VictorJuiz/thesis huggingface dataset:
Defining natural killer cell responses to HIV

Human immunodeficiency virus (HIV) remains a major global public health issue, and in the continued absence of a cure or vaccine, novel treatment and prevention strategies are needed to combat the ongoing epidemic. Many lines of evidence have suggested that natural killer (NK) cells, effector cells of the innate immune system that rapidly respond to virus-infected and malignantly transformed cells, can contribute to protection against HIV acquisition and disease progression. Here provide a characterization of methods of NK cell targeting of HIV, encompassing both natural receptor-ligand interactions in the setting of in vitro infection as well as in HIV-infected individuals, as well as via the use of bispecific antibodies to specifically target NK cells to HIV-infected cells. We first optimize an in vitro co-culture system to detect HIV-specific NK cell responses to autologous infected cells. We then use a combination of single cell transcriptomics and mass cytometry to characterize the features of NK cells in these co-cultures. Using single cell RNA-seq, we find a dominant interferon-driven gene signature in NK cells responding to HIV-infected cells. In addition, by mass cytometry profiling of NK cell phenotype and function, paired with profiling of ligand expression on infected CD4 T cells, we identify candidate receptor-ligand interactions (NKG2D/MIC-A/B and ULBP-1/2/5/6, and NKp30-B7-H6) involved in recognition mechanisms, which we then validate using CRISPR knockout of the corresponding ligands on target cells. We thus identify mechanisms of NK cell activation and response against HIV. We then study whether HIV-infected individuals treated with antiretroviral therapy (ART) possess alterations in NK cells that may make them more responsive to a second, in vitro exposure to HIV. We once again use mass cytometry to profile NK cell phenotype and function in both treated, HIV-infected individuals and healthy controls and find that, while there is a shift in the pattern of expression of NK cell receptors including NKp30 and CD2, the overall phenotype and frequency of the subset of cells that respond to in vitro HIV stimulation is not changed. We thus find that while the NK cell repertoire is altered in treated, HIV-infected individuals, it does not become more HIV-specific. Lastly, we develop and test a bispecific antibody that targets HIV gp41 and the NK cell activating receptor CD16. We show that this bispecific antibody has increased affinity and avidity to CD16, and is thus able to robustly enhance NK cell targeting of infected cells. This provides a means for controlled targeting of NK cells to infected cells. Overall, we identify multiple mechanisms that may hold promise to improve NK cell activity against HIV-infected cells. We discuss the extension of these findings in improving NK cell-mediated immunotherapy in HIV infection

Keywords: Immunology.
Advisor: Blish Catherine
Kim Peter
Sarnow P. (Peter)
Sunwoo John B.
Defining the human innate immune response to dengue virus infection

Dengue virus (DENV), a serious cause of morbidity in the Americas and Southeast Asia, is the most prevalent arthropod-borne virus in the world. During DENV infection, innate immune cells not only serve as a first line of defense, but also as sites of viral replication. Consequently, their response to infection affects the extent of viral spread and activation of the adaptive immune response. Here we present three stories exploring the innate immune response to DENV infection with a focus on natural killer (NK) cells and monocytes. We first examine how upregulation of HLA class I molecules by DENV-infected cells serves to suppress the NK cell response. Next, we investigate how the immune response to DENV infection differs between children and adults, with a particular focus on changes in the NK cell receptor-ligand repertoire. Finally, we explore the susceptibility of different monocyte subsets to the two different routes of dengue infection: direct infection and antibody-dependent enhancement (ADE). To conclude, we discuss some new questions that have arisen from this work and propose future studies

Keywords: Immunology.
Advisor: Blish Catherine
Carette Jan
Kim Peter
Martinez Olivia
Wang Taia
Deranging the Senses through Space and Time: European Classical Music Festivals in the Twenty-First Century

