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Pesto: Cooking up High Performance BFT Queries
No full textThis paper presents Pesto, a high-performance Byzantine Fault Tolerant (BFT) database that offers full SQL compatibility. Pesto intentionally forgoes the use of State Machine Replication (SMR); SMR-based designs offer poor performance due to the several round trips required to order transactions. Pesto, instead, allows for replicas to remain inconsistent, and only synchronizes on demand to ensure that the database remain serializable in the presence of concurrent transactions and malicious actors. On TPC-C, Pesto matches the throughput of Peloton [20] and Postgres [21], two unreplicated SQL database systems, while increasing throughput by 2.3x compared to classic SMR-based BFT-architectures, and reducing latency by 2.7x to 3.9x. Pesto's leaderless design minimizes the impact of replica failures and ensures robust performance
Discrete Subdomains Establish Epigenetic Diversity in Subtelomeric Heterochromatin
No full textSubtelomeres are imperfect repeats adjacent to telomeres that are repressed by heterochromatin. Although essential for genome integrity, their repetitive nature has thwarted dissection of local heterochromatin assembly and maintenance mechanisms. Here, we engineered Schizosaccharomyces pombe strains carrying fluorescent reporters at a single subtelomere. We find that subtelomeric heterochromatin is organized into discrete subdomains that nucleate at telomere-proximal and cryptic internal sites. Telomere-proximal regions depend on canonical shelterin or RNA interference nucleation pathways, while telomere-distal regions require nucleosome remodelers, histone chaperones, and boundary-associated factors. Using multi-generational live imaging and targeted perturbations, we show that subtelomeric subdomains display position-specific, clonally variable silencing across a spectrum of robust to fragile epigenetic states. This clonal variegation is also induced by naturally occurring subtelomeric structural variants. These findings demonstrate that subtelomeric heterochromatin maintenance is not uniform but rather governed by local chromatin context and architecture
Design and Aerodynamic Performance Characterization of Bio-Inspired Multi-Piece Winglets
No full textThis dissertation presents a design and analysis of multiple-piece winglets based on the wingtip feathers of birds. The biomimetic multi-winglet designs proposed in this work have the potential to improve aerodynamic performance. Biomimetic designs draw inspiration from biological organisms for engineering design. The hypothesis was that the designs cause splitting of the standard large single tip vortices into multiple, smaller tip vortices. This separation into smaller vortices have the potential to reduce induced aerodynamic effects. The proposed biomimetic multi-piece winglets have the following design parameters: number of winglets, individual winglet dimensions, dihedral/anhedral angles, angles of incidence, and sweep angles. The simulations were performed using a reduced order potential flow method known as Vortex Lattice Method (VLM) and its variants. These modified VLM simulations in an available computational OpenVSP/VSPAERO tool were used to calculate values like lift, total drag, and induced drag of the various designs, which were tabulated to establish the efficacy of each design parameter. Various combinations of these parameters were studied to find the optimal designs. The simulation data is provided for this comparative design study, which include the effects on the variation of chordwise positions and dihedrals of the winglets.
Given the main hypothesis of this study, Aim 1 proposed that, given the limitations in designs of previous similar research, the design parameters of multi-winglets must be expanded to study the performance changes in detail. The design parameters of the biomimetics multi-piece winglets were thus defined: number of winglet pieces, dimensions, dihedral angles, angles of attack, and sweep. With these parameters, test cases were established, which are comparable to conditions in available experiments on bird wings and/or existing aircraft conditions. In order to establish the test cases for the following comparative study, flight conditions for the next phases of the research were also identified. The computational methods were compared and selected for the study as well. First, an exploratory series of 2D finite volume simulations were completed, but was deemed insufficient for this study. Next, a 3D vortex lattice method was selected and validated for use in the analysis of the comparative section of this study.
