VictorJuiz/thesis huggingface dataset:
From affirmative action to diversity [electronic resource] : rationales for faculty diversification efforts in a state anti-affirmative action regulatory environment

This dissertation examines how state bans on affirmative action affect rationales for diversity in faculty recruitment and hiring at a public university and a private university. The study is motivated by concerns regarding the ability of universities to attract a diverse professoriate, particularly within an anti-affirmative action climate. The study employs a qualitative research design and uses a framework that incorporates concepts from neoinstitutional theory. Interviews with 21 faculty and administrators from a public university and a private university coupled with a review of documents from both universities form the basis of the analysis. The two universities examined in this study navigated the state anti-affirmative action regulatory environment similarly and drew upon a nearly identical set of rationales to support faculty diversity policies and practices. Affirmative action programs were eliminated or reconstituted into programs that were legally permissible. Explicit discussions of affirmative action have been largely replaced with a broadening use of the term "diversity." Faculty accounts reveal myriad interpretations of the diversity rationale, leading to heightened confusion in faculty search deliberations. The state anti-affirmative action regulatory environment did not result in diversity no longer mattering in higher education; rather, it changed how diversity mattered. The study generates knowledge about the relationship between public policy and higher education and produces insights on whether universities acquiesce to or resist pressures to alter behavior and rationales as a result of public mandates. The study also illustrates how the interaction of internal and external pressures for and against affirmative action in faculty searches leads to how faculty recruitment and hiring policies are understood, re-interpreted, and put into practice. Ultimately, the study furthers our understanding of the regulatory factors that may contribute to the persistent underrepresentation of scholars of color.

Keywords: Education.
Advisor: Antonio Anthony Lising
Gumport Patricia J. advisor. Thesis advisor
Jiménez Tomás R. (Tomás Roberto)
Strober Myra H. advisor. Thesis advisor
Functional imaging of cysteine proteases in cancer and inflammation using novel activity-based probes [electronic resource]

Cysteine proteases use a catalytic thiol to cleave amide bonds of protein substrates. This activity serves as an important regulatory mechanism for diverse cellular processes necessary for normal physiology. Dysregulated protease activity is a hallmark of numerous diseases, including atherosclerosis, arthritis, stroke, macular degeneration, neurodegenerative disorders, inflammatory diseases, and cancer. In the last decades, the field of activity-based proteomics has produced a number of tools for dissecting protease function. In the introductory chapter, I will discuss the current state of the field and describe the two main classes of probes for cysteine proteases: substrate-based and activity-based probes. I will then describe my own contribution to the field, which includes the design and characterization of several new and improved activity-based probes. We have applied these probes to optical imaging and biochemical characterization of three families of cysteine proteases: caspases, cathepsins and legumain. In particular, I have used these tools to aid in understanding the regulation of complex signaling pathways associated with cancer and inflammation. Caspases are key mediators of a programmed form of cell death called apoptosis. One of the key features of tumor cells is their ability to evade apoptosis, and therefore, a major therapeutic goal is to reactivate latent death pathways. We have developed fluorescent activity-based probes to image the induction of caspase activity in tumors in response to chemotherapy. In addition to non-invasive optical imaging, we have utilized these new probes to assess the kinetics of caspase activation in response to various death stimuli and identified a unique activation mechanism for the caspase-6 enzyme. Another emerging hallmark of cancer is infiltration of stromal-derived immune cells into the tumor, resulting in an inflammatory microenvironment. Crosstalk between tumor and immune cells can lead to enhanced proliferation, angiogenesis, and metastasis of tumor cells. The cysteine proteases legumain and cathepsins have been shown to play critical roles within the tumor microenvironment. I have developed new tools for optical imaging of their proteolytic activity in several cancer models as well as inflammation associated with pancreatitis. In the future, these new probes will have great value in further dissecting the roles of cysteine proteases in basic biology and disease. Since legumain and cathepsins are used as biomarkers for cancer, the ability to detect their proteolytic activity has much diagnostic and prognostic value in both pre-clinical and clinical settings. Furthermore, these new agents will be integral in validating these enzymes, particularly legumain, as drug targets.

