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Impact of Immune Reactions and Crosslinking Chemistry on Hydrogel Properties and Performance
No full textHydrogels are hydrophilic, three-dimensional structures that can be synthesized from synthetic and natural polymers for use in various tissue engineering applications. Their efficacy, however, is heavily dependent on the immune reaction to the material used. Another feature of hydrogels is their tunability in physicochemical properties, which can be modulated based on the crosslinking chemistries used to synthesize the structure. While often treated as being interchangeable, recent evidence suggests crosslinking chemistry���s potential to significantly impact material properties. Here, we sought to investigate the implications of polymer immunogenicity and crosslinking chemistry on hydrogel design and application.
Our first goal was to investigate poly(ethylene glycol) (PEG), a synthetic polymer considered to be bioinert, and how sensitization to the polymer impacts tissue engineering efficacy. To this end, PEG-based microporous annealed particle (MAP) hydrogels were assembled in situ of critical-sized calvarial defects through bioorthogonal tetrazine click reactions, and bone formation and morphology was found to be significantly influenced by PEG sensitization. Next, a head-to-head comparison of annealing chemistry used during MAP hydrogel assembly was further characterized between tetrazine-norbornene click reactions and radically-mediated thiol-norbornene click reactions. Differences in materials properties, such as storage moduli and susceptibility to enzymatic degradation, emerged as a result of annealing chemistry and were further modulated with respect to TNCP concentration. We deduced tetrazine-norbornene click products (TNCPs) induce secondary interactions that contribute to these changes, but these distinctions were negligible when applied in vivo.
Next, we evaluated whether the modulatory effects of TNCP-induced interactions could be applied in polymer-based biomaterials other than PEG. Specifically, we applied various concentrations of TNCPs to a hyaluronic acid (HA)-based bulk hydrogel and observed tetrazine-mediated changes to material properties. We also were able to leverage these interactions to assemble a supramolecular HA hydrogel that demonstrated shear-thinning and self-healing behavior that suggest potential as an injectable material, which was assessed in vitro using a genetically engineered strain of bacteria. Finally, TNCP-induced secondary interaction were leveraged in development of a hydrogel platform where a mock therapeutic was directly conjugated onto the HA backbone. Retention of the conjugated molecule and minimal degradation of the platform was observed after one week
Nuclear Safeguards Feasibility Study for a Molten Salt Reactor Using MCNP Modeling and Simulations
No full textThe technological developments within the last couple of decades have exponentially increased the demand for reliable and sustainable energy. The successful fulfillment of this energy demand shows a strong correlation with the Human Development Index, which is based on health, education, and income parameters. Among other energy sources, nuclear energy has become prominent in providing clean energy by protecting air quality, having a small footprint with high energy density, and being a reliable and stable option. However, considering the dual nature (peaceful and non-peaceful uses) of nuclear energy, nuclear safeguards are an important international instrument to prevent nuclear material diversion for non-peaceful purposes. This work focused on developing a nuclear safeguards monitoring approach for a generic Molten Salt Reactor (MSR) designed at Texas A&M University.
This thesis includes a comprehensive neutronics modeling of the MSR using the Monte Carlo radiation transport code, MCNP��6.2. The modeled MSR has a 300 MWth power and operates in a thermal neutron spectrum at 900 K. It uses molten fluoride salt (2LiF:BeF2) as a coolant with UF4 fuel mixture with 3.5% low-enriched uranium (LEU). The reactor core design used graphite as the neutron moderator and reflector. Non-soluble fission products (FP) were extracted through gaseous extraction, and FP removal was conducted to improve the performance. A High-Purity Germanium (HPGe) detector, a widely used Non-Destructive Assay (NDA) equipment was modeled for Special Nuclear Material (SNM) mass quantification. In this methodology, the first step was determining the relationship between the Pu amount and fuel burnup. In the second step, the fuel burnup relationships with the radioactivity of 137Cs, the radioactivity ratios of 134Cs/137Cs, and 154Eu/137Cs were established. In the last step, these relationships were used to estimate SNM mass.
