VictorJuiz/thesis huggingface dataset:
Determining parentage in a population of harvester ants

Reproduction in ant species takes place at the colony level, and daughter queens disperse after mating, two facts that make it difficult to track descent in ants. Genetic analysis can provide invaluable information about parent-offspring relationships in ants, making it possible to quantify reproductive success, a crucial measure for relating phenotype, fitness and environmental factors in ecology.
The Gordon Lab has been tracking a population of Pogonomyrmex barbatus colonies in a field site in the Chihuahuan desert in southeastern Arizona since 1985. Sequencing of the cox1 mitochondrial gene and five polymorphic microsatellite loci was performed on samples from 10 colonies, which were taken from the field in August 2013.
Like other harvester ant populations, the P. barbatus colonies on the site show an asymmetric ratio of two interbred but genetically distinct lineages. The ratio for the 10 colonies sampled in this project was not significantly different from samples taken in 1999 and 2010.
The sequencing data collected in this project will enable the lab to properly identify colonies that have relocated their nests or for which marking tags have been lost. Additionally, the lab will be able to determine if the colonies sampled have parent or offspring colonies living on the site.

Keywords:  Department of Biology
Department of Biology
Gordon Lab
ant colony population
Pogonomyrmex
parentage analysis
microsatellites
lineage ratio
Thesis
Advisor: Gordon Deborah
Peay Kabir
Determining the role of gamma-glutamyl transferase 7 in glioblastoma tumorigenesis

Glioblastoma (GBM) is the most malignant primary brain tumor in adults, with a median survival time of one and a half years. Traditional treatments including radiation, chemotherapy and surgery are not curative, and it is crucial to explore novel targets for therapeutic treatment. Gamma-glutamyl transferase (GGT) is a family of enzymes involved in the metabolism of glutathione, the cell’s main water-soluble antioxidant. GGT7 is a novel GGT family member whose function has not been fully determined and has not been previously studied in cancer. Recent reports have demonstrated that GBM patients have decreased expression of GGT7 but not GGT1 or GGT5, suggesting that loss of GGT7 may enhance glial tumor growth. We hypothesize that GGT7 could be acting as a tumor suppressor in GBM due to its role in pro-oxidation and detoxification. In this thesis project we sought out to determine if GGT7 plays a role in GBM tumorigenesis. To determine if GGT7 is involved in GBM tumorigenesis we transduced GBM cell lines with GGT7. We determined that an increase in GGT7 resulted in a minimal decrease in proliferation and 3-fold reduction in anchorage independent growth at normal serum conditions. Surprisingly, we observed a more pronounced reduction in GBM growth under starvation conditions, yielding a 2-fold decrease in proliferation and 3-fold decrease in anchorage independent growth. This suggests that when GBM cells undergo stressful situations GGT7 reduces tumorigenic phenotypes. Correspondingly, we reduced expression of GGT7 using both siRNAs and shRNA. We found that reducing GGT7 expression increased proliferation in the GBM cells. This was seen at both normal (1.5-fold increase) and low serum conditions (2-fold increase), with a greater increase at low serum conditions. GGT7 expression also modulated the activity of reactive oxygen species (ROS) in the cell. ROS levels were decreased by 14-15% at normal serum conditions and 11-33% at low serum conditions. Together, our study suggests that GGT7 may act as a tumor suppressor in glial tumorigenesis by protecting the cells from ROS damage and decreasing proliferation under stressful, low nutrient conditions. Further analysis will be conducted to determine if GGT7 can be used as a biomarker or therapeutic target for GBM.

