Time-Resolved Cryo-EM Studies on Translation and Cryo-EM Studies on Membrane Proteins

Fu, Ziao Columbia University ProQuest Dissertations & These 2019 해외박사(DDOD)

Single-particle reconstruction technique is one of the major approaches to studying ribosome structure and membrane proteins. In this thesis, I report the use of time-resolved cryo-EM technique to study the structure of short-lived ribosome complexes and conventional cryo-EM technique to study the structure of ribosome complexes and membrane proteins. The thesis consists three parts. The first part is the development of time-resolved cryo-EM technique. I document the protocol for how to capture short-lived states of the molecules with time-resolved cryo-EM technique using microfluidic chip. Working closely with Dr. Lin's lab at Columbia University Engineering Department, I designed and tested a well-controlled and effective microspraying-plunging method to prepare cryo-grids. I demonstrated the performance of this device by a 3-A reconstruction from about 4000 particles collected on grids sprayed with apoferritin suspension. The second part is the application of time-resolved cryo-EM technique for studying short-lived ribosome complexes in bacteria translation processes on the time-scale of 10-1000 ms. I document three applications on bacterial translation processes. The initiation project is collaborated with Dr. Gonzalez's lab at Chemistry Department, Columbia University. The termination and recycling projects are collaborated with Dr. Ehrenberg's lab at Department of Cell and Molecular Biology, Uppsala University. I captured and solved short-lived ribosome intermediates complexes in these processes. The results demonstrate the power of time-resolved cryo-EM to determine how a time-ordered series of conformational changes contribute to the mechanism and regulation of one of the most fundamental processes in biology. The last part is the application of conventional cryo-EM technique to study ribosome complexes and membrane proteins. This part includes five collaboration projects. Human GABA(B) receptor project is the collaboration with Dr. Fan at Department of Pharmacology, Columbia University. Cyclic nucleotide-gated (CNG) channels project is the collaboration with Dr. Yang at Department of Biological Sciences, Columbia University. The cryo-EM study of Ybit-70S ribosome complex and Cystic fibrosis transmembrane conductance regulator (CFTR) project are the collaboration with Dr. Hunt at Department of Biological Sciences, Columbia University. The cryo-EM study of native lipid bilayer in membrane protein transporter is the collaboration with Dr. Hendrickson at Department of Biochemistry and Molecular Biophysics, Columbia University and Dr. Guo at Department of Medicinal Chemistry, Virginia Commonwealth University.

Structure-Conductivity Relationships in Group 14 Based Single-Molecule Wires

Su, Timothy A Columbia University ProQuest Dissertations & These 2016 해외박사(DDOD)

Single-molecule electronics is an emerging subfield of nanoelectronics where the ultimate goal is to use individual molecules as the active components in electronic circuitry. Over the past century, chemists have developed a rich understanding of how a molecule's structure determines its electronic properties; transposing the paradigms of chemistry into the design and understanding of single-molecule electronic devices can thus provide a tremendous impetus for growth in the field. This dissertation describes how we can harness the principles of organosilicon and organogermanium chemistry to control charge transport and function in single-molecule devices. We use a scanning tunneling microscope-based break-junction (STM-BJ) technique to probe structure-conductivity relationships in silicon- and germanium-based wires. Our studies ultimately demonstrate that charge transport in these systems is dictated by the conformation, conjugation, and bond polarity of the sigma-backbone. Furthermore, we exploit principles from reaction chemistry such as strain-induced Lewis acidity and ?-bond stereoelectronics to create new types of digital conductance switches. These studies highlight the vast opportunities that exist at the intersection between chemical principles and single-molecule electronics. (Abstract shortened by ProQuest.).

