VictorJuiz/thesis huggingface dataset:
Elucidating the role of the PRC2 sub-unit Ezh2 during early xenopus development and investigating human placentation and pregnancy using first trimester chorionic villi

The Polycomb Repressive Complex 2 (PRC2) is of central importance to the establishment and maintenance of transcriptional silencing during development. Limited research on the role of PRC2 during early vertebrate development has produced very different, species-specific results, and recent studies have uncovered roles for the catalytic subunit, Ezh2, independent of its ability to tri-methylate lysine 27 of histone 3 (H3K27me3). In Chapter 1, I review recent findings on the role and regulation of Ezh2 in vertebrate models. In Chapter 2, I present my findings on the role of the Xenopus laevis ezh2 homolog during early development. Embryos deficient for ezh2 failed to specify the mesoderm and were unable to proceed successfully through gastrulation. The effects of ezh2 knockdown seemed to occur prior to the deposition of H3K27me3 in the Xenopus embryo, suggesting a non-canonical role of ezh2 during germ layer specification. Furthermore, deposition of H3K27me3 by the neurula stage was unaffected by depletion of ezh2. In Chapter 3, I present the findings from a collaboration between our laboratory and the Lucille Packard Children's Hospital studying placentation during the first trimester of human pregnancy. Chorionic villus sampling (CVS) is routinely used for prenatal diagnosis of cytogenetic disorders, but the potential of these samples to provide insights into the etiology of pregnancy complications like pre-eclampsia remains largely unexplored. After examining the morphology and transcriptomes of first trimester chorionic villi, we found that pre-eclampsia markers were associated with villi with low morphological complexity and identified the gene SVEP1 as a possible biomarker for determining gestational age.

Keywords: genetics) degree supervisor.
Developmental Biology.
Advisor: Fuller Margaret T.
Nusse Roel
Wysocka Joanna
Enacting environmentalism : opportunities for inclusion in environmental education programming

The sustainability crisis becomes increasingly pressing with each passing year, and, as a result, the issue of the environment becomes more prominent in daily discourse. As part of the environmental movement, environmental education has the potential to play an important part in reorienting the environmental movement. However, while environmental education can be an enormous leverage point in the environmental movements, it may not be operating effectively in reaching diverse audiences and increasing momentum toward environmental problem solving. While young people may represent the appropriate audience for fostering environmental problem solving, efforts are ineffective unless young people feel that they are able to, at least partially, identify as an environmentalist . These feelings of inclusion will help them to feel part of a movement and a community, which, in turn, will help them feel that it is worth their effort and time to think critically and creatively about sustainability solutions and to work collectively with others towards mitigation. In this dissertation, I conducted such research to suggest one way in which programming can be improved to better reach more students. By bringing in diversity, equity, and inclusion research from the field of formal education, I apply new theories to the relatively nascent diversity, equity, and inclusion research within environmental education. I also use these theories to build a model of how small moments, the connection points, are crucial to negotiating communities in which students can start to envision new identifies for themselves. I suggest ways that educators and students can bring attention to and use these connection points to build stronger communities from which students can safely explore new identities. While only one avenue of diversity, equity, and inclusion research within environmental education, it as an important one—without successful connection points, students risk being excluded from a new environmental community. This, in turn, means students cannot explore and enact new environmental identities, meaning they cannot participate fully in the environmental movements.

Keywords: Education.
Advisor: Ardoin Nicole M. (Nicole Michele) 
Brown Bryan Anthony 
Gould Rachelle 
Rosa Jonathan
Energy harvesting using CMOS image sensor pixels

