VictorJuiz/thesis huggingface dataset:
Secondary Predication in Polish

This thesis explains how secondary predication is constructed. It focuses on Polish, with some comparisons to other languages, and provides analysis on the syntactic, morphological and semantic level in the paradigm of Minimalism./nIt starts with a definition of primary and secondary predication, maintaining that only adjuncts are true secondary predicates. This is followed by an introduction of a new phrase type, bipartite, to Polish linguistics – an expression consisting of a preposition and adjective or, sometimes, a noun. It is shown that bipartites are not simply adverbs, for which they have been taken so far, but they can serve in a variety of functions, some of them typical for adjectives, such as attributive modifier or predicative use. That predicative use, especially in secondary predication, is then in the focus of the rest of this work./nThe morphosyntactic composition of secondary predication is discussed in detail, showing that lexically secondary predicates involve both adjectives and nouns (to a much lesser extent). Structurally, secondary predicates are divided into bare ones, consisting of an adjective or noun, and prepositional ones, involving bipartites, and thus consisting of a combination of a preposition and adjective or noun. Semantically, secondary predicates can be depictive or resultative. It is also illustrated that although secondary predicates fall into the category of adjuncts, they must be clearly distinguished from adverbials, attributives, interjections and absolutes./nThe second part of this study concentrates on the syntax of secondary predication. It shows that secondary predicates are best described as small clauses with a predicator serving as Pr head. Three attachment sites are proposed that allow for unambiguous subject and object control, as well as separation of depictives and resultatives from circumstantials./nSecondary predicates can both agree and not agree with controlling NPs. Cases are discussed where agreement is obligatory, optional or blocked. In order to account for this variety, two types of Pr head (small clause head) are assumed: the full one blocks agreement and may assign its own case, the defective one allows agreement. The agreement involves both Agree and feature sharing between the controlling NP and secondary predicate. Finally, long distance control of secondary predicates in non-finite constructions and verbal nouns is explained./nAdditional to dichotomy depictive vs. resultative, a third group, the co-called circumstantials, is identified which differs significantly from the former ones not only in semantics, but also in lexical composition (they are predominantly nominal) and attachment site (inside NP).

Advisor: Nichols, Johanna
Mechanisms of cyclic dinucleotide signaling: from prokaryotes to humans

Cyclic dinucleotides (cdNs) are novel second messengers that are synthesized directly from two “molecular units of energy” in the cell, namely ATP and GTP. In prokaryotes, all three combinations of cdNs have been discovered: cyclic di-AMP, cyclic AMP-GMP, and cyclic di-GMP. Their effects on bacterial host physiology have been shown to be important and diverse, impacting processes ranging from biofilm formation to motility to sporulation. Many of their prokaryotic effectors are protein-based; however, cyclic dinucleotides have also been shown to exert genetic expression control at the RNA level by binding to mRNA regulatory elements called riboswitches. While cyclic dinucleotide signaling in prokaryotes has been appreciated for over 25 years, it was not until the last few years that cyclic dinucleotide signaling has been shown to exist and have a profound impact in mammals. cGAMP (a non-canonically linked cyclic AMP-GMP) has been discovered endogenously within humans and found to be a critical second messenger for signaling pathogen invasion to the host. cGAS, a cytosolic mammalian cyclic dinucleotide synthase, produces cGAMP upon binding pathogen DNA. Subsequently, cGAMP binds to the ER-resident transmembrane protein STING, which triggers a downstream cascade of interferon, cytokine, and chemokine production. Therefore from prokaryotes to humans, cyclic dinucleotide signaling spans billions of years in evolution, and today has led to great interest in its therapeutic targeting./nThis work details the discovery of cyclic AMP-GMP and its cognate riboswitch within the bacteria Geobacter sulfurreducens. Interestingly, cyclic AMP-GMP signaling through its riboswitch plays a previously unappreciated role in exoelectrogenesis within Geobacter. The structural elucidation and signaling role of cyclic AMP-GMP (cGAMP) in humans is subsequently described, showing that humans utilize a novel regioisomer of cyclic AMP-GMP containing mixed 2′-5′ and 3′-5′ phosphodiester bonds. The ancient origin of human cGAMP signaling is illuminated by the discovery of a functional cGAS-cdN-STING pathway in Nematostella vectensis, an anemone species >500 million years diverged from humans. The structure of anemone STING is highly conserved compared to human STING, yet anemone cGAS appears to produce only a 3′-5′ linked cdN. Finally, the signaling space of the cGAS-cdN-STING pathway is examined with a focus on its potential functions in lower organisms. Taken holistically, this work details the signaling mechanisms of cyclic dinucleotides in multiple organisms, while profiling the chemical evolution of a unique second messenger.

