VictorJuiz/thesis huggingface dataset:
Genomic adaptation for organohalide respiration of vinyl chloride and other priority pollutants by the anaerobic bacterium Dehalococcoides [electronic resource]

Vinyl chloride (VC) is a widespread groundwater pollutant and Group 1 carcinogen. Microbial respiration of VC is both critical for complete remediation of chloroethenes in situ, and a unique physiology only observed by certain strains of Dehalococcoides. Two different genes independently encoding VC respiration in Dehalococcoides, vcrA and bvcA, were identified previously, each a member of the diverse family of reductive dehalogenase homologous genes, or rdhA. In this thesis I report that vcrA and bvcA are among a subset of putative 'foreign' rdhA with a low GC3 codon usage that favors the nucleotide T, even though tRNAs recognizing T-ending codons are categorically absent in Dehalococcoides genomes. Comparative genomics of the first two complete genome sequences of microorganisms able to respire VC, Dehalococcoides strains VS and BAV1, reveals that vcrA and bvcA are both located within recently integrated, but different, genomic islands (GIs). These islands have different predicted integration sites and different relative positions in the genome, suggesting that bvcA and vcrA were acquired independently and through different mechanisms. In particular, the vcrA-containing GI appears to have integrated at the single-copy tmRNA encoding gene, ssrA, along with many other homologous elements that site-specifically integrate/excise at ssrA -- some of which contain other rdhA. A detailed analysis of these 'ssrA-GIs' in Dehalococcoides identifies the precise position of insertion as well as a conserved module of syntenic integration-associated genes that includes the likely ssrA-specific integrase. Further analysis of (meta)genomic data, as well as targeted sequencing from 4 additional VC-respiring cultures, provided a total of 8 syntenic vcr-GIs from independently derived cultures. Evolutionary estimates for the age of divergence of these 8 vcrA sequences is not confidently distinguishable from the first industrial synthesis of chlorinated ethenes approximately 100 years ago. By contrast, the estimated age of divergence of Dehalococcoides strains far precedes industrial civilization. Overall, ssrA-GIs appear to be a major contributor to the second of two high plasticity regions, genetically dynamic regions that interrupt an otherwise stable, syntenic, and streamlined Dehalococcoides genome -- among the smallest of any free living microorganism. The apparent compartmentalization of Dehalococcoides genome dynamics within specialized regions may enhance opportunistic adaptation to (new) organohalide respiratory niches while protecting a core genome that is highly adapted to life in the anoxic subsurface, exemplified here by the recent site-specific acquisition of VC reductase genes.

Advisor: Spormann Alfred M. primary advisor. Thesis advisor
Francis Christopher advisor. Thesis advisor
Holmes Susan
Genomic analysis of neuron-restrictive silencer factor activity in neuronal and non-neuronal human cell lines [electronic resource]

The neuron-restrictive silencer factor/RE-1 silencing transcription factor (NRSF/REST) is thought to be a negative regulator of neuronal genes in non-neuronal cells. However, evidence of its continued expression and activity in neurons suggests that NRSF may play other roles. A complete knowledge of NRSF target genes in neuronal and non-neuronal cells is the first step to understanding its functions. Using chromatin immunoprecipitation and quantitative PCR, I experimentally tested the occupancy of NRSF in living non-neuronal cells on 113 candidate binding sites predicted on the basis of conservation across the human, mouse, and dog genomes. These tests helped to further refine the prediction algorithm and identified a number of NRSF-bound regulatory microRNAs that may work in a feedforward loop to downregulate NRSF and its co-repressor, CoREST. I next focused on understanding NRSF recruitment in neuron-derived versus non-neuronal cell lines, using chromatin immunoprecipitation paired with ultrahigh-throughput sequencing (ChIP-seq) to get a direct, genome-wide picture of NRSF binding in human neuron-derived and non-neuronal cell lines. I found a large overlap in the NRSF binding pattern between the two cell types, particularly in binding sites found to be strongly or commonly bound. There is a subset of strong sites bound in all cell types, and weaker sites that are more likely to be cell-type specific. These common sites contain the canonical NRSE while the cell line unique sites do not. Finally, I used another ultrahigh-throughput sequencing based method to catalog and quantify all mRNA transcripts in each of the cell lines (RNA-seq) to add target gene expression to the analysis of NRSF function. Common target genes were more likely to be highly expressed in the neuron-derived cell line than in non-neuronal cell lines despite NRSF binding in both. I also found that the neuron-specific binding sites were primarily located in exons and promoters, while common or non-neuronal specific binding sites were primarily located in introns and intergenic regions. Differences in binding strength and target gene expression levels suggest that NRSF has different binding mechanisms and functions in neuron-derived and non-neuronal human cell lines.

