VictorJuiz/thesis huggingface dataset:
Mechanistic analysis of circular RNA biogenesis from yeast to man

The past decades have seen a seemingly ever-growing list of diverse non-coding RNA species with functional capacity expressed in eukaryotic cells. Circular RNAs (circRNAs), whose 3' and 5' ends are covalently linked, constitute a class of RNA recently discovered to be widespread and abundant. circRNAs are generally formed by alternative splicing of pre-mRNA in a process known as 'backsplicing.' However, it is unknown why some exons are predisposed to circularization while others are not. Early studies on backsplicing suggest that complementary intronic sequences are responsible for the promotion of circRNA biogenesis, but some of the most abundant circRNAs lack any noticeable secondary structure in their introns. In this dissertation, I describe my work to uncover the mechanisms underlying the biogenesis of two abundant circRNAs: first, the mrps16 circRNA in fission yeast, and second, the ciRS-7 circRNA in human. In the case of mrps16, we find that circRNA can be generated through an exon-containing lariat precursor and that the length of the circularized exon is a significant determinant in this process. For ciRS-7, we identify the broader locus in which this circRNA is housed, defining the boundaries of flanking introns and exons which were previously unknown, and determine regulatory features governing its expression. In the final part of this dissertation, I describe my attempts to create a high-throughput screen to discover the trans-acting factors governing the alternative splicing of both linear and circular RNA isoforms, discussing pitfalls and potential adaptations for future experiments.

Keywords: Biochemistry.
Advisor: Salzman Julia
Das Rhiju
Rohatgi Rajat
Sarnow P. (Peter)
A media genealogy of literary fame in modern China : paper, stage, screen, and sphere

Zooming in on the radical transformations of literary interface in the shift from print to digital media ecologies, A Media Genealogy of Literary Fame in Modern China: Paper, Stage, Screen, and Sphere analyzes an assemblage of historically contingent material artifacts, networks, and processes that afford and shape the production of literary fame in 20th-and 21st-century China. Drawing on critical lines of thinking regarding the materialities of communication, I explore the nonhuman bases and media forms where the authorial texts, images, and voices appear, and reveal how the whereabouts of authorial presences facilitate or scandalize the fame of particular authors. Through close examinations of paratextual extensions, performative imitations, screen interactions, and digital serialization in relation to the spreadable texts by four reputed Chinese authors, my dissertation argues that the material means, delivery devices, and intermediary operations not only underpin the making of literary fame in the first place, but also shape the larger aesthetic, political, and social value the Chinese mass audience ascribe to famed authorship against specific historical currents. Among the notable authors I analyze are the self-proclaimed genius Eileen Chang, the Communist "model" writer Zhao Shuli, the cynical celebrity author Han Han, and the industrious serial storyteller Tangjia sanshao. This study has implications for not only the field of modern Chinese literature and culture, but also for sociological and anthropological studies of literary celebrity and communication media.

Keywords: Comparative Literature.
Advisor: Gumbrecht Hans Ulrich 
Wang Ban
Lee Haiyan 
Phelan Peggy
The media marshmallow test : psychological and physiological effects of applying self-control to the mobile phone

This research draws on a classic delay of gratification framework from psychology, the Marshmallow Test, to examine the effects of exercising self-control with the mobile phone. A total of 125 subjects were randomly assigned to sit in an unadorned room for six minutes and either (a) use their mobile phone, (b) sit with their device but resist using it, or (c) sit alone with no phone. Participants self-reported more concentration difficulty and more mind wandering with no device present compared to using the phone, while resisting the phone reduced concentration difficulty relative to sitting without the device. Baseline-subtracted skin conductance data were consistent with this pattern, as participants eventually displayed more physiological arousal without their phone relative to those who resisted their phone. Subjects also wrote about their experience and their verbal descriptions revealed that participants who used the phone reported the content of their mobile phone activities (e.g., applications used, videos watched) and assigned agency to the device compared to people who did not use the phone and assigned agency to the self. Participants who resisted the phone and felt tempted to use it wrote about their self-control challenge and displayed negative psychological costs (e.g., less enjoyment, less entertainment, more boredom), while participants who were not tempted did not face negative consequences. Together, the dissertation findings suggest that self-control with media is a complex psychological phenomenon that can affect an individual to the extent that he or she perceives the device as a temptation.

