VictorJuiz/thesis huggingface dataset:
Into thinner air [electronic resource] : how pikas live on the roof of the world and implications for their persistence in the Anthropocene

The human-dominated epoch of the Anthropocene is putting new pressures on species, threatening the persistence of many. One such pressure is anthropogenic climate change. In many species, climate change is causing parts of their range, generally lower latitudes and lower elevations, to no longer be habitable. As a result, we are seeing a general movement of species to higher latitudes and higher elevations. However, as montane species move to higher elevations, they will encounter greater physiological stress due to high-elevation hypoxia -- the decrease of available oxygen at high elevations due to a reduction in barometric pressure. The limitations that hypoxic stress may put on species' ability to alter their distributions have never been explored. One montane organism particularly vulnerable to climate change and already experiencing elevational range shifts at up to ten times the global average are pikas, genus Ochotona. There are at least 28 pika species, each occupying a unique elevational range between 0 -- 6,100 m with at least 14 species inhabiting elevations above 4,000 m. Little is known about how pikas can tolerate the hypoxic stress of their high-elevation habitat. By learning more about the mechanisms underlying hypoxia tolerance in pikas, I aim to gain understanding of what role hypoxic stress may play in their future range adjustments in response to projected climate change. Through the utilization of museum tissue samples, extensive field work in the Indian Himalayas, and the only captive colony of pikas in the world, I have investigated hypoxia tolerance in pikas from three different angles: (1) molecular evolution in mitochondrial candidate genes; (2) variation in gene expression along an elevational gradient within a population between 3,600 and 5,000 m; and (3) changes in gene expression within an individual when exposed to varying levels of hypoxia for a 5-day period. Our results indicate that while different pika species have genetic adaptations seemingly specializing them to the general elevational range of the species, on a local and even individual scale, changes in gene expression may offer a mechanism by which pikas can rapidly acclimate to hypoxic conditions. Our findings suggest that pika species may be genetically adapted to the elevational range they occupy, potentially limiting range movement; however, changes in gene expression may enable rapid range shifts within a species' elevational envelope.

Keywords: Biology.
Advisor: Hadly Elizabeth Anne
Dirzo Rodolfo advisor. Thesis advisor
Palumbi Stephen R.
Ramakrishnan Uma
Sherlock Gavin advisor. Thesis advisor
Intrinsic and extrinsic signals modulate planarian stem cell fate decisions [electronic resource]

Regeneration is a process that requires tightly regulated proliferation, differentiation, and tissue remodeling. Classical model organisms such as C. elegans, D. melanogaster, and M. musculus have limited regenerative capabilities therefore we present the freshwater planarian Schmidtea mediterranea, which provides an ideal system to study the role of stem cells in regeneration. This immortal adult organism boasts excellent regenerative capabilities driven by a stem cell population called neoblasts. The neoblast population is the only mitotically active cell type in planarians and can be easily manipulated without concern for embryonic requirements. This unique model also allows for the study of human embryonic stem cell genes in a simpler in vivo system. Thus S. mediterranea offers the opportunity to accelerate the studies and understanding of stem cell biology and regeneration in the environment of a living organism. GATA transcription factors are DNA binding proteins that are well-known master regulators of development. Through the activation and repression of transcription, these factors direct cellular differentiation toward lineage specification. Here we used loss-of-function experiments to understand the role of the GATA4/5/6 subfamily in the differentiation of neoblasts. S. mediterranea has a single homolog of mammalian GATA-4, -5, and -6, Smed-gata4/5/6, which is expressed primarily in the planarian intestine and in some neoblasts. Smed-gata4/5/6 knockdown results in perturbed homeostasis and regeneration, eventually leading to planarian death. Loss of Smed-gata4/5/6 disrupts intestinal differentiation and also affects non-intestinal lineages. During late time points of regeneration, Smed-gata4/5/6 loss leads to decreased neoblast proliferation and gene expression of neoblast subpopulations. These data support the conserved role of Smed-gata4/5/6 in intestinal differentiation and indicate the intestine may act as a neoblast niche. Our preliminary work on Experimental Evolution through irradiation exposure shows a sub-lethal dose of irradiation eliminates neoblast expression after 24 hours and expression recovery occurs after 3-4 weeks. This demonstrates S. mediterranea is a malleable model organism that can be used to study the link between regeneration and cancer.

