Master's Theses: Recent submissions
Now showing items 1-20 of 15972
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Variable Selection in Economic Applications of Remotely Sensed Weather Data: Evidence from the LSMS-ISAThe rise in the availability of remotely sensed weather data has resulted in economists predicting different outcomes using rainfall as an explanatory or instrumental variable (IV). We analyze 174 papers to identify common rainfall metrics used as an instrument and show the extent of their ad hoc use in predicting a range of outcomes. We use agricultural productivity as a case study to examine the suitability of using different rainfall metrics as an IV. To that extent, we test the predictive power of the 14 most common rainfall metrics in the economics literature, calculated through six remote sensing products across six countries, on agricultural productivity. We find a large amount of heterogeneity in the performance of rainfall metrics. We also find concerning evidence about the validity of using rainfall metrics as an instrument, especially regarding possible exclusion restriction violations and weak instrument problems. Our findings emphasize the need for researchers to carefully select and justify their use of a particular rainfall metric to improve the reliability of their analysis.
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The Spatial and Dynamic Patterns of Climate Variability and Change in the United StatesMany adaptation and mitigation measures related to climate change require a temporally relevant understanding and for action to be taken at all levels of political jurisdiction. We analyze the developments of county experiences from the years 1895 to 2023 within the CONUS, Western U.S., Arizona, and Minnesota by employing numerous methods. The first descriptive statistical methods examine overall trends and discern how average, maximum, and minimum temperatures and precipitation patterns have changed in variability, spatial variation, as well as how the distributions have developed over time. Polarization indices are then used to analyze how the climatic experiences of counties have grown, be it more similar or less similar. We find that, for most counties, temperature variables have decreased in variability and precipitation has negligibly changed, implying a convergence of temperature ranges and minute shifts in the variability of precipitation. For most counties, the polarization of temperature variables has also decreased, while the polarization of precipitation has changed very little, suggesting that county experiences of temperature across the United States have generally become more alike and that precipitation experiences have changed little. Meanwhile, elements of spatial variation are exhibited through varying levels of significance across our selected regions, and the primarily opposing directions of results in Arizonan summers, which frequently exhibit increases in both variability and polarization.
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The Seasonal Variability of Trace Metals and their Transport Mechanisms in Intermittent StreamsMany intermittent and ephemeral washes drain metals-rich catchments, but the natural concentrations andtransport mechanisms of metals in their streamwater discharge are mostly unknown. In the 1960s, anomalously high metal content detected in southeastern Arizona streams led to the discovery of porphyry copper deposits in upstream areas of the Santa Rita Mountains. Although no large-scale mining operations have yet occurred, ground preparation activities have taken place in a catchment that is drained by the Barrel Canyon wash. Mine disturbances have the potential to not only impact water quality in Barrel Canyon, but also downstream in Davidson Canyon and in Cienega Creek Natural Preserve—sections of which are designated as “Outstanding Arizona Waters” by the State of Arizona. In addition to compiling historical records of trace metals concentrations in Davidson Canyon and CienegaCreek since 2002, this study also collected 128 new samples at four different sites between January 2021 and February 2024. Three of the four sites are connected in series via ephemeral surface washes and intermittent/perennial sections of streamflow, and could be potentially impacted by mobilized contaminants originating from the porphyry copper deposit in the Santa Rita Mountains. The fourth site is a perennial reach of Lower Cienega Creek, and is upstream of potential contamination originating from the Santa Rita Mountains. ISCO autosamplers were installed and used at each site to capture stormwater discharge brought on by heavy rains and monsoonal thunderstorms. Additionally, surface water baseflow at each site was frequently sampled throughout the study’s sample-collection period. Results from all four sites indicate that the concentrations of trace metals and major dissolved ions instormflow generally have opposite behaviors. When groundwater-fed baseflow is the primary contributor to streamflow, the concentrations of both particulate and dissolved trace metals are low, while the concentrations