VictorJuiz/thesis huggingface dataset:
Engineering Gradient Hydrogels with Brain-mimicking Niche Cues for High-throughput Screening of Brain Cancer-ECM Interactions in 3D
Keywords:  Department of Biology
Biology
Engineering
Bioengineering
Oncology
Glioblastoma
Brain Cancer
3D Gradient Hydrogel
PEG
Cell Proliferation
Cell Morphology
Drug Resistance
Gene Expression
Extracellular Matrix
Thesis

Brain cancer is a devastating disease that affects both adults and children, yet effective therapies remain elusive. Glioblastoma (GBM) makes up 15.1% of primary brain tumors, and represent one of the most common types of brain cancers. One key hallmark of brain tumors is the significantly increased tissue stiffness as the cancer progresses, likely due to changes in cell fates and extracellular matrix (ECM) compositions of tumor tissues. Elucidating the role of ECM cues such as matrix stiffness in modulating brain cancer progression would be critical in improving the therapeutic outcomes of this devastating disease. Previously, the Fan Yang laboratory has engineered a novel gradient platform to study tissue zonal organization in a 3D environment. In this project, we focused on employing such platform for high-throughput screening of matrix stiffness effects on brain cancer cells, and we chose patient-derived GBM 270 as a model cell type. Using a syringe pump and gradient maker system, we were able to create and characterize a PEG-based gradient hydrogel with brain-mimicking biochemical cues and tunable stiffness. We found that patient derived glioblastoma cells were able to survive and proliferate in this gradient hydrogel platform over 21 days. We then evaluated the effects of matrix stiffness in modulating patient-derived GBM cell proliferation and invasion in 3D using such platform. We observed significant differences in cell morphology between different zones, specifically in cell spreading indicated by their actin filament organization. We found zonal- dependent upregulation of genes responsible for the ECM degradation, which is integral to cell spreading and cancer metastasis. We finally examined the drug resistance of GBM 270 cells encapsulated within different zones in gradient hydrogels, and found that they exhibited differential resistance to Temozolomide (TMZ), indicating the significant effect of matrix stiffness on cell phenotype changes. This project has demonstrated that 3D gradient platform can be broadly adapted with tunable biochemical and mechanical matrix cues for elucidating complex niche interactions in the progression of brain cancer or other cancer types in 3D using reduced materials, cells and time.
Engineering non-antibody proteins to modulate cancer cells and tumor microenvironment interactions [electronic resource]
Keywords: Bioengineering.

Tumor cell proliferation, migration, and survival and the formation of stromal blood vessel networks are all directed by aberrant signaling from protein ligands and their cognate receptors in the tumor microenvironment. These molecules play a central role in a wide range of biological systems by allowing intercellular communication. Thus, therapeutics that can effectively modulate these processes have been developed and highlighted as important drugs. Traditionally, tumor targeting of cell surface receptors and ligands is accomplished using neutralizing antibodies. However, this approach is limited by the high affinity of ligand-receptor interactions that often cannot be effectively inhibited by monoclonal antibodies, which typically have affinities in the low nanomolar range. To overcome this challenge, we have taken two approaches to developing new cancer therapeutics: 1) Creating a high affinity (pM) dimeric tumor targeting protein scaffold using site-specific chemical conjugation; 2) Engineering high affinity (pM) inhibitors of a natural ligand, and its cognate receptor, to block crosstalk between tumor cells and cancer-associated fibroblasts. In this work, we developed a strategy for incorporating a non-natural amino acid for site-specific chemical conjugation to create dimeric integrin-targeting cystine knot (knottin) miniproteins that bound tumor cells with pM affinity and more effectively inhibited tumor cell migration and proliferation compared to the knottin monomers or the small molecule drug cilengitide. Additionally, based on a novel mode of crosstalk between tumor cells and cancer-associated fibroblast discovered by our collaborator, professor Alejandro Sweet-Cordero (University of California, San Francisco), we developed inhibitors of ciliary neurotrophic factor receptor (CNTFR) and its ligand, cardiotrophin-like cytokine factor 1 (CLCF1), by engineering the molecules themselves to function as a high affinity 'decoy receptor' and an antagonistic ligand, respectively. In the process of engineering the antagonistic ligand we also identified potent receptor agonists, which may have beneficial effects in neuroregeneration.
Enhancing the light-matter interaction in graphene [electronic resource]
Keywords: Materials Science and Engineering.

