48670 research outputs found
Sort by
Preclinical Investigations Of Genetic Correlates Of Alcohol Use Disorder
No full textAlcohol use disorder (AUD) is a common neuropsychiatric condition characterized by uncontrolled alcohol use that has serious medical and social consequences. AUD is heritable and intense work has been done to characterize its genetic basis. Preclinical studies have been critical in describing the functional significance of genes associated with AUD and have advanced our understanding of the neurobiological underpinnings of this disorder. This dissertation presents a collection of mouse studies that describe behavioral and neurochemical consequences of genetic or pharmacological manipulations of three systems genetically implicated in AUD: (i) the ZIP8 transporter, (ii) the GluK1-containing kainate receptors, and (iii) the α5-containing nicotinic acetylcholine receptors (nAChR). First, we describe disturbances in baseline behavior and increased volitional alcohol intake in animals lacking the ZIP8 transporter. We then report the effects of selective inhibition of GluK1-containing kainate receptors using LY466195 on ethanol consumption, reinforcement, and withdrawal. In the third study, we describe how disruption of α5-containing nAChR function influences adolescent ethanol and nicotine consumption, as well as adult drug intake in a sex-specific manner. Finally, we propose a framework to investigate the spontaneous manifestation of ethanol withdrawal in mice voluntarily drinking alcohol in a model with high face validity. Altogether, this body of work contributes to the current understanding of the etiology of AUD
Essays On The Market For Ipv4 Addresses
Get PDFIn this dissertation I study the market for IPv4 addresses - a multi-billion dollar market that is crucial for seamless internet communication. As this market has been understudied due to lack of accessible data, I collect data from various sources and create novel datasets that make this study possible.
In the chapter, ``Technology transition with frictions: Evidence from the market for IP addresses , I introduce IP addresses and the market for IPv4 addresses. Each IPv4 address is a durable, homogenous resource and has zero fundamental value once the standard changes from IPv4 to IPv6. Yet in the market prices have been continuously increasing. Understanding this pricing puzzle is not just interesting from a theoretical perspective, but also crucial for applied policy analysis.
To understand these and other empirical facts I explore the transition of firms from IPv4 to IPv6 in the presence of market frictions. The two key frictions in the market are switching costs and network effects. To substantiate this, I develop a dynamic model of firm behavior and calibrate the model to get a plausibly parametrized version of the model. This model can explain the striking increase in prices observed and the delay in IPv6 adoption.
In the parameterized version of the model I find that it would take 33 years to reach near complete IPv6 adoption. In counterfactual simulations, I examine the role of frictions and optimal adoption path by a social planner. A regulation that aims to shut down the market by a certain period leads to a coordination in IPv6 adoption and increase in producer surplus, thus making it in an effective policy tool to enable transition to IPv6. Thus, in the presence of market frictions, the market on its own could fail in efficiently transitioning to the next protocol
On Remembering, Ceasing To Be: For String Quartet & Chamber Ensemble
Get PDFOn remembering, ceasing to be is a four movement work for large chamber ensemble featuring string quartet. The work focuses on the act of remembering and the disorienting sensation this act can produce. The form intends to question, critique, and reconcile the existential detachment of examining one’s present against the romanticized past and memories of the present imagined in the past. The piece centers the string quartet, both as a genre and ensemble, within this form and tasks the quartet with pervasive elements of what I call “group virtuosity:” a virtuosity that is a focused objective (and also a natural result) of countless hours practicing and performing with the same people. Throughout the work the quartet is asked to periodically abandon the temporality and intonation of the winds and harp and cling to their identity as a single instrumental unit. These episodes come in the forms of insertions of historically important and personally meaningful string quartet literature, sudden shifts between disparate performance practice styles, and long, focused timbral and harmonic juxtapositions against the winds and harp. In these ways, On remembering, ceasing to be musicalizes the moments of separation from the present, both brief and lingering, that occur when remembering the past self and the present self the past imagined
Causal Inference Methods For Addressing Positivity Violations And Bias In Observational And Cluster-Randomized Studies
Get PDFObservational data are increasingly used to evaluate the effects of treatments on health outcomes. Causal inference provides a framework for formulating estimands of interest in this setting; however, identifiability of these estimands relies on certain assumptions. One assumption is called positivity, which requires the probability of treatment to be bounded away from 0 and 1. That is, for every covariate combination, we should observe both treated and control subjects. If the positivity assumption is violated, population-level causal inference necessarily involves some extrapolation. Ideally, a greater amount of uncertainty around the causal effect estimate is reflected in areas of non-overlap. With that goal in mind, we construct a Gaussian process model for estimating treatment effects in the presence of practical violations of positivity. Our method does not rely on strong parametric assumptions, provides a cohesive model for estimating treatment effects, and incorporates more uncertainty in areas of the covariate space where there is less overlap. Our work also focuses on the