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Background The East North Central Census division (aka the Great Lakes region) experienced a decrease in life expectancy of 0.3 years from 2014 to 2016 – one of the largest declines across the nine Census divisions. Disadvantaged groups that typically have below-average life expectancy, including Black individuals and those without a college education, may have been disproportionately affected by this longevity shift. This investigation examines life expectancy changes among different sex, race, and education groups in the Great Lakes region, and how specific causes of death contributed to within-group longevity changes over time and across age. Methods We used 2008 to 2017 death counts from the National Center for Health Statistics and American Community Survey population estimates to measure within-group change in life expectancy at age 25 among non-Hispanic Black and white males and females by educational attainment. We decomposed life expectancy change over time for each subgroup by 24 causes of death and measured their contribution to longevity change across 13 age groups. Results Among persons with ≤ 12 years of education, white males and females experienced 1.3- and 1.7-year longevity declines respectively, compared to a 0.6-year decline among Black males and a 0.3-year decline among Black females. Life expectancy declined among all groups with 13–15 years of education, but especially Black females, who experienced a 2.2-year loss. With the exception of Black males, all groups with 16 + years of education experienced longevity gains. Homicide contributed 0.34 years to longevity decline among Black males with ≤ 12 years of education. Drug poisoning made large contributions to longevity losses among Black females with ≤ 12 years of education (0.31 years), white males and females with 13–15 years of education (0.35 and 0.21 years, respectively), and white males and females with ≤ 12 years of education (0.92 and 0.65 years, respectively). Conclusions Public health efforts to reduce the risks of homicide among Black males without a college education and drug poisoning among all groups could improve life expectancy and reduce racial and educational longevity disparities in the Great Lakes region.

Using a 6‐week porcine full‐thickness excisional wound grafting model, we evaluated the Autologous Regeneration of Tissue (ART®) System, a novel skin harvesting device designed to collect autologous full‐thickness autologous microcolumns (FTAM) at 0.5 mm in diameter. The donor skin sites were harvested using the ART® System and compared to split‐thickness skin grafts (STSGs). Recipient sites were divided into three treatment groups: FTAM, STSG and Untreated control. Comparing the FTAM donor sites to the STSG donor sites, we observed significantly faster re‐epithelization by Day 4 (p < 0.05), earlier adnexal structures and rete ridge formation by Week 3, and increased collagen and elastin content by Week 6. We also observed an increased rate of healing at the FTAM donor site whilst limiting donor site morbidity compared to traditional STSG donor sites. Time to recipient site closure was 2.4 weeks for STSG treated, 3.3 weeks for FTAM treated and 4.1 weeks for the Untreated control (p < 0.05). The STSG and FTAM recipient sites reached complete re‐epithelialization by Weeks 4 and 5, respectively which was significantly faster compared to the Untreated control. However, the FTAM recipient site received only 10% of the donor site tissue relative to the recipient site area and the amount of donor site tissue grafted on the STSG recipient sites was 5× more than the FTAM recipient sites. Additionally, the FTAMs harvested by the ART® System augmented recipient wound site healing as a result of ‘epithelial island’ expansion in contrast to Untreated control sites that closed primarily by contracture.

Life expectancy is not the same for all people in the United States. While so me enjoy life expectancies of more than 80 years, others are at risk of dying much sooner. The following studies investigate how different causes of death such as homicide, diabetes, heart disease, and drug poisoning contribute across the life span to: 1) life expectancy gaps across different sex, racial, ethnic, and education groups, and 2) life expectancy change over time for different sex, racial, ethnic, and education groups. Each study focuses on a different area of the U.S., with Chapter 2 focusing on the national-level, Chapter 3 focusing on the Great Lakes region, and Chapter 4 focusing on Washington, D.C. In Chapter 2, I find that homicide among low-educated, young males contributes to life expectancy gaps between Black and white males, and also life expectancy gaps between Hispanic and white males. Additionally, heart disease among older, higher-educated males and females contributes to life expectancy gaps between Blacks and whites. In Chapter 3, I find that drug poisoning among all Black and white males and females has contributed to reductions in life expectancy over time in the Great Lakes region, but drug poisoning has decreased life expectancy particularly for low-educated, white males and females. In Chapter 4, I find that homicide contributed most to the life expectancy gap between Black and white males at young ages in Washington, D.C., while heart disease and cancer contributed most to Black-white life expectancy gaps among both males and females at later stages of life in Washington, D.C. The findings from these studies can inform future research on life expectancy differences and guide targeted public health interventions to help reduce life expectancy disparities in the U.S.