Under Wendy Bishop's Eye: An Autofictional Account of Teaching and Learning in a 21st Century (Creative) Writing Program

Amy Roosevelt, Maura Columbia University ProQuest Dissertations & These 2023 해외박사(DDOD)

"Under Wendy Bishop's Eye" examines the teaching, learning, and social environment of a graduate student in an American creative writing MFA program in the early years of the 21st century. This dissertation is a work of autofiction; it is both an autoethnography and a fictionalized story written in the form of a novel. The project uses the scholarship of writing studies' leader Wendy Bishop to discuss and analyze the dynamics of graduate student learning in creative writing courses, undergraduate learning in creative writing courses, graduate student teaching in creative writing courses, and graduate student teaching in expository writing or first-year composition courses at a four-year college. The project addresses the limitations of the "workshop method" for teaching creative writing, while supporting the benefits of writing pedagogy that includes cross-genre writing exercises in all university-level writing courses, specifically bringing "personal writing" and creative non-fiction into both creative writing and first-year composition course.

Nuclear Schiff Moment Search in Thallium Fluoride Molecular Beam: Rotational Cooling

Wenz, Konrad Columbia University ProQuest Dissertations & These 2021 해외박사(DDOD)

The search for physics beyond the Standard Model has been a main focus of the scientific community for several decades. Unknown physics in the form of new interactions violating the simultaneous reversal of charge and parity symmetries (CP) would, for example, provide a significant step towards understanding the baryon matter-antimatter asymmetry observed in the Universe. Such parameters are predicted to also manifest themselves in atomic and molecular systems in the form of both: permanent electric dipole moments and nuclear charge distribution asymmetries described by the nuclear Schiff moment. Both can be measured to a high degree of precision in modern experiments, allowing us to place stringent limits on parameters appearing in new fundamental theories.The Cold Molecule Nuclear Time Reversal Experiment (CeNTREX) is the latest approach to probing these effects. CeNTREX is a molecular beam experiment that uses thallium fluoride (205Tl19F) as its test species to measure energy shifts induced by the interaction of thallium's nuclear Schiff moment. It does so by performing nuclear magnetic resonance using a separate oscillatory fields technique. The precision of this measurement is dictated by the free precession time and the number of interrogated molecules, and is significantly enhanced by thallium fluoride's inherent properties.Employing novel methods, CeNTREX strives to achieve significant improvements to limits placed on the fundamental parameters. One such method is rotational cooling. It was thoroughly analyzed, simulated and experimentally confirmed - with the help of optical and microwave pumping, we collapsed the initial Boltzmann distribution of molecules amongst their rotational states into one chosen hyperfine state of the ground rotational state manifold.The efficiency of this process depends on multiple factors, the most crucial being the approach towards dark state destabilization and remixing. After careful investigation, we chose the most appropriate method and devised an efficient rotational cooling scheme. Experimental confirmation showed an enhancement factor of rf = 23.70 ± 1.13, very close to our theoretical predictions. This allows us to conclude that CeNTREX should provide a 2500-fold improvement over the current best measurements of the nuclear Schiff moment in thallium nucleus.

The Effect of Gun-Free Zones on Crimes Committed with a Firearm and Active Shootings in the United States

Reeping, Paul Michael Columbia University ProQuest Dissertations & These 2022 해외박사(DDOD)

Gun-free zones have the potential to increase or decrease the risk of gun crime and active shootings that occur within their borders. People who assume that gun-free zones increase gun related outcomes believe that the lack of the ability for law-abiding citizens to carry a firearm, and thus an inability to engage in defensive gun use if a threat presented itself, makes gun-free zones a soft target for crime. Those that assume gun-free zones decrease gun related outcomes believe the absence of firearms eliminates the risk of an escalation of violence to gunfire. Up until this point, there has been no quantitative research on the effectiveness of gun-free zones, despite the topic being highly controversial. This dissertation was therefore the first to: create and describe a dataset of active shootings in the United States, and assess the extent to which defensive gun use occurs during these events (Aim 1); conduct a cross-sectional ecological analysis for the in St. Louis, Missouri (2019), both city and county, comparing the proportion of crimes committed with a firearm that occur in gun-free school zones compared to gun-allowing zones immediately surrounding the gun-free zone to quantify the effectiveness of gun-free school zones and (Aim 2); conduct a spatial ecological case-control study in the United States where cases are the locations or establishments of active shootings between 2014 and 2020, to quantify the impact of gun-free zones on active shootings, and assess if active shooters target gun-free zones (Aim 3). The results of Aim 1 of this study suggested that defensive gun use during active shootings was rare, usually does not stop the attack, and does not decrease the number of casualties compared to active shootings without defensive use. Aim 1 also thoroughly described the novel active shooting dataset. I found in Aim 2 that gun-free school zones had fewer crimes committed with a firearm than corresponding gun-allowing zones in St. Louis, MO in 2019. There were 13.4% fewer crimes involving a firearm in gun-free school zones, with a confidence interval ranging from 23.6% fewer to 1.8% fewer (p-value: 0.025). Aim 3 determined that the conditional odds of an active shooting in an establishment that was gun-free were 0.375 times the odds of an active shooting in a gun-allowing establishment with a confidence interval ranging from 0.193 to 0.728 (p-value<0.01), suggesting that gun-free zones did not attract active shooters, and may even be preventative. In conclusion, gun-free zones did not appear to increase gun related outcomes and may even be protective against active shootings. Efforts across the United States to repeal laws related to gun-free zones, due to the belief that gun-free zones are targeted for violence, are therefore not backed by data. However, these are the first quantitative studies ever conducted on the effectiveness of gun-free zones, so more research is needed to build on the results of this dissertation.