causal analysis of cluster randomized trials (CRTs) with a small number of clusters and a rare binary outcome. While estimation and covariate adjustment via generalized estimating equations (GEE) can account for chance imbalances and increase statistical power, analytical challenges frequently arise in such settings. For example, traditional GEE models tend to produce negatively biased standard error estimates, and regression adjustment often fails to converge with a rare outcome. We evaluate the utility of propensity score weighting and regression adjustment both in conjunction with bias-corrected sandwich variance estimators to precisely estimate a causal odds ratio and to obtain valid inference. In each project, we assess the proposed approaches and compare with alternative methods through simulation studies and then demonstrate their implementation with real use cases, including an observational study of right heart catheterization in female patients and a CRT that tests a sedation protocol in 31 pediatric intensive care units
Food Literacy Beyond The Plate: Exploring Creativity, Criticality, And Citizenship With Youth Of Color Working In Urban Agriculture
No full textYouth of color are navigating an unjust food system that disproportionately harms their health and education. In addition, their civic contributions to community health are often ignored or replaced with narratives of apathy or helplessness. This negatively affects their desire and ability to contribute to healthier, more just, and more sustainable futures. This dissertation centers the experiences and perspectives of youth of color who are working to promote community health through an urban agriculture internship program. Drawing from critical literacy studies, and employing ethnographic and practitioner inquiry methods, I analyze how youth of color (de)construct and interpret texts as they navigate their food landscapes.The first finding of this study reveals that participants saw food literacy as an opportunity for critical inquiry, rather than as a prescriptive practice for “healthy eating”. They inquired into the stories of food “before and beyond the plate” (Widener & Karides, 2014) and showed that the social, political, cultural, and historical aspects of food are just as important as the nutritional composition of food. The second finding shows that the literacy practices participants engaged in while at the farm—food label analyses, food justice walks, seed keeping, and intergenerational foodways interviews—foregrounded opportunities for them to interrogate hidden power structures within food systems. The third finding shows that imaginative and speculative storytelling about food and environmental justice can facilitate nuanced and rigorous understandings of “real world” problems and solutions within food systems. The study concludes with a discussion of how critical and creative inquiry into the stories behind food can provide opportunities for bridging formal and non-formal learning, fostering interdisciplinary collaboration, and facilitating intergenerational dialogue. In addition to sharing insights about how to better prepare young people for the world they will one day lead, the study presents an argument for building food systems that are more responsive to the realities, goals, needs, and strengths of the communities they are meant to serve
The Brazilian Stratup Ecosystem and the Potential Effects of Regulatory Sandboxes for Fintech Companies
Get PDFThis thesis examines the impact regulatory sandboxes could have in Brazil by analyzing what are the effects ‘Sandboxes’ have had in the United Kingdom. First, it adopts a literature review that aims to aggregate information about the current Startup Ecosystem in Brazil, briefly mentioning the introduction of new initiatives such as regulatory sandboxes. Then, it shows what research has found could be the benefits and risks of adopting ‘Sandboxes,’ with a special focus on developing countries. Finally, there is a case study about the United Kingdom and what are the effects regulatory sandboxes have had there. The analysis compares the UK with France because France do not have ‘Sandboxes’, but still have similar macroeconomic variables. Trough such analysis, the thesis argues that these results can be replicable in Brazil
Essays In Online News Consumption
Get PDFThis thesis focuses on the impact of the consumption environment on consumer preferences and decision making in consuming online news. The two chapters explore the effects of variation in the consumption environment in two different ways: offline, via differences in environmental factors, and online, via news-delivery platform changes.
The first chapter addresses whether the offline news environment affects online news consumption choices, focusing on whether consumers are more influenced by their innate preferences or outside environments when choosing to consume news - do consumers trade off online and offline news consumption? We build and estimate a model extending the standard discrete choice framework that allows us to identify this relationship via recovery of a single structural parameter. This parameter interprets the relationship between inside goods (online news) and the outside option (offline environmental news options). To estimate our model, we take advantage of a large novel data set of a subset of US users from a major web browser. We exploit the migration patterns of users as our source of identifying variation. In particular, we analyze consumer browsing before and after a move to identify our model. This exercise leads to evidence of independence between online and offline news goods at the population level, suggesting minimal offline environmental influence. However, further investigation points to significant between-individual heterogeneity in the relationship between online and offline news, which we then show is partially explained by observable consumer characteristics via machine learning methods. We explore the implications of this heterogeneity and propose additional analysis to identify the potential mechanisms behind our findings.