of major dissolved ions are high. During stormflow, when the stream is composed mostly of precipitation runoff, dissolved ion concentrations are low, while the concentrations of both particulate and dissolved trace metals are at their highest. These results suggest that the sources of trace metals in the Davidson Canyon and Cienega Creek subwatersheds are not from groundwater, but instead are being flushed out from the soil profile at relatively shallow depths during heavy rains. A seasonal cycle of dissolved arsenic concentrations increasing and decreasing in tandem withstreamwater temperature was observed at the three sites connected in series. Dissolved arsenic concentrations at the fourth site were generally higher but also more variable than at the other three sites. Possible reasons for these observed trends, such as the redox environment and the activity of iron-cycling microbes are discussed. Results from water quality analyses were compared to relevant federal and state water quality standardsspecific to trace metals. 14 of the 128 new samples exceeded at least one water quality standard, and many samples exceeded multiple different standards concurrently. 11 out of the 14 samples that exceeded thresholds were found in either Barrel Canyon or Davidson Canyon—the two sites closest to potential mine runoff. The five primary contaminants of concern were arsenic, lead, copper, iron, and zinc. This study found evidence that the concentrations of trace metals in Barrel Canyon wash, DavidsonCanyon, and Lower Cienega Creek have increased from their historic norms, beginning around late 2022. In particular, dissolved zinc concentrations in baseflow were found at unprecedented levels. It is possible that metals-rich soil from the Santa Rita Mountains was disturbed during mine preparation activities, and is now reacting with and/or being transported downstream by oxygenated rainwater, causing metals concentrations to increase along the drainage flow path. These results highlight the vital importance of continual water quality monitoring in areas that could be impacted by mining activities.
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Revegetation Strategies for Ecological RestorationSeed-based revegetation is often unsuccessful in ecological restoration efforts in drylands, mainly due to an unfavorable environment for germination and establishment, as well as poorly understood germination behaviors of restoration-relevant plant species. We conducted two experiments in order to first identify potential revegetation methods for enhancing emergence and establish through the use of seed balls, and then to identify specific germination behaviors of a pollinator restoration plant known as milkweed (plants belonging to the genus Asclepias). In our seedball field experiment, we tested different seed ball types by observing how altering seedball shapes and additives impacted emergence and establishment. We found that overall, seedballs significantly enhanced early emergence, but had no long term beneficial effects on establishment, with no significant differences between the seedball types. We then conducted a germination study of various milkweed species sourced from different regions throughout the U.S. to detect differences in germination behaivour in response to warm incubation temperatures and cold stratification. Overall we found that dormant milkweed populations responded postively to a six week period of cold stratification, but that two southern populations of A. asperula and A.syriaca may have higher sensitivty to warm incubation temperature. We also found that non dormant milkweeds displayed similar germinaiton rates across a range of warm incubation temperatures, but that one populuation of A. incarnata may have higher sensitivty to warm incubation temperature while two populations of A. angustifiulia and A. speciosa have a stronger preference for warmer incubation temperatures. We suspect these differences in germinaiton behavior are linked to last frost date and precipitation seasonality of the source climate.
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Reexamining Preference for Online Social Interaction: Compulsion and Close Interactants as Moderators for Positive and Negative OutcomesPreference for online social interaction (POSI) has primarily been studied as an aspect of problematic Internet use and as an antecedent to negative outcomes of Internet use. This study examines the potential that POSI alternatively or additionally contributes to positive outcomes. Two moderators are proposed for situations when POSI may contribute to negative and positive outcomes: compulsive Internet use and frequency of interaction with strangers and close partners. An online questionnaire was used to test these moderators. Although the results show no significant interaction effects, the study finds that POSI is associated with positive outcomes of Internet use (but not negative outcomes), compulsive Internet use contributes to negative outcomes, and more frequent online interaction with both strangers and close partners contributes to positive outcomes.