Leaving and Returning Home: Insights on Migration Attitudes and Policies

Jaiteh, Salif Columbia University ProQuest Dissertations & These 2022 해외박사(DDOD)

This dissertation is about policies and attitudes toward emigration and return migration. It explores these topics in two parts. First, it asks what policies states employ to regulate emigration and what might explain the adoption of these policies and what form they take. It presents a variety of emigration-encouraging and -discouraging policies along with a rich set of examples of countries that have adopted them across the world. Using the UN World Population Policies database, it then shows how policies vary by region, with emigration-encouraging policies being more common in Asia and emigration-discouraging policies more present in Latin America. Moreover, it finds that having larger populations, receiving more remittances, being less democratic and having less state capacity are attributes of states that correlate positively with the adoption of emigration policies. Likewise, being more populous, receiving more remittances and having a lower share of the population that intends to migrate are characteristics of states that positively correlate with the adoption of policies that are more emigration-encouraging.The second part asks how social identity and economic concerns affect people’s attitudes toward emigration and return migration policies, respectively. By analyzing multiple survey experiments that were embedded in an original large-scale phone survey in The Gambia, it finds some support for the centrality of economic as well as ethnic concerns in the formation of attitudes toward emigration and return migration. These findings are in line with the main arguments developed in the dissertation. On the one hand, it argues that individuals hold other-regarding preferences, are concerned with the political demography of their country and receiving remittances when it comes to ethnicity. Which of these mechanisms is the strongest depends on the context of migration. On the other hand, people are concerned with the labor market effects of emigration in their country and therefore support policies encouraging the emigration of people with the same occupation as themselves and oppose policies encouraging their return. Regarding interaction effects, it finds some suggestive evidence that low-skilled people are more concerned with the economic dimension of migration policy than high-skilled people are.This dissertation makes essential contributions to the existing literature and policy debates as it advances our understanding of policies and attitudes toward less frequently studied areas of migration, including emigration, return migration and migration in the Global South.

The Cryogenic Infrastructure of the Xenon1T Dark Matter Experiment: From Design to Performance During the One Ton-Year WIMP Search

Zhang, Yun Columbia University ProQuest Dissertations & These 2021 해외박사(DDOD)

