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.

Terrestrial Things War, Language and Value in Afghanistan

Mojaddedi, Fatima Columbia University ProQuest Dissertations & These 2016 해외박사(DDOD)

This dissertation is an ethnographic engagement with the social and political space of Afghanistan and how it has been shaped by the intensities of warfare in the last decade, with a focus on the realms of language, representation and economy. Taking Kabul as the panoramic ground of profound social and epistemological transformations, the dissertation traces a crucial shift beginning in 2011-2012, from a highly speculative war economy (a "green zone economy" that privileged the commodification of language and culture and the privatization of war, with crisis as an alibi for governmentality) to one based on equally speculative practices of prospecting for natural resources in the Afghan underground: where an estimated three trillion dollars' worth of copper, gold, iron-ore, marble and oil & gas is presumed to lie in wait. I illustrate the nuanced epistemological concerns and political contestations that stem from an Afghan effort to distinguish between sources of violence and sources of economic value (especially in the aftermath of Kabul's demilitarization) in a milieu where foreign militaries presuppose that civilians and insurgents cannot be distinguished, except through the medium of war-time translation and collaboration. The twin concern with generalized forms of death dealing and tragedy, on one hand, and the moral and political exigency for Afghans to distinguish between a world of appearances and one of essences (the Islamic and Quranic interpretation of zahir (exterior/surface) and batin (interior/ground), on the other, opens onto a set of epistemological concerns undergirded by several oppositions, which I argue, are central to American war making. I illustrate that the movement between these artificial binaries (Persian/Pashto and English, literacy and illiteracy, rationality and irrationality, repetition and transformation) inspires aspirational fantasy on an economic frontier and invests some Afghans (especially those who speak English and are literate) with the power of calculative reason (aql) and understanding (fahm and dânish), while condemning those who are illiterate (and sometimes those who only speak Persian and/or Pashto) to forms physical supplementarity and crisis--from literally being expendable prosthetic bodies (human body armor) to the breakdown of meaning in incestuous relations and the intensification of moral crisis. In this context, conventional writing and the felt lack of its absence illustrate for us the logic of war in more consequential ways. The belief that writing is the domain of what can be known (rationally understood) and universally applied invigorates the ideology of literate persons and war-time collaborators with shocking breadth and tenacity. It organizes antagonisms between persons and structures forms of death-dealing. I trace how the production of a binary around literacy and illiteracy produces, even in moments of technological acquisition, the retrospective fantasy that orality is not only the prior but also the locus of unfettered subversion and ignorance of the law. This misrecognition of linguistic diversity as lack comes to inform, in contexts of unprecedented transnational war-time activity, the charge that Afghans are beholden to an excessive localism that fuels the predicaments of the Afghan State and errors of judgement (such as incestuous transgressions, and suicide bombing) which would destroy society altogether. The issue of vulnerability to ideological suasion and excess emerges alongside these presuppositions. It informs the belief that the incapacity to exercise reason (due to illiteracy) renders Afghans vulnerable to diverse forms of propaganda and the inability to distinguish between the world of appearances (both technological media images and the Islamic notion of the zahir (surface manifestation)) and reality. I trace these complexities through a series of intense contact points where these oppositions come into play and determine forms of access and violence 1) in translational contexts during combat missions where linguistic transformation results in deadly misunderstanding 2) in familial contexts and contestations over property, where the failure of interpersonal and extrajudicial mediation results in mass murder 3) in courtrooms where failed suicide bombers (who did not detonate out of technological error or because they were attacked by members of the Afghan National Police) are subject to the limitations of oral testimony and to the belief that photographic evidence proves that they will repeat their crimes if released from prison 4) instances of incest that arise out of illiteracy and, when exposed, generate moral crisis 5) the production of zones of exteriority and interiority (especially in Kabul's Green Zone) that rely on phamakological inclusion and reproduce the literal supplementarity of Afghan bodies 6) the attempt to find the "real" sources of economic value as part of a multi-national gold and mineral extraction endeavor---the continuation of an obsession with the Afghan ground that has a long imperial history from the 1800's onwards (when it was assessed through botanical, railway and coal prospecting missions). Together, these sites and the consideration of the earthen terrain alongside the terrain of rationality and linguistic difference situate us in the midst of wartime catastrophe. They foreground the fantasy that rationalism is the sine qua non of modernism, and the belief that literacy is the basis for reflective and intellectual thought, and for being human. But what they also disclose for us is that in its absence you can (and sometimes must) die. (Abstract shortened by ProQuest.).