For Aim 2, it was hypothesized that the multi-piece winglet designs proposed for aircraft wings can improve aerodynamic performance by altering the standard large single vortex shedding by dispersing it into multiple much smaller strength vortices. In this phase, the purpose is to perform simulations for test cases using both low-fidelity and high-fidelity methods that take into account the three-dimensional nature of flow. The conditions of interest initially are low Reynolds numbers and low Mach numbers to validate results with available wind tunnel data. Methods are based on Vortex Lattice/Panel Method, and high-fidelity full 3D simulations using finite volume discretization of Navier-Stokes equations.
Finally, Aim 3 posited that the multi-piece winglet designs proposed have the potential to improve aerodynamic performance for transport aircraft as well. For this final section, the purpose is to use the best multi-piece design identified and implement it for a commercial aircraft wing test case. Since vortex shedding affects aircraft in particular during proximity operations (takeoff, landing, refueling, etc.), multi-winglet designs have the potential to alleviate the performance losses during such operations.
The design parameters for multi-winglets were comprehensively established to be able to cover as much variation as possible using the traditional wing design parameters. Gaps were studied which showed varying degrees of how induced flow might split to benefit performance. The results of this study, which included variations in the number of winglets, individual winglet dimensions, dihedral angles, angles of attack, and sweep angles, have shown that performance of wings can be improved by adding well-designed multi-piece winglets. The best case multi-winglet was demonstrated to have significant improvements over an equivalent extended rectangular wing, for higher angles of attack. When evaluating transport aircraft, using panel methods are likely less useful in finding improved designs, since the wings of commercial aircraft may be more inherently restrictive for multi-winglet modifications. This could be circumvented with more design comparisons or optimizations
Ambits of Illiteracy in American State Capitalism: Four Scenes of the 20th Century
No full textThis dissertation examines four epistemic and spatial scenes in the history of twentieth century American capitalism. It probes the meaning, relations, and associations of illiteracy, cast as a historical-philosophical category, and linked to relations of the state, society, and market. Traced across the century, these relations illuminate the shifting boundaries of state power, social movements, and market exchange. Each signals toward the broader problem of how illiteracy, rather than literacy, functions as a social, spatial, and historical condition through which class society can be studied. Altogether, the challenge for this dissertation is to treat and develop illiteracy as a category of analysis that articulates conflicts and contradictions of the mutations and faltering of planning regimes, the rise and fall of the welfare state, and the variegated spatial-linguistic landscape throughout twentieth century American capitalism. As an interdisciplinary study it examines each historical conjuncture through the use of archival documents, literary sources, journalistic media, and extensive theoretical literature. It makes use of conjunctural analysis as well as theoretical provocations at the cross section of urban studies, critical geography, and critical theory. It investigates the twentieth century United States with attention to state formation, political economic conditions, and the nexus of power and knowledge. It makes use of different planning literatures at each turn (i.e., modern, communication, education, and defense) which together form a planning problematic that serves as a throughline in this study and grounds the comparative frame through which illiteracy is examined as a feature of American capitalism. Taken together, the two threads of illiteracy as spatial-linguistic condition and planning a state and historical problem establish the overarching stakes. The project reads planning as a state problem that discloses instability across the century. So, this study unfolds through two interwoven logics: planning, approached as a recurring state problem, and illiteracy, approached as the analytic that both registers and reconfigures those problems.First, illiteracy operates as an analytic interface through which to study the transformations of capitalist modernity and its shifting epistemic and spatial orders. It serves as a category of analysis to interrogate asymmetries of discernment, anti-signification, and limits to intelligibility that shaped the state, market, and society across the twentieth century. By treating illiteracy as an analytic, this dissertation examines transformations in American capitalism from welfare state