An abundance of evidence from a wide range of astrophysical and cosmological observations suggests the existence of nonluminous cold dark matter, which makes up about 83% of the matter and 27% of the mass-energy of the Universe. Weakly Interacting Massive Particles (WIMPs) have been one of the most promising dark matter candidates. Various detection techniques have been used to directly search for the interaction in terrestrial detectors where WIMP particles are expected to scatter off target nuclei. Over the last fifteen years, dual-phase time projection chambers (TPCs) with liquid xenon (LXe) as target and detection medium have led the WIMP dark matter search. The XENON dark matter search project is a phased program focused on the direct detection of WIMPs through a series of experiments employing dual-phase xenon TPCs with increasing target mass operated at the Gran Sasso underground laboratory (LNGS) in Italy. The XENON1T experiment is the most recent generation, completed at the end of 2018. The XENON1T dark matter search results from the one ton-year exposure have set the most stringent limit on the WIMP-nucleon spin-independent elastic scatter cross-section over a wide range of masses, with a minimum upper limit of 4.1 x 10-47 cm2 at 30 GeV ∙ c-2 and a 90% confidence level.XENON1T is the first WIMP dark matter experiment which has deployed a dual-phase xenon TPC at the multi-ton scale, with 3.2 t of LXe used. The large xenon mass posed new challenges in reliable and stable xenon cooling, in achieving and maintaining ultra-high purity as well as in efficient and safe xenon storage, transfer and recovery. The Cryogenic Infrastructure was designed and constructed to solve these challenges. It consists of four highly interconnected systems --- the Cryogenic System, the Purification System, the Cryostat and Cryogenic Pipe, and the ReStoX System. The XENON1T Cryogenic Infrastructure has performed successfully and will continue to serve the next generation experiment, called XENONnT, with a new Cryostat containing a total of 8.4 tons of xenon.I first give an instrument overview of the systems in XENON1T. I then review the cooling methods in LXe detectors which led to the design of the cooling system implemented in the XENON1T experiment, and suggest a design of the cooling system for future LXe dark matter experiments at the 50 tons scale. I describe and discuss in detail the design and the performance of the XENON1T Cryogenic Infrastructure. Finally, I describe the detector stability and the corresponding data selection in all three XENON1T science runs, and describe the dark matter search results from the one ton-year exposure.

The Making of Liberal Intellectuals in Post-Tiananmen China

Li, Junpeng Columbia University ProQuest Dissertations & These 2017 해외박사(DDOD)

This dissertation takes a relational approach to the intellectual debates in contemporary China by analyzing the formation of political ideas and crystallization of intellectual positions. It asks two questions: who are the Chinese liberals, and how were their distinctive bundles of political views formed? Drawing on 67 semi-structured interviews with Chinese intellectual elites across the ideological spectrum, as well as detailed historical and textual analyses, this dissertation examines the social forces that have shaped the political attitudes of liberal intellectuals in contemporary China. It argues against the prevailing attempts to define Chinese liberalism as a social category with a coherent ideology comparable to its Western counterpart; rather, as a community of discourse that contains a number of competing and contradictory discourses, it is embedded in China's social reality as an authoritarian regime governed by a communist party, and contingent on China's history straddling the Maoist and post-Mao eras. Rather than a monolithic or tight-knit group, Chinese liberals are comprised of an array of social actors, including scholars, journalists, lawyers, activists, and house church leaders. They are liberal not because of what they are for, but because of what they are against; more specifically, Chinese liberals are united by an anti-authoritarian mentality, which is a historical product of the Cultural Revolution from 1966 to 1976 and the Tiananmen Square protests of 1989. In addition to biographical factors, the views of Chinese liberals have been shaped by structural factors represented by the neoliberal reforms and the rise and growth of the intellectual field since the 1990s, as well as interactive factors manifested by the polar opposition between the liberals and the New Leftists. On the one hand, as state-driven capitalism unleashed China's economic potential, China was well on its way to becoming a major player in the international community toward the end of the 1990s; on the other hand, the fusion of the free market and political power led to rampant corruption and social injustice. How to make sense of China's crony capitalism became an important dividing line between the New Left and liberalism. As the intellectual debates were increasingly cast as part of global cultural production, how to appropriate Western thinkers and concepts became a site of contestation. While the dramatic expansion of higher education led to the growth of the intellectual field with its own logic and rules, in which both liberals and New Left intellectuals were struggling for symbolic power, the penetration of the political field remained, not only in terms of visible incentives and punishments, but also in terms of its subtle influence on the manner of problem construction and debate. Through combative interactions, the liberals and the New Leftists have defined themselves by reference to each other. In the process of binary opposition, the views of both sides have moved further and further apart with little overlap. This dissertation contributes to political sociology and the sociology of knowledge in three ways. First, departing from the conventional approach that takes political orientations for granted, it takes a relational approach by analyzing the dynamic processes of ideological formation and polarization. Second, it traces the process of ideological alignment and differentiation on three levels: structural, interactive, and biographical. Third, while it has been observed that intellectual elites have been the collective agents responsible for many democratic transitions worldwide since the early twentieth century, the internal division of the intellectuals has received much less attention. My work addresses this issue by analyzing how the Chinese intelligentsia has structuralized into binary opposition since the Tiananmen Square protests. In particular, I treat political ideas as historical contingencies, rather than fixed properties, that are internally shaped by "fractal distinctions." (Abstract shortened by ProQuest.).