Keywords: Communication.
Advisor: Hancock Jeffrey
Bailenson Jeremy 
Pennebaker James W.
Reeves Byron
The medieval art of fear : Christ Pantokrator after iconoclasm

Centuries before the modern conception of surveillance, medieval subjects imagined an entity that monitored their every move: Christ Pantokrator (Ruler of All). My dissertation, The Medieval Art of Fear, investigates how Byzantine image-makers constructed this all-seeing figure in three-dimensions and manipulated spaces in order to create immersive encounters with the fearsome image. Following the crisis of Byzantine Iconoclasm (726-843), the making and display of Christ Pantokrator structured the visual perception of absolute power. Dramatic poetry, rituals and theologies, replete with fear of the Last Judgment, established the modes through which the faithful would perceive the image. My study taps into this textual evidence as it engages in close analysis of how specific monuments and objects were embedded in public and private rituals that invoked this all-seeing figure. Ultimately this dissertation argues for the critical significance of the image of Christ Pantokrator to the study of fear as a visual, spatial and material experience.

Keywords: Art and Art History.
Advisor: Pentcheva Bissera V. 
Barry Fabio 
Kessler Herbert L.
Nemerov Alexander
Melodies in context : the semantics and pragmatics of English rising declaratives

Intonation, in particular, terminal contours, interacts with morphosyntactic features of clause-types (declaratives, interrogatives, imperatives, etc.) to help determine the speech act of the utterance and generate complex additional inferences about the context and the speaker. This dissertation addresses the question of how this comes about, focusing on a particular tune + clause-type combination, namely, rising declaratives of American English. English rising declaratives have been associated with a wide range of seemingly disparate meanings. They may be used as tentative assertions (the so-called 'uptalk' uses, often accompanied by social stigma), and they may be used as biased questions. In the latter case, they can sometimes convey positive epistemic bias of the speaker, but other times may convey negative epistemic bias instead. They often convey particular interactional and social meanings, like speaker politeness, but may also convey opposite social meanings, like speaker annoyance or exasperation. Characterizing the core, conventional effect of rising declaratives that crosscuts all of these varied uses has been a challenge. This dissertation presents a series of experimental studies and a theoretical analysis that reconcile these disparate, potentially conflicting observations that have been made about English rising declaratives data. It establishes the existence of two distinct types of rising declaratives, and derives additional, enriched meanings from the conventional effects of these two clause-types and their interactions with context and pragmatic reasoning.

Keywords: Linguistics.
Advisor: Condoravdi Cleo A.
Potts Christopher
Podesva Robert 
Sumner Meghan
Membrane curvature-dependent intracellular signaling induced by nanoscale surface topography

Nanoscale surface topography serves as physical signal that induce behavior changes of cells. Despite the potential applications of nanoscale surface topography for cell engineering, the mechanism of how these topographies induce series of intracellular signaling is still not well studied. In this thesis, we investigate several intracellular signaling induced by nanoscale surface topography. We introduce the idea that plasma membrane curvatures generated by these topographies are the key signal transducers in between the cells and the surface, and apply this theory for applications such as cell detection and capture. Rearrangement of the actin cytoskeleton by nanoscale surface topography is one of the major responses that has been observed in many studies. These topographies, with various materials and shapes, induce the local accumulation of filamentous actin (F-actin) around the individual topographies inside cells. These studies, however, did not provide the molecular mechanism of F-actin reorganization. Here we proved that nanostructure-induced plasma membrane curvatures with diameter less than 400 nm are found to effectively trigger Arp2/3 nucleated actin polymerization by recruiting membrane-curvature-associated proteins. Besides actin polymerization, we also observed that nanoscale topography can induce clathrin-mediated endocytosis (CME), which involves the bending and budding of plasma membrane. We found that CME happened more frequently on the nanostructure-induced membrane curvatures with diameters < 400 nm. These curvatures are also found to preferentially recruit several key CME proteins such as clathrin and dynamin, but not non-CME endocytic proteins, such as caveolin-1. With the knowledge of strong interaction between nanoscale surface topography with cells, we develop a topography-based platform for capturing circulating tumor cells (CTC). Capture of CTCs is important for cancer detection and monitor, but also very challenging due to its extremely low concentration within bloodstream. Here we combine nanopillar substrates with antibody-functionalized supported lipid bilayer to both increase capture efficiency and decrease non-specific cell-nanopillar interaction, respectively. In conclusion, this thesis summarizes our approaches of study how nanoscale surface topography induce specific intracellular signaling by inducing plasma membrane curvatures and showing its potential application.