expansion and decline to contractions of planning regimes and the emergence of post-industrial class society in the United States. Each chapter stages illiteracy as a historical-philosophical category through which contradictions come into view and that render the spatial and linguistic registers of twentieth century American capitalism. Secondly, each scene condenses a historical geography of planning that locates illiteracy/illiterateness as its central problem space. In this way, the twentieth century planning episteme serves as a backdrop in different registers: illiteracy as modern genre; as mediating relation; as social-spatial condition; and, as an index of conjunctural crisis.The following questions are unfurled in this project: how might illiteracy, including notions of semi-literacy and functional illiteracy, offer conceptual purchase as shifting categories that register and mediate the contradictions of twentieth century American capitalism? Additionally, what forms of difference, unintelligibility, and incommensurability emerge when illiteracy is treated not merely as corporeal lack, but as a conceptual analogue for the limits of intelligibility in modernity and American capitalism? Chapter 1 situates illiteracy in the historical imagination of national education by reconstructing a U.S. literacy movement from 1860 to 1915 as more than an attempt to teach reading and writing. Instead, these campaigns and debates over illiteracy as a social problem are examined as part of a shifting social imaginary, where illiteracy became a proxy for disputes over national belonging, the organization of society, and the conceptual grammar of modernity itself. Chapter 2 examines two political entities as part of the development of early tricontinental mode of communication and planning to explore how the interwar geography of communication emerged within a broad semi-literate public. It highlights how information campaigns operate as communication planning and leads toward a view of the uneven and patchiness of illiterateness as a social relation. Semi-literacy and illiteracy figure as social relations that shape people's encounters with new genres of print and aesthetic forms at this time. This chapter draws closer the qualities of fragmentation and insecurity of political communication by literate populations to the defining aspects of semi-literacy. This chapter explores the fragility of interpretive capacities such as reading and writing as uneven discernment and misperception to them as modern traffic of interwar communication and planning across an early tricontinental network. Chapter 3 draws closer the connection between illiteracy and planning through a history of human capital from Cold War educational economics to neoclassical economics. This chapter explores how human capital came to define postwar educational economics and extended its influence beyond its disciplinary and institutional boundaries. By tracing human capital through the exigencies of postwar economic planning and the search for trained manpower, this chapter demonstrates how skilled labor, and technical labor took on new meaning and precarity in a changing landscape of new middle classes, bloating war industries, and emergent single-commodity cities. This chapter relates postwar economic planning and educational policy to the emergence of human capital planning, which can be regarded as a mechanism that sought to redefine labor and value in the postwar and Cold War era. With these conditions in mind, I explore how the welfare state and the public sector — now with an emergent educational sector — were being skirted and how human capital planning was used to divert from the public sector from the 1960 to the 1990s. Chapter 4 theorizes state illiterateness as a spatial and epistemic limit of state rationality exemplified in the poly-crisis of the late-1960s. It suggests the Kerner commission, and the Kerner Report offer a key point of departure to theorize the way that illiterateness is a condition mediating the state-society relation at a moment when the former attempts to understand spatial changes to class society. This chapter provides a theoretical exposition of three objects: security nationalism, the Kerner Report, and state illiteracy. As such, the question of state rationality is all the more important and interesting considering that defense planning literature, discourse, and ideology — aspects which were formalized, institutionalized, and expanded since the postwar era — come to an inflection point in the late-1960s when discerning the spatial transformations of US state capitalism becomes increasingly multifaceted and contingent. Tasked with making sense of the manifold spatial changes of the moment, the state’s tools of security nationalism and Cold War defense planning failed to discern its own spatialized poly-crisis. Ultimately, this chapter theorizes state illiteracy as a spatial and epistemic limit of state rationality