Two-photon excited fluorescence adaptive optics ophthalmoscopy of retinal function

Thesis (Ph. D.)--University of Rochester. The Institute of Optics, 2019.The retina is the light-sensitive tissue at the back of the eye which carries out the first steps in vision. Specialized neural cells in the retina known as photoreceptors are responsible for detection of light and its transduction by initiating an electrical signal to the brain. Adaptive optics scanning light ophthalmoscopy (AOSLO), which dynamically corrects aberrations of the ocular media in the living eye and affords a lateral resolution of 2 μm, has revolutionized our ability to visualize photoreceptors and many other microstructures in the retina. The implementation of two-photon excited fluorescence (TPEF) imaging in AOSLO has enabled not only complementary structural information throughout the retina, but an objective, non-invasive measure of visual function in photoreceptors by measuring TPEF kinetics from these cells. The aim of the present thesis is to further develop and apply TPEF ophthalmoscopy as a novel measure of in vivo cellular function in the retina. First, TPEF ophthalmoscopy was used in conjunction with other imaging modalities to evaluate the extent of photoreceptor dysfunction in a non-human primate model of retinal degeneration. TPEF ophthalmoscopy was essential in determining that photoreceptors were non-functional. Second, the sensitivity of TPEF kinetics to detect changes in photoreceptor function in conditions relevant to disease pathogenesis was investigated. Systemic hypoxia was employed in non-human primates as a model of physiological change, reducing oxygen supply to the retina, and TPEF kinetics were shown to be slowed as a consequence. Finally, the capabilities of TPEF ophthalmoscopy were expanded by implementing intrinsic fluorescence lifetime imaging. TPEF lifetime imaging was shown to distinguish retinal cell classes that are functionally disparate, and lifetimes were altered in regions of retinal damage. TPEF ophthalmoscopy has the potential to yield advances in understanding of both the basic physiology and pathology of the retina. If translated successfully into humans, TPEF ophthalmoscopy demonstrates promise as a valuable imaging modality that may, when used in conjunction with other clinical measures, identify early cellular dysfunction and longitudinally track pathological changes. Ultimately, it may assist in timely diagnosis, intervention, and development of treatments or vision restoration methods to combat blindness as a consequence of retinal disease

Strings in variations, op. 33, no. 2 / Rudoph Ganz.

For solo harp and string orchestra. Digital images made available during the final 20 years of US copyright in accordance with the Digital Millennium Copyright Act

Schema-based dialogue management : from friendly peer to virtual standardized cancer patient

Thesis (Ph. D.)--University of Rochester. Department of Computer Science, 2024.Generalist conversational agents are a longstanding goal for dialogue researchers; however, this goal remains elusive owing to the often divergent roles of robust “analogical” reasoning and rigorous formal reasoning in computer dialogue. This dissertation proposes a general dialogue management framework, Eta, for creating conversational agents using an explicit schema representation that subsumes both modes of behavior. The schemas used by Eta represent expected or prototypical dialogue events, and can be used to dynamically guide dialogue through incremental matching of schemas to Eta’s observed dialogue context. Deploying an agent to a particular domain requires only the creation of a set of schemas and the integration of modular, portable pattern transduction methods; the latter allows for the flexible integration of both symbolic methods and large language models in processes such as interpretation, reasoning, planning, and generation. I demonstrate the generality of this approach by presenting a chronology of case studies of conversational agents created using Eta across three highly diverse domains: beginning with a friendly peer for social skill assistance; then turning to a spatially situated collaborative agent in a physical “blocks world” domain; and finally I present a virtual standardized cancer patient for end-of-life communication practice, representing the most elaborate application of Eta to date. I conclude the dissertation by shifting to an empirical investigation of how prototypical knowledge about cognitive attitudes – such as that contained within dialogue schemas – is reflected in natural language itself, laying the groundwork for more precise methods of inference about such event knowledge

A novel conceptual framework for cognitive reserve : using a multidimensional psychosomatic approach

Thesis (Ph. D.)--University of Rochester. Department of Brain and Cognitive Sciences, 2024.Older adults aged 85 years and older are at highest risk for Alzheimer's disease (AD), a progressive neurodegenerative disease characterized by abnormal accumulation of amyloid beta and tau proteins, neurodegeneration, and cognitive impairment. However, not all older adults with AD neuropathology ultimately develop AD, suggesting that there are unaccounted for factors that contribute to the nonlinear relationship between brain aging and cognition. This observation motivated the concept of cognitive reserve (CR) to explain why some individuals are better able to cope with brain pathology than others. However, existing operationalizations fail to capture the fundamental conceptual components of CR, particularly cognitive change (i.e., plasticity). As a result, there is little to no mechanistic evidence for CR. This dissertation presents a novel conceptual framework for CR that uses multidimensional (i.e., trait, state, level, and stability) psychosomatic factors to explain individual variability in the relationship between brain aging and cognition, encompassing both cognitive level and cognitive change. First, we establish a relationship between a psychosomatic factor, trait fatigue, and brain topology, and second, we identify a potential brain mechanism associated with brain aging and fatigue (Chapter 2). Next, we assess the relationship between fatigue and CR and examine how different dimensions of fatigue affect this relationship in older adults with and without mild cognitive impairment (MCI; Chapter 3). Finally, we test the moderating role of a second psychosomatic factor, positive affective experience, on the relationship between neurodegeneration and cognitive change in MCI, and whether preserved resting-state network functional connectivity attenuates the adverse effects of neurodegeneration on older adults' capacity for plasticity (Chapter 4). By using psychosomatic dimensions as different "operational" definitions of timescale, we show that psychosomatic factors differentially moderate the adverse effects of neurodegeneration on cognition, which in turn promote cognitive resilience or exacerbate vulnerability to brain aging. The inclusion of timescale captures an individual's capacity for plasticity, a component that has been theoretically implied in the existing literature but not operationally implemented. To our knowledge, these findings provide the first empirically viable evidence for CR and establish a foundation for future confirmatory research