Advisor: Sage Julien primary advisor. Thesis advisor
Giaccia Amato J.
Kim Stuart
Morrison Ashby J.
Investigating the importance of host nutrient systems for plant pathogens in Arabidopsis thaliana [electronic resource]

This thesis explores the importance of host nutrient transporter systems in plant pathogen infections focusing on the one hand on UmamiT amino acid and SWEET sugar transport proteins, and on the other hand on bZIP transcription factors as potential regulators of transporter genes using the plant model Arabidopsis thaliana and three pathogens. The pathogens investigated are the hemibiotrophic bacterium Pseudomonas syringae pv. tomato DC3000 as well as the hemibiotrophic fungus Colletotrichum higginsianum and the necrotrophic fungus Botrytis cinerea.

Keywords: Biology.
Advisor: Frommer Wolf B.
Mudgett Mary Beth
Fire Andrew Zachary advisor. Thesis advisor
Long Sharon R. advisor. Thesis advisor
Investigating the role of neurexins in synapse formation in the retina and lateral geniculate nucleus

Neurexins (NRXN) are a family of three presynaptic cell-adhesion molecules that regulate synaptic function and organization via binding with myriad postsynaptic partners. The discovery of neurexin mutations in human patients with neurodevelopmental disorders, like Autism Spectrum Disorder and schizophrenia, introduced a greater clinical focus to neurexin research. The link between NRXN mutations and these human disorders remains nebulous, however, due to incomplete understanding of neurexins’ full synaptic role.
I injected viral CRE into the retinas of newborn mice from a novel triple-neurexin “floxed” line to produce an in vivo, conditional neurexin knockout (cKO) and avoid embryonic lethality. I found that triple-NRXN cKO retina exhibited a significantly decreased excitatory synapse density than their control counterparts. The number of retinal ganglion cell (RGC) axonal projections from triple-NRXN cKO retina to the dorsal lateral geniculate nucleus (dLGN) was also significantly decreased compared to control densities. Surprisingly, this reduction in RGC projections did not correspond to a decrease in excitatory synapse density in the dLGN contralateral to the triple-NRXN cKO retina compared to control. Together, these results indicate a potential role for the neurexin family in facilitating proper synapse formation within the visual system, thereby augmenting our current understanding of these crucial molecules.

Keywords:  Department of Biology
neurexin
retina
LGN
biology
IPL
Thesis
Advisor: Sudhof Thomas C.
Shen Kang
Investigating the transcriptional network of ELF5 in colorectal cancer

According to the American Cancer Society, colorectal cancer (CRC) is the third most commonly diagnosed cancer in men and women the United States, with estimation of 96,000 new cases in 2017. ELF5, an ETS-family transcription factor, has been known to specify cell-fate in the developing embryo, lung, and mammary gland; however, it is not normally expressed highly in the colon, and its role in the colon remains unclear. Here, we investigate ELF5’s role in CRC. Kuo et al. has previously demonstrated that ELF5 exhibits promoter hypomethylation and upregulation in CRC, and that ELF5 overexpression promotes over-proliferation and dysplasia in vitro and increased tumorigenicity in vivo. Based on these findings, we hypothesize that that abnormal upregulation of ELF5 in the colon activates an oncogenic transcriptional network capable of driving tumor progression. We perform ChIP-seq on HCT116, a colon cancer cell line, and HCT116 overexpressing ELF5 to identify binding sites and potential target genes of ELF5 in the HCT116 genome. We show that overexpression of ELF5 results in the increased binding of ELF5 at promoter regions that potentially regulate key genes involved in the PI3K/AKT pathway, p53-mediated apoptosis, and cell cycle control. The data presented here provide novel insight into the mechanism by which overexpression of ELF5 drives tumor progression in the colon. Better understanding of tumor progression from these results may yield new therapeutic strategies for targeting CRC.

Keywords:  Department of Biology
ELF5
colorectal cancer
HCT116
promoter hypomethylation
ChIP-seq
molecular biology
Thesis
Advisor: Kuo Calvin
Fernald Russell
Investigating Wnt signaling in the developing and adult mouse spinal cord [electronic resource]