and as a condition which mediated the crisis of the late-1960s. This chapter builds a basis for how the classical question of state rationality and its limits can be interrogated through the idea of illiteracy. With this in mind, this chapter covers historical and theoretical ground to make the case that illiteracy/illiterateness can be evoked as a conceptual analogue within planning literature, discourse, and epistemology. It consults interdisciplinary literature, especially critical geography, critical theory, and Marxian literature to navigate this inquiry and build a theoretical framework. In broad view, this project examines twentieth century American capitalism through the vantage points of planning theory and critical theory on one hand, and on the other by drawing on provocations from the spatial and linguistic turns in Anglophone research and literature. What connects these theoretical orientations is a shared attention to the limits of meaning and the breakdown of sign-systems. Indeed, the salience of anti-signification, unintelligibility, and asymmetries of intelligibility are categorical inflections that have upended and challenged postwar intellectual debates and political economic conditions, especially through philosophical terms of difference and incommensurability. These categorical disruptions are not only intellectual debates but emerge historically in the contraction of different planning regimes, the rise and waning of welfare and security institutions, and in the shifting spatial-linguistic terrain of American capitalism. In short, Chapter 1 and 2 trace the idea of illiteracy as a conjuncture of social movements, nonstate political entities, and social planning. Chapter 3 explores a case of resignification when illiteracy shifts to functional illiteracy, changing the meaning of human interiority and capacity at the level of political economy through the concept of human capital from midcentury to the 1980s. And Chapter 4 theorizes modern nation-state illiteracy as a spatial condition by probing the state-society relation in the late-1960s polycrisis
Remote Sensing-Based Estimation of the Nitrogen Nutrition Index Enhances Diagnosis of Nitrogen Use Efficiency in Wheat
Get PDFAgronomic research has long aimed to quantify plant N status, and recent work has focused on estimating plant N using non-destructive methods from remote sensing tools. The nitrogen nutrition index (NNI) is a metric of plant N status relative to a sufficiency threshold derived from the allometric relationship between plant N concentration and biomass. Previous research has explored the quantitative relationship between NNI and both physiological and agronomic nitrogen use efficiency (NUE) metrics, though no prior work has examined how a remotely sensed NNI (NNIRS) relates to NUE. To explore this, we tested the hypothesis that NNIRS estimated at anthesis in wheat (Triticum spp.) is correlated with four commonly reported physiological and agronomic NUE metrics. Across two site-years where four nitrogen rates were applied to contrasting genotype groups, we found that NNIRS determined N status across site-years (P = 0.031) and nitrogen rates (P < 0.001), independent of interactions among agronomic factors such as genotype and environment, indicating that NNIRS was a uniquely stable measurement of N status. NNIRS also had a significant linear relationship (P < 0.001) with all four NUE metrics, though the relationships differed across the metrics. N utilization efficiency had the strongest direct linear relationship to NNIRS (R2m = 0.36, P < 0.001), and N balance had the strongest relationship when site-year and N rate were included (R2m = 0.83, P < 0.001). We also found that NNIRS was able to detect phenotypic differences between two genotype groups with documented differences in N use (P < 0.001. Our results indicate that NNIRS measured near anthesis in wheat is a valuable diagnostic tool for understanding N recovery efficiency and can augment existing NUE metrics with relatively small investments of labor and time
A Study on the Inclusion of Persons with Mobility Disabilities in the Infrastructure and Transportation System of Davis, California
Get PDFPeople with mobility disabilities face difficulties in accessing public transportation and infrastructures in Davis that were not designed with them in mind. People with mobility disabilities have equal rights as other people in a community to access the physical environment, including buildings, roads, schools, medical facilities, workplaces, and other facilities. My research identifies the challenges faced by people with mobility disabilities in Davis while accessing transportation and infrastructure services. I conducted personal interviews with six people with mobility disabilities from the University of California, Davis. The interviews reveal that the most common barriers faced by people with mobility disabilities include negative attitudes from ride-hail drivers, the