Advisor: Myers Richard (Richard M.) primary advisor. Thesis advisor
Barsh Gregory Stefan advisor. Thesis advisor
Brunet Anne
Fuller Margaret T.
Genomic convergence association studies of expression and aging in the human kidney [electronic resource]

Although family studies have shown that genes play a role in longevity and tissue aging, it has proven difficult to identify the specific genetic variants involved. Kidneys age at different rates, such that some people show little or no effects of aging whereas others show rapid functional decline. We developed a sequential transcriptional profiling and expression quantitative trait loci (eQTL) mapping approach known as genomic convergence to find genes associated with aging in the kidney. We first performed whole-genome transcriptional profiling to find 630 genes that change expression with age in the kidney. Next, we used two methods to determine which of these age-regulated genes are eQTLs, which means they contain SNPs whose alleles associate with expression level. We found that 101 of the age-regulated genes are eQTLs. We also found that the allele-specific eQTL detection method, which compares the mRNA levels of the two alleles within heterozygous individuals, was more sensitive than the total expression method in detecting allelic expression differences. We tested the eQTLs for association with kidney aging, measured by glomerular filtration rate (GFR) using combined data from the Baltimore Longitudinal Study of Aging (BLSA) and the InCHIANTI study. We found a SNP association (rs1711437 in MMP20) with kidney aging (uncorrected p = 3.6E-05, empirical p = 0.01) that explains 1-2% of the variance in GFR among individuals. The results of this sequential analysis may provide the first evidence for a gene association with kidney aging in humans. Our approach of combining both expression and genotype data can be applied to any phenotype of interest to increase the power to find genetic associations.

Keywords: Genetics
Advisor: Kim Stuart
Barsh Gregory Stefan advisor. Thesis advisor
Brunet Anne
Tang Hua (Geneticist) advisor. Thesis advisor
Given-before-new, the effects of discourse on argument structure in early child language [electronic resource]

Child language researchers, particularly those studying the acquisition of syntax, have often viewed young children's utterances as isolated and self-contained units of analysis. But "language does not exist in a vacuum" (Clark & Clark 1978:227), and utterances don't either. This dissertation explores the influence of conversational context on early word order. Specifically, I consider how discourse givenness affects the order of postverbal arguments in the speech of preschool children. In three elicited production studies, I systematically varied the structure of the discourse children heard just before they were asked to describe a filmed vignette. Study 1 targeted verbs of locative transfer, both alternating locative verbs (cf. She squirted the hotdog with the ketchup. vs. She squirted the ketchup on the hotdog.) and non-alternating ones (cf. She filled the cup with sand. vs. *She filled sand into the cup.). Studies 2 and 3 targeted alternating dative verbs (cf. She gave the man the hat. vs. She gave the hat to the man.). These studies provide converging evidence that (i) givenness has a robust effect on early argument ordering—like adults, children tend to use given-before-new ordering, (ii) this discourse effect can be largely, but not fully, attributed to the effect of discourse on referring expressions (viz. that given arguments tend to be pronominal and new ones tend to be lexical), (iii) givenness does not influence all verbs and all arguments equally. I argue that several factors are needed to explain the asymmetrical effects of givenness across verbs and arguments. These include patterns of distribution in the input, conceptual biases, and semantic and pragmatic properties of the verbs. I also evaluate several mechanisms that might drive early given-before-new ordering: those that are addressee-based, speaker-based, or experience-based. My data do not decide between these, but they do offer preliminary evidence in favor of a speaker-based account. Ultimately, my dissertation highlights the importance of approaching syntactic acquisition from several directions simultaneously. Children must learn to attend to cues from form, function, and discourse and use their limited processing capacities to integrate these cues into a larger model of language production. Linguists must do likewise.