Ependymal cells in the adult mammalian spinal cord are thought to be a population of "latent neural stem cells" with more regenerative potential than any other cell types in the adult spinal cord. In spite of their unique functions, the molecular signals that regulate ependymal cells in the postnatal and adult spinal cord remain poorly understood. In addition, there remain many gaps in our knowledge about the developmental origin and the generation of spinal cord ependymal cells. In Chapter 3, I begin my investigation of the developmental origin of spinal cord ependymal cells by analyzing Wnt-responsive neural progenitor cells in the developing spinal cord and show that Wnt signaling activity is concentrated in the dorsal midline neural progenitor cells throughout embryogenesis. Ependymal cells appear to be generated in a ventral to dorsal direction, with the dorsal midline ependymal cells generated last. Indeed, they are derived from Wnt-responsive dorsal midline radial glial cells give rise to towards the end of embryogenesis. These results suggest an important role of Wnt signaling in ependymal cell generation and highlights a region-specific allocation of ependymal cells which is consistent with the process during both neurogenesis and gliogenesis. In Chapters 4-6, I demonstrate that ependymal cells in the postnatal and adult spinal cord continue to be dependent on Wnt-signaling. Inhibiting Wnt signaling results in impaired ependymal cell proliferation. Ependymal cells also produce Wnt ligands which are required for maintaining ependymal cell proliferation. In Chapter 7, I investigate another Wnt-responsive cell population in the developing and adult spinal cord -- astrocytes. I also show evidence suggesting that Wnt signaling may be enriching for a more proliferative population of astrocytes at the periphery of the white matter, which serve as a source of new astrocytes in the adult spinal cord. Lastly in Chapter 8, I describe our efforts in elucidating the contribution of Wnt-responsive cells to long term glial scar formation after spinal cord injury. Taken together, these studies highlight the importance of Wnt signaling in the ependymal cell population throughout development, postnatal growth and homeostasis. The results also provide insights into the involvement of Wnt signaling in astrocyte proliferation and scar formation after spinal cord injury.

Keywords: Developmental Biology.
Advisor: Nusse Roel
Palmer Theo advisor. Thesis advisor
Plant Giles advisor. Thesis advisor
Talbot William
The investigation of mechanisms governing small cell lung cancer metastasis [electronic resource]

Small cell lung cancer (SCLC) is a prevalent and almost uniformly lethal malignancy. One of the major factors that lead to the poor outcome of SCLC patients is the ability of cancer cells to leave the primary tumors and establish inoperable metastases. Thus, the molecular mechanism of metastasis is one of the major unanswered problems in tumor biology and an area of investigation highly pertinent to patient survival. Using genetically engineered mouse model of SCLC, we identified a global increase in chromatin accessibility in SCLC metastases compared to primary tumors. This striking chromatin opening is linked to the activity of the Nfib transcription factor, which controls the expression of metastatic gene programs likely via its action at gene distal regulatory elements. Nfib expression is necessary and sufficient for multiple steps of the metastatic cascade. This identification of widespread chromatin changes during SCLC metastasis reveals an unexpected global reprogramming of cancer cells and the resulting activated neuronal differentiation gene program can facilitate invasion and migration during metastatic progression. Unexpectedly, when we used an approach to specifically initiate SCLC in pulmonary neuroendocrine cells (which is thought to be the cell of origin of SCLC), we found that while the mice still developed metastatic SCLC, the metastases almost never expressed Nfib. Unbiased analyses of gene expression programs (RNA-seq) and chromatin structure (ATAC-seq) of cancer cells isolated from primary tumors and liver metastases from the two mouse models conclusively showed that metastatic progression of each subtype is molecularly distinct. Furthermore, our work investigates inter-tumoral heterogeneity at a new level and shows that tumors with identical histology but distinct molecular profiles evolve entirely different. Our data showed for the first time that the inter-tumoral heterogeneity is attributed to the identity of the cells-of-origin from which SCLC is initiated and this can further determine the evolution of primary tumors towards specific metastatic states.

Advisor: Sage Julien primary advisor. Thesis advisor
Winslow Monte primary advisor. Thesis advisor
Giaccia Amato J.
Krasnow Mark
Is Emancipation Enough?: Civic Humanism and New Media

How is the rise of new media affecting democracy? It has been popularly expected that the rise of the network society would spell the rise of a newly-reflective and civic-minded citizenry. This expectation is critical because new media allow everyday people to circumvent gatekeepers like never before, placing on them a heightened responsibility to maintain their democracies. However, the empirical record—information cascades, echo chambers, a right-wing populist backlash, a “tyranny of emotions”—suggests that the pervasiveness of new media disrupt democracies around the world. These phenomena challenge the enduring popular characterization of new media as a vessel for democratic participation and a force for evoking this new critical consciousness in the polity. This paper confronts the framework presented by optimistic analysts and explores how the heuristics that it relies on for measuring the relationship between new media and democracy are blind to an important aspect of freedom. Instead, a civic humanist ideal of good citizenship is presented, tested in comparison of a forum-based textual internet culture and a visual-based meme culture, and demonstrated to better account for the intervening factors that support or prevent the emergence of democracy-strengthening cultural sensibilities in the context of new media.