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Quantifying Adaptive Mechanisms and Ovarian Dynamics in Developing Heat Stress Beef HeifersThe objective of this study was to quantify the adaptive mechanisms and ovarian dynamics in developing beef heifers which influence reproduction. We hypothesized that heat stress conditions would have negative implications for reproduction in heifer. A total of 12 crossbred heifers were obtained from the University of Arizona (U of A) Experiment Station V-V Ranch near Camp Verde, Arizona. Inclusion criteria for the study included matured mix breed heifers with an ideal pubertal weight and showing signs of estrus cyclicity. Heifers were stratified by body weight (BW) and randomly assigned to one of two treatment groups: heat stress (HS) or thermoneutral (TN) for 40-days (40d). HS was defined as exposure to a temperature humidity index (THI) of 73–83 while the TN (control) group was defined as exposure to a THI of 68. Over the 40d period, vital parameters (respiratory rate [RR], rectal temperatures [RT]) and water intake (WI) were taken twice daily. Blood samples, body weight (BW) and body condition scores (BCS) were collected biweekly. Average concentrations of cortisol, progesterone, non-esterified fatty acids (NEFA) and beta-hydroxybutyrate (BHB) were obtained from plasma samples. At day 40, non-terminal bilateral ovariectomies were performed and ovarian metrics were measured and analyzed. For repeated measurements, outcome variables were analyzed using a mixed-effects regression model with the inclusion of day and treatment as fixed effects and the random effect of the individual. Pairwise comparisons of the estimated marginal means were performed, and statistical significance was set at a Tukey corrected p-value of <0.05. For ovarian measurements, an ANOVA was performed with a threshold for significance set at a p-value <0.05.Results showed that there was a significant difference between average RR, where HS heifers had higher breaths per minute in the morning and afternoon (P<0.05). Afternoon RTs were significantly increased in HS heifers while morning RT were not statistically different. This indicated that our heat stress model was effective in inducing heat stress conditions within our experimental group. Regarding body metrics, BW and gain to feed ratios were not significantly different between groups. Although statistical differences were observed for average BCS (P<0.05), with HS heifers having an average BCS of 5 versus TN which had an average BCS of 4.8, this was not considered biologically significant. These results suggest that HS was not a major factor contributing to weight gain or feed efficiency. Average NEFA concentrations were significantly higher in TN heifers (P < 0.04); however, BHB concentrations did not differ between groups. This indicates that the HS group were high mobilizers for fatty acids but low oxidizers. Average plasma cortisol and progesterone were not statistically different, suggesting heat adaptation within our cohort. Out of the ovarian tissue metrics analyzed, a significant difference was observed in combined total antrafollicle surface count of both ovaries, where TN heifers had a higher count (P=0.05). This suggests that heat stress conditions caused a reduction of antra follicles, which decreases ovarian reserve, and, consequently, overall fertility. In conclusion, for this cohort a higher threshold for heat stress conditions would be needed to see differences in all outcome variables. This suggests that our cohort had as adaptive advantage to heat tolerance given that the heifers were native to Arizona. This pilot study is the first to assess heat stress in Arizona beef heifers, providing preliminary data on their early-stage physiological adaptations. It lays the groundwork for further research aimed at developing a selection tool to help producers identify ideal replacement heifers. Selecting the right replacements is crucial for cattle producers, as it enhances long-term herd productivity, reduces costs, and ultimately lowers meat prices for consumers.
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Proteomic Assessment of Post-Translational Modifications in the Brain of 5x-FAD FemalesDementia prevalence is expected to more than double in the next three decades stressing numerous healthcare systems and caregivers across the globe. Alzheimer’s disease (AD), the most common form of dementia, is a multi-factorial neurodegenerative disease without a cure due to the incomplete understanding of its complex progression. Our aim is to report hypothesis generating data for targeted functional studies to understand the mechanisms underlying differential expression and post-translational modifications in AD using the 5x-FAD murine model. The bulk proteome, S-nitrosylated proteome, phosphoproteome, and acetylome were assessed by unbiased tandem mass spectrometry and label-free quantitative proteomics. Affinity purification assays were utilized to enrich samples to evaluate S-nitrosylated proteins. Western blots analysis was performed on specific protein targets of interest from the bulk proteome and S-nitrosylated proteome to validate proteomic results. We observed 426 proteins with differential expression patterns across the whole proteome and 225 proteins with alterations in S-nitrosylation in 6-monthold female 5x-FAD mice. Additionally, 161 phosphopeptides and 23 acetylated peptides were found to be significantly different compared to wild-type (WT) littermates. Gene ontology (GO) analysis implicated enrichment of glutamateric signaling, oxidoreudctase activity, and cytoskeletal proteins, supporting current AD literature, while also elucidating the novel targeting that post translational modifications could have on the electron transport chain, transcription, and histone and mitochondrial acetylation. We further show primary validation of increased glial fibrillary acidic protein expression patterns, known to occur in AD patients, and revealed a conserved decrease in S-nitrosylation of myelin proteolipid protein. However, myelin-associated oligodendrocyte basic protein quantification did not allow for conclusive inferences to an under investigated aspect of AD. These proteomic data concur with well-documented protein changes, post-translational modifications, and enriched signaling pathways found in humans living with AD and animal models of the disease, linking specific proteins involved with cytoskeletal organization, mitochondrial ATP genesis, ion homeostasis, transcription, translation, and myelin sheath maintenance contributing to the multifactorial nature of AD.