Keywords: Linguistics
Advisor: Clark Eve V. primary advisor. Thesis advisor
Clark Herbert H. advisor. Thesis advisor
Levin Beth
Wasow Thomas advisor. Thesis advisor
Global hepatitis B prevention and treatment [electronic resource] : models and insights

Hepatitis B (HBV) is a vaccine-preventable viral disease that, if untreated, can lead to death from liver disease in 25 percent of patients. Infection with HBV is a major global public health problem, particularly in Asian populations. In an era of limited healthcare budgets, mathematical models can be useful tools to identify cost-effective programs and to support policymakers in making informed decisions. This dissertation describes research on public health policies related to screening, vaccination, and treatment for HBV. It also describe contributions to the theoretical literature on when to stop catch-up vaccination for chronic infectious diseases. In the United States as many as 10% of Asian and Pacific Islander adults are chronically infected with HBV, and up to two thirds are unaware that they are infected. Using Markov models of infection, treatment and disease, I find that screening programs for HBV among Asian and Pacific Islander adults are likely to be cost effective and have clinically significant benefits from identifying chronically infected persons for medical management. Liver disease associated with childhood-acquired HBV is a leading cause of death among adults in China. Approximately 20% of children under age 5 years and 40% of children aged 5 to 19 years remain unprotected from HBV. Using a Markov model of infection and disease progression I find that HBV catch-up vaccination for children and adolescents in China would improve the health of the population and save costs over the long term. Although the 20th century has seen incredible development of safe and effective vaccines, many people remain susceptible to vaccine-preventable diseases. "Catch-up vaccination" for age groups beyond infancy can be an attractive and effective means of immunizing people who were missed earlier. However, as vaccination rates increase, catch-up vaccination may become less attractive. This chapter addresses the question of when to discontinue catch-up vaccination programs as immunization rates increase. I use a cost-effectiveness framework: I consider the cost per quality-adjusted life year gained of catch-up vaccination efforts, as a function of immunization rates over time and consequent disease prevalence and incidence. I illustrate the results with the example of HBV catch-up vaccination in China. I contrast results from a dynamic modeling approach with an approach that ignores the impact of vaccination on disease incidence.

Keywords: Management Science and Engineering
Advisor: Brandeau Margaret L. primary advisor. Thesis advisor
Owens Douglas K. advisor. Thesis advisor
So Samuel advisor. Thesis advisor
Glop theory [electronic resource] : a new trope ontology

The dissertation has two parts, one critical and one positive. Part One presents arguments against bare particulars, zero-dimensional material objects, extended simples, universals, and three-dimensionalist accounts of persistence over time. Part Two posits and defends a novel property—markedness (a Grounding Local Ontological Primitive, or GLOP)—that marks out certain regions of spacetime, thus furnishing a sort of binary code for fundamental ontology. Glop theory is then used to develop new accounts of property exemplification, ontological fundamentality, and persistence. What emerges is an ontology according to which material objects are four-dimensional trope bundles that need not be composed of simple parts. This result is desirable if, as Part One maintains, we should resist commitment to bare particulars, material simples, universals, and three-dimensionalism.

