VictorJuiz/thesis huggingface dataset:
Indole-3-Carbinol Mediated Anti-Proliferative Regulation of Breast Cancer Stem Cells and Malignant Melanoma-Initiating Cells

The cancer stem cell theory ascertains a subpopulation of tumorigenic cells that selectively possess the ability for tumor initiation and self-renewal capacity to differentiate into nonmalignant cancer cells, known as bulk tumor cells. Cancer stem cells were first identified in hematopoietic cancers but subsequently have been implicated in ovarian, melanoma, liver, sarcoma, head and neck, pancreatic, glioblastoma, and breast cancers since. As a result, malignant tumors can be composed of genetically and morphologically heterogeneous cell populations with varying degrees of differentiation, self-renewal ability, and metastatic capacity. Experimental pursuits have sought to isolate and analyze the cancer stem cell population in primary tumors and molecularly strategize to identify phenotypic targets. A lack of standardized cancer stem cell in vivo and in vitro models have slowed down the development of proper therapies as well as the elucidation of scientific mechanisms that dictate cancer stem cells. One method of detection has been the utilization of various stem cell markers to categorize molecular phenotypes. In breast cancer stem cells, biomarkers such as the nucleolar GTPase nucleostemin; the detoxifying enzyme, ALDH-1; and cell surface marker, CD44 aid in identification and isolation of cancer stem cells for research studies. Furthermore, exclusion of the Hoescht Dye assays for the cell’s ability to efflux current therapeutic molecules extra-cellullarly, evading apoptosis and cell cycle arrest. Furthermore, melanoma cancer stem cells, also known as malignant melanoma-initiating cells (MMICs), contain subpopulations expressing CD133, CD20, and ABCG5 have defined features of unlimited self-renewal and proliferative capacities for melanoma cancers. While cancer incidence overall has decreased, melanoma continues to rise, with patients with metastatic and malignant melanoma continue to relapse from current therapeutic strategies. This thesis details the characterization of human breast cancer and melanoma cell lines of varying tumorigenic potential and their subsequent response to the phytochemical, indole-3-carbinol, and its synthetic derivative, 1-benzyl-I3C. I3C selectively targets breast cancer stem cells through different molecular mechanisms such as protein-protein interactions of the stem cell marker nucleostemin and its binding partner, murine double mutant 2 (MDM2) in the nucleolus, thereby freeing p53 to activate apoptosis. Furthermore, I3C sensitizes cells with a wild type p53, wild type PTEN phenotype or even more tumorigenic melanoma cells that possess the rare BRAF V600D mutation and PTEN deletion. Given I3C’s and its more potent derivative, 1-benzyl-I3C’s, anti-proliferative modulation of the p53 pathway in breast cancer cells and the PTEN/ Wnt pathways in malignant melanoma cell lines, preclinical results can implicate I3C as a novel chemopreventative molecule that selectively targets cancer stem cells.

Advisor: Firestone, Gary L
Hip Actuation Designs to Support the Back while Stooping and Walking

Back injuries are the most common musculoskeletal disorder in the workplace and cost employers billions of dollars each year. Although these are widely known statistics, no comprehensive solution exists to reduce back injuries. While products like dollies and carts have been designed to solve particular tasks like moving materials, an all-encompassing solution to alleviate back injuries has yet to be proposed. This is largely due to the dynamic complexity involved with accommodating the various tasks required by different occupations. While the majority of some workers spend their days stooping to move materials, others predominantly walk bent over to perform duties like vacuuming./nBut at the most basic level, professions with high rates of back injuries mainly have two common motions: stooping and walking. Therefore, to successfully reduce back injuries, a device must reduce back muscle strain by supporting the torso during stooping while still permitting walking. This dissertation proposes five hip actuation designs to solve this fundamental problem. The intent is for the hip actuators to be incorporated into a full exoskeleton which interfaces with the user’s torso and legs to support the lower back during stooping and/or walking./nThe first hip actuation design is a simple wrap spring clutch which is beneficial for tasks like static stooping and bent walking (walking while stooped). The second hip actuation design adds a spring to the first design to conserve energy and dynamically support the back during stooping and standing upright. The third hip actuation design adds a locking feature to the spring in the second design to control when the spring’s energy is released. The fourth hip actuation design uses one large, high-torque motor to support the torso during bending and walking. The fifth hip actuation design adds a wrap spring clutch to the fourth design to reduce the complexity of the control system when a user walks./nAlthough the proposed designs are discussed in order of increasing design complexity, the enhanced systems also accommodate additional worker tasks, making them applicable to broader audiences. Ultimately, a cost-benefit analysis weighing design complexity versus applicable tasks is necessary to determine which designs are most beneficial for production.