The results indicate that the Pu amount relationships with 137Cs radioactivity and the ratio of 134Cs/137Cs can be utilized to quantify SNM mass at all fuel burnup levels. The ratio of 154Eu/137Cs is applicable even for very-high fuel burnup levels. However, it does not provide accurate results at ultra-high fuel burnup levels due to its saturation. The proposed safeguards monitoring approach in this thesis provides a method for estimating the Pu mass in the MSR at different fuel burnup levels so that any diversion of Pu for non-peaceful purposes can be prevented through early detection and deterrence
On Fatalism: Revitalizing Durkheim's Theory in the Current Milieu
No full textEmile Durkheim���s fatalistic form of suicide serves as the sociological theory necessary for understanding contemporary social problems with the imbalance of fatalism in society. This has been disastrous throughout the twenty-first century. Specifically, the newer and more virtual the generation, the greater the impact of fatalism as the consequence of modernity from the twentieth century. Fatalism has been neglected or even omitted in both Durkheimian studies and social research on generations. Recontextualizing Durkheim���s theory in the current milieu serves to not only rediscover his works, but to apply them with relevance to the current social malaise that is afflicting society across demographic categories. The current social environment is excessively confining and enforces social behavior through undifferentiating bureaucracy. The increased dehumanization of the average person requires a comprehensive approach to social thought, exemplified by Durkheim and works that are connected to him. Specifically, this thesis draws on Durkheim���s opus, Suicide, and various other literature to study the current generations Millennial and Generation Z. Fatalism linkages impact: public health, suicide, autonomy, mental health, and other social problems. Productivity in sociological research relies on clear, substantive theoretical understanding and policy implications exist in addressing social problems by comprehending their commonalities and clarifying interdisciplinary perspectives
Characterization of Soil Physical and Hydraulic Properties of TexMesonet Monitoring Sites
No full textOperated by the Texas Water Development Board, the TexMesonet comprises 100 monitoring stations across Texas. These stations record 11 environmental variables, which include soil moisture measurements at depths of 5, 10, 20, and 50 cm. While soil moisture data from other networks have been utilized to enhance crop yield estimation, develop drought indices, estimate potential groundwater recharge, and validate remote sensing soil moisture data, TexMesonet soil moisture data remain underutilized for such applications. This underutilization is due to the absence of comprehensive, site- and depth-specific data on soil physical and hydraulic properties. The objectives of this project are twofold: firstly, to characterize the soil physical and hydraulic properties at TexMesonet sites, and secondly, to estimate site- and depth-specific soil hydraulic parameters using the Rosetta3 pedotransfer function. This was achieved through extensive field sampling and laboratory measurements at 30 stations, including determining sand, silt, and clay percentages, bulk density, and volumetric water content at field capacity (-33 kPa) and permanent wilting point (-1500 kPa). These measurements were then applied in the Rosetta3 pedotransfer function to derive site-and depth-specific soil hydraulic parameters. The resulting database includes ten soil physical and hydraulic properties for each site and depth, leading to 218 data points across the 30 study sites. Within the TexMesonet, ten of the twelve USDA soil textural classes were identified, with silt and sand not represented. The mean absolute error (MAE) between the measured and predicted water retention curves ranged from 0.025 cm�� cm- �� to 0.13 cm�� cm- ��. Additionally, the MAE for volumetric water content estimates from TexMesonet sensors versus direct sampling was 0.081 cm�� cm- ��. With further sampling and expansion to all TexMesonet sites, this database has strong potential to provide critical information for improving water resource management applications in Texas, including irrigation scheduling and predicting floods and droughts
Investigating the Impact of Timing of Basal Leaf Removal and Fruit Thinning on Potassium Accumulation in Red Wine Grapes
No full textIn hot climates such as Texas, high juice/wine pH represents a serious challenge for wineries. The objective of this study was to evaluate the impact of timing of basal leaf removal and cluster thinning on potassium (K+) concentration in ���Tempranillo��� and ���Camminare Noir��� grapes as a possible vineyard management practice to mitigate high pH. This research took place during the 2021 and 2022 growing seasons in two vineyards, one in the Texas Gulf Coast and the other in the North Texas region. Treatments consisted of basal leaf removal (removal of lowest three basal leaves), cluster thinning (thinning to one cluster per shoot), and leaf removal plus cluster thinning conducted at either berry set or veraison. Differences in fruiting zone canopy density were consistently observed between treatments, across years, cultivars, and sites. Leaf removal treatments averaged a 35.83% reduction in canopy density in the fruiting zone, determined by occlusion layer, leading to an increase of 124.17% in cluster exposure flux availability. However, differences in yield (yield per vine, clusters per vine), berry chemical composition (alpha amino nitrogen, ammonium, fructose, malic acid, soluble solids, tartaric acid, titratable acidity, and pH) and tissue nutrient content were only observed in singular instances, with no consistent differences between years, cultivar, or site. Berry K + concentrations and juice pH varied by rootstock, year, and cultivar, but there was no clear impact of leaf removal or cluster thinning on berry K+ or pH. In both years of the study, very low yields were observed as a result of a severe winter event and possibly negated any effects from leaf removal or cluster thinning
Electrokinetic Convection-Enhanced Delivery of Macromolecules to the Brain