Advisor: Bogyo Matthew
Giaccia Amato J. advisor. Thesis advisor
Sage Julien advisor. Thesis advisor
Sweet-Cordero Eric advisor. Thesis advisor
A GATA transcription factor, egl-27, delays aging by promoting stress resistance in C. elegans [electronic resource]

Stress is a fundamental aspect of aging as accumulated damage from a lifetime of stress can limit lifespan, and protective responses to stress can extend lifespan. In this study, we identify a conserved C. elegans GATA transcription factor, egl-27, that is involved in several stress responses and aging. We found that overexpression of egl-27 extends the lifespan of wild-type animals. Furthermore, egl-27 is required for the pro-longevity effects from impaired insulin/IGF-1 like signaling (IIS), as reduced egl-27 activity fully suppresses the longevity of worms that are mutant for the IIS receptor, daf-2. egl-27 expression is inhibited by daf-2 and activated by pro-longevity factors daf-16/FOXO and elt-3/GATA, suggesting that egl-27 acts at the intersection of IIS and GATA pathways to extend lifespan. Consistent with its role in IIS signaling, we found that egl-27 is involved in stress response pathways. egl-27 expression is induced in the presence of multiple stresses, its targets are significantly enriched for many types of stress genes, and altering levels of egl-27 itself affects survival to heat and oxidative stress. Finally, we found that egl-27 expression increases between young and old animals, suggesting that increased levels of egl-27 in aged animals may act to promote stress resistance. These results identify egl-27 as a novel factor that links stress and aging pathways.

Advisor: Kim Stuart
Brunet Anne
Chua Katrin Faye advisor. Thesis advisor
Snyder Michael
Gene expression control by nuclear phosphoinositides and chromatin [electronic resource]

The physiological state of the genome is chromatin. Chromatin is a dynamic polymer composed of genomic DNA, histone proteins, and other factors. Dysregulation of chromatin homeostasis can lead to diverse human pathologies including cancer. This work focuses on chromatin-based mechanisms of gene regulation; more specifically the (1) targeting and (2) stabilization of gene-regulatory proteins on the chromatin template. In regard to chromatin targeting, not much is known about how gene-regulatory proteins selectively associate with their targets. Herein we detail the discovery of a new targeting factor, the nuclear phospholipid phosphatidylinositol-5-phosphate (PtdIns(5)P). PtdIns(5)P directly interacts with the tumor suppressor ING2 (inhibitor of growth family member 2) in the nucleus to coordinate gene expression of select ING2 targets. In regard to chromatin stabilization, lysine methylation is a principle mechanism for retaining chromatin-effector modules at discrete chromatin zones. Numerous lysine methylation events have been discovered on the major protein component of chromatin, histones, but relatively few specific modules have been characterized to sense these modifications. We screened through a library of putative methyl-lysine binding domains, which resulted in the identification of three novel chromatin binding modules. Taken together these data shed insight into the molecular modes of action of gene regulation by chromatin and phosphoinositide pathways.

Keywords: Biology.
Advisor: Gozani Or Pinchas primary advisor. Thesis advisor
Morrison Ashby J. advisor. Thesis advisor
Nelson W. J. (W. James) advisor. Thesis advisor
Generation of extremely low frequency waves via modulated ionospheric heating for communications applications [electronic resource]