Capriccio, harp

For harp. green text and ar

Effects of Dietary and Environmental Exposures on Infant Immune Development

Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Microbiology and Immunology, 2023.Disturbances in the immune development during the first year of life can result in the development of atopic diseases such as atopic dermatitis (AD), food allergy (FA), asthma, and allergic rhinitis. Exposure to a farming lifestyle has been shown to protect against atopic disease. However, the mechanisms behind this phenomenon remain unclear. Our laboratory has recruited a birth cohort from farming (low risk for allergy) and urban (high risk for allergy) lifestyle communities to begin to address this. One of the lifestyle differences between our cohorts is increased rates of breastfeeding in the farming population. Most studies examining the immunomodulatory function of human milk (HM) have focused on its effect on professional immune cells, but only a handful of studies have examined this in intestinal epithelial cells (IECs), which are another coordinator of mucosal immunity. The first goal of this thesis is to examine the effects of HM on IEC immune function. Using the colon cancer cell line (Caco-2), we analyzed the effects of HM on microbial sensing by IECs. Our findings show that HM enhances lipopolysaccharide (LPS)-induced production of inflammatory chemokines as well as NF-κB transcription regulators in Caco-2 cells, suggesting that HM influences toll-like receptor 4 (TLR4) signaling. Fractionation of HM revealed human serum albumin (HSA) to be a mediating factor in this process.The second goal of this thesis is to immunophenotype helper T (Th) cell populations, which play a critical role in tolerance and atopic disease, in infants from our lifestyle cohorts utilizing full spectrum flow cytometry. Through high dimensional analyses, we discovered a unique, recently activated effector memory CD25+CD127+CD161-CCR4+CRTH2+ population, termed Th2B cells, that is elevated in 6-month-old high allergy risk urban infants and those who developed AD, FA, and/or allergic sensitization in compared to farming lifestyle infants and those without allergic disease or sensitization outcomes. RNA sequencing and protein secretion assays confirmed this population to be Th2-skewed, as evidenced by their production of Th2 cytokines. Overall, this thesis explores the effects of exposure to HM and a farming lifestyle on both IEC and T cell immunity, respectively

Hugoniot measurements of silicon and radiance transition in shocked silica aerogel

Thesis (Ph. D.)--University of Rochester. Department of Physics and Astronomy, 2022This dissertation describes the study of crystalline silicon (Si) and silica (SiO2) aerogel shock-compressed to extreme conditions. Shock waves were generated by laser irradiation and recorded using time-resolved optical diagnostics. The behavior of these materials at high pressure is important to understanding the structure and evolution of terrestrial planets, as well as the performance of ICF capsule designs. Principal Hugoniot and sound speed measurements were performed on silicon to 2100 GPa using high-intensity laser drivers and impedance matching techniques. A change in the shock velocity versus particle velocity (us-up) slope was detected along the fluid silicon principal Hugoniot at 200 GPa. Density functional theory-based quantum molecular dynamics simulations suggest that an increase in ionic coordination and average ionization are coincident with the observed change in slope. Thermodynamic behavior of shock-compressed silica aerogel was studied to test its viability as a bright optical source for high energy density physics experiments. Radiance, reflectance, and shock velocity measurements were performed on singly-shocked SiO2 aerogel at initial densities of 0.3, 0.2, and 0.1 g/cm3 . A change in brightness temperature versus pressure slope is observed along the aerogel Hugoniot, which could be due to radiative, conductive, or microstructure effects. A shock front radiance model is presented to enhance predictive capabilities for shock physics experiments using silica photon sources

A geometric journey toward genuine multipartite entanglement

Thesis (Ph. D.)--University of Rochester. Department of Physics and Astronomy, 2024.This thesis focuses on the challenge of characterizing multipartite entanglement. While the study of bipartite entanglement is well-documented in scientific literature, recognizing that entanglement can involve more than two parties—i.e. three or more parties—is crucial, as multipartite entanglement enables the completion of more complicated tasks in quantum information science. Previous discussions on entanglement, especially within scenarios such as information scrambling, primarily concentrated on bipartite entanglement, thus overlooking the rich landscape of multipartite entanglement. By involving more parties, multipartite entanglement exhibits a larger degree of nonlocality, significantly deepening our insights into the dynamical properties of quantum many-body systems, going far beyond what has been revealed through bipartite entanglement. Despite its long-recognized importance, a proper quantification of multipartite entanglement, along with the understanding of the “genuine multipartite entanglement” criterion, continues to pose substantial challenges. The work in this thesis reveals an unexpected connection between multipartite entanglement and the geometry of simplices. Specifically, we demonstrate that every three-qubit state can be associated with a triangle, with its area measuring the genuine tripartite entanglement within that state. Similarly, every four-qubit state can be associated with a tetrahedron, with its volume measuring the genuine quadripartite entanglement within that state. With these results, we embark on a geometric journey toward addressing the quantification problem of genuine multipartite entanglement, offering new perspectives on the complexity of even larger quantum many-body systems