VictorJuiz/thesis huggingface dataset:
Single-molecule measurements of transcript elongation and termination by RNA polymerase [electronic resource]
Keywords: Biophysics.

Transcription by RNAP is highly regulated in both prokaryotic and eukaryotic cells, and the ability of the cell to differentiate and respond to its environment is largely due to this regulation. During elongation, for example, RNAP is known to momentarily halt in response to certain cellular signals, and this pause state has been implicated in the regulation of gene expression in both prokaryotic and eukaryotic organisms. In addition, once RNAP reaches the end of a gene, it must reliably terminate and release the newly-transcribed RNA, providing another potential point of regulation within different cell types. Both of these steps are crucial to ensure proper gene expression. In this dissertation, I focus on transcription elongation by both prokaryotic and eukaryotic RNA polymerases, as well as their regulation through pausing and termination. To probe the role of RNA hairpins in transcriptional pausing, a novel single-molecule "RNA-pulling" assay was used to block the formation of secondary structure in the nascent transcript. Force along the RNA did not significantly affect transcription elongation rates, pause frequencies, or pause lifetimes, indicating that short "ubiquitous" pauses are not a consequence of RNA hairpins. Force-based single-molecule techniques were also used to study the mechanism and energetics of transcription termination in bacteria. The data suggest two separate mechanisms for termination: one that involves hypertranslocation of RNAP along the DNA, and one that involves shearing of the RNA:DNA hybrid within the enzyme. In addition, a quantitative energetic model is presented that successfully predicts the termination efficiency of both wild-type and mutant terminators. Finally, the implementation of a novel optical-trapping assay capable of directly observing transcription by eukaryotic RNA polymerase II (RNAPII) molecules is described. This approach was used to probe the RNAPII nucleotide-addition cycle, as well as the role of the trigger loop (a conserved subdomain) in elongation. The results are consistent with a Brownian ratchet model of elongation which incorporates a secondary NTP binding site, and the trigger loop was found to modulate translocation, NTP binding, and catalysis, as well as substrate selection and mismatch recognition by RNAPII.
Small heat shock proteins as novel anti-inflammatory therapeutics for neurological diseases [electronic resource] : multiple sclerosis and stroke
Keywords: Biology.

This thesis explores the use of small heat shock proteins as anti-inflammatory therapeutics in the context of neurological diseases, specifically multiple sclerosis (MS) and stroke. The family of small heat shock proteins (sHSPs) has been extensively studied as intracellular molecular chaperones. However, recent studies looking at the role of sHSPs in neurological diseases have demonstrated a near universal upregulation of certain sHSPs in damaged and diseased brains. Initially, it was thought that sHSPs are pathological in these disease states, but transgenic overexpression and exogenous administration of sHSPs in various experimental disease paradigms have shown just the contrary -- that sHSPs are protective, not pathological. In this thesis, I have found that members of the family of sHSPs are protective and therapeutic in mouse models of multiple sclerosis and stroke, experimental autoimmune encephalomyelitis (EAE) and middle cerebral artery occlusion (MCAO), respectively. Alpha B crystallin (cryab), a member of the sHSP family, is elevated in stroke and deficiency of cryab leads to worse disease outcome, illustrating the protective role of alpha B crystallin. Exogenous administration of small heat shock proteins, including alpha B crystallin, decreases disease severity by modulating the immune system. This leads to the conclusion that sHSPs are endogenous anti-inflammatory and neuroprotectant molecules produced after neurological disease, whose beneficial properties can be augmented when administered therapeutically.
Social influence in online environments [electronic resource] : models and analysis
Keywords: Management Science and Engineering

In this thesis we study the effects of social influence on the decisions of individuals in online environments. We focus on two different applications, social media and peer-to-peer lending. We initially propose a model for the evolution of market share in the presence of social influence. We study a simple market in which individuals arrive sequentially and choose one of the available products. Their decision of which product to choose is a stochastic function of the inherent quality of the product and its market share. Using techniques from stochastic approximation theory, we show that market shares converge to an equilibrium. We also derive the market shares at equilibrium in terms of the level of social influence and the inherent fitness of the products. In a special case, when the choice model is a multinomial logit model, we show that inequality in the market increases with social influence and with strong enough social influence, monopoly occurs. These results support the observations made by Salganik et al. [SDW06] in their experimental study of cultural markets. Next, we consider the effects of social influence in an online P2P lending service. Online peer- to-peer (P2P) lending services are a new type of social platform that enable individuals to borrow and lend money directly to each other. In this part of the thesis, we study the dynamics of bidder behavior in a P2P loan auction website, prosper.com. We investigate the change of various attributes of loan request listings over time, such as the interest rate and the number of bids. We observe the effects of social influence during bidding: for most listings, the rate of bids peaks at very similar time points. We explain these phenomena by showing that there are economic and social factors that lenders take into account when deciding to bid on a listing. We also observe that the profits that lenders make are tied with their bidding preferences. Finally, we build a model based on the temporal progression of the bidding, that reliably predicts the success of a loan request listing, as well as whether a loan will be paid back or not.
Soft X-ray coherence and coherent diffractive imaging [electronic resource]
Keywords: Applied Physics

