VictorJuiz/thesis huggingface dataset:
Mechanism of non-neuronal fate repression during C. elegans neurogenesis

Cellular differentiation is defined by tuning of the cell's transcriptional program into its target. Examples of developmental repressors such as REST suggest that non-target programs need to be repressed in parallel to activating the target programs. While it is well established that proneural genes activate neuronal transcription programs, little is known about how differentiating neurons repress non-neuronal programs to ensure neuronal fates. Myt1 family factors are transcriptional repressors that contribute to neuronal reprogramming from non-neuronal cells in vitro, but their function during neuronal differentiation remain unclear. In this dissertation, I characterize the sole C. elegans Myt1 family ortholog ZTF-11. We show that ZTF-11 is required for neurogenesis in multiple neuronal lineages from previously differentiated epithelial cells, including a neuron generated from a developmental neuronal transdifferentiation event. ZTF-11 is exclusively expressed in all neuronal precursors with remarkable specificity at single cell resolution, likely through direct activation by proneural genes. ZTF-11 is required to eliminate epithelial identity from neurons generated from epithelial precursors. In these neurons, loss of ztf-11 results in loss of neuronal identity. Ectopic expression of ZTF-11 is sufficient to generate additional neurons through repressing epithelial identity. In contrast, neurons generated from dedicated neuronal lineages are still generated without ZTF-11, suggesting that neurons face different developmental challenges from non-neuronal programs. Loss of ztf-11 results in upregulation of many non-neuronal genes. ZTF-11 functions together with MuvB corepressor complex to repress its target genes. These results provides insights on the ability of Myt1l to drive neuronal transdifferentiation in vitro as well as the developmental role of Myt1 family factors. Taken together, I identify an evolutionarily conserved mechanism to specify neuronal fates by repressing non-neuronal genes.

Keywords: Biochemistry.
Advisor: Shen Kang
Krasnow Mark
Rohatgi Rajat
Straight Aaron
Mechanisms and kinetics of silicon under dynamic compression

This thesis analyzes the dynamic material response of crystalline silicon to laser-driven shock loading. As a shockwave passes through the silicon, it generates a high-pressure, high-temperature environment that causes the material lattice to compress, deform, adopt new high-pressure phases, and eventually enter a melt state. Measuring these responses utilizes an ultra-bright, ultrafast x-ray source capable of capturing the lattice and atomic motions in-situ. The first experiment (Chapter 3) characterizes the loading source, a high-power optical laser at the Matter in Extreme Conditions endstation of the Linac Coherent Light Source. Analysis of the drive system optimized the experimental setup to send steady-pressure, spatially-uniform shockwaves through the silicon. The second experiment (Chapter 4) builds on the results of the first experiment, driving high-pressure (> 20 GPa) shocks through pure crystalline silicon samples. Using a setup configuration that places the x-rays transverse to the optical drive laser beam, this experiment takes simultaneous, ultrafast x-ray diffraction and direct x-ray imaging data of the lattice response. A series of focused spatial and temporal scans determines the kinetics of the elastic, inelastic, and melt waves. Additionally, wide field-of-view x-ray imaging spatially resolves these responses and illuminates an intermediate elastic wave. The third experiment (Chapter 5) analyzes additional data to extract the density of the imaged silicon melt in-situ, a long-standing challenge in the dynamic compression community. It establishes a positive trend between drive pressure and melt density while simultaneously quantifying the change in transformed material volume. A final experiment (Appendix B) examines the photon flux on-target in the Matter in Extreme Conditions endstation. It determines the effect of beamline configuration on the delivered number of x-rays - a critical value for expanding the results of this thesis to new low-transparency and/or high-Z materials.

