Matching Items (45)
Description
A numerical study of wave-induced momentum transport across the tropopause in the presence of a stably stratified thin inversion layer is presented and discussed. This layer consists of a sharp increase in static stability within the tropopause. The wave propagation is modeled by numerically solving the Taylor-Goldstein equation, which governs the dynamics of internal waves in stably stratified shear flows. The waves are forced by a flow over a bell shaped mountain placed at the lower boundary of the domain. A perfectly radiating condition based on the group velocity of mountain waves is imposed at the top to avoid artificial wave reflection. A validation for the numerical method through comparisons with the corresponding analytical solutions will be provided. Then, the method is applied to more realistic profiles of the stability to study the impact of these profiles on wave propagation through the tropopause.
ContributorsCole, Alexandra Shea (Author) / Moustaoui, Mohamed (Thesis director) / Kostelich, Eric (Committee member) / Mahalov, Alex (Committee member) / School of International Letters and Cultures (Contributor) / School of Geographical Sciences and Urban Planning (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Mycobacterial infections, as represented by leprosy and tuberculosis, have persisted as human pathogens for millennia. Their environmental counterparts, nontuberculous mycobacteria (NTM), are commodious infectious agents endowed with extensive innate and acquired antimicrobial resistance. The current drug development process selects for antibiotics with high specificity for definitive targets within bacterial metabolic and replication pathways. Because these compounds demonstrate limited efficacy against mycobacteria, novel antimycobacterial agents with unconventional mechanisms of action were identified. Two highly resistant NTMs, Mycobacterium abscessus (Mabs) a rapid-growing respiratory, skin, and soft tissue pathogen, and Mycobacterium ulcerans (MU), the causative agent of Buruli ulcer, were selected as targets. Compounds that indicated antimicrobial activity against other highly resistant pathogens were selected for initial screening. Antimicrobial peptides (AMPs) have demonstrated activity against a variety of bacterial pathogens, including mycobacterial species. Designed antimicrobial peptides (dAMPs), rationally-designed and synthetic contingents, combine iterative features of natural AMPs to achieve superior antimicrobial activity in resistant pathogens. Initial screening identified two dAMPs, RP554 and RP557, with bactericidal activity against Mabs. Clay-associated ions have previously demonstrated bactericidal activity against MU. Synthetic and customizable aluminosilicates have also demonstrated adsorption of bacterial cells and toxins. On this basis, two aluminosilicate materials, geopolymers (GP) and ion-exchange nanozeolites (IE-nZeos), were screened for antimicrobial activity against MU and its fast-growing relative, Mycobacterium marinum (Mmar). GPs demonstrated adsorption of MU cells and mycolactone, a secreted, lipophilic toxin, whereas Cu-nZeos and Ag-nZeos demonstrated antibacterial activity against MU and Mmar. Cumulatively, these results indicate that an integrative drug selection process may yield a new generation of antimycobacterial agents.
