VictorJuiz/thesis huggingface dataset:
Capacitive micromachined ultrasonic transducers with vented cavities [electronic resource]
Keywords: Mechanical Engineering.

Capacitive micromachined ultrasonic transducers (CMUTs) are increasingly seen as a better alternative than piezoelectric transducers for many ultrasound applications. Ultrasonic flow metering presents one such case where CMUTs are much better suited. Due to their lower mechanical impedance, CMUTs are more efficient at coupling sound into a fluid medium than piezoelectric transducers. Unlike piezoelectric transducers which suffer from depoling at temperatures above their Curie point, CMUTs can easily be used in higher temperatures. This should make CMUTs ideal candidates for ultrasonic flow metering in extreme environments such as those that exist in flare stacks, high temperature steam lines in industrial plants, etc. Despite these benefits, conventional CMUTs are not suited for the highly variable pressure conditions that many flowmeters have to operate under. CMUTs with vented or pressurized cavities can overcome this limitation. This dissertation presents the design and modeling for such CMUTs. A reliable fabrication process for CMUTs vented through the plate or through the substrate is also presented. The fluid squeeze film formed in the cavity between the CMUT plate and the substrate provides a way to control the bandwidth and sensitivity of such CMUTs. The dissertation presents CMUTs with bandwidth ranging from 1% to over 20% in air. These CMUTs were tested under a pressure of up to 20 bar and maintained good bandwidth and SNR. The dissertation also discusses the importance of packaging for CMUTs vented through the substrate and presents a way to utilize acoustic resonances in the package for maintaining a steady operating frequency under varying pressure. The wide bandwidth of such CMUTs can be utilized in many other application of ultrasound in air. The dissertation briefly discussed the application of these CMUTs for thermoacoustic imaging as well as for gesture sensing.
Catalytic enantioselective dihalogenation of allylic alcohols and its application to the stereoselective total syntheses of chlorosulfolipids [electronic resource]
Keywords: Chemistry.

The dihalogenation reaction is one of the most fundamental reactions in organic chemistry, but few methods exist which render the transformation asymmetric. Here, a catalytic, enantioselective dihalogenation reaction is described which is capable of effecting selective dibromination, dichlorination, and bromochlorination to allylic alcohols of wide scope. This methodology was applied to a short, stereoselective synthesis of the chlorosulfolipid, danicalipin A. The reaction was further applied to the synthesis and crystallographic stereochemical confirmation of deschloromytilipin A and polybrominated analogs.
Cell free metabolic engineering for the production of hydrogen from cellulosic biomass [electronic resource]
Keywords: Chemical Engineering.

Establishing alternative methods to produce petrochemicals from renewable resources is a critical step toward a sustainable society. Hydrogen is a key commodity chemical with over 50 million metric tons produced annually with a market value of over 0 billion. The majority of this hydrogen is used for synthesis of ammonia and petroleum refining but also has the potential for use as a clean burning fuel. However, current methods rely primarily on the steam reformation of natural gas. We sought to develop a new platform for synthesis of hydrogen from cellulosic biomass using E.coli cell free extracts. By coupling the native E.coli metabolic pathways with a heterologous synthetic pathway, we established a method to produce hydrogen from glucose. In order to accomplish this, a synthetic pathway to produce hydrogen from a native redox source, NADPH, was developed using a ferredoxin NADP+ reductase, ferredoxin, and a [FeFe] hydrogenase. The pathway was constructed by screening natural proteins for the capacity to support maximal hydrogen production rates. Careful characterization of the interactions of the three protein synthetic pathway through UV/Vis spectroscopy and gas chromatography enabled further improvements. The synthetic pathway was then coupled to a cell free extract to demonstrate the feasibility of producing hydrogen from glucose with a cell extract. In order to maximize the yields of hydrogen from the cell extract, we knocked out three metabolic proteins, phosphofructokinase, 6-phosphogluconate dehydratase, and glyceraldehyde-3-phosphate dehydrogenase that eliminate undesirable side reactions in glycolysis and Entner Doudoroff pathways. With these cell lines, we established protocols for cell extract production and in vitro hydrogen production that demonstrate significant improvements in hydrogen yield. Finally, in order to further improve the cell extracts, we then developed a strategy for selective metabolic silencing (SeMs) of key enzymatic activities. Using this technique, specific enzymatic activities could be provided in vivo for efficient cell growth and enzyme production, but then these activities could be inactivated in the cell extract to avoid the loss of the reducing equivalents required for hydrogen production. To demonstrate this principle, we engineered a library of glyeraldehyde-3-phosphate dehydrogenase mutants with insertion of a recognition sequence for human rhinovirus 3C protease. Many of these mutants were active in vivo, but through protease treatment could be inactivated to improve hydrogen production. Together, these advances explore the feasibility of using cell free extracts for biochemical synthesis, as well as contribute to ongoing research on in vitro enzymatic biocatalysis.
Challenges, solutions, and biological applications of three-dimensional nanoscale spatial localization of single molecules [electronic resource]
Keywords: Chemistry.