unfriendly built environment, the high cost of ride-hailing services, long distances between bus stops and home, rough road surfaces with cracks, narrow ramps to buildings, and fear of crashes while crossing roads. It is important to provide transportation and infrastructure access to persons with mobility disabilities so that they can live independently in their communities. Some recommendations to improve transportation and infrastructure services for people with mobility disabilities include providing proper training for bus drivers, more effort from UC Davis in repaving roads and sidewalks that have worn out, as well as reconstructing roads to improve wheelchair accessibility, meeting with disability advocates from UC Davis to understand their needs to improve accessibility for people with mobility disabilities, immediately renovating the road towards the Accommodated Exam Service Center, promoting social awareness, consulting with people with mobility disabilities about their specific design requirements, and implementing a proper monitoring system
Investigating neuroinflammation and blood-brain barrier dysfunction as pathogenic mechanisms of Alzheimer's disease using a transgenic rat model
No full textDeveloping strategies for preventing or treating Alzheimer’s disease (AD) has been the focus of significant research for decades. AD was first discovered in the early 1900s and defined by its two hallmark neuropathologies, amyloid-beta plaques and neurofibrillary tangles. These characteristic pathologies have been the primary targets for AD therapies, but decades of research have only recently culminated in two FDA-approved therapies that slow AD pathogenesis when administered early in the disease. Moreover, these treatments are associated with significant side effects, including infusion reactions, brain swelling, headaches, and cerebral microbleeding. These observations underscore the urgent need to identify novel therapeutic targets for AD therapies that can modify disease progression, and for identifying biomarkers that detect AD early in disease progression.With increased research genetic advancements, it became clear in the early 21st century that genetic mutation alone can account for only 1-6% of AD cases; thus, research began to focus towards environmental factors that influence individual risk for developing AD and/or the time-to-onset and rate of progression of AD. Traffic-related air pollution (TRAP) has gained increasing recognition as a modifiable environmental risk factor for AD. Just in the past six years, over 80 epidemiological studies have linked air pollution and/or near roadway exposure to increased risk for AD and AD-related dementias; experimental animal studies have corroborated these findings. However, most of the experimental animal studies used acute exposure paradigms or unrealistically high concentrations of specific components of TRAP that do not realistically model chronic human exposure to TRAP. It therefore remains unclear what specific components of ambient, real-life TRAP are the primary drivers of increased AD risk or exacerbated AD pathology; it is also unknown what the mechanisms are by which TRAP influences AD-relevant phenotypes.This dissertation seeks to address these data gaps by using the TgF344-AD rat as an animal model for AD to identify novel biomarkers and determine the effects of specific components of ambient TRAP as well as its potential mechanisms in modulating AD pathogenesis. Chapter 2 demonstrates the plasminogen activation system (PAS) as a potential therapeutic target and/or biomarker of blood-brain barrier (BBB) modulation by comparing male and female TgF344-AD rats to wild-type Fischer rats. In both Chapters 3 and 4, male and female TgF344-AD rats were exposed to ambient TRAP drawn real-time from the Caldecott Tunnel, which was either delivered unchanged or fractionated into gaseous vs. particulate matter components from light-duty vehicles (LDV) only, or a mixture of LDV and heavy-duty vehicles (HDV). Chapter 3 shows that specific components of ambient, real-life TRAP have sex-specific effects on AD pathology; Chapter 4 identifies endothelial-mesenchymal transition (EndoMT) as a potential mechanism by which TRAP promotes blood-brain barrier (BBB) breakdown, a key pathogenic process in AD. These findings have important implications for future research as they highlight both AD and TRAP as public health issues that can be mitigated and modified through public education and policy. The data suggest sex to be an important biological factor and BBB modulation as a key process in both AD alone and TRAP-exposed AD pathogenesis. Ambient TRAP effects observed in our transgenic rat model further contributes to the larger body of research on TRAP as a modifiable environmental risk factor for AD, which can initiate changes in the regulation of TRAP from near-roadway exposures to decrease AD risk
Miniaturized and Microfabricated Systems for Trace Gas Analysis
