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Essays On Financial Crises
Get PDFThis dissertation studies financial crises of the Sudden Stop type where large reversals in the current account are triggered by a deflation mechanism that tightens the borrowing capacity of individuals, and amplifies the effects of negative shocks. These episodes are characterized by large drops in consumption and domestic asset prices. The first chapter argues that inequality in wealth and leverage across households plays an important role in determining the aggregate effects of a crisis. Next, the second chapter studies the role that foreign direct investment flows have on the different frequency of crises observed in advanced and emerging economies. Finally, the third chapter develops a new algorithm that allows solving dynamic stochastic general equilibrium (DSGE) models with occasionally-binding constraints much faster than existing methods
Lymphocyte Egress Signal Sphingosine-1-Phosphate Promotes Erm-Guided, Bleb-Based Migration
Get PDFEzrin, radixin, and moesin (ERM) family proteins regulate cytoskeletal responses bytethering the plasma membrane to the underlying actin cortex. Mutations in ERM proteins lead to severe combined immunodeficiency, but the function of these proteins in T cells remains poorly defined. Using mice in which T cells lack all ERM proteins, we demonstrate a selective role for these proteins in facilitating egress from lymphoid organs in response to sphingosine-1-phosphate (S1P), a pleiotropic signaling lipid abundant in the blood and lymph. ERM-deficient T cells display defective S1P-induced migration in vitro, despite normal responses to standard protein chemokines that control entry into and migration within lymphoid organs. Analysis of these defects revealed that S1P promotes a fundamentally different mode of migration than chemokines, characterized by intracellular pressurization and bleb-based motility. ERM proteins facilitate this process, controlling directional migration by limiting blebbing to the leading edge. We propose that the distinct modes of motility induced by S1P and chemokines are specialized to allow T cell migration across lymphatic barriers and through tissue stroma, respectively
Desmin And Microtubules Maintain Nucear Shape And Chromatin Organization In The Adult Cardiomyocyte
Get PDFMechanical forces are transduced to nuclear responses via the linkers of the nucleoskeleton and cytoskeleton (LINC) complex, which couples the cytoskeleton to the nuclear lamina and associated chromatin. While disruption of the LINC complex can cause cardiomyopathy, the relevant interactions that bridge the nucleoskeleton to cytoskeleton are poorly understood in the cardiomyocyte, where cytoskeletal organization is divergent from that of other cell types. Furthermore, while microtubules and desmin intermediate filaments associate closely with cardiomyocyte nuclei, the importance of these interactions is unknown. Here, we sought to determine how cytoskeletal interactions with the LINC complex regulate nuclear homeostasis in the cardiomyocyte and health of the myocyte as a whole.To this end, we acutely disrupted the LINC complex, microtubules, actin, and intermediate filaments and assessed the consequences on nuclear morphology and genome organization in rat ventricular cardiomyocytes via a combination of super-resolution imaging, biophysical, and genomic approaches. We find that a balance of dynamic microtubules and desmin intermediate filaments is required to maintain nuclear shape and the fidelity of the nuclear envelope and lamina. Upon depletion of desmin (or nesprin [nuclear envelope spectrin repeat protein]-3, its binding partner in the LINC complex), polymerizing microtubules collapse the nucleus and drive infolding of the nuclear membrane. This results in DNA damage, a loss of genome organization, and broad transcriptional changes. The collapse in nuclear integrity is concomitant with compromised contractile function and may contribute to the pathophysiological changes observed in desmin-related myopathies
Confronting The System: How Local Cross-Sector Education Collaborations Address Barriers To Postsecondary Access & Attainment
