VictorJuiz/thesis huggingface dataset:
Targeting Lipogenesis Suppresses Myc, Ras, and Bcr-Abl Lymphomas

MYC, RAS, or BCR-ABL oncogenes are responsible for causing at least 70% of all lymphomas. Each of these oncogenes individually, and through interactions with one another, regulates different pathways involved in cellular metabolism and can lead to increased cell proliferation causing tumor formation. Many studies have shown that glucose and glutamine metabolisms are implicated in tumorigenesis, making some lymphomas susceptible to metabolic inhibition. However, lipid metabolism in lymphomas remains poorly understood. Preliminary analysis of the MYC protein’s binding to metabolic genes shows a temporal progression from glucose to glutamine to lipid transcriptional regulation, spurring interest in the role of lipogenesis in lymphoma development and growth. In this study, we show via RNA-seq, Microarray and RT-qPCR functional validation that although MYC, RAS, and BRC-ABL differentially regulate glucose and glutamine metabolic genes, they all converge and upregulate lipid metabolic genes in MYC, RAS, and BCR-ABL lymphoma models. Moreover, inhibition of the lipid synthesis pathway by a drug, TOFA, induces a dose-dependent decrease of proliferation in all three oncogene-driven lymphomas, providing the potential for the development of a novel class of drugs targeting transcription in the treatment of lymphomas.

Keywords:  Department of Biology
Biology
Molecular Genetics
MYC
RAS
BCR-ABL
Lipogenesis
Thesis
Advisor: Felsher Dean
Bergmann Dominique
Targeting the CD47-SIRP alpha interaction to stimulate macrophage destruction of cancer [electronic resource]

Cancer cells develop mechanisms to avoid detection by the immune system, and therapeutic approaches aimed at overcoming these mechanisms form the basis of cancer immunotherapy. In this dissertation, I employed macrophages as effector cells by targeting the CD47/SIRPa axis, which is a critical regulator of macrophage activation. CD47 is highly expressed on many different types of cancer, and it transduces inhibitory signals through SIRPa, a receptor on macrophages and other myeloid cells. Thus, the CD47/SIRPa axis serves as a myeloid-specific immune checkpoint. To create next-generation CD47 antagonists, we engineered high-affinity SIRPa variants that exhibited ~50,000-fold higher affinity for human CD47 relative to wild-type SIRPa. When produced as high-affinity SIRPa-Fc fusion proteins, these therapeutics acted as single agents for cancer with moderate on-target toxicity to normal cells expressing CD47. When produced as 14 kDa high-affinity SIRPa monomers, the therapeutics had minimal activity as single agents but instead acted as universal adjuvants to anti-cancer antibodies. Therefore, CD47 blockade is not sufficient to induce macrophage phagocytosis, but instead lowers the threshold for phagocytosis in the presence of a separate, tumor-opsonizing antibody. I demonstrated these principles could be extended to models of small cell lung cancer (SCLC), and I identified additional therapeutic targets on the surface of SCLC cells. Last, I generated anti-SIRPa antibodies and characterized KWAR23 as a clone that binds and antagonizes SIRPa directly on macrophages. Therapies targeting the CD47/SIRPa axis are now under investigation in clinical trials. These agents may differ in their pharmacokinetic, pharmacodynamic, and toxicity profiles, raising important considerations for further development and clinical evaluation. Overall, the therapies developed in this dissertation could be broadly applied to cancer and may benefit many patients suffering from disease.

Advisor: Weissman Irving L. primary advisor. Thesis advisor
Garcia K. Christopher
Kohrt Holbrook E.
Levy Ronald
Mitchell Beverly S. advisor. Thesis advisor
Technocracy in black and white [electronic resource] : nature, race, and nation in the management of Namibian uranium

In the mid-2000s, the southern African country of Namibia experienced what many involved called a "uranium rush, " as high prices for uranium ore concentrate sparked a frenzy of exploration activities and mining development. In a bid to manage this development, Namibia's government joined with established mining companies, environmental NGOs, donors, and some activists to establish "good governance" of the industry. This dissertation examines how such "good governance" came to be constituted in the context of contested claims about the need to consider environmental protection, about Namibia's place in the world as a modern, industrializing nation, and about Namibia's post-apartheid racial transformation. Based on eighteen months of ethnographic fieldwork in Namibia between 2009 and 2013, the dissertation examines the daily practices and discursive productions of environmental managers and technocrats in government and industry, as well as scientists and activists less directly involved in governance. Through this work, the dissertation describes how three at times conflicting projects came together in the uranium rush: industrial development, environmental protection, and racial transformation. The dissertation examines such conflicts first at the level of the bureaucratic tools and processes involved in environmental management. Then it considers the institutional context of environmental management in a time of racial transformation and, according to some, declining state "capacity." After this, the dissertation takes up the question of how uranium is a peculiarly political matter at the level of national politics. In a final substantive chapter, the dissertation takes up the question of uranium and the politics of belonging in the Central Namib Desert. The dissertation closes with a consideration of the reflexive practices of environmental managers.

