VictorJuiz/thesis huggingface dataset:
Human development and disease [electronic resource] : lessons from induced pluripotent stem cells with X chromosome aneuploidies

1 -- 2% of all human fetal conceptions result in Turner syndrome -- the complete or partial loss of the second sex chromosome (45, X karyotype). 90% of Turner cases terminate in spontaneous abortion during the first two trimesters; however, those who survive have a wide array of clinical characteristics. Infertility is very common in Turner syndrome women, making a link between the X chromosome and causes of infertility. Induced pluripotent stem cells (iPSCs) offer a means of obtaining insight on the genetic requirements of germ cell development. I have used iPSCs to characterize XIST, a non-coding RNA that initiates X chromosome inactivation (XCI), and shown that newly reprogrammed female iPSCs reflect the developmental state of the preimplanation embryo following embryonic genome activation. From the generation of iPSCs from four Turner syndrome, one premature ovarian failure and a control female, I demonstrated that two X chromosomes are not necessary for reprogramming to pluripotency. Single cell analysis of genes that escape XCI within control, Turner syndrome and Triple X iPSCs revealed minimal expression differences when compared to a female human embryonic stem cell (hESC) line. Next, I investigated the ability of X chromosome aneuploidy and control iPSCs to form germ cells by differentiating iPSCs and analyzing single cells and populations throughout a differentiation protocol using BMP4/8 and Retinoic acid. An increase in germ cell associated genes was not observed, but rather a loss. Finally, xenotransplantation was used to assess germ cell formation across different X chromosome aneuploidy states. All lines were capable of forming early germ cells in vivo, independent of their X chromosome composition. These results demonstrate that two complete X chromosomes are not necessary for the formation of early germ cells, and X aneuploidy iPSCs are amenable for the study for germ cell formation.

Keywords: Genetics.
Advisor: Reijo Pera Renee primary advisor. Thesis advisor
Baker Julie (Professor of genetics) advisor. Thesis advisor
Brunet Anne
Snyder Michael
Human reproduction and low fertility in urban Taiwan [electronic resource]

From an evolutionary perspective, this research asks whether human beings have any natural inclination to reproduce. By examining biological, social, and interpersonal influences on women's reproductive behavior, the study argues that fertility outcomes result more from social influences than from a "maternal instinct" to want children. The absence of a biological basis for human desire to bear children is a primary cause of the ubiquitous fertility decline in the modern world.

Keywords: Anthropological Sciences.
Advisor: Wolf Arthur
Luhrmann T. M. (Tanya M.)
Tuljapurkar Shripad
Hybrid organic-inorganic films for high-performance adhesive bonding [electronic resource]

Hybrid organic-inorganic materials can be engineered to exhibit unique property sets intermediate to oxides and polymers by the intermixing and covalent bonding of organic and inorganic chemical components at the molecular scale. This class of materials has enabled a range of new technologies in diverse applications including protective coatings, adhesion promoting layers, ultra-low-k dielectrics and optical waveguides. This dissertation presents results from several studies investigating the correlation between hybrid molecular structure and fracture properties. A low-cost, low-temperature sol-gel approach is utilized to synthesize ZrOx/epoxysilane hybrid films for adhesion promoting applications across a wide range of metal oxide / epoxy interfaces. XPS depth profiling reveals a unique compositionally graded structure capable of forming durable bonds between metal oxides and structural adhesive organic resins. The influence of the underlying substrate isoelectric point on the synthesis and deposition of compositionally graded hybrid networks is investigated. Subsequently, linear elastic fracture mechanics experiments are utilized to develop a correlation between substrate isoelectric point and fracture properties, showing increasing adhesion with decreasing isoelectric point. Using bulk metallic glass substrates, the fracture properties of hybrid organic-inorganic films are optimized by investigating variations in sol-gel synthesis parameters. In addition to significant increases in adhesion strength, the efficacy of hybrid layers in mitigating moisture-assisted debonding is demonstrated. Finally, the application of hybrid organic-inorganic adhesion promoting layers is explored in titanium composite (TiGr) aerospace laminates. The roles of mode mixity and fiber orientation under monotonic and fatigue loading are investigated, revealing critical effects on failure pathways and resultant fracture resistance.