Extremely low frequency (ELF) electromagnetic waves (0.3—3 kHz) have many applications including communications with submerged submarines, remote sensing of the lower ionosphere, and active wave-particle interaction experiments involving energetic particles trapped in Earth's radiation belts. However, waves in this frequency range are difficult to generate due to their large wavelengths (~100—1000 km) and therefore the large antennas required for efficient radiation. One relatively new and unconventional technique for ELF generation uses modulated heating of the lower ionosphere. The modulated ionospheric heating technique utilizes a high frequency beam (HF, 3—10 MHz) amplitude modulated at ELF frequencies to create a time-varying change in the conductivity of the lower ionosphere. When performed in regions where natural, large-scale horizontal ionospheric currents exist, such as the auroral electrojet at polar latitudes, the conductivity change results in a time-varying current that radiates at the ELF modulation frequency. While sidestepping the challenges of constructing a conventional ELF antenna, the modulated heating technique introduces new difficulties. The amplitude of the ELF waves depends strongly on the strength of the electrojet and the conversion between HF power and the ELF field is highly nonlinear. The purpose of this work is to characterize the dependence on electrojet strength and mitigate or utilize the nonlinearity between HF power and ELF fields so that experimenters and communication systems operators can optimize the generation of ELF waves using modulated ionospheric heating. Higher ionospheric density results in a large increase in the electrojet current strength but only a small increase in the generated ELF amplitude while lower ionospheric density can result in a weaker electrojet but only a small decrease in ELF generation. Harmonic content can be reduced by transmitting a predistorted HF power envelope that results in a sinusoidal ELF current at a particular altitude. This technique depends on a correct model of the ionosphere, which is highly variable in practice. Other modulation envelopes explored, such as square wave modulation, create stronger harmonics but can also result in higher generated ELF power or greater efficiency. Finally, we conduct experiments using quaternary phase shift keying (QPSK) to transmit digital data and examine how the bit error rate (BER) varies with generation conditions and changes in transmitter parameters.

Keywords: Electrical Engineering
Advisor: Cox Donald C. primary advisor. Thesis advisor
Inan Umran S. primary advisor. Thesis advisor
Spasojević Maria
Genetic and chemical studies towards the mechanistic understanding of Gli activation [electronic resource]

The activation of the Hedgehog (Hh) pathway leading to Gli-dependent transcription plays critical roles in tissue patterning, homeostasis, and transformation. Despite the initial discovery of the pathway 30 years ago, a complete mechanistic understanding of Hh signal transduction remains elusive. By conducting a genome-scale overexpression screen using mammalian open reading frames (ORFs), I have identified the Rho GAP domain-containing protein Arhgap36, the homeodomain-interacting protein kinase Hipk4, and MED26, a subunit of the Mediator complex, as regulators of Gli function. This study represents the first report describing a functional role of Arhgap36 in any signaling process, and demonstrates Hipk4 modulates the cellular response to Hh ligand. The activity of MED26 was revealed in the context of the small molecule Hedgehog Pathway Inihibitor-1 (HPI-1), giving further insight to its mechanism of action. In addition, we describe the relevant mechanism of action of the small molecule JK184, a microtubule-disrupting agent that can have both positive and negative effects on pathway activity, depending on the nature of pathway perturbation. These findings provide new insights into how cells regulate Gli-dependent transcription and suggest strategies for the therapeutic intervention of Hh pathway-dependent disease.

Keywords: Chemical and Systems Biology.
Advisor: Chen James
Kuo Calvin Jay advisor. Thesis advisor
Meyer Tobias advisor. Thesis advisor
Wandless Thomas advisor. Thesis advisor
Genome-wide probing of RNA structures [electronic resource]

RNA plays an important role in regulating cellular gene expression. Its ability to fold into secondary and tertiary structures underlies the RNA's ability to function and be processed in every step of its life cycle, including transcription, splicing, cellular localization, translation and turnover of the RNA. However, structural information for most RNAs in the cells, such as mRNAs, is missing due to the low throughput nature of RNA structure probing and the traditional difficulty of probing long RNAs, making it difficult to assess the full impact of RNA structure in biology. To fulfill the need to understand the roles of RNA structure on a global scale, we developed for the first time a novel strategy termed Parallel Analysis of RNA Structure (PARS), which couples structure-specific probing to high throughput sequencing to simultaneously generate secondary structures for thousands of RNA species at single nucleotide resolution. Applying PARS to the yeast transcriptome identified distinct structural organization of mRNAs, including a three nucleotide periodicity in the coding region and increased accessibility near the start codon for translation. Furthermore, we demonstrated that PARS can be used to study dynamics by probing the yeast transcriptome across a temperature gradient to identify functional structural regions that have differential propensity to melt. PARS can be readily applied to different organisms and conditions, to identify structural determinants that regulate gene expression changes across organisms in different cellular states. This expansion of RNA structural data will likely enhance our understanding of how RNA structure translates into RNA function in cellular systems, as well as open doors to potentially targeting these structural elements to regulate cellular behavior in diseases.