In the postwar period, classical music festivals have increased in number and risen in stature as more marketable alternatives to traditional forums like local symphony orchestras and opera houses. In the summer of 2019, I visited three festivals to experience firsthand their interventions in redefining classical music today. Cloistered gardens, concert halls, and open-air plazas filled with audiences and music became my field sites, and I interviewed festival organizers, music critics, and audience members to interrogate what compelled their decision-making. How do festivals toggle between a universal ideal latent in classical music and the inherent particularities of the audiences, venues, performers, and histories that form their identities? How do they participate in the cultivation of refined aesthetic palettes in their audiences, while proselytizing classical music as an inclusive pedagogy that might bridge differences in class, language, and culture? In the first chapter, I consider how festivals are impelled to beget the new, that evergreen mandate for sponsors of the arts. In the second chapter, I question how festivals forward their own interpretations of place, one that is always necessarily a “meeting place” between local, national, and global identities.

Keywords: Stanford Anthropology
classical music
festivals
arts management
Thesis
Design and clinical applications of protease-activated optical chemical probes

Tumor resection remains one of the best ways to ensure a positive outcome for cancer patients. Intraoperative differentiation between tumor and healthy tissue is critical and tools that can aid surgeons make these important surgical decisions are being pursued in various biomedical/engineering disciplines. Here, I describe chemical tools that are designed to sense the tumor microenvironment, activate in the tumors, and produce an observable signal, thus allowing for surgical margin detection. Proteases are enzymes that hydrolyze peptide bonds and play key roles in normal physiology as well as in disease. In cancer, tumor-associated macrophages, which are immune cells, release various proteases which cleave molecules used for signaling, tissue repair, angiogenesis, and degrade the extra-cellular matrix. While there are methods to analyze protease mRNA and protein levels, they do not reflect the proteolytic activity of the cancer micro-environment. Using fluorescently-quenched optical chemical probes, we are able to dynamically monitor this protease activity. This work is broadly divided into two parts: 1) Clinical applications of optical chemical probes for imaging disease and 2) Design strategies of protease-activated optical chemical probes. Chapters 2-4 describe how clinical considerations guided us to optimize chemical probes to be compatible with imaging equipment used in the clinic. We find that these optical chemical probes augment surgical workflows in the operating room and enhance pathology analyses, allowing clinicians to make more accurate diagnoses. In Chapter 6, we discuss the development of protease-activated chemical probes by directly screening tumor samples. This unbiased approach allows us to design chemical tools that responds more accurately to the complex milieu of proteolytic activity found in actual tumor microenvironments

Keywords: Chemical and Systems Biology.
Advisor: Bogyo Matthew
Chen James
Grimes Kevin
Rosenthal Eben
Design and control of soft shape-changing robots

For robots to be useful in the real world, they must be human-safe, adaptable to different tasks, robust to uncertainty, and untethered from external power. Enabling these capabilities requires the codesign of both the physical robot and its controller. In this talk, I will illustrate this approach through the development of a large-scale, shape-changing, inflated soft robot. First, I will describe the control of robotic trusses, or robots that consist of many linear actuators connected at universal joints to form a shape-changing structure. Using techniques from rigidity theory, I present a kinematic model and control methodology that enables control of arbitrary structures. Then, I will demonstrate these controllers in practice for a new type of inflated truss robot called an "Isoperimetric" Truss Robot, or a truss in which the total edge length is conserved. In this case, the vertices of the truss-structure consist of robotic rollers that pinch inflated fabric tubes that comprise the robot's structure, inducing effective joints. The robot changes its shape by driving the rollers along the tube, lengthening one edge and shortening another by moving the joint. As the overall edge length, and hence inflated volume, remains constant no tether to external air is required. The resultant robot can locomote with a punctuated rolling gait, grasp objects using its inherent compliance, operate safely around humans, and can be manually reconfigured based on its task. Last, I will present a distributed control framework for truss-like robots. In this framework each individual actuator utilizes local computation and communication to determine how to act individually to allow the overall robot to accomplish a task. Together these contributions allow for modular, human-safe robots that are capable of controllably changing their shape