The Internet of Everything (IoE) ecosystem of sensor nodes, hubs, and cloud services has grown at a rapid pace, with currently three interconnected devices for every human on earth. Powering these sensor nodes using batteries is not scalable and poses major limitations in terms of their size, cost, and accessibility. Thus, energy harvesting (EH) has been widely considered as a viable alternative for several applications. However, harvesters add their own size and cost to the sensors. To alleviate this shortcoming, the sensor is time-multiplexed to operate as an energy harvester. Specifically, this work focuses on energy harvesting using a CMOS image sensor (CIS) pixels. Many applications like tracking warehouse inventory, detecting structural faults, or detecting movements through a door require image capture at a very low frame rate. A dual-mode image sensor is well suited for such applications. The objective of this work is to demonstrate a self-powered energy harvester using CIS pixels that support the dual-mode operation. Traditional EH image sensors have used increased pixel sizes to incorporate a multiplexer in each pixel. This leads to reduced fill factor and limits its use to certain applications. Under office lighting conditions, the incident power is limited and designing an energy-autonomous system with high efficiency is challenging. The low voltage output from the pixels needs stepping up to generate the power supply rails for the imager readout circuitry. Generating two simultaneous outputs in a fully integrated solution (without using any external inductors) was the primary goal for this work. Further, the harvester needs to operate over a wide range of light intensity and loads as demanded by the application. Another challenge that must be addressed for an EH system is to enable startup without using external batteries or external components that might increase the size and weight of the solution. In this thesis, we employ conventional 4-T CIS pixels that share the mode multiplexers outside the array. In this fashion, we can harvest energy irrespective of the pixel pitch. We achieve the highest fill factor of 60.4% at a pitch of 5 µm with our EH pixels. Fully integrated switched capacitor (SC) DC/DC converters boost the pixel output to the required supply rails. An analytical framework to evaluate the effect of various parasitic capacitances and the load impedance was developed to select the topology with minimum loss. Using this approach, our chip, implemented in a 130 nm CMOS process, achieves a peak power efficiency of 52.4% at an output power of 266 nW. Our self-powered energy harvester can cold start at low light of 25 lux (comparable to a dimly lit room) and tracks light intensity variations to deliver maximum power to the output.

Keywords: Electrical Engineering.
Advisor: Murmann Boris 
Chowdhury Srabanti 
Rivas-Davila Juan
Enforcing Network Security in an Embedded Operating System via Rust’s Type System

Internet of things (IoT) devices are rapidly proliferating along with the applications that run on these devices. Oftentimes, developers write these applications without much regard for security. As a result, IoT applications often contain vulnerabilities that can compromise entire networked systems. One OS that targets this issue is Tock, which is geared toward low-power embedded devices (e.g. sensors, wearables, authentication devices). Tock is written in Rust, a type- safe systems programming language. In this paper, we discuss how we leverage the Rust type system to guarantee certain network security properties in Tock. Among these properties are (1) restricting access to network resources, (2) ensuring that only one UDP client is able to send from a particular port at any given time, and (3) the limitation of sending unencrypted data. These security mechanisms provide a low-overhead way to reduce audit space for vulnerabilities dramatically and to force the developer to explicitly express the security properties of their applications.

Keywords:  Department of Computer Science
Rust
Tock
Embedded Systems
IoT
Security
Type System
Networks
Thesis
Advisor: Levis Philip
Engagement drivers in a lending marketplace : the case of Kiva

Online crowdfunding, facilitated by platforms such as Lending Club (with over 5 billion in loans originated by early 2019) and Kickstarter (over billion in funds raised for 160,000 projects by early 2019), is an innovative application of Information Technology (IT) that uses peer-to-peer interactions to create an important channel for funding entrepreneurs, small businesses and consumers. As digitization has reduced the costs of interaction and trading in online marketplaces, crowdfunding platforms have grown dramatically over the past decade. Lending transactions alone consummated through crowdfunding reached $5.32 billion globally in 2018, funding over 26 million new loans, after facilitating $3.98 billion of borrowing in 2017. In this dissertation, we study data from Kiva, a philanthropic online crowdfunding marketplace that facilitates microcredit lending to borrowers in the developing world. Arguably the most visible new player in microfinance over the past decade, Kiva marries online technologies with the long-standing mission of microfinance to extend market access and fund availability to small entrepreneurs in the developing world. By aggregating lenders and small loans on its website, Kiva has successfully raised to date $1.3 billion in microcredit for 3.2 million borrowers, enabling microfinance institutions (MFIs) to draw upon ordinary web users as lenders. Kiva originates about $2.5 million in loans weekly. Funds are crowdsourced through Kiva's portal from web users in the developed world. This dissertation is dedicated to investigate the engagement drivers in online lending marketplaces from the lens of Kiva. In Chapter 1, we focus on the lender side of the market. In particular, we study how Kiva's lenders are influenced by rational, social and behavioral motivations and discuss how Kiva may exploit these effects when making user acquisition decisions and determining loan quality requirements. In Chapter 2, we focus on the practical problems faced by Kiva and its field partners to manage the loan requests and expedite the funding process. Utilizing the cutting-edge deep learning and natural language processing techniques, we develop a model to predict the funding speed of the loans and examine potential factors that have significant impacts the funding speed of loans. In Chapter 3, we look at Kiva as a platform from both sides of the marketplace and study network effects as an important engagement driver on Kiva. In particular, we divide Kiva's growth into two stages, a growth stage and a steady stage, and explore what role the network effects play in each stage.