The increased brightness of third-generation synchrotron X-ray sources using undulator insertion devices has opened up new fields for coherent lensless imaging experiments. While in the optical regime, coherent light sources allowed the pursuit of holography and imaging of non-periodic micron-sized objects, hard X-ray crystallography relied on the constructive interference of periodic lattices to image atomic structures. In the intermediate regime of soft X-rays, we now have the capability to coherently image non-periodic nanoscopic structures. Several elemental resonances, from carbon, nitrogen and oxygen to iron, cobalt and nickel, fall into the soft X-ray range of 100 eV to 1 keV. In order to pursue soft X-ray coherent imaging experiments at a synchrotron, an understanding of the origin of coherence is required. The first part of this work thus addresses the coherence properties of the undulator source. Imaging in this regime is both photon and spatial coherence thirsty and there is an inherent trade-off between these two resources. The incoherent source structure and the Heisenberg uncertainty principle lie at the heart of this matter. In reconstructing images of materials from intensity diffraction patterns, one faces the well-known phase problem. The second part of this work addresses two imaging techniques that were extended to the imaging of magnetic domains using X-ray magnetic circular dichroism. Fourier transform holography encodes the lost phase information into the intensity diffraction pattern, while multi-wavelength anomalous diffraction utilizes the energy dependence of the material's refractive index to regain the phase information. This latter method simplifies the sample preparation process and has the potential for coherent scanning microscopy.
The solution path of the generalized lasso [electronic resource]
Keywords: Statistics

We present a path algorithm for the generalized lasso problem. This problem penalizes the l1 norm of a matrix D times the coefficient vector, and has a wide range of applications, dictated by the choice of D. Our algorithm is based on solving the dual of the generalized lasso, which facilitates computation and conceptual understanding of the path. For D=I (the usual lasso), we draw a connection between our approach and the well-known LARS algorithm. For an arbitrary D, we derive an unbiased estimate of the degrees of freedom of the generalized lasso fit. This estimate turns out to be quite intuitive in many applications.
Solution processing for copper indium sulfide solar cells [electronic resource]
Keywords: Chemistry

In recent years, the field of photovoltaics has become increasingly important due to rising energy demand and climate change. While most solar cells are currently composed of crystalline silicon, devices with thinner films of inorganic absorber materials might allow production at a greater scale due to their lower materials cost. In particular, thin films of CuInS2 are promising solar absorber materials due to their high efficiencies and low required thicknesses. However, the fabrication of thin film solar cells currently requires expensive vacuum techniques. As an alternative, solution-based deposition techniques have been proposed as a route to low-cost and high-throughput electronic device fabrication. I have studied how film growth depends on solutuion deposited precursor film quality, with the goal of producing large grained films of CuInS2 through solution processing. In the first approach, we used solvothermal decomposition of organometallic precursors at moderate temperatures to produce nanoparticles of CuInS2. Thin films of these nanoparticles were cast onto molybdenum coated glass and further processed to create CuInS2 solar cells. We found that performance was dependent on film porosity, grain size, and stoichiometry of the nanoparticles. Films with grain sizes of ~200nm were attained, from which 1.3% efficient solar cells were made. In addition, we showed that this synthesis could be extended to produce CuInS2 nanoparticles with partial substitution of Fe, Zn, and Ga. In the second approach, we synthesized an air-stable hybrid organometallic/nanoparticle ink at room temperature in ambient conditions through a vulcanization reaction. This ink could be coated onto substrates in smooth layers, and further reactive annealing formed large grained CuInS2 films. This process was characterized, and a correlation between residual carbon and grain growth was found. Additionally, the chemical transformation between precursor layers and final sulfide thin film was analyzed, with an emphasis on the difference between sulfurization and selenization. We demonstrated that the sulfurization process was producing morphological defects due to its nucleation limited growth mechanism. However, it was modified to more closely resemble the diffusion limited selenization mechanism, thus producing flat films of CuInS2 with grain sizes of ~500nm.
Source variation and ground accessibility of magnetospheric mid-latitude ELF/VLF chorus and hiss [electronic resource]
Keywords: Electrical Engineering

