VictorJuiz/thesis huggingface dataset:
Investigating Patient Quality of Life in San Francisco Homeless Health Facilities

The Centers for Disease Control and Prevention, along with the American Psychological Association, emphasize that homelessness is a public health concern (CDC, 2017; Donovan & Shinseki, 2013). Concurrently, the U.S. Department of Housing and Urban Development (HUD) listed in its most recent report to Congress that San Francisco County has one of the highest rates of unhoused individuals in the nation, with roughly 6,211 people experiencing homelessness in 2018. HUD also estimates that roughly 65% of the unhoused population in the U.S. resides in physical shelters (Henry et al., 2018), many of which offer access to health services. Healthcare design research points to a number of factors that can influence patient wellbeing, one of which may be the size, in square feet, of healthcare facilities (Stichler, 2008). This qualitative thesis aims to summarize what staff members at facilities providing healthcare services to unhoused individuals in San Francisco County understand to be the salient healthcare needs of their clients, as well as to examine relationships between perceived quality of life of patients and characteristics of facilities. This research specifically seeks to assess whether the size of the facility as reflected in the square footage is associated with better or worse perceived quality of life, as reported by facility staff. Access to care was a central theme highlighted by facility staff, notably including addiction and psychological services; however, several aspects of the design of facilities were regarded as having the potential to be improved, with the availability of space particularly noted by staff at the smaller facility. The research findings emphasize that healthcare designs should aim to be both healing and efficient in order to enable patients to rapidly achieve their medical and social objectives.

Keywords:  Department of Civil and Environmental Engineering
healthcare
healthcare design
healthcare architecture
homeless
unhoused
design
architecture
staff
patient
health
human rights
Civil and Environmental Engineering
Architectural Design Program
Thesis
Advisor: Barton John
Billington Sarah
Investigating Patient Quality of Life in San Francisco Homeless Health Facilities: An Architectural Exploration

For her capstone project, Janet Coleman-Belin designed a healthcare facility that would provide critical resources to individuals experiencing homelessness in the Bay Area. Drawing upon her skills in Engineering and Architectural Design, Janet developed architectural plans, sections, and elevations; utilized a 3D computerized model in Revit (an industry standard building modeling program); and created a narrative explaining the spatial design decisions. Janet also consulted health design literature and first-hand accounts from various clinic staff as a way of fully creating a holistic architectural design. Her goal with this project is to envision a multi-level and multi-use community resource equipped with essential health, educational, and social resources dedicated to assisting homeless populations.

Keywords: Architectural design
Homeless persons
Public health
Text
Report
Thesis
Investigating single-molecule interactions and photodynamics in solution by counteracting Brownian motion

Single-molecule fluorescence methods have become a mature and powerful tool to unravel the fundamental mechanisms of biological phenomena. These approaches enable researchers to investigate individual components on the nanoscale for heterogeneous mixtures and to monitor the dynamics of single biomolecules. Unfortunately, traditional burst-based methods are often limited by short observation time, and the immobilization of single biomolecules that enables long observation time is often undesirably perturbative. To address these limitations, a solution-based technique known as the Anti-Brownian ELectrokinetic (ABEL) trap has been developed. In the ABEL trap, high-speed feedback electronics sense position and compensate Brownian motion of a single molecule by applying electrokinetic forces, which keep the molecule in the trapping region for an extended period of time. This dissertation describes my work on the investigation of single-molecule interactions and photodynamics using the ABEL trap technology. First, I show how to measure and monitor single-molecule rotational diffusivity by combining the ABEL trap and maximum likelihood analysis of time-resolved fluorescence anisotropy based on the information inherent in each detected photon. The rotational diffusivity is extremely sensitive to the size of the molecule, and thus can be used to detect and monitor size-changing events, such as association and dissociation. We demonstrate this approach by resolving a mixture of single- and double-stranded fluorescently-labeled DNA molecules at equilibrium, freely rotating in a native solution environment. Next, we investigate photosynthetic photoprotection mechanisms at the level of individual antenna complexes (LHCII), the fundamental units which green plants use to harvest sunlight. We access the intrinsic conformational dynamics of individual LHCII complexes. In addition to an unquenched state, two partially quenched states of LHCII are observed. One of the quenched conformations significantly increases in relative population under environmental conditions mimicking high light. Our results suggest that there are at least two distinct quenching sites with different molecular compositions, meaning multiple dissipative pathways in the LHCII complex. Last, we describe the theoretical basis of a new method to measure the diffusion coefficient of diffusing objects on the surface of individual nanoscale lipid vesicles. We discuss how to probe diffusion in these highly confined environments using FRET pairs and fluorescence intensity correlation, and illustrate that this method is essentially a fluorescence correlation spectroscopy (FCS) experiment with a nanometer-sized probing volume.