Advisor: Doudna, Jennifer A
Vance, Russell E
Spin-Orbit Coupled Quantum Magnetism in the 3D-Honeycomb Iridates

In this doctoral dissertation, we consider the significance of spin-orbit coupling for the phases of matter which arise for strongly correlated electrons. We explore emergent behavior in quantum many-body systems, including symmetry-breaking orders, quantum spin liquids, and unconventional superconductivity. Our study is cemented by a particular class of Mott-insulating materials, centered around a family of two- and three-dimensional iridium oxides, whose honeycomb-like lattice structure admits peculiar magnetic interactions, the so-called Kitaev exchange. By analyzing recent experiments on these compounds, we show that this unconventional exchange is the key ingredient in describing their magnetism, and then use a combination of numerical and analytical techniques to investigate the implications for the phase diagram as well as the physics of the proximate three-dimensional quantum spin liquid phases. These long-ranged-entangled fractionalized phases should exhibit special features, including finite-temperature stability as well as unconventional high-Tc superconductivity upon charge-doping, which should aid future experimental searches for spin liquid physics. Our study explores the nature of frustration and fractionalization which can arise in quantum systems in the presence of strong spin-orbit coupling.

Advisor: Vishwanath, Ashvin
Recognition, Activation, and Signaling Functions of the Arabidopsis NLR receptor RPP1

Microbial pathogens of plants secrete effector proteins into host cells to suppress basal immunity and manipulate host metabolism, but can be detected by a repertoire of innate immune receptors known as nucleotide-binding leucine rich repeat (NLR) proteins. Though NLRs were identified nearly 25 years ago, are ubiquitous across plant species, and are important components of pest resistance strategies in crops, the molecular mechanisms of NLR function are still unclear. This dissertation presents work on RPP1 (Resistance to Peronospora parasitica), an Arabidopsis NLR receptor that specifically recognizes the effector protein ATR1 from the naturally occurring oomycete pathogen Hyaloperonospora arabidopsidis. Genetic and molecular analysis of ATR1-RPP1 direct association demonstrates a variety of allele-specific recognition surfaces on the tandem WY-domain structure of ATR1. Mutations on these surfaces specifically activate a series of closely related RPP1 homologs, which show surprising structural variation in their recognition domain, a series of C-terminal leucine-rich repeats. Specificity is dictated by LRR binding affinity and full-length receptor sensitivity to activation, as demonstrated by chimeric NLR constructs and specific LRR mutations along a predicted ligand binding surface. Finally, recognized and unrecognized ATR1 alleles are used to probe inter-domain interactions and receptor oligomerization events upon effector binding. In addition, components of downstream signaling are studied using the autoactive, effector-independent TIR signaling domain of RPP1. Mechanistic details for how NLR receptors recognize pathogenic signatures may allow engineering of expanded NLR recognition specificity, yielding broad-spectrum, durable disease resistance in crop plants.