Popular Propaganda in Pop Culture: How China Sells Its Ideology

Yao, Linan Columbia University ProQuest Dissertations & These 2023 해외박사(DDOD)

Why is authoritarian propaganda often uninspiring, and how can states create captivating content that competes in the modern information landscape? This dissertation theorizes that dictators must strike a balance between controlling the creative process of cultural elites to promote a specific ideology and unleashing their creative potential. Overbearing ideological constraints can suppress creativity, thus necessitating powerful incentives to produce engaging propaganda. This research empirically focuses on the resurgence of propaganda films in Chinese cinemas from the mid- to late-2010s, particularly following the 2018 administrative reform when the Central Propaganda Department assumed control of the film industry. This serves as a case study demonstrating how an authoritarian state can make propaganda interesting. Utilizing novel film industry data and qualitative fieldwork, I uncover a state propaganda strategy that effectively shapes popular culture in China. I show that the Chinese government has successfully enlisted the cultural expertise of the private sector to craft entertaining and marketable propaganda through direct mandates and through shaping a market environment favorable to propaganda. Additionally, I conducted an online field experiment that demonstrates that such propagandist entertainment likely sways the majority of viewers' opinions toward the regime. However, it is worth noting that these propaganda movies may backfire among a small portion of the audience - approximately 20% of participants - who already harbor a distaste for propaganda before watching the movie. The production and reception of propagandist entertainment beyond the film industry and outside China are also discussed in this dissertation.

Relationships as Regulatory Systems

Zee, Katherine S Columbia University ProQuest Dissertations & These 2021 해외박사(DDOD)

Interpersonal relationships are among the most important contributors to health and well-being. This dissertation investigates how and why relationships confer such benefits and proposes that relationships function as dynamic regulatory systems that enable people to cope effectively with challenging situations and pursue important goals. Across five Chapters, this work reveals the role of relationships in scaffolding effective individual self-regulation, dyadic coregulation (how partners dynamically modulate each other’s responses and regulate as a unit), and developmental regulation (adaptation to age-related challenges across the lifespan), particularly in the context of social support interactions. Chapter 1 introduces past research on the importance of social relationships, summarizes the rationale for focusing on social support interactions as a key context in which interpersonal regulation occurs, and presents an overview of the research and methods discussed in this dissertation. Chapter 2 investigates the role of social support in promoting effective self-regulation by conceptualizing, validating, and testing a new theoretical construct, Regulatory Effectiveness of Social Support (RES). RES proposes that recipients benefit from social support to the extent that it addresses their motivations to understand and manage their situation. In eight studies and a meta-analysis, this chapter reveals that receiving social support higher on RES predicts downstream outcomes that are important for effective self-regulation. Chapter 3 examines how social support interactions give rise to dyadic coregulation—dynamic coupling of partners’ physiological states. Results from this chapter demonstrate that social support interactions may be a context in which such coregulation is especially likely to occur, in order to help partners return to an equilibrium of responding, and underscore the importance of considering how dyads regulate as a single, interdependent unit. Chapter 4 presents preliminary evidence for how coregulation among older couples might influence developmental regulation. This chapter shows how between-dyad differences in coregulation processes in turn predict individual self-regulation processes in the face of a stressor. Chapter 5 synthesizes findings across chapters and highlights new avenues for future research. Overall, these findings suggests important self- and coregulatory implications of social support interactions, which may be a crucial mechanism through which interpersonal relationships influence health and well-being over time.