VictorJuiz/thesis huggingface dataset:
Measuring force in the developing zebrafish embryo using an expressible tension sensor [electronic resource]
Keywords: Molecular and Cellular Physiology.

Early vertebrate development is a mechanically dynamic process. Embryos undergo radical morphologic changes to mold a ball of cells into the recognizable planes of a frog or fish or mouse. In the last 40 years, the zebrafish has emerged as a powerful system for studying these early movements in a vertebrate system. Its large, optically transparent embryos make it a good candidate for advanced microscopy techniques, and in recent years this model organism has been the setting for a host of cutting edge microscopy methodologies. One technique that has been comparatively overlooked in the fish is the use of Fluorescence Lifetime Imaging (FLIM), specifically in conjunction with Forster Resonance Energy Transfer (FRET). FRET is a powerful technique for studying real time, in vivo protein dynamics on the nanometer scale. FLIM allows us to apply this technique in the noisy embryo background without the need for cumbersome spectral bleed-through corrections. In this work, we adapt previously published controls for use in the zebrafish system and then take a systematic approach to developing the best analytical practices for FLIM-FRET in the zebrafish embryo. After developing FLIM-FRET in the early embryo background, we adapt a recently published expressible, FRET-based stress sensor capable of measuring piconewton levels of force in vivo (Grashoff et. al. 2010). We insert this Tension Sensor Module (TSMod) into the zebrafish Epithelial Cell Adhesion Molecule (EpCAM) and use it to make direct measurements of the tensions experienced during early development. In doing so we show that the EpCAM molecule holds between 0.5 and 1.5 piconewtons of force during zebrafish epiboly and that the leading margin is under greater tension than other regions of the developing embryo. This work represents the first use of FLIM-FRET in the zebrafish embryo and the first direct measure of molecular tension in a developing vertebrate.
Measuring microbes [electronic resource] : leveraging quantitative imaging to characterize heterogeneous systems across length scales
Keywords: Physics.

This dissertation addresses the question of spatial organization in living systems, a fundamental problem in understanding the physics of living systems. The structure and layout of the cell plays a key role in biophysical processes such as force transduction, diffusion, transport, and signaling. Using bacteria as a model system, I will present two examples of how cells generate, exploit, and interact with the spatial organization of their intracellular and extracellular environments. First, at the single-cell scale, I will discuss how L-forms (spheroplast-like, cell-wall deficient bacteria) of Escherichia coli can recover their normal rod-like shape without a pre-existing template. I will give a detailed, quantitative characterization of the recovery process at the morphological, biochemical, and molecular level. I will also discuss how our study of L-forms led us to investigate the mechanical properties of the bacterial outer membrane. Finally, I will propose that cell-wall synthesis is regulated by the local shape of the cell, giving rise to a biophysical model for rod morphogenesis. Second, at the community scale, I will discuss the vast, diverse, and poorly understood microbial ecosystem that resides in our digestive systems. I will present a quantitative image analysis platform for measuring host-microbe and microbe-microbe association in fixed sections of the intestinal tract, and show how diet shifts drive changes in the organization of the gut microbiome in gnotobiotic mice. In particular, I will demonstrate that polysaccharide starvation thins the host mucus layer, drives bacteria closer to host tissue, and alters clustering of several bacterial taxa.
Measuring the standard model and searching for new physics with jet substructure using the ATLAS detector [electronic resource]
Keywords: Physics.

Collisions at the Large Hadron Collider have offered an unprecedented window into some of the highest energy scales ever observed in experiments. Understanding these collisions, especially those that produce particles charged under quantum chromodynamics (QCD), requires a deep understanding of jets: the collimated sprays of particles produced by the parton shower and hadronization processes which emerge from the asymptotic freedom of QCD. Recent theoretical advances and the unprecedented capabilities of the ATLAS detector have enabled a new class of jet physics measurements based on the internal structure of jets, referred to as jet substructure. Three new types of measurements relying on jet substructure are presented. The first is a set of measurements sensitive which can discriminate between jets initiated by quarks and gluons. Separation is possible by studying variables sensitive to the magnitude of the color charge. Several such variables are measured, and a data-driven technique is used to construct a tagger, the first of its kind at a hadron collider, which can improve the sensitivity of searches for new physics in hadronic final states. A second measurement studies the color connections of jets in top-antitop events using an observable called the jet pull angle: sensitivity to the color representation of particles decaying to dijet pairs at a hadron collider is demonstrated for the first time. A final analysis searches for R-parity violating supersymmetry (SUSY) in all hadronic final states. These classes of models remove the characteristic missing energy signature which existing SUSY searches rely on, and require new discrimination techniques. Jet substructure provides a powerful handle to analyze these very high multiplicity states using a variable called the total jet mass. No signal is observed over the Standard Model (SM) prediction, and new limits are set on these previously unexplored models. The techniques of jet substructure lie at the hearts of all of these analyses, enabling both new measurements of SM phenomena and entirely new searches for physics beyond the SM.
Mechanisms of deformation and instability in crystalline rocks at the pore scale [electronic resource]
Keywords: Civil and Environmental Engineering.