The distribution of relativistic electrons that form the Earth's radiation belts is extremely variable, with the trapped flux changing by several orders of magnitude on timescales of a few hours to days. These energetic particles pose a significant hazard to satellites and astronauts in the near-Earth space environment. The dynamic evolution of the radiation belts is believed to be controlled in large part by two separate but related classes of naturally occurring plasma waves: extremely low frequency/very low frequency (ELF/VLF) chorus and hiss. This dissertation explores characteristics of chorus and hiss observed at Palmer Station, Antarctica with the goal of improving our ability to differentiate between variations in emission generation and the effects of emissions' propagation to the ground. Results are presented from a two-part study, consisting of both observations and modeling, which explores the manner in which the plasmapause affects the propagation of chorus from its magnetospheric source to the ground. Results indicate that the observed chorus propagates in a non-ducted mode, which is contrary to a long-standing belief that guiding structures are necessary for chorus to propagate to the ground. This newly-explored mode of ground propagation indicates that ground stations may be able to observe a larger portion of waves than previously thought and provides for a more accurate interpretation of ground-observed waves and their influence on energetic particle distributions. Following this, an automated system of detecting chorus and hiss in broadband ELF/VLF data using neural networks is discussed. Results of running the automated detector on ten years of data are discussed including diurnal, seasonal and solar cyclical variations of emissions.
Spatial regulation of cellulose synthase trafficking [electronic resource]
Keywords: Biology.

Plants owe their distinctive shapes, in large part, to the anisotropic expansion of constituent cells. During growth and development, a strong yet pliant cell wall constrains turgor-driven expansion along specific directions in the cell. This process relies on the function of two polymer arrays separated by the plasma membrane: the cortical microtubule cytoskeleton in the cytoplasm and the cellulose microfibril array in the cell wall. Live cell imaging previously confirmed that one function of the cortical microtubule array is to guide the trajectories of active cellulose synthase (CESA) complexes in the plasma membrane, thus orienting the deposition of nascent microfibrils. Here, I present evidence that cortical microtubules also position the delivery of CESA complexes to the plasma membrane and interact with small CESA-containing compartments by an unusual mechanism that permits motility driven by microtubule depolymerization. The association of CESA compartments with cortical microtubules is greatly enhanced during osmotic stress and other treatments that limit cellulose synthesis. Upon recovery from osmotic stress, delivery of CESA complexes to the plasma membrane is observed in association with microtubule-tethered compartments. While cortical microtubules appear to exert local control on CESA translocation and exocytosis, actin influences the global distribution of CESA at the plasma membrane. To study more general patterns of exocytosis, a probe based on the Arabidopsis SM protein KEULE was developed. Fluorescently labeled KEULE formed discrete, transient clusters at the plasma membrane, some of which coincided in space and time with the exocytosis of CESA complexes. Consistent with known SM function, KEULE facilitates vesicle fusion in growing plant cells. Thus, KEULE recruitment to the plasma membrane defines an intermediate step in the exocytosis of CESA and possibly other secreted cargo. KEULE localized preferentially near cortical microtubules and recent sites of cellulose synthesis, suggesting the microtubule cytoskeleton and nascent microfibrils define dynamic secretion domains at the plasma membrane. A genetic screen was conducted to identify factors that mediate the physical association of CESA, and organelles that traffic CESA, with the cortical microtubule cytoskeleton. I isolated two Arabidopsis mutants exhibiting reduced anisotropic growth, an inability to tether CESA-containing compartments to microtubules, and aberrant patterns of CESA motility at the plasma membrane. This phenotype is consistent with a general decoupling of CESA and microtubules. This thesis establishes new roles for the cortical microtubule cytoskeleton in organizing vesicular trafficking, and provides new genetic tools to examine the mechanism and regulation of CESA-microtubule interaction.
Specialization and interchangeability of the cellulose synthase complex [electronic resource]
Keywords: Biology.

Cellulose is an essential component of the plant cell wall, where it serves as the major load bearing structure. Cellulose is synthesized by cellulose synthases (CESAs), which act in a large complex at the plasma membrane. In Arabidopsis, certain primary CESAs synthesize the primary cell wall, while others synthesize the secondary cell wall. Both the primary complex and the secondary complex are composed of three distinct genetic positions which are filled by specialized isoforms. It this thesis, I analyze the sequences of the cellulose synthase family to show that these genetic positions reflect a specialization found in all seed plants. I identify a number of regions within the CESA sequences which may be responsible for the specialized "class-specific" properties of these CESAs. By generating catalytic inactivations to various primary CESAs, I show that a catalytically inactivated CESA6 construct is able to rescue a CESA6 null mutant, while a catalytically inactivated CESA3 construct is unable to rescue its respective mutant. This indicates differences in the importance of catalytic activity between CESAs. Because the CESA6 family is the most expanded, this suggests that control of cellulose properties could occur through regulation of CESA6 catalytic activity. I demonstrate that expressing the secondary CESA7, it is possible to partially rescue a mutation to the primary CESA3 gene, even though the CESA3 and CESA7 families diverged early in plant evolution and no primary CESAs can rescue other primary CESA mutants. This suggests that the primary and secondary complexes share a common architecture with limited interchangeability. Finally, I characterize two fluorescent dyes which bind preferentially to cellulose and which are suitable for confocal microscopy. These dyes allow cellulose fibrils to be visualized in vivo for the first time. This revealed that cellulose fibrils reorient over the course of root cell elongation, generating a multilaminar network strengthened against forces along all axes from a set of microfibrils which are initially synthesized in a transverse orientation at the membrane.
Spectacles of authenticity [electronic resource] : the emergence of transnational entertainments in Japan and America, 1880-1905
Keywords: Art and Art History