Keywords: stanford
sts
science technology and society
2017
2016
honors
thesis
civic
humanism
emancipation
emancipation rhetoric
media
ecology
neil postman
zygmunt bauman
positive liberty
negative liberty
isaiah berlin
survey
framework
new media
democracy
decentralization
democratization
digital
media
populism
gatekeepers
freedom
Thesis
It's (Not) Ours To Reason Why: A Comparative Analysis of Algorithms for the Division of Fractions

This research project takes a deep look at how division of fractions problems, known as some of the most complex to teach and learn in school mathematics, can be approached. It takes a look at the two main algorithms for division of fractions present in the literature and compares them in order to consider each algorithm's benefits and drawbacks in answering the following question: How do the common-denominator and invert-and-multiply algorithms for the division of fractions compare in terms of their algorithmic efficiency, curricular fit, and mathematical integrity? Through an analysis of efficiency based on the upper bound of the number of single-digit basic operations required to solve a division of fractions problem with each algorithm, and of the meaning and coherence based on multiple representations of the two algorithms and their grounding in the mathematics methodized by the Common Core State Standards, I found that the flip-and-multiply algorithm is more efficient because requires fewer single digit basic operation to produce an answer, but the common-denominator algorithm is more closely tied to the instructional content that typically precedes it in teaching fractions. However, this analysis also established the extent to which both algorithms have the potential to be taught with a strong grounding on mathematical ideas rather than just for the ability to give a numerical answer, which is arguably more important for learning mathematics than algorithmic efficiency.

Keywords: mathematics education
division of fractions
fractions
division
efficiency
honors thesis
Stanford Graduate School of Education
comparative analysis
mathematics
Thesis
Advisor: Boaler Jo
Justice by Geography: After Proposition 57, Some Kids Left in Legal Limbo

Last November, Californians voted to eliminate direct filing – a procedure that gave prosecutors exclusive power to decide whether to try youth as adults. Direct file was being applied unevenly across counties in California and it targeted youth of color at alarming rates. Champions of juvenile justice reform celebrated. Now, judges – who are seen as more impartial - decide who to send to adult court. But seven months after Proposition 57’s passage, some prosecutors are still fighting to keep minors – whose trials began before last November - in adult court, putting those kids’ futures in limbo.

Keywords:  Department of Communication
Juvenile Justice
California
Proposition 57
Direct File
Thesis
Advisor: Zacharia Janine
Kant and the structure of the given [electronic resource]

The aim of this dissertation is to provide an interpretation that can resolve the prima facie tension between Kant's simultaneous commitment to the duality of the faculties (the Duality Principle) and the claim that they must work together to produce cognition (the Togetherness Principle). This tension is at the center of the recent debate between conceptualist and nonconceptualist interpretations of the Critique of Pure Reason. I aim to resolve the tension by accommodating Kant's commitment to the non-conceptual nature of space and time (the Duality Principle) while explaining the fundamental role of the understanding not only in judgment but also in perception (the Togetherness Principle). Drawing on the contemporary distinction between the content of perception and the requirements for the possession of that content, I argue that the primary content of empirical and pure intuition is non-conceptual. Against most nonconceptualists, however, I argue that this content can only be "given" to subjects who possess certain conceptual capacities that, for Kant, are fundamentally linked to the conditions for the unity of apperception. There is an important sense in which conceptual capacities transform what is given in intuition, so that what Kant calls "perception" involves the introduction of a conceptual structure into the non-conceptual given.

Keywords: Philosophy.
Advisor: Anderson R. Lanier primary advisor. Thesis advisor
De Pierris Graciela Teresa
Friedman Michael
Wood Allen W. advisor. Thesis advisor
Laboratory study on the effects of carbonates and clay content on viscoplastic deformation of shales at reservoir conditions [electronic resource]

Inelastic time-dependent deformation or viscoplsatic behavior in clay-rich and carbonate-rich reservoir rocks causes wellbore instability in the scale of days, changes the response to hydraulic fracturing stimulation in the scale of years, and it also can change the state of stress in sedimentary basins in the larger time scales of millions of years. The main focus of this thesis is on how the inelastic time-dependent deformation affects hydraulic fracturing operations in unconventional oil and gas reservoirs. Horizontal drilling and hydraulic fracturing developments have made hydrocarbon production from very low-permeable unconventional reservoirs economically feasible. Hydraulically stimulated fractures propagate perpendicular to the direction of least principal stress, while the state of stress determines the growth of these fractures. Viscoplastic rock formations are more likely to have higher values of the least principal stress (or frac gradient), which makes them potential barriers to vertical hydraulic fracture propagation. In this thesis, I have studied viscoplasticity of rock samples from different formations using conventional experimental methods at various reservoir conditions. Additionally, I have used multi-scale imaging techniques to investigate the sources of inelastic deformations in shale rocks.

Keywords: Geophysics.
Advisor: Zoback Mark D. primary advisor. Thesis advisor
Kovscek Anthony R. (Anthony Robert) advisor. Thesis advisor
Mavko Gary
Sleep Norman H. advisor. Thesis advisor