Keywords: Mechanical Engineering.
Advisor: Cappelli Mark A. (Mark Antony) 
Mao Wendy (Wendy Li-wen) 
Nagler Bob
Mechanisms of co-differentiation : the D. melanogaster germ cell cyst as a model for cell-cell interactions in development

Adult stem cells are required throughout life to replenish differentiated cells lost to normal cell turnover or to injury in many tissues. Regulating the balance between stem cell renewal and differentiation by the microenvironment that surrounds cells in a stem cell lineage is crucial for long-term tissue maintenance and disease prevention. While the adult stem cell field has focused primarily on identifying self-renewal signals for tissue-resident stem cells, in this dissertation I focus on identifying mechanisms by which the niche or microenvironment promotes differentiation down a cell lineage in vivo. In this study, I identified mechanisms of crosstalk between cells in an adult stem cell lineage with cells in their surrounding environment that promote cell survival, stem cell bipotentiality, and proper progression through multiple stages of differentiation. I used the genetic model system of the Drosophila male germ line to determine the molecular mechanisms by which somatic cyst cells promote the transition of germ cells from stem cells, to transit amplifying progenitors, to differentiating germ cells that will undergo meiosis. Germ line stem cells (GSCs) divide asymmetrically to produce daughter cells that will undergo four mitotic transit-amplifying divisions before beginning meiosis and terminal differentiation. Following division of a GSC, the daughter cell displaced away from the hub is encapsulated by two somatic cyst cells, which will influence the entire process of germ cell differentiation into mature sperm. The germ cell-cyst cell "mini organ" is an excellent system to study how two cell types co-differentiate to form a functional unit. I identified molecular signaling events in cyst cells that are required at three stages of germ cell differentiation. 1) Cyst cells repress JNK signaling via activity of the Baz/Par-6/aPKC polarity complex to promote survival of germ cells entering early stages of meiotic prophase. 2) Cyst cells respond to BMP signals in order to dampen the GSC response to BMP self-renewal signals, maintaining germ cells in a bipotential state with the capacity to produce differentiated progeny. 3) Cyst cells must stop dividing, change transcriptional programs, and encapsulate the neighboring germ line for germ cells to cleanly enter the transit amplifying progenitor stage. Together, this work highlights the importance of cell-cell communication throughout the development of the germ cell cyst "mini organ, " which may parallel the interactions that promote co-differentiation of neighboring cell types in development and adult tissues.

Keywords: Kim, Seung K. degree committee member.
Developmental Biology.
Advisor: Fuller Margaret T.
Nusse Roel
O'Brien Lucy Erin
Medicaid Work Requirements: Do They Work?

There has never been a consensus in the United States as to whether healthcare is a human right, as evidenced by the fierce political debate that continues over the Affordable Care Act. Most recently this debate has centered on attaching conditions to Medicaid coverage. Most prominently among these are Medicaid work requirements, which arise out of the misguided idea that people on Medicaid use it as a way to avoid work and that Medicaid actively discourages them from working. In reality, a significant majority of people on Medicaid are either unable to work or are already working. Work requirements lead to large coverage losses, more often due to an inability to properly document their hours, rather than a failure to meet the requirements. This creates a vulnerable uninsured population, who are unable to get necessary health care. Medicaid work requirements thus negatively impact the health of low-income individuals, while states spend more money to cover fewer people.

Keywords: Medicaid
work requirements
health policy
Stanford University Community Health and Prevention Master's Program
Thesis
Advisor: Donald Barr MD
Tom Glynn PhD
Gary Swann PhD
Medieval commentaries on the Tale of Genji, 1367-1500 : figuring a classic

