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Interaction of Rhodococcus equi with Innate Immune Cells: In Vitro and In Vivo Studies
No full textRhodococcus equi is a facultative intracellular bacterium and an opportunistic pathogen that exploits foals��� immature immune system and causes severe pyogranulomatous pneumonia. Currently, no vaccine is available to prevent R. equi pneumonia in foals, and previous vaccine trials have focused on adaptive immune responses. Evidence exists about the importance of induction of enhanced innate immune responses; thus, we focused on studying the interaction of R. equi with the innate immune system. The first objective of this dissertation was to provide a literature review summarizing the current understanding of interactions between R. equi and the host innate immune system, and to describe features of the immune response that are associated with resistance or susceptibility to R. equi infection. Second, we evaluated in vitro the impact of Toll-like receptor 2 (TLR2), complement receptor 3 (CR3), and Fc gamma receptor III (Fc��RIII) on R. equi phagocytosis and intracellular replication in macrophages. Phagocytosis of R. equi was not affected the absence of TLR2 or CR3. Absence of TLR2, CR3, or Fc��RIII did not affect intracellular replication of virulent R. equi; however, avirulent R. equi had increased survival in TLR2-/- and CR3-/- macrophages than in WT or Fc��RIII-/-. Therefore, TLR2 and CR3 downstream pathways limit replication of avirulent but not virulent R. equi. Third, we examined in vivo the effects of enteral vaccination with live, virulent R. equi, the only foal vaccination strategy that protected against pneumonia, in the innate immune system. We demonstrated that administration of enteral R. equi to foals soon after birth overcame neonatal vaccination challenges and protected against pulmonary challenge with R. equi at age 28 days. Enteral R. equi reprogramed blood monocyte epigenetics, altered the expression of over 1,000 genes in neutrophils, and induced higher levels of R. equi-specific IgG���, IgG���/���, and Th1 response. Therefore, early life exposure to R. equi in the gastrointestinal tract enhanced innate immune cells response, possibly facilitating the development of adaptive immune responses, and protected neonates against pneumonia. Collectively, we unveiled the impact of macrophage receptors in controlling R. equi infection and the effects of enteral R. equi stimulation on foal innate immune cells
Interaction of Rhodococcus equi with Innate Immune Cells: In Vitro and In Vivo Studies
No full textRhodococcus equi is a facultative intracellular bacterium and an opportunistic pathogen that exploits foals��� immature immune system and causes severe pyogranulomatous pneumonia. Currently, no vaccine is available to prevent R. equi pneumonia in foals, and previous vaccine trials have focused on adaptive immune responses. Evidence exists about the importance of induction of enhanced innate immune responses; thus, we focused on studying the interaction of R. equi with the innate immune system. The first objective of this dissertation was to provide a literature review summarizing the current understanding of interactions between R. equi and the host innate immune system, and to describe features of the immune response that are associated with resistance or susceptibility to R. equi infection. Second, we evaluated in vitro the impact of Toll-like receptor 2 (TLR2), complement receptor 3 (CR3), and Fc gamma receptor III (Fc��RIII) on R. equi phagocytosis and intracellular replication in macrophages. Phagocytosis of R. equi was not affected the absence of TLR2 or CR3. Absence of TLR2, CR3, or Fc��RIII did not affect intracellular replication of virulent R. equi; however, avirulent R. equi had increased survival in TLR2-/- and CR3-/- macrophages than in WT or Fc��RIII-/-. Therefore, TLR2 and CR3 downstream pathways limit replication of avirulent but not virulent R. equi. Third, we examined in vivo the effects of enteral vaccination with live, virulent R. equi, the only foal vaccination strategy that protected against pneumonia, in the innate immune system. We demonstrated that administration of enteral R. equi to foals soon after birth overcame neonatal vaccination challenges and protected against pulmonary challenge with R. equi at age 28 days. Enteral R. equi reprogramed blood monocyte epigenetics, altered the expression of over 1,000 genes in neutrophils, and induced higher levels of R. equi-specific IgG���, IgG���/���, and Th1 response. Therefore, early life exposure to R. equi in the gastrointestinal tract enhanced innate immune cells response, possibly facilitating the development of adaptive immune responses, and protected neonates against pneumonia. Collectively, we unveiled the impact of macrophage receptors in controlling R. equi infection and the effects of enteral R. equi stimulation on foal innate immune cells