Keywords: Materials Science and Engineering.
Advisor: Dauskardt R. H. (Reinhold H.) primary advisor. Thesis advisor
Melosh Nicholas A. advisor. Thesis advisor
Nix William D. advisor. Thesis advisor
Hydrodynamics within the reef [electronic resource] : a closer look at flow-coral interactions

Coral reefs are valuable marine ecosystems. Moreover, their importance extends beyond the oceans, as they protect coastlines and are a source of income for coastal communities and fisheries. The decline of reefs over the past decades has led to the need for bettering our understanding of the processes that take place on the reef, as we strive to conserve and restore them. Small-scale hydrodynamics are vital to survival within the reef canopy and enhance mixing to ensure the high productivity of this benthic community. By supplying nutrients, removing waste material and applying forces to coral colonies, influencing their distribution and growth, flows within the reef canopy determine its shape. However, there is still much to be learned about the role of small-scale hydrodynamics in sustaining coral health and facilitating the biological processes needed for survival. The interactions between flow on the reef and individual coral colonies forms a feedback loop where flow affects coral morphology and as the corals adapt and grow, they in turn affect the flow. This dissertation focuses on deepen our understanding of how this feed-back loop works through a series of laboratory experiments. The work here addresses inaccuracies in using simplified geometries, cylinders and spheres, to model the forces on coral colonies as well as how colony position in the reef affects the forces it experiences. Additional work also examines the downstream evolution of flow after it has passed a colony and its role within the reef canopy as well as how nighttime polyp tentacle extension affects the floe in the boundary layer. The implications of these results on the colony dislodgment, biological processes and mixing within the reef are also presented.

Keywords: Civil and Environmental Engineering.
Advisor: Monismith Stephen Gene primary advisor. Thesis advisor
Dunbar Robert B.
Koseff Jeffrey Russell advisor. Thesis advisor
Identification of deer antler proliferation genes for accelerating the growth of hMSCs

Deer antlers are fascinating models for mammalian epimorphic appendage regeneration, and their meticulous study could provide insight for addressing the unmet medical need of regenerating skeletal defects and losses. In this study, RNA-Seq was used to compare differentially expressed genes in human mesenchymal stem cells (hMSCs) and fallow deer reserve mesenchyme cells (FDRMCs) under proliferating conditions. Over 40 genes uniquely upregulated in proliferating FDRMCs were identified, and 2 gene candidates—esm1 and has2—were successfully subcloned from FDRMC cDNA. These genes were transfected into mouse mesenchymal fibroblasts to determine if their proliferation rate could be accelerated, as a mouse model for hMSCs. Although the transfection of these candidates into mouse mesenchymal fibroblasts did not result in any change to their doubling time, semi-quantitative non-competitive RT-PCR results suggest that the genes may not have been expressed at high enough levels to cause changes in the cells’ behavior. Additionally, ALP staining conducted on BMP-2 transfected cells confirmed that transfection did not significantly alter the cells’ differentiation behavior. In summary, the developed in vitro methodology developed in this project allowed for the identification of genes involved in FDRMC proliferation separately from other antler growth-related processes, and this work opens future avenues for investigating the successful expression of subcloned FDRMC genes for the acceleration of hMSC growth.

