VictorJuiz/thesis huggingface dataset:
Defining and predicting the peptide-MHC repertoire of the T cell receptor [electronic resource]

[alpha] [beta] T cells are central mediators of the adaptive immune system, tasked with cytotoxic functions and coordinating the B cell and innate immune responses. The T cell response relies upon the T cell receptor, rendered hugely diverse through V(D)J recombination, sampling peptides bound to MHC molecules to instill antigen specificity to the immune response. However, the number of possible peptide-MHC greatly outstrips the theoretical number of possible T cell receptors and surpasses the total number of T cells in any given organism by an even larger margin. The basis for how T cell receptors can be cross-reactive enough to ensure all possible antigens can be recognized while retaining enough specificity to avoid promiscuous T cell activation and autoimmunity has not been systematically examined. To address this, I harness a manmade system to generate large degrees of molecular diversity, yeast display (introduced in Chapter 1), to directly assay the degree and mechanism of T cell receptor cross reactivity. Upon exhaustively examining the peptide-MHC recognition repertoire for five T cell receptors (in Chapter 2), I find a surprisingly limited degree of diversity in the recognized sequences. Instead, cross-reactivity is accomplished via relatively conservative mutations in the T cell receptor contact epitope mated to a larger degree of mutation elsewhere in the presented peptide. Even the most seemingly diverse sequences recognized by any T cell receptor are recognized in structurally similar ways and can be connected via intermediate related sequences. I then leverage these close relationships to find naturally occurring peptide ligands for T cell receptors with a high rate of success. In Chapter 3, I further refine our system to find even lower affinity peptide-MHC ligands, relevant for T cell development, through evolving a piece of 'molecular velcro' that provides an additional point of attachment between the peptide and T cell receptor while preserving discrimination between binding and nonbinding peptides.

Advisor: Garcia K. Christopher primary advisor. Thesis advisor
Cochran Jennifer R. advisor. Thesis advisor
Davis Mark advisor. Thesis advisor
Jardetzky Theodore advisor. Thesis advisor
Defining Environmental Literacy: Perspectives on Environmental Education in the Galápagos Islands School System

The Galápagos Islands are a UNESCO World Heritage Site and a popular destination for international travelers and researchers. However, the islands have often been overlooked as a center of local education in the large school system on the islands for young residents of Galápagos. This study investigates educators’ perceptions of environmental literacy as an outcome in both schools and organizations, spanning informal and formal environmental education programs. Using an ethnographic research approach, I carried out participant observation and semi-structured interviews with administrators and leaders in schools and organizations. The research included on-site observation of environmental education programs in both informal and formal settings. Through these interviews, I investigate the complications of providing environmental education for students on the islands. I also review the current state of student environmental literacy and explore how it can be supported with collaboration between schools and organizations for more frequent, comprehensive environmental education programs. The implications for adult residents living alongside a National Park and World Heritage Site are explored as well, with emphasis on the importance of environmental literacy for continued conservation and protection of the islands.

Keywords:  Department of Anthropology
 Goldman Honors Program
Galápagos Islands
Ecuador
Environmental Education
Environmental Literacy
Goldman Honors Program
Stanford Woods Institute for the Environment
Stanford University Department of Anthropology
Qualitative
Schools
Formal Education
Informal Education
Thesis
Advisor: Ardoin Nicole M
Durham William H
Diffenbaugh Noah
Defining Nanoproteomic Profiles of Hypoxia Signaling to Diagnose Clear Cell Renal Cell Carcinoma