Keywords: Philosophy
Advisor: Crimmins Mark primary advisor. Thesis advisor
Perry John primary advisor. Thesis advisor
Ryckman Thomas advisor. Thesis advisor
Growth and Characterization of Rubidium Copper Sulfide

In this thesis I describe the synthesis and physical properties of a novel ternary compound RbCu4S3. The material is a bilayer variant of the familiar ThCr2Si2 structure (adopted, for instance, by several members of the iron-pnictide family of superconductors, including BaFe2As2 [1]). Interest in this quasi-low-dimensional compound revolves around its potential to harbor an electronic instability, for example a charge density wave. After establishing a suitable procedure to grow high quality single crystals, my ongoing experiments have probed the nature of the RbCu4S3 ground state via a combination of transport and thermodynamic measurements. The results of these experiments have been compared with band structure calculations performed using the WIEN2K software package. Additional x-ray diffraction and transmission electron microscopy (TEM) structural characterization has been performed by collaborators.
The calculated Fermi surface of RbCu4S3 reveals one three-dimensional pocket and two quasi-two-dimensional pockets with considerable potential for nesting. However, neither single crystal x-ray diffraction refinements nor high resolution TEM measurements indicate the presence of a lattice modulation in this material. The electrical resistivity is that of a good metal, with a very low residual resistivity and a correspondingly high residual resistance ratio (RRR[typical] = [rho](300K)/[rho] naught >=600). Such high quality samples permit the observation of quantum oscillatory effects in high magnetic fields, providing a direct probe of the Fermi surface morphology and the quasiparticle effective mass. Preliminary measurements of Shubnikov-de Haas oscillations in the magnetoresistance for fields oriented along the crystalline c-axis reveal several frequencies corresponding to different extremal orbits of the various Fermi surface pockets. Comparison with the calculated band structure leads to a tentative assignment for at least one of these orbits with the three-dimensional hole pocket, but additional angle-dependent measurements will be necessary to make an unambiguous comparison. Heat capacity measurements yield a Sommerfeld coefficient [gamma] = 13:1 +/- .04 mJ/mol K2, which is larger by a factor of ~ 1.6 over that estimated from our band structure calculations, presumably reflecting mass renormalization due to many-body effects. Taken together, the preponderance of the evidence suggests that RbCu4S3 does not suffer an electronic instability, although further experiments will be necessary to conclusively establish whether or not this is the case.

Keywords: Physics
RuCu4S3
rubidium copper sulfide
Thesis
Advisor: Fisher Ian R.
Geballe Theodore H.
"Havoc of matter", détournement in the films of Debord, Rouch, Godard [electronic resource]

The dissertation addresses the significance of the practice of détournement in the films of Guy Debord, Jean Rouch, and Jean-Luc Godard. The purpose is threefold: to see détournement 1) as part of a re-conceptualization of montage after World War II; 2) as a critique of the reification of political representation during les trentes glorieuses, the so-called Golden Age of capitalism from 1950's to the 1970's; 3) as a method for the (de)construction of subjectivities. For Debord and the Situtionist International [SI], détournement was a re-conceptualization and radicalization of montage -- a method of appropriating an image, of turning it away and leading it astray from its seemingly natural, normal use. Emphasizing various contemporaneous critiques of the relation between power, knowledge, and subjection/subjectivation (especially, the critiques of Debord, Michel Foucault, Gilles Deleuze), I argue for the practice of cinematic détournement as a deconstruction of the image that not only dissociates it from its source, but also dissociates our habituated modes of perception and experience, action and reaction, of relating to the world and to oneself -- especially those modes through which one constitutes and recognizes oneself as a subject. The dissertation underscores the affective force of such dissociations, especially its implications for the struggles against subjection/subjectivation, that is, the struggles against a form of power in which procedures of subjection become ever more implicated with the processes of subjectivation. Particularly, I point to how détournement is deployed in attempts to respond to the unsettling, disjunctive encounter with the new political subjectivity of the colonized subject in France of the 1950's, 60's -- not only in relation to the struggles for decolonization (for example, the Algerian War, an especially significant example for France at this moment), but also in relation to the struggles against "the colonization of everyday life" (for example, the SI's call to address the problem of the quality of life, of "happiness, " during the period of an aggressive, at times violent, form of state-led modernization). In short, the dissertation aligns the practice of cinematic détournement with a method of analysis that seeks to deconstruct the habituated truths about one's relation to oneself and others (particularly, the psychoanalysis of Jacques Lacan and Jean Laplanche). And it addresses the significance of this method in the films of not only Debord but also his contemporaries, Rouch (cinéma-vérité) and Godard (French new wave, Dziga Vertov group) -- two of the foremost practitioners of a new mode of filmmaking that unsettles the dichotomy between documentary and fiction, objective and subjective, true and false, and poses the question of how truth is articulated, imposed, enacted upon and for whom.