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.).

Deep Learning for Action Understanding in Video

Shou, Zheng Columbia University ProQuest Dissertations & These 2019 해외박사(DDOD)

Action understanding is key to automatically analyzing video content and thus is important for many real-world applications such as autonomous driving car, robot-assisted care, etc. Therefore, in the computer vision field, action understanding has been one of the fundamental research topics. Most conventional methods for action understanding are based on hand-crafted features. Like the recent advances seen in image classification, object detection, image captioning, etc, deep learning has become a popular approach for action understanding in video. However, there remain several important research challenges in developing deep learning based methods for understanding actions. This thesis focuses on the development of effective deep learning methods for solving three major challenges. Action detection at fine granularities in time: Previous work in deep learning based action understanding mainly focuses on exploring various backbone networks that are designed for the video-level action classification task. These did not explore the fine-grained temporal characteristics and thus failed to produce temporally precise estimation of action boundaries. In order to understand actions more comprehensively, it is important to detect actions at finer granularities in time. In Part I, we study both segment-level action detection and frame-level action detection. Segment-level action detection is usually formulated as the temporal action localization task, which requires not only recognizing action categories for the whole video but also localizing the start time and end time of each action instance. To this end, we propose an effective multi-stage framework called Segment-CNN consisting of three segment-based 3D ConvNets: (1) a proposal network identifies candidate segments that may contain actions; (2) a classification network learns one-vs-all action classification model to serve as initialization for the localization network; and (3) a localization network fine-tunes the learned classification network to localize each action instance. In another approach, frame-level action detection is effectively formulated as the per-frame action labeling task. We combine two reverse operations (i.e. convolution and deconvolution) into a joint Convolutional-De-Convolutional (CDC) filter, which simultaneously conducts downsampling in space and upsampling in time to jointly model both high-level semantics and temporal dynamics. We design a novel CDC network to predict actions at frame-level and the frame-level predictions can be further used to detect precise segment boundary for the temporal action localization task. Our method not only improves the state-of-the-art mean Average Precision (mAP) result on THUMOS'14 from 41.3% to 44.4% for the per-frame labeling task, but also improves mAP for the temporal action localization task from 19.0% to 23.3% on THUMOS'14 and from 16.4% to 23.8% on ActivityNet v1.3. Action detection in the constrained scenarios: The usual training process of deep learning models consists of supervision and data, which are not always available in reality. In Part II, we consider the scenarios of incomplete supervision and incomplete data. For incomplete supervision, we focus on the weakly-supervised temporal action localization task and propose AutoLoc which is the first framework that can directly predict the temporal boundary of each action instance with only the video-level annotations available during training. To enable the training of such a boundary prediction model, we design a novel Outer-Inner-Contrastive (OIC) loss to help discover the segment-level supervision and we prove that the OIC loss is differentiable to the underlying boundary prediction model. Our method significantly improves mAP on THUMOS14 from 13.7% to 21.2% and mAP on ActivityNet from 7.4% to 27.3%. For the scenario of incomplete data, we formulate a novel task called Online Detection of Action Start (ODAS) in streaming videos to enable detecting the action start time on the fly when a live video action is just starting. ODAS is important in many applications such as early alert generation to allow timely security or emergency response. Specifically, we propose three novel methods to address the challenges in training ODAS models: (1) hard negative samples generation based on Generative Adversarial Network (GAN) to distinguish ambiguous background, (2) explicitly modeling the temporal consistency between data around action start and data succeeding action start, and (3) adaptive sampling strategy to handle the scarcity of training data. Action understanding in the compressed domain: The mainstream action understanding methods including the aforementioned techniques developed by us require first decoding the compressed video into RGB image frames. (Abstract shortened by ProQuest.).

Essays on price discrimination

Ngwe, Donald Columbia University ProQuest Dissertations & These 2014 해외박사(DDOD)

