VictorJuiz/thesis huggingface dataset:
Designing Sketch and Learn: Creating a Playful Sketching Experience that Helps Learners Build a Practice Toward Visual Notetaking (aka Sketchnotes)
Keywords: sketchnotes notetaking learning design technology stanford education
Thesis

Notetaking is an important practice in classrooms around the world and is useful for capturing information and forming connections between large amounts of information and ideas. However, traditional notetaking methods tend to follow a linear structure, and students are often trained to capture information in a verbose text-based format. Visual notetaking, also known as sketchnoting, is an under-recognized strategy that can enhance the practice of notetaking. Sketchnoting taps into both the verbal and visual processes of decoding and encoding information, allowing learners to use a combination of words and images to make meaning from verbal or text-based information. Not only do studies show the potential benefits of sketchnoting, educators who have taught sketchnotes in their classrooms have also reported that it opened up opportunities for minority students such as neurodiverse individuals and language learners, providing them with another means of expressing their ideas and showing their understanding of content.
To facilitate the learning of sketchnotes, we designed Sketch & Learn, a web-based game that engages learners in playful sketching quests that help them build a visual library and a dedicated practice toward sketchnoting. Drawing insights from learning theories on scaffolding, game design, and best practices from educators, Sketch & Learn uses a relevant narrative and short challenges to recruit interest from novice learners and support long-term engagement. Pedagogically, we used gameplay to establish a playful low-stakes learning environment and used worked examples to ease learners into sketchnoting.
Preliminary testing results showed that the narrative and quests sparked interest, promoted engagement from users, and elicited learning gain. Users expressed interest in further engagement, and a digital version of the visual library feature. With promising results from our design concept, we are one step closer to our mission to equip learners with tools that help them take control of the information around them, form connections, express ideas, and make their learning visible.
Detection & degradation of stalled nascent chains by ribosome-associated quality control
Keywords: Biochemistry.

Cells invest an enormous portion of their resources into translation. This task involves tight coordination between hundreds of macromolecules, enabling the ribosome to decode mRNA and produce mRNA-encoded polypeptides. Complications during the translation cycle can cause translation to fail, leaving a potentially defective nascent polypeptide chain attached to a stalled ribosome. Organisms across all clades of life have evolved responses to detect these stalled ribosomes and degrade their associated nascent chains. I introduce the eukaryotic response, called "Ribosome-associated quality control" or RQC, in Chapter 1. Ribosomes can stall due to stochastic processes such as mRNA damage, so cells need to degrade any stalled nascent chain regardless of its identity. Two facets of RQC enable cells to meet this challenge. First, RQC initiates by recognizing a stereotyped state of stalled ribosomes rather than their attached nascent chains, which may vary in their properties. In Chapter 2, I discuss a pathway that detects stalled ribosomes and commits them to RQC. Second, RQC utilizes a non-templated form of protein synthesis (called "CATylation") to widen the spectrum of stalled nascent chains that RQC can degrade. Chapter 3 describes how CATylation enables RQC to degrade structured nascent chains as well as those that detach from the ribosome. In Chapter 4, I discuss how CATylation can also harm cells by forming aggregates. These aggregates exert proteotoxic stress and corrupt the function of CATylation as a degradation enhancer. While the complete picture of RQC is not yet in view, the work in this thesis illuminates key strategies that cells employ to degrade stalled nascent chains.
Developing angular intensity correlations of X-ray photons as a tool for studying structures of proteins in non-crystalline solutions
Keywords: Physics.

This dissertation offers lessons learned and tools developed as we attempt to apply correlated X-ray scattering (CXS) to non-crystalline proteins in solution. It builds on our previous work of extracting correlation signals from scattering intensities of ensembles of mental nanoparticles, which has led to three-dimensional (3D) structural insights not reflected in azimuthally averaged measurements. In his 1977 paper, Zvi Kam proposed the idea of correlating X-ray photons scattered by an ensemble of randomly oriented particles suspended in solution. He found that if the exposure time is much shorter than the diffusion timescale of Brownian motion, correlations between photons scattered into different angles encode 3D structural information of the particles not accessible via conventional small or wide-angle X-ray scattering. The advent of the X-ray free electron laser (XFEL) renders Kam's idea feasible for non-crystalline solutions of proteins. With femtosecond pulses and extremely high fluences, the XFEL is not only capable of probing ensembles of molecules essentially frozen in time but also delivering a large number of photons per pulse, a capability critical for enhancing angular intensity correlation signals. Meanwhile, probing proteins in solution removes the need for crystallization, allows measurements of mixtures of conformational states under physiological conditions, and broadens opportunities for time-resolved experiments. The body of work in this dissertation draws from scattering data collected with samples containing the G-protein Gi alpha subunit during two separate beam times conducted at the Linac Coherent Light Source. The Gi alpha subunit was chosen for these proof-of-principle experiments because of its important role in the G-protein coupled receptor signaling pathway. This dissertation has taken the first steps in developing and validating CXS as a tool for probing ensembles of biomolecules in solution. These first steps as well as ideas described in this dissertation to improve CXS towards a mature pipeline that yields reliable and detailed structural insights aim to inspire others in the solution scattering community to engage with the unique challenges and rewards of this technique.
Developing new expression parts and biosynthetic pathways for yeast synthetic biology
Keywords: Bioengineering.