Keywords: Chemistry.
Advisor: Cui Bianxiao 
Boxer Steven G. (Steven George)
Cegelski Lynette
Merchants, commerce, and the making of San Francisco's Chinatown [electronic resource]

This dissertation is an economic history of Chinatown with a focus on the role of the Chinese merchants. It begins in the 1850s as the Chinese arrived in California in greater numbers and concludes with the dramatic changes in Chinatown in the years that followed the San Francisco earthquake of 1906. The dissertation is framed around the idea of doux-commerce, that the spread of commercial relations can foster civility and tolerance among disparate populations, an idea originating with Enlightenment thinkers and articulated in Albert Hirschman's essay Rival Views of Market Society. Specifically, this dissertation builds upon a model presented in Saumitra Jha's 2013 paper, Trade, Institutions and Ethnic Tolerance: Evidence from South Asia, which suggests commercial relations can have such an effect when the two populations are complementary rather than competitive in their economic functions. The story of the Chinese merchants and Chinatown presented in this dissertation appears to fit this model on a prima facie basis—"complementarity" helps explain the relatively better treatment enjoyed by the Chinese merchants compared to other Chinese. It also helps explain the transformation in attitudes toward Chinatown from fierce hostility in the late nineteenth century to a celebration of the rebuilt neighborhood after the 1906 earthquake as the new Chinatown was valued by the city for its contributions to trade and tourism. The dissertation argues, however, that on closer inspection, complementarity is not an exogenous feature of the situation. Rather, it was a perception that required active cultivation. The dissertation thus describes how American perceptions of the Chinese and Chinatown changed and the significant role the Chinese merchants had in developing these perceptions over time. The dissertation pays particular attention to the institution of the Oriental Bazaar, which served as an important intersection between the Chinese and Americans cultures and which served as the basis for the redevelopment of Chinatown.

Keywords: Economics.
Advisor: Wright Gavin
Gordon Robert
Satz Debra advisor. Thesis advisor
Metabolic engineering of defense pathways from cruciferous plants

Different families of plants have evolved unique defensive strategies to protect themselves from pests and pathogens. For example, cruciferous plants, such as broccoli (Brassica oleracea) and turnip (Brassica rapa), use a set of small molecule biopesticides, called phytoalexins, to inhibit pathogenic fungi. Engineering phytoalexin biosynthesis into commodity crop plants, which do not make these molecules, could be an effective and more efficient strategy for curbing disease. Traditional pesticides are over applied, less than 1% of a sprayed molecule reaches its target. Plants engineered to synthesize phytoalexins could produce their own biopesticides specifically when under pathogen attack. However, before phytoalexin biosynthesis can be engineered, metabolic pathways for making these molecules must first be discovered. In this dissertation, I describe my efforts to expand the number of phytoalexins which can be engineered for enhanced plant defense, with a focus on sulfur containing phytoalexins from cruciferous plants. First I will describe the identification of 7 genes from a previously unsequenced plant, Nasturtium officinale, for the biosynthesis of phenethyl-based phytoalexins. Then I discuss the metabolic engineering of this pathway and novel pathways to create 9 new-to-nature phytoalexins in plants, two of which are more potent anti-fungals than natural molecules. Finally I will describe two enzymes which can cyclize phenethyl-based phytoalexins towards more anti-microbial products. This work not only expands the genetic toolkit for engineering plant defense, but also increases our understanding of the biosynthesis and evolution of plant defense metabolism.

Keywords: Chemical Engineering.
Advisor: Sattely Elizabeth 
Spormann Alfred M. 
Swartz James R.
Methods and applications of computation in complex trait evolution and associated fields [electronic resource]

As evolution targets traits relevant to fitness, by studying the evolution of complex traits, we can more easily discover the mechanisms behind phenotypic variation in humans. I present a series of projects using these methods to understand the landscape of human evolution in the past 50 thousand years. First, I discuss a method and applications for identifying signatures of selection in the most recent past. Over just the last 2000 years we detect signals of evolution in anthropometric (body measurements) and other phenotypic traits, suggesting the continued alteration of complex polygenic traits by selection. Second, I present work understanding the impact of novel variation with separate history -- derived in Neanderthals, now present in modern-day humans -- on tissue development and gene regulation. Finally, I discuss applications of these methods in alternative fields, including bibliometrics and quantitative behavior; I apply these techniques to study scientific history, and to measure subtle disparities and differences in gendered behaviors of scientists.

Keywords: Biomedical Informatics.
Advisor: Pritchard Jonathan (Jonathan K.) primary advisor. Thesis advisor
Altman Russ advisor. Thesis advisor
Petrov Dmitri Alex
Rosenberg Noah advisor. Thesis advisor
Methods for scalable Markov chain Monte Carlo inference