CD8+ T cells are important for pathogen clearance and have many intrinsic and extrinsic factors that can determine how they differentiate into effector and memory cells. The Y-box binding protein (YBX) family of genes have been identified as potential regulators of CD8+ T cell differentiation as early as the first division (Kakaradov et al. 2017). Previous studies have shown that YBX1 and YBX3 affect various cellular pathways and functions; however, none have focused on YBX genes affecting CD8 + T cell differentiation and function. To address this gap in knowledge, this thesis investigated the effects on CD8+ T cell differentiation at early and late time points in an acute infection model using a shRNA approach. To do this, we validated retroviral shRNAs that knocked down YBX1 and YBX3, and a control non-targeting retroviral construct. Activated P14 CD45.1 and CD45.1.2 CD8+ T cells were transduced with targeting and non-targeting retroviruses, respectively, and adoptively transferred into recipient mice that were subsequently infected with Lymphocytic Choriomeningitis Virus (LCMV) Armstrong. Seven days and thirty days after infection, mice were sacrificed, and spleen and small intestine tissue were analyzed using flow cytometry. Relative to the non targeting control-transduced cells, cells knocked down for YBX1 and YBX3 expression exhibited reduced CD8+ TE and CD8+ TCM populations. Knock down of YBX1 and YBX3 expression also resulted in an increase of CD8+ TRM cells within the small intestine, and an increase of circulating TEM cells and cytokine-producing cells.

The efficient manipulation, sorting, and measurement of optical modes and single-photon states is fundamental to classical and quantum science. Here, we realise simultaneous and efficient sorting of non-orthogonal, overlapping states of light, encoded in the transverse spatial degree of freedom. We use a specifically designed multi-plane light converter (MPLC) to sort states encoded in dimensions ranging from \\(d = 3\\) to \\(d = 7\\). Through the use of an auxiliary output mode, the MPLC simultaneously performs the unitary operation required for unambiguous discrimination and the basis change for the outcomes to be spatially separated. Our results lay the groundwork for optimal image identification and classification via optical networks, with potential applications ranging from self-driving cars to quantum communication systems.

The process of tracking human anatomy in computer vision is referred to pose estimation, and it is used in fields ranging from gaming to surveillance. Three-dimensional pose estimation traditionally requires advanced equipment, such as multiple linked intensity cameras or high-resolution time-of-flight cameras to produce depth images. However, there are applications, e.g.~consumer electronics, where significant constraints are placed on the size, power consumption, weight and cost of the usable technology. Here, we demonstrate that computational imaging methods can achieve accurate pose estimation and overcome the apparent limitations of time-of-flight sensors designed for much simpler tasks. The sensor we use is already widely integrated in consumer-grade mobile devices, and despite its low spatial resolution, only 4\\(\\)4 pixels, our proposed Pixels2Pose system transforms its data into accurate depth maps and 3D pose data of multiple people up to a distance of 3 m from the sensor. We are able to generate depth maps at a resolution of 32\\(\\)32 and 3D localization of a body parts with an error of only \\(\\)10 cm at a frame rate of 7 fps. This work opens up promising real-life applications in scenarios that were previously restricted by the advanced hardware requirements and cost of time-of-flight technology.

High-dimensional entangled states are of significant interest in quantum science as they increase the information content per photon and can remain entangled in the presence of significant noise. We develop the analytical theory and show experimentally that the noise tolerance of high-dimensional entanglement can be significantly increased by modest increases to the size of the Hilbert space. For example, doubling the size of a Hilbert space with local dimension d=300 leads to a reduction of the threshold detector efficiencies required for entanglement certification by two orders of magnitude. This work is developed in the context of spatial entanglement, but it can easily be translated to photonic states entangled in different degrees of freedom. We also demonstrate that knowledge of a single parameter, the signal-to-noise ratio, precisely links measures of entanglement to a range of experimental parameters quantifying noise in a quantum communication system, enabling accurate predictions of its performance. This work serves to answer a simple question: \"Is high-dimensional photonic entaglement robust to noise?\". Here we show that the answer is more nuanced than a simple \"yes\" or \"no\" and involves a complex interplay between the noise characteristics of the state, channel, and detection system