ContributorsDermody, Roslyn June (Author) / Haydel, Shelley E (Thesis advisor) / Bean, Heather (Committee member) / Nickerson, Cheryl (Committee member) / Stephanopoulos, Nicholas (Committee member) / Arizona State University (Publisher)
Created2022
Description
Mycobacterium tuberculosis (Mtb), the etiological agent of the tuberculosis disease, is estimated to infect one-fourth of the human population and is responsible for 1.5 million deaths annually. The increased emergence of bacterial resistance to clinical interventions highlights the lack in development of novel antimicrobial therapeutics. Prototypical bacterial two-component systems (TCS) allow for sensing of extracellular stimuli and relay thereof to create a transcriptional response. The prrAB TCS is essential for viability in Mtb, presenting itself as an attractive novel drug target. In Mtb, PrrAB is involved in the adaptation to the intra-macrophage environment and recent work implicates PrrAB in the dosR-dependent hypoxia adaptation. This work defines a direct molecular and regulatory connection between Mtb PrrAB and the dosR-dependent hypoxia response. Using electrophoretic mobility shift assays combined with surface plasmon resonance, the Mtb dosR gene is established as a specific target of PrrA, corroborated by fluorescence reporter assays demonstrating a regulatory relationship. Considering the scarce understanding of prrAB essentiality in nontuberculous mycobacteria and the presence of multiple prrAB orthologs in Mycobacterium smegmatis and Mycobacterium abscessus, CRISPR interference was utilized to evaluate the essentiality of PrrAB beyond Mtb. prrAB was found to be inessential for viability in M. smegmatis yet required for in vitro growth. Conversely, M. abscessus prrAB repression led to enhanced in vitro growth. Diarylthiazole-48 (DAT-48) displayed decreased selectivity against M. abscessus but demonstrated enhanced intrinsic activity upon prrAB repression in M. abscessus. Lastly, to aid in the rapid determination of mycobacterial drug susceptibility and the detection of mycobacterial heteroresistance, the large volume scattering imaging (LVSim) platform was adapted for mycobacteria. Using LVSim, Mtb drug susceptibility was detected phenotypically within 6 hours, and clinically relevant mycobacterial heteroresistance was detected phenotypically within 10 generations. The data generated in these studies provide insight into the essential role of PrrAB in Mtb and its involvement in the dosR-dependent hypoxia adaptation, advance the understanding of mycobacterial PrrAB essentiality and PrrAB-associated mycobacterial growth dependency. These studies further establish molecular and mechanistic connection between PrrAB and DAT-48 in Mtb and M. abscessus and develop a rapid phenotypic drug susceptibility testing platform for mycobacteria.
ContributorsHaller, Yannik Alex (Author) / Haydel, Shelley E (Thesis advisor) / Bean, Heather (Committee member) / Nickerson, Cheryl (Committee member) / Plaisier, Christopher (Committee member) / Acharya, Abhinav (Committee member) / Arizona State University (Publisher)
Created2023
Description
This work presents a thorough analysis of reconstruction of global wave fields (governed by the inhomogeneous wave equation and the Maxwell vector wave equation) from sensor time series data of the wave field. Three major problems are considered. First, an analysis of circumstances under which wave fields can be fully reconstructed from a network of fixed-location sensors is presented. It is proven that, in many cases, wave fields can be fully reconstructed from a single sensor, but that such reconstructions can be sensitive to small perturbations in sensor placement. Generally, multiple sensors are necessary. The next problem considered is how to obtain a global approximation of an electromagnetic wave field in the presence of an amplifying noisy current density from sensor time series data. This type of noise, described in terms of a cylindrical Wiener process, creates a nonequilibrium system, derived from Maxwell’s equations, where variance increases with time. In this noisy system, longer observation times do not generally provide more accurate estimates of the field coefficients. The mean squared error of the estimates can be decomposed into a sum of the squared bias and the variance. As the observation time $\tau$ increases, the bias decreases as $\mathcal{O}(1/\tau)$ but the variance increases as $\mathcal{O}(\tau)$. The contrasting time scales imply the existence of an ``optimal'' observing time (the bias-variance tradeoff). An iterative algorithm is developed to construct global approximations of the electric field using the optimal observing times. Lastly, the effect of sensor acceleration is considered. When the sensor location is fixed, measurements of wave fields composed of plane waves are almost periodic and so can be written in terms of a standard Fourier basis. When the sensor is accelerating, the resulting time series is no longer almost periodic. This phenomenon is related to the Doppler effect, where a time transformation must be performed to obtain the frequency and amplitude information from the time series data. To obtain frequency and amplitude information from accelerating sensor time series data in a general inhomogeneous medium, a randomized algorithm is presented. The algorithm is analyzed and example wave fields are reconstructed.