Deformation mechanisms at the pore scale are responsible for producing large strains in porous rocks. They include cataclastic flow, dislocation creep, dynamic recrystallization, diffusive mass transfer, and grain boundary sliding, among others. In this work, we focus on two dominant pore-scale mechanisms resulting from purely mechanical, isothermal loading: crystal plasticity and micro-fracturing. We examine the contributions of each mechanism to the overall behavior at a scale larger than the grains but smaller than the specimen, which is commonly referred to as the mesoscale. Crystal plasticity is assumed to occur as dislocations along the many crystallographic slip planes, whereas micro-fracturing entails slip and frictional sliding on microcracks. It is observed that under combined shear and tensile loading, micro-fracturing generates a softer response compared to crystal plasticity alone, which is attributed to slip weakening where the shear stress drops to a residual level determined by the frictional strength. For compressive loading, however, micro-fracturing produces a stiffer response than crystal plasticity due to the presence of frictional resistance on the slip surface. Behaviors under tensile, compressive, and shear loading invariably show that porosity plays a critical role in the initiation of the deformation mechanisms. Both crystal plasticity and micro-fracturing are observed to initiate at the peripheries of the pores, consistent with results of experimental studies. We next develop a computational framework that captures the microfracture processes triggering shear band bifurcation in porous crystalline rocks. The framework consists of computational homogenization on a representative elementary volume (REV) that upscales the pore-scale microfracture processes to the continuum scale. The assumed enhanced strain (AES) finite element approach is used to capture the discontinuous displacement field generated by the microfractures. Homogenization at the continuum scale results in incrementally nonlinear material response, in which the overall constitutive tangent tensor varies with the stress state as well as with the loading direction. Continuum bifurcation detects the formation of a shear band on the REV level; 3D strain probes, necessitated by the incremental nonlinearity of the overall constitutive response, determine the most critical orientation for shear band bifurcation. Numerical simulations focus on microfracturing at the pore scale with either predominant interface separation or predominant interface contact modes. Results suggest a non-associative overall plastic flow and shear band bifurcation that depends on the microfracture length and the characteristic sliding distance related to slip weakening.
Mediating digital participation [electronic resource]
Keywords: Education.

Research on the ways that digital tools mediate broader social inequality has traditionally focused on the "digital divide". As social and technological realities shifted over the last two decades, scholars interested in digitally mediated inequality have also shifted to focus on "participation divides". This concept offers a way of understanding how people from different groups are or are not benefitting equally from new information and communication technologies. Participation divides is currently a broad and multiform concept that seeks to understand how people use technology to their benefit, and how technology can be better used for social equity. In this dissertation, I employed study participant accounts to generate a concept of digital participation in communities that connect online. I then used that concept to study participation divides and identify factors related to these divides. I conducted a two-part, mixed-methods study involving responses from 272 college students of varying ages, races, majors, and income levels. Using study participant interviews, I identified 11 forms of community participation that interviewees engaged in online. These forms of participation generally focused on consuming and creating content. Content consumption was viewed as a less engaged approach to participation, and content creation was viewed as a more engaged form of participation. Based on their online activities, study participants occupied positions along a spectrum of depth of engagement in relation to online sites for community participation. Using survey responses, I found that most study participants engaged in moderate levels participation in community practices online. Those whose behavior reflected a deeper level of engagement were seen as more full community participants, even though their behavior was not reflective of the norm. Deeply engaged participants created content more often, and tended to use the Internet in a more robust manner for life goals. There were gender and income differences among the population of deeply engaged participants: women were more likely to be deeply engaged than men, and low-income students were more likely to be deeply engaged than middle-income and high-income students. This represented a divide of sorts, but was a reversal of the classical approach to digital divides. "Feelings of similarity in terms of web use" was a psychological variable that significantly predicted deep engagement. This study contributes to existing research by suggesting that participation be measured through multifaceted profiles with meaning derived from study participant experiences. It further adds nuance to existing accounts of digitally mediated participation by tying together specific forms of participation, goals of participation, and relevant psychological, social, and contextual factors.
Meetings of the minds [electronic resource] : knowledge integration processes in transdisciplinary science
Keywords: Education.