Keywords: Mechanical Engineering.
Advisor: Okamura Allison 
Schwager Mac
Follmer Sean
Design and demonstration of on-chip integrated laser-driven particle accelerators

In this thesis, I present the first demonstration of a waveguide-integrated dielectric laser accelerators (DLA), designed using a photonic inverse design approach. I first review the operation of DLAs and describe how one can formulate a figure-of-merit for the optimization of these structures. I then briefly introduce the inverse design framework that allows for efficient free-form optimization of these structures, enabling search of a design-space that goes far beyond that of the tuning of a few geometric parameters. With an integrated accelerator design obtained, attention is turned to on-chip coupling methods for DLA applications. Here again, the inverse design framework is employed to produce broadband grating couplers. Experimental results of our single-stage on-chip integrated accelerator are shown, from which a maximum energy gain of 0.915 keV over 30 um, corresponding to an acceleration gradient of 30.5 MeV/m is inferred. Lastly, I explore new directions to reach higher on-chip acceleration gradients and larger energy-gain, including utilizing foundry fabrication for multi-stage accelerators

Keywords: Physics.
Advisor: Hollberg Leo (Leo William)
Vuckovic Jelena
Byer R. L. (Robert L.)
Design and fabrication improvements for the dielectric laser accelerators

Accelerated particle beams have already played and will continue a growing role in the analysis and fabrication of commercially important products, particularly in the development of the next generation of electronics, advanced engineering and smart materials. Without accelerators, major advances in the biosciences of the past 50 years would not have happened, and future developments in accelerator technology will stimulate a better understanding of living processes, leading to new medicines and therapies. However, the size and cost of the conventional radio-frequency (RF) accelerators limit the wide distribution of the accelerator technology. Dielectric laser accelerators (DLAs) aim to shrink down the dimension of the RF accelerators by using near-infrared (NIR) ultrafast femto-second laser to drive dielectric structures as well as provide higher acceleration gradient. The driving wavelength for DLA is 1000X smaller than RF accelerators, which leads to 1000X smaller in accelerator dimension. Additionally, dielectric material, like silicon and silicon dioxide, can survive under one to two orders of magnitude higher energy compared with metal used in RF accelerators. DLA can provide acceleration gradient upwards of 1GV/m, compared to 30-100MV/m for RF accelerators limited by material damage. In this thesis, I will discuss the design and fabrication improvements for DLA in both sub-relativistic and relativistic regime. In the sub-relativistic regime, silicon pillars have been used as accelerators. Hydrogen annealing process can decrease the variation of laser induced damage threshold (LIDT) for silicon pillars, and also makes the damage site positions agree with corresponding field hotspots. A thin film of low-stress nitride coating on silicon pillars can improve LIDT by 27% and acceleration gradient by 11%. In the relativistic regime, eutectic bonding is applied in chip-level fused silica bonding to fabricate accelerators. Single grating /DBR design is proposed and fabricated to provide better symmetric acceleration gradient distribution and remove alignment requirement during bonding process. In order to move towards multi-stage integrated DLA, silicon nitride waveguide-based power delivery DLA is proposed and fabricated. Nitride grating coupler efficiency is measured to be 20.5% and damage at input pulse energy of 15nJ. These results enable the accelerators powered by on-chip couplers and waveguides

Keywords: Electrical Engineering.
Advisor: Solgaard Olav
Fan Shanhui
Harris J. S. (James Stewart)
Design of a Current Source for Low-Power Electromagnet Excitation in Giant Magnetoresistive-based Biosensors