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PNA5 Restores BK Channel Function in Cerebral Arteries of Female 5x-FAD MiceFew therapeutic options exist for treatment of Alzheimer’s disease (AD), the most prevalent type of dementia, particularly therapies focusing on cerebral microvascular function. AD is associated with impaired neurovascular coupling (NVC) in the brain, a process that ensures blood flow to regions of increased neuronal activity through functional cerebral microvascular dilation. This dilation involves opening of large conductance, Ca2+-activated K+ channels (BKCa), a channel known to be a target for oxidative modulation in the early-onset 5x-FAD model of AD. PNA5, an agonist of the vasculo-protective Mas receptor, prevents heart failure-induced dementia partially by antioxidant mechanisms, but its effects on AD remain undetermined. Thus, we hypothesized that PNA5 improves cerebral microvascular BKCa function in 5x-FAD mice. Five-month-old female 5x-FAD mice were treated with PNA5 (100 µg/kg/day, s.c.) or saline (vehicle) for 1 month. We measured Ca2+ sparks by spinning-disk confocal microscopy, BKCa-dependent vasoreactivity by pressure myography and NVC by laser speckle contrast imaging. Data are means ± SEM, WT vs 5x-FAD or 5x-FAD + saline vs. 5x-FAD + PNA5. We observed a significant increase in Ca2+ spark frequency in 5x-FAD compared to WT mice (0.5905 ± 0.08609 vs. 1.346 ± 0.1459, n=15, p = 0.0001, Student’s t-test) with no significant differences in Ca2+ spark frequency between vehicle and PNA5-treated 5x-FAD (1.236 ± 0.1367 vs. 1.188 ± 0.1226, n = 15, p = 0.7979, Student’s t-test). We also observed that 5x-FAD + PNA5 restored BKCa vasoreactivity, seen as a larger constriction after BKCa inhibition with iberiotoxin (30 nM, Vasoconstriction (%): 6.074 ± 0.3481 vs 14.65 ± 3.174, N = 3, p = 0.0129, Student’s t-test), without additive effects of the reducing agent dithiothreitol (DTT, 10 μM) in 5x-FAD + PNA5 (Vasoconstriction (%): 15.92 ± 3.442 vs. 11.80 ± 2.292, N = 3, p = 0.133, unpaired two-tailed Student’s t-test). Further, we observed an increase in cerebral functional hyperemia in 5x-FAD + PNA5 when compared to 5x-FAD + vehicle (Increase in perfusion (%): 3.596 ± 0.6964 vs. 8.614 ± 0.6589, N = 4 / 6, p = 0.0014, Student’s test). In conclusion, these data suggest that PNA5 improves BKCa activity and neurovascular function in 5x-FAD. Ongoing studies will expand on these findings to further investigate mechanisms that underlie the effects of PNA5 and how it may serve as a potential therapeutic drug for AD.