Baker's yeast (Saccharomyces cerevisiae) has been used in bioproduction for millenia. Current efforts in synthetic biology seek to further extend yeast's capabilities, enabling applications such as producing useful and valuable plant natural products in a cheaper and less resource-intensive manner than current methods, which rely on cultivation of the native producer plants. This dissertation opens with a review (Chapter 1) of current synthetic biology strategies for producing plant natural products in heterologous hosts: model plants, bacteria, and yeast. As a case study of heterologous phytochemical production, we describe a functional reconstitution of the dhurrin pathway from sorghum (Sorghum bicolor) in yeast (Chapter 2). We produced this plant defense compound at titers of over 80 mg/L, and demonstrated a workflow using our dhurrin-producing strain to explore the activities of other S. bicolor genes. Further, we developed a method for model-driven generation of artificial yeast promoters (Chapter 3). Promoters - DNA sequences that appear 5' to genes and modulate their expression - play a central role in controlling gene regulation; however, a small set of native promoters is used for most genetic construct design in S. cerevisiae, limiting engineers' ability to control gene expression in this organism. The ability to generate and utilize models that accurately predict protein expression from promoter sequence may enable rapid generation of novel useful promoters, facilitating synthetic biology efforts in yeast. We measured the activity of over 675,000 unique sequences in a constitutive promoter library, and over 327,000 sequences in a library of inducible promoters. Training an ensemble of convolutional neural networks jointly on the two datasets enabled very high predictive accuracies on multiple prediction tasks. We developed model-guided design strategies which yielded large, sequence-diverse sets of novel promoters exhibiting activities similar to current best-in-class sequences. In addition to providing large sets of new promoters, our results show the value of model-guided design as an approach for generating DNA parts. The final chapter discusses the outlook for the field and possible extensions to the work presented here (Chapter 4). Taken together, our work shows the value of yeast as a heterologous host for producing plant natural products, and offers a means to develop novel genetic parts to further expand its usefulness.
Development of a high-resolution fluorescent reporter system for clonal analysis
Keywords:  Department of Biology
Biology
Developmental Biology
Stem Cell
Lineage Tracing
Clonal Analysis
Fluorescent Protein
GFP
Thesis

Lineage tracing techniques, which track cells and their progeny through development, are an essential tool to identify stem cells and characterize their regenerative capacities. The past decade has seen the emergence of lineage tracing tools that use 3-4 fluorescent proteins as labels. Such tools have been widely employed to characterize the regenerative capacity of mouse organs, including the brain, kidney, and liver. However, the small number of labels they employ limit their use in settings that exhibit cell migration, like early embryonic development, where the movement of cells makes it difficult to resolve whether certain cells share the same lineage. For the lineage tracing of these systems, a tool with a higher resolution is required.
This study demonstrates that multiple fluorescent labels can be used to mark a single cell by localizing fluorescent proteins to different cellular compartments. We then used these localized proteins to design a high-resolution reporter system that achieves 25 discernible labels by confocal microscopy. We derived and plan to validate a mouse line and mouse embryonic stem cell line that stably express the construct which we hope will be widely used for lineage tracing studies in the future.
Development of a modular virus-like particle vaccine platform
Keywords: Chemical Engineering.

Well-designed prophylaxis is always preferable to therapeutic treatment of a disease, and vaccines are second only to sanitation and clean drinking water in promoting global health. Despite their success, current vaccination strategies do not provide broad access to vaccines in the developing world largely due to the expense and cold-chain requirements. Finally, current development and production methods are poorly equipped to respond rapidly to emerging or altered pathogens. This thesis describes the use of the Swartz Lab engineered Hepatitis B core (HepBc) virus-like particle (VLP), a protein-based nanoparticle, as a vaccine platform which overcomes the concerns with current vaccines. Because of the T4 icosahedral assembly of the HepBc dimers, the engineered HepBc VLP scaffold provides 120 sites for the multivalent display of the relevant antigen in a manner that mimics presentation on the natural virus. Here we discuss the development of three antigens to be used in different vaccine candidates based on the HepBc VLP. The first antigen is derived from the Zika virus Protein E, Domain III. This antigen is difficult to produce using traditional protein production methods, but the flexibility of cell-free protein synthesis allows it to be produced with high yields and appropriate folding. The second antigen is derived from the Influenza virus Hemagglutinin Stem and has proven to require extensive protein engineering expertise to stabilize both the correct monomeric and trimeric conformations to provide broadly neutralizing protection against most strains of influenza. Finally, we have worked to produce an antigen derived from the gp41 protein of HIV. This antigen was originally developed in the Kim Lab at Merck Research Labs and had only been produced using peptide synthesis which is not practical for worldwide distribution. Ultimately, these antigens, together with the HepBc VLP scaffold will serve as novel vaccine candidates for Zika, Influenza, and HIV respectively.
Development of a quantum-based superconducting radio-frequency voltage standard
Keywords: Electrical Engineering.