In the late-nineteenth and early twentieth centuries, America and Japan were in the process of establishing their positions as powers in a world dominated by Western Europe. The two nations with unconnected histories and cultures found themselves in momentary sympathy as they embarked on their first forays into military imperialism, expanded their trade, and constructed civic institutions intended to compete with those of Europe. It was during this period that mass entertainments developed and began circulating across national borders and, drawing on tourist practices, helped create a "universal" visual culture which coexisted with local particularities. This dissertation undertakes a study of Japanese and American shared visual culture and modern entertainments with the goal of nuancing current scholarship on East/West exchanges and expanding the definition of modernity. Three modern phenomena, panoramas, World's Fairs, and film, form the core of my three main chapters and describe a process of appropriation, assimilation, and collaboration through their movements from Europe, across America to Japan, and ending with a return to America. Many scholars have observed that Americans viewed Japan as a confusing cultural other with a baffling skill at appearing modern. This dissertation begins with the premise that Japan was modern and re-examines American and Japanese cultural exchanges from this position with the aim of shifting the paradigms of modernity and modern visuality.
Spectroscopic and theoretical studies of mononuclear non-heme iron enzymes [electronic resource] : insight into the role of the facial triad and substrate effects on reactivity
Keywords: Chemistry

Mononuclear non-heme iron enzymes are an important class with a wide range of medical, pharmaceutical and environmental applications. Within this class, the oxygen activating enzymes use Fe(II) to activate O2 for reaction with the substrate. The focus of this thesis is on understanding two major themes of the oxygen activating enzymes - the role of the (2His/1 carboxylate) facial triad and the initial O2 reaction steps of alpha-keto acid-dependent dioxygenases - using a combination of spectroscopic techniques and DFT calculations. For ferrous systems, abs/CD/MCD/VTVH MCD studies define the geometric and electronic structure of the ferrous site. In combination with DFT calculations, a structure/function picture of the ferrous sites is developed. To extend these studies to the initial steps of O2 binding, studies with NO as an O2 analogue ({FeNO}7/{FeO2}8) utilize EPR/abs/CD/MCD/VTVH MCD spectroscopy with DFT calculations to elucidate important effects of the substrate on the {FeNO}7 bond. These effects are used in the computational extension to the experimentally inaccessible O2 bound complexes giving insight into the initial steps of O2 binding and activation. Taken together, these studies shed light on the rational for facial triad ligation at the Fe(II) site in the oxygen activating enzymes and how the Fe(II) ligand set tunes the specific reactivity of these enzymes.
Strictly proper mechanisms with cooperating players [electronic resource]
Keywords: Management Science and Engineering

In order to obtain accurate information about the uncertainty in a decision situation, a decision maker may rely on the judgment of experts to obtain useful probabilistic forecasts. Strictly proper scoring rules have been shown to incentivize forecasters to provide truthful probabilistic forecasts and can be interpreted as a contract between a decision maker and a risk neutral forecaster rewarding greater expertise as well as truthful revelation. In recent years, prediction markets have been created to provide an efficient means to assess uncertain quantities from forecasters, and strictly proper scoring rules have been proposed for prediction markets, where the payment depends on the forecaster's score relative to others. However, we show that when those players can cooperate, these mechanisms can instead discourage them from reporting what they really believe. When players with different beliefs are able to cooperate and form a coalition, these mechanisms admit arbitrage and there is a report that will always pay coalition members more than their truthful forecasts. If the coalition were created by an intermediary, such as a web portal, the intermediary would be guaranteed a profit from this risk free surplus. Specifically, for the three most commonly used strictly proper scoring rules, we provide a cooperative report for coalition members and show the magnitude of the surplus from cooperation with numerical examples. We analyze the optimal behavior of coalition members within a coalition. Given a choice whether to participate in any coalition, players should participate. We show conditions under which coalition members should invite new members. We evaluate the optimal strategy of each coalition member under a set of simple assumptions including a quadratic scoring rule, and show that honest revelation within the coalition is a Bayesian Nash equilibrium. We show the consequence of players' cooperation to the decision maker receiving aggregated probabilities, and conclude with open challenges in the design and understanding of strictly proper mechanisms.