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Partitioning Forage Use among Wild and Domestic Ungulates in New MexicoManaging multispecies grazing on rangelands presents significant challenges, especially in distinguishing and balancing the specific forage utilization of wild and domestic species amid variable resource availability. Traditional grazing management primarily focuses on the quantity of animals in a pasture and the duration of their presence, yet assessing the intensity of grazing becomes complex when involving wild species like elk and feral horses. To improve our understanding and enhance grazing management practices, we deployed camera traps to observe cattle, elk, and horses within the critical habitat of the endangered New Mexico meadow jumping mouse (NMMJM). By applying animal use equivalents to these observations and comparing them with end-of-season utilization data, we gained detailed insights into species-specific forage use throughout the grazing season and across different life stages of the NMMJM. Additionally, we documented how cattle and elk abundance varied in response to season, fencing types, and presence of sympatric herbivore, with a particular focus on habitat use in relation to NMMJM critical habitat. Our findings indicate that cattle were more prevalent than elk, particularly near stream edges when accessible. Drier, resource limited conditions, further concentrated habitat use by cattle over the course of the grazing season and displaced elk into fenced portions of critical habitat. These dynamics underscore the complexity of managing grazing areas to support biodiversity, suggesting that adjustments in stocking rates, seasonal grazing schedules, and fencing maintenance are essential to mitigate the impacts of multispecies grazing and preserve critical habitats.
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Optical Characterization of Heat Transport in Vertically Aligned Carbon Nanotube ArraysVertically aligned carbon nanotube (VACNT) arrays, absorbing virtually all incident light, are a novel material with unique applications including as sensors, solar energy converters, and as nearly ideal blackbody radiators. Their superior thermal and optical properties are attributed to their structure, which can vary with how they are grown. In applications where insulation between tubes is of high importance, measurement of transverse thermal diffusivity is critical. In contrast with methods that measure transverse thermal diffusivity by measuring the back surface, here, the distal ends of the nanotubes are flash-irradiated with a Gaussian laser pulse with 1µm wavelength and the infrared emission of the VACNT front surface is captured as a function of time. Analysis of the captured images provides measurement of the thermal diffusivity in the transverse direction of the VACNT array. This method has been used for other anisotropic materials, but has not yet been applied to VACNT arrays. The optical characterization method demonstrated here enables feedback for application-tailored optimization of VACNT synthesis processes.
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Mulheres Negras Brasileiras No Mercado De Trabalho Informal De SalvadorCom o objetivo de construir espaços de transformações igualitárias dentro do mercado de trabalho brasileiro, esta pesquisa teve como principal objetivo entender quais os motivos que levam as mulheres negras a estarem no mercado de trabalho informal em Salvador/BA. No campo, foram realizadas observação participante, entrevistas individuais e em grupo e grupo focal com o grupo “Mulheres Unidas", vinculado ao Instituto Odara. A pesquisa teve duração de 4 meses, entre maio e agosto de 2023. O local escolhido foi Salvador, considerada a cidade mais populosa de pessoas negras fora do continente africano, devido à herança escravagista da cidade. As consequências da colonização se perpetuam em Salvador, vinculadas às questões interseccionais, como gênero e classe. A partir dos resultados obtidos pude constatar que as políticas anti negritude no Brasil reverberam de forma sistêmica na vida destas mulheres, seja na solidão que enfrentam como consequência da invisibilidade social ao longo das suas vidas, como também dentro do mercado de trabalho brasileiro, seja ele formal ou informal, já que este perpetua a desumanização destas mulheres.
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Moral Non-Naturalism (Finally) Meets Moral Twin EarthMany believe that one reason to accept moral non-naturalism, as opposed to moral naturalism, is that Terry Horgan and Mark Timmons’ Moral Twin Earth argument poses no threat to moral non-naturalism, whereas it does pose a threat to moral naturalism. Drawing from the work of Cole Mitchell, I argue that this belief is mistaken, and that Moral Twin Earth poses a threat to moral non-naturalism as well. I then attempt to figure out what kind of metasemantic theories, if any, would give the non-naturalist the right to cite Moral Twin Earth as a reason to prefer their own view over the naturalist’s. I consider three different theories that defenders of non-naturalism have proposed, and I conclude that none of them are sufficient to grant the non-naturalist such a right. However, by drawing from these view’s shortcomings, I provide a rough blueprint of what a theory that successfully grants the non-naturalist this right would look like.