Improving the In Vitro-to-In Vivo Extrapolation to Predict Environmental Chemicals Toxicokinetics and Hazard by Construction of New In Silico Models with In Vitro Testing Data
No full textIn light of the vast number of chemicals present in diverse environmental media, necessitating exposure assessments to protect human health, in vivo studies have traditionally been considered gold standards for providing hazard and kinetic data for risk assessments. However, their limited throughput and higher costs mean only a fraction of chemicals possess sufficient toxicity data for assessing health risks. To address this crucial data gap, New Approach Methodologies (NAM), particularly the application of in vitro-to-in vivo extrapolation (IVIVE) with in vitro studies and in silico computational models, have been developed. The demand for assessing risks for numerous chemicals necessitates effective and high-throughput methodologies. Nonetheless, IVIVE faces challenges, including the accuracy of in silico predictions on toxicokinetic (TK) properties based on in vitro datasets and linking in vitro adverse outcomes to whole-organ level phenotypes.
We here hypothesized that that innovative computational approaches integrated with in vitro studies will enhance TK predictions and hazard identification for environmental chemicals while advancing high-throughput screening methodologies. To test this hypothesis, three specific aims were proposed: (1) developing a physiologically-based gut absorption model for probabilistic prediction of environmental chemical bioavailability based on in vitro permeability measurements, (2) improving the prediction of renal clearance for per- and polyfluoroalkyl substances by integrating in vitro toxicokinetic datasets from different assays with physiologically-based kidney model to implement IVIVE, and (3) identifying the proarrhythmic potential of environmental chemicals by integrating an in vitro human model with Bayesian population modeling.
The achievement of these aims will demonstrate how novel in silico models and in vitro datasets can enhance the prediction of hazards and toxicokinetics for environmental chemicals. Additionally, these studies will facilitate the application of in vitro datasets in high-throughput screening of chemicals for risk assessment. Ultimately, we anticipate that these endeavors will contribute to filling critical data gaps related to TK properties and hazards for environmental chemicals, aligning with the long-term goal of protecting human health from exposures to hazardous environmental chemicals
Characterizing Effects That Influence Measured Range Hood Capture Efficiency
No full textKitchen range hoods remove harmful contaminants released by cooking, and they are essential for maintaining healthy indoor air quality. Standardized range hood capture efficiency (RHCE) experiments and tests were performed, and the resulting data were used to calculate RHCE, which is a parameter that provides a measure of how contaminants are removed. The goal of the studies reported herein is to improve the repeatability and reproducibility of RHCE tests performed in accordance with ASTM E3087.18. Changes to the standard aligning with the results of these reported studies will contribute to a reduction in error between measurements made at different testing laboratories, as well as a reduction in test variability. Achieving these goals is an essential step in ensuring further widespread adoption of the testing standard and RHCE as a metric, which in turn will lead to improved indoor air quality and human health, along with less energy consumed and greenhouse gas released.
A detailed experimental study was performed to analyze the effect of tracer gas injection rate, emitter assembly surface temperature, and chamber volume on measured RHCE. One study herein found that when the chamber volume was reduced from 36.6 m3 to 21.0m3 then a sample produced average results 3.6%CE lower at its higher operating speed and 7.8%CE lower at its lower operating speed. In contrast, in another study herein, a more extreme volume reduction led to a decrease in RHCE for another sample���s high-speed setting and an increase on its low-speed setting, suggesting that while chamber volume change has a definite effect on measured RHCE, this effect is not always consistent between samples or operating conditions.
