VictorJuiz/thesis huggingface dataset:
Modeling the role of epigenetic inheritance in adaptation and phenotypic heritability [electronic resource]

Although genetic variation provides the basis upon which traits are inherited and respond to selection, non-genetic inheritance can also play a role in phenotypic heritability and adaptation. Epigenetic inheritance, the inheritance of changes in gene expression and function, has been shown to contribute to heritability in a range of model systems. This thesis presents population genetic models of epigenetic inheritance, characterizing the role of epigenetic inheritance in adaptation and heritability, how epigenetic variation may interact with the environment, and the ecological scenarios in which epigenetic inheritance may evolve. Chapter 2 outlines a model of epigenetic inheritance as a mutational process, and derives analytical properties of inheritance and the response to selection. Chapter 3 extends this model, incorporating environmental influences on epigenetic state to explore the interaction between epigenetics and the environment. Chapter 4 models the evolutionary invasion of novel epigenetic regulatory mechanisms, finding the regimes of selection and temporal environmental variation that may select for epigenetic regulation. Chapter 5 focuses on a specific type of epigenetic regulation, stochastic switching, to understand how spatial and temporal variation in selective pressures interact to influence the evolution of epimutation rates and the corresponding fidelity of phenotypic transmission. These chapters show that epigenetic inheritance can allow for rapid adaptation, though the specific details of selection through space and time will determine its relative importance in the adaptive process. Laboratory and field experiments in epigenetics must carefully incorporate spatial and temporal effects to accurately evaluate the role of epigenetic inheritance in evolution.

Keywords: Biology.
Advisor: Feldman Marcus W. primary advisor. Thesis advisor
Fraser Hunter B. advisor. Thesis advisor
Petrov Dmitri Alex
Tuljapurkar Shripad
Models of species interactions in evolution and ecology [electronic resource]

This thesis presents theoretical models exploring how species interactions influence evolutionary and ecological processes. Chapters 2 and 3 examine how host-parasite interactions affect the evolution of mutation rate and non-random mating respectively. Chapter 4 verbally addresses whether the Allee effect could have a role in species co-existence, and Chapter 5 investigates this question with a model.

Keywords: Biology.
Advisor: Feldman Marcus W. primary advisor. Thesis advisor
Petrov Dmitri Alex
Rosenberg Noah
Tuljapurkar Shripad
Modification and manipulation of one-dimensional carbon materials for electronics [electronic resource]

As Moore's Law demands ever smaller transistors, it becomes necessary to solve the deleterious effects of scaling. Graphene, with its intrinsically two-dimensional nature, offers a potential solution to the short channel effects seen with traditional geometries and materials. Using a 2D material, or one-dimensional in the form of either graphene nanoribbons (GNRs) or single walled carbon nanotubes (SWNTs), instead of bulk Si allows for an intrinsically compact device geometry, which should offer the ability to maintain high gate control far into the sub-10 nm regime. Graphene based materials also show considerably higher carrier mobility than Si. It is anticipated then that SWNT/Graphene transistors will show significantly better metrics in both speed and energy delay than Si based transistors. There are critical challenges that currently prevent the wider implementation of carbon electronics, the lack of bandgap in graphene, the roughness of GNRs, and the variability of SWNTs. This thesis will describe several projects aimed at addressing these challenges by modification and manipulation of these carbon materials. In the first project described in this thesis, we cover high-field transport in GNRs on silicon dioxide, up to breakdown. Next, in the third chapter, we investigate chlorine plasma reaction with graphene and GNRs and compare with hydrogen and fluorine plasma reactions. In the fourth chapter, we investigate the effect of uniaxial strain (0%-6%) introduced into individual GNRs by atomic force microscopy (AFM). In the fifth chapter, we characterize ~98% pure semiconducting single walled carbon nanotubes (s-SWNTs) obtained by gel filtration of arc-discharge grown SWNTs with diameters in the range of 1.2-1.6 nm. In the sixth chapter, we present a process where highly pure s-SWNTs are separated from bulk materials and self-assembled into densely aligned rafts driven by depletion attraction forces. In the seventh chapter, s-SWNTs are self-assembled using these same depletion attraction forces into rafts along lithographically defined patterns of narrow pitch of 100 and 200 nm.