No full textExhaled breath vapor contains hundreds of volatile organic compounds (VOCs), which are the byproducts of health and disease metabolism, and they have clinical and diagnostic potential. Simultaneous collection of breath VOCs and background environmental VOCs is important to ensure analyses eliminate exogenous compounds from clinical studies. We present a mobile sampling system to extract gaseous VOCs onto commercially available sorbent-packed thermal desorption tubes. The sampler can be connected to several commonly available disposable and reusable sampling bags, in the case of this study, a Tedlar bag containing a breath sample. Alternatively, the inlet can be left open to directly sample room or environmental air when obtaining a background VOC sample. The system contains a screen for the operator to input a desired sample volume. A needle valve allows the operator to control the sample flow rate, which operates with an accuracy of −1.52 ± 0.63% of the desired rate, and consistently generated that rate with 0.12 ± 0.06% error across repeated measures. A flow pump, flow sensor and microcontroller allow volumetric sampling, as opposed to timed sampling, with 0.06 ± 0.06% accuracy in the volume extracted. Four samplers were compared by sampling a standard chemical mixture, which resulted in 6.4 ± 4.7% error across all four replicate modular samplers to extract a given VOC. The samplers were deployed in a clinical setting to collect breath and background/environmental samples, including patients with active SARS-CoV-2 infections, and the device could easily move between rooms and can undergo required disinfection protocols to prevent transmission of pathogens on the case exterior. All components required for assembly are detailed and are made publicly available for non-commercial use, including the microcontroller software. We demonstrate the device collects volatile compounds, including use of chemical standards, and background and breath samples in real use conditions.We have developed a statistical model-based approach to the quality analysis (QA) and quality control (QC) of a gas micro preconcentrator chip (µPC) performance when manufactured at scale for chemical and biochemical analysis of volatile organic compounds (VOCs). To test the proposed model, a medium-sized, university-led production batch of 30 wafers of chips were subjected to rigorous chemical performance testing. We quantitatively report the outcomes of each manufacturing process step leading up to the final functional chemical sensor chip. We implemented a principal component analysis (PCA) model to score individual chip chemical performance, and we observed the first 2 principal components represent 74.28% of chemical testing variance with 111 of 118 viable chips falling into the 95% confidence interval. Chemical performance scores and chip manufacturing data were analyzed using a multivariate regression model to determine the most influential manufacturing parameters and steps. In our analysis, we find the amount of sorbent mass present in the chip (variable importance score = 2.6) and heater and RTD resistance values (variable importance score = 1.1) to be the manufacturing parameters with the most impact on chemical performance. Other non-obvious latent manufacturing parameters also had quantified influence. Statistical distributions for each manufacturing step will allow future large-scale production runs to be statistically sampled during production to perform QA/QC in a real-time environment. We report this study as the first data-driven, model-based production of a microfabricated chemical sensor.We have designed a microfabricated microneedle array atmospheric pressure plasma ionization source. This ionization combines electrical discharge and microfluidic design principles in a chip-based platform for delivering and ionizing neutral volatile organic compounds for quantification and identification when coupled with a detector. The 250µm interelectrode spacing and microfabricated tungsten plated silicon needles have a corona onset voltage of 2196 volts. The ionization chip is coupled to two separate types of detectors. First, a gold-standard atmospheric pressure mass spectrometer is used to confirm ionization of four chemicals, DMMP, 2-butanone, 1-octanol, and naphthalene. Second, the chip is coupled to portable faraday plate style electrometer ion counter. The device was able to detect DMMP at a trace level of 280 ppb concentration. We report this microchip ionization source as the first microfabricated needle array atmospheric pressure ionization source for chemical detection verified by mass spectrometry
Development and Evaluation of a Comprehensive Mechanistic Model of Enteric Fermentation in Dairy Cattle Supplemented with Methane-Inhibiting Feed Additives