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Inspection of Affection Selection and Selection ExceptionsFrom the perspective of affection exchange theory (AET), the tendency to communicate affection is an evolved adaptation in humans. Whereas the health and social outcomes of affectionate communication have been explored, there is much to learn about the desirability of affectionate communication in romantic relationships. AET proposes that affectionate behavior is a desired quality in romantic and sexual partners as well as fit parents. This study sought to discern how desirable an individual might be based on their portrayal of how affectionate they are, as well as how others might assess their fitness to be a parent or partner. The study found partial support for AET’s subpostulate 3c, indicating that the assessment of fit parenthood or partnerhood is moderated by gender. No association between portrayal affection or physical attraction, social attraction, or dating desirability was identified.
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Increasing Water Retention in Arid Soils through Biological Amendments: Adaptive Rotational Grazing, Cyanobacteria Inoculation, and Compost ExtractIf drought conditions continue, as expected, how can land managers prepare their fields to endure ongoing water rationing? Often adding biodiversity to land is seen as a liability to water resources, but perhaps biodiverse soil treatments can be a cost-effective tool for land managers. This research and literature review will synthesize experiments using compost extract and cyanobacteria inoculations as soil amendments to improve water retention and compare those results with experiments using adaptive rotational grazing (ARG) of livestock as a biological soil amendment positively impacting water retention. The experiment will also compare one year of ARG to three years of ARG. Data show that neither microbial inoculation helped to create more soil organic carbon, lower soil bulk density, or increase soil water infiltration. However, ARG did significantly increase soil organic carbon and marginally significantly decrease soil bulk density in the short term. Longer term increases were smaller. Based on these results, we suggest ARG is a more effective treatment for affecting soil hydrology compared to microbial treatments in hot arid systems.
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Green Infrastructure's Impact: Urban Rainwater Garden Influences on Semi-Arid Soil HealthClimatic and anthropogenic pressures, such as extreme weather and urban heat island, are felt now and will continue to worsen in the future. Such effects exacerbate urban environments that suffer considerably from environmental degradation as well as reduce ecosystem services. On a global scale, nature based solutions, like green infrastructure (GI) are argued to reduce these societal pressures in addition to restoring ecosystem functioning and resilience. While there are many benefits derived from green infrastructure, an intended element of the feature is enhanced soil health. Although a restorative function, the relationship between green infrastructure and soil health is understudied. Historically, the study of soils is an established discipline, yet soil assessments and indicators remain unclear, uninterpretable, and uncreative. We clarify these gaps by analyzing soil health correlations as well as the influence of seasonal precipitation regimes, GI treatments, and site on important and innovative indicators of physical, biological, and chemical soil health properties. At three locations, we sampled rain garden basins soils across semi-arid Tucson during the pre and post monsoon seasons. We hypothesized that variations in physical, biological and chemical indicators would be discernible across various seasonal regime inputs, treatment, and site. Results showed that biological and chemical indicators drove significant variation in overall soil health. Seasonal precipitation regimes significantly influenced biological indicators, while GI treatments only influenced change in carbon stabilization and decomposition, suggesting that rain gardens are regulators of soil nutrient cycling and respiration. Site effects strongly influenced differences in all three component soil health properties, highlighting the importance of site land management impacts. Though newly introduced indicators of soil health proved feasible, more research should be granted to better interpret their role and solidify their induction.