Two analytical models were derived to predict chamber and exhaust concentrations during an RHCE test. The second model, which is the more useful model, assumes that there are two bodies of chamber air with limited interaction. It was validated by comparing its predicted results against experimentally measured ones. While the model predicted chamber CO2 concentration within 1.8% for a high-RHCE case, its accuracy was just 14.8% for a low-RHCE case. Further analysis found the model to have a consistent decrease in accuracy with decreasing nominal RHCE. The models can be used to predict performance and trends if one keeps in mind the limitations of the model with regards to its accuracy in specific flow ranges.
Another experimental study was performed herein to characterize the distribution of tracer gas throughout the test chamber. Results of this study confirmed that the concentration of tracer gas decreases as distance from the emitters increases, but that there is also a local zone of relatively low tracer gas concentration along the centerline of the room.
A reference range hood frame without a blower was constructed and tested for comparison against conventional range hoods. This test series aimed to determine whether the fan blower and motor selection impacts low-CE results. Using the exhaust as a prime mover, the reference box achieved capture efficiencies of 96.5% at 250 CFM, 93.3% at 160 CFM, and 81.3% at 100 CFM, outperforming other range hoods while showing lower test variance, with the result that fan and motor installation have a negative effect on RHCE. While design refinement is needed to better satisfy the initial goal of replicating low-RHCE results, the box���s low variance between tests suggests only minor modification of the design should be needed to do so.
A chamber inlet modification was performed and validated to ensure it did not severely impact the quality of measured RHCE. Three units were tested before and after installing the inlet modification. The results show that the inlet modification slightly reduced variance without noticeably affecting mean RHCE in four of five tested cases, but in one case it led to an increase in mean RHCE from 75.6%CE to 87.2%CE accompanied by an increase in variance from 0.94%CE to 3.06%CE. The results of this study found that the inlet change does not noticeably interfere with RHCE measurements
The Genetic Basis of Seasonal Migration and Its Role in Reproductive Isolation
No full textSeasonal migration has been suggested to play a role in speciation through environmentally induced selection against hybrids. Many migratory divides occur between groups that take different migratory routes. For example, the songbird Swainson���s thrush forms a migratory divide in western North America. This species includes two subspecies; coastal thrushes migrate along the west coast of North America while inland thrushes migrate east of the Rocky Mountains, through central North America to South America. These routes are largely genetically determined and involve navigation around geographic barriers. Hybrids in the divide have been shown to take intermediate routes that lead them through these barriers, potentially reducing their fitness. I used this system, spatial modeling, state-of-the-art tracking and genomic techniques to test the role migratory behavior plays in speciation.
First, I used spatial modeling and habitat preferences of birds on migration to show that hybrids taking intermediate routes have less access to highly suitable habitats and encounter more resistance on their routes compared to parental forms. These findings suggest that intermediate routes are inferior to routes taken by parental birds and there could be selection against hybrids contributing to speciation. Second, I individually tracked over 500 adult and juvenile Swainson���s thrushes from the center of the hybrid zone, obtaining detailed data on several migratory traits (e.g., orientation, timing, and wing morphology). Genomic mapping showed that most migratory traits are highly heritable and genetically correlated. I also mapped these traits to specific genomic regions, gaining insight into how these traits may be co-regulated and generating a list of candidate loci that are associated with these traits. Third, I used genomic data and analyses of viability selection to identify signatures of selection along the genome. I connected these regions with the genes associated with migration and showed that these loci are under selection. Combined, results from this dissertation provide one of the most comprehensive tests of seasonal migration as a driver of environmentally induced selection against hybrids in a free-living population that has ever been conducted. My results also provide insight into additional fields, including behavioral genetics and conservation biology