This dissertation contains three methods aiming at improving the scalability of Markov Chain Monte Carlo (MCMC) sampling. The first method addresses the computation bottleneck of Metropolis-Hastings in Bayesian models with a large number of observations. As an extension to the first method, we have developed a new MCMC algorithm to handle multimodal high-dimensional posterior distributions with a large number of observations. Our objective with the third method is to improve the efficiency of MH in high dimension, by designing a novel local MH move to make an effective use of the gradient information of the log target density. In the first part, we propose a general framework of performing MCMC with only a mini-batch of data. We show that by estimating the MH ratio with only a subset of data, one can sample from the true posterior raised to a known temperature. We show by experiments that our algorithm, ``Mini-batch Tempered MCMC'', can efficiently explore the landscape of a multimodal posterior distribution. In addition, based on the Equi-Energy sampler \citep{kou2006discussion}, we propose a new MCMC algorithm, which enables exact sampling from high-dimensional multimodal posteriors with well-separated modes. In the second part, we introduce a novel local MH move which we shall refer to as the ``Cone Move''. Our goal is to address a crucial limitation of Langevin Dynamics, namely its inherent inefficiency in utilizing the gradient information in exploring the target distribution. Compared with Langevin Dynamics, Cone Move makes better use of the gradient information and thus generates more targeted moves along the shape of the target distribution. We propose a new MCMC algorithm, the Cone Sampler, which adapts to the geometry of the target density by alternating between Cone Move and Langevin Dynamics. We demonstrate the effectiveness of Cone Sampler by testing its performance on challenging sampling problems in high dimensions.

Keywords: Computational and Mathematical Engineering.
Advisor: Wong Wing Hung 
Lai T. L. 
Sabatti Chiara
Microniches in the gastric glands control helicobacter pylori colonization of the stomach

Lifelong infection of the gastric mucosa by Helicobacter pylori can lead to peptic ulcers and gastric cancer. This bacterium resides in possibly the harshest niche in the human body, an organ which secretes liters of microbicidal acid, mucus, and digestive enzymes daily to aid in food digestion and to destroy ingested microbes. How is H. pylori able to survive in this harsh environment and persistently colonize their hosts for a lifetime? Previously, we reported that H. pylori can penetrate deep in the stomach mucosa and reside within a specialized compartment, or "microniche" in the gastric glands that contain epithelial precursor and stem cells. In this thesis, we investigated the significance of this microniche from the perspective of the microbe. We engineered isogenic, differentially-labeled H. pylori strains that we mixed and introduced into mice to understand the kinetics of how these gland-associated populations establish and spread, and to ask questions about intraspecies competition in these niches. Using 3D confocal microscopy and passive CLARITY technique (PACT), which renders tissues optically transparent, we mapped bacterial location within entire infected organs with unprecedented spatial resolution. We discovered that gland-associated populations do not intermix with free-swimming bacteria in the surface mucus. Rather, gland-associated H. pylori form stable clonal populations that compete for space and prevent newcomers from establishing in this specialized niche. Bacterial mutants unable to colonize the glands are outcompeted by wild-type strains. Additionally, we found that a combination of bacterial, host, and environmental factors control the density of these gland-associated populations. Collectively, our results show that the gastric glands provide a protective niche, or safe haven, for H. pylori to maintain a stable bacterial reservoir that likely replenishes the more transient populations in the surface mucus.

Keywords: Microbiology and Immunology.
Advisor: Amieva Manuel 
Huang Kerwyn Casey
Monack Denise M. 
Sonnenburg Justin
Microwave impedance microscopy : from acoustics to photovoltaics

This thesis details my efforts to expand the capabilities of microwave impedance microscopy (MIM), and apply those capabilities to variety of systems of technological relevance. MIM is a sensitive microwave measurement of the change in impedance of a scanned, nanoscale probe. By measuring this impedance, properties of the sample under study, including conductivity and permittivity, can be obtained at nanoscale resolution without direct electrical contact. How this tip impedance relates to the quantities of interest can depend on many details of the measurement and measured device, however. In this thesis I explore some of those details. Chapter 1 includes the standard interpretation of MIM as a qualitative measurement of local permittivity and conductivity, in addition to background on related scanning probe methods. This understanding is largely sufficient for many systems, including the phase change materials (e.g. Ge2Sb2Te5) studied in Chapter 5. Such materials have dramatically different conductivities between their amorphous and crystalline states, making MIM an ideal tool for studying various types of phase change devices. Chapter 2 explores a number of measurement techniques and principles which can expand the capabilities of MIM and address some of its limitations, including quantitative measurement. A class of such techniques, those involving modulated optical illumination of the tip-sample interface during MIM measurement, is explored in detail in Chapter 4. These include MIM measurement of photoconductivity, band-gap, and carrier lifetime. Finally, chapter 3 covers the application of MIM to ferroelectric domains and domain walls. The primary topic of this chapter is the radically different measurement mechanism possible in piezoelectric materials, in which MIM can be used to measure the transduction of electrical energy to acoustic waves.

Keywords: Applied Physics.
Advisor: Shen Zhi-Xun 
Fox John D. 
Suzuki Yuri (Applied physicist)