Keywords:  Department of Biology
Biology
glioblastoma
gamma-glutamyl transferase 7
tumorigenesis
reactive oxygen species
Thesis
Advisor: Li Gordon
McConnell Susan
Development and application of whole-cell computational models for science and engineering [electronic resource]

A central challenge in biology is to understand how phenotype arises from genotype. Despite decades of research which have produced vast amounts of biological data, a complete, predictive understanding of biological behavior remains elusive. Computational techniques are critically needed to assemble this wealth of data into a unified theory. We have developed an integrative approach to computational modeling which enables comprehensive predictive models. We used this approach to construct the first "whole-cell" model. The model predicts the life cycle dynamics of the Gram-positive bacterium Mycoplasma genitalium from the level of individual molecules and their interactions, including its metabolism, transcription, translation, and replication. We validated the model by broadly comparing its predictions to a wide range of experimental data. We have demonstrated that the model can guide biological discovery including determining how the M. genitalium metabolic network can regulate the cell cycle, enumerating the modes of cellular death, and determining metabolic kinetic parameters. We have also demonstrated how whole-cell models can guide rational biological design. In addition, we have developed several software tools to facilitate whole-cell modeling, including databases for organizing training data and storing model predictions, and software for visually analyzing model predictions. Together, these technologies will accelerate bioengineering and medicine by enabling rapid in silico experimentation, facilitating experimental design and interpretation, and guiding rational biological design.

Advisor: Covert Markus primary advisor. Thesis advisor
Huang Kerwyn Casey
Ferrell James Ellsworth advisor. Thesis advisor
Development of a low-temperature cavity ring-down spectrometer for the detection of carbon-14 [electronic resource]

This thesis covers the development and performance analysis of a cavity ring-down spectrometer (CRDS) prototype for the measurement of carbon-14. The overarching goal of the project was to build a prototype spectrometer using simple hardware to elucidate the hurdles in bringing a commercial carbon-14 CRDS analyzer to market. The development of the CRDS system is described. First, the theoretical analysis of the mid-IR spectra and line selection are presented. Then the hardware design choices that would enable measurements at low temperatures are discussed. Finally, the operation of the instrument is covered. This includes the experimental condition control systems and a model-based, closed-loop, PZT-creep-compensation, data-acquisition routine. Performance analysis of the spectrometer was conducted. Initial spectroscopic measurements characterized the interfering spectra surrounding the 14CO2 P(40) line candidate. This characterization was later used to quantify carbon-14 in room temperature carbon dioxide with a spectroscopic model. Finally, low-temperature trial measurements were made to elucidate any design flaws. The alpha prototype showed promise, but design flaws prevented measurements at the ideal temperature and wavelength. However, it demonstrated low-temperature measurement capabilities and resolved room temperature samples with a 14C/C concentration approximately 50 times contemporary atmospheric levels with 6.6% 1-sigma error. These results are reviewed, and possible options for moving forward are discussed.

Keywords: Mechanical Engineering.
Advisor: Hanson Ronald primary advisor. Thesis advisor
Ognibene Ted
Zare Richard N. advisor. Thesis advisor
Development of diamidophosphite ligands towards the palladium-catalyzed trimethylenemethane cycloaddition [electronic resource]

The synthesis of complex molecules in an efficient and selective fashion remains to be one of the driving forces in the development of the field of organic chemistry. Towards that end, the study of cycloaddition reactions has garnered much attention due to its ability to form multiple bonds in a single step while accessing complicated ring structures. Since its inception in 1979, the palladium-catalyzed trimethylenemethane (TMM) [3+2] cycloaddition has been heavily studied by the Trost group. It was found that the key zwitterionic palladium-TMM intermediate is capable of performing cycloaddition reactions with various coupling partners, forming cyclopentanes, tetrahydrofurans, and pyrrolidine rings, as well as seven- and nine-membered rings in good yields and selectivities. Additionally, substituents placed on the starting TMM-precursor, also known as the TMM donor, are also directly introduced onto the cycloadduct, allowing for the synthesis of highly-substituted ring systems. In 2006, the Trost group was able to perform the reaction in an enantioselective fashion through the development of BINOL-derived phosphoramidite ligands. While these cycloadducts were generated with high yields and enantioselectivities, the substitution on the TMM precursor was limited, owing to the reactivity of the phosphoramidite ligand employed. Herein, we describe the development of a new class of ligands, diamidophosphites, and their utility in the substituted-TMM cycloaddition. These ligands are easily accessed in a two-step procedure with high levels of modularity, allowing for the fine-tuning of the catalyst system. The effectiveness of these ligands will first be discussed in a vinyl-substituted TMM cycloaddition, where tetrasubstituted cyclopentanes bearing three contiguous stereocenters are synthesized in high yields, diastereo- and enantioselectivities. Additionally, a new disubstituted TMM donor was developed for the synthesis of pyrrolidine ring systems bearing a quaternary stereocenter. Finally, this method is applied towards the total synthesis of jogyamycin, where the core cyclopentane ring is accessed through the TMM cycloaddition.