The loss of function of the von-Hippel-Lindau (VHL) tumor suppressor gene leads to the development of clear cell Renal Cell Carcinoma (ccRCC) through activation of hypoxia signaling. ERK 1/2 is an important protein downstream of many hypoxia pathways, known to play a critical role in ccRCC disease progression. ERK activation occurs through phosphorylation. Previous studies have shown that total ERK 1/2 and phosphorylated ERK1/2 expression levels are higher in RCC cells compared to normal cells. However, ERK1/2 has two phosphorylation sites, and standard methods cannot distinguish between its different phosphorylated states. We hypothesized that ccRCC cells might exhibit selectivity for specific phosphorylated isoforms of ERK (such as mono-phospho-ERK1, denoted as pERK1). Further, we hypothesized that the relative percentage of ERK1 and ERK2 phospho-isoforms (pERK1, ppERK1, pERK2, ppERK2) can distinguish ccRCC tumor cells from adjacent normal renal parenchyma. Using a high-throughput nanoscale immunoassay (NIA), we measured the percent phosphorylation of ERK 1/2 and its respective isoforms within tumor and adjacent normal tissue in 20 ccRCC patients. For the first time, we showed that there was a significant difference in the percentage phosphorylation of each of the ERK 1/2 phospho-isoforms between ccRCC tumor and normal renal tissue. Through paired analysis, we found that the percentage phosphorylation of both mono-phosphorylated ERK1 and dual-phosphorylated ERK1 were higher in tumor tissue versus normal tissue (p<0.002 and p<0.00004, respectively). Similar results were obtained for mono-phosphorylated ERK2 and dual-phosphorylated ERK2 (p<0.01, for both). Thus, these results demonstrate that quantifying percent phosphorylation of key signaling molecules might be useful in defining signatures of ccRCC.

Keywords:  Department of Biology
clear cell Renal Cell Carcinoma
Nanoscale immunoassay
Hypoxia signaling
ERK 1/2
Thesis
Advisor: Felsher Dean
Gozani Or
Democratizing opera in America, 1895 to the present [electronic resource]

Despite opera's well-known exclusivity, the genre has in fact consistently been the target of popularizing initiatives, a point often overlooked in accounts of its history. This dissertation identifies and explains trends in efforts to democratize opera in the United States from the late nineteenth century to the present day. Examining both traditional live performance and opera's dissemination through new media formats, this research is the first to illuminate patterns in the great variation in the presentation style of popularly oriented opera in America over the last century, revealing novel source materials that challenge existing views of the genre. I argue that these little-explored democratizing initiatives have been dominated by ideals of uplift (1895-1920), integration (1920-1970), and authenticity (1970-present). Three case studies represent the prevailing trend of each era: Henry Savage's English Grand Opera Company (1895-1912), the NBC-TV Opera Theater (1949-64), and the Metropolitan Opera's Live in HD broadcasts (2006-present [2014]). I also show how changing ideologies about the role of "high culture" in society, sociodemographic shifts in the composition of the middle and upper classes and the immigrant population, and technological advances in mass media such as TV and HD satellite broadcasts have informed the emergence and character of these opera popularization strategies.

Keywords: Music.
Advisor: Berger Karol
Grey Thomas S.
Hinton Stephen
Dense random fields [electronic resource]

Random field models are commonly used to express prior knowledge about image formation and are one of the central tools of computer vision and image processing. Prior random field algorithms were restricted to sparse graph structures, such as grids in which only adjacent image pixels are connected and exchange information. In this thesis, we introduce dense random fields (DRFs), in which all image pixels are connected directly. DRFs encode a much richer prior, capturing interactions between distant elements in an image. Dense random fields have billions of edges, making traditional algorithms impractical. I will show that a representation of pairwise connections by combinations of Gaussian kernels enables highly efficient algorithms for inference and learning in DRFs. Our main inference algorithm, based on the mean field approximation, converges in a fraction of a second and yields state-of-the-art results on semantic image segmentation. This algorithm forms the basis for a family of learning algorithms that further improve DRF performance. Finally, we present an inference algorithm for continuous DRFs that can be used for dense motion estimation.