Rapid biomarker identification and detection at low concentrations in biological fluids opens the door to early-detection and treatment of not only chronic diseases that develop over many years, but also acute infectious diseases where rapid diagnosis is often a necessity. To enable rapid-testing, high sensitivity biosensors have to be moved to the point-of-care (POC). One of the most sensitive biosensors cited in literature are giant-magneto-resistive spin-valve (GMR-SV) biosensors. Proof-of-concept point-of-care GMR platforms have been developed but suffer from high power consumption and low in-field life-time. To transfer this GMR biosensor into a point-of-care setting for DNA detection it must be readily integrated with a method of DNA amplification, such as polymerase-chain reaction (PCR). PCR is also a very power-intensive process needed for sample preparation for sensing and analysis, further constraining the power budget of the GMR system and increasing the sizes, voltages, currents, and converter sizes for a deployable POC device. This honors thesis aims to significantly decrease the power consumption needed for the PCR-GMR POC platform by (1) decreasing the power budget needed for GMR-biosensor readout, (2) improving efficiency of on-board voltage conversion and regulation, and (3) exploring the feasibility and opportunity in integrating PCR and GMR into a single die using multi-physics simulations.

Keywords:  Department of Electrical Engineering
GMR
PCR
power
point-of-care
biosensor
Thesis
Advisor: Yao Bryce
Wang Shan
Design principles of green fluorescent proteins - Why are they green and fluorescent?

Since its discovery in jellyfish around the early 1960s, green fluorescent protein (GFP) and its derivatives have become the most widely used in vivo imaging tools for biological studies. Mutants of GFPs have been engineered to exhibit a palette of colors, wide range of fluorescence quantum yields (FQYs), and photoswitching characteristics, enabling advanced applications such as optogenetics and super-resolution microscopy. However, tailoring GFPs for specific purposes heavily relies on extensive screening and/or directed evolution as it is unclear how the protein environment modulates the photophysics of the chromophore in quantitative terms. Thanks to the semisynthetic split GFP method and the recently popularized technique for incorporating noncanonical amino acids (i.e., amber suppression), we created conventionally inaccessible GFP mutants with systematically altered electrostatic properties and/or steric bulk of the chromophore and the surrounding protein environment. Correlations between various photophysical properties of these mutants led to transparent models describing how the protein-chromophore interactions affect the chromophore's color and FQY. The models provide quantitative predictions for designing GFPs with desired phenotypes and infer physically imposed limitations. In addition, our finding of how electrostatics biases photoisomerization pathways in GFPs could shed light on the general phenomenon of bond-specific photoisomerization, a defining characteristic of the retinal chromophore within rhodopsins central to vision and important to the field of photoactive molecular devices

Keywords: Chemistry.
Advisor: Boxer Steven G. (Steven George)
Cui Bianxiao
Martinez Todd J. (Todd Joseph)
Designing bioinks for 3D bioprinting in gel-based support baths

3D bioprinting has emerged as a powerful tool to pattern extracellular matrix (ECM) and living cells to produce biological structures that mimic native tissues and organs ex vivo. Bioinks, the cell- and ECM-laden mixtures used during bioprinting, have primarily been composed of biopolymers appropriated from traditional 3D tissue engineering to form hydrogels following printing. These materials are not particularly well suited to meet the challenges introduced through bioprinting, namely, cell sedimentation, mechanical damage while printing, printing in gel-based support baths, and tunability of the mechanics and bioactivity of the biopolymer hydrogels. New bioink materials can be produced through intentional design of the crosslinking scheme of the hydrogel network before and after bioprinting into a gel-based support bath. The work presented in this thesis explores the benefits of designing new bioink materials for 3D bioprinting that move beyond the simplest crosslinking strategies used in traditional tissue engineering materials. Specifically, bioinks that employ two different stages of crosslinking, a first-stage crosslinking before the material is printed and a second stage following printing in a bath, prove to be effective for 3D bioprinting. One example of the increased versatility of bioinks from a dual-crosslinking approach is a bioprinted stem cell expansion lattice for stem cell manufacturing made using a traditional bioink material, sodium alginate. The second half of this thesis introduces two new crosslinking schemes that are made possible only by bioprinting into a gel-based support bath. Both bioorthogonal and hydrazone dynamic covalent chemistries are explored for producing new bioinks. The work put forward in this thesis is a step toward designing new bioinks for 3D bioprinting. An array of crosslinking schemes for bioinks are presented alongside creative uses of existing biopolymers to produce more adaptable bioinks