No full textElectrokinetic convection-enhanced delivery (ECED) utilizes an external electric field to drive the delivery of molecules and bioactive substances to local regions of the brain through electroosmosis and electrophoresis, without the need for an applied pressure. We studied the implementation of ECED to direct a neutrally charged fluorophore (3 kDa) from a doped biocompatible acrylic acid/acrylamide hydrogel placed on the cortical surface. Ex vivo (N = 18) and in vivo (N = 12) experiments were conducted to compare fluorophore infusion using ECED (time = 30 min, current = 50 ��A) and diffusion-only control trials. The linear intensity profile of infusion was significantly higher in ECED compared to control trials, both for in vivo and ex vivo. The linear distance of infusion, area of infusion, and the displacement of peak fluorescence intensity along the direction of infusion in ECED trials compared to control trials were significantly larger for in vivo trials, but not for ex vivo trials. These results demonstrate the effectiveness of ECED to direct a solute from a surface hydrogel towards inside the brain parenchyma based predominantly on the electroosmotic vector
Development of a Constant-Volume Bomb Experiment for the Study of Lithium-Ion Battery Thermal Runaway and Its Associated Hazards
No full textLithium-ion battery (LIB) thermal runaway (TR) has increasingly become a serious concern for consumer safety. As a result, many different LIB TR experiments have been developed to study this phenomenon. The present study outlines the development of a LIB TR experiment that seeks to improve upon the preexisting methodologies. The experiment centers around a constant-volume vessel with a programmable heating controller and external gas system to allow for complete control of testing parameters. The results for representative tests of a single cell are presented to illustrate the experiment���s fidelity. Two different LIBs were utilized for these tests which were performed in air at standard ambient conditions and heated at a rate of ~5 ��C /min. The first test was an LG INR18650 cell at 100% state-of-charge (SoC) which had a TR onset temperature of 142 ��C to 175 ��C and produced 0.18 �� 0.004 moles of gas. These values and the composition of the gas were consistent with literature.
The next three tests were performed with Panasonic NCR 18650b cells at 0%, 50%, and 100% SoC. It was found that increasing the SoC of the battery led to increased reactivity and agreed with relevant literature. Particles ejected from these batteries were also characterized using scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDS), x-ray diffraction (XRD), and x-ray photoelectron spectroscopy (XPS). The 0% SoC battery produced no ejected particles, so the debris was collected from the 50% and 100% tests. Additionally, the particles collected from the 50% test were sieved into the following size ranges: (1) > 212 ��m; (2) 75-212 ��m; (3) 25-75 ��m; and (4) ��� 25 ��m. Qualitative and quantitative sizing of SEM images taken from these samples found particles ranging from the microscale to nanoscale. It was found that approximately 75% of the particles in the ��� 25 ��m were less than 8 ��m. The EDS, XRD, and XPS techniques identified various compounds created from reactions which took place between the different battery components. Future testing efforts seek to further validate the processes developed for this experiment and continue investigating the hazards associated with LIB TR
Essays on Hospital Performance
No full textThis dissertation consists of three essays that focus on hospital service quality and healthcare delivery performance issues. I provide insights on how hospital administrators can leverage hospital personnel, accreditation, and community outreach services to influence hospital performance.
The first essay provides empirical associations regarding impacts of the extent of use of midlevel providers (MLPs) on (i) hospital quality, as measured by the Triple Aim Performance (TAP) metrics, and (ii) hospital costs. Hospital administrators are shifting care delivery models toward an approach that uses more caregivers in the form of mid-level providers (MLPs), such as nurse practitioners, physician assistants, and clinical nurse specialists. To date, however, healthcare operations management (OM) literature remains ambiguous about longitudinal empirical associations between mid-level providers and hospital costs, quality, and other performance measures. This essay, by providing one of the first panel data analyses of midlevel provider impacts in general service hospitals, improves upon existing case studies found in the extant literature. I find that MLPs can improve hospital clinical quality, technical efficiency, and patient experience without impacting hospital costs.
The second essay analyzes associations of hospital accreditation with hospital technical efficiency. As the U.S. healthcare marketplace becomes more competitive, many hospitals face problems of communicating with potential patients about the process conformance of their services. Similarly, patients face uncertainty when choosing a hospital from which to obtain care. A possible solution to this problem involves a hospital obtaining an accreditation. Hospital accreditation is a publicly visible indicator that a hospital provides care and services that should meet a high standard, as defined by an accreditation body. Hospitals can use accreditation as a signal to potential patients to help reduce information asymmetry between the two parties. I contribute to healthcare OM literature by providing one of the first panel-based SFA analyses of associated impacts that hospital accreditation has with hospital efficiency. I find that hospital accreditation is associated with improved hospital technical efficiency, but this association is moderated by government efficiency mandate signals. Since obtaining and maintaining hospital accreditation is a resource intensive and expensive process for administrators, the findings give hospital administrators and other stakeholders useful knowledge that should help in the decision-making process of whether or not to obtain hospital accreditation.