Advisor: Staskawicz, Brian J
Russian Literary Portraiture in the Twentieth Century: Collecting and Re-Collecting Lichnosti in Criticism and Memoir

This dissertation offers a select history of the literary portrait genre in Russian culture from its genesis in the 1890s through the 1960s. I define the literary portrait as a succinct account of a particular author's individual or creative personality – in Russian, lichnost' – that readily lends itself to anthologization, in which that literary portrait acquires additional meaning through the comparative or cumulative format in which it participates. In tracing the developments in the genre through a series of representative portrait collections, I focus in particular on two historical moments: 1905-1914, when literary portraiture moved beyond its original Symbolist confines, courted a wider reading audience, and became a key genre for the theorization and explication of Russian modernity; and the post-Revolutionary period, when writers both in emigration and within the Soviet Union repeatedly turned to the genre as a means of shaping narratives about late imperial and early Soviet culture. In the first period, I consider the literary critical portraiture of Iulii Aikhenval'd, Kornei Chukovskii, and Maksimilian Voloshin, and in the second, I consider the memoir-portraits of Vladislav Khodasevich, Kornei Chukovskii, and Iurii Annenkov, as well as Annenkov's work in visual portraiture. I posit that these writers, each in their own way and to their own ends, sought common variables that would unite the heterogeneous literary field of late imperial Russia. In doing so, they created forms of literary historical periodization that focused on cultural continuity rather than aesthetic displacement, and on webs of connections between individual authors rather than distinctions between nominally antithetical movements. These holistic interpretations of late imperial Russian literature demonstrate the pedagogical utility of comparative frameworks that take individuals (lichnostoi) as their units of observation. In constructing such frameworks, these portraitists consistently demonstrate that our understanding of dominant aesthetic movements of the time (the Symbolists and Modernists) and the dominant paradigm of cultural periodization that followed it (the Silver Age) are best calibrated against certain figures (especially Leonid Andreev and Maksim Gor'kii) who are otherwise afforded narrow parts in our inherited literary histories. Thus, I aspire to present literary portraiture as a telling artifact of Russian modernity writ large, and a valuable means of re-examining the literary historical narratives that structure our study of early twentieth-century Russian culture.

Advisor: Ram, Harsha
Dual mechanism for APC/C activation by integrated ubiquitylation and dephosphorylation

The Anaphase Promoting Complex (APC/C) is a multi-subunit ubiquitin ligase that is essential for cell cycle progression. Ube2S and Ube2C are dedicated APC/C E2-conjuating enzymes that build ubiquitin chains upon mitotic substrates. Two critical outcomes exist for this activity. First, proteins that have fulfilled their mitotic roles are removed by proteasomal degradation. Second, ubiquitylation is required to disrupt inhibitory binding of the mitotic checkpoint complex (MCC) to APC/C through the promotion of CDC20 degradation, thereby silencing the spindle assembly checkpoint (SAC). Surprisingly, however, depletion of Ube2S and Ube2C does not prevent mitotic exit. We decided to perform a Ube2S genetic interaction screen in order to better understand the functional importance of the E2 enzymes in mitosis. We discovered that Ube2S activity is essential for cell survival when one of several regulators of kinetochore-microtubule dynamics is depleted, such as the mitotic kinesin Kif18A. Co-depletion of Ube2S with one or more of these regulators results in a prolonged or permanent prometaphase arrest dependent upon the SAC. These data suggest a role for Ube2S and the APC/C in prometaphase, a time in which APC/C activity has been thought to be low. Further analysis of Ube2S in prometaphase has revealed that Ube2S contributes heavily to proper oscillatory movement of kinetochores. We also examined changes in APC/C composition when its ubiquitylation activity had been compromised, to mimic Ube2S depletion. We found that when APC/C activity is limited in prometaphase, phosphatases interact with APC/C in a Cdc20-dependent manner. Furthermore, removal or depletion of phosphatase activity results in decreased ubiquitylation of APC/C substrates and subsequent stabilization of proteins such as geminin. Reduced APC/C activity when dephosphorylation is blocked is likely due to less activity of Ube2S and to loss of co-activator function by CDC20. Taken together, these data have identified a necessary, integrated function for ubiquitylation and phosphatase activity in the regulation of cell division.