Metrology science is continuously transitioning toward a paradigm in which standard definitions of SI units are represented by systems that use quantum mechanical effects to relate measurement units to fundamental constants. This dissertation describes research efforts to achieve this transition for voltage and power metrology at frequencies above the audio range. In particular, this dissertation presents the design and experimental testing of a superconducting programmable radio-frequency waveform synthesizer intended for quantum-based metrology applications. The waveform synthesizer incorporates high-speed active superconducting circuit elements known as Josephson junctions and produces output waveforms with spectral power distributions that are traceable to the values of fundamental constants. This synthesizer has practical applications for calibration and characterization of communications-frequency electronics, and will supplement existing radio-frequency metrology tools that are not quantum-based.
The development of conceptual representations of mental life
Keywords: Psychology.

Attributions of thoughts, beliefs, desires, intentions, emotions, perceptions, and sensations are at the core of human social life—but "mental life" is a complex concept, encompassing a wide range of experiences and abilities that vary along many dimensions. This makes ordinary people's representations of mental life a fascinating case study of abstract reasoning and its development: How do children come to represent this complex conceptual space? In this dissertation I describe a series of large-scale studies designed to explore this question among children (4-9y) and adults in the modern US context, using an empirical approach that unites recent work on the "dimensions of mind perception" with rich traditions of research on the development of the animate-inanimate distinction, lay biology and psychology, and theory of mind. These studies address three ontological questions about ordinary people's representations of mental life: (1) What are the conceptual units that anchor representations of mental life at different points in development? (2) How are these conceptual units organized in relation to each other, and how does this organization change over development? and (3) How do people of different ages deploy their conceptual representations of mental life to reason about specific entities in the world—namely, animate beings vs. inanimate objects? Results suggest that, over the course of early and middle childhood, US children's representations of mental life undergo substantial development in all three of these respects. These findings have important implications for children's social cognitive development.
Development of novel methods for the formation of C-C and C-N bonds
Keywords: Chemistry.

Carbon-carbon and carbon-nitrogen bonds are some of the most common motifs in organic molecules and as a result, the invention of new methods for selectively forming these bonds is highly important. The first half of this thesis describes the discovery of two novel and unexpected carbon-carbon bond forming reactions, and also includes a review on the unique chemistry of geminal and vicinal bis(sulfones). The second half of this work deals with enantioselective carbon-nitrogen bond formation, and describes the development of two transition metal-catalyzed asymmetric allylic alkylation reactions. It also contains a review on annulative allylic alkylation reactions between dual electrophiles and dual nucleophiles and their applications in complex molecule synthesis.
Development of real time calibration for an integrated additive manufacturing platform for tissue engineering constructs
Keywords: Yang, Yunzhi
tissue engineering
scaffolds
biomechanical
mechanical
calibration
additive manufacturing
orthopedic surgery
3d printing
computer vision
Thesis

Next generation development of tissue engineering scaffolds increasingly leverages the ability of additive manufacturing methods in order to generate highly complex designs that can be customized to unique conditions found in the patient. Specifically, the development of integrated manufacturing methods, whereby multiple additive processes are utilized in conjunction with one another represent a potentially novel solution for how to create bio-mimetic scaffolds that can replicate natural tissue structures. In this paper, we discuss the development of a novel integrative manufacturing platform that aims to create next generation scaffolds for tissue engineering. Specifically, we discuss the overall design of the platform and our creation of a real-time calibration scheme that corrects for error during our manufacturing process.
Development of synthetic and semi-synthetic transporters for drug and gene delivery
Keywords: Chemistry.