Keywords: hMSC
proliferation
RNA-Seq
deer antlers
tissue engineering
bone regeneration
Thesis
Advisor: Yang Yunzhi Peter
Ker Elmer
Identifying oncogenic attributes and protein binding partners of the NKX2-1 lung cancer oncogene

Lung cancer is the leading cause of cancer death in the United States, and the oncogene NXK2-1 has been previously been implicated in a subset of lung cancers. NKX2-1 encodes a transcription factor known to be important in controlling normal lung development. However, NKX2-1 is also found to be amplified and overexpressed at the DNA and protein levels, respectively, in approximately 15% of lung cancers, where it contributes to abnormal cell proliferation and survival, and thus it is classified as an oncogene. Although it is presumed that NKX2-1 must be behaving differently in cancer compared to normal cells, the mechanisms by which it increases cancer cell proliferation are not well understood. Possible mechanisms include altered NKX2-1 transcriptional activity by expression of distinct NKX2-1 protein isoforms, or by NKX2-1 association with distinct protein binding partners. Here, we examined the phenotype of lung cancer cells overexpressing different NKX2-1 isoforms, to better understand the protein’s function. We also used co-immunoprecipitation to isolate proteins that associate with NKX2-1 in lung cancer cells, and then employed mass spectrometry to identify the co-immunoprecipitated proteins. The resulting findings provide unique and novel insight into the mechanisms of NKX2-1 oncogenic activity, which may lead to future efforts in targeted molecular therapy for these lung cancers.

Keywords:  Department of Biology
lung cancer
NKX2-1
co-immunoprecipitation
oncogene
protein cofactors
Department of Pathology
Department of Biology
Stanford University
Thesis
Advisor: Pollack Jonathan
Mudgett Mary Beth
Identifying the function for a conserved region on the surface of calcineurin

Calcineurin is a conserved Ca2+/calmodulin-activated phosphatase that plays a crucial role in many signaling pathways in both mammals and yeast. In mammals, calcineurin plays a role in T-cell activation, cardiac hypertrophy, and neuronal development. The widely used FDA-approved immunosuppressants cyclosporin A and FK506 both inhibit calcineurin, yet are associated with various side effects. Calcineurin is a heterodimer consisting of a catalytic A subunit (CNA) and a regulatory B subunit (CNB). When Ca2+ binds to the B subunit and the Ca2+-calmodulin complex binds to the A subunit, a conformational change causes the auto-inhibitory domain (AID) to be removed from the active site, allowing access to substrates. While some substrate interaction sites have been identified and well characterized, there is evidence that more sites may exist. A bioinformatics approach was used to identify conserved regions on the surface of calcineurin.

This research aims to elucidate the function of one such conserved surface region. Site-directed mutagenesis was used to replace conserved amino acids on CNA to alanine, a non-interacting amino acid, creating two mutants: CNA(N287A) and CNA(C292A, F294A). Calcineurin’s high degree of evolutionary conservation permits the study of the protein in S. cerevisiae (baker’s yeast). In vivo and in vitro assays were used to measure calcineurin-dependent transcription and dephosphorylation. None of the mutations led to decreased protein expression compared to wild-type calcineurin. Results showed that CNA(N287A) has increased activity in vivo, while decreased activity in vitro, and CNA(C292A, F294A) has decreased activity both in vivo and in vitro. While it is currently not understood why there is a discrepancy between the results for CNA(N287A), this project shows that the conserved region defined by these residues allosterically affects enzymatic activity. Experiments are already underway to determine if this region is also implicated in calcineurin activation through an AID-dependent mechanism.
Understanding how calcineurin is activated and regulated provides valuable information for studying the various pathways in which it is a part of. Furthermore, learning more about calcineurin’s structure provides vital information for better drug design.

Keywords:  Department of Biology
Biology
calcineurin
calcium
dephosphorylation
Thesis
Advisor: Cyert Martha
Jones Patricia
Roy Jagoree
Ideological sorting and the transformation of American politics [electronic resource]