Keywords: Art and Art History
Advisor: Levi Pavle primary advisor. Thesis advisor
Bukatman Scott
Ma Jean
McDonough Tom
Helicobacter pylori [electronic resource] : molecular mechanisms for the utilization of the cell surface as a replicative niche

Helicobacter pylori is a bacterium that chronically infects the stomachs of more than half the human population, in some cases leading to serious diseases such as gastric cancer and ulcers. H. pylori intimately interact with the gastric epithelial surface, but much remains unknown about its life on the cell surface. The bacterium possesses several tools for its close interaction with the gastric epithelia, including a type IV secretion system, through which the virulence factor CagA is directly translocated into host cells. This dissertation focuses on how H. pylori's close interactions with the epithelial cells allows it to modify the apical cell surface to turn it into a replicative niche for the bacterium. Using live-cell microscopy to follow the fate of individual bacteria on the cell surface, we find that H. pylori is able to utilize the apical cell surface as a replicative niche, even in conditions that do not support the growth of free-swimming bacteria. Experiments with a polarized epithelial model system show that the bacterium's major virulence factors CagA and VacA both play important roles in enabling H. pylori growth and microcolony formation on the apical cell surface, by mediating perturbation of host cell polarity and intracellular trafficking processes. We find that iron is one important micronutrient that H. pylori acquires from host cells during colonization of the polarized epithelium. CagA and VacA act in concert to affect the polarized process of transferrin/transferrin receptor recycling and iron uptake in the host cells, resulting in the mis-sorting of a subset of the transferrin/transferrin receptor complex to the colonizing bacteria on the apical cell surface. This process is functionally important for the bacteria, as downregulation of transferrin receptor expression resulted in a decreased ability of H. pylori to colonize the polarized epithelium. These studies establish the cell surface as a replicative niche, which presents challenges that require bacterial adaptation for its successful utilization. Our findings also illustrate the concept that contact-dependent bacterial virulence factors may be used for the perturbation of host cell physiology for the bacterium's benefit, allowing acquisition of needed factors directly from host cells, and colonization of the apical cell surface.

Keywords: Microbiology and Immunology
Advisor: Amieva Manuel primary advisor. Thesis advisor
Falkow Stanley advisor. Thesis advisor
Nelson W. J. (W. James) advisor. Thesis advisor
Theriot Julie advisor. Thesis advisor
The heroine's journey [electronic resource] : representing female desire and self in premodern Chinese romance

This dissertation examines the evolution of the caizi-jiaren mode, and ideas about the self, gender, and ethics exhibited in it. My investigation will cover a broad range of texts spanning from the ninth century through the eighteenth century--from Tang chuanqi tales, through Ming-Qing drama, fiction, and tanci--aiming to show how the conventions of romance address cultural and ideological changes, and participate in broader social discourses. I argue that the heroine's quest for love and self is always part of a larger cultural project, fostered by a questioning and new awareness of the place of the individual within the social matrix. I read these romances in the light of the more dynamic modes of gender and desire, with a focus on the working of desire as a dialogue with moral systems and public power, and gender's relation to cultural expression.

Keywords: East Asian Languages and Cultures.
Advisor: Wang John C. Y. (John Ching-yu)
Zhou Yiqun
Wang Ban