Keywords: Chemistry.
Advisor: Moerner W. E. (William Esco)
Dai Hongjie
Fayer Michael D.
Investigating the entorhinal code for spatial navigation

Navigation through an environment to a remembered location is a critical skill we use every day, and accurate navigation is necessary for survival for many animals. How do neural cir-cuits accomplish such a task? Over the last few decades, several lines of evidence have suggested that a brain region called medial entorhinal cortex (MEC) supports navigation by encoding information about location and movement within an environment. In particular, MEC contains grid cells, which are cells that encode current position by firing in specific loca-tions that tessellate an environment. Beyond grid cells, MEC has also been found to contain a variety of direction, speed, and position-modulated cells, which encode navigational variables in dynamic and heterogeneous ways. Despite the wealth of knowledge quickly amassing re-garding the role of this region in navigation, several key questions have arisen regarding the degree to which external or internal variates (e.g. landmarks or animal state) can influence entorhinal coding properties, how these properties influence downstream regions, and how we can statistically capture the wide diversity of coding properties found in MEC. Over the course of my PhD work, I used a combination of rodent in vivo electrophysiology, behavioral exper-iments, and computational and statistical modeling to address these questions. In this dissertation, I first present evidence supporting a model in which grid cells use input from en-vironmental landmarks to update their position code. Second, I employ computational models that reveal how changes to grid cell patterns alter the stability of downstream codes for space in the hippocampus. Third, I apply a statistical modeling framework that uncovers heteroge-neous entorhinal coding for navigational variables in an unbiased manner, and reveals more mixed selectivity, heterogeneity, and adaptivity based on running speed than previously thought. Finally, by recording entorhinal activity during tasks with different reward structure, I reveal that grid and other spatial-coding cells modulate their activity with reward. Combined, my thesis work probes how external variates, like boundaries or reward, or internal variates, like animal state, influence entorhinal coding properties, and suggests that entorhinal cortex uses flexible representations of navigationally-relevant information to support spatial naviga-tion.

Advisor: Ganguli Surya
Giocomo Lisa
Baccus Stephen A. 
McClelland James L. 
Raymond Jennifer L.
Investigating the molecular effects of the 16P11.2 copy number variant using an induced pluripotent stem cell model

The 16p11.2 copy number variant (CNV) locus is known to increase the risks of autism spectrum disorders (ASD), schizophrenia, and many other developmental problems in humans. However, it not understood as to how the CNVs at this locus, which occur as a heterozygous deletion or duplication of ~600 kbp in size, contribute to the development of these disorders. Previous studies have generated possible gene targets and pathways of interest for further investigation but due to the early onset nature of the phenotypes of the 16p11.2 CNVs, the studies were done using cell types that are not directly applicable (e.g. LCLs) or animal model systems. Here, we investigate the changes to gene expression and DNA methylation using a 16p11.2 CNV patient-derived induced pluripotent stem cell (iPSC) to induced neuron (iN) cell model system. This revealed global alterations to both gene expression and to DNA methylation patterns which further yielded new leads of genes potentially contributing to known patient phenotypes. Specifically, PCSK9 is identified as a possible contributing factor in the development of facial abnormalities in patients, along with also being involved with the reciprocal head circumference and body mass index (BMI) phenotypes seen in the deletion and duplication patients. Additionally, the protocadherin (PCDH) gene family is seen to have significantly altered methylation patterns in the CNV patient samples which could implicate these genes in the etiology of neuropsychiatric disorders.