Advisor: Kazerooni, Homayoon
The Interaction of Neonatal Intensive Care Unit Microbes with the Microbiome of the Developing Preterm Infant Gut

Humans spend approximately 90% of their time indoors, yet we know very little about the microbial ecosystem of the built environment and how it impacts occupants. Here we use infants hospitalized in a neonatal intensive care unit (NICU) as a model system to track the exchange of microbes between room and occupants. By leveraging high-throughput sequencing and other “omics” technologies, we conducted four major studies to broadly address the composition of microbes populating NICU surfaces, how these microbes migrate to the infant gut, and once in the gut, how these microbes compete for resources. Over the course of these campaigns we collected and processed over 5,000 samples from hospital room surfaces and over 300 infant fecal samples creating the largest collection of hospital samples to be interrogated with next-generation sequencing techniques. Using an approach that reassembles the entire 16S rRNA gene from room amplicons and gut metagenomics data, we discovered several organisms on room surfaces before their detection in the infant gut. Once in the gut, we used a metaproteomics technique to investigate the metabolisms of early infant gut colonizers. Unlike the anaerobic gut environment of older children and adults, we discovered a relatively high utilization of aerobic pathways in many of the facultative anaerobes colonizing the infant gut. We also observed niche partitioning amongst closely related Citrobacter strains in our strain- resolved proteomics data, providing insight into how early colonizers compete in the nascent infant gut. To better understand biomass trends inside and outside the gut, we developed an assay to quantify 16S rRNA gene copies using droplet digital PCR (ddPCR). We discovered a surprising amount of variation in bacterial densities across different NICU environments. These data also allowed us to adapt a novel in silico data cleaning method that leverages the quantification of negative controls to provide data less impacted by the inherent noise of low- biomass amplicon workflows. Cleaner data allowed us to apply a machine learning classifier that showed each infant’s room had a distinct microbial fingerprint. To validate this result, we conducted a metagenomics campaign on pooled room samples from six different infants. After assembly and binning, we were able to recover hundreds of high quality genomes. Utilizing genomes from this dataset and previously isolated genomes from our lab, we discovered the same strains in the room as in infants. Further, we found several taxa frequently isolated from infant gut samples in this NICU are the same strains in the NICU room metagenomes. Overall, the analysis from this work suggests that where a premature infant is born and the history of room occupancy can impact its gut microbiome development.

Advisor: Banfield, Jillian F
Characterizing and Modeling Spin Polarization from Optically Pumped Nitrogen-Vacancy Centers in Diamond at High Magnetic Fields