Get PDFCross-sector education collaborations, sometimes termed “collective impact” or “cradle-to-career” initiatives, have emerged in recent years across the U.S. as local interventions attempting to align services among educational institutions, local government, businesses, other community-based organizations, and philanthropies to improve educational outcomes. This study utilizes case study methods to focus on how one cross-sector education collaboration, Graduate Tacoma, works to improve postsecondary degree attainment in its local community and ensure equitable outcomes across student groups in the process. Drawing on 26 interviews with organizational stakeholders, internal documents, and a variety of other secondary data sources, the study addresses three facets of cross-sector collaboration implementation: 1) strategies utilized in Graduate Tacoma’s Tacoma College Support Network to address postsecondary readiness, enrollment, and attainment, 2) how those strategies relate to influencing postsecondary-related outcomes and equity in outcomes, and 3) conditions contributing to how those strategies connect to targeted educational outcomes. Findings suggest that strategies are most shaped by organizational missions and leadership of those stakeholders willing to collaborate. Those strategies where the local school district was heavily involved have had the most influence in shaping targeted educational outcomes. The relationships created among collaboration stakeholders also produce other kinds of public value, improving understanding of how sustained collaboration strategies impact organizational responses addressing postsecondary enrollment, attainment, and educational equity concerns. Study conclusions point to conceptual and methodological considerations for researchers in understanding the forces that need to be considered in assessing how cross-sector education collaborations contribute to systemic educational improvements. By describing the challenges and opportunities in implementing this cross-sector education collaboration, this study also has implications for how policymakers and practitioners can leverage school district and other partnerships in their communities for systemic change
The Role of Interleukin-4 Receptor Signaling in Neonatal Adipocyte Precursors
No full textAdipose tissue has multiple functions including defense against the cold through thermogenesis of brown and beige adipocytes. The type 2 immune cytokine Interleukin-4 (IL-4) can increase beige adipogenesis in mature rodents. However, developing animals use a distinct adipocyte precursor compartment for adipogenesis compared to adults. In this body of work, we analyze the effects of IL-4 on the adipose tissue of developing rodents. In rats, we found that exogenous IL-4 induced an acute increase in beige adipogenesis and a persistent decrease in overall adipogenesis in neonatal inguinal white adipose tissue (iWAT). We determined that DPP4+ progenitors and ICAM1+ preadipocytes were the populations expressing IL-4 receptor in neonatal mice. Isolating neonatal ICAM1+ preadipocytes for RNA-seq, we discovered no significant differentially regulated genes in IL-4RαKO compared to WT. After adipogenic differentiation of IL-4RαKO and WT ICAM1+ preadipocytes, we also found no changes in adipocyte gene expression. However, using neonatal WT ICAM1+ preadipocytes, we show that IL-4 pretreatment increases Ucp1 expression. We also identified that IL-4 directly interferes with the process of adipogenesis, decreasing adipocyte maturation. Overall, these findings describe the role of IL-4 in developing iWAT, identify the precursor population altered by IL-4 receptor signaling and characterize long term effects of IL-4 that may influence the later onset of obesity
Functional Characterization of TRIB1, a Gene Associated with Multiple Cardiometabolic Traits
No full textGenetic variants near the TRIB1 gene are significantly associated with plasma lipid traits and coronary artery disease. While data suggest TRIB1 is the causal gene for these traits, the mechanisms by which TRIB1 affects plasma lipids are not fully understood. In these studies, I sought to elucidate the physiological and molecular mechanism by which TRIB1 affects plasma lipids. Using a Trib1 hepatocyte specific deletion mouse model (Trib1Δhep), I demonstrated that Trib1Δhep mice have significantly increased plasma total cholesterol, HDL cholesterol, non-HDL cholesterol, LDL cholesterol and apoB protein levels, as well as impaired postprandial triglyceride clearance. I also showed that Trib1Δhep mice have markedly delayed catabolism of LDL-apoB and VLDL-apoB due to significantly decreased Ldlr mRNA and protein expression. Since TRIB1’s most studied molecular function is the COP1-mediated ubiquitination and proteasomal degradation the transcription factor CEBPa, I explored if this interaction is responsible for TRIB1 effects on plasma lipids and LDLR. I demonstrated that hepatic deletion of Cebpa in Trib1Δhep mice eliminated the effects on plasma lipids, apoB catabolism and hepatic LDLR regulation. Additionally, I identified the Activating Transcription Factor 3 (Atf3) as a possible novel mechanism linking TRIB1 to the regulation of LDLR in a CEBPa dependent manner. We also discovered that Trib1 whole body deletion (Trib1 KO) on a pure C57BL/6 background leads to a highly penetrant neonatal lethal phenotype, with less than 5% of Trib1 KO mice making to weaning stages. Our studies determined that Trib1 KO perish between day 0 and day 1 after birth likely due to severely low blood glucose levels. I also determined that about adult Trib1 KO mouse have decreased fasting glucose levels, and improved glucose and insulin tolerance. Overall, my studies stablish Trib1 and its regulation of CEBPa as critical factors in the regulation of multiple metabolic pathways affecting plasma lipids, as well as novel regulators of the LDLR and glucose metabolism