Single fluorescent molecules and particles can be localized in space with precision on the order of tens of nanometers (i.e. "super localized") using state-of-the-art microscopy techniques. The ability to probe complex environments at the sub-diffraction size scale has proven invaluable in revealing fundamental heterogeneity and improving overall understanding across the applied physical sciences. Super-localization microscopy is at the heart of both single-molecule super-resolution microscopy and single-particle tracking. The work presented in this dissertation concerns the application of super-localization microscopy to problems of biophysical interest, as well as theoretical and experimental advances in the methodology of this class of techniques. While the most common methods of super-localized position estimation ensure high localization precision, they might not always ensure high accuracy. In particular, the anisotropy of single-molecule dipole emission can result in mislocalizations of hundreds of nanometers, depending on the orientation of the molecule and its distance from the focal plane. In this dissertation I discuss different ways to correct this potential source of error. On the one hand, a theory based on a wobbling-in-a-cone model is presented that shows how this error is mitigated by molecular rotational mobility. On the other hand, for the worst-case scenario of a rotationally fixed emitter, an experimental approach based on Fourier optics is also discussed that allows for estimation of molecular orientation and enables active correction of mislocalization effects. The last third of this dissertation discusses applications of super-localization microscopy to three-dimensional tracking of fluorescently labeled genetic loci in budding yeast. In order to localize loci in the axial dimension, I used a Fourier optics approach to engineer the point spread function of the microscope into a Double-Helix Point Spread Function (DH-PSF). With this method, many single copies of a specific locus were analyzed, each with 3D spatial precision on the order of 10 nm at a rate of 10 Hz. A two-color implementation of the microscope allowed measurement of the correlations of 3D motion between pairs of loci under variable transcriptional pressure. I also discuss the importance of properly accounting for the inescapable effects of static and dynamic tracking errors caused by finite photon statistics and motion blur, respectively. These errors affect the statistics of the estimated motion and distort common metrics for characterizing stochastic motion such as the mean-squared displacement (MSD) and velocity autocorrelation (VAC). Analytical expressions for the MSD and VAC in the presence of these errors are given, along with applications to chromosomal locus tracking.
Characterization of CD90 as a Therapeutic Antibody Target on Cancer Stem Cells
Keywords: Stanford University
Stanford University Department of Biology
Stanford University School of Medicine
Institute for Stem Cell Biology and Regenerative Medicine
CD90
Thy-1
cancer stem cells
monoclonal antibody therapy
cancer immunotherapy
tumorigenesis
breast cancer
bladder cancer
xenotransplantation
Thesis

Cancer stem cells (CSCs) are essential for the growth and proliferation of some tumors, and therapies aimed at clearance of CSCs have potential as treatments, and possibly cures, of these cancers. Here we demonstrate that the cell surface antigen CD90 (Thy-1), which has been previously established as a marker of neoplastic stem cells, can be targeted by monoclonal anti-CD90 antibodies to modulate tumor growth. Anti-mouse and anti-human monoclonal CD90 antibodies were used to evaluate the potential of CD90 as a therapeutic antibody target in mouse breast, human bladder, and human breast cancers engrafted in mice. In treating transplanted mice with anti-CD90 antibodies, we found that anti-CD90 antibodies accelerated mouse breast tumor growth. Simultaneously, there was a decrease in T cell frequency when transplanted mice were treated with anti-mouse CD90 antibodies. However, bone marrow transplant and adoptive T cell transfer experiments revealed that hematopoietic cells or T cells did not mediate the increase in tumor growth. In the xenotransplantation models, we discovered that anti-CD90 antibodies inhibit growth of human bladder tumors engrafted in immunodeficient mice in a preliminary experiment, but in a second experiment, the antibodies had no significant effect on tumor growth. Anti-CD90 antibodies also had no significant effect on the growth of human breast cancer cells. These results indicate that in some tumors, antibody targeting of CD90 modulates proliferation or death of tumor cells via activating/blocking downstream CD90 signaling or affecting anti-cancer immune response. It may be possible to manipulate the CD90 signaling pathway or anti-CD90-mediated immune mechanism so as to promote or inhibit tumor growth. These findings can lead to the development of therapeutic agents that control CD90 signaling to inhibit tumor development, progression, and/or relapse.
Characterization of the INO80 Subfamily of Chromatin Remodelers in Microtubule Dynamics in S. cerevisiae
Keywords:  Department of Biology
Biology
mitosis
chromosome segregation
chromatin remodelers
INO80
SWR1
spindle assembly
microtubules
kinetochore
S. cerevisiae
Thesis