The delivery of small molecules, probes, and nucleic acids across impenetrable biological barriers represents a challenge for many current clinical strategies. Nucleic acids are of particular interest for delivery with potential clinical applications in cancer immunotherapy, gene editing and vaccines. Chapters 2-5 describe the development and use of charge-altering materials for the delivery of nucleic acids. The charge-altering materials described are dubbed Charge-Altering Releasable Transporters (CARTs), diblock or triblock oligomers consisting of a lipid-modified oligocarbonate block(s) followed by a charge-altering block. The charge-altering blocks, derived from either morpholinones or poly(serine esters), are initially cationic for complexation of the polyanionic nucleic acid cargo but degrade under basic conditions over time to neutral byproducts, providing a mechanism for nucleic acid release. These chapters describe the use of CARTs to deliver a range of nucleic acid cargos (plasmid DNA, messenger RNA, small interfering RNA) across a variety of cell types, including lymphocytes, as well as for in vivo gene delivery. Chapter 6 explores vault proteins as another scaffold for drug or probe delivery. Vaults are naturally occurring, large (13 MDa), hollow ribonucleic protein complexes. These proteins have the potential to be promising delivery agents based on their biocompatibility, size, and internal compartment that can encapsulate hundreds to thousands of molecules. In this chapter, we systematically study the chemical modification of vault proteins and used the developed strategies to prepare vaults modified with cell penetrating peptides for enhanced uptake into cells. Chapter 7 describes the synthesis and evaluation of prodrugs of PKC modulators. Prostratin, bryostatin 1, ingenol esters and their analogs, are potent PKC modulators and have been identified as latency reversing agents (LRAs) for HIV eradication. LRAs can be used to activate the HIV provirus in latent viral reservoir cells, which can then be subject clearance using a "kick and kill" approach. While promising agents, a major challenge associated with the clinical use of LRAs is sustaining therapeutically meaningful levels of the active agent while minimizing side effects. In this chapter, we describe the synthesis of PKC modulator prodrugs designed to slowly release the active drug over time. These PKC modulator prodrugs exhibit comparable but delayed in vitro activity relative to the parent compounds and avoid the problems associated with bolus administration in vivo.
Development of the capsule ultrasound (CUS) device
Keywords: Bioengineering.

Currently, there is a lack of medical imaging tools required to investigate the multiple layers of the entire small intestine in the gastrointestinal (GI) tract. Some of the existing imaging modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI), used for examining the GI tract, expose the patient to radiation and/or are expensive. To make GI tract assessment easier, doctors use endoscopic ultrasound (EUS) and capsule endoscopy (CE). While EUS provides adequate penetration depth, it is unable to look at the entire small bowel. On the other hand, while CE is able to survey the entire small bowel, it only observes at the superficial layer due to its use of optics. To increase the prevalence of GI tract screening, with particular emphasis on small bowel, we propose to develop the capsule ultrasound (CUS) device, a diagnostic capsule with ultrasound imaging capability. Our envisioned device will measure 2.5 cm in height and 1 cm in diameter. Upon being swallowed by the patient, the CUS device will collect images of the GI tract with 360 degrees field-of-view (FOV) and wirelessly transmit the images to an external recorder for image reconstruction and display. To accomplish this goal, the CUS device will be equipped with a cylindrical transducer array around its perimeter and the associated imaging electronics, for regulating the image acquisition process, as well as a wireless transmitter, for wirelessly sending the ultrasound data to the external recorder, inside the capsule. This thesis highlights research towards the development of the CUS device, which, once developed, could be a revolutionary product for diagnosis of diseases in the GI tract, in particular the small intestine. Even though the development of the CUS device is a collaborative research project involving several students, in this thesis I demonstrate and share aspects of the research onto which I have contributed. In this thesis, I first discuss the system-level optimization of the CUS device through image simulations. Next, I highlight the transducer array fabrication process and the characterization results. Moreover, I demonstrate preliminary imaging results of the CUS device through wire and small bowel phantoms. Lastly, I share an integration scheme for the transducer array to increase patient safety. The research presented in this thesis for the design and development of the CUS device can be used to produce other wearable, disposable, and wireless-based medical devices to improve healthcare.
Differentiation and maturation of oligodendrocytes in human three-dimensional neural cultures
Keywords: Stem Cell Biology and Regenerative Medicine.

Investigating human oligodendrogenesis and the interaction of oligodendrocytes with neurons and astrocytes would accelerate our understanding of the mechanisms underlying white matter disorders. However, this is challenging due to limited accessibility of functional human brain tissue. Here, we developed a novel differentiation method of human induced pluripotent stem cells (hiPS cells) to generate three-dimensional (3D) neural spheroids that contain oligodendrocytes as well as neurons and astrocytes, called human oligodendrocyte spheroids (hOLS). We demonstrate that oligodendrocyte-lineage cells derived in hOLS transition through developmental stages similar to primary human oligodendrocytes and that the migration of oligodendrocyte-lineage cells and their susceptibility to lysolecithin exposure can be captured by live imaging. Moreover, their morphology changes as they mature over time in vitro and start myelinating neurons. We anticipate that this method can be used to study oligodendrocyte development, myelination, and interactions with other major cell types in the central nervous system.