Keywords: Genetics.
Advisor: Urban Alexander E. 
Bassik Michael 
Sherlock Gavin 
Snyder Michael
Investigating the role of the myeloid circadian clock in aging

The circadian clock regulates daily rhythms across the entire organism, ranging from rhythmic gene transcription to daily cycles in mood. The intrinsic cellular clock consists of a transcription-translation feedback loop between the heterodimers Bmal/Clock and Per/Cry. In healthy immune cells, this clock drives circadian rhythms in cell trafficking, phagocytosis, and cytokine release among many other homeostatic activities. Animals lacking innate immune cell rhythms experience higher rates of sepsis and mortality during an infection. Since aging is often characterized by a loss of homeostatic immune functions, we hypothesized that dysfunction of the cellular circadian clock with aging contributes dysfunction in the immune system and an increased risk for disease. In this study, we used transcriptomic approaches to identify rhythmically expressed genes and pathways and observed that the core cellular clock remains rhythmic with aging. While aged animals still expressed a high number of rhythmic genes, the coordination of these rhythms became impaired. We also used genetic approaches to disrupt the intrinsic cellular clock and observed mild cognitive impairment in middle aged animals. These results suggest that the circadian clock may contribute to age-associated dysfunction in systemic inflammation.

Advisor: Andreasson Katrin
Huguenard John 
Reimer Richard J. 
Wyss-Coray Anton 
Lecea Luis de
Investigating the Spreading of Gene Silencing and Reactivation through the Chicken HS4 Insulator

Chromatin modifications help control gene expression in mammalian cells and spread through positive feedback mechanisms. This spreading can help coordinate gene expression programs, but can also lead to accidental silencing of transgenes. Insulators are genetic elements that can protect transgenes from background silencing. It is hypothesized that they act as barriers against heterochromatin spreading. However, the spreading of heterochromatin-induced gene silencing across insulators has not been directly tested. By engineering Chinese Hamster Ovary (CHO) cells with site-specifically integrated dual reporters, we developed a method to measure the spreading of gene silencing and reactivation across insulators. Each of the dual reporters contains two genes expressing fluorescent proteins separated by different insulator geometries containing the most widely used eukaryotic insulator, HS4, and its core region. Using a doxycycline-inducible system, chromatin regulators associated with histone methylation (KRAB, EED) and DNA methylation (DNMT3B) were recruited for five days at varying strengths to the upstream gene to induce gene silencing. The cells were monitored for their silencing and reactivation dynamics using flow cytometry. Surprisingly, neither the HS4 insulator nor its core region prevented spreading of silencing from the upstream target gene to the downstream gene. However, the presence of insulators hindered the ability to silence both genes when compared to spacer DNA. Moreover, after the end of EED and KRAB recruitment, the reactivation rates of both genes were 2-3x higher when the upstream gene was flanked by core insulators. This element also led to reactivation of both genes after DNMT3B silencing, despite previous reports that DNA methylation leads to permanent epigenetic memory. Therefore, rather than acting as a barrier to spreading, the HS4 insulator activates the entire gene locus.

Keywords:  Department of Bioengineering
chromatin
insulators
spreading
epigenetics
HS4
Department of Bioengineering
Thesis
Advisor: Bintu Lacramioara
Covert Markus
Investigating the switching mechanism of interfacial phase change memory