The INO80 subfamily of chromatin remodelers, which includes the complexes INO80 and SWR1, have been known to play an important role in rearranging chromatin, hydrolyzing ATP to change the structure of nucleosomes. However, recent research has suggested that these complexes may also play a role during mitosis, specifically in microtubule dynamics. Preliminary studies from our lab have shown that ino80Δ shows ploidy defects and abnormal microtubule dynamics. Furthermore, high-throughput genetic analyses have shown negative interactions for both INO80 and SWR1 with various mitotic genes of interest, further suggesting that these complexes are involved in mitosis. However, the exact mechanisms underlying INO80 and SWR1’s mitotic functions remain unknown, particularly for the latter. This study sought to elucidate the roles of both complexes during mitosis, using an integrative approach of genetics, molecular biology, and microscopy techniques to answer this question. We hypothesized that INO80 and SWR1 affect chromosome segregation by affecting microtubule dynamics. Our genetic analyses show that INO80 and SWR1 function in parallel pathways to BIM1 and BIK1, two genes critical for microtubule dynamics in S. cerevisiae. Our in vivo live-cell imaging reveals that ino80Δ mutants have short spindles and elongated cell morphology. These results suggest that INO80 is involved in stabilizing microtubules and potentially affects other components of the cytoskeleton, including actin. On the other hand, although swr1Δ mutants also show shortened spindles, they also tend to have exaggerated astral microtubules (aMTs) as opposed to ino80Δ mutants, which show fewer aMTs. This finding opens the possibility that SWR1 and INO80 have complementary but opposite roles during mitosis. Further studies conducted on domain and module mutants of INO80 revealed that the HSA and spacer domains are specifically involved in the complex’s microtubule-stabilizing activity, which also apparently requires the ATPase function of the catalytic subunit. Genetic and fitness assays of SWR1 in conjunction with various kinetochore genes (CBF1, BUB1, MCM21, and CHL4) show negative interactions between the two groups. These results suggest that SWR1 may be acting at the microtubule-kinetochore interface, helping to define a mechanism for its effect on microtubule dynamics as observed through live-cell imaging. The findings of this study provide a novel view of a subfamily of chromatin remodelers, defining a mechanistic level of understanding for their function in mitosis. Chromosome missegregation is associated with many diseases such as cancer and congenital disorders. Because proper chromosome segregation is largely dependent on microtubule dynamics, determining the INO80 subfamily’s role in this process has meaningful implications for disease treatment in the future.
Characterizing molecular interactions in polymer [electronic resource] : fullerene solar cells
Keywords: Materials Science and Engineering.

The global demand for energy is on the rise, but reliance on power production via fossil fuels has resulted in the emission and accumulation of greenhouse gases which cause global warming. Solar energy provides a clean power generation alternative, and polymer solar cells (PSCs) composed of semiconducting polymers and functionalized fullerenes provide a path to solar power production on a large scale. In this dissertation, I will discuss the mixed polymer:fullerene phase and its implications for polymer solar cell (PSC) performance. Using X-ray diffraction, NMR, and computational modeling, the crystal structure of a polymer:fullerene bimolecular crystal is determined. Using electrochemistry and photoelectron spectroscopy, I show that a strong intermolecular coupling between the polymer and fullerene exists. This intermolecular interaction has a large impact on the PSC energetic landscape which not only drives the formation of the mixed phase, but also impacts device performance. I will also discuss the physical mechanisms responsible for this intermolecular interaction, and use vibrational spectroscopy to determine which mechanism is most likely occurring. Finally, I will discuss how the polymer:fullerene intermolecular interaction impacts open circuit voltage and energetic disorder. Using this understanding of the polymer:fullerene intermolecular interaction, design guidelines are provided for future semiconducting polymers to raise PSC PCE.
Characterizing the role of the INO80 chromatin remodeler in mammalian metabolism
Keywords:  Department of Biology
Biology
chromatin remodeler
metabolism
Thesis

With today’s advances in technology, whole genomes can be sequenced in a matter of hours and the genetic basis of diseases can now be studied more closely. Even so, our understanding of disease is still incomplete without knowledge about the dynamic regulation of DNA and the consequent changes in the transcriptional profile of the cell. In the context of chromatin, the highly organized and packaged form of DNA, there are large multi-subunit protein complexes called chromatin remodelers that modulate the accessibility of DNA elements and the transcription of genes. In particular, the INO80 (inositol requiring 80) subfamily of ATP-dependent chromatin remodelers has been identified as a transcriptional regulator, and has been implicated in the regulation of cell proliferation. To further investigate the role of the INO80 chromatin remodeler in cell proliferation, RNA-sequencing was performed on INO80 yeast mutants and it was found that mitochondria related transcripts were up-regulated. Knowing that mitochondria play a significant role in metabolism and that the INO80 chromatin remodeler is also present in mammals, an in vitro mammalian model system with Ino80 knockouts was developed, and proliferation rates were studied. It was determined that there was no statistically significant difference in cellular proliferation rate between wild type and knockout cells. However, trends suggest Ino80 knockout MEFs rely more on mitochondrial function compared to wild type. Ultimately, understanding the INO80 complex’s role in cellular metabolism and cell proliferation is important to our understanding of what conditions a cell prefers to continue growth and to possibly even differentiate. This has some implications for the development of drugs that exploit the metabolic dependencies of cancer cells as a treatment option.
Charge to spin current efficiency studied by spin torque ferromagnetic resonance in various metal heterostructures [electronic resource]
Keywords: Materials Science and Engineering.

