VictorJuiz/thesis huggingface dataset:
A developmental roadmap for the diversification of human tissue fates from pluripotent cells [electronic resource]
Keywords: Developmental Biology.

One aspiration of regenerative medicine has been to produce pure populations of human tissue progenitors from differentiating pluripotent stem cells, potentially providing limitless tissues for patients-in-need. Yet, the developmental process through which pluripotent cells become diversified into a broad array of human tissue progenitors in vivo remains poorly ambiguous. Consequently in vitro stem-cell differentiation often generates an impure mixture of cell-types poorly suited for therapeutic purposes. To more accurately guide stem-cell differentiation, I have systematically mapped the pairwise lineage choices through which pluripotent cells become diversified into a broad array of derivatives belonging to the human endoderm germ layer (which gives rise to lungs, liver, pancreas, intestines and so forth) and mesoderm germ layer (which yields bone, heart and blood amongst other cell-types). At each binary lineage choice, I determined the signals that drove cells to one fate or the other. By providing the inductive signals to steer stem cells towards one lineage while inhibiting the repressive signals that instead instructed alternate fates, I could "force" pluripotent stem cells to differentiate into a pure population of a single cell-type at each lineage juncture. This approach of logically guiding stem-cell differentiation by inhibiting alternate lineage choices yielded highly pure populations of transplantable human liver progenitors, bone progenitors and heart progenitors that could each engraft in vivo in respective animal models, providing the starting point for future cell replacement therapy. Moreover by profiling transcriptional and chromatin changes between purified populations of different human endoderm and mesoderm progenitors, I defined stepwise changes in gene expression and revealed opening and closing of chromatin elements at each developmental step. Collectively, I have reconstituted aspects of human development in culture, providing a versatile platform to produce purified populations of tissue progenitors for regenerative medicine, to systematically identify the positive and negative signals that guide cell-fate choice at each lineage transition, and to understand the molecular underpinnings of human development. Akin to the relationship of biochemistry to genetics, the ability to synthetically reconstitute a process in a reductionist system demonstrates a causal understanding of how the process naturally works, and these are the goals of pluripotent stem cell differentiation as pertains to developmental biology; to artificially reconstitute complex developmental processes in a dish, to causally understand development at increasingly-higher resolution; and ultimately to achieve precise control over stem-cell differentiation to realize a new era of regenerative medicine.
Device application of metafilms and metasurfaces [electronic resource]
Keywords: Electrical Engineering.

The phase reversal that occurs when light reflects from a metallic mirror produces a standing wave profile that features a reduced light intensity and thus light-matter interaction near its surface. This is highly undesirable in optoelectronic devices that employ metal films as electrical contacts and optical mirrors; it dictates a minimum spacing between the metal and active semi-conductor layers in a device and poses a fundamental limit to their practical thickness. In this thesis, we illustrate how a metamaterial-mirror can be created in the visible spectral range whose reflection phase is tunable from that of a perfect electric mirror to a perfect magnetic mirror . We then demonstrate the benefits of implementing such a mirror in two real device. Specifically, we show how light absorption and photocurrent generation in a sub-100-nm active semiconductor layer can substantially be enhanced over a broad spectral band. Based on the reciprocity principle for light waves, metamaterial mirrors are expected to also enable more effective light extraction from thin light emitting devices. High-performance light-emitting diodes (LEDs) rely on high sheet- conductivity metallic contacts to facilitate effective charge injection. Unfortunately, such contacts also support surface plasmon polariton (SPP) excitations that guide and ultimately dissipate optical energy in the metal. The coupling of quantum emitters to SPPs constitutes one of the key loss processes that limit the external quantum efficiencies of LEDs. In this thesis, we also illustrate how high-impedance metamaterial-electrodes can be created that do not support propagating SPPs on their surfaces. These superior electrodes greatly suppress dissipative losses while providing a desirable Lambertian emission profile. Our claims are verified by studying the emission enhancement and photoluminescence lifetime changes for a 15 nm thick Rhodamine 6G dye emitter placed on metamaterial electrodes.
Diet-driven shifts of the microbiome reveal taxa vulnerable to extinction in industrialized populations [electronic resource]
Keywords: Microbiology and Immunology.