Neutron Cross Section Measurement in the Protodune-SP Experiment
No full textUnderstanding the detector response to neutrons will be critical for performing neutrino oscillation analyses in the next-generation Deep Underground Neutrino Experiment (DUNE). The DUNE physics program is centered around measuring the neutrino flavor composition as a function of their energy both at the near and the far detector. Neutrinos in the DUNE beam will have energies ranging between 100 MeV and 10 GeV, which is significant, because individual neutrino energies will not be known beforehand and will have to be reconstructed. Neutrino interactions in DUNE will produce leptons and hadrons – including protons, pions, and neutrons. Neutrons can transport energy away from their origin and sometimes go undetected. In addition to the primary neutrons produced by the neutrino, subsequent interactions of the charged hadrons can result in secondary neutrons. Neutrons are a source of missing energy and will bias the neutrino energy measurement. Currently, there is also a 20% energy scale uncertainty and a 40% uncertainty on the energy resolution for neutrons in DUNE, which must be addressed. ProtoDUNE Single-Phase (ProtoDUNE-SP) is a 770-ton prototype for the DUNE far detector and was designed to both validate the technology that will be employed in DUNE and to measure cross sections for the charged hadrons (pions, protons, and kaons) at the relevant energies for DUNE. The ProtoDUNE-SP experiment, therefore, is in a unique position to characterize the secondary neutron component for DUNE. This is achieved by searching for candidate neutron interactions in ProtoDUNE-SP events and using these to facilitate a measurement of the neutron inelastic cross section as well as an estimate of the neutron energy and number. The cross section measurement presented here is based on neutrons produced in 1 GeV, π+ events captured in 2018 by ProtoDUNE-SP in accordance with the production and cross section models in theGEANT4 simulation toolkit, version 4.10.6p1. The best-fit neutron inelastic cross section, in the kinetic energy range of 114 to 314 MeV, is 1.24+0.10−0.08 (stat. ⊕ syst.) barns
Imagining Classrooms: A Comparative Case Study of Pedagogy and Learning in Teacher Education
No full textThis dissertation is motivated by the urgent uncertainty of teacher education pedagogy. The work is urgent because students and schools need teachers to be proficient, equitable, and self-sufficient from the moment they take the helm of the classroom, and it is uncertain because teacher education research has struggled to definitively articulate how most teacher educators teach and whether it affects teachers’ beliefs or practices in the long term. This uncertainty reflects the complexity of teaching and learning as well as the limitations of prior research on teacher education pedagogy, which has historically relied on small-scale self-studies in which teacher educators describe the workings of their own classrooms. Difficult to aggregate, disseminate, or evaluate, these studies often struggle to shed light on the broader field. In this dissertation, I compare the enacted practices of six secondary social studies and English Language Arts teacher educators at three institutions representing a range of pedagogical perspectives, and investigate the implications of those practices for teacher candidate learning. Data collection combined observations of teacher education coursework in six methods classes, with interviews with both teacher educators and candidates, as well as videos of teacher candidates’ teaching in the field. Analysis investigates three questions: How do teacher educators prompt candidates to engage in reflection about instructional practices? How does the discourse about practice construct images of students? And how do candidates take up teacher educators’ pedagogical content knowledge? The findings reveal that each methods course created its own imagined classroom, a projected space where novices and teacher educators constructed projections of teachers and students. The imagined classroom affords teacher educators substantial latitude to curate discussions of teaching, student learning, and the disciplines. Engaging in these projected spaces, novices appeared to internalize some elements of their instructors’ vision while retaining some of their own perspectives on teaching. Contrary to canards about education schools’ lack of rigor, this dissertation finds teacher educators and candidates engaged in nuanced reflective work. Further exploring the complexities of teacher learning and the challenges facing teacher educators will continue to support the systems responsible for developing future teachers