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Excitation of Type 1 HMM with a Grating for Biosensing ApplicationsThis thesis explores the excitation of bulk plasmon polariton (BPP) modes in type 1 hyperbolic metamaterials (HMMs) for biosensing applications. Utilizing a nanorod array embedded in a dielectric and enhanced by a diffraction grating, the study demonstrates the potential for achieving high sensitivity in refractive index biosensors. The methodology involves finite-difference time-domain (FDTD) simulations using Tidy3D software, focusing on the reflectance response and field intensity distributions of the nanostructures. Initial simulations of a nanorod array revealed standing wave patterns indicative of surface plasmon polariton (SPP) modes. The introduction of a grating structure, with a pitch optimized for BPP mode excitation, resulted in significant enhancement of the electromagnetic field intensity. This enhancement was particularly notable at a wavelength of 1.2625 μm, demonstrating a maximum normalized intensity approximately nine times that of the incident field. Further analysis showed that the BPP modes exhibited a strong dependence on the grating pitch and the dielectric refractive index, underscoring their potential for high-sensitivity biosensing. For the BPP mode, the calculated figure of merit (FOM) was 66.67 and the sensitivity (S) was 800 nm/RIU, substantially higher than the 16.00 FOM and S=400 nm/RIU observed for SPP modes. While the grating-based approach offers a compact and practical platform for exciting BPP modes, the sensitivity results were lower than those achieved with prism coupling methods. This suggests the need for further simulations and experimental validation to optimize the grating design and improve coupling efficiency. In conclusion, this work advances the understanding of BPP mode excitation in HMMs, highlighting the feasibility of using grating structures for biosensing applications. Future research should focus on refining the grating parameters and conducting experimental tests to validate these findings and explore their practical implementations in compact biosensing devices.
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Effects of Peroxynitrite on Vascular Smooth Muscle Cell BKCa ChannelsOxidative stress impairs vascular function in the brain and has been linked to neurodegenerative diseases, such as Alzheimer’s Disease (AD). Peroxynitrite is an oxidant produced in the cerebral vasculature via the reaction between superoxide and nitric oxide. A major target of oxidants is the thiol-containing residues of ion channels in the vascular smooth muscle cells, leading to impairment in their function. One of such targets is Ca2+-activated, large-conductance K+ channel (BKCa), which plays a vital role in maintaining cerebral vascular control and is impaired in the 5x-FAD mouse model of AD. However, the direct effects of peroxynitrite on BKCa function remain unknown. We hypothesized that peroxynitrite will decrease BKCa currents in a reversible manner in wild-type and 5x-FAD mice. Cerebral arteries of 5-6 month-old C57BL/6J and 5x-FAD mice were isolated and underwent a mild enzymatic digestion to obtain single smooth muscle cells for patch-clamp electrophysiology experiments. Data are means ± SEM, all curves analyzed by 2-way ANOVA with Sidak correction for multiple comparisons, bar graphs by Student’s t-test. Using the inside-out patch clamp electrophysiology configuration, BKCa channel activity was assessed through single channel open probability (Po) after chemical intervention or stepwise increases in membrane voltage. We observed that peroxynitrite (10 µM) did not alter BKCa voltage sensitivity (PoVehicle = 0.0102 ± 0.0001 vs. PoPeroxynitrite = 0.0105 ± 0.0058, 60 mV, 1 µM Ca2+, P=0.7413). However, peroxynitrite significantly decreased BKCa sensitivity to Ca2+ (in 10 μM Ca2+: PoVehicle = 0.0082 ± 0.0033 vs. PoPeroxynitrite = 0.0013 ± 0.0004, 40 mV, 10 µM Ca2+, P=0.0312). Partial recovery of channel activity was achieved via reducing agent DTT (10 µM, PoPeroxynitrite = 0.0080 ± 0.0020 vs PoPeroxynitrite+DTT = 0.0169 ± 0.0062, 60 mV, 10 µM Ca2+, P=0.0197). Next, we assessed BKCa function in cerebral artery smooth muscle cells from male 5x-FAD mice, and observed that single channel activity is similar to WT littermates (PoWild-type =0.0430 ± 0.0143 vs Po5x-FAD = 0.0258 ± 0.0058, P = 0.217, 60 mV, 10 µM Ca2+), despite a reported vascular BKCa dysfunction (% Vasoconstriction following iberiotoxin application: Wild-type = 6.600 ± 1.300 vs 5x-FAD = 1.551 ± 0.4645, P=0.0051). Further, in male 5x-FAD mice, channel activity was not improved with DTT treatment (PoVehicle=0.0203 ± 0.0051 vs PoDTT=0.0204 ± 0.0062, 60 mV, 10 µM Ca2+, P=0.9865). We conclude that peroxynitrite reversibly oxidizes BKCa channels by decreasing the channel’s Ca2+-sensitivity, independent of voltage, and that reversible oxidation or other channel modifications are not the root cause of BKCa impairment in male 5x-FAD mice
