VictorJuiz/thesis huggingface dataset:
Development of RNA Sensors for Cyclic Dinucleotide Second Messengers in Bacteria

Second messengers are intracellular signaling molecules that enable cells to respond to environmental changes by relaying signals received at the cell surface to enact downstream physiological effects. A recently expanded class of second messengers in bacteria are the cyclic dinucleotides, which include cyclic di-GMP (cdiG), cyclic di-AMP (cdiA), and 3',3' cyclic AMP-GMP (cAG). In bacteria, these messengers regulate processes ranging from chemotaxis and sporulation to antibiotic resistance and virulence. Recent studies have found that bacterial cyclic dinucleotides, as well as a mammalian 2',3' cAG homolog, trigger the innate immune response upon detection in the mammalian cell cytosol. However, many components and roles of cyclic dinucleotide signaling remain unidentified or poorly understood. A clear understanding of cyclic dinucleotide signal transduction would further the pursuit of these signaling pathways as therapeutic targets and the effects of using cyclic dinucleotides as small molecule adjuvants. Herein, novel strategies for cyclic dinucleotide detection are reported that use that natural ability of riboswitch RNAs to discriminate between these nucleotide-based messengers./nFirst, a microfluidic electrophoretic mobility shift assay (µMSA) is presented that enables highly sensitive and rapid detection of cdiG in vitro. This method takes advantage of the ligand-induced conformational change of a natural cdiG GEMM-I class riboswitch aptamer, termed Vc2. This same aptamer was then converted to a fluorescent biosensor for live-cell imaging by fusing it to the Spinach aptamer, an RNA mimic of GFP. This Vc2-Spinach RNA-based biosensor senses low levels of endogenous cdiG in Escherichia coli and responds to increased levels of cdiG upon coexpression of a heterologous cdiG synthase. A similar Spinach-based strategy was used to develop a cdiA RNA-based biosensor through fusion to riboswitches from the recently reported ydaO class. This cdiA sensor is the first tool for live cell imaging of cdiA and provided the first demonstration of the Spinach system in Listeria monocytogenes, an important gram-positive intracellular pathogen. Finally, as no known biosensor existed for 3',3' cAG, rational engineering of a cdiG aptamer led to the discovery of a subclass of GEMM-I riboswitches in Geobacter species that is naturally specific for 3',3' cAG. Further analysis revealed that this novel riboswitch subclass, which represents the first known effector for this messenger, is important in regulating the process of extracellular electron transfer in Geobacter and these riboswitches were used to develop the first biosensor specific for 3',3' cAG. It is envisioned that the use of these cyclic dinucleotide-specific sensors can be used to further identify unknown components in the signal transduction of these important regulatory molecules.

Advisor: Hammond, Ming C
Materials Science and Device Physics of 2-Dimensional Semiconductors

Materials and device innovations are the keys to future technology revolution. For MOSFET scaling in particular, semiconductors with ultra-thin thickness on insulator platform is currently of great interest, due to the potential of integrating excellent channel materials with the industrially mature Si processing. Meanwhile, ultra-thin thickness also induces strong quantum confinement which in turn affect most of the material properties of these 2-dimensional (2-D) semiconductors, providing unprecedented opportunities for emerging technologies./nIn this thesis, multiple novel 2-D material systems are explored. Chapter one introduces the present challenges faced by MOSFET scaling. Chapter two covers the integration of ultrathin III V membranes with Si. Free standing ultrathin III-V is studied to enable high performance III-V on Si MOSFETs with strain engineering and alloying. Chapter three studies the light absorption in 2-D membranes. Experimental results and theoretical analysis reveal that light absorption in the 2-D quantum membranes is quantized into a fundamental physical constant, where we call it the quantum unit of light absorption, irrelevant of most of the material dependent parameters./nChapter four starts to focus on another 2-D system, atomic thin layered chalcogenides. Single and few layered chalcogenides are first explored as channel materials, with focuses in engineering the contacts for high performance MOSFETs. Contact treatment by molecular doping methods reveals that many layered chalcogenides other than MoS2 exhibit good transport properties at single layer limit. Finally, Chapter five investigated 2-D van der Waals heterostructures built from different single layer chalcogenides. The investigation in a WSe2/MoS2 hetero-bilayer shows a large Stokes like shift between photoluminescence peak and lowest absorption peak, as well as strong photoluminescence intensity, consistent with spatially indirect transition in a type II band alignment in this van der Waals heterostructure. This result enables new family of semiconductor heterostructures having tunable optoelectronic properties with customized composite layers and highlights the ability to build van der Waals semiconductor heterostructure lasers/LEDs.