ContributorsBarclay, Bryce Matthew (Author) / Mahalov, Alex (Thesis advisor) / Kostelich, Eric J (Thesis advisor) / Moustaoui, Mohamed (Committee member) / Motsch, Sebastien (Committee member) / Platte, Rodrigo (Committee member) / Arizona State University (Publisher)
Created2023
Description
Climate is a critical determinant of agricultural productivity, and the ability to accurately predict this productivity is necessary to provide guidance regarding food security and agricultural management. Previous predictions vary in approach due to the myriad of factors influencing agricultural productivity but generally suggest long-term declines in productivity and agricultural land suitability under climate change. In this paper, I relate predicted climate changes to yield for three major United States crops, namely corn, soybeans, and wheat, using a moderate emissions scenario. By adopting data-driven machine learning approaches, I used the following machine learning methods: random forest (RF), extreme gradient boosting (XGB), and artificial neural networks (ANN) to perform comparative analysis and ensemble methodology. I omitted the western US due to the region's susceptibility to water stress and the prevalence of artificial irrigation as a means to compensate for dry conditions. By considering only climate, the model's results suggest an ensemble mean decline in crop yield of 23.4\% for corn, 19.1\% for soybeans, and 7.8\% for wheat between the years of 2017 and 2100. These results emphasize potential negative impacts of climate change on the current agricultural industry as a result of shifting bio-climactic conditions.
ContributorsSwarup, Shray (Author) / Eikenberry, Steffen (Thesis director) / Mahalov, Alex (Committee member) / Barrett, The Honors College (Contributor) / Computer Science and Engineering Program (Contributor)
Created2023-05
Description
One of the identified health risk areas for human spaceflight is infectious disease, particularly involving environmental microorganisms already found on the International Space Station (ISS). In particular, bacteria belonging to the Burkholderia cepacia complex (Bcc) which can cause human disease in those who are immunocompromised, have been identified in the ISS water supply. This present study characterized the effect of spaceflight analog culture conditions on Bcc to certain physiological stresses (acid and thermal as well as intracellular survival in U927 human macrophage cells). The NASA-designed Rotating Wall Vessel (RWV) bioreactor was used as the spaceflight analogue culture system in these studies to grow Bcc bacterial cells under Low Shear Modeled Microgravity (LSMMG) conditions. Results show that LSMMG culture increased the resistance of Bcc to both acid and thermal stressors, but did not alter phagocytic uptake in 2-D monolayers of human monocytes.
ContributorsVu, Christian-Alexander (Author) / Nickerson, Cheryl (Thesis director) / Barrila, Jennifer (Committee member) / Ott, Mark (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2023-05
Description
Earth-system models describe the interacting components of the climate system and
technological systems that affect society, such as communication infrastructures. Data
assimilation addresses the challenge of state specification by incorporating system
observations into the model estimates. In this research, a particular data
assimilation technique called the Local Ensemble Transform Kalman Filter (LETKF) is
applied to the ionosphere, which is a domain of practical interest due to its effects
on infrastructures that depend on satellite communication and remote sensing. This
dissertation consists of three main studies that propose strategies to improve space-
weather specification during ionospheric extreme events, but are generally applicable
to Earth-system models:
Topic I applies the LETKF to estimate ion density with an idealized model of
the ionosphere, given noisy synthetic observations of varying sparsity. Results show
that the LETKF yields accurate estimates of the ion density field and unobserved
components of neutral winds even when the observation density is spatially sparse
(2% of grid points) and there is large levels (40%) of Gaussian observation noise.
Topic II proposes a targeted observing strategy for data assimilation, which uses
the influence matrix diagnostic to target errors in chosen state variables. This
strategy is applied in observing system experiments, in which synthetic electron density
observations are assimilated with the LETKF into the Thermosphere-Ionosphere-
Electrodynamics Global Circulation Model (TIEGCM) during a geomagnetic storm.
Results show that assimilating targeted electron density observations yields on
average about 60%–80% reduction in electron density error within a 600 km radius of
the observed location, compared to 15% reduction obtained with randomly placed
vertical profiles.