Phase Change Memory (PCM) is a leading candidate for next generation data storage, but it typically suffers from high switching (RESET) current density (20--30 MA/cm2). Interfacial Phase Change Memory (IPCM) is a type of PCM using multilayers of Sb2Te3/GeTe, with up to 100× lower reported RESET current compared to the standard Ge2Sb2Te5-based PCM. Several hypotheses involving fundamentally new switching mechanisms have been proposed to explain the low switching current densities, but consensus is lacking. IPCM switching is investigated by analyzing its thermal, electrical, and fabrication dependencies. First, the effective thermal conductivity (∼0.4 Wm−1K−1) and thermal boundary resistance (∼3.4 m2KGW−1) of Sb2Te3/GeTe multilayers is measured. Simulations show that IPCM thermal properties account only for ∼13% reduction of current vs standard PCM and cannot explain previously reported results. Interestingly, electrical measurements reveal that IPCM RESET indeed occurs by a melt-quench process, similar to PCM. High deposition temperatures are shown to cause defects including surface roughness and voids within the multilayer films. Thus, the substantial RESET current reduction of IPCM appears to be caused by voids within the multilayers, which migrate to the bottom electrode interface by thermophoresis, reducing the effective contact area. These results shed light on the IPCM switching mechanism, suggesting that an improved control of layer deposition is necessary to obtain reliable switching. Finally, finite element simulations are performed to predict time and volumetric scaling trends of PCM switching. Usage of pulse widths beyond a few nanoseconds are shown to be essentially wasting energy due to the time scales of device heating and is experimentally verified. Finally, current densities are predicted to become worse at ultra-scaled dimensions (bottom electrode diameter < ~10 nm) due to thermal and current confinement problems.

Keywords: Electrical Engineering.
Advisor: Wong Hon-Sum Philip
Pop Eric 
Saraswat Krishna
Investigation of AZGP1 as a marker and driver of prostate epithelial differentiation

Prostate cancers exhibit a range of clinical behaviors, from indolent to highly aggressive, reflecting differences in underlying biology. Tailored treatments are needed to match those differences. Our lab previously identified a subset of prostate cancers marked by expression of Alpha-2-Glycoprotein 1, Zinc-Binding, (AZGP1) that is associated with more favorable patient outcomes. AZGP1 is also expressed in mature prostatic secretory epithelium, and we have speculated that it marks a particular state of prostatic epithelial differentiation where the corresponding cancerous cells are clinically less aggressive. Here, we have investigated the connection between AZGP1and prostatic epithelial differentiation using a three dimensional (3D) cell culture model system. We show that prostatic epithelial cells grown in a basement membrane rich extract form spheroid cell aggregates that exhibit morphologic differentiation, and that AZGP1 expression is induced in a subset of cells coincident with morphologic differentiation. To investigate a functional link between AZGP1 and prostatic epithelial differentiation, we used CRISPR/Cas9 genome editing to knock out AZGP1 in prostatic epithelial cells. Notably, AZGP1 knockout disrupts normal morphologic differentiation, producing spheroids with increased pyknotic and fragmented nuclei. By transcriptome profiling, the AZGP1 knockout spheroids also exhibit lost induction of genes associated with epithelial differentiation, and lost repression of genes of the mitotic cell cycle. Finally, the genes regulated by AZGP1 in 3D culture show enrichment among the genes co-expressed with AZGP1 in normal prostate tissue, validating our 3D model system. Taken together, our findings reveal that AZGP1 not only marks prostatic epithelial differentiation, but likely functions as a master regulator of cell fate, inducing a molecular differentiation program while repressing cell division. Agents that induce or mimic AZGP1 activity may provide novel therapies for prostate cancer.

Keywords:  Department of Biology
biology
cancer
prostate cancer
cancer biology
AZGP1
differentiation
Thesis
Advisor: Jonathan Pollack
Patricia Jones
Investigation of therapeutic effects of a novel adrenergic ligand in mouse models of Alzheimer’s disease