The Spin Hall effect (SHE) has been intensively studied because of its capability to generate pure spin currents and its potential application in manipulating magnetic moments. Several candidate materials have been reported to have a large spin Hall angle (SHA) through a variety of experiments. This dissertation summarizes my work on the SHE in several different heterostructures using spin torque ferromagnetic resonance (STFMR). In the first part of this work, I describe the construction of a high frequency probe system for STFMR measurement and use the technique to determine the SHA. We carefully study the interface in the SHE measurement. In most of the prior experiments, the ferromagnetic layer was attached to the candidates and used to detect the spin current intensity from the spin transfer torque. However, this introduces a new interface and causes barrier for spin diffusion. Careful study of the interface is discussed in this thesis and possible improvement of the interface is demonstrated. We use different ferromagnetic (FM) materials to measure the SHA of platinum in STFMR and prove the importance of the interface in this measurement. We derive the spin transparency of the interface from the spin diffusion model and find its relationship to spin mixing conductance, which can be extracted from FMR. In the second part of this work, Ir-Mn alloys, which are typical antiferromagnetic materials over certain compositions due to the special spin structure of Mn, are tested for SHE. Large SHA is observed in 1:1 and 1:3 for polycrystalline films and even larger SHA is observed in single crystalline IrMn3 grown on (001) MgO grown by magnetron sputtering. We observe a strong crystallographic orientation dependent SHE in IrMn3 and Ir20Mn80 films, but not in IrMn and Ir60Mn40 films.
Charge transport in semiconducting polymers [electronic resource] : connecting microstructure to electronic properties
Keywords: Materials Science and Engineering.

Organic semiconductors have emerged as an alternative to conventional silicon-based electronics in a number of large-area applications including lighting, displays, and sensors. Their ease of processing and compatibility with solution-based deposition techniques makes them attractive for low-cost, roll-to-roll production processes. However, despite significant progress in recent years, the electronic performance of these materials remains modest relative to silicon, limiting their potential applications. In order for organic semiconductors to truly flourish in industry, electronic figures of merit such as charge carrier mobility must be improved further. The material microstructure is one of the key determinants of charge carrier mobility in organic semiconductors. While many new microstructure characterization tools have been developed and our understanding of the relationship between microstructure and electronic properties has greatly improved, significant questions remain, limiting our ability to rationally design and process new materials with improved performance. The focus of this dissertation has been in attempting to improve this understanding. In this dissertation, I discuss several ways in which the microstructure of semiconducting polymers affects their electronic properties. First, I present a procedure for determining the precise thin-film structure of a semiconducting polymer using two-dimensional grazing incidence X-ray diffraction. These packing structures can then be used in a variety of electronic structure calculations. Next, I discuss the role of molecular weight distribution as well as the impact of film confinement on the microstructure and electronic properties of two semicrystalline polythiophenes. I show how disorder, crystallinity, and chain orientation are strongly influenced by these factors and quantify their impact on charge carrier mobility. Finally, I describe our latest understanding of the factors governing charge transport in state-of-the-art materials. I suggest that disorder is an inextricable feature of semiconducting polymers that need not be highly detrimental to charge transport if it is embraced and planned for by designing materials which are resilient to this disorder.
Charity Work Abroad and the Unintended Democratic Deficit
Keywords:  Program in International Relations
charity work
democratic deficit
Program in International Relations
Thesis

Ethical debates suggest that aid, overall, has contributed to a democratic deficit. This thesis explores how modes of charitable giving affect the democratic deficit created by NGO aid in developing countries. Democratic deficit is defined by shifting the dependency of local individuals, communities, and governments towards outside organizations, and in the process diminishes the need for local political systems. This thesis provides an analytical framework that will consider two different forms of aid investments--human skills and physical capital--and assess which one leads to the lesser democratic deficit at the village level. Modes of giving which lead to a lesser democratic deficit include higher levels of local interaction, local independence, and collective benefits. This thesis concludes that human skills, as a mode of charitable giving, are inherently more effective at achieving a more democratic approach than physical capital.