Advisor: Koltun Vladlen
Li Fei Fei
Savarese Silvio advisor. Thesis advisor
Densely integrated interface circuits for structural health monitoring [electronic resource]

The field of aerospace structural health monitoring (SHM) has envisioned embedding piezoelectric sensors inside the airframe to actuate and sense ultrasounds for the detection of defects. This will bring tremendous safety and economic benefits. One technical improvement that will make the whole system embeddable and reliable is integrating the sensor interface electronics in a silicon chip to replace the current bulky solution. This can potentially enable mass deployment of SHM. The key challenge for implementing such an IC lies in the piezo actuation, due to the simultaneous requirements for high drive voltage (several tens of volts), relatively high excitation frequencies (several hundred kilohertz) and low-distortion continuous excitation waveform. This is beyond what existing IC products can achieve. This research investigates a piezo driving scheme in which the required wave-form is generated by a pulse width modulated (PWM) class-D power amplifier (PA) with off-chip filtering. The pulse transition times are pre-computed through a least square optimization problem, and stored digitally to take advantage of the a priori knowledge of the SHM excitation signal. A digital calibration technique is introduced to achieve sub-nanosecond timing accuracy and -40 dB signal dis-tortion spec. To evaluate this concept, a four-channel, ±36 V, 780 kHz piezo driver chip was designed and fabricated in a 0.25 [mu] m BCD process. The IC achieves output signal distortion of -40.5 dB after calibration, improved more than 13 dB from the uncalibrated performance. An SHM system based on Flex-PCB, which combines the IC and the piezos, was designed and built. The IC and the system were demonstrated using an SHM test bed.

Keywords: Electrical Engineering.
Advisor: Murmann Boris primary advisor. Thesis advisor
Chang Fu-Kuo advisor. Thesis advisor
Khuri-Yakub Butrus T.
Design and characterization of synthetic microRNA based gene expression circuits [electronic resource]

The complexity of mammalian cells is largely due to the sophisticated control mechanisms employed to modulate the expression of endogenous genes. Various molecules in the cell are organized into circuits, which can respond to both changes in levels of intracellular molecules, as well as changes in the environment, by upregulating or downregulating the expression of any number of genes. The ability to interface with these endogenous programs to create novel molecular circuits would greatly advance our cellular engineering capabilities for a variety of applications. I first present a method to design and characterize synthetic circuits incorporating microRNAs (miRNAs). I derived and experimentally validated a model to capture the relationship between miRNA and target gene expression levels. I then extended the model to a more complex circuit incorporating an miRNA-based molecular switch to predict the impact of ligand levels on miRNA levels, and ultimately target gene expression levels, in the cell. Finally, I demonstrate the utility of this framework by using the model to inform the development of a synthetic circuit incorporating miRNAs responsive to intracellular protein levels, and show that this genetic circuit can serve as a sensitive, noninvasive sensor of nuclear protein concentration. Next, I extended the regulatory capabilities of synthetic miRNAs by developing a circuit that could perform OFF logic in response to levels of endogenous proteins within cells. This circuit was created by combining two different synthetic RNA-based regulators, a ligand-responsive ribozyme and a miRNA, to achieve the desired behavior. I developed a model that incorporates the component parameters and accurately described the behavior of this circuit. Finally, I combined a MS2-responsive ribozyme with a miRNA that targeted an MS2-dsRed fusion protein into this circuit architecture such that the system exerted negative feedback over MS2 levels within the cell. These powerful tools will enable the much more sophisticated engineering of biological systems as well as highlight the importance of methods for guiding the quantitative design of genetic circuits to achieve robust, reliable, and predictable systems-level behaviors.

Keywords: Bioengineering.
Advisor: Smolke Christina D. primary advisor. Thesis advisor
Covert Markus advisor. Thesis advisor
Kay Mark Allan advisor. Thesis advisor
Design, control, and simulation strategies for haptic interfaces [electronic resource]