Advisor: Chang Howard
Fire Andrew Zachary advisor. Thesis advisor
Sarnow P. (Peter) advisor. Thesis advisor
Sherlock Gavin advisor. Thesis advisor
The genomic basis of yeast adaptation to limiting glucose [electronic resource]

Adaptive evolution by natural selection is largely responsible for the variety of forms and functions observable in the natural world. Identifying the genetic changes underlying adaptive evolution of organisms to their environment is of fundamental importance in understanding the history of life, as well as predicting how organisms will evolve to novel environments in the future. Experimental evolution of microbes in the laboratory provides a precisely controlled environment for investigations into the genetic basis of adaptation, while also allowing for large population sizes and experimental replication, benefits that are often not available in natural populations. Recent technologies have enabled the identification of the genetic changes responsible for adaptive evolution genome-wide, giving us a genomic view of adaptation during evolution experiments. Here, I have added to our understanding of the genomic basis of adaptation by investigating how Saccharomyces cerevisiae adapts to limiting glucose environments during experimental evolution. Throughout this work, I utilize next- generation, whole-genome sequencing to identify the mutations responsible for adaptation. In Chapter 1, I investigate how genetic interactions define the fitness landscape, and find that very strong negative epistasis between two beneficial mutations creates a fitness valley, so each mutation effectively determines the evolutionary trajectory of adaptation. In Chapter 2, I take a step back and look more broadly at adaptation while asking the question: is there a general functional theme for the genomic basis of adaptation to limiting glucose? To facilitate answering this question in an unbiased manner, I develop a whole-population, whole-genome sequencing technique, and find that the theme of adaptation in the constant and predictable environment of the glucose-limited chemostat is for the yeast to lose function of signaling networks responsible for sensing environmental stimulus, effectively decoupling environmental sensing from response. In Chapter 3, in a collaborative project, we seek to understand the extent that genotypic convergence underlies phenotypic convergence by evolving genetically distinct yeast under different conditions. We find a single gene is recurrently mutated across most genetic backgrounds, suggesting that genotypic convergence plays a large role in adaptive evolution.

Keywords: Genetics
Advisor: Sherlock Gavin primary advisor. Thesis advisor
Petrov Dmitri Alex
Sidow Arend advisor. Thesis advisor
Tang Hua (Geneticist) advisor. Thesis advisor
Geology and 40-argon/39-argon geochronology of the mid-miocene high rock caldera complex, northwest Nevada [electronic resource]