Keywords: Anthropology.
Advisor: Ferguson James
Malkki Liisa H. (Liisa Helena) advisor. Thesis advisor
Yanagisako Sylvia Junko
Tendons and toes [electronic resource] : experimentation and simulation of TRIP JR, an articulated robotic leg

One of legged robotic locomotion's greatest advantages over other forms of robotic locomotion is the ability to traverse a variety of terrains at a variety of speeds. This includes bipedal humanoid robots that are designed to exist in the world that we live in, from our homes to disaster areas. However, despite numerous advances in the field, there remains to be seen a humanoid robot capable of transitioning seamlessly between walking, running, sprinting and jumping gaits in all three dimensions. TRIP JR, a pneumatically actuated articulated robotic leg with multiarticular tendons and an articulated toe capable of performing single non-consecutive hops in 1-D, was built by the author to explore the potential for using tendons and toes in legged robotic design. Two novel multiarticular tendon systems are introduced along with an articulated toe/metatarsal-jointed foot design, whose benefits to one dimensional hopping are shown through experimentally validated results. Additionally, a fully integrated dynamic computer simulation of TRIP JR involving pneumatic modeling, ground contact/friction modeling and discontinuous event handling was developed by the author to further explore and understand one dimensional hopping. A simplified airflow model for efficient optimization through simulation is introduced and validated. The overall system simulation results demonstrate robustness and good correlation with multiple experimental datasets, each of which includes pressure, joint angle, and hip height data and some including ground reaction force data, taken from testing with TRIP JR. The advantages shown in using tendons and toes in articulated robotic legs and the ability to create experimentally validated simulations of legged robots add to the tools available to roboticists for future designs and research in the field.

Keywords: Mechanical Engineering.
Advisor: Waldron Kenneth J. primary advisor. Thesis advisor
Cutkosky Mark R. advisor. Thesis advisor
Mitiguy Paul
Tensile-strained Ge/SiGe quantum wells for on-chip light emission [electronic resource]

An efficient silicon (Si)-compatible light source is one of the most crucial building blocks for Si-based photonic integrated circuits. However, obtaining a high quality light source with emission wavelength around 1.55 um for coupling to the optical fiber network on a Si platform has proven extremely difficult since Si and other common materials compatible with existing Si processing technology have indirect band gaps, which are not desired for optoelectronic devices. Germanium (Ge) has attracted more and more attention in recent years due to its pseudo-direct band gap behavior and its compatibility with Si processing technology. In this dissertation, we explore and discuss the materials growth, optical properties and device design of Ge on a Si platform for silicon photonics. After discussing the Ge/SiGe quantum-well material growth techniques, we first demonstrate the enhanced direct-bandgap photoluminescence from Ge/SiGe quantum wells compared to bulk Ge, indicating that Ge/SiGe quantum-well material is a promising candidate for making an efficient light source on a Si platform. Then, we discuss the design of tensile-strained Ge/SiGe quantum-well microdisks for laser applications for silicon photonics. We fabricate suspended Ge/SiGe quantum-well microdisks with tensile strain by using an all-around silicon nitride stressor, on a Si substrate. A novel etch-stop technology is demonstrated that allows the capability of removing the defective buffer layer, as well as providing precise thickness control of the microdisks. The photoluminescence and Raman spectra indicate that we have achieved biaxial tensile-strain as high as 0.88% transferred from the silicon nitride stressor to the microdisks. Optical gain calculations show that positive net gain can be achieved in the gain medium of Ge quantum wells with 0.5% external biaxial tensile-strain at an electron doping concentration of 5x10^19 cm^{-3} and an injected carrier concentration of 2x10^19 cm^{-3}.

Keywords: Electrical Engineering.
Advisor: Harris J. S. (James Stewart)
Kamins Theodore I.
Saraswat Krishna advisor. Thesis advisor
Testing the Prevalence Elasticity of Demand for HPV Vaccination

I investigate how HPV vaccination decisions respond to changes in the prevalence of cervical cancer using state-level cancer incidence and mortality data from the United States Cancer Statistics and individual-level vaccination data from the National Immunization Survey. I use a linear probability model, a logistic model, and a Cox proportional hazard model. Across all specifications, I find that cervical cancer prevalence has little to no effect on HPV vaccination. This unresponsiveness to prevalence may be due to a lack of awareness of HPV and its causal link to cervical cancer.