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Effects of Natural and Managed Disturbances on Soil Microbial CommunitiesDisturbances in both natural and managed ecosystems can significantly influence soil microbial communities, which play a critical role in ecosystem functionality through biogeochemical processes, soil development, and plant-microbe interactions. Understanding how disturbances impact these communities is essential for developing effective conservation and restoration strategies, particularly in the context of climate change and land degradation. In a study of coastal sand dune systems at St. George Island, Florida, USA, I investigated the soil microbial communities across successional habitats subjected to varying levels of disturbance to elucidate dune function and resilience. Using bacterial and fungal amplicon sequencing, I found that microbial communities varied significantly across successional habitats, with bacterial diversity peaking in interdune areas and fungal diversity highest in foredunes. Key drivers of microbial community composition included plant and soil characteristics, particularly pH and soil moisture. In a separate study aimed at restoring a former cropland to perennial grassland in Davis, California, USA, I assessed the effects of varying vegetation management intensities on soil microbial communities. By implementing combinations of targeted sheep grazing, controlled burning at different frequencies, and native plant strip seeding, I evaluated changes in microbial diversity, composition, and functional group abundances. These findings revealed that while microbial taxonomic diversity remained largely unchanged, the composition and inferred functional groups of soil microbial communities shifted in response to changes in plant community composition and soil properties, such as carbon:nitrogen ratios and pH. These investigations highlight that disturbances, whether through natural processes or human-induced management, differentially impact soil microbial communities. The resilience and adaptability of these communities are crucial for maintaining ecosystem processes and achieving land management objectives. Future research should continue to explore how shifts in microbial communities influence broader ecosystem functions, ensuring that management practices align with the goals of ecosystem restoration and conservation in the face of environmental change.
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Design of Carnitine-Fatty Acids Ionic Liquids Self Nano Emulsifying Systems To Enhance Oral Drug DeliveryThe solubility and bioavailability of Biopharmaceutics Classification System (BCS) class IV drugs, characterized by their low solubility and low permeability pose significant challenges for oral drug delivery. Drugs such as venetoclax, olaparib, and vemurafenib exhibit limited therapeutic efficacy due to their poor bioavailability. This thesis explores the potential of amphiphilic carnitine-fatty acid ionic liquids for enhancing drug solubility via self-nanoemulsifying systems (SNES). Thermally stable ionic liquids were synthesized with a relatively unexplored biocompatible quaternary ammonium cation called carnitine and several fatty acids as counter ions. The ionic liquids demonstrated improved solubility of several highly insoluble drugs. The development of SNES was conducted with a series of rigorous screening and optimization experiments, leading to formation of stable nano emulsions. The drug loaded SNES formulations showed reduced globule sizes (<150 nm) and uniform dispersion in various pH buffers, equivalent to the environment of the gastrointestinal tract. A comprehensive pharmacokinetics study compared traditional drug (venetoclax) suspension with drug (venetoclax) loaded SNES with one of the selected emulsion formulations, revealing a notable increase in drug absorption and prolonged drug action. This work underscores the potential of ionic liquids and SNES in revolutionizing drug delivery systems, enhancing drug solubility, stability, and bioavailability, leading to more efficient and effective treatments.
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Depolarization Characteristics of Biological Tissues in Transmissive Imaging Configurations Over the Visible SpectrumImages of gastrointestinal cancer samples taken in a transmission configuration have shown an increase in depolarization in the tumor relative to the healthy tissue. Furthermore, the depolarization of the cancerous tissue increases with wavelength. This conflicts with previous measurements taken in the reflection (backscatter) configuration. Monte-Carlo analysis was done using Rayleigh and Mie scattering objects to attempt to model the polarization properties of the tissue in a transmissive imaging configuration. Results show that increased cellular density can lead to the increase in depolarization of the tumor compared to the healthy tissue, however, Rayleigh and Mie based scattering theory can not explain the increase in depolarization with wavelength that was measured across the visible spectrum.