The increasing availability of detailed, individual-level data from retail settings presents new opportunities to study fundamental issues in product design, price discrimination, and consumer behavior. In this set of essays I use a particularly rich data set provided by a major fashion goods manufacturer and retailer to illustrate how observed firm strategies correspond to predictions from producer theory. I present evidence on the importance of multidimensionality in consumer preferences, both within the theory of price discrimination and as a factor in actual firm decisions. Finally, I explore the applicability of concepts from signaling theory and behavioral economics in explaining consumer purchase decisions. The first chapter describes the empirical setting used throughout the entire dissertation. Data is provided by a luxury goods firm that dominates its category of fashion goods in the United States. The firm operates hundreds of stores in the US, with different types of stores differing markedly in their geographic accessibility to consumers. I present and estimate a model of demand that admits consumer heterogeneity in two dimensions: travel sensitivity and product age sensitivity. I show that consumer heterogeneity in these two dimensions outweigh that in observable characteristics, such as household income. Furthermore, I estimate a high correlation in the two dimensions, such that consumers who are most averse to travel are also those for whom product newness is most valuable. The second chapter focuses on the firm's store location and product introduction strategies. I introduce a model of product introduction wherein the firm selects only the parameters of the distribution of product characteristics, rather than the characteristics of each new product. This dramatically simplifies the firm's optimization program. I use this model to simulate counterfactual product assortments given alternative store location decisions. I show that the optimality of observed store locations depends substantially on the correlation in consumer values for travel distance and product quality. I also show that increased differentiation in geographic accessibility enables the firm to profitably increase differentiation in product quality. The third chapter studies how consumers respond to different price signals conditional on store visitation. Many firms employ price comparisons as a selling strategy, in which actual prices are framed as discounted from a high list price, occasionally even when no units are sold at list prices. I show that high list prices enhance demand both on product and store levels. I present evidence that suggests that consumers infer quality from list prices. I also demonstrate that these demand-enhancing effects are dependent on characteristics of the retail context, such as the general level and dispersion of discounting. These essays study in isolation components of consolidated selling strategies that have been widely adopted by US manufacturers and retailers across a wide variety of categories. My hope is to achieve a deeper understanding of the aspects of consumer behavior and firm incentives that have led to the prevalence of these selling strategies. This understanding is central in forming prescriptions for managers as well as measuring welfare implications, both of which I leave for future work.

Micro-data in Macroeconomics

Chen, Tuo Columbia University ProQuest Dissertations & These 2018 해외박사(DDOD)

This dissertation contains three essays on Macroeconomics. Detailed micro-level data is used in all three essays. The first chapter studies wealth inequality problems. More specifically, it focuses on capital return inequality among university endowments. It combines university-level data on endowment size, capital returns, and portfolio allocations into a unified dataset. Using panel data regression, I show a strong impact of size on investment return. Everything else the same, the biggest endowment has a capital return 8 percent higher than the smallest endowment. However, after adjusting for risk using Sharpe ratios, the strong positive correlation turns negligible or even negative. This result suggests that the higher return of bigger endowments can be attributed to risk compensation rather than to an informational premium. The second and the third chapters employ firm-level data to study macroeconomic productivity. The second chapter documents the sectoral growth paths of measured total factor productivity (TFP) in southern Europe during the boom that proceeded the great contraction (1996 to 2007). Using both aggregate and firm-level panel data, I show that TFP in sectors that displayed fast expansion, such as construction, dropped significantly, while in non- expanding sectors, such as manufacturing, it stayed stable. I evaluate the relevance of two alternative explanations of this phenomenon: capital misallocation (the increase in capital was directed to less productive firms) and labor quality mismeasurement (lower quality of incoming labor was not fully captured in the TFP calculation). I find that the misallocation channel is almost negligible. Moreover, worker-firm matched data shows that labor quality did deteriorate in the expanding sectors but not in the others, giving credence to the labor-quality mismeasurement hypothesis. A model featuring both the misallocation and the mismeasurement channels and calibrated to match the micro-level productivity distribution and labor quality distribution predicts that the drop in true TFP was small if labor quality is measured properly. The third chapter documents the total factor productivity growth path in China from 1998 to 2015 using both the aggregate and the firm-level data. We find that measured TFP growth is positive from 1998 to 2011, before turning flat and even negative. A careful comparison between state-owned enterprises (SOEs) and private firms reveals that the slowing down of TFP growth of SOEs is the major contributor to the TFP growth reversal of the whole manufacturing sector. The reversal is not due to changes in the composition of production in different sub-sectors, but mostly due to changes within existing firms.

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.