Advisor: Rape, Michael
Biochemical Analysis of the COPII Coat Reveals Cargo Recruitment Is a Distinct Step from Vesicle Packaging

The endomembrane system is the defining feature of eukaryotic cells and ensures that the appropriate proteins are sorted and transported to their correct subcellular location where they perform their biological functions. The coat protein complex II (COPII) mediates the formation of COPII vesicles, which are responsible for exporting proteins and lipids from the endoplasmic reticulum (ER). The core COPII coat consists of five proteins: the small GTPase Sar1, the Sec23/24 heterodimer, and the Sec13/31 heterotetramer. The recognition and subsequent packaging of cargo into COPII vesicles is mediated by interaction with the Sec24 subunit./nThe development of a cell-free vesicle budding reaction has facilitated a biochemical analysis of COPII trafficking. Initial experiments examining COPII packaging of mammalian cargo proteins suggested that while some cargo proteins could be packaged directly by the core COPII components, other cargo proteins seemed to require additional cytosolic factors for efficient packaging. Whether auxiliary cytosolic factors exist to promote the COPII packaging of a specific subset of cargo proteins is the central question that motivated the work described in this dissertation./nThis question was first approached using Vangl2, a cell surface localized transmembrane protein involved in planar cell polarity signaling, as a model cargo molecule. However, during the course of characterizing COPII packaging of Vangl2 in vitro, it was determined that this was not the appropriate system to address this question. As a result, proTGFα, the precursor form of transforming growth factor alpha, was chosen as a model cargo protein to continue to address the central question./nHere, I describe the key observations that show the existence of auxiliary cytosolic factor(s) that are required for efficient COPII packaging of specific cargo. In the particular case of proTGFα, both its recruitment by the COPII machinery and its final packaging into COPII vesicles require the cooperation of one or more auxiliary cytosolic factors and a transmembrane cargo receptor, Cornichon-1. Moreover, I present evidence showing that interaction of cargo proteins with the COPII coat is insufficient for packaging into COPII vesicles. This suggests that cargo recruitment and vesicle packaging are two distinct steps of COPII vesicle formation. Taken together, these observations provide novel insights into the molecular mechanism of COPII vesicle formation in mammals.

Advisor: Schekman, Randy W
Wideband Signal Acquisition via Frequency-Interleaved Sampling

High-speed analog-to-digital converters (ADCs) are key enabling blocks for emerging wideband applications in communication, high-end instrumentation, and medical imaging. Larger signaling bandwidth improves system performance and necessitates high-speed ADCs for accurate digitization. As an example, current state-of-the-art oscilloscopes have an acquisition bandwidth exceeding 60GHz with effective sample rates greater than 100GS/s. This places significant difficulty in the design of sample-and-hold (S/H) and analog-to-digital conversion circuitry that can operate at such high speeds while providing moderate resolution. As a result, the front-end of these systems are often complex, multi-chip solutions that are fabricated in expensive processes such as indium-phosphide (InP). With the increased demand for battery-operable, low-power systems it is desirable to have these high-performance signal acquisition systems in a fully-integrated CMOS implementation in order to harness the power of scaling as dictated by Moore's law. To achieve this, several advancements on current data conversion techniques need to be made./nIn this thesis, we explore the design and optimization of a frequency-interleaved ADC (FI-ADC) as an alternative to conventional high-speed ADC architectures, which are often heavily time-interleaved. Due to the large interleaving factor and timing sensitivity, the conventional architectures are often very power hungry and offer typical resolutions of 4 bits or less. FI-ADCs, in which the input signal is divided into various frequency bands which are independently digitized and digitally recombined, show less susceptibility to jitter, the primary bottleneck in high-speed ADCs. System simulations have shown a potential improvement in SNR performance for a frequency-interleaved ADC versus a direct sampling, time-interleaved architecture./nThe focus of this thesis is to provide a fundamental understanding of the operation of the FI-ADC and investigate the similarities and differences to the conventional time-interleaved ADC in respect to design complexity, design challenges and overall performance.

