children With Croup, Children's Mercy Kansas City

Clinical Critically Appraised Topics

No abstract provided.

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Serpentine Micromixers Using Extensional Mixing Elements, George Tomaras, Chandrasekhar R. Kothapalli, Petru S. Fodor Oct 2022

Serpentine Micromixers Using Extensional Mixing Elements, George Tomaras, Chandrasekhar R. Kothapalli, Petru S. Fodor

Physics Faculty Publications

Computational fluid dynamics modeling was used to characterize the effect of the integration of constrictions defined by the vertices of hyperbolas on the flow structure in microfluidic serpentine channels. In the new topology, the Dean flows characteristic of the pressure-driven fluid motion along curved channels are combined with elongational flows and asymmetric longitudinal eddies that develop in the constriction region. The resulting complex flow structure is characterized by folding and stretching of the fluid volumes, which can promote enhanced mixing. Optimization of the geometrical parameters defining the constriction region allows for the development of an efficient micromixer topology that shows …

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Animals, Quality And The Pursuit Of Relevance., Karen L. Svenson, Stephen D Krasinski, Michael Ellis, Nadia Rosenthal, Edison Liu, Kenneth H Fasman Oct 2022

Animals, Quality And The Pursuit Of Relevance., Karen L. Svenson, Stephen D Krasinski, Michael Ellis, Nadia Rosenthal, Edison Liu, Kenneth H Fasman

Faculty Research 2022

In 2021, the National Institutes of Health Advisory Committee to the Director (ACD) announced recommendations to improve the reproducibility of biomedical research using animals. In response, The Jackson Laboratory faculty and institutional leaders identified key strategies to further address this important issue. Taking inspiration from the evolution of clinical trials over recent decades in response to similar challenges, we identified opportunities for improvement, including establishment of common standards, use of genetically diverse populations, requirement for robust study design with appropriate statistical methods, and improvement in public databases to facilitate meta-analyses. In this Perspective, we share our response to ACD recommendations, …

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A Standardized Nomenclature For Mammalian Histone Genes., Ruth L Seal, Paul Denny, Elspeth A Bruford, Anna K Gribkova, David Landsman, William F Marzluff, Monica Mcandrews, Anna R Panchenko, Alexey K Shaytan, Paul B Talbert Oct 2022

A Standardized Nomenclature For Mammalian Histone Genes., Ruth L Seal, Paul Denny, Elspeth A Bruford, Anna K Gribkova, David Landsman, William F Marzluff, Monica Mcandrews, Anna R Panchenko, Alexey K Shaytan, Paul B Talbert

Faculty Research 2022

Histones have a long history of research in a wide range of species, leaving a legacy of complex nomenclature in the literature. Community-led discussions at the EMBO Workshop on Histone Variants in 2011 resulted in agreement amongst experts on a revised systematic protein nomenclature for histones, which is based on a combination of phylogenetic classification and historical symbol usage. Human and mouse histone gene symbols previously followed a genome-centric system that was not applicable across all vertebrate species and did not reflect the systematic histone protein nomenclature. This prompted a collaboration between histone experts, the Human Genome Organization (HUGO) Gene …

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Autosomal Recessive Lrp1-Related Syndrome Featuring Cardiopulmonary Dysfunction, Bone Dysmorphology, And Corneal Clouding., Paul R Mark, Stephen A Murray, Tao Yang, Alexandra Eby, Angela Lai, Di Lu, Jacob Zieba, Surender Rajasekaran, Elizabeth A Vansickle, Linda Z Rossetti, Lucia Guidugli, Kelly Watkins, Meredith S Wright, Caleb P Bupp, Jeremy W Prokop Oct 2022

Autosomal Recessive Lrp1-Related Syndrome Featuring Cardiopulmonary Dysfunction, Bone Dysmorphology, And Corneal Clouding., Paul R Mark, Stephen A Murray, Tao Yang, Alexandra Eby, Angela Lai, Di Lu, Jacob Zieba, Surender Rajasekaran, Elizabeth A Vansickle, Linda Z Rossetti, Lucia Guidugli, Kelly Watkins, Meredith S Wright, Caleb P Bupp, Jeremy W Prokop

Faculty Research 2022

We provide the first study of two siblings with a novel autosomal recessive LRP1-related syndrome identified by rapid genome sequencing and overlapping multiple genetic models. The patients presented with respiratory distress, congenital heart defects, hypotonia, dysmorphology, and unique findings, including corneal clouding and ascites. Both siblings had compound heterozygous damaging variants, c.11420G > C (p.Cys3807Ser) and c.12407T > G (p.Val4136Gly) in