Keywords: Business.
Advisor: Mendelson Haim 
Bayati Mohsen 
Weintraub Gabriel
Engineering an improved bioconjugation enzyme : a case study in yeast surface display

Enzyme engineering is a valuable tool for generating powerful and robust biocatalysts for a broad range of applications. Directed evolution using cell surface display has been previously applied for enzyme engineering, and involves iterative optimization of a protein sequence to yield a desired phenotype. However, previous applications have been carefully tailored for specific enzymes, and this process of developing a good screen is a significant bottleneck in engineering. Co-display of an enzyme and its substrate on the yeast surface is a promising general strategy for evolving bond-forming enzymes, but has only been used to engineer one enzyme. We extended yeast surface co-display to engineer Sfp, a bioconjugation enzyme, for improved activity with a non-native substrate. Sfp library screening identified mutational hotspots in the enzyme and led to the design of Sfp variants with orders of magnitude enhancements in activity. However, these activity improvements were only apparent in contexts similar to yeast surface co-display, reflecting artifacts in the use of this approach for enzyme engineering. Based on our results, we offer suggestions for improving the success of engineering strategies based on yeast surface display.

Keywords: Bioengineering.
Advisor: Cochran Jennifer R. 
Bertozzi Carolyn R.
Fordyce Polly
Engineering cell sensing and responses using a GPCR-coupled CRISPR-Cas system

Synthetic biology is changing the way we engineer living systems by providing frameworks to manage information flow and designed system complexity. Applying these concepts to engineer useful input-output devices in human cells has paved the way for engineered receptor technologies. A particular subset of these, Chimeric Antigen Receptors (CARs), are FDA approved for treat cancer. CAR therapy functions by enabling engineered T-cells to sense a surface marker (or cue) on cancer and convert that into an anti-tumoral program. Yet, this technology cannot interpret soluble markers that can be hallmarks of the disease, especially those from G-protein coupled receptor (GPCR) signaling systems. The CAR technology also cannot execute arbitrary gene programs to modulate either tumor cell behavior, or host T cell behavior. In this thesis, to bridge these technological gaps, I develop a new molecular input-output device, CRISPR-ChaCha. The technology leverages the ligand sensing diversity of GPCRs with the genome targeting flexibility of CRISPR-Cas systems. I first determine a functional architecture to fuse GPCR signaling proteins and CRISPR-Cas activators. I then show that the CRISPR ChaCha is dose-dependent, reversible, and can activate multiple endogenous genes simultaneously in response to extracellular ligands. The system displays a high degree of modularity, which is the ability to swap components and maintain function. I adopt this modular design to diverse GPCRs that sense a broad spectrum of ligands and to function with an additional CRISPR-Cas protein. I also make perturbations to device function to derive CRISPR-ChaCha design rules, to later build next generation devices with little optimization required. We hope that this flexible input-output device can be used for "smart" therapeutics, and rational engineering of cellular behavior.