Keywords: Chemistry.
Advisor: Trost Barry M. primary advisor. Thesis advisor
Du Bois Justin advisor. Thesis advisor
Wender Paul A. advisor. Thesis advisor
The development of miniature Raman-based clinical imaging devices to detect targeted SERS nanoparticles [electronic resource]

Better screening strategies for early cancer detection and the identification of tumor boundaries during surgical resection are essential to improve patient care. The current standard relies on white-light visualization of tissue and the use of non-specific dyes to highlight the vasculature. As a result, lesions are often missed and the identification of the tumor boundaries during removal can be difficult, often resulting in the need for multiple random biopsies at the perimeter of the suspect tissue. Success in the detection and resection of malignant tissue is dependent on skilled and experienced surgeons and endoscopists. Sophisticated optical technologies that show biomarker-specific contrast are nearing clinical translation, and rapid detection of targeted surface enhanced Raman scattering (SERS) nanoparticles is a promising approach for sensitive detection of cancer. The advantages of SERS nanoparticles include multiplexing capabilities, high sensitivity, and consistent and stable signal over time. This thesis describes the development of miniature, highly sensitive fiber-optic-based Raman imaging devices that are capable of imaging a panel of SERS nanoparticles, which are being functionalized to target a multitude of cancer-specific biomarkers. The overreaching objective is to provide real-time diagnostic information during screening procedures by adding molecular specificity that complements white-light imaging. Here, I present two clinically translatable devices that I developed −a point-detection device and a circumferential scanning device− which were designed to be used in humans for detection of targeted SERS particles. The accomplishments of this work include the first clinically translatable Raman-based imaging device capable of simultaneously detecting mixtures of up to 10 distinct SERS nanoparticles. The non-contact nature of these designs enables them to scan large areas in short periods of time. The system is highly sensitive, rapid, and can be used in real-time. The techniques presented here open up new opportunities to significantly improve the detection and diagnosis of small and otherwise hard to detect lesions in a variety of clinical settings.

Keywords: Mechanical Engineering.
Advisor: Andriacchi Th. P. (Thomas P.) primary advisor. Thesis advisor
Contag Christopher H. primary advisor. Thesis advisor
Solgaard Olav advisor. Thesis advisor
Development of novel optogenetic and molecular tools and their application to understanding the neurological basis of behavior [electronic resource]

Successful interaction between an animal and its environment requires the execution of meaningful action in response to external cues and, in most situations, interpretation and integration of sensory inputs in the context of experience. Neurological and psychiatric diseases encompass dysfunction at any point in this pipeline. Neuroscientists seek to understand how the brain is able to complete these tasks in the healthy individual as well as the changes that underlie impairment in disease. The heterogeneous and highly interconnected structure of the brain creates unique hurdles to scientists that ask these questions. In many cases, traditional tools of the trade, namely, electrical and pharmacologic interventions, both fall short when used to derive definitive and generalizable conclusions. To facilitate neuroscience research, our laboratory has discovered, optimized, and diversified an array of single component, optically activated ion channels and pumps for neuronal control. These may be selectively introduced to neurons based on genetic or topological parameters, thereby selecting needles in the haystack of cells within the brain, and are modulated by light on the order of milliseconds, a scale relevant to neuronal activity. The purpose of the studies described here was two-fold: 1) to expand the toolbox through opsin engineering, light delivery methods, and molecular targeting strategies and 2) to apply these to understand the neurological basis of some psychiatric diseases. The use of these tools in understanding anxiety and social behavior circuitry is described briefly, while the application of two novel opsin variants to understanding the role of increased amounts of excitation relative to inhibition within the prefrontal cortex is detailed. The tools described here are designed for and validated within the brain, but may be applied within most biological systems. As experimental approaches expand, so do the range of questions available to science. Answers to these will lead to advances in understanding, managing, and curing injury and disease.