Topic III proposes a methodology to account for systematic model bias arising
ifrom errors in parametrized solar and magnetospheric inputs. This strategy is ap-
plied with the TIEGCM during a geomagnetic storm, and is used to estimate the
spatiotemporal variations of bias in electron density predictions during the
transitionary phases of the geomagnetic storm. Results show that this strategy reduces
error in 1-hour predictions of electron density by about 35% and 30% in polar regions
during the main and relaxation phases of the geomagnetic storm, respectively.
technological systems that affect society, such as communication infrastructures. Data
assimilation addresses the challenge of state specification by incorporating system
observations into the model estimates. In this research, a particular data
assimilation technique called the Local Ensemble Transform Kalman Filter (LETKF) is
applied to the ionosphere, which is a domain of practical interest due to its effects
on infrastructures that depend on satellite communication and remote sensing. This
dissertation consists of three main studies that propose strategies to improve space-
weather specification during ionospheric extreme events, but are generally applicable
to Earth-system models:
Topic I applies the LETKF to estimate ion density with an idealized model of
the ionosphere, given noisy synthetic observations of varying sparsity. Results show
that the LETKF yields accurate estimates of the ion density field and unobserved
components of neutral winds even when the observation density is spatially sparse
(2% of grid points) and there is large levels (40%) of Gaussian observation noise.
Topic II proposes a targeted observing strategy for data assimilation, which uses
the influence matrix diagnostic to target errors in chosen state variables. This
strategy is applied in observing system experiments, in which synthetic electron density
observations are assimilated with the LETKF into the Thermosphere-Ionosphere-
Electrodynamics Global Circulation Model (TIEGCM) during a geomagnetic storm.
Results show that assimilating targeted electron density observations yields on
average about 60%–80% reduction in electron density error within a 600 km radius of
the observed location, compared to 15% reduction obtained with randomly placed
vertical profiles.
Topic III proposes a methodology to account for systematic model bias arising
ifrom errors in parametrized solar and magnetospheric inputs. This strategy is ap-
plied with the TIEGCM during a geomagnetic storm, and is used to estimate the
spatiotemporal variations of bias in electron density predictions during the
transitionary phases of the geomagnetic storm. Results show that this strategy reduces
error in 1-hour predictions of electron density by about 35% and 30% in polar regions
during the main and relaxation phases of the geomagnetic storm, respectively.
ContributorsDurazo, Juan, Ph.D (Author) / Kostelich, Eric J. (Thesis advisor) / Mahalov, Alex (Thesis advisor) / Tang, Wenbo (Committee member) / Moustaoui, Mohamed (Committee member) / Platte, Rodrigo (Committee member) / Arizona State University (Publisher)
Created2018
Description
Two urban flows are analyzed, one concerned with pollutant transport in a Phoenix, Arizona neighborhood and the other with windshear detection at the Hong Kong International Airport (HKIA).
Lagrangian measures, identified with finite-time Lyapunov exponents, are first used to characterize transport patterns of inertial pollutant particles. Motivated by actual events the focus is on flows in realistic urban geometry. Both deterministic and stochastic transport patterns are identified, as inertial Lagrangian coherent structures. For the deterministic case, the organizing structures are well defined and are extracted at different hours of a day to reveal the variability of coherent patterns. For the stochastic case, a random displacement model for fluid particles is formulated, and used to derive the governing equations for inertial particles to examine the change in organizing structures due to ``zeroth-order'' random noise. It is found that, (1) the Langevin equation for inertial particles can be reduced to a random displacement model; (2) using random noise based on inhomogeneous turbulence, whose diffusivity is derived from $k$-$\epsilon$ models, major coherent structures survive to organize local flow patterns and weaker structures are smoothed out due to random motion.