Keywords: Bioengineering.
Advisor: Qi Lei (Professor of Bioengineering) 
Cochran Jennifer R. 
Kobilka Brian K.
Engineering devices for efficient and stable photoelectrochemical water splitting

Solar water splitting using photoelectrochemical cells (PEC's) is a promising pathway toward clean and sustainable storage of renewable energy. However, developing a PEC device that is efficient, durable, and also scalable has been a huge challenge so far. This dissertation addresses these challenges by developing photocathodes based on inexpensive absorber materials such as germanium and silicon. In particular, efficient silicon heterojunction solar cells are studied in order to stabilize them under corrosive hydrogen evolution environments while maintaining their excellent photovoltaic performance using TiO2 protection layers deposited using atomic layer deposition. High activity oxygen evolution electrocatalysts are also fabricated on porous substrate materials in order to minimize the overpotential required. Finally, we combine the photocathode and the anode in a novel integrated solar water splitting architecture, and demonstrate a solar-to-hydrogen (STH) efficiency in excess of 10%, a record high STH efficiency for an integrated silicon photosynthesis device, and stable operation for > 120 hours.

Keywords: Materials Science and Engineering.
Advisor: McIntyre Paul Cameron 
Chidsey Christopher E. D. (Christopher Elisha Dunn)
Triplett Baylor
Engineering the nervous system

During differentiation of a totipotent zygote to multipotent progenitors and later to fully differentiation cells, morphogen gradients; and consequently, differential transcription factor expressions play important roles in directing the fates of different progenitor cells down the Waddington epigenetic slope into terminally differentiated cell types. It was later discovered that forced expression of some of those lineage-specifying transcription factors can be used to convert terminally differentiated cells to regain pluripotency or to other mature committed cell types. These discoveries open up a new avenue for the use of those cells for therapy or drug screening. Despite these novel discoveries, there are still concerns regarding the efficiency of direct conversion process and the identity of those converted cells. In this thesis, I will describe the background of induced neuronal cells, the functions of Ascl1 in induced neuronal reprogramming, a novel protocol to convert a readily available cell type into induced neuronal cells and the application of induced neuronal cells in disease modelling.

Keywords: Bioengineering.
Advisor: Wernig Marius 
Bintu Lacramioara 
Chang Howard Y. (Howard Yuan-Hao)
Engineering virus-like particles for targeted delivery of anti-cancer drugs

Targeted anti-cancer drug delivery is important both to improve the drug efficacy at the tumor site and to reduce side effects. For this purpose, virus-like particles (VLPs) offer several potential advantages. VLPs are non-infectious and self-assembled nanoparticles derived from viral capsids. Compared to traditional antibody-drug conjugates, they have the potential to provide a better delivery system by encapsulating a high number of drugs, while protecting the drugs from the surrounding environment before reaching to the cancer cell. The Swartz Lab has been developing Hepatitis B core (HepBc) VLPs to have high stability during manufacture and storage, and to present a non-immunogenic surface that can be easily modified with multiple ligands. The HepBc VLPs were further engineered to load and retain > 300 anti-cancer drugs per particle. Taking advantage of the previous developments in bioconjugation, multiple ligands have been attached to the surface of the VLPs for immune system avoidance and specific targeting. First, displaying the CD47 extracellular domain, or endogenous "marker of self", avoids immune clearance by phagocytes. Second, displaying a DNA aptamer specific to prostate-specific membrane antigen (PSMA) allows the VLPs to specifically target PSMA+ prostate cancer cells, our model disease target. This triggers internalization of the VLPs into the cells where the VLPs will open to release their cytotoxic cargo. Compared to the systemic administration of anti-cancer drugs, this VLP-based delivery vehicle will greatly increase drug efficacy while reducing side effects. Taken together, this will dramatically increase the patient's survival as well as quality of life.