The small thermal polarization of nuclear spins currently limits the capabilities of nuclear spin based technologies such as nuclear magnetic resonance spectroscopy (NMR) and magnetic resonance imaging (MRI). Existing techniques for polarizing nuclear spins beyond their thermal equilibrium, called dynamic nuclear polarization (DNP), utilize cryogenic temperatures and expensive microwave technologies to transfer the larger thermal polarization of electron spins to targeted nuclei. Ubiquitous access to polarized nuclei through a room temperature, microwave-free alternative to DNP would revolutionize the capabilities of NMR and MRI./nOptically pumping nitrogen-vacancy (NV) defects in diamond can generate room temperature, microwave-free 13C nuclear polarization at the high magnetic fields used in NMR (7.05T, 9.4T). The mechanism of NV center electronic polarization is well understood, and 13C polarization has been observed, but the mechanism for polarization transfer from NV to 13C remains unknown. Here we present NMR and EPR results characterizing the polarization dependence of 13C and NV in diamond, as well as a quantum mechanical model describing a possible polarization transfer mechanism./nThe sign and magnitude of the 13C polarization sensitively depends on the orientation of the diamond with respect to the directions of the applied magnetic field and laser polarization. The polarization magnitude further depends on the defect concentrations, magnitude of the applied magnetic field, temperature, and the illumination conditions: wavelength, power, and exposure time./nTo better understand the source of polarization, the NV defects were characterized with EPR to determine relaxation times, concentrations, and homogeneity. EPR was also used to determine the orientation dependence of NV polarization. The NV polarization is constant in the defect frame, which, when rotated into the laboratory frame, results in highest polarization when aligned with the field, zero polarization at 54 degrees, and inverted polarization at higher angles. These EPR insights into the NV physics were incorporated into models for 13C polarization mechanisms./nDipolar coupled pairs of NV centers are proposed as the source for 13C polarization in NV- diamonds at high magnetic fields. Our model shows these dipolar-coupled manifolds have transitions matching the frequency of the 13C nuclei, making them a feasible source of spontaneous polarization transfer. The model also qualitatively captures the observed polarization sign changes as a function of crystal orientation.

Advisor: Reimer, Jeffrey A
Molecular Design of Polymerized Ionic Liquids

Polymerized ionic liquids are an emerging class of functional materials with ionic liquid moieties covalently attached to a polymer backbone. As such, they synergistically combine the structural hierarchy of polymers with the versatile physicochemical properties of ionic liquids. Unlike other ion-containing polymers that are typically constrained to high glass transition temperatures, polymerized ionic liquids can exhibit low glass transition temperatures due to weak electrostatic interactions even at high charge fractions. Promising applications relevant to electrochemical energy conversion and CO2 capture and sequestration have been demonstrated for polymerized ionic liquids, but a molecular design strategy that allows for elucidation of their structure-property relationships is yet to be developed./nA combination of anionic polymerization, click chemistry, and ion metathesis allows for fine and independent control over polymer properties including the number of repeat units, fraction of ionic liquid moieties, composition, and architecture. This strategy has been exploited to elucidate the effect of lamellar domain spacing on the ionic conductivity of block copolymers based on hydrated protic polymerized ionic liquids. The conductivity relationship demonstrated in this study suggests that a mechanically robust material can be designed without compromising its ability to transport ions./nThe vast set of ion pair combinations in polymerized liquids provides a unique opportunity to develop functional materials where properties can be controlled with subtle changes in molecular structure via ion metathesis. We illustrate the case of a polymerized ionic liquid that combines the low toxicity and macromolecular dimensions of poly(ethylene glycol) with the magnetic functionality of ion pairs containing iron(III). This material can yield novel theranostic agents with controlled residence time within the human body, and paramagnetic functionality to enhance 1H nuclei relaxation rate required for medical imaging./nFinally, the molecular design strategy is expanded to incorporate ion pairs based on metal-ligand coordination bonds between cations and imidazole moieties tethered to the polymer backbone. This illustrates a general approach for using chelating polymers with appropriate metal-ligand interactions to design high conductivity and tunable modulus polymer electrolytes

Advisor: Segalman, Rachel A
Balsara, Nitash P
Predictive Control under Uncertainty for Safe Autonomous Driving: Integrating Data-Driven Forecasts with Control Design