Academic institutions invest in interdisciplinary research centers to promote innovative knowledge creation. As prior work on these research efforts has examined either established interdisciplinary collaborations or completed intellectual products, we have a limited understanding of how interdisciplinary research centers emerge and develop over time. This longitudinal ethnographic study on a new Transdisciplinary Premature Birth Research Center sheds light on the early stages of knowledge integration and their impact on the outcomes of interdisciplinary science. The Center's research efforts consisted of four heterogeneous teams: Placental Function, Pattern Recognition, Bioinformatics, and Microbiome. In order to promote knowledge integration among the scientists, the Center organized research group meetings for the different projects. These meetings occurred at various knowledge boundaries that created conditions for the emergence of boundary struggles. Across the four projects, boundaries were established around different objects of contention. I define them as either abstract or concrete scientific objects that demonstrate the points where the scholars' perspectives begin to differ and create boundary struggles in meeting discussions. Whereas in the Placental Function, Pattern Recognition, and Bioinformatics meetings the objects of contention hindered knowledge integration efforts over time, in the Microbiome meetings the actors successfully integrated their varied expertise around a shared goal. I suggest this outcome related to the concrete goal and the fact that the meeting participants navigated differences in their cross-functional roles, rather than disciplinary backgrounds. The different objects of contention and their long-term impact on scientific work shine light on how difficult interdisciplinary collaboration actually is.
Mentoring and the College Experience: Narratives of Filipino American Undergraduate Students at Stanford
Keywords: Filipino Americans
Asian Americans
mentorship
college students
support
Stanford University
Thesis

This study of the impact of mentoring relationships on the undergraduate experience of Filipino Americans at Stanford University involved extensive interviews with four male and four female self-identified Filipino/ Filipino American fourth-year undergraduate students. The literature review discussed relevant scholarship on Asian Americans, student development theory, and mentorship. Museus and IfItikar’s (2013) AsianCrit Theory and Nora and Crisp’s (2007) multi-dimensional conceptual framework of mentoring laid the foundation for this project. An in-depth phenomenological, semi-structured interview methodology was used to deepen our understanding of student development throughout college. The results of the study contextualized the ways in which students receive advice, counseling, and support from various mentors. The conclusion discusses implications and suggestions for research, policy, and practice in higher education on how to better support college students through mentorship.
Metafluids and parity-time symmetric metamaterials [electronic resource] : new optical material phases and phenomena
Keywords: Electrical Engineering.

Textbook conceptions of light-matter interactions have been challenged by two recent material advances - the development of metamaterials and the introduction of parity-time (PT)-symmetric media. Metamaterials allow considerable control over the electric and magnetic fields of light, so that the permittivity, permeability, and refractive index can be tuned throughout positive, negative, and near-zero values. They have enabled negative refraction, optical lensing below the diffraction limit of light, and invisibility cloaking. Complementarily, PT-symmetric media allow control over electromagnetic field distributions in systems with balanced amounts of gain and loss, so that light propagation can be asymmetric and directional. They have enabled lossless Talbot revivals, unidirectional invisibility, and, combined with non-linear media, optical isolators. In this thesis, I will elaborate on our efforts to make new types of optical and asymmetric metamaterials, including metamaterials with negative optical permeability, metamaterials in liquid phase, and parity-time symmetric metamaterials. In the first part, I will describe our theoretical and experimental works on plasmonic metamaterials both in the solid state and liquid phase. Here we have designed and demonstrated the first fluidic metamaterial, utilizing protein directed assembly to synthesize the constituent metamolecules. Both individual metamolecules and the bulk metamaterial solution show a strong isotropic magnetic polarizability at optical frequencies. Our calculations also indicate that these meta-molecules could enable negative refractive index liquids. In the second part, I will introduce the concept of PT-symmetric nanophotonic materials. We show how planar metallo-dielectric structures with balanced inclusion of gain and loss can be used for a variety of applications, including i) directional nanophotonic waveguides and modulators; ii) directional metamaterials that have different refractive indices when viewed from different sides; and iii) flat Veselago lenses which can overcome the Rayleigh diffraction limit of conventional optical microscopy. Further, I will show how these metamaterials can be used to control the emission of the electric, magnetic, and chiral emitters and suggest a non-chiral platform for enantio-specific identification and selection.
Methods for quantiative dissection of gene regulation [electronic resource]
Keywords: Genetics.