Keywords: Electrical Engineering.
Advisor: Dai Hongjie
Pop Eric advisor. Thesis advisor
Wong Hon-Sum Philip
A modular framework for performance-based durability engineering [electronic resource]

This dissertation lays the foundation for performance-based assessment of structural durability, and demonstrates the possibility and value of integrating multi-disciplinary research to support the design of sustainable infrastructure. The design and renewal of sustainable and resilient infrastructure pose challenges to managers operating under funding constraints and changing use and climate conditions. An approach to durability design that predicts quantitative sustainability metrics, considers uncertainty, and incorporates long-term socioeconomic and climate changes, is desirable and not currently available. A proposed framework for performance-based durability engineering (PBDE) has these desired features. The proposed PBDE framework assesses structural durability in three analysis stages: (1) exposure, (2) deterioration and repair, and (3) impact. Corrosion in reinforced concrete coastal structures has been selected as the case study deterioration mechanism. This dissertation develops the PBDE framework, evaluates the PBDE methodology against an existing probabilistic methodology, assesses the sensitivity of deterioration predictions and decision-support information to a variety of sources of uncertainty, and illustrates PBDE's use in informing infrastructure management decision-making. Advantages of the proposed framework include the incorporation of uncertainty in climate change, the ability to deaggregate sources of uncertainty and to update results to reflect new information, and the facilitation of sensitivity assessment. Additional research motivated by PBDE's development identifies the high sensitivity of a fully-coupled numerical heat and mass transport model to short-term fluctuations in surface boundary conditions, and this sensitivity's down-stream implications in predicting greenhouse gas emissions related to structural deterioration. Areas of future research to fully realize PBDE's potential in practice are discussed.

Keywords: Civil and Environmental Engineering.
Advisor: Billington Sarah L. (Sarah Longstreth)
Baker Jack W. advisor. Thesis advisor
Lepech Michael advisor. Thesis advisor
Molecular imaging and mathematical modeling approaches to interrogate the liquid phase of cancer [electronic resource]

Metastasis, the cause for 90% of cancer mortality, is a complex and poorly understood process, often involving the invasion of blood vessels by circulating tumor cells (CTCs). CTCs can be detected and harvested from a blood sample and are potentially ideal candidates for a real-time "liquid biopsy" of cancer. How and when these cells are circulating in the blood, on their way to potentially give rise to metastasis, is a question that remains largely unanswered. To address this issue, in this thesis, we developed new mathematical and molecular imaging approaches to interrogate CTCs and characterize their dynamics in an orthotopic mouse model of breast cancer metastasis. We summarize current approaches and major findings in the field of CTC research. We then describe a 1-compartment mathematical model describing how a metastasizing cancer is giving rise to CTCs in the bloodstream. Next, we describe how we developed a simple bioluminescence imaging assay to detect and quantify CTCs in any cancer mouse model. We demonstrate how this method allows to uncover the dynamics of CTCs during cancer progression and provide in vivo measurements of the mathematical model parameters. We then show the first reported use of a miniature mountable intravital microscopy setup for in vivo imaging of CTCs in awake animals. This novel technology will become a useful technique for the precise characterization of the long-term dynamics of CTCs in vivo. Finally, we present our early results in investigating the metabolomics of CTCs, a promising avenue to characterize the properties of a cancer using the "liquid biopsy". This approach could lead to the identification of metastasis-initiating cells among CTCs, as well as provide critical information for the prediction of response to therapy.