Self-driving vehicles have attracted a lot of interest due to their potential to significantly reduce traffic fatalities and transform people's lives. The reducing costs of advanced sensing technologies and the increasing capabilities of embedded computing hardware have enabled the commercialization of highly automated driving features. However, the reliable operation of autonomous vehicles is still a challenge and a major barrier in the large scale acceptance and deployment of the technology./nThis dissertation focuses on the challenges of designing safe control strategies for self-driving vehicles due to the presence of uncertainty arising from the non-deterministic forecasts of the driving scene. The overall goal is to unify elements from the fields of vehicle dynamics modeling, machine learning, real-time optimization and control design under uncertainty to enable the safe operation of self-driving vehicles. We propose a systematic framework based on Model Predictive Control (MPC) for the controller design, the effectiveness of which is demonstrated via applications such as lateral stability control, autonomous cruise control and autonomous overtaking on highways. Data collected from our experimental vehicles is used to build predictive models of the vehicle and the environment, and characterize the uncertainty therein. Several approaches for the control design are presented based on a worst-case or probabilistic view of the uncertain forecasts, depending on the application. The proposed control methodologies are validated by experiments performed on prototype passenger vehicles and are executed in real-time on embedded hardware with limited computational power. The experiments show the ability of the proposed framework to handle a variety of driving scenarios including aggressive maneuvers on low-friction surfaces such as snow and navigation in the presence of multiple vehicles.

Advisor: Borrelli, Francesco
Principles of Quantum Dot Photoexcited Charge Transfer

Photoexcited charge transfer is essential to light energy conversion processes in photosynthesis and solar cells. While fundamental theories governing these molecular and bulk charge transfer reactions are well established, the same level of understanding and agreement for nanoscale systems has not been achieved. It is essential to address this knowledge gap, as nanomaterials are becoming attractive candidates for optoelectronics and electrocatalysis. In this dissertation, hole transfer from high photoluminescence quantum yield CdSe-core CdS-shell semiconductor nanocrystal quantum dots to covalently linked molecular ferrocene acceptors is investigated in the context of Marcus Theory of Electron Transfer (Nobel Prize Chemistry 1992). This model quantum dot donor-acceptor system was thoughtfully designed to address the unique properties of QDs that complicate the proper characterization of the rate constants./nIn this model system, modulating the electronic coupling and thermodynamic driving force for the reaction was done reliably and the hole transfer rate constant per acceptor, kht, was extracted by measuring steady-state and transient photoluminescence to determine the photoluminescence quantum yield in conjunction with quantitative NMR to determine the number of bound acceptors. Our studies varied the electronic coupling by six orders of magnitude by changing the shell thickness and the alkyl chain length. We find that there is a family of universal curves for PLQY as a function of coverage, spanning linear to nonlinear which depends critically on the ratio of the total hole transfer rate to the sum of the native recombination rates in the QD. Thermodynamic driving force was explored by molecular functionalizations on ferrocene that change the oxidation potentials of the acceptor. The rate's dependence on the driving force elucidated that there is no Marcus inverted region, and a new multistate model was posited to explain the result./nParameters that affect the reorganization energy such as the surface ligands were also explored. Our model charge transfer system allowed us to examine the rate of ligand exchange to determine the rate law and the rate order, and explore mechanisms of this exchange reaction. Single particle absorption and photoluminescence via fluorescence and photothermal microscopy were also explored to explore photophysical properties of single QDs, such as how its photoluminescence and absorption degrades over time and how the photoluminescence quantum yield varies in a given batch of this material.

Advisor: Alivisatos, Paul
Chaucer's French Tradition: Coterie Poetics in Late Medieval England