No full textAnimal agriculture plays a critical role in human health by providing nutrient-dense foods that combat malnutrition and nutrient deficiencies. Global demand for animal-source foods is expected to rise, with a concomitant rise in the global ruminant herd size. Livestock agriculture contributes to greenhouse gas (GHG) emissions through enteric fermentation, producing methane (CH4), and manure management, producing nitrous oxide (N2O) and CH4. Mitigation of the CH4 emissions of this growing ruminant population is therefore essential to balance global food security and climate impact. Recent advancements in antimethanogenic feed additives (AMFA), such as 3-nitrooxypropanol (3NOP) or bromoform (CHBr3) in red seaweed, offer tools to reduce enteric CH4 emissions by directly inhibiting methanogenesis. However, many interacting factors in the rumen impact CH4 production, such as particle and fluid outflow, microbial populations, pH, and fermentative cofactor dynamics. In addition, basal diet, animal factors, and their interactions affect AMFA efficacy. Finally, AMFA may have indirect effects that impact animal-level net GHG emissions and nutrient excretion.Characterizing the response of rumen fermentation to methanogenic inhibition is essential for optimizing AMFA implementation and ultimately reducing enteric CH4 emissions. However, this task is challenging when studied in vivo or using empirical models, which do not account for complex interacting variables in the rumen or potential indirect or downstream effects. In contrast, because mechanistic models are constructed to represent physiological processes, they can be used to characterize the dependency of AMFA efficacy on rumen factors and optimize AMFA implementation. The overall objective of this dissertation was to develop and evaluate a dynamic, mechanistic model of rumen fermentation that accurately predicts diurnal CH4 production, net GHG production, and nutrient excretion in lactating dairy cattle with or without AMFA supplementation by incorporating thermodynamic control of fermentation pathways and mechanistic control of rumen fractional outflow rates and pH. The purpose of this model was to provide a research tool for investigating the impact of AMFA supplementation on rumen dynamics, including applying the model to design feeding schemes for maximum AMFA efficacy and interrogate the mechanism of improved efficacy. In the first chapter of this dissertation, we review the current state of rumen mechanistic modeling with an emphasis on representations of CH4 production. We discuss the first rumen mechanistic models to include AMFA and emphasize future model needs for improved representation of rumen dynamics under CH4-inhibition due to AMFA supplementation, including the representation of microbial populations, rumen pH, fractional outflow rates, and thermodynamic control of fermentative pathways. In the subsequent chapters, we outline the development, evaluation, and application of a rumen mechanistic model that incorporates key elements identified in the first chapter.The second chapter of this dissertation outlines the process by which we developed and parameterized this updated mechanistic model of rumen fermentation. State variables related to the model objective were selected and flux equations describing transactions between state variable pools were developed based on enzyme kinetics equation forms. Parameters were estimated or adapted from literature. This model incorporates a comprehensive representation of dietary feed fractions and variable feed intake patterns and includes thermodynamic control of VFA fermentation pathways via the NAD+/NADH ratio, and mechanistic control of rumen fractional outflow rates and pH. It includes the AMFA CHBr3 and 3NOP, as well as anti-methanogenic 3NOP metabolites nitrate and nitrite, and alternative hydrogen (H2) sinks, including biohydrogenation and microbial growth, enhancing the representation of H2 partitioning under CH4-inhibition.The third chapter of this dissertation describes the process used to optimize model parameters, evaluate our model’s predictions of diurnal CH4, CO2, and H2 production and other rumen parameters against independent in vivo data under different AMFA supplementation scenarios, and compare prediction errors to similar models. Model predictions were compared to treatment group averages at several diurnal timepoints from two separate studies: one with dairy cattle receiving no AMFA supplementation (“base scenario”) and another with dairy cattle supplemented with CHBr3-containing seaweed at 0.5 and 1% organic matter (OM) (“low” and “high CHBr3 scenarios”, respectively). Diurnal CH4 predictions were also evaluated against data from dairy cattle supplemented with 3NOP at 6 doses. Model performance was assessed using the square root of mean square prediction error (RMSPE, % of observed mean) and Lin’s Concordance Correlation Coefficient (CCC). The model demonstrated the lowest prediction error for diurnal CH4 emissions under the 3NOP scenarios (RMSPE = 42, 41, 44, 32, 32, and 33% for 40, 60, 80, 100, 150, and 200 mg 3NOP/kg