Graphene, a two-dimensional sheet of hexagonally arranged carbon atoms, can absorb 2.3 % of the incident light over a broad range of wavelengths. Whereas the single-layer-absorption is impressive, it is not strong enough for many optoelectronic applications as virtually all the light is transmitted. Moreover, for active devices such as electro-optical modulators and actively controlled thermal emitters, dynamic control over absorption is required as well. We will discuss an electrically-tunable Salisbury screen device configuration that involves placing graphene about a quarter wavelength (λ/4) distance away from a metal back reflector. This design is capable of achieving both increased absorption and active absorption modulation in a single graphene sheet. However, there is an increasing desire to build ultra-compact devices such that the costs of these devices are minimized without compromising on their performance. To satisfy this additional requirement, we combine graphene with metamaterial mirrors that enhance the electric field and hence light-matter interaction within graphene at the mirror surface. We employ Raman spectroscopy to explore the interesting dependence of the electric fields within graphene on the underlying metamaterial mirror dimensions and project the graphene-coated metamaterial mirrors as uniform and tunable SERS (Surface Enhanced Raman Spectroscopy) substrate. As a final step, we perform reflectance measurements on these metamaterial mirrors and establish a direct correlation of these measurements with Raman measurements. We conclude, therefore, that it is possible to predict the strength of our SERS substrate using reflectance measurements solely.
Entanglement and Transport Properties of Non-Equilibrium Steady States of 1-D Quantum Systems
Keywords:  Department of Physics
Stanford University
Department of Physics
Senior Thesis
Non-equilibrium Dynamics
Steady State
Lindblad Dynamics
Quantum Spin Chain
Entanglement
Transport
Thermalization
Matrix Product States
MPS
Numerical Simulations
Thesis

We numerically study the non-equilibrium steady states of two 1-D models, a free fermion quantum wire model and a Heisenberg XXZ chain, both governed by open system Linblad dynamics. The physical setup consists of a unitarily evolving "bulk" coupled via its boundaries to two dissipative "leads".
For the quantum wire, the open system dynamics is designed to drive the leads to thermal equilibrium, and by choosing different temperatures and chemical potentials for the two leads we may drive the bulk into a non-equilibrium current carrying steady state. We report two main results in this context. First, we show that for an appropriate choice of dynamics of the leads, the bulk state is also driven to thermal equilibrium even though the open system dynamics does not act directly on it. Second, we show that the steady state which emerges at later time, even in the presence of currents, is lightly entangled in the sense of having small mutual information and conditional mutual information for appropriate regions. We also report results for the rate of approach to the steady state.
For the Heisenberg model, the leads impose fixed magnetizations at the ends of the chain, and can be tuned to enforce a spin density gradient across the chain. We use the matrix product formalism to study the transport properties of this model in two qualitatively different regimes: ideal conductor and diffusive conductor. We show numerically that matrix product states are a good approximation for the steady states of this model.
More generally, our work has bearing on recent attempts to formulate numerically tractable methods to compute transport properties in strongly interacting models.
Entangling atoms for quantum metrology [electronic resource]
Keywords: Applied Physics.

Atomic sensors, such as atomic clocks and atom interferometers, have to date achieved very precise measurements of various quantities such as time, acceleration, gravitational fields and distances. However they currently use coherent (or unentangled) states of atoms, which imply that their precisions are limited by the standard quantum limit and their precision scales as $\sqrt{N}$ where $N$ is the number of atoms being used in the sensor. However this limit of these sensors can be reduced by using atoms that are in an entangled states. This work's main focus is on the creation of specific type of entangled states known as spin-squeezed states. The creation of a 20dB spin-squeezed state an ensemble of ultracold $^{87}$Rb atoms using a cavity-mediated light-atom interaction is demonstrated, with which proof-of-principle metrology is performed. More specifically, a tipping measurement resolving more than 18dB beyond the standard quantum limit and a clock measurement with a quantum enhancement of over 10dB are shown. The single-shot phase resolution of the apparatus of 147 $\mu rad$ achieved is the most precise to have been shown to date. In addition, preliminary results in which retention of squeezing of in free-space for over 1ms are discussed. Another experiment showing a ``quantum phase magnification'' method is also implemented. This method allows for entanglement-enhanced measurements without low-noise detection. We perform squeezed-state metrology 8dB below the standard quantum limit with a detection system that has a noise floor of 10dB above the standard quantum limit. Finally, the highly non classical nature of the squeezed states created is discussed, and the collective measurements of our state showing Bell correlations significant to 124 standard deviations are presented.
Entrepreneurship in emerging economies [electronic resource] : institutions and relationships
Keywords: Management Science and Engineering.