Keywords:  Department of Economics
Stanford Department of Economics
Prevalence elasticity
human papillomavirus
vaccination
immunization
rational disease dynamics
Thesis
Advisor: Bhattacharya Jay
Textual memorials of a transatlantic America [electronic resource] : heritage tourism of the African diaspora in Hispanic and U.S. Latin@ narratives

"I put it down on paper and then the ghost does not ache so much" - Sandra Cisneros, A House on Mango Street Meditating on Sandra Cisneros' earth-shattering words reminds us of the simple task of writing as an unequivocal act of memory reflection. This simple statement — one that conjures ghosts by the simple act of reprocessing — begs the question: What is the relationship between memory and writing that moves us towards spiritual redemption? Can writing have an impact on interpretive practices of affect in a way that an environment cannot? "Textual Memorials of a Transatlantic America" takes a transatlantic approach to Latin@ and Latin American studies by examining historical multilingual slave records and applying trans-global theoretical constructs. As a result, this work is interested in how monuments and texts, as structures creating memory through infrastructure and fiction, enable similar rituals of engagement and African Diasporic presence through the spaces they create. By reviewing a selection of "postmemory" authors, I explore how the diverse genres of their cultural production all share a regional and Afro-historical reconstitution of slave trade memory over former plantation spaces. Caribbean thinker Édouard Glissant states that the African Diaspora's history is "fragmented, if not totally shattered" (Caribbean Discourse 9). My dissertation reveals how this "shattered" infrastructure shapes a renewed dynamic of memorialization throughout the foundations of the Hispanic-American landscape. Ultimately, my project proposes a reassessment of Hispanic-American history and literary genealogy by theorizing in the physical terms of "memorials" the understudied black presence in the Global South. In this dissertation, I develop the aesthetic concept of "textual memorials, " where I carefully examine authors in a range of postmemory works from the novel, to the essay, to film. Each chapter integrates anthropological inspections of memorial spaces and it is through this lens that we can interpret a particular dynamic between space and narrative that fosters a level of memorialization aesthetics regarding the African Diaspora. In peeling back the layers of nation-building myths where aristocracy sought to keep the memory of slavery buried, I argue that various cultural products from the Hispanic Caribbean complement memorial sites made invisible by modernity's edifices. At times, these aesthetic structures in narrative make up for the lack of a physical memorials on the ground in both Latin America and the U.S., but in other cases, these aesthetic practices we can conjure onto the page (or scene, in the case of film), chart out the effects of the plantocratic economy made visible by memorializing reading practices.

Keywords: Iberian and Latin American Cultures.
Advisor: Ruffinelli Jorge primary advisor. Thesis advisor
Saldívar José David primary advisor. Thesis advisor
García Peña Lorgia
Greene Roland
The Biomolecular Landscape of Obesity-mediated Type II Diabetes: An Integrative Multi-Omics Study

According to the World Health Organization, three million deaths worldwide are attributed to obesity. Insulin resistance characterizes approximately half of obese individuals and has been identified as a major risk factor of diseases such as Type II Diabetes Mellitus (T2DM). Therefore, it is important to characterize the biomolecular mechanisms that link adiposity, insulin resistance, and T2DM onset. The advent of new quantitative high-throughput multi-omics technologies now provides opportunities to analyze biomolecular landscapes of complex diseases such as T2DM. In this study, control and insulin resistant patients each underwent a period of weight-gain on a high caloric diet, followed by a period of restricted dieting, and subsequent return to baseline weight. Patient blood samples were then collected at various time points and subjected to longitudinal multi-omics (transcriptomics, proteomics, and glycoproteomics) profiling. A suite of statistical analyses revealed a wealth of blood-based biomolecular signatures associated with insulin resistance and rapid weight-gain. Moreover, machine-learning algorithms then supported the diagnostic power of these biomolecular signatures. Finally, complex novel data types revealed biologically relevant implications on post-translational modifications (in particular, glycosylation) of these signatures. This study not only elucidated potential diagnostic and therapeutic targets in obesity-mediated T2DM, but also matured novel methodologies to produce and analyze multi-omics data comprehensively.

Keywords: Obesity
Insulin Resistance
Type II Diabetes
Multi-omics
Biology
Stanford University
Precision Medicine
Thesis
Advisor: Snyder Michael
Simon Michael
The Combined Effects of Gabrb3 Heterozygosity and Maternal Immune Activation on Placenta Pathology