DM, respectively). Prediction error for diurnal CH4 was similar under the base scenario compared to the low CHBr3 scenario (RMPSE = 47 and 46%, respectively), but greater under high CHBr3 scenario (RMPSE = 67%). Predictions of diurnal CH4 were more accurate than H2 (RMPSE = 100%) predictions under the base scenario. Diurnal CH4 predictions under low and high CHBr3 scenarios were more accurate than H2 (RMSPE = 823% and 1261%, respectively) predictions. While the increased complexity of our model may have contributed to greater prediction errors, particularly in H2 emissions, its CH4 predictions remain comparable to existing models while offering a more detailed representation of rumen dynamics.In the fourth chapter of this dissertation, we conducted a global sensitivity analysis (GSA) and uncertainty analysis (UA) on our model. We quantified the sensitivity of model outputs to changes in parameters by first ranking all parameters using the Morris screening method, followed by a variance-based GSA approach which estimated first- and total-order Sobol’ indices for parameter influence on CH4 and H2 emissions. We also assessed the overall uncertainty in model outputs by calibrating parameters using Approximate Bayesian Computation and running the model using parameter sets sampled from the joint posterior distribution to generate likely prediction ranges. The Morris screening identified parameters related to methanogenic H2 metabolism, carbohydrate and protein fermentation, protozoal protein metabolism and microbial predation as most influential for CH4 and H2 production. The most influential parameter by first-order Sobol’ index on the CH4 and H2 emission rate under the Base scenario, on the CH4 emission rate under the CHBr3 scenario, and on the H2 emission rate under the 3NOP scenario was the maximum velocity of H2 uptake by methanogens for CH4 formation. According to the UA, the most uncertain model outcome under the Base scenario was the fibrolytic bacterial storage polysaccharide pool. The results allow identification of influential parameters that should be prioritized in future parameterization and improve our understanding of likely ranges of rumen conditions under supplementation of different AMFA.The efficacy of AMFA depends on both intake level and basal diet composition, with greater dry matter intake (DMI), less dietary neutral detergent fiber (NDF) content, and greater dietary starch associated with greater efficacy. In addition, while AMFA may directly reduce enteric CH4 emissions, they may have indirect impacts on emissions of other enteric gases or manure nitrogen (N) excretion. In the fifth and final chapter of this dissertation, we applied our model to identify the basal diet parameters that, when constrained to support the same level of milk production, maximized the efficacy of 3NOP and CHBr3 on inhibiting methanogenesis. We also identified AMFA dose/basal diet combinations that minimized CH4 emissions, net GHG emissions (enteric and hindgut CH4 and enteric N2O) or total manure N excretion. For the diet optimized for CHBr3 efficacy, relative to the original diet, NDF decreased by 0.33% but starch also decreased by 21%, while DMI increased by 8%, leading to a reduction in CH4 emissions of 8.8% from the original diet with CHBr3. For the diet optimized for 3NOP efficacy, CH4 emissions decreased by 8.7% from the original diet with 3NOP, starch increased by 5%, NDF decreased by 6%, and DMI decreased by 8%. Diets for minimizing absolute GHG emissions and total manure N excretion supplemented relatively more CHBr3 than 3NOP, potentially due to its metabolism to other nitrogenous compounds in the rumen. These results demonstrate how a complex mechanistic model of rumen fermentation, once properly parameterized and evaluated, can be applied to optimize the implementation of AMFA on-farm
Quantitative Imaging of the Choroid Plexus and the Blood-Brain Barrier with Arterial Spin Labeling MRI in Human Subjects
Get PDFThe choroid plexus and blood-brain barrier are both structures that could offer insights into the mechanistic development of various neurological diseases. Here, we explore a relatively new noninvasive technique called arterial spin labeling MRI and its capacity to assess choroid plexus perfusion and water exchange rate across the blood-brain barrier as proxy measures for their functional status. We conclude that multi-delay arterial spin labeling is a promising technique to estimate markers of cerebral health. This is exciting given that arterial spin labeling is a water-based method that does not utilize any toxic contrast agents, thereby making this technique appropriate for use in both younger psychiatric populations and research subjects that may require multiple scans. The work presented in this dissertation represents the foundational analysis that will support future studies to validate this relatively new usage of arterial spin labeling toward the care of patients in a clinical setting