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Structural Basis For The Assembly Of Omcs And Omcs-Like Cytochrome Nanowires In Diverse Microbial Species, Vishok Srikanth Oct 2022

Structural Basis For The Assembly Of Omcs And Omcs-Like Cytochrome Nanowires In Diverse Microbial Species, Vishok Srikanth

Yale Graduate School of Arts and Sciences Dissertations

Microbial extracellular electron transfer (EET) via surface appendages called microbial nanowires is important in a wide range of globally significant environmental phenomena and for applications in bioremediation, bioenergy, and biofuels. Since 2005, these nanowires have been thought to be type IV pili composed solely of PilA-N protein. However, structural analyses demonstrated that during EET, rather than pili, cells produce nanowires made up of cytochromes OmcS and OmcZ. The micrometer-scale OmcS nanowires show seamless heme stacking along the length of the filament, allowing for efficient electron transfer to extracellular acceptors or syntrophic partner cells.Polymerization of cytochromes is important in several biological …

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Abl2 Regulates Microtubule Dynamics Through Interaction With Both The Microtubule Lattice And Tubulin Dimers., Wanqing Lyu Oct 2022

Abl2 Regulates Microtubule Dynamics Through Interaction With Both The Microtubule Lattice And Tubulin Dimers., Wanqing Lyu

Yale Graduate School of Arts and Sciences Dissertations

Abl family kinases are believed to serve as central signaling nodes to transduce signals from upstream receptors to downstream signaling and cytoskeletal-associated proteins. Genetic studies in Drosophila indicate that Abl2 interacts functionally with microtubules (MTs), but the underlying mechanism(s) is (are) completely unclear. Here, I report that Abl2 directly binds MTs and tubulin to regulate MT dynamics. Abl2 binds with MTs via the C-terminal half, which is also mediated by the phosphorylation level of the N-terminus. Abl2 recognizes different MT lattice states, with a higher preference for GMPCPP-MTs than GDP-MTs. Abl2 also binds tightly to tubulin dimers, which is mediated …

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Data-Driven Analyses In Obesity And Chemosensory Neuroimaging, Michael Charles Farruggia Oct 2022

Data-Driven Analyses In Obesity And Chemosensory Neuroimaging, Michael Charles Farruggia

Yale Graduate School of Arts and Sciences Dissertations

Data-driven functional connectivity analyses in the chemical senses are relatively uncommon, with current literature largely predominated by Psychophysiological Interaction (PPI), Dynamic Causal Modeling (DCM), or Structural Equation Modeling (SEM) techniques. The aim of this dissertation is to expand data-driven analyses in the chemical senses (and using chemosensory stimuli) to promote the use of techniques not based on a priori hypotheses or derived from potentially irreproducible literature.Chapter One details a systematic review of functional connectivity analysis in the chemosenses, which demonstrates that, out of 103 studies examined, the vast majority use hypothesis-driven techniques. Moreover, these studies comprise topics of olfaction, gustation, …

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Monitoring Translation Regulation By Structured Rna Elements, Caroline Focht Oct 2022

Monitoring Translation Regulation By Structured Rna Elements, Caroline Focht

Yale Graduate School of Arts and Sciences Dissertations

Translation initiation across domains of life is a tightly regulated process, and functional RNA motifs are critical regulatory features. This dissertation largely focuses on developing a novel technique with which to quantify the effect these RNA elements have on translation initiation and on unraveling the functional requirements of these structures. I have leveraged RelE’s ribosome-dependent endonuclease activity to develop a quantitative assay for translationally regulated mRNAs and validated this method on two bacterial translational riboswitches. I have also demonstrated its applicability to eukaryotic systems by showing that RelE can measure isoform-driven differences in ribosome loading between yeast 5′ leader sequences. …

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Discovery Of Novel Covalent And Non-Covalent Inhibitors Of Hiv-1 Reverse Transcriptase, Zachary Carter Oct 2022

Discovery Of Novel Covalent And Non-Covalent Inhibitors Of Hiv-1 Reverse Transcriptase, Zachary Carter

Yale Graduate School of Arts and Sciences Dissertations

The HIV/AIDS crisis remains a major world health problem, particularly in under-developed countries. Though advancements made in highly active retroviral therapy (HAART) in recent years have significantly reduced the annual deaths, the emergence of problematic mutant variants, coupled with issues of dosing, pill burden, and compliance, have necessitated the continued improvement of these therapeutics. Diversifying the scaffolds of non-nucleoside reverse transcriptase inhibitors (NNRTIs) used in combination therapy has the benefit of overwhelming the virion and raising the genetic barrier to resistance-associated mutations (RAMs). Additionally, the emergence of covalent RT inhibitors (CRTIs) opens the possibility of complete, irreversible eradication of the …