A well-established sign of early-stage Alzheimer’s disease (AD) is degeneration of the noradrenergic network, the circuit of neurons charged with producing and distributing the neurotransmitter noradrenaline (NA) throughout the brain. Thus, a substantial decrease in NA signaling is believed to underlie AD-related cognitive deficits and pathological changes within the brain. Studies have demonstrated that reduction or inhibition of NA signaling exacerbates cognitive symptoms of AD in mice and humans, and reduction of NA signaling has also been shown to increase AD-related neuropathological changes in animal models. Collectively, such findings suggest that activation of the adrenergic system could alleviate AD progression. Previous mouse studies on the therapeutic potential of beta-adrenergic system activation have utilized compounds that are largely ineffective at crossing the blood-brain barrier (BBB) to exert an effect within central nervous system (CNS). The current study investigates the capacity of a novel small molecule modulator, initially believed to be a selective beta1-adrenergic receptor (ADRB1) partial agonist with high BBB permeability, to alleviate neuropathological changes in Thy1-hAPPLond/Swe+ (APP) and 5XFAD mouse models of AD. Tissue from two chronic dosing studies performed in these transgenic lines with the compound SHSU01010 was processed for evidence of three key neuropathological AD hallmarks – amyloid beta plaque accumulation, neuroinflammation, and synaptic loss. Data from immunohistochemistry, quantitative RT-PCR, and ELISA show that chronic SHSU01010 administration was ineffective at alleviating the AD neuropathology for which a phenotype was observed in APP and 5XFAD mice. We believe the lack of therapeutic efficacy exhibited by SHSU01010 may be attributed to its existence as two stereoisomers, where one may agonize beta-adrenergic signaling while the other antagonizes the system. Additionally, further characterization of SHSU01010 has demonstrated that the compound shows in vivo instability due to degradation of the compound by liver enzymes, and that the compound may not be selective for ADRB1. While the findings from the current study are inconclusive, we believe ADRB1 agonism with CNS-permeable compounds still shows substantial promise for AD treatment.

Keywords:  Department of Biology
Alzheimer’s disease
noradrenaline
beta1-adrenergic receptor
biology
Thesis
Advisor: Shamloo Mehrdad
Heller H. Craig
Investing in socialist Poland : a transnational history of finance in the Cold War, 1944-1991

This dissertation explores socialist Poland's ties to international financial institutions during the Cold War era. Revealing the extent to which individuals and institutions cooperated across the Iron Curtain, it challenges the idea of a bipolar world order as an all-encompassing description of international relations in the second half of the twentieth century. Studying socialist Poland solely within the framework of Soviet politics and the bipolarity of the Cold War omits a crucial part of its international history; the country's development followed worldwide patterns of globalization, not just the rhythm of superpower politics. This dissertation argues that the end of communist rule in Eastern Europe cannot be understood without considering the region's integration into global financial markets.

Keywords: History.
Advisor: Naimark Norman M. 
Holloway David
Weiner Amir
Invisible cages : algorithmic evaluations in online labor markets

Artificial Intelligence systems, powered by algorithms, are seemingly everywhere: in corporations, hospitals, classrooms, cars, and even baby monitors. Despite the prevalence and breathless rhetoric, fewer studies have examined how these systems impact people in practice. This dissertation focuses on understanding the impact of algorithms on people using online labor markets to find work. Existing organizational and social science theory suggests that artificial intelligence and algorithmic systems are "tightening" the iron cage by providing a more sophisticated, rational method of controlling the way people work and interact. This dissertation, however, reveals how an online labor market's use of algorithms is creating modern day invisible cages, in which platforms deliberately hide the norms and expectations for how people should behave. To unpack and theorize this central finding, I draw upon field work collected from one of the world's largest online labor markets. Using participant observation, interviews, and extensive archival data, I first show how people using the online labor market unwittingly gave the platform full permission to implement algorithms that were completely opaque to them. I highlight how the way in which people agree to the terms of service in an online labor market context represents a significant shift compared to previous agreements people consented to in similar, offline labor market settings. I then show how the online labor market implemented an inscrutable algorithm dictating people's success on the platform. The implementation of this algorithm led to what I call "superstitious reactivity, " because people were never able to verify if and how their actions contributed to their success on the online labor market. Taken together, this dissertation has implications for our understanding and the literature on algorithms, evaluations, reactivity, reputation, labor market intermediaries, employment relationships, digital contracts, and agnotology.

Keywords: Management Science and Engineering.
Advisor: Barley Stephen R. 
Valentine Melissa (Melissa A.) 
Powell Walter W.