In the second chapter, we examine a change in the Facebook algorithm and its impact on online news browsing. We ask the question whether social media increases or decreases online news consumption, specifically of opinion-oriented content. The key to our identification of this impact is a change in the Facebook news algorithm that occurred over the first few months of 2018. Facebook deprioritized content that a users\u27 connections did not interact with, resulting in a large reduction in news consumption. We employ a matching design wherein we match treatment users who use Facebook - and thus are affected by changes in the Facebook algorithm - to those who do not use Facebook using characteristics of these users\u27 browsing habits. When news content is reduced on Facebook, we see a drop in news browsing behavior for these users relative to their peers who do not use Facebook, suggesting that social media use does increase news consumption as users do not merely substitute to other media. However, we also observe that compared to control users, our treatment users experience an increase in opinion-oriented content browsing when their access to social media news is reduced. This runs counter to our original speculation that social media would be correlated with increased opinion-oriented media consumption. We hypothesize potential mechanisms for these effects and propose tests to distinguish them. Overall, we see evidence consistent with online consumption environments having impact on consumption decisions, with much less impact coming from offline consumption environment
Monsters In The Cabinet: Anatomical Collecting, Embryology, And Bodily Difference In Holland, 1664-1850
Get PDFMonsters in the Cabinet uses the historical collection of abnormal fetuses to examine how scientific knowledge about non-normative bodies was produced. It asks how the collection, anatomical study, and comparison of real embryos and fetuses with congenital abnormalities—once called monsters—produced scientific knowledge which was embedded with claims about how a body’s form marked its place in the natural and social orders. The dissertation uses a range of Dutch sources, such as the records of midwives, museum collections, public health topographies, and scientific publications. These reveal the networks, scientific practices, and conceptual frameworks that transformed a fetal body into a research object from which knowledge about nature and physiology could be extracted. Seeking to understand the historical relationship between “monstrous births” and disability, the dissertation shows how the scientific knowledge and professional expertise gained from the study of fetal bodies was applied to living people by medical practitioners. It demonstrates that the comparative, synthetic, and material study of “monstrous” bodies was the basis upon which a normal model of development was scientifically produced. Moreover, anatomical preparations elevated the scope and authority of medical expertise in a way that endowed physicians with substantial bureaucratic influence in the early-nineteenth century, particularly with regards to public health initiatives addressing infant and maternal mortality and poor relief for disabled citizens
Network, Network Regression, And Equity Holding Network
No full textNetworks play a ubiquitous and crucial role in our lives and are powerful vehicles for us to perceive the interconnected relationships among agents. Understanding the structure of networks helps reveal the underlying mechanism of how agents interact and how networks affect agents\u27 behaviors and decision-making. In this dissertation, we study the network structure of the equity holding network in China and a fundamental network metric, centrality, which is often used in regression models to study the network effect on outcomes of interest. We further propose a novel supervised network centrality estimation (SuperCENT) methodology that improves upon a widely-used method for network regression with centrality
Copper A Novel Regulator Of Perk
No full textPERK is a transmembrane kinase located on the ER with a luminal domain that senses ER stresses, such as protein misfolding, and a cytosolic kinase domain. Upon stress sensing, PERK activates and phosphorylates eIF2α to attenuate global translation while upregulating select transcripts to re-establish protein homeostasis. In a secondary phase of signaling PERK can also induce apoptosis to dispose of terminally stressed and damaged cells. The thus delineated bi-phasic nature of PERK signaling requires tight regulation for homeostatic function, as evidenced by dysregulation of this pathway being implicated in many diseases, including cancers and neurodegenerative conditions. Pursuant attempts to therapeutically modulate PERK and its signaling outcomes have highlighted that our understanding of the determinants of adaptive vs. mal-adaptive signaling remain ambiguous, and further delineation of PERK regulation is required. Here we follow-up on a screen for copper regulated kinases in which PERK was identified as a potential hit. Copper binding activity was confirmed by selective pull-down with copper charged resin and ICP-MS quantification of bound copper. Furthermore a putative binding site identified based on homology copper-binding was determined to be necessary for kinase activity in in vitro kinase assay. PERK-copper binding was also determined to be a physiological method of PERK regulation as manipulations of copper availability in cells were able to modulate PERK activity and signaling. We are now using this relationship to examine how copper can be used to manipulate ER stress tolerance and cell fate outcomes. This novel regulatory mechanism has broad implications for modulating PERK activity in different diseases and disease models, and may constitute a previously unaccounted for variable in determining when PERK inhibition vs. activation is therapeutically beneficial. Our identification of PERK, with its known regulation of and by calcium, as a copper regulated kinase lays the groundwork for future studies evaluating how PERK may itself act as a node of integration and regulation between these two signaling networks, lending vast implications for the role of PERK in physiology and disease, as well as potential elucidation of the mechanisms driving some of the complex biological processes involved