In the past few decades, the prevalence of Autism Spectrum Disorders (ASD) has risen to 1 in 68 live births (CDC, 2014), and no lone gene has been named as a single cause of ASD. The 15q11-13 region is a hotspot of ASD-related genes, and found within this area is a gene of interest, GABA-receptor type A beta 3 subunit (GABRB3), implicated in both ASD and innate immune inhibition. Activation of a maternal innate immune response during pregnancy is also a known risk factor for ASD (Croen, Grether, Yoshida, Odouli, & Van de Water, 2005; Mazina et al., 2015). Both Gabrb3 haploinsufficiency and maternal immune activation (MIA), i.e., the exposure to infectious agents resulting in a measurable maternal immune response during gestation, are used in our model. With a mouse model, both factors have been combined at a previously determined critical time-point of placental vulnerability, embryonic day 12.5, to study the combined effects of gene-immune interaction. Immune activation may influence brain development in part by its effects on the placenta, and placental injury is exacerbated by the partial loss of Gabrb3. While previous studies have shown that Gabrb3 deficiency and MIA impact fetal outcome, there is limited work on the expected synergy of combinatorial gene-environment effects or the roles of the placenta in neocortical development. Using lipopolysaccharide (LPS), a Gram-negative bacteria mimic, and Gabrb3-deficient mice, this research explores the combined effects of a gene-environment interaction in relation to ASD. Preliminary results of these experiments suggested the placenta as an important organ in this model of a gene-immune interaction. Novel automated analysis of placental hemorrhage has shown significant variation in the level of visible placental hemorrhage, with saline-treated, wild-type placentas having less hemorrhage than LPS 30-treated, Gabrb3 heterozygous placentas (Figure 7A; P<0.0001; n=158). In addition to this, confirmation of protein levels of GABRB3 in mouse placenta provides greater insights into how Gabrb3 deficiency impacts placental development and can be further exacerbated upon MIA in this model. Understanding this relationship could lead to the elucidation of a novel mechanism underlying ASD development and provide crucial insights into preventative strategies and therapeutic targets.

Keywords:  Department of Biology
Biology
Autism Spectrum Disorders
Maternal Immune Activation
Placenta
Thesis
Advisor: Palmer Theo
Jones Patricia
The Effect of Indian Community Health Workers: Multiple Tasks and Few Results

The Government of India’s Accredited Social Health Activist (ASHA) program is the largest community health worker program in the world and is credited with improving the healthcare of rural Indians. However, there have been no comprehensive quantitative evaluations of this program. This paper exploits the early rollout of the ASHA program in high focus states to identify the effect of the ASHA program using a year and state fixed effects model. I find no evidence that the ASHA program had a positive effect on health inputs or health outcomes. I propose that the ASHA program's performance payment scheme may create a multitasking problem that explains this absence of a measureable effect.

Keywords:  Department of Economics
Stanford Department of Economics
India
Accredited Social Health Activist program
healthcare
rural
Thesis
Advisor: Miller Grant
The Effect of Inflammation and Inhibition on the Coding of Cutaneous Temperature in the Spinal Cord

Hyperalgesia and allodynia, two frequent symptoms of persistent pain, arise from either heightening the sensitivity of previous painful stimuli or making innocuous stimuli noxious, respectively. Understanding the neural circuitry mechanism underlying this persistent pain is of significant scientific and clinical interest. At the periphery, application of pro-inflammatory compounds lead to exaggerated responses to stimuli; while in the central nervous system, pro-inflammatory compounds suppress the inhibitory gate and exaggerate the responses to stimuli as well. Previous literature has shown that there are specific neural substrates that contribute to the gating of pain, but these studies rely on genetic strategies to ablate a large population of neurons, thereby creating a lack of specificity. We combined a novel in vivo two-photon spinal cord imaging preparation with the formalin injection model of persistent pain to systematically examine spinal neurons’ responses to thermal stimuli in a large population of neurons with single cell resolution. This platform allowed us to identify the specific populations of neurons that are modulated by pain and characterize their behaviors. We show that formalin produces warmth allodynia while decreasing the response to cold stimuli preferentially in broadly tuned cells. This increase in response to warmth and decrease in response to cold is partially mediated by the circuitry crosstalk of TRPV1 DRG inputs. Finally, we show that the application of glycine receptor antagonist, strychnine, and GABAA receptor antagonist, bicuculline, lead to an increase in neuronal response to temperature stimulation suggesting a critical role of the inhibitory circuitry in gating of pain.

Keywords: Chen, Xiaoke
Biology, 2016
Biology
Neurobiology
Pain
Inflammation
Inhibition
Thesis
The Lines We Draw: Nationalism and Border Creation at Sèvres and Lausanne

This thesis describes the multi-faceted political modernization of the Middle Eastern Region and the transformation of the Ottoman Empire into a system of modern states. To that end, this thesis examines two cases: the treaties of Sèvres (1920) and Lausanne (1923) to understand why some groups garnered statehood rather than others in the succession of treaties both during and after the First World War. It ultimately finds that the groups that were most nationalized were able to claim the most territory in each of these treaties, despite other geopolitical pressures. In this liminal period, national movements could actively argue a state into being.

Keywords: Sèvres
Lausanne
borders
nationalism
state creation
International Relations Honors Program
International Relations
Thesis
Advisor: Crenshaw Martha