The third essay examines the association that alignment between hospital community outreach services and community needs may have with hospital readmission and mortality rates. One of the tools hospital administrators may employ to potentially reduce readmissions and improve care quality is providing community outreach services within the surrounding community. Individuals��� health is largely determined, in part, in the geographic community and context that they live and/or work in. Community-based hospital outreach programs may serve to educate community members about the availability of care services at the hospital or inform recently discharged patients about proper post-discharge care. I investigate whether these community outreach programs are associated with reduced hospital readmissions and reduced mortality. Overall findings suggest that alignment between hospital community outreach services and community needs are not significantly associated with hospital readmission rates but may be associated with higher hospital mortality rates depending on how hospital community outreach services are operationalized
Improving the Accuracy, Reliability, and Throughput of Nanoindentation Hardness and Modulus
No full textInstrumented nanoindentation is a form of load and depth sensing indentation that characterizes material properties on the micro- and nanoscale. This form of indentation is widely used for its ability to measure a variety of material properties on very small scales in a high-throughput manner without extensive sample preparation and with minimal sample damage after testing. However, this versatility introduces a level of complexity, and due to the various methods for performing nanoindentation tests and collecting data, there are inevitably opportunities to encounter and cause experimental errors. Common sources of error include not accounting for pile-up or other area-related issues, frame stiffness and sample mounting issues, and using improper sample preparation and testing parameters as well as testing non-ideal samples. This thesis provides a background for these sources of error and expands on best practices from research and literature to overcome or avoid these sources of error. To this end, a highly ordered pyrolytic graphite sample was tested and the lack of residual indent impression and sample anisotropy was examined in detail, with methods used to account for such sample non-idealities and provide more reliable data presented. This thesis further investigates how sample mounting conditions affect and can sometimes produce error in the compliance of the nanoindentation system. Such research expands and improves the minimal research that currently exists in the literature by providing concrete methods for avoiding issues caused by sample mounting in order to produce accurate and reliable data
Immunomodulatory Roles of Renal Lymphatic Endothelial Cells in Kidney Injury
No full textAcute Kidney Injury (AKI) is defined as a sudden decrease in renal filtration and is found to be associated with increased risk of developing chronic renal conditions such as Chronic Kidney Disease (CKD) and End-Stage Renal Disease (ESRD). While the mechanisms of the AKI-to-CKD transition remain unclear, AKI associated injury promotes an environment of persistent renal inflammation and fibrotic remodeling which may drive irreversible loss of nephrons and other renal cell types. Inflammation associated lymphangiogenesis (IAL) maintains tissue homeostasis through the uptake of proteins, fluids, macromolecules, and immune cells. IAL occurs upon AKI insult and is driven by Vascular endothelial growth factor D (VEGF-D) and VEGF-C. Recent work has demonstrated lymphatics and their components, lymphatic endothelial cells (LECs), have immunomodulatory roles such as antigen presentation, major histocompatibility complex (MHC) expression, and chemokine receptors. This dissertation investigates how renal lymphangigogenesis and LEC genetic adaptations in various models of kidney injury alter the adaptive immune cells in the kidney and the outcomes of renal function post-injury. Increased renal lymphatic density prior to the onset of kidney injury in a mouse model of kidney specific inducible overexpression of VEGF-D (KidVD) demonstrated an altered CD4:CD8 T cell ratio, decreased fibrotic remodeling, and improved functional recovery. Single cell RNA sequencing (scRNA seq) revealed that after AKI isolated renal LECs have T cell related immunomodulatory roles. To address the direct effect of LEC- T cell interactions, a murine genetic model with a LEC specific deletion of the Sphingosine-1- Phosphate (S1P) transporter Spinster 2 (SPNS2), key for S1P chemokine gradients to direct tissue immune cell egress, revealed altered renal immune cell subtypes and differential responses to injury challenge. Additionally, mice with disrupted LEC-S1P signaling demonstrate increased renal immunoglobulin deposition and, with nephrotoxic serum challenge, increased B cell activation and B effector subtype presence. This dissertation strengthens the connection between lymphangiogenesis and immunomodulation in kidney injury through the alteration of the adaptive immune response and demonstrates lymphatic targeted therapeutics may provide a novel renal targeted treatment option to prevent inflammatory progression to CKD