Keywords: Neurosciences.
Advisor: Deisseroth Karl primary advisor. Thesis advisor
Hestrin Shaul
Huguenard John advisor. Thesis advisor
Luo Liqun
Development of optogenetics for motor systems neuroscience in non-human primates [electronic resource]

Voluntary movement is such an integral part of common tasks that the loss of this ability is detrimental to quality of life. Effective functional restoration for patients with a limited ability to move requires deep understanding of movement control. However, despite decades of motor system research, the mechanism by which motor cortex controls movement is still unclear. Although technological advances such as electrical microstimulation have been used to investigate this mechanism, its limitations in simultaneous recording and perturbation have prevented us from obtaining more informative measurements. To address this challenge, a multidisciplinary approach was taken to further examine the underlying mechanism of motor control. Specifically, we used optogenetics along with the analytical framework of dynamical systems theory to probe the dynamics of motor preparation. Three major results are presented in this work. Firstly, we characterized and assessed the functionality of optogenetics electrophysiologically and histologically in non-human primates. Although optogenetics has been used extensively in rodents, it is still in a developmental state in primates. Hence, the efficiency of virus transfection, the reliability of neural responses to optical stimulation, the pattern of opsin expression and the safety to animals were investigated to minimize any potential risk and to aid future experimental designs. We also discovered that, in contrast to electrical microstimulation, optical stimulation in cortical motor and premotor areas did not evoke overt skeletal movements. Secondly, we continued the characterization process by injecting a red-shifted opsin, C1V1(TT), in dorsal premotor cortex (PMd) and optically perturbed the neural activity while the animals were actively engaged in an instructed-delay reach task. We found that the optical perturbation in PMd resulted in increased reach reaction times. Moreover, using the dynamical systems perspective, we discovered that, post-perturbation, the neural state did not return to its pre-perturbed state. Instead, it proceeded directly to re-join the normal neural trajectory path to execute the movement. We also observed that optical stimulation did not obliterate task-related activity in light-responsive neurons. In fact, the relationship between task-related and optically-evoked activities appeared to be linearly additive. Lastly, we developed a decoding algorithm to extract kinematics information from optogenetically-perturbed data. We trained a Kalman filter based on a mixture of perturbed and unperturbed data, and found that it provided us with an effective decoder. This decoding performance was achieved despite the fact that the decoder made no attempt to detect whether or not the neural activity was perturbed.

Keywords: Bioengineering.
Advisor: Shenoy Krishna V. (Krishna Vaughn) primary advisor. Thesis advisor
Deisseroth Karl advisor. Thesis advisor
Delp Scott advisor. Thesis advisor
Development of the brain's reading circuitry [electronic resource]

Learning to read is at the foundation of academic success. Understanding how the developing brain builds circuits to rapidly translate arbitrary printed symbols into meaningful language representations is a scientific challenge with important implications for education. Successfully learning to read requires the coordination of signals between visual, auditory and language processing regions of the cortex; white matter is essential for the development of this cognitive function. New magnetic resonance imaging (MRI) techniques make it possible to measure the structure and function of the living brain's reading circuitry and understand the coupling between changes in circuit structure, circuit function and human behavior The following sections develop a methodology for measuring the white matter connections of the brain's reading circuitry and quantifying changes in tissue properties over the course of reading instruction. A series of functional MRI and diffusion-weighted MRI experiments elucidate the cortical regions that perform reading related computations and the white matter fascicles that transmit signals between these regions. These measurements show that the dynamics of an individual's white matter development predicts their acquisition of skilled reading. Learning to read is intricately related to active developmental processes in specific white matter tracts. This collection of findings highlights the important role of non-neuronal biological processes in the development of complex cognitive functions.