Keywords: Bioengineering.
Advisor: Gambhir Sanjiv Sam primary advisor. Thesis advisor
Graves Edward (Edward Elliot)
Pelc Norbert J. advisor. Thesis advisor
Molecular mechanisms regulating neural circuit assembly in caenorhabditis elegans [electronic resource]

Nervous system function, from sensory perception to motor control, requires precisely neural circuit assembly. Therefore, elucidating the molecular and cellular mechanisms which establish and maintain functional neural circuit is of fundamental importance to our understanding of the brain. We develop a novel repressible binary expression system in C. elegans being able to manipulate neural circuit more precisely. We demonstrate that the unfolded protein response (UPR) regulates dendrite morphogenesis of a polymodal nociceptive neuron PVD. Finally, we propose the sex-dimorphic Dosage Compensation Complex (DCC) may regulate synaptic specificity in the pheromone sensory circuit. These results suggest that a diverse assemblage of molecular and cellular mechanisms are necessary for the precise and appropriate assembly of neural circuits. These mechanisms can be elucidated using simple nematode C. elegans in a reductionist manner.

Keywords: Biology.
Advisor: Shen Kang
Clandinin Thomas R. (Thomas Robert)
Kopito Ron Rieger
Luo Liqun
Molecular regulation of muscle-resident mesenchymal stem cells [electronic resource]

The platelet-derived growth factor receptor alpha (PDGFR [alpha]) exhibits divergent effects in skeletal muscle. At physiological levels, signaling through this receptor promotes muscle development in growing embryos and proper angiogenesis in regenerating adult muscle. However, increased PDGF ligands and enhanced PDGFR [alpha] pathway cause pathological fibrosis. This excessive collagen deposition, which is seen in aged and diseased muscle, interferes with proper muscle contraction and limits the effectiveness of gene- and cell- based therapies for muscle disorders. Although compelling evidence exists for the role of PDGFR [alpha] in fibrosis, little is known about the cells through which this pathway acts. Here we show that PDGFR [alpha] signaling regulates a population of muscle-resident mesenchymal stem cells (MSCs) that play a supportive role in muscle regeneration but may also cause fibrotic buildup when aberrantly regulated. Unexpectedly, our investigation revealed that changes in alternative polyadenylation of PDGFR [alpha] control MSC activation and consequently tissue regenerative potential. MSCs produce multiple transcriptional variants of PDGFR alpha] with different polyadenylation sites including an intronic variant of PDGFR [alpha] that codes for a protein isoform containing a truncated kinase domain. This variant, upregulated during regeneration, inhibits PDGF signaling and prevents MSC over-activation. Increasing expression of this isoform through administration of specified morpholinos limits fibrosis in vivo. Furthermore, in our global analysis of polyadenylation patterns in MSCs, we show that intronic polyadenylation is not limited to PDGFR [alpha]. Rather, it is a widespread phenomenon, and the levels of intronic polyadenylation variants compared to their full-length counterparts increases with cell activation on a global level. Overall, our findings suggest both biological relevance and therapeutic potential of modulating polyadenylation patterns in stem cell populations.

Advisor: Rando Thomas A.
Brunet Anne
Chang Howard Y. (Howard Yuan-Hao)
Fire Andrew Zachary advisor. Thesis advisor
Monetary policy with heterogeneous beliefs [electronic resource]

This paper studies the impact of monetary policy with heterogeneous beliefs in a micro-founded New Keynesian model (as developed in Kurz(2012) and Kurz, Piccillo and Wu(2013)) when there are demand shocks in the economy. The main question asked in this paper is the effect of agents' heterogeneity on monetary policy. How would heterogeneity of beliefs affect the dynamics of the economy, and most importantly, the policy rules to be adopted to maximize individual welfare on average? This paper explores the unique characteristics of belief heterogeneity by looking at the volatilities and impulse response functions derived from the model. Stabilization of the economy is no longer only evaluated by the objective of the stabilization of macro variables, it is also important to minimize fluctuations in individual consumption. The traditional policy efficient frontier changes when agents' heterogeneity is introduced and the impact of monetary policy is divided into two major regions. Policy rules interact with the dynamics of beliefs differently in each region, and therefore reach different stabilization results. I study the causes of the two policy regions and discuss how policy rules should be implemented. In this paper, I demonstrate how to generalize the system to incorporate different monetary policies into the economy. I also perform accuracy tests by computing the errors in euler equations to evaluate various assumptions of the model.