“Chaucer’s French Tradition: Coterie Poetics in Late-Medieval England” shows the influence of literary coteries on the formation of the earliest articulations of the English literary tradition, emerging from the founding figure of Geoffrey Chaucer. Chaucer himself engaged in coterie practices as part of his negotiation of continental, particularly French, literary traditions, and his 15th-century successors adopt and adapt the coterie model as they construct an English literary tradition. These successors — figures like Thomas Hoccleve, John Lydgate, Stephen Scrope, Richard Roos, William Dunbar, and John Skelton—articulate their own places within this tradition in terms of the intimacy of their relationships to its founder; in other words, these are coterie relationships. They are also fictive; the coterie has entered the realm of the imaginary, where it can be populated by dead writers, literary patrons, and other figures. By the end of the fifteenth century, this move to the imaginary results in a shift from the intimate logic of the coterie to the more abstract idea of a tradition – what we now know as the Chaucerian tradition, which forms the foundation of the English literary tradition./nChaucer’s coterie practices lay the groundwork for those writers who follow him. Chaucer’s relationship to the French tradition is mediated by his coterie relationship to his French contemporaries, especially Eustache Deschamps and Oton de Granson. The existence of a coterie, however, depends on making distinctions between members and non-members, which becomes clear by turning to Thomas Hoccleve’s relationship with Chaucer and Christine de Pizan. Despite having Chaucer’s model of a French and English coterie to follow Hoccleve emphasizes his relationship to Chaucer at the expense of his relationship to Christine. If Hoccleve works by exclusion, Lydgate works by inclusion. He constructs "virtual coteries," a literary trope in which a writer characterizes the production of his or her work as the combined effort of the older writers who may be its source or inspiration, the patrons or audience who have commissioned the work, and the writer himself or herself who brings all of these different strands together in order to create the final product. They are a half-step between coterie and tradition, abstracting the intimacy of coteries into a relationship that exists primarily on the page. A generation after Lydgate, beyond the close-knit networks found in virtual coteries, one arrives at the Chaucerian tradition, displayed in the work of Scrope, Roos, Dunbar, and Skelton. These writers signal their participation in that tradition by way of allusions that do not function to create a sense of intimacy with the older poet, but signal an affiliation to a whole body of material that travels under his banner, under the rubric of the Chaucerian tradition.

Advisor: Nolan, Maura
Position Sensitive Proximity Charge Sensing Readout of HPGe Detectors

Electrode segmentation is a necessity to achieve position sensitivity in semicon-/nductor radiation detectors. Traditional segmentation requires decreasing electrode/nsizes while increasing channel numbers to achieve very fine position resolution. These/nelectrodes can be complicated to fabricate, and many electrodes with individual/nelectronic channels are required to instrument large detector areas. To simplify/nthe fabrication process, we have moved the readout electrodes onto a printed cir-/ncuit board that is positioned above the ionization type detection material. In this/nscheme, charge from radiation interactions will be shared amongst several electrodes,/nallowing for position interpolation. Because events can be reconstructed in between/nelectrodes, fewer electrodes are needed to instrument large detector areas. The prox-/nimity charge sensing method of readout promises to simplify detector fabrication/nwhile maintaining the position resolution that is required by fields such as home-/nland security, astrophysics, environmental remediation, nuclear physics, and medical/nimaging./nWe performed scanning measurements on a proof of principle detector that we/nfabricated at Lawrence Berkeley National Laboratory (LBNL). These measurements/nshowed that position resolution much finer than the strip pitch was achievable using/nthe proximity charge readout method. We performed analytic calculations and Monte/nCarlo modeling to optimize the readout electrode geometry for a larger detector to/ntest the limits of this technology. We achieved an average position resolution of 288/nμm with eight proximity electrodes at a 5 mm pitch and 1 mm strip width, set 100/nμm away from the detector surface by a Kapton spacer. To achieve this resolution/nusing standard technologies, 300 μm pitch strips are necessary, and would require/n100 channels to instrument the same area. Through our optimization calculations,/nwe found that there is a trade-off between position resolution and energy resolution,2/nand this system provided comparatively poor energy resolution by HPGe standards,/nwith 4.7 keV FWHM at 59.5 keV. With another electrode geometry, we were able/nto achieve 2.9 keV FWHM at 59.5 keV. This dissertation describes the work we/ncompleted to achieve these results.

Advisor: Vetter, Kai