Advisor: Javey, Ali
Ramesh, Ramamoorthy
Inference From Two Non-Equilibrium Models In Population Genetics

Improvements in sequencing technologies and the resulting increased availability of genetic data call for new and more sophisticated analysis methods. Particularly in ecological genetics and evolutionary biology, questions that can be addressed are often limited by the availability of analysis tools and statistical inference procedures. Non-equilibrium models in particular have been relatively poorly studied, mainly because analytical approaches are challenging and many useful and well-known results make equilibrium assumptions. However, using heuristic methods and strongly simplified models, we can make progress and arrive at procedures that help us gaining new insights from population genetic data. After an introductionary first chapter, in the second chapter, I develop an Approximate Bayesian Computation procedure to distinguish selection from standing variation from selection on a \textit{de novo} mutation. This method is applied to human genetic data where we identify two genes, ASPM and PSCA, that are most likely affected by selection on standing variation. In the third chapter, I develop an inference procedure to infer the origin of a range expansion, introducing the directionality index statistic psi. Applying this method to human data, we find a most likely origin of humanity in southern Africa, and evidence of the main expansion routes into Asia, finding evidence for a Southern route. In the fourth chapter, I extend the work on range expansions by developing an analytical model based on branching processes, which gives a biological interpretation to psi, and allows us to measure the decay of genetic diversity with distance. An application to Arabidopsis thaliana reveals that we are able to infer both recent expansions in the Americas, as well as expansions from the last glacial maximum in Europe. Between these three chapters, I use different approximation procedures to introduce inference procedures for models where direct likelihood calculations are not available.

Advisor: Nielsen, Rasmus
Courtly Institutions, Status, and Politics in Early Imperial China (206 BCE-9 CE)

This dissertation investigates the imperial court during the Western Han dynasty, the first period of sustained, unified rule in imperial China. It asks the following questions: What was the court? How was it conceived? How did these conceptions of the court change over the two centuries of the Western Han? As in many European languages, the word for "court" in classical Chinese, chao 朝, could refer equally to a space, a ritual action, or a group of people. The dissertation investigates changes in these three meanings of the word in order to answer the above questions. In the process, it shows that key changes in Western Han political culture were rooted in the transformation of the imperial court, which grew significantly in size, population, and wealth over the course of the dynasty. Participants in court life and political began to fashion their own definitions of court institutions, articulating new ideals about courtly status and life at court and fashioning new conventions in administrative and literary writing. This capacity of the imperial court to absorb more people and afford them a personal interest in the court ultimately contributed to the longevity of the dynasty. The dissertation thus argues that the imperial court was just as much a product of courtier writings and political struggles as it was a tool for the exertion of centralized political power./nIn making this argument, the dissertation emphasizes that almost all of our extant received sources from the Western Han period, particularly the Shiji and Hanshu, were produced at the imperial court. It highlights the problems of culling these court sources in order to outline institutions of power and court social groups. As an alternative approach, the dissertation instead emphasizes critical readings of these same sources in order to understand how members of the court during the Western Han characterized and understood the world that they inhabited. In doing so, it draws connections between studies of court culture and literature on the one hand and court institutions and political power on the other.

Advisor: Nylan, Michael
On Sannikov's Continuous-Time Principal-Agent Problem

The principal-agent problem is a classic problem in economics, in which the principal seeks an optimal way to delegate a task to an agent that has private information or hidden action. A general continuous-time stochastic control problem based on the moral hazard problem in Sannikov (2008) is considered, with more general retirement cost and structure. In the problem, a risk-neutral principal tries to determine an optimal contract to compensate a risk-averse agent for exerting costly and hidden effort over an infinite time horizon. The compensation is based on observable output, which has a drift component equal to the hidden effort and a noise component driven by a Brownian motion./nIn this thesis, a rigorous mathematical formulation is posed for the problem, which is modeled as a combined optimal stopping and control problem. Conditions are given on how a solution to the control problem could be implemented as a contract in the principal-agent framework with moral hazard. Our formulation allows for general continuous retirement profit functions, subject to an upper bound by the first-best profit. The optimal profit function is studied and proved to be concave and continuous. It is shown that the optimal profit function is the unique viscosity solution of the Hamilton-Jacobi-Bellman (HJB) equation.

Advisor: Guo, Xin
Solution-Processed Carbon Nanotube and Chemically Synthesized Graphene Nanoribbon Field Effect Transistors.