Haptics is an emerging technology that involves transmitting information through the sense of touch. This hands-on form of interaction is achieved by using small actuated interfaces called haptic devices that apply forces, vibrations, and/or motions to the user. This work explores three different areas of haptics: hardware design, device control, and dynamic simulation. First, we explore the limitations of traditional haptic devices that rely on motors for actuation, and propose a new hybrid actuation design that is safer and more energy efficient. This new hybrid design addresses safety concerns by combining the use of brakes, springs, and mini-motors. The new design also overcomes many of the force rendering limitations of passive haptic displays. Second, we introduce a new control strategy to effectively map the physical workspace of haptic devices inside virtual simulations. The proposed technique relies on progressively relocating the physical workspace of the device mapped inside of the virtual environment towards the operator's area of activity without disturbing his or her tactile perception of the environment. This approach is based on the observation that humans are greatly influenced by what they perceive visually and do not notice small deviations of their hand, unless that small deviation has a corresponding visual component. Finally, we propose a unified framework for the real-time dynamic simulation and contact resolution of rigid articulated bodies. This work builds on previous developments in the field of dynamic simulation, collision detection, contact resolution, and operational space control. However, the key to efficiency and real-time performance is a new parallel implementation of our collision detection and contact resolution algorithm which decomposes the problem into tasks that can be concurrently executed.

Advisor: Khatib Oussama primary advisor. Thesis advisor
Cutkosky Mark R. advisor. Thesis advisor
Salisbury J. Kenneth advisor. Thesis advisor
Design of high-speed, high-resolution SAR A/D converters in nano-scale CMOS processes [electronic resource]

This research investigates the design of high-speed SAR ADCs to identify circuit techniques that improve their conversion speed while maintaining low energy operation. In addition, it explores the limitations of pipelined-SAR ADCs, which recently have demonstrated high power efficiency at conversion rates of several tens of MS/s and SNDR > 65 dB. A modified pipelined-SAR architecture is proposed, which uses two switched-capacitor digital-to-analog converters (DACs) at the ADC frontend. This technique separates the high-speed SAR operation from the low noise residue computation and improves the conversion speed to over 150 MS/s while maintaining an SNDR > 65 dB with good power efficiency. Three prototype ICs were designed during this work. First, a test structure to extract mismatch information of small (~1fF) on-chip single-metal MOM capacitors was designed in the IBM 32 nm SOI CMOS process. Measurement results show very good matching characteristics with a matching coefficient of approximately 0.85%×1fF. Next, an 8-bit SAR ADC was designed in a 65 nm CMOS process. This design uses 0.75 fF unit capacitors in the DAC, top-plate sampling with symmetric DAC switching, SAR loop delay optimization, and a fast comparator optimized for regeneration and reset. Measured results show an SNDR of 47.3 dB (Nyquist input) at 450 MS/s with a Walden FOM of 72 fJ/conv-step. Lastly, to evaluate the proposed pipelined-SAR architecture, a prototype ADC was implemented in a 65 nm CMOS process. Measured results show an SNDR of 68.3/66 dB at low frequency/Nyquist inputs, respectively with a sampling frequency of 160 MS/s, which corresponds to a Schreier FOM of 167/164.7 dB respectively. These results validate the concept of the proposed two switched-capacitor DAC pipelined-SAR architecture, and the achieved performance compares favorably with the state of the art.

Keywords: Electrical Engineering.
Advisor: Murmann Boris primary advisor. Thesis advisor
Arbabian Amin advisor. Thesis advisor
Wooley Bruce A.
Design requirements for car-to-driver interaction in the context of semi-autonomous driving [electronic resource]

Autonomous driving at scale is approaching, yet human drivers are reluctant to relinquish control over their safety to a machine. Autonomous vehicle designers are thus challenged to mitigate user concern and promote trust—as well as to ensure safety under the new driving paradigm. If autonomous cars are to become commonplace, the car-to-driver interface must be designed around the user—driver and passenger. This research adopts a human-centered approach to interface design, studying the emotional responses and preferences of drivers in autonomous and semi-autonomous driving situations. The dissertation posits that the complex, rapid-response driving context calls for the car to provide advance, feed-forward information rather than just traditional feedback. This approach was tested in a set of four experiments: two involved semi-autonomous driving in a simulator environment using voice alerts, and two involved more fully autonomous driving in an actual car on public roadways using a visual display as the messaging medium. In all cases, drivers strongly preferred being kept in the information loop. Advance alerts, whether vocal or visual, alleviated anxiety, and increased the driver's alertness, sense of control, and trust in the technology. Messaging should be succinct; too much information overwhelmed drivers, who could not process multiple messages in the rapid-response driving context. Drivers considered the reasoning behind the car's autonomous action (e.g., "Obstacle ahead!") more salient than mere announcement of the car's action (e.g., "Car is braking"). Designers must beware that consumer preferences do not dictate the best (or safest) performance; study results anticipate potential tradeoffs between market appeal and safety. Beyond empirical results for specific message models, this work developed simulator and field research platforms that can be adapted for future investigations. The research culminates in core guidelines for designing an autonomous vehicle interface that satisfies driver needs.