Today the Tale of Genji (c. 1000) has come to be associated unambiguously with the Classical Heian period (794-1192) and its peaceful, court-centered society of cultivated aristocrats—this in contrast to the troubled ages that followed it, defined by seven long centuries of almost unbroken warrior supremacy (1192-1868). During the latter period, the Genji is often assumed to have languished under various "medieval" misconstruals in Buddhist, didactic, or antiquarian mode, until in the 18th century a group of revisionist scholars associated with Motoori Norinaga fought successfully to read the work, once more, as the fiction of human passions Murasaki Shikibu had always intended it to be. My thesis begins with the fact that such a narrative is almost entirely contradicted by available documentary evidence. Unlike most other works of our 21st-century Heian canon, the Genji is blessed with a library of commentary literature almost as old as the work itself. The direct light this affords on the concerns of readers across the ages reveals quite a different history of reception. Particularly thorough and long-lasting were the changes that occurred during a brief period of more innovative medieval commentaries clustered thickly in the short span from 1376-1500. This was the early middle Muromachi shogunate, an era that saw the physical concentration of court and warrior elite in the same Capital, and at the same time the social expansion of traditional court civilization to ever broadening circles of incipient cultural literacy. This study seeks to delineate the conceptual changes effected during this short spell, and explain how they produced the Tale of Genji known to us today.

Keywords: East Asian Languages and Cultures.
Advisor: Carter Steven
Reichert Jim (James Robert) 
Levy Indra A.
Meeting Patients Where They Are

Introduction
Research has shown that the quality of the patient-physician relationship directly affects patient health outcomes.The character of this relationship can determine the amount of information exchanged, the nature of questions patients ask, the decision-making process, and other aspects of clinical communication central to care delivery. The impact of this relationship is reflected in its effects on important outcomes, including patient
satisfaction, physiological markers, adherence to treatment recommendations, and physician satisfaction. Many have reported that “meeting patients where they are” is a core strategy of building a strong relationship, however, how one achieves this is unclear. In this study, we sought to identify physicians’ conceptual and behavioral strategies for “meeting patients where they are.”
Methods
As part of a 3-year study on fostering humanism in the primary care setting, semi-structured interviews were conducted with ten exemplary primary care physicians at three diverse clinic settings: a family medicine clinic affiliated with an academic medical center, a safety-net clinic serving a low-income primarily immigrant population, and a Veterans Affairs outpatient primary care clinic. The interviews were approximately 25 minutes long and explored how providers build connections and trust with their patients. Using a general descriptive qualitative approach with two independent coders, we identified strategies that physicians utilize to meet patients where they are.
Results
Five themes emerged from the thematic analysis that physicians used to meet patients where they are:
1) Respect the expertise of the patient – recognize the validity of a patient’s beliefs, values, personal experience, and perspective.
2) Engaged curiosity – use statements and questions to demonstrate interest and understanding of what the patient is saying.
3) Attentive listening – give patient undivided attention and demonstrate this with body language and affirmations.
4) Mutual participation – ensure the interaction is based on equal power, mutual independence, and equal satisfaction.
5) Authenticity – conduct yourself in a manner that is consistent with genuine beliefs and values.
Conclusion
Primary care providers employ a number of strategies to “meet patients where they are.” The themes capture foundational behaviors which provide the groundwork for creating a safe space for patients by helping clinicians learn how to communicate their sincerity, respect of, and interest in the patient and his or her lived experience. This approach can encourage patients to disclose information that provides insight into their values, perspectives, goals, and other factors that are important for developing an effective treatment plan. The strategies proposed in this study, and the range of examples provided for how to personalize the approach, allow other physicians to adopt these conceptual practices using an approach that feels authentic and can be tailored to fit their clinical
style.

Keywords: doctor-patient relationship
communication
Stanford Prevention Research Center
Thesis
Mesenchymal stromal cells in wound healing