Keywords: Economics.
Advisor: Kurz Mordecai primary advisor. Thesis advisor
Judd Kenneth L.
Taylor John B. advisor. Thesis advisor
Monolithic three-dimensional integration of carbon nanotube digital VLSI [electronic resource]

Today's two-dimensional integrated circuits (2D ICs) generally consist of a single layer of transistors and multiple layers of interconnects that are integrated vertically using inter-layer vias (ILVs). In contrast, three-dimensional ICs (3D ICs) consist of two or more layers of transistors (and multiple interconnect layers) that are integrated vertically using ILVs. For 3D ICs to achieve high energy-efficiency and small form factor, high-density ILVs, such as conventional vias used in today's 2D ICs, are preferred. Monolithic 3D integration can achieve this objective through sequential integration of multiple layers of circuits on a single wafer. However, monolithic 3D integration is difficult because the circuits on the upper layers of monolithic 3D ICs must be fabricated at temperatures below 400 °C; otherwise, the circuits on the lower layers can degrade. Carbon Nanotube Field-Effect Transistors (CNFETs) offer a unique opportunity to achieve monolithic 3D integration. This is because the high-temperature Carbon Nanotube (CNT) growth can be decoupled from CNFET circuit fabrication process through a low-temperature (130°C) CNT transfer technique. Moreover, CNFETs are excellent candidates for building highly energy-efficient digital systems of the future. Unfortunately, CNTs are subject to substantial inherent imperfections resulting from mis-positioned CNTs and metallic CNTs. In this dissertation, we experimentally demonstrate, for the first time, monolithic 3D ICs using CNFETs with the following features: 1. Scalable monolithic 3D integration of CNFET circuits that are immune to mis-positioned CNTs and metallic CNTs. 2. Flexible monolithic 3D integration where complementary CNFETs can be placed on arbitrary layers of monolithic 3D ICs and connected using conventional vias to build monolithic 3D logic circuits. 3. Functional CNFET monolithic 3D circuits operating using supply voltages from 3V down to sub-0.4V, with a fully-complementary CNFET inverter operating at 0.2V. Such CNFET monolithic 3D ICs, together with ultra-low voltage operation, create exciting opportunities for high-performance and highly energy-efficient digital system design.

Keywords: Electrical Engineering.
Advisor: Mitra Subhasish primary advisor. Thesis advisor
Wong Hon-Sum Philip
Wong S. Simon advisor. Thesis advisor
Motor skill learning with local trajectory methods [electronic resource]

Motor or sensorimotor skills are behaviors that require close coordination of motor control with feedback from the environment. This includes a wide range of human and animal behaviors, such as locomotion and manipulation. Constructing effective and generalizable motor skills is crucial for creating naturalistic, versatile, and effective virtual characters and robots. However, constructing such motor skills manually requires extensive engineering and, quite often, nontrivial insights into the structure of the behavior. For a robot or virtual character to reproduce a motor skill repertoire as wide as that of a human being, the required engineering effort would be staggering. A more scalable approach is to acquire motor skills autonomously, by combining concepts from optimal control with machine learning. In this thesis, I discuss several algorithms based on local trajectory methods that can be used to construct motor skills for walking, running, swimming, traversal of uneven terrain, and recovery from strong perturbations. I show how example demonstrations can be used to automatically learn the objective or goal of the skill, and how local trajectory methods can be used to train general-purpose controllers, represented by large neural networks, without the need for extensive manual engineering or domain knowledge about the task at hand.