This dissertation explores how American politics entered the current era where it is characterized by close electoral competition between two increasingly polarized political parties. The first and second chapters of the dissertation examine how the changing party identification of the American electorate led to close competition in congressional elections, which had been dominated by the Democratic Party from the 1930s through the 1980s. The first chapter applies a Bayesian changepoint model to identify periods where the macropartisanship of the American public (measured by Gallup surveys from 1950 to 2011) underwent major equilibrium shifts. The model identifies two distinct regimes of American politics, from 1950 to 1983 and 1983 to the present, puncuated by a large decrease in Democratic macropartisanship. The second chapter considers the sources of the equilibrium shift in party identification that was identified in the first chapter and how this equilibrium shift changed the balance of power in elections. Democrats enjoyed a large advantage in party identification until conservative Democrats (both in the South and non-South) shifted out of the party during the 1980s. The Democrats' long standing advantage in party identification had given them a major advantage in House elections and the loss of this advantage made Republicans competitive in congressional elections for the first time since the 1920s. The third chapter examines the electoral incentives for congressional polarization, studying how the ideological extremism of House incumbents has affected their probability of losing during the 20th and early 21st centuries. This chapter shows that incumbents tended to face a higher penalty for extremism during periods of low polarization, so increasing polarization has not hurt the ability of incumbents to win re-election.

Keywords: Political Science.
Advisor: Brady David W. primary advisor. Thesis advisor
Fiorina Morris P. advisor. Thesis advisor
Jackman Simon
Illegible [electronic resource] : asexualities in media, literature, and performance

This dissertation argues that asexuality, "an orientation describing people who do not experience sexual attraction" (Asexual Visibility and Education Network), presents a queer way of thinking about sexual subjectivity, desire, and intimacy. I chart the growth of a global asexual community through a mixed archive of novels, documentary film, television shows, websites, and sexological literature. My analyses indicate that asexuality remains illegible in a culture that valorizes sexual relationships and follows a sex-normative ideology that upholds sexual desire as an innate drive. For example, asexual and celibate people are often regarded as immature, in need of hormonal or medical intervention, as repressed, or as victims of sexual abuse. My project uncovers counter-narratives that challenge these assumptions in order to refigure asexuality not as an absence or lack, but as a way of desiring differently and creating new queer intimacies. I make the case for an expansive conceptualization of asexualities that may consist of identity, sexual orientation, a set of practices, a style, or a temporal inhabitance that bears a relationship to disability, a medical condition, psychological trauma, or spiritual practice, with the understanding that these are non-pathological ways to express asexuality.

Advisor: Love Heather primary advisor. Thesis advisor
Moya Paula M. L. primary advisor. Thesis advisor
Brody Jennifer DeVere advisor. Thesis advisor
Sohn Stephen Hong advisor. Thesis advisor
I'm better than you, and I can prove it [electronic resource] : games, expertise, and the culture of competition

This dissertation examines the relationships between and among video games as media objects, player communities, and the development of expertise using the competitive fighting game community (FGC) as its point of departure. Having self-organized around a shared gaming fandom and desire for competition, the FGC has developed into a robust subculture that challenges and encourages its members, most of whom are outsiders, providing them with a sense of belonging while also facilitating the development of both abstract and concrete skills useful beyond the sphere of their chosen games. Taking the FGC as a model, I theorize that many of its principles of motivation might be repurposed toward other kinds of learning. I begin in chapter I by proposing a new theory for analyzing video games as texts which takes into account their overt narrative elements, the implicit narrative of their rules, and the ways in which both of those shape players' reception practices. I suggest that the clearest notion of what a game "means" can be gleaned from where these threads intersect with one another. Chapter II addresses the FGC more directly as a subculture, engaging with its members' beliefs and practices, tracing their origin back to the influence of fighting games themselves and of urban arcade culture. I propose in chapter III that the FGC constitutes what I call a "community of expertise, " or a social group wherein not only shared practice, but shared proficiency is required for membership, and I highlight the ways in which FGC practices align with what research tells us are the optimal methods for developing expert-like abilities in various fields. Finally, in chapter IV, I propose a means of designing for expertise by borrowing from proven elements within the FGC's mode of operation.