Large igneous provinces are characterized by eruption of > 100,000 cubic km of magma over time scales of less than a few million years. Although most studies of large igneous provinces focus on flood basalt magmatism, there is increasing evidence that voluminous eruptions of silicic ignimbrites and lavas occur contemporaneous with global flood basalt magmatism. Estimated volumes of silicic magma range from 1 to 6% of the volume of coeval flood basalt lavas. Although these volumes are significant, poor preservation has resulted in relatively few detailed geologic investigations of cogenetic silicic deposits in large igneous provinces. In this dissertation, I investigate silicic caldera-forming eruptions that are contemporaneous with eruptions of the youngest and best exposed continental flood basalt province on Earth, the Columbia River flood basalt province, located in the northwestern United States. I present new 40-Argon/39-Argon ages and geologic evidence for silicic volcanism in northwest Nevada and southern Oregon at the High Rock Caldera Complex (HRCC). The HRCC consists of the products of four major overlapping calderas, 24- to 40-km in diameter, which collapsed between 16.4 and 15.7 Ma, shortly after initiation of flood basalt eruptions at Steens Mountain at ca. 16.7 Ma. Regionally, silicic volcanism that was contemporaneous with the peak flood basalt eruption interval between 16.7 and 15.0 Ma was more voluminous and occurred over a wider area than previously recognized. The most voluminous silicic eruptions were early and peralkaline, occurring at HRCC and McDermitt Caldera. The largest calderas are located along a narrow NNE trend near the transition between continental and accreted oceanic crust, and occur peripheral to zones of intense basaltic diking. I present a new model in which flood basalt magmas that intruded along the edge of the western margin of continental North American craton controlled the timing, location, and composition of 16.6 to 15.0 Ma silicic calderas at the HRCC and McDermitt Caldera. I also present evidence for the Steens basalt being the source for peralkaline rhyolite magmatism at the HRCC. These new findings are important because they agree with observations from other large igneous provinces that these massive eruptive events are predominantly bimodal. These observations require modification of models for the initiation of the Snake River Plain-related silicic magmatism.

Keywords: Geological and Environmental Sciences.
Advisor: Mahood Gail A.
Grove Marty
Miller Elizabeth advisor. Thesis advisor
Ge/SiGe electroabsorption modulators for Si-based photonic integrated chips [electronic resource]

In chapter 1, we explain how optical interconnects can drastically improve data transmission performance while reducing power use. This is critical to the economic and environmental sustainability of the projected growth of data transmission needed for the rapid expansion of communication, commerce, and computation. We explain the importance of Si-CMOS process compatibility and energy requirements for optical components, and describe our solution using the quantum-confined Stark effect in Ge/SiGe quantum wells. In chapter 2, we summarize our improvements to the Ge/SiGe material system, requisite to the success of the surface-normal and microdisk modulators described in chapters 3 and 4. These devices are capable of high-speed, efficient modulation and compact form factors necessary for CMOS process integration. The advances described in this thesis help pave the way for widespread adoption of Ge/SiGe electroabsorption modulators for Si-based photonic integrated chips.

Keywords: Electrical Engineering
Advisor: Harris J. S. (James Stewart)
Miller D. A. B. primary advisor. Thesis advisor
Vuckovic Jelena advisor. Thesis advisor
Global characterizations of antibody repertoires [electronic resource]

The adaptive immune system enables individuals to defend against previously un-encountered pathogens by trial and error. It does so by employing receptors, known as antibodies, whose active genetic diversification fine-tunes this defensive response. Tremendous progress has been made in understanding the mechanisms by which antibodies develop and signal activation. However, it was not until a few years ago, with the advent of affordable in-house high-throughput DNA sequencing, and our publication of whole zebrafish antibody repertoires, that any organism's antibody diversity was characterized comprehensively. In this dissertation, we demonstrate the power of this "top-down" approach to illuminate global, system-wide changes of immune receptor repertoires during organism development and immune response. Special attention is given to applying these measurements to build predictive dynamical models that elucidate the interplay between antibody-sequences and the B-cells that produce them. While we use zebrafish liberally as a model organism for these purposes, cross-species comparisons establish far more general principles of repertoire organization. We go further to evaluate the efficacy of high-throughput immune receptor sequencing to advance clinical goals by inferring which vaccines were received by human patients based on antibody-sequences obtained from whole blood afterward. Finally, we demonstrate the usefulness of single B-cell measurements to correlate antibody mutations to gene expression, thereby providing insight into how these variables co-vary system-wide. This work serves to illustrate the potential of global characterizations of antibody repertoires for providing newer and clearer pictures of immune dynamics in general.

Advisor: Fisher Daniel S. primary advisor. Thesis advisor
Quake Stephen Ronald primary advisor. Thesis advisor
Boyd Scott
Davis Mark M. advisor. Thesis advisor