Keywords: Materials Science and Engineering.
Advisor: Heilshorn Sarah 
Appel Eric (Eric Andrew) 
Chaudhuri Ovijit
Designing Embodied Dialogue Systems: A Way of Thinking about Character Conversation in Video Games

This thesis argues for a new way of thinking about designing engaging dialogue systems for video games. The proposed approach – called designing “embodied dialogue” systems – stands in contrast to and goes beyond designing traditional “descriptive” dialogue systems to create an intrinsically engaging moment-to-moment dialogue experience. On this basis, this work proposes three design principles for creating embodied dialogue systems, namely, such systems should be (1) expressive, (2) autonomy-inspiring, and (3) true to the underlying game genre. These principles are put into motion in a proof of concept game prototype called Embodied Dialogue; the ways in which the design approach shaped the game design are discussed in detail. This tangible instantiation of the proposed approach was qualitatively evaluated by play-testers as a way of assessing its initial effectiveness. Furthermore, the game itself serves as a critical exploration of embodied dialogue elements including strongly-timed audiovisual sonification of dialogue, audiovisual inner speech, and an expressive personality system. Overall, this thesis argues that designing embodied dialogue systems (and the various game elements that can be derived from using this approach) is a compelling way of thinking for creating more engaging video game dialogue systems.

Keywords:  Symbolic Systems Program
RPG
Game Design
Sonification
Embodied Dialogue
Dialogue System
Symbolic Systems Program
School of Humanities and Sciences
Symbolic Systems
SYMSYS
Thesis
Advisor: Wang Ge
Bennett Chris
Designing in situ interaction with ubiquitous robots

We are nearing an era of ubiquitous robots. They will be in our home doing our dishes and laundry, in our workplace helping us carry heavy loads and performing repetitive tasks, and on the road driving us to our destinations and delivering packages. Due to this wide variety of potential tasks, robots will take different forms, sizes, and numbers resulting in a diverse set of robots ranging from a humanoid robot, specifically designed for interacting with humans, to a swarm of small mobile robots, used to collectively gather information in a large unstructured environment. Of these, particularly important are swarms of centimeter-scale non-anthropomorphic robots. Their appearance and size enable seamless transition between blending into the environment, becoming "invisible" to the users, and doing everyday tasks such as object manipulation through collective means and interaction with users through their motion and touch. While roboticists have made great strides in enabling swarms to move objects and control formation, the topic of in situ human-multirobot interaction is crucial and timely, given the rise in interaction with a group of robots in our daily environment. My thesis centers on ubiquitous human-centered robotics that facilitate in situ interactions with people. I introduce the concept of Ubiquitous Robotic Interfaces (URIs), multi-robot systems that are capable of mobility, manipulation, sensing, display, and interaction both with the user and the environment. In order to better understand interaction with this new class of robots, specifically on how to enable robots to effectively interact and communicate with people, I develop new tabletop swarm robot platforms, design multimodal multi-robot interaction, and evaluate them through a set of human subject experiments. As non-humanoid robots lack anthropomorphic features that have been heavily relied upon for human interaction, I leverage a feature common across most, if not all, types of robots: mobility. Specifically, I study how to visually display information like expresssivenss and intent to users through multi-robot motion, and how to convey information through touch from the robots. Closing the loop, I also investigate how people naturally communicate with a swarm of robots. In summary, this thesis provides a deeper understanding of interactive ubiquitous robots as well as generating a rich set of guidelines to increase effective human-multirobot interaction

Keywords: Mechanical Engineering.
Advisor: Follmer Sean 
Landay James A.
Okamura Allison