The human gut microbiota is a complex ecosystem consisting of trillions of members that closely interface with their host. Maintenance of this association predates our existence as a species and over time has formed a complex co-evolutionary relationship, yet recent asymmetrical changes such as the major shift to a low fiber diet in the process of modernization are affecting this human-microbiota relationship. The reduction in microbiota accessible carbohydrates (MACs), complex dietary fibers that serve as the primary fuel for gut-resident microbes, coincides with the decreased diversity in species observed in the Western microbiota. While the impact on human biology of the this recent disruption to long-standing microbial relationships remains to be studied in detail, current data suggest a potential contribution to Western diseases driven by a heightened inflammatory state. An introduction to the microbiota and the key works upon which this study is founded is provided in Chapter 1. The work in Chapter 2 evaluates the compositional changes that coincides with low-MAC diets, the transfer of those microbial members across generations and interventions that can reverse diet-induced species-loss. Chapter 3 reports the effect of defined MAC substrates on multiple human donors both at compositional and functional levels. In Chapter 4 the findings from the previous chapters are applied to identify features of modernization using fecal samples from a rapidly disappearing hunter-gatherer population in Tanzania. Finally, Chapter 5 summarizes the findings of this study in a proposed model of modernization and concludes with a discussion of future directions.
Differential calculus on graphon space and statistical applications of graph limit theory [electronic resource]
Keywords: Mathematics.

In this thesis, we build on the beautiful work on dense graph limit theory in two directions. In the first, we develop a framework for differential calculus on the space of graph limits. In the process, we discover a structure theory for differentiable graphon parameters and find that homomorphism densities can be used to expand such parameters in Taylor series. The methods developed are novel, robust and can be generalized. In the second, we use dense graph limit theory to provide a new framework for the study of stability of graph partitioning methods. By formulating statistical consistency as a continuity result on the graphon space, we obtain robust consistency results independent of needing to assume a specific form of the data generating mechanism. We derive the consistency of commonly used clustering algorithms such as clustering based on local graph statistics as well as spectral clustering using the normalized Laplacian. In the final chapter, we indicate how this work can lead to the discovery of new necessary mathematical abstractions to serve as foundations for modern data analysis in areas such as network science or machine learning.
Differential expression of MHC class II molecules provides insight into the role of human monocyte subsets
Keywords:  Department of Biology
Biology
Immunology
Monocytes
MHC Class II
Thesis

Monocytes circulate the bloodstream and are important to the immune system because they differentiate into macrophages and dendritic cells. Traditionally, monocytes were identified as two populations using CD14 and CD16 surface markers: classical monocytes are CD14+ and nonclassical monocytes are CD16+. However, a third intermediate monocyte has been described and these intermediate monocytes express both CD14+ and CD16+. The role of these intermediate monocytes is not well known, but the expression of HLA-DR, an MHC class II molecule, is known to be highest in the intermediate monocytes. To further understand the role of these intermediate monocytes, flow cytometry was used to look at the expression of HLA-DM and HLA-DP at the protein level across the different monocyte subsets. HLA-DM and HLA-DP were most highly expressed by the intermediate monocytes, suggesting they can load foreign antigen peptide onto class II molecules the most. To learn more about the differential antigen presentation capacity across the monocyte subsets, surface CLIP, a placeholder peptide in the binding groove of HLA class II molecules, was analyzed. Ratios of CLIP/DR were determined because they show how much CLIP makes it to the surface of the cell on the class II molecule without being replaced by foreign antigen peptides, a function performed by HLA-DM. The intermediate monocytes showed the lowest CLIP/DR ratios as expected, further showing that the intermediate monocytes possess the strongest antigen presentation capacity amongst the monocytes. Additionally, an antibody known to bind against HLA-DR1/CLIP, HLA-DR3/CLIP, and HLA-DR4/CLIP complexes (14-23) was used to calculate 14-23/DR ratios to provide more specific functional information about CLIP accumulation on the cell surface. The 14-23/DR ratios were calculated and found to be the lowest in the intermediate monocytes, which correlates with our finding of high expression of HLA-DM in the intermediate monocytes. Overall, our data support the accumulating evidence that human intermediate monocytes possess the highest antigen presentation capacity through elevated expression of class II pathway molecules. This information is vital in helping determine the role of intermediate monocytes, which are implicated in many diseases, including rheumatoid arthritis, coronary artery disease, and HIV.
Differential optical shadow sensor for drag-free satellites [electronic resource]
Keywords: Mechanical Engineering.

The basic idea of a drag-free satellite is to shield a free floating test mass inside a satellite from all forces other than gravity. This puts the test mass into a geodesic orbit. A control system ensures that the satellite closely follows the test mass, thus putting the entire satellite into a geodesic orbit Drag-free satellites have a long history since the first such satellite was launched in 1972. The mission scenarios in which drag-free satellites have been used range from navigation to geodesy to fundamental physics. There are plans for future missions using drag-free technology, mainly for geodesy and fundamental physics applications. This led to the development of a new gravitational reference sensor at Stanford, the Modular Gravitational Reference Sensor (MGRS). One of the building blocks of the MGRS is the Differential Optical Shadow Sensor (DOSS), a sensor to precisely measure the displacement of the free floating test mass inside the satellite. This thesis describes the experimental design and results of the DOSS in its current form as a laboratory experiment that meets and exceeds the requirements for the MGRS mission. The Differential Optical Shadow Sensor has a sensitivity of better than 1 nm/rtHz above 1 Hz and 10 nm/rtHz above 100 mHz. The sensor enables a drag-free satellite mission on a small satellite (100 kg class) with a state of the art drag-free performance of 1e-12 m/s^2/rtHz. Previous design iterations of the DOSS, mainly designed for the CubeSat Standard, are listed in the appendix.
Digital Technology Use at Çatalhöyük: Social experiences and the digital workflow in archaeology
Keywords:  Department of Anthropology
archaeology
anthropology
technology
Thesis