Interaction of Rhodococcus equi with Innate Immune Cells: In Vitro and In Vivo Studies
No full textRhodococcus equi is a facultative intracellular bacterium and an opportunistic pathogen that exploits foals��� immature immune system and causes severe pyogranulomatous pneumonia. Currently, no vaccine is available to prevent R. equi pneumonia in foals, and previous vaccine trials have focused on adaptive immune responses. Evidence exists about the importance of induction of enhanced innate immune responses; thus, we focused on studying the interaction of R. equi with the innate immune system. The first objective of this dissertation was to provide a literature review summarizing the current understanding of interactions between R. equi and the host innate immune system, and to describe features of the immune response that are associated with resistance or susceptibility to R. equi infection. Second, we evaluated in vitro the impact of Toll-like receptor 2 (TLR2), complement receptor 3 (CR3), and Fc gamma receptor III (Fc��RIII) on R. equi phagocytosis and intracellular replication in macrophages. Phagocytosis of R. equi was not affected the absence of TLR2 or CR3. Absence of TLR2, CR3, or Fc��RIII did not affect intracellular replication of virulent R. equi; however, avirulent R. equi had increased survival in TLR2-/- and CR3-/- macrophages than in WT or Fc��RIII-/-. Therefore, TLR2 and CR3 downstream pathways limit replication of avirulent but not virulent R. equi. Third, we examined in vivo the effects of enteral vaccination with live, virulent R. equi, the only foal vaccination strategy that protected against pneumonia, in the innate immune system. We demonstrated that administration of enteral R. equi to foals soon after birth overcame neonatal vaccination challenges and protected against pulmonary challenge with R. equi at age 28 days. Enteral R. equi reprogramed blood monocyte epigenetics, altered the expression of over 1,000 genes in neutrophils, and induced higher levels of R. equi-specific IgG���, IgG���/���, and Th1 response. Therefore, early life exposure to R. equi in the gastrointestinal tract enhanced innate immune cells response, possibly facilitating the development of adaptive immune responses, and protected neonates against pneumonia. Collectively, we unveiled the impact of macrophage receptors in controlling R. equi infection and the effects of enteral R. equi stimulation on foal innate immune cells
Effects of Horizontal Resolution on Precipitation Simulations
No full textPrecipitation simulated by climate models in different resolutions, including the mean state of global precipitation, regional precipitation response to mesoscale SST variability, global extreme precipitation in present-day and its future projections, are investigated using both observational (reanalysis) data and global climate model simulations.
The hydrological cycle and its anticipated alterations in the face of global warming are analyzed and compared based on observations, reanalysis datasets, and climate models with different horizontal resolution. Notably, CESM-HR demonstrates a remarkably more robust oceanic water cycle than CESM-LR, a difference possibly stemming from the warmer SSTs in CESM-HR in contrast to CESM-LR. Under global warming, the impact of increased horizontal resolution on future projected changes in the hydrological cycle becomes apparent. Specifically, CESM-HR exhibits a slightly higher percentage increase in ocean-to-land water vapor transport. Therefore, it plays a role in the amplified increase in precipitation over land under climate change.
Precipitation and associated atmospheric response to mesoscale SST forcing is explored. By filtering out mesoscale SST variability, CESM-HR produces a realistic precipitation response as observed, while CESM-LR fails to capture such a response because of absent mesoscale SST variability. Further analyses in CESM-HR and ERA5 reveal a similar vertical velocity response extending up to 500hPa, suggesting a possible free-atmosphere response to mesoscale SST anomalies. Composite analysis further validates this local deep response. The poor representation of mesoscale SST variability in CESM-LR hampers model���s ability to simulate precipitation and associated circulation response.