How can entrepreneurial firms in emerging economies effectively innovate, grow, and achieve high performance? In this dissertation, I conduct a detailed examination of the institutional and relational challenges that entrepreneurial ventures in emerging economies face as well as strategies they may utilize to overcome these challenges. Three distinct papers constitute the core of this cumulative dissertation. In the first paper, I examine how inconsistencies in the institutional environment affect entrepreneurial ventures' ability to innovate and achieve high performance. In the second paper, I examine how entrepreneurial ventures may establish new organizational roles and responsibilities in spite of contradictory roles and hierarchical positions in the social lives of the entrepreneurs that founded these ventures. In the third paper, I examine how the social relationships of venture founders may sometimes give rise to malfeasance—and how these founders may curb this distinct form of malfeasance. Taken together, I examine the institutional and relational challenges that entrepreneurial ventures in emerging economies face while also presenting insights on how such challenges may be overcome.
Environmental Justice and Climate Policy: Is California’s Cap and Trade Failing Disadvantaged Communities?
Keywords:  Department of Economics
environmental justice
cap and trade
equity
criteria pollutants
Thesis

Pollution pricing policies offer advantages over traditional environmental regulation in compliance flexibility and cost effectiveness, but introduce more uncertainty over where emissions will occur. Consequently, environmental justice organisations have raised equity concerns about California’s flagship cap-and-trade program; greenhouse gas emissions trading could generate increased local concentrations of criteria air pollutants in socioeconomically disadvantaged neighborhoods. Using U.S. Environmental Protection Agency (EPA) air quality monitoring station data, I use spatial interpolation to construct a census tract-level ten-year panel of concentration for six pollutants. I estimate a difference-in-differences model with fixed effects, and find that cap and trade generally improved relative equity for CO, NO2, PM2.5, PM10 and SO2 but worsened it for O3.
Equilibrium and non-equilibrium realizations of topological states of matter [electronic resource]
Keywords: Applied Physics.

Topological states of matter are a class of quantum states that exhibit topologically-protected properties which are insensitive to weak perturbations or disorder. Spurred by recent progress in melting, enhancement and induction of electronic order out of equilibrium, a tantalizing prospect concerns instead inducing topological phases as transient non-equilibrium steady states via broad optical pulses, to affect electronic or magnetic properties. This thesis will discuss a two-pronged approach of optically manipulating the band topology of a semiconductor, as well as inducing topological order in strongly-interacting topological band structures and frustrated Mott insulators. We will first discuss a non-equilibrium generalization of electronic band structure theory to show that irradiating transition-metal dichalcogenide monolayers with circularly-polarized light can induce tunable topological band transitions and chiral edge modes out of equilibrium. We then draw on an intrinsic position-momentum duality of the fractional quantum Hall (FQH) effect to discuss a formalism to capture FQH states in interacting topological band structures in the absence of an external magnetic field. Finally, we will extend these ideas to frustrated Mott insulators and show that pumping a Kagome antiferromagnet with a broad circularly-polarized light pulse can dynamically break time-reversal symmetry and transiently stabilize a chiral spin liquid -- the ν=1/2 FQH effect of spins. The results presented suggest new avenues to marry dynamical symmetry breaking, strong interactions, and ab initio materials modelling, to access elusive phase transitions that are not readily accessible in equilibrium.
Essays in applied microeconomics [electronic resource]
Keywords: Economics.

This dissertation focuses on the financing and occupation decisions of graduate students in the United States, as well as on federal policies related to student loan and health care expansions. In the first chapter I investigate why federal student loans crowd out the private market by exploiting the 2006 introduction of graduate PLUS loans. I show that access to PLUS loans led students to replace private with PLUS loans almost one-for-one, but that most borrowers could receive lower interest rates through the private market for student loans. I model graduate student's borrowing decisions and find that the decision to take out federal loans can be rationalized by federal income-based repayment plans which functions as insurance against low future wages. The second chapter of this dissertation is co-authored with Paul Oyer and focuses on the positions taken by MBA graduates and summer interns. We show that the excess returns for firms that MBAs join are higher in the year leading up to the start of employment. These excess returns are mean reverting in the following year and are much smaller. We find some evidence that the firms that recruit MBAs, but do not hire, have the opposite pattern and exhibit higher excess returns in the year after the recruiting process. We go on to show that the relationship between MBA hiring and stock returns is similar to that for other non-executive employee hires but very different from CEOs. The third and final chapter of this dissertation is co-authored with Vilsa Curto. We study the short term affects of Medcaid expansion on enrollment into Medicaid and access to care by focusing on four states that were early adopters of the 2010 Affordable Care Act's Medicaid expansion. We find that Medicaid expansion leads to a 13 percent increase in overall enrollment, a 27 percent increase in enrollment among adults ages 23 to 65, and a 16 percent increase in the number of Medicaid patients seen by primary care physicians. We also find that Medicaid expansion increases physician participation on the intensive margin but not on the extensive margin.
Essays in finance and macroeconomics [electronic resource]
Keywords: Economics.