Keywords: Bioengineering.
Advisor: Swartz James R. 
Dunn Alexander Robert 
Kim Peter
Entangled archaeology, industry, and labor in El Tajín, Mexico, 1880-2018

In this dissertation, I analyze the indigenous histories silenced in the creation of a bounded and delimited archaeological site from a landscape of pre-Hispanic mounds. I center these questions on the Epiclassic (c. 350-1200 CE) urban center of El Tajín, Mexico. Using a community-grounded counter-mapping methodology, I explore three historical processes relevant to the area's Totonac residents that nevertheless remain undercovered in the literature: transformations in land use, changes in vanilla cultivation, and the effects of oil exploration. I further argue that these three processes constituted the modern archaeological site. In this analysis, government land surveyors, vanilla merchants, and foreign oil companies play foundational roles in the archaeological work of delimiting, managing, guarding, and reconstructing the pre-Hispanic past. Shifting my focus to the present, I then take an ethnographic approach to the archaeological site as a workplace. While the site's managers may have epistemological authority over the interpretation of the past, I take a political-economic focus that reveals that their ability to manage the site is limited by precarious working conditions. Meanwhile, the site's Totonac guards are more often able to carry out their political objectives, thanks to their long histories of labor at the site and organization as a union. For heritage ethnography, my research demonstrates the importance of engaging archaeology and archaeologists as interlocutors, rather than just discourses and subject-positions to be criticized. For archaeologists interested in the politics of the discipline, my dissertation argues for a broadly political-economic focus complimenting current emphases on identity and representation.

Keywords: Anthropology.
Advisor: Meskell Lynn 
Hodder Ian 
Inoue Miyako
Joyce Rosemary A.
Enteric pathogens : measurement, metrics, and mitigation

Enteric pathogens, long acknowledged for their role in diarrheal disease, are increasingly recognized as important factors in child growth and development, even when detected in subclinical quantities. Polymicrobial pathogen carriage is common in low- and middle-income countries, frequently occurring without diarrheal symptoms. Comprehensive enteric pathogen panels are cost-prohibitive, and thus infrequently used in large population-based studies. However, these studies are necessary to evaluate the complex interactions between asymptomatic pathogen carriage and long-term outcomes such a growth and development. Furthermore, Koch's postulates, implying a single etiologic agent for a disease, discount the synergistic potential of enteric pathogens to disrupt host gut physiology and upset microbial ecological niches. Information on both the presence and quantity of known pathogens is important for understanding these complex systems; but the current analytical methods for assessing polymicrobal infection fail to integrate the quantitative data afforded by modern molecular techniques. Finally, quantitative enteropathogen measures are needed to assess the efficacy of low-cost water, sanitation, and handwashing interventions to reduce pathogen transmission and exposure in low-income countries, in lieu of the caregiver reported diarrhea outcomes commonly used. To address these gaps, the work that comprises this dissertation offers a lower-cost measurement option, provides a metric for composite pathogen assessment, and evaluates the potential for low-cost interventions to mitigate enteric pathogen carriage for children in rural Bangladesh. Chapter 2 describes the design and evaluation of a novel nano-liter qPCR chip that detects 17 intestinal pathogens for a quarter of the cost and 12x higher throughput than the leading technology, allowing for pathogen panels to be used in large-scale epidemiological studies. In Chapter 3, I developed a new enteric pathogen composite metric - a single endpoint that incorporates quantitative data across multiple intestinal pathogens - as a measure of total pathogen load within the gut. I show that this metric is associated with symptomatic diarrheal disease, child growth, and subsequent cognitive development. Finally, Chapter 4 evaluated the potential of low-cost water, sanitation, handwashing (WSH) and nutritional interventions to mitigate enteric pathogen carriage in a cohort of 1411 children 14 months old from a randomized controlled trial in rural Bangladesh. I found that WSH interventions reduce the burden of enteric viruses for children, but do not substantially reduce bacterial or parasitic pathogens - the pathogens that have displayed the strongest associations with child growth deficits in observational studies. My work offers new means of measuring and evaluating panels of multiple enteric pathogens and provides insights for directing the efforts of the WSH field toward interventions that mitigate bacterial and parasitic enteropathogens.

Advisor: Spormann Alfred M. 
Criddle Craig 
Holmes Susan
Luby Stephen