There is an increasing trend in archaeological methodology towards incorporating digital technologies, both hardware and software, into excavation and data processing. Such is the case at Çatalhöyük, a Neolithic period archaeological site located in South-central Turkey. The current Çatalhöyük Project has been under excavation by site director Ian Hodder and a group of international archaeologists since 1993. Throughout the project’s excavation history, more and more digital technologies have been integrated into the excavation and data processing activities on site. For the purposes of this paper, I specifically examine the digital technologies used by most excavation/research teams at the site: tablet PCs (specifically, Microsoft Surface tablet PCs), the computer application ArcGIS, the site’s Microsoft Access database, and 3D and digital photography techniques.
Digital technologies at Çatalhöyük are typically discussed in terms of their ability to foster project goals of reflexivity, the breaking down of traditional site hierarchies and divisions of knowledge in archaeology, and multivocality, the acknowledgement and facilitation of input from the many stakeholder groups of an archaeological excavation. This paper examines the social and academic impact of digital technology use at Çatalhöyük in an attempt to discover the extent to which digital technologies can intervene in academic and social processes on site. In particular, I examine the relationship between the reflexive and multivocal capabilities of the digital technologies used at Çatalhöyük, and the ways in which these capabilities have been successfully and unsuccessfully applied to pre-digital workflows at the site.
Direct numerical simulation of electroconvective chaos near an ion-selective membrane [electronic resource]
Keywords: Mechanical Engineering.

Electrokinetic transport plays an essential role in mature industrial applications and emerging technology such as: electrochemical devices, microfluidic chips, and electrodialysis used for water purification and chemical production. These systems use ion-selective surfaces and applied electric fields to manipulate aqueous electrolytes. In this dissertation we investigate a model system comprised of an ion-selective surface and a liquid electrolyte subject to an applied electric field. The applied field creates steep gradients in concentration and charge density which lead to an electrohydrodynamic instability referred to as electroconvection. At voltages of O(1)V, this instability can lead to chaotic dynamics. We investigate the onset of the instability and transport in the chaotic regime by formulating a specialized parallel numerical algorithm to solve the coupled Poisson-Nernst-Planck and Navier-Stokes equations. We developed a direct numerical simulation code called EKaos that can simulate chaotic electrokinetic phenomena in three dimensions with high resolution. The EKaos code was developed using numerical algorithms designed to efficiently solve the governing equations on parallel platforms. The equations are spatially discretized using a second order central finite difference scheme on a structured, staggered mesh. Time integration is performed with a specialised iterative procedure that uses physical and analytical insights to develop discrete operators that are easily invertible and converge quickly to second order temporal accuracy. EKaos efficiently solves 2D and 3D systems using non-dissipative algorithms that capture the high wavenumber physics critical to accurately simulating chaotic phenomena. 2D and 3D simulations from EKaos reveal interesting similarities between electroconvective chaos and turbulent flows such as: energy spectra with a wide range of spatiotemporal scales, vortices that interact with each other in an irregular manner, and substantial enhancement of transport and mixing. Quantitative analysis of statistics shows that although 2D and 3D simulations of electroconvective chaos are qualitatively very similar, inclusion of the third dimension is important for the prediction of mean quantities such as concentration, charge density, and current density. We assess the impact of electroconvection on the mean current density and appearance of instantaneous high current density hotspots on the membrane surface. Finally, we introduce ensemble averaged equations and discuss the relative importance of closed and unclosed terms for reduced order modeling.
Discovering the QCD axion with black holes and gravitational waves [electronic resource]
Keywords: Physics.

Advanced LIGO is the first experiment to detect gravitational waves. Through su- perradiance of stellar black holes, it may also be the first experiment to discover the QCD axion with decay constant above the GUT scale. When an axion's Comp- ton wavelength is comparable to the size of a black hole, the axion binds to the black hole, forming a "gravitational atom." Through the superradiance process, the number of axions occupying the bound levels grows exponentially, extracting energy and angular momentum from the black hole. Axions transitioning between levels of the gravitational atom and axions annihilating to gravitons can produce observable gravitational wave signals. The signals are long-lasting, monochromatic, and can be distinguished from ordinary astrophysical sources. We estimate up to O(1) transition events at aLIGO for an axion between 10^−11 and 10^−10 eV and up to 10^4 annihila- tion events for an axion between 10^−13 and 10^−11 eV. In the event of a null search, aLIGO can constrain the axion mass for a range of rapidly spinning black hole formation rates. Axion annihilations are also promising for much lighter masses at future lower-frequency gravitational wave observatories; the rates have large uncertainties, dominated by supermassive black hole spin distributions. Our projections for aLIGO are robust against perturbations from the black hole environment and account for our updated exclusion on the QCD axion of 6 × 10^−13 eV < μa < 2 × 10^−11 eV suggested by stellar black hole spin measurements.
Discovery of FeFe hydrogenase variants with enhanced O2 tolerance [electronic resource]
Keywords: Chemical Engineering.