Advisor: Alim H. Samy primary advisor. Thesis advisor
Lunsford Andrea A.
Lowood Henry advisor. Thesis advisor
Imaging of ultrafast phase separation in magnetite and spin injection into copper [electronic resource]

In the recent years, there has been a renewed interest in magnetic materials and correlated oxides due to major advance in thin-film growth technology. Materials showing metal insulator transition with orders of magnitude drop in conductivity, have become a potential candidate for novel electronics and photonics devices. While in data storage, the discovery of Giant Magnetoresistance (GMR) effect has revolutionized read head technology of the hard disk drives. The subsequent investigation of the Spin Transfer Torque phenomenon, promises to be a good candidate for Magnetic Random Access Memory devices. In the first part of my thesis project I focused on the metal insulator transition (Verwey transition) in magnetite triggered by optical excitation. Magnetite, is the first oxide where a relationship between electrical conductivity and fluctuating/localized charges was observed, with a drop in conductivity by two orders of magnitude at 123 K. The Verwey transition is also accompanied by a structural change from monoclinic to cubic symmetry. Recently, three-Fe-site lattice distortions called trimerons have been identified as the true microscopic face of electronic order in low temperature insulating phase. I studied the real time response of insulating magnetite to optical excitation with ultrafast soft X-ray scattering as well as optical pump probe experiments and discovered this to be a two-step process. After an initial femtosecond (300 fs) destruction of individual trimerons in the corresponding lattice, a phase separation into residual insulating trimeron and cubic metallic phases on a 1.5 picosecond timescale is observed. The second part of my thesis project involves understanding spin transport phenomena in spin transfer torque devices with a focus on ferromagnet-paramagnet interface. It has been predicted that near such an interface Copper develops a small nonequilibrium magnetization due to spin accumulation. I use x-ray magnetic circular dichroism to determine the magnitude and the sign of this transient magnetization in Copper. As the induced magnetization is extremely small, I employ time resolved x-ray microscopy to modulate the current on/off signal at MHz rates. Using this technique we have directly imaged the transient magnetization in Copper for the very first time and deduced its magnitude and sign.

Keywords: Materials Science and Engineering.
Advisor: Lindenberg Aaron Michael primary advisor. Thesis advisor
Stöhr Joachim primary advisor. Thesis advisor
Reed Evan J. advisor. Thesis advisor
Imaging Redshift Estimates for Fermi BL Lacs

We have measured i images of BL Lacertae objects (BL Lacs) to detect or constrain the flux of the host galaxy. Under common standard candle assumptions these data provide estimates of, or lower bounds on, the redshift. Our targets are a set of flat-spectrum radio counterparts of high flux Fermi Large Area Telescope (LAT) sources, with deep spectral observations showing them to be continuum-dominated BL Lacs. In this sample, 6 of 11 BL Lacs yielded significant host detections, with standard candle redshifts z=0.13-0.58. Our estimates and lower bounds are generally in good agreement with other redshifts estimates for these sources.

Keywords:  Department of Physics
BL Lac
Thesis
Advisor: Romani Roger
Church Sarah
The impact of campaign promises on voter behavior [electronic resource]

How does a candidate's rhetoric affect a voter's understanding of the candidate's position? Campaign promises, specifically, seem like they would affect voter opinion differently than position statements made without a promise. This dissertation develops a theory of how promises affect voter opinions of candidates with regard to non-promise position statements. Specifically, I argue that promises serve as commitments to voters of an action the candidate will take on a specific issue when in office. By increasing their perceived commitment to an issue, promises alter voter opinions both prospectively and retrospectively. Through a descriptive study of promise-making throughout the televised, presidential election debates, I show that there is a distinction between promises and non-promise position-taking in actual campaigns. I then present data from several survey experiments that demonstrate that promises have an impact on voter evaluations of candidates, and how they affect voter opinions. Ultimately, this dissertation points to the importance of understanding political rhetoric in position-taking.

Keywords: Political Science.
Advisor: Tomz Michael primary advisor. Thesis advisor
Grimmer Justin advisor. Thesis advisor
Sniderman Paul M. advisor. Thesis advisor