Keywords: Mechanical Engineering.
Advisor: Leifer Larry J. primary advisor. Thesis advisor
Beach David
Steinert Martin
Destabilizing the Photograph: The Process of Image-Making as a Discursive Exercise in Self-Making Through Photovoice Engagement With Children

This thesis examines questions about representation as they emerged from my fieldwork with children and youth ages 5 to 14-years-old who attended a farm-based education summer camp in Sunnyvale, CA, during the summer of 2013. I argue that the participatory and dialogic framework of Photovoice, a participatory photography methodology, allows for the empowerment and validation of research participants in the construction of their self-representation. Through an analysis of the participants’ transformative and exploratory responses to Photovoice, I highlight the experiences of five children as case studies in order to better understand what I call photographer persona as a concept for self-making, through which memory, empathy, awareness, sharing, and play emerge as extensions of the self and ways of being in the world. For this study, I draw upon the fields of child development, photography, anthropology, and engaged scholarship. I focus on the process of image-making as a conduit for self-making vis à vis the effects of participatory research on the empowerment of the self.

Keywords:  Department of Anthropology
Stanford University Department of Anthropology
Public Service Scholars Program Haas Center for Public Service
Photovoice
photography
participatory research
children
case studies
child development
anthropology
engaged scholarship
memory
empathy
awareness
sharing
self-making
Thesis
Advisor: Ebron Paulla
Hurd Clayton
Determination of the S. Cerevisiae INO80 Chromatin-Remodeling Complex in Mitotic Stability Pathways

The INO80 chromatin-remodeling complex was originally characterized as a transcriptional regulator that dynamically restructures chromatin, the packaging material of DNA. Recently, however, the complex has been implicated in chromosome segregation, as yeast deficient in INO80 subunits exhibit abnormal DNA ploidy. Currently, the precise mechanism by which the INO80 complex regulates mitotic stability remains unclear. This study sought to elucidate mechanisms for the INO80 complex in chromosome segregation by utilizing an integrative approach of genetics, molecular biology, and cell microscopy in S. cerevisiae. The hypothesis of this research is that the INO80 complex affects chromosome segregation by influencing microtubule dynamics. Through the assessment of genetic interactions between INO80 subunits and genes with characterized roles in mitosis, we find that INO80 subunits function in pathways related to kinesins, kinesin-like proteins, kinetochore-related, and cortical/microtubule associated proteins. Biochemical assays reveal a physical association between the INO80 complex and alpha-tubulin during G2/M-phase of the cell cycle. Cell microscopy provides further support for a role of the INO80 complex with microtubules, as fluorescently-labeled INO80 subunits localize to nuclear and cytoplasmic microtubules. Moreover, deletion of INO80 subunits results in an increased frequency of cells with shorter or undetectable cytoplasmic microtubules and non-elongated spindles. Interestingly, these results implicate the INO80 complex in microtubule function, which is important for kinesin (plus-end directed) and dynein (minus-end directed) motor proteins to generate the appropriate push/pull forces to separate sister chromatids, orient the spindle, and pull the nucleus into the daughter bud. This represents a novel mechanism by which INO80 regulates the critical mitotic machinery needed for chromosome segregation and to ensure accurate propagation of genetic materials into daughter cells.

Keywords:  Department of Biology
mitosis
chromosome segregation
chromatin remodelers
INO80
ARP5
IES6
spindle assembly
microtubules
microtubule motor proteins
S. cerevisiae
Biology
Stanford
Thesis
Advisor: Morrison Ashby
Stearns Tim