The first chapter of this dissertation, Due Diligence and Security Design, studies equilibrium security design in a setting in which firms possess private information about the quality of their projects but investors have access to an information production technology. In the model, firms and investors enter into contracts directly and seek counterparties in a competitive environment. Once a deal is reached, investors have an opportunity to perform due diligence on the target firm before deciding whether to accept or reject the offer. I show that when information acquisition is endogenous, firms with higher quality projects may actually be more information-averse, choosing to deter screening by issuing more valuable and more information-insensitive securities while firms with lower quality projects do the opposite. The second chapter, Inequality Shocks and Redistribution, is co-authored with Michael Boskin and studies how democratic political systems generally respond - through redistributive fiscal policy - to changes in income inequality. Using data from the Current Population Survey, we explore the mapping between the distribution of market income and the distribution of post-tax, post-transfer disposable income among U.S. states over the last quarter century. Various instrumental and control variables make it possible to isolate shocks to inequality which are both pure (independent of overall prosperity as well as the demography of need/social insurance) and exogenous (e.g. unrelated to the reverse causal effects of taxes and transfers on work incentives, etc.). The third and final chapter, Production, Predation, and Path Dependence, is co-authored with Mohammad Akbarpour and studies the choice between production and predation (e.g. petty crime, fraud, rent-seeking, corruption) in the pursuit of income. We show that the influence of aggregate behavior on individual incentives generates strategic complementarity and multiple equilibria. A given set of institutions and policies may be consistent with a range of possible crime rates, and the ultimate outcome is determined by history. As a result of this path dependence, temporary changes in enforcement policy can have permanent effects on output and welfare.
Essays in firm performance with macroeconomic implications [electronic resource]
Keywords: Economics.

This thesis is concerned with how firms interact with factors in their economic environment, and the implications this has for the macroeconomy. First, I examine the role of bank lending frictions and housing collateral for small business credit during the Great Recession. I use a new dataset from the leading online accounting software in the United States with millions of financial transactions for small businesses. I find that bank failures during the Great Recession are associated with declines in credit for small firms but not micro firms. In contrast, movements in house prices at the owner's ZIP code are positively associated with credit for micro firms but not small firms. The results suggest differences within small businesses in the channels used to overcome asymmetric information: micro firms appear to depend more on housing collateral and small firms on lending relationships, consistent with the associated costs to lenders. Next, I study how weak institutional environments in poor countries lead to low tax compliance, especially for firms where owners have high-powered incentives and managerial control. Using evidence for publicly-traded manufacturing firms in India, this paper shows that when there is continued involvement of the founding family, firms pay less excise tax than in other firms. In addition, firms respond by less to an increase in the tax rate compared to non-family firms. I find that the difference between family and non-family firms' tax compliance decreases with the introduction of mandatory online filing. These family firm tend to be smaller and less productive, indicating that the lower effective tax rates may divert resources away from larger, more productive firms and reduces aggregate output and productivity. Finally, in work with with the US Census Bureau and coauthors, a new survey of "structured" management practices in 32,000 US manufacturing plants is conducted and studied. We find an enormous dispersion of management practices across plants, with 40% of this variation across plants within the same firm. We find evidence for four "drivers" of management: competition, business environment, learning spillovers and human capital. Collectively, these drivers account for about a third of the dispersion in structured management practices.
Essays in health care economics [electronic resource]
Keywords: Economics.

This dissertation presents new empirical evidence on how three related aspects of health insurance regulation affect productivity of health care delivery in the US. First, it addresses the potential role of managed care in decreasing costs in Medicaid by examining evidence on use of C-sections for Medicaid beneficiaries in Florida. I find HMO enrollees are nearly 40% less likely to receive a C-section compared to those on traditional Medicaid, all else equal. This effect is heterogeneous and declines in magnitude as patient complications become more severe - with no difference in case of patients with severe delivery complications. I interpret these results as evidence that managed care influences physicians to choose lower cost treatments, without sacrificing patient health. Second, I address the role of recent payment reforms in enhancing quality of care. I exploit the introduction of a large federal program that penalizes hospital readmissions and policy-driven variation in penalty across hospitals to identify causal effects on quality of care as well as selective admission of patients. I begin by documenting a modest decline in readmission rates due to the penalty. Next I show that both channels are quantitatively important and that improvements in quality account for 50-60% of the decrease in readmission rates. I also find substantial heterogeneity in effectiveness of the penalty incentive across different types of conditions. Third, in a paper co-authored with Mark Duggan and Emilie Jackson I consider the recent Medicaid expansion mandated by the Affordable Care Act and identify causal effects on a) crowd-out of existing informal insurance, and b) consumer moral hazard and health effects. We deploy administrative data from hospitals and emergency rooms in California over 2008-15. We find evidence of substantial crowd-out of county insurance programs -- implying a large transfer from federal taxpayers to local governments. We estimate a large increase in the rate of hospital and ER use due to insurance coverage among the near-elderly. However we find only suggestive improvements in patient health. Financial benefits for hospitals are more readily apparent. Hospitals previously serving a high share of uninsured patients benefit disproportionately with a 10\% increase in total revenue relative to remaining hospitals.