Defined regulatory programs effecting diverse cellular processes such as chromatin accessibility, RNA localization or protein modifications largely determine the establishment and maintenance of a cell's identity. Here, we describe the development of quantitative and high-throughput methods for understanding principles of gene regulation. In this work, we repurpose a high-throughput sequencing instrument to develop a platform for high-throughput biochemical assays of RNA. We then develop a method for profiling chromatin accessibility within rare cellular populations or single-cells, called Assay for Transposase Accessible Chromatin with sequencing (ATAC-seq). Furthermore, we apply ATAC-seq to measure chromatin accessibility within defined cellular populations across the human hematopoietic hierarchy and primary Acute Myeloid Leukemia (AML) in effort to determine regulatory principles governing normal hematopoiesis and leukemogenesis. Together, we demonstrate that these methods provide unique insights into the molecular effectors governing normal human development and disease.
Methods for quantum field theories at finite density [electronic resource]
Keywords: Physics.

This dissertation discusses several approaches to study quantum systems at finite density, in the general framework of quantum field theory. The thesis consists of four parts. The first two parts discuss the application of dualities to study strongly-coupled quantum field theories at finite density. Part one consists of applications of the holographic dualities at finite density; part two extends the three-dimensional mirror symmetry dualities among certain supersymmetric gauge theories to finite density. The later two parts of the thesis study a specific class of finite density system, namely a fermi-surface coupled to critical scalar. In part three, a systematic RG framework tailored to such systems is developed; the framework is then applied in part four to study various possibilities for the low energy phases of a fermi-surface coupled to critical scalar.
Microfluidic fractionation and analysis of cytoplasmic versus nuclear acids in single cells [electronic resource]
Keywords: Mechanical Engineering.

Single-cell gene expression studies have matured and are now widely used to uncover cell-to-cell variability, transcript processing and inhomogeneous response to external stimuli. Despite great progress, significant challenges remain including understanding fundamental questions of human genome transcription, gene expression ranges, localization, and processing destinies of RNAs. Eukaryotic cells make different types of primary and processed transcripts, which are either exclusively found in particular sub-cellular compartments or dispersed throughout the whole cell. These sub-cellular localizations of RNAs are weakly understood at a single-cell level, and are important for fully realizing gene functions. Understanding sub-cellular transcript localization is particularly important for studying the process of splicing, a pathway during which introns of pre-messenger RNA's are excised and exons are stitched together to form mature mRNA transcript. We here introduce a single-cell-isotachophoresis (sc-ITP) method to analyze co-transcriptional and alternative splicing in reference lymphoblastoid cell line (LCL-Snyder), and two sub-lines of CML cells (K562-ATCC and K562-ENCODE). The method is unique in that we physically separate the contents of cell nucleus from those of the cytoplasm and analyze independently. It allows for rapid, electric-field-based selective lysis of cytoplasmic membrane (leaving nucleus intact); and then purification and simultaneous fractionation of total RNA in cytosol (cyt-RNA) and total RNA in the nucleus (nuc-RNA) from single cells with no intra-compartment cross-contamination. We then use our system and state-of-the-art NGS technologies to perform single-cell nuclear and cytoplasmic RNA-seq to study fundamental questions of human genome transcription, differential gene expression, localization, and processing destinies of RNAs for various cell types, disease, and differentiation states. We evaluate the distribution of whole transcriptome gene features and gene expression of precursor and processed transcripts and find that there are considerable differences in expression levels across sub-cellular compartments and among individual cells. We then evaluate cell-to-cell variability of the highly expressed GAPDH housekeeping gene in alternative splicing between the lymphoblastoid and leukaemia cells using sequencing-specific probes and RT-qPCR. The data suggest evidence of significant distinction in splicing patterns. By analyzing nuclear and cytoplasmic compartments of a single cell individually at a whole transcriptome level, we achieve an unprecedented precision in splicing quantification. Together, our results describe an experimental method for single-cell fractionation and an analytical tool for gene and isoform expression analysis in rare cell types, cell differentiation and disease states.