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Design, Synthesis, And Characterization Of Novel Mgmt-Dependent, Mmr-Independent Agents For The Treatment Of Glioblastoma Multiforme, Kingson Lin Oct 2022

Design, Synthesis, And Characterization Of Novel Mgmt-Dependent, Mmr-Independent Agents For The Treatment Of Glioblastoma Multiforme, Kingson Lin

Yale Graduate School of Arts and Sciences Dissertations

Glioblastoma multiforme (GBM) is a devastating disease afflicting over 20,000 new patients per year in the US with a 5-year survival rate of ~5%. The current standard of care treatment for GBMs consists of radiation therapy with concurrent and adjuvant chemotherapy with temozolomide (TMZ). TMZ is a prodrug that generates methyl diazonium in vivo, which in turn methylates DNA. O6-Guanine is the clinically significant site of DNA alkylation by TMZ. In healthy cells these lesions are reversed by O6-methylguanine methyltransferase (MGMT), a suicide DNA repair enzyme. However, loss of MGMT expression is common in many cancers such as grade 2/3 …

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The Immunologic And Epigenomic Regulation Of Hiv-1 Persistence, Jack A. Collora Oct 2022

The Immunologic And Epigenomic Regulation Of Hiv-1 Persistence, Jack A. Collora

Yale Graduate School of Arts and Sciences Dissertations

Curing HIV-1 is challenging due to the presence and persistence of CD4+ T cells harboring HIV-1 proviruses. Understanding the epigenetic and transcriptional regulation that enables HIV-1 to persist despite antiretroviral therapy (ART) and immune pressure is critical to counteracting this latent reservoir. A first chapter consists of an edited published review and preview covering a relevant subset of known features of HIV-1 persistence and HIV-1-T cell interaction biology. The remaining three chapters are parallel projects to understand the multifaceted nature of HIV-1: the interrogation and longitudinal tracking of HIV-1 RNA+ cells from infected individuals, the identification HIV-1 silencing host factors …

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Identifying Immunological Biomarkers In Massive Public Data, Daniel G. Chawla Oct 2022

Identifying Immunological Biomarkers In Massive Public Data, Daniel G. Chawla

Yale Graduate School of Arts and Sciences Dissertations

Recent advances in high-throughput experiments and systems biology approaches have resulted in hundreds of publications profiling immune responses to exposures such as pathogens and vaccines. Immune profiling is important for an emerging class of disease diagnostic technologies, as well as for understanding the mechanisms underlying disease pathogenesis and vaccine response. Massive amounts of public data are available for biomarker discovery and mechanistic profiling, including both datasets capturing transcriptional profiles of the immune system as well as published signatures describing changes that occur (e.g., in gene expression or cellular phenotypes) following infection or vaccination. This wealth of public data presents both …

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Leveraging Individual Differences To Gain Insight Into The Developing Functional Connectome, Corey Horien Oct 2022

Leveraging Individual Differences To Gain Insight Into The Developing Functional Connectome, Corey Horien

Yale Graduate School of Arts and Sciences Dissertations

Studying individual differences in functional connectomes provides a powerful framework to tackle questions in developmental human neuroscience. In this work, I use such a framework to study a multitude of factors, ranging from data quality control issues to building predictive models of clinically relevant phenotypes in neurodiverse youth. The first empirical chapter explores how factors related to the reliability of functional connections, namely the amount of scan data, in-scanner head motion, and the spatiotemporal resolution of data acquisition affect the detection of individual differences. In the second empirical chapter, I demonstrate that individual differences in connectomes are stable in developing …

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Elements Of The Ubiquitin Ligase Doa10 Regulating Protein Ubiquitylation And Er Membrane Extraction, Adrian Mehrtash Oct 2022

Elements Of The Ubiquitin Ligase Doa10 Regulating Protein Ubiquitylation And Er Membrane Extraction, Adrian Mehrtash

Yale Graduate School of Arts and Sciences Dissertations

In endoplasmic reticulum-associated degradation (ERAD), misfolded proteins at the endoplasmic reticulum (ER) are degraded by the proteasome after undergoing ubiquitylation. In yeast, Doa10 (MARCHF6/TEB4 in humans) is a conserved membrane-embedded E3 ubiquitin ligase that functions with the E2 ubiquitin-conjugating enzymes Ubc6 and Ubc7. These E2s use a sequential E2 mechanism where Ubc6 attaches a single ubiquitin molecule to a lysine, serine, or threonine residue of a substrate that is subsequently elongated by Ubc7 to form a poly-ubiquitin chain. How the Doa10 complex mediates non-canonical and sequential poly-ubiquitylation of its substrates is unclear. I determine the conserved 16-residue C-terminal element (CTE) …