Carbon nanotubes (CNTs) possess great potential as high performance semiconducting channels due to their one-dimensional nature, extremely high mobility, and their demonstrated ability to transport electrons ballistically in transistors. However, the presence of metallic CNTs in CNT films and arrays represents a major impediment towards large-scale integration. Methods of solution purification have demonstrated partial success in metallic CNT removal, although their effects on device performance are unknown. While this problem may be solvable, new synthesis techniques have recently resulted in the creation of high-density films of graphene nanoribbons (GNRs) with atomically smooth edges, uniform widths, and uniform band structure. These may ultimately supplant CNTs in device applications due to their theoretically similar, but uniform electronic properties./nThis work aims to study the effects of purification of semiconducting CNTs in thin film transistors (TFTs) and to develop methods to increase device performance when metallic CNTs are present. Devices consisting of large networks of CNTs as well as short channel, single CNT devices are characterized to determine the effects of solution processing on CNTs themselves. Short channel, bottom-up GNR devices are fabricated to compare their performance to CNT transistors./nThe first half of this dissertation describes the methods of integrating CNTs from various sources into transistors. Growth and transfer are described, as well as methods of creating aqueous suspensions for solution processing. Development of novel surfactant materials based on biomimetic polymers used to suspend CNTs in solution are reported and characterized. Methods of deposition out of solution and onto insulating substrates are covered. Device fabrication from start to finish is detailed, with the subtleties of processing required to produce sub 10-nm channel length devices explained./nThe second half reports devices produced via these techniques in order to study the performance of solution-processed CNT devices. TFT performance is limited by metallic CNTs that can short channels, but can be improved by structuring the CNT film, either through patterning or induced alignment. Increasing semiconducting CNT purity does not necessarily increase device performance because of the decreased lengths of the purified CNTs. Extremely high purity semiconducting CNT solutions, however, are not subject to these same limitations, with transistors exhibiting improved mobilities while also scaling to sub-µm channel lengths. Short channel devices down to 15 nm are then presented, demonstrating ballistic transport in solution-processed CNTs, despite their inferior electronic performance at µm-scale lengths. Finally, short channel devices utilizing chemically synthesized GNRs as channels are presented and characterized to directly probe the mechanisms of electron transport in these materials for the first time.

Advisor: Bokor, Jeffrey
A Trichome Glass House: Phenotypic and biochemical analysis of TRICHOME BIREFRINGENCE1 - a study in Homogalacturonan O-acetylation and Cellulose Crystallinity.

Abstract - The nascent plant cell wall begins with the deposition of pectin into the apoplastic space between two developing daughter cells. This polysaccharide has three distinct domains of which homogalacturonan (HG) is the largest. Consisting of a repeating α- 1-4 linked D-galacturonic acid (GalA) homopolymer, HG can be further modified with methyl (C6) and/or O-acetyl (C2 or C3) esters. GalA and associated divalent cations play a critical role in the formation of a complex called the "egg box" which can be modified through the esterification of HG. The construction and strength of this egg-box structure is believed to play an important role in plant cell wall plasticity and integrity throughout development. Another cell wall component, cellulose, is similarly critical in its role as the main load-bearing polysaccharide in the primary cell wall. Co-expression analysis of primary cellulose synthase genes has led to the identification of several critical genes necessary for cell wall development. One such gene is TBR1 (TRICHOME BIREFRINGENCE1). Subsequent research confirmed that mutation of TBR1 causes aberrant phenotypes with reduction of cellulose content and altered pectin composition./nIn this thesis, the function of TBR1 in plant cell wall development has been studied through the detailed characterization of cell wall composition, which has demonstrated that loss of TBR1 results with depreciated HG O-acetyl transferase activity. Pectinolytic enzymes were developed, characterized and used as novel tools to probe changes in native pectin esterification structure. Research on the tbr1 mutant demonstrated that the resulting decrease in cellulose deposition is accompanied by a decrease in HG and HG O-acetylation due to the absence of a functional TBR1. This suggests that the changes in HG O-acetyl esterification observed in mutants of TBR1 impacts the divalent cation interactions in such a way that the deposition and potentially the arrangement of the cellulose fibers are affected. This ultimately results in a decrease in cellulose deposition and cell wall elasticity in specific cell types, in this case trichomes and hypocotyls. These results contribute to a novel understanding of how pectin influences cell wall dynamics.

Advisor: Somerville, Chris
Actin filaments and networks under force: A computational study

Rich understanding of a complex system can often emerge from simple but carefully constructed models. With an appropriate model, we can ask questions about how tuning the parameters of the model or modifying the constraints of the system changes the system behavior. My research involves applying such an approach to actin, an essential biopolymer in the cell. In this work, we explore how forces affect actin at the filament and network length scales./n/nIn the first part, we investigate how different forces modulate the interaction between actin filaments and actin-binding proteins. One such protein complex, Arp2/3, can cause filaments to form branches. Experiments indicate that branches preferentially form on the convex side of bent filaments. Using a coarse-grained model discretized at the monomer pair level, we show that binding is dependent upon a high local curvature fluctuation of the filament. The results indicate that actin can sense and respond to mechanical environmental cues to regulate the binding of Arp2/3. We further believe such a picture can serve as a useful framework for studying the effects of force on the binding and function of other proteins. In a follow-up project, we derive analytical expressions for the nanoscale curvature distribution of a worm-like chain and membrane as a function of applied tension. These expressions can be used to understand the force dependence of protein binding on actin filaments and membranes within a biological context./n/nIn the second part, we focus on actin network elasticity. Specifically, we explore how actin networks respond to large external forces. However, the theoretical toolkit for such a task is incomplete. First we develop a constant-stress framework to apply large forces on soft but strongly nonlinear materials. Additionally, we create a toy model of a soft elastic solid with a nonlinear elastic response on which we test our constant-stress method. Finally, we utilize the constant-stress method and a coarse-grained model for short, semiflexible chains to explore actin network elasticity under compression. We consistently observe stress softening under compression, which we analyze from a single filament perspective and using normal mode analysis.