Hydrogenases catalyze the reversible formation of H2 from two protons and two electrons. They are classified as [FeFe], [NiFe], or [Fe]-only with respect to the metal atoms included in the active site. Among the three, [FeFe] hydrogenases have a catalytic bias toward H2 formation. The most prolific enzymes require overpotentials lower than that for platinum, one of the best metal catalysts reported to date. Consequently, [FeFe] hydrogenases offer significant potential for biological production of H2. We have approached such applications with a particular focus on the [FeFe] hydrogenase from Clostridium pasteurianum (CpI). It is a 63.8 kDa protein with one of the highest reported H2 production-specific activities in the order of 1,500 s-1 (or an order of magnitude higher when coupled with an electrode). However, it is also a complex enzyme with three accessory [4Fe-4S] clusters and one [2Fe-2S] cluster that deliver electrons to or from the active site consisting of an [FeFe] sub-cluster bridged to a [4Fe-4S] cluster by a cysteinyl thiol. Much work has been done during the past decade to enable the heterologous expression, maturation, and purification of the active form of CpI in Escherichia coli. Based on these advances, we are now working on two distinct routes of biological H2 production using this enzyme: Fermentative and photosynthetic. Unfortunately, [FeFe] hydrogenases are highly sensitive to O2, imposing a significant technical barrier for biological H2 production. The half-life of CpI in air-saturated buffer is estimated to be only 2--3 min. We worked on three projects to overcome this limitation with the end goal of engineering more O2-tolerant CpI variants. We first developed physiological assays for characterizing the O2 sensitivity of [FeFe] hydrogenases. Next, we developed a highthroughput screening platform for measuring H2 production rates in a biochemical context, including these assays. Empowered by the results of these projects, we evaluated over 300 CpI mutants and discovered several mutations that significantly impact the O2 tolerance of the enzyme. The best combination of mutations enabled greater than 4-fold improvement in aerobic (5.0 vol% O2) H2 yield over an hour. Our work provide the tools that allow convenient assessment of the O2 tolerance of [FeFe] hydrogenases and engineered mutants. The throughput has been improved by more than 10-fold. More importantly, we showed the first successful case of engineering [FeFe] hydrogenases with higher O2 tolerance, further promoting the research towards biological production of H2 for use as a renewable fuel and chemical.
Disk resonator gyroscope within a wafer-scale encapsulation process [electronic resource]
Keywords: Mechanical Engineering.

Recently, MEMS gyroscopes have been widely adopted into consumer devices thanks to their small size, low cost, and efficient power consumption. In particular, wine- glass mode MEMS gyroscopes have received attention because of their potential to enter into high-performance applications such as gyro-compassing, spacecraft navigation, and dead-reckoning. In this dissertation, we present the development of Disk Resonator Gyroscopes (DRG) within a wafer-scale encapsulation process. First, we describe the fundamental principles of wineglass mode MEMS gyro- scopes, design of the DRG, its fabrication platform, and the different material choices for the device. The wafer-scale encapsulation used in this work, known as epi-seal, has been proven to be a highly stable, robust MEMS fabrication process. Disk-shaped resonator design implemented in epi-seal shows a high quality factor (Q) in excess of 100,000 at the resonant frequency of 250kHz; this high Q, along with the ability to minimize frequency splits via different material choices, drastically improves the scale factor of the DRG. Next, we discuss the implementation of the rate measurement demodulation technique with the DRG. The rate measurement reveals an angle random walk (ARW) of 0.1 ̊/√hr and a bias instability of ~1 ̊/hr. These noise specifications are compatible with low-end tactical grade gyroscopes, which are currently dominated by fiber-optics gyroscopes (FOG) and ring-laser gyroscopes (RLG). In addition, parametric amplification effects are discussed in further improving the performance of the DRG. Furthermore, we demonstrate improvements in stability of the scale factor and bias output with single-chip ovenization (micro-oven) of a fully-encapsulated DRG. During temperature-controlled operation, the scale factor stability holds to less than 0.3% and the bias remains less than 0.2 ̊/s, allowing for stable operation over a wide operating temperature range (0-80 ̊C).