PLases (phospholipases) participate in a wide variety of cellular signals for healthy and diseased processes. PLA (phospholipase A), PLC (phospholipase C), and PLD (phospholipase D) enzymes cleave PLs (phospholipids) to give distinct, bioactive products. Fluorogenic substrate analogues offer the possibility of detecting PLase activity in vitro and in living cells and tissues in real-time and with high sensitivity. Here, fluorogenic analogues of the PLs PA (phosphatidic acid), PC (phosphatidylcholine), PE (phosphatidylethanolamine), PG (phosphatidylglycerol), and PS (phosphatidylserine) were synthesized as PLA substrates for determining the influence of PL head group modifications on cell signaling in vitro and in cells. The initial synthetic route to a fluorogenic analogue of PA used exclusively chemical transformations. Later, an enzyme-assisted synthetic route was employed, which included remodeling of the sn-2 position of the diacylglyceryl moiety with cobra venom PLA2 and transphosphatidylation with a particular PLD. This enzyme-assisted synthesis allowed the PA analogue to be synthesized more efficiently than by purely chemical methods and also provided ready access to a variety of different head groups. The resulting fluorogenic Dabcyl- and BODIPY-containing PL analogues---DBPA, DBPC, DBPE, DBPG, and DBPS---were used to determine PLA 2 kinetics in mixed micelle assays. DBPC was then used to determine the Xi(50) value of a common PLA2 inhibitor. Finally, the head group selectivity of a series of commercially available PLA2 enzymes was established using the DBPL substrates. For assaying PLD activity in vitro and in cells, a series of fluorogenic analogues of PC and LPC (lysophosphatidylcholine), including DDPB and lysoDDPB, were synthesized, again by an enzyme-assisted strategy. The analogues were evaluated as substrates for PLC, PLD, and lysoPLD (lysophospholipase D). DDPB was cleaved by PC-PLC and by bacterial, plant, and human PLD and represents the first direct fluorogenic substrate for mammalian-type enzymes. Inositol polyphosphates, products of PL hydrolysis by PLC, also mediate cell signaling. In the concluding chapter, metabolically stabilized inositol polyphosphate analogues are proposed that are designed to be long-lived agonists/antagonists at intracellular inositol polyphosphate binding sites. Synthetic studies toward these analogues are detailed, culminating in a new synthetic route to the stabilized inositol analogue inositol(1,4,5)tris(methylphosphonate).

The purpose of this research is to develop the tools necessary to create tristable compliant mechanisms; the work presents the creation of models and concepts for design and a demonstration of the feasibility of the designs through the fabrication of tristable compliant mechanism prototypes on the macro scale. Prior methods to achieve tristable mechanisms rely on detents, friction, or power input; disadvantages to these methods include a high number of parts, the necessity for lubrication, and wear. A compliant tristable mechanism accomplishes tristability through strain energy storage. These mechanisms would be preferable because of increased performance and cost savings due to a reduction in part count and assembly costs. Finite element analysis and the pseudo-rigid-body model are used to design tristable compliant mechanisms. The mechanisms are initially designed by considering symmetrical or nearly symmetrical mechanisms which achieve a stable position if moved in either direction from the initial (fabrication) position, thus resulting in a total of three stable positions. The mechanisms are fabricated and tested in both partially and fully compliant forms, and efforts to miniaturize the mechanism are discussed. The basic mechanism design is used as a starting point for optimization-based design to achieve tailored stable positions or neutrally stable behavior.An alternative to fabrication methods commonly used in compliant mechanisms research is introduced. This method integrates torsion springs made of formed wire into compliant mechanisms, allowing the desired force, stiffness, and motion to be achieved from a single piece of formed wire. Two ways of integrating torsion springs are fabricated and modeled, using either helical coil torsion springs or torsion bars. Because the mechanisms are more complex than ordinary springs, simplified models are presented which represent the wireform mechanisms as four-bar mechanisms using the pseudo-rigid-body model. The method is demonstrated through the design of mechanically tristable mechanisms. The validity of the simplified models is discussed by comparison to finite element models and experimental measurements. Finally, fatigue testing and analysis is presented.