Advisor: Hanrahan P. M. (Patrick Matthew) primary advisor. Thesis advisor
Koltun Vladlen
Liang Percy advisor. Thesis advisor
mSWI/SNF (BAF) and Topoisomerase II alpha synergize in the regulation of chromatin accessibility, cancer, and neurologic disease [electronic resource]

Mammalian BAF (also known as mSWI/SNF) ATP-dependent chromatin remodeling complexes modulate chromatin and nucleosome structure to regulate chromatin processes such as transcription and DNA replication. Recent sequencing studies have implicated BAF complexes in a variety of human diseases, including a wide variety of neurodevelopmental syndromes and up to 20% of cancers. We have demonstrated that these complexes promote normal cell cycling by facilitating the activity and recruitment of Topoisomerase II [alpha] (TOP2A). We have also shown that BAF complexes mediate chromatin accessibility primarily at distal regulatory regions. Finally, we provide evidence that BAF complexes, along with Topoisomerase II [beta], regulate depolarization-activated ASD-related gene networks. These data illuminate the molecular mechanisms of BAF complexes in both normal and disease settings.

Keywords: Genetics.
Advisor: Crabtree Gerald R. primary advisor. Thesis advisor
Baker Julie (Professor of genetics) advisor. Thesis advisor
Sidow Arend advisor. Thesis advisor
Snyder Michael
Multi-armed bandits with side information [electronic resource]

Development of personalized strategies has attracted much attention in recent years. Advances in Information Technology has led to the inundation of information, which has provided the impetus for the development of personalized strategies in diverse fields such as medicine, marketing, finance, and education. A methodological framework for the development of these personalized strategies is the theory of multi-armed bandits with side information, also called "contextual" bandits theory, which is an extension of classical (i.e., context-free) multi-armed bandits. This thesis represents an attempt to develop this theory To begin with, we consider the design of clinical trials for developing and testing biomarker-guided personalized therapies. Biomarker-guided personalized therapies offer great promise to improve drug development and patient care, but also pose difficult challenges in designing clinical trials for the development and validation of these therapies. After a review of the existing approaches, we describe new adaptive designs to address these challenges, first for clinical trials in new drug development and then for comparative effectiveness trials involving approved treatments. With the insight from the real-world application, we next consider general multi-armed bandits with side information, and categorizes the approaches to address the multi-armed bandit problems with side information into two groups. One approach uses parametric regression model and the other uses nonparametric regression for the relationship between the reward function of the side information for each arm. We review the existing literature and describe new treatment allocation policies inspired by the design of the biomarker-guided personalized therapy problem. We show that the new treatment allocation policies are applicable to a much more general class of problems than the policies proposed in the literature, and show the improvement of the new policies in simulation studies.

Keywords: Electrical Engineering.
Advisor: Lai T. L. primary advisor. Thesis advisor
Boyd Stephen P. advisor. Thesis advisor
Van Roy Benjamin advisor. Thesis advisor
Multivariate ground motion intensity measure models, and implications for structural reliability assessment [electronic resource]

This dissertation focuses on developing models for ground motion intensity, to formulate improved design spectra for use in assessing the performance of buildings under earthquakes. Most seismic building codes and design guidelines are based on implicit performance goals that structures should achieve. Despite the significant uncertainty in future ground motion occurrence, building codes commonly check a structure's behavior under a single level of earthquake loading, quantified with a design spectrum. However, this explicit design check is often not defined with respect to the performance goals. The objective of this dissertation is to provide the link between the explicit design check and the implicit performance goals. Models for multivariate distributions of ground motion properties are refined (specifically, spectral accelerations at multiple periods and locations) and tractable methods to utilize those models to assess seismic reliability of systems are developed. Using structural reliability approaches, with environmental contours of spectral accelerations at multiple periods, a justification of the use of multiple conditional mean spectra for design checks is achieved. Performance assessment procedures for the response spectrum method as well as nonlinear response history analysis are proposed based on these conditional mean spectra. Finally, this dissertation provides an original spatial cross-correlation model for spectral accelerations at multiple periods, which allows one to conduct the design checks simultaneously for multiple structures in a region.

Keywords: Civil and Environmental Engineering.
Advisor: Baker Jack W. primary advisor. Thesis advisor
Deierlein Gregory G. (Gregory Gerard)
Miranda Eduardo (Miranda Mijares) advisor. Thesis advisor