Advisor: Geissler, Phillip
Spatiotemporal receptor dynamics during early T cell signaling

A given T cell receptor (TCR) can robustly discern a pathogen-derived agonist peptide amidst a myriad of background peptides, all bound to major histocompatibility complexes (MHC). This remarkable degree of discrimination is the culmination of physical operations happening at the membrane-membrane junction between a T cell and an antigen-presenting cell. In the research described in this dissertation, I applied optical methods to hybrid interfaces between a live primary T cell and a supported lipid bilayer mimicking an antigen-presenting cell (APC) surface. In this manner, I revealed a number of novel mechanisms by which ligand-receptor dynamics dictate T cell signaling output. First, a two-parameter titration of two ligands - agonist peptide-MHC and the costimulatory surface molecule CD80/B7-1 - revealed that the density of CD80 influences the TCR activation threshold. Additionally, co-presentation led to an interdependent trafficking scheme of these surface molecules that may serve to boost the effectiveness of CD80 costimulation at low agonist peptide-MHC densities and reduce spurious activation under other conditions. Second, it was possible to resolve TCR microclusters by size using a nanoparticle array embedded in the ligand-presenting bilayer. This innovative form of size-based membrane-receptor chromatography in live cells revealed that the maximal size of the TCR microclusters was regulated by engagement with MHC molecules occupied by our model agonist peptide (moth cytochrome c). T cell antigen recognition and subsequent activation was found to be unaffected by the percolation of actively signaling TCR microclusters through this nanoparticle array. Third, myosin activity was responsible for the rapid centripetal burst of TCR microclusters in the initial 60 seconds after antigen exposure. Importantly, inhibition of myosin-induced forces abolished T cell activation, a process potentially mediated by the force-tension sensor CasL. In summary, T cell response potency results from spatiotemporal coordination of a massive interconnected signaling network undergoing continuous feedback with ligand-receptor binding events.

Advisor: Groves, Jay T
Kuriyan, John
The Politics of Visibility: Urban Housing Struggles in Post-Katrina New Orleans

This dissertation compares three housing and land struggles that emerged in post-Hurricane Katrina New Orleans. I analyze the politics that emerge around the closure of public housing, the razing of a neighborhood for a dual-hospital complex, and the attempt to repopulate the predominately Black, working-class Lower Ninth Ward. The dissertation broadly asks: what are the techniques of governance in an era of neoliberalism and how do local actors respond to the physical and political dispossession that comes with these techniques? Using ethnographic research, I uncover the spatial politics of poverty that developed around contested rebuilding and redevelopment policies in an increasingly privatized urban environment.

Advisor: Burawoy, Michael
Intraparty Organization in the U.S. Congress

The purpose of this dissertation is to supply a simple and synthetic theory to help us to understand the development and value of organized intraparty blocs. I will argue that lawmakers rely on these intraparty organizations to resolve several serious collective action and coordination problems that otherwise make it difficult for rank-and-file party members to successfully challenge their congressional leaders for control of policy outcomes. In the empirical chapters of this dissertation, I will show that intraparty organizations empower dissident lawmakers to resolve their collective action and coordination challenges by providing selective incentives to cooperative members, transforming public good policies into excludable accomplishments, and instituting rules and procedures to promote group decision-making. And, in tracing the development of intraparty organization through several well-known examples of party infighting, I will demonstrate that intraparty organizations have played pivotal -- yet largely unrecognized -- roles in critical legislative battles, including turn-of-the-century economic struggles, mid-century battles over civil rights legislation, and contemporary debates over national health care policy.

Advisor: Schickler, Eric
The Order of Appearances, Urban Renewal in Johannesburg

This dissertation explores the representation of urban renewal in `post'-apartheid Johannesburg and the co-constitution of subjectivities therein. It is particularly concerned with how regimes of representation, embodied in public art projects, were enlisted in the construction of national identity and the expansion of neo-liberal capitalist accumulation in the inner city. By focusing on these representational practices, this study hopes to make a contribution to a broader understanding of how regimes of representation constitute a new domain of politics in post-apartheid Johannesburg.

Advisor: Alsayyad, Nezar