Keywords: Psychology.
Advisor: Wandell Brian A. primary advisor. Thesis advisor
Dougherty Bob advisor. Thesis advisor
Norcia Anthony Matthew advisor. Thesis advisor
Wagner Anthony David advisor. Thesis advisor
Dichotomy between structure and randomness in combinatorial number theory [electronic resource]

This dissertation is about exploring the dichotomy between structure and randomness in analytic number theory and additive combinatorics. We explore various problems including bounds for character sums, Goldbach-type questions, and a Freiman-type result.

Keywords: Mathematics.
Advisor: Soundararajan Kannan
Chatterjee Sourav advisor. Thesis advisor
Venkatesh Akshay
Differential sensitivity of oligodendrocyte precursor cells to methotrexate in the developing brain

Patients exposed to chemotherapy during cancer treatment frequently present with neurocognitive deficits that are debilitating and lasting, commonly known as “chemobrain.” This set of symptoms is anatomically localized to the hippocampus and frontal subcortical white matter, where oligodendrocyte precursor cells (OPCs) are essential to development and maintenance of white matter. Previous studies have shown that these cells are especially vulnerable to chemotherapeutic exposure, suggesting the possibility that OPCs might be a therapeutic target in future treatments for chemotherapy-induced dysfunction. Methotrexate (MTX), an antimetabolite used frequently to treat childhood cancers, has been shown to impair white matter integrity in human patients, but the specific mechanisms of its effects on OPCs have not been elucidated. We show here that there is a significant depletion of the white matter OPC population following chemotherapy administration, while the grey matter OPC population remains intact. This incongruity is not explained by differential survival, as when grey or white matter OPCs are exposed to methotrexate in vitro, neither population exhibits significant cell death at concentrations achieved in the brain following systemic MTX administration. By gaining a better understanding of the cell-intrinsic and microenvironmental mechanisms that govern OPC population dynamics and function, and by creating a faithful mouse model for continued investigation, this research provides compelling evidence for the OPC as a therapeutic target candidate in the treatment of “chemobrain.”

Keywords:  Department of Biology
Oligodendrocyte Precursor Cell
Methotrexate
Chemobrain
Biology
Thesis
Advisor: Monje-Deisseroth Michelle
McConnell Susan
Diffusion distance of MAC1 protein when secreted by Ustilago maydis in Zea mays anthers

The Maize multiple archesporial cells 1 (mac1) gene plays a crucial role in anther development by regulating cell proliferation and determining cell identity. Archesporial (AR) cells in the anther are hypothesized to secrete MAC1 into the apoplast during development, where it binds to leucine-rich-repeat (LRR) receptor kinases on surrounding L2-d somatic cells. To investigate the function of MAC1 in planta, the basidiomycete fungus Ustilago maydis was used to deliver MAC1 protein directly into the apoplast of anther tissues. A U. maydis construct was generated by homologous recombination to express and secrete a MAC1-mCherry-HA fusion protein into the maize anther apoplast. Confocal microscopy verified successful infections of maize by U. maydis, and the presence of mCherry signal. However, the signal is not confirmed to be MAC1-mCherry-HA fusion protein signal; Western blot data is needed to ensure that the fusion protein is not cleaved in planta by the host plant cell’s proteases.

Keywords:  Department of Biology
Stanford University
Biology Department
Zea mays
maize
multiple archesporial cells 1
mac1
anther
Ustilago maydis
U. maydis
Thesis
Advisor: Walbot Virginia
Hanawalt Philip