A comprehensive overview of the impact of horizontal resolution on presenting extreme precipitation shows that, CESM-HR not only replicates the observed spatial distribution of extreme precipitation but also accurately captures the intensity across the global land. Significantly, the discernible influence of horizontal resolution on precipitation extremes predominantly manifests itself through its effect on the representation of resolved large-scale precipitation. Under global warming, extreme precipitation over most of the global land is shown to be intensified. After decomposing projected changes of extreme precipitation by moisture budget analysis in CESM-HR, we find that across most of the global land area, the projected changes are predominantly attributed to shifts in atmospheric circulation features, rather than contributions from thermodynamics
Remote and Proximal Imaging Methods for Cotton Nitrogen Status Estimation
No full textNitrogen (N) is an essential plant nutrient and also a major environmental pollutant. Plants require N for amino acid synthesis, chlorophyll health, canopy growth, and yield. In cotton, both N deficiency and excessive N applications affect plant growth and yield. Studies showed that the growth period between squaring and peak flowering corresponded to peak N uptake in cotton plants. Here we explored remote and proximal imaging methods to quantitatively estimate N status in cotton.
A multi-year N management field experiment was conducted to observe cotton development between vegetative growth and early flowering stages. Extraction of precise spatiotemporal features and robust modeling were the topics emphasized in this dissertation. Objective 1 determined the effect of exposure settings on image radiometric accuracy. The results favored the use of fixed exposure settings for UAV flights and the ideal exposure time and gain were empirically determined for the camera. The object-based empirical line calibration method was proposed for images acquired with fixed exposure settings. Objective 2 explored the systematic integration of the downwelling light sensor (DLS) to compensate for changing illumination conditions. The proposed DLS-based methods effectively removed radiometric errors due to illumination changes in fixed and auto-exposure images.
Objective 3 assimilated results from Objectives 1 and 2 to extract calibrated spectral and morphological cotton canopy features to quantify canopy N and predict stress levels. Plant biological parameters ��� plant N concentration, plant N uptake, dry biomass weight ��� were best estimated when spectral and morphological features were combined through random forest regression and gradient boosting regression models. Model estimated parameters were used to derive nitrogen nutrition index to predict stress levels with good precision and recall (F1 = 0.75). Objective 4 explored extracting spectral and morphological features from oblique ground-based images. The goal was to see if cotton had differences in spectral vegetation indices in the top and bottom canopy layers due to N stress. An algorithm was developed to correct perspective distortion in oblique images. The results showed scope for further exploration of oblique images for early detection of N stress
Feasibility of Mixed-Integer Linear Programming for Onboard Planning in Distributed Earth Observation Satellite Systems
No full textPlanning is traditionally completed on the ground, which limits swift response to events of interest. As a result, there is an expanding need for onboard planning for satellites. This sparks exploration of the feasibility of reactive Earth observation using optimization for onboard, edge processing of plans. Reactive Earth observation lowers response time to events of interest, such as tropical storms or the formation of algal blooms.
This thesis compares a global optimization method, mixed-integer linear programming (MILP), with two less computationally expensive local optimization methods: greedy and forward search algorithms. This planning problem models a satellite constellation operating within an inland water quality remote sensing mission over a 24-hour simulation period. The water quality mission poses a challenge due to the small swath of relevant onboard instruments used to observe the large quantity of water bodies.
Two respective cases of 5- and 10-satellite constellations are applied to investigate scalability of the problem. On average, the local optimization methods achieve 64% of MILP performance. Smaller 1- to 2-hour planning horizons generally have little effect on MILP performance. Additionally, the MILP successfully solves problem sets of up to 580,000 variables for the 5-satellite problem and up to 900,000 variables for the 10-satellite problem. The MILP achieves these metrics in planning horizons of up to 8-hours for the 5-satellite problem and in planning horizons up to 4-hours in the 10-satellite problem.
A Raspberry Pi was employed to characterize the feasibility of using MILP for onboard planning. The Raspberry Pi could solve problems that did not exceed its memory capacity and was able to solve at least half as many problems as the PC was able to solve, depending on the size of the problem set.
Performance results build an argument to use small planning horizons to create plans in a reasonable amount of time. Raspberry Pi results suggest that smaller problem sets that do not exceed memory capacity during solving ensure that onboard planning is feasible for MILP. Overall, results suggest that MILP is a great method for satellite planning for relatively small problems
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