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Neoantigen-Driven B Cell And Cd4 T Cell Collaboration Promotes Anti-Tumor Cd8 T Cell Responses In Lung Adenocarcinoma, Can Cui Oct 2022

Neoantigen-Driven B Cell And Cd4 T Cell Collaboration Promotes Anti-Tumor Cd8 T Cell Responses In Lung Adenocarcinoma, Can Cui

Yale Graduate School of Arts and Sciences Dissertations

Lung cancer is the leading cause of cancer-related mortality worldwide, accounting for ~1.8 million deaths annually. Lung adenocarcinoma (LUAD) is the most common form of non-small cell lung cancer (NSCLC; 40% of cases) and is most frequently associated with mutations in KRAS proto-oncogene (30% of cases). Traditionally, therapeutic options for KRAS-mutant LUAD have been limited, but the successful application of immune checkpoint blockade (ICB) targeting the PD-1 pathway has changed the therapeutic landscape. The success of PD-1-blockade therapy has also changed the perception that LUAD is a non-immunogenic cancer type because anti-PD-1/PD-L1 treatment potentiates the function of previously activated T …

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Paleoenvironmental Context Of Early Stone Age Archaeology: An Analysis Of The Gona Fauna Between ~3 And 1 Ma., Amanda Christie Leiss Oct 2022

Paleoenvironmental Context Of Early Stone Age Archaeology: An Analysis Of The Gona Fauna Between ~3 And 1 Ma., Amanda Christie Leiss

Yale Graduate School of Arts and Sciences Dissertations

The advent of tool-making has long been associated with expanding grasslands in Africa. My dissertation reconstructs paleoenvironments at Gona, in the Afar region of Ethiopia, between ~3–1 Ma (1) to make inferences about how hominins were utilizing the paleo-landscape and interacting with mammalian communities and (2) to investigate whether the environment was influential in the development of stone tools. This time period spans the origin of our genus Homo and the evolution of Homo erectus, and it provides evidence of increased behavioral complexity (stone tools), brain expansion, and the acquisition of large nutrient-rich food sources (animal carcasses). Because of the …

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Understanding Distinct Roles Of Egfr Family Mutations In Different Cancers, Chun Hu Oct 2022

Understanding Distinct Roles Of Egfr Family Mutations In Different Cancers, Chun Hu

Yale Graduate School of Arts and Sciences Dissertations

The epidermal growth factor receptor (EGFR) is frequently mutated in human cancer and is an important therapeutic target. EGFR inhibitors have been successful in lung cancer, where mutations in the intracellular tyrosine kinase domain activate the receptor, but not in glioblastoma multiform (GBM), where mutations occur exclusively in the extracellular region. In this dissertation, I show that common extracellular GBM mutations prevent EGFR from discriminating between its activating ligands. Different growth factor ligands stabilize distinct EGFR dimer structures that signal with different kinetics to specify or bias outcome. EGF itself induces strong symmetric dimers that signal transiently to promote proliferation. …

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The Resurgence Of The Nuu-Chah-Nulth First Nations In The Clayoquot Sound Bio-Cultural Landscape: A Case Study Of Iisaak Forest Resources, Ltd., Cintra Cady Agee Oct 2022

The Resurgence Of The Nuu-Chah-Nulth First Nations In The Clayoquot Sound Bio-Cultural Landscape: A Case Study Of Iisaak Forest Resources, Ltd., Cintra Cady Agee

Yale Graduate School of Arts and Sciences Dissertations

The Central Region Nuu-chah-nulth First Nations (NCN) are an alliance of five First Nations: the Ahousaht, the Tla-o-qui-aht, the Hesquiaht, the Toquaht, and the Ucluelet. Their traditional territories cover the central west coast of Vancouver Island, British Columbia (BC)—known as Clayoquot Sound. Industrial logging concessionaires had clearcut much of the ‘old-growth’ forests in Clayoquot. These were public lands, and multiple forest values important to multiple stakeholders had been reduced. In 1984, the NCN obtained a logging injunction for Meares Island in Clayoquot Sound. The NCN publicly protested for additional curbs on logging in their traditional territories. In the early 1990s, …

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