Abnormal wound healing is a significant healthcare problem with rising at-risk patient populations. Despite the multitude of treatment modalities available, few therapies can reverse the deficiencies that contribute to delayed or non-healing wounds. Mesenchymal stromal cells (MSCs) have emerged as a promising next-generation therapy for wound repair due to their ability to secrete trophic factors that modulate inflammation and promote regeneration. This work first provides a comprehensive overview of the intricate process of wound healing and the individual roles of resident cell types to identify potential points of therapeutic intervention at each stage of the wound healing cascade. Secondly, using lineage tracing, multiple models of ischemic injury, and single cell transcriptional analysis, we identify a population of non-hematopoietic, non-endothelial circulating progenitor cells that homes to regions of ischemia and may contribute to tissue repair. We demonstrate that these cells engraft adjacent to endothelial cells, display mesenchymal morphology, and deposit extracellular matrix, suggesting that they may be the in vivo equivalent of MSCs cultured in vitro. Thirdly, we explore the fate of mesenchymal stromal cells following intravenous infusion and their impact on wound healing. Using a mouse excisional wound healing model, we demonstrate that infusion of MSCs leads to pulmonary entrapment followed by rapid clearance from the recipient, but also significantly accelerates wound closure. Using single cell RNA-sequencing of the wound, we show that following MSC delivery, innate immune cells, particularly macrophages, exhibit distinctive transcriptional changes. We identify the appearance of a pro-angiogenic CD9+ macrophage subpopulation, whose induction is mediated by several proteins secreted by MSCs, including COL6A1, PRG4, and TGFB3. These findings suggest that MSCs do not need to act locally to induce broad changes in the immune system and ultimately treat disease. Finally, we investigate the age-related impacts on cellular function of MSCs. We demonstrate that delivery of MSCs from young donors resulted in significantly faster healing compared to delivery of MSCs from older donors. Using single-cell transcriptomic analysis to provide potential molecular insights into these observations, we demonstrate that cells from young donors contain a higher proportion of cells characterized by a higher expression of genes involved in tissue regeneration. In addition, we identify a unique, quiescent subpopulation that is exclusively present in young donor cells. These findings may explain a novel mechanism for the enhanced healing capacity of young stem cells and may have implications for autologous cell therapy in the extremes of age.

Keywords: Stem Cell Biology and Regenerative Medicine.
Advisor: Gurtner Geoffrey
Longaker Michael T.
Majeti Ravindra
Meteoroid mass from head echoes using particle-in-cell and finite-difference time-domain simulations

The increasing accessibility of space has enabled new technologies that have significantly affected our society. These technologies rely on spacecraft that must operate in the space environment, a domain that presents unique risks and dangers. Therefore, there is a significant motivation to understand the dangers of the space environment, one of which are meteoroids, defined by the International Astronomical Union as ``a solid natural object of a size roughly between 30 micrometers and 1 meter moving in, or coming from, interplanetary space." Spacecraft-meteoroid collisions are high energy and potentially destructive events due to the high meteoroid velocities relative to Earth that range from 11.2-72.8 km/s. Studies have shown that every square meter of exposed spacecraft surface area experiences a meteoroid impact that causes a crater with a diameter $> 40$ micrometers approximately once a day. The increasing reliance on spacecraft motivates a better understanding of the threats that meteoroids present, but estimates of the meteoroid mass distribution have orders of magnitude differences due to large uncertainties in meteoroid mass models. One method of calculating meteoroid mass uses radar reflections of the plasma surrounding an ablating meteoroid, otherwise known as meteor head echoes. High-Power Large-Aperture (HPLA) radars can detect approximately one head echo per second, enabling the collection of vast data sets of meteors and a better understanding of the meteoroid mass distribution. However, current methods used to calculate meteoroid masses from head echoes contain large uncertainties and result in distributions that are orders of magnitude different from distributions derived using other methods, such as crater analysis of spacecraft and optical observations. This thesis presents and validates a method to estimate meteoroid masses from head echo observations. First, the plasma distribution around an ablating meteoroid with Particle-In-Cell (PIC) simulations are calculated and the effects of parameters such as the Earth's magnetic field on the distribution are explored. Also, the PIC derived plasma distributions are compared to a simplified analytical model based on kinetic theory that neglects electric and magnetic fields. Second, The radar cross section (RCS) of various meteor head plasma density distributions are calculated with Finite-Difference Time-Domain (FDTD) electromagnetic simulations. The simulation results are then used to develop a new model to map a head echo radar observation to a meteoroid mass. This new model is validated with head echo radar observations from the Canadian Meteor Orbit Radar (CMOR), and analysis shows that it outperforms previously used models used for head echo derived meteoroid mass estimation.