Multisensory Smartphone Applications in Vibration-Based Structural Health Monitoring

Ozer, Ekin Columbia University ProQuest Dissertations & These 2016 해외박사(DDOD)

This dissertation utilizes multisensory smartphone features to solve citizen-induced uncertainties and develops a smartphone-based SHM methodology which enables a cyber-physical system through mobile crowdsourcing. Using smartphone computational and communicational power, combined with a variety of embedded sensors such as accelerometer, gyroscope, magnetometer and camera, spatiotemporal and biomechanical citizen-induced uncertainties can be eliminated from the crowdsourced smartphone data, and eventually, structural vibrations collected from numerous buildings and bridges can be collected on a single cloud server. Therefore, unlike the conventional platforms designed and implemented for a particular structure, citizen-engaged and smartphone-based SHM can serve as intelligent, scalable, fully autonomous, cost-free, and durable cyber-physical systems drastically changing the forthcoming trends in civil infrastructure monitoring. In this dissertation, iOS is used as the application development platform to produce a smartphone-based SHM prototype, namely Citizen Sensors for SHM. In addition, a web-based software is developed and cloud services are implemented to connect individual smartphones to an administrator base and automate data submission and processing procedure accordingly. Finally, solutions to citizen-induced problems are provided through numerous laboratory and field test applications to prove the feasibility of smartphone-based SHM with real life examples. Through collaborative use of the software, principles and methodologies presented in this dissertation, smartphones can be the core component of futuristic smart, resilient, and sustainable city and infrastructure systems. And this study lays down an innovative and integrated foundation empowering citizens to achieve these goals. (Abstract shortened by ProQuest.).

Essays in Development Economics

Desai, Kunjal Columbia University ProQuest Dissertations & These 2017 해외박사(DDOD)

This dissertation consists of three essays. In the first chapter, I investigate the effect. of long-term income shocks that affect only one side of the marriage market in India. The asymmetric shock is due to two factors - (1) a jobs-based affirmative action program. that affects the occupations and wages of a group of castes that were historically. against, with a strict upper age limit on eligibility and, (2) a social norm that determines. which member works outside the household. The program results in a differential positive. income shock for young men in the treated group. The income shock is found to. affect the marriage market in several ways. First, there is no effect on the marriage rate. of treated men. However, conditional on marriage, treated men pair up with spouses. that have higher educational attainment, are taller, and have a higher BMI. They are. also more likely to marry outside their own community. Second, treated women are. overall less likely to marry, and their choice of spouse is unaffected conditional on marriage. Finally, controlling for observables, treated husbands are found to have greater. decision making power within the households that are formed. There is no significant. effect for treated wives. A structural model of the marriage market based on Choo and. Siow (2006) is used to investigate the aggregate marital welfare effects of the policy. The estimates find that up to 80% of the benefit of the affirmative action policy accrues. to men within the treated group. These findings suggest that (1) a larger share of the. welfare gains from affirmative action policies accrue to the household member that. actually receives them, and (2) that the marriage market is one mechanism through. which the distribution operates, in addition to the intra-household bargaining process. that is standard in the literature. In the second chapter (joint with Ashna Arora, Rakesh Banerjee and Siddharth Hari). we study the political economy of public service delivery. Local governments in developing. countries play a crucial role in the provision of local public goods and the. functioning of social welfare programs. This chapter investigates the relationship between. the size of elected local government councils and public service delivery. We. use a natural experiment from India, where the number of politicians at the village. level is an increasing, discontinuous function of village population. We set up a regression. discontinuity design to study the impact of a larger elected council on the. targeting of welfare schemes as well as the allocation of private benefits by politicians. to themselves. We find that larger councils improve access to a large scale workfare. program, especially for traditionally disadvantaged communities. We also find that. increasing the number of council members increases appropriation of private benefits. by the council head but not by ordinary members. These results have implications for. policy design. In the third chapter (joint with Ritam Chaurey), we investigate the relative effects of. manager supervision on different types of labor. Across a large cross section of firms. we find that managers spend more time in supervisory roles when a larger share of. contract labor is employed. This finding is then established causally using a differencein-. differences approach, exploiting variations in labor regulations across Indian states. and rainfall-driven demand shocks. Using the causal approach, we find that (i) there. is no significant change in total management input in response to short run demand. shocks, suggesting that the institutional factors of the market for managers has larger. search/firing costs than that for industrial workers. However, (ii) managers are observed. to spend more time in supervisory roles when relatively more contract labor is. employed in response to demand shocks. Contrary to the literature, we also find that. (iii) there is no productivity change when there is an influx of contract labor. These. findings suggest that there are complementarities between manager supervision and. contract labor input, even relative to other types of labor, and that the manner of deployment. of management capital within a firm is endogenous, conditional on the total. amount.These findings could account for one of the features that is widely observed. in empirical studies - firms in regions with strong employee protections have lower. steady state productivities.

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.