Advisor: Niknejad, Ali M
Structural and Biochemical Characterization of the XPC DNA Repair and Stem Cell Coactivator Complex

The regulation of eukaryotic gene expression is critical for proper cell homeostasis and development and relies largely on appropriate initiation of transcription. Transcriptional regulators, such as sequence-specific transcription factors, coactivators, general transcription factors, and chromatin remodelers, are often expressed in a cell-type specific manner to drive cell fate decisions and developmental transitions. Recently, the XPC DNA repair factor was identified as the Stem Cell Coactivator (SCC) complex, a key transcriptional coactivator required to assist OCT4 and SOX2 in driving the expression of key pluripotency genes in embryonic stem cells./nChapter 1 provides an introduction to mechanisms of eukaryotic transcriptional regulation, eukaryotic DNA repair, and the involvement of the XPC/SCC complex in both of these capacities./nIn chapter 2, I describe the first structures of the human apo and DNA-bound XPC holo-complex, as solved by electron microscopy. Comparison of the apo and DNA-bound structures identified key regions that become locally disordered upon engagement with DNA. Using a combination of sequence homology, computational docking of a partial homolog crystal structure into the EM density, and mapped interaction domains, I present a predictive model illustrating regions of key contacts on the XPC/SCC complex./nIn chapter 3, I describe the involvement of largely non-specific RNA but not DNA or heparin in mediating the interaction between SOX2 and SCC in a dose-dependent fashion, a novel mode of potentially RNA-mediated transcriptional regulation. I provide evidence that there are little or no sequence or structural requirements for the RNA I also show that while this interaction is RNA-dependent, direct contacts can be formed between SCC and SOX2, suggesting that RNA is stabilizing and possibly even multimerizing existing protein-protein contacts between SCC and SOX2./nIn summary, the findings described in this dissertation provide a structural and biochemical framework for understanding the molecular and cellular mechanisms of SCC-driven gene regulation.

Advisor: Tjian, Robert
Ultrafast X-Ray Absorption Spectroscopy of Isochorically Heated Warm Dense Matter

This dissertation will present a series of new tools, together with new techniques, focused on the understanding of warm and dense matter. We report on the development of a high time resolution and high detection efficiency x-ray camera. The camera is integrated with a short pulse laser and an x-ray beamline at the Advanced Light Source synchrotron. This provides an instrument for single shot, broadband x-ray absorption spectroscopy of warm and dense matter with 2 picosecond time resolution. Warm and dense matter is created by isochorically heating samples of known density with an ultrafast optical laser pulse, and X-ray absorption spectroscopy probes the unoccupied electronic density of states before the onset of hydrodynamic expansion and electron-ion equilibrium is reached. Measured spectra from a variety of materials are compared with first principle molecular dynamics and density functional theory calculations./nIn heated silicon dioxide spectra, two novel pre-edge features are observed, a peak below the band gap and absorption within the band gap, while a reduction was observed in the features above the edge. From consideration of the calculated spectra, the peak below the gap is attributed to valence electrons that have been promoted to the conduction band, the absorption within the gap is attributed to broken Si-O bonds, and the reduction above the edge is attributed to an elevated ionic temperature./nIn heated copper spectra, a time-dependent shift and broadening of the absorption edge are observed, consistent with and elevated electron temperature. The temporal evolution of the electronic temperature is accurately determined by fitting the measured spectra with calculated spectra. The electron-ion equilibration is studied with a two-temperature model./nIn heated nickel spectra, a shift of the absorption edge is observed. This shift is found to be inconsistent with calculated spectra and independent of incident laser fluence. A shift of the chemical potential is applied to the calculated spectra to obtain satisfactory agreement with measured spectra.

Advisor: Falcone, Roger W