Keywords: Aeronautics and Astronautics.
Advisor: Close Sigrid
Alonso Juan José
Cantwell Brian
Methods development for computational simulation of protein-ligand binding

Molecular dynamics (MD) simulation offers both high spatial and time resolution into biological processes at an all-atom level, but presents many unique computational challenges in terms of both system setup and compute time. To address the former, I introduce a software package, Dabble, that simplifies system building for MD simulation in a way that supports all commonly used force fields and simulation programs. To increase the accessibility of observing protein-ligand binding in simulations, I developed an adaptive sampling method that guides simulations towards interesting regions of protein-ligand conformational space while requiring no prior knowledge of binding pose or site. Together, these two computational methods improve the ability of researchers to use MD simulation for examining biological processes.

Keywords: Biophysics.
Advisor: Dror Ron
Van den Bedem Henry 
Huang Possu 
Kobilka Brian K.
Methods for energy-efficient compute and communication in deep learning

Deep neural networks (DNNs) have recently achieved state-of-the-art accuracies on visual and speech recognition. However, DNNs require millions of weights and activations for communication, and billions of compute operations. Both the design of compute and communication influence the energy-efficiency of DNN hardware. We present ways to improve the communication overhead and compute for DNN inference. To improve communication overhead, we propose low-precision logarithmic encoding (LogNet) on non-uniform weights with minimal loss in classification accuracy as compared with conventional fixed-point approaches. For example, even without retraining on Inception-Resnet, logarithmic encoding with 4 bits achieves only 3% degradation in top-5 accuracy. For both the encoding of weights and activations, we find that distortion error can be a very useful metric in the training of quantized DNNs. We propose dynamic clipping and dynamic resolutions on activations. We show that with all of our approaches, an approximate 2-bit complete ResNet-50 can achieve 70% (state-of-the-art) top-1 accuracy. Furthermore, with proposed techniques on 4-bit weights and activations, we achieve less than 1% degradation in top-1 accuracy on ImageNet and little degradation in object detection tasks. To improve compute, we propose and implement two strategies: 1) bitshift-add, which is motivated by LogNet, to replace expensive multipliers, and 2) passive charge-domain computation. In our second approach, we design and fabricate a chip that demonstrates energy-efficient matrix operations, called the Switched-Capacitor Matrix Multiplier (SCMM) in 40 nanometer CMOS. By replacing expensive digital multipliers and accumulate-registers with 40-nanometer switches and 300 attofarad unit capacitors, the SCMM achieves an energy per bit of 11 femtojoule or 5x lower energy than digital at 2.5 GHz. Finally, we briefly conclude to expand our findings to show how LogNet can also achieve more graceful model compression over conventional with limited retraining in data-sensitive environments.

Keywords: Electrical Engineering.
Advisor: Wong S. C. 
Murmann Boris 
Yeom Kristen
Metropolis-Hastings MCMC with dual mini-batches and reversible SGLD proposal

Traditional MCMC algorithms are computationally intensive and do not scale well to large data. In particular, the Metropolis-Hastings (MH) algorithm requires passing over the entire dataset to evaluate the likelihood ratio in each iteration. We propose a general framework for performing MH-MCMC using dual mini-batches (MHDB) of the whole dataset each time and show that this gives rise to approximately a tempered stationary distribution. We prove that MHDB preserves the modes of the original target distribution and derive an error bound on the approximation with mild assumptions on the likelihood. To further extend the utility of the algorithm to high dimensional settings, we construct a proposal with forward and reverse moves using stochastic gradient and show that the construction leads to reasonable acceptance probabilities. We demonstrate the performance of our algorithm in both low dimensional models and high dimensional neural network applications. Particularly in the latter case, compared to popular optimization methods, our method is more robust to the choice of learning rate and improves testing accuracy.

Advisor: Wong Wing Hung 
Owen Art B. 
Ye Yinyu