Educationalizing Assets: Framing Children’s Savings Accounts as an Educational Solution
No full textThis qualitative study explores the case of Children’s Savings Accounts or CSAs (also called Child Development Accounts or CDAs) by constructing a case study that includes both the national landscape of CSAs and a focal CSA program. Through a corpus of over 150 texts related to CSAs, 30 semi-structured interviews with proponents and supporters, and participant observation of CSA meetings and conferences and program activities for over one year, this study explores the role of framing and cultural discourses in making CSAs more focused on education. This shift occurred in how proponents talk about them, frame them, and how they are implemented. Though proponents initially framed CSAs as solving problems of welfare and poverty in the early 1990s, over the last three decades, proponents shifted toward framing CSAs in terms of educational aspirations and attainment. This educational aspiration frame resonates with cultural discourses about education and social mobility and serves to create consensus among diverse policy designs across the national landscape of CSA programs. Proponents today frame CSAs as a solution for educational problems such as racialized achievement gaps. This framing shapes the meaning of CSAs and their implementation: schools are seen as crucial partners as CSAs attempt to build ‘college-bound identity’ and metrics like academic achievement are proposed for judging the success of CSAs for changing students’ orientation toward their futures. This case illuminates the role of framing and discourse in the process of educationalization, wherein broader social problems are transformed into educational problems and the implications of this process for the organizational structures and practices. These practices elaborate and institutionalize CSAs in particular ways. This study contributes conceptually to identifying mechanisms of educationalization and implications of educational frames ‘winning out’ over other alternative frames for new social policies
Early Experience and the Development of Dopaminergic Circuitry
No full textThe developing brain is highly malleable, meaning that children are acutely sensitive to their early experiences, for better or for worse. Early adversity significantly increases the risk for psychopathology and learning challenges. Recent work in animal models powerfully suggests that the ventral tegmental area (VTA), a major source of dopaminergic projections to the rest of the brain, is a key mediator for how early stressful experiences can become biologically embedded: in mice, absent or disrupted caregiving results in latent vulnerability of the dopaminergic system to stress well into adulthood. Thus, it may be that early adversity causes a shift in the developmental trajectory of the VTA, with cascading effects on later motivational and socioemotional processes. However, little is known about whether similar disruptions in VTA circuitry are detectable in children. Thus, I leveraged fMRI methods in 4- to 10-year-old children, to examine the functional integrity of dopaminergic circuitry early in development. In Chapter 2, I tested whether stress exposure relates to VTA resting-state functional connectivity. I found an age x stress exposure interaction, such that only children with lower stress exposure showed a positive relationship between age and VTA-mPFC connectivity, consistent with an interpretation that high stress exposure is related to blunted VTA maturation. Chapter 3 examined children’s neural responses to naturalistic emotional content using movie fMRI, and linked to parenting behaviors observed in the lab. I found that children who experienced more negative parenting showed reduced VTA activity during positive emotion scenes. Finally, Chapter 4 examined curiosity, a behavior that is supported by dopaminergic circuitry, and that encourages greater learning by engaging positive interest and intrinsic motivation. I tested whether individual differences in curiosity are reflected in resting-state connectivity patterns, and can be predicted by environmental experiences. Together, this work suggests that early experiences play a critical role in tuning dopaminergic neurocircuitry in children, with potentially enduring consequences for reward and socioemotional processing. This has implications both for education and for policy: how can we protect children in negative environments, and provide positive support that will allow them to best thrive as learners