A study of three-dimensional Lagrangian coherent structures (LCS) near HKIA is then presented and related to previous developments of two-dimensional (2D) LCS analyses in detecting windshear experienced by landing aircraft. The LCS are contrasted among three independent models and against 2D coherent Doppler light detection and ranging (LIDAR) data. Addition of the velocity information perpendicular to the lidar scanning cone helps solidify flow structures inferred from previous studies; contrast among models reveals the intramodel variability; and comparison with flight data evaluates the performance among models in terms of Lagrangian analyses. It is found that, while the three models and the LIDAR do recover similar features of the windshear experienced by a landing aircraft (along the landing trajectory), their Lagrangian signatures over the entire domain are quite different - a portion of each numerical model captures certain features resembling those LCS extracted from independent 2D LIDAR analyses based on observations. Overall, it was found that the Weather Research and Forecast (WRF) model provides the best agreement with the LIDAR data.
Finally, the three-dimensional variational (3DVAR) data assimilation scheme in WRF is used to incorporate the LIDAR line of sight velocity observations into the WRF model forecast at HKIA. Using two different days as test cases, it is found that the LIDAR data can be successfully and consistently assimilated into WRF. Using the updated model forecast LCS are extracted along the LIDAR scanning cone and compare to onboard flight data. It is found that the LCS generated from the updated WRF forecasts are generally better correlated with the windshear experienced by landing aircraft as compared to the LIDAR extracted LCS alone, which suggests that such a data assimilation scheme could be used for the prediction of windshear events.
Lagrangian measures, identified with finite-time Lyapunov exponents, are first used to characterize transport patterns of inertial pollutant particles. Motivated by actual events the focus is on flows in realistic urban geometry. Both deterministic and stochastic transport patterns are identified, as inertial Lagrangian coherent structures. For the deterministic case, the organizing structures are well defined and are extracted at different hours of a day to reveal the variability of coherent patterns. For the stochastic case, a random displacement model for fluid particles is formulated, and used to derive the governing equations for inertial particles to examine the change in organizing structures due to ``zeroth-order'' random noise. It is found that, (1) the Langevin equation for inertial particles can be reduced to a random displacement model; (2) using random noise based on inhomogeneous turbulence, whose diffusivity is derived from $k$-$\epsilon$ models, major coherent structures survive to organize local flow patterns and weaker structures are smoothed out due to random motion.
A study of three-dimensional Lagrangian coherent structures (LCS) near HKIA is then presented and related to previous developments of two-dimensional (2D) LCS analyses in detecting windshear experienced by landing aircraft. The LCS are contrasted among three independent models and against 2D coherent Doppler light detection and ranging (LIDAR) data. Addition of the velocity information perpendicular to the lidar scanning cone helps solidify flow structures inferred from previous studies; contrast among models reveals the intramodel variability; and comparison with flight data evaluates the performance among models in terms of Lagrangian analyses. It is found that, while the three models and the LIDAR do recover similar features of the windshear experienced by a landing aircraft (along the landing trajectory), their Lagrangian signatures over the entire domain are quite different - a portion of each numerical model captures certain features resembling those LCS extracted from independent 2D LIDAR analyses based on observations. Overall, it was found that the Weather Research and Forecast (WRF) model provides the best agreement with the LIDAR data.
Finally, the three-dimensional variational (3DVAR) data assimilation scheme in WRF is used to incorporate the LIDAR line of sight velocity observations into the WRF model forecast at HKIA. Using two different days as test cases, it is found that the LIDAR data can be successfully and consistently assimilated into WRF. Using the updated model forecast LCS are extracted along the LIDAR scanning cone and compare to onboard flight data. It is found that the LCS generated from the updated WRF forecasts are generally better correlated with the windshear experienced by landing aircraft as compared to the LIDAR extracted LCS alone, which suggests that such a data assimilation scheme could be used for the prediction of windshear events.
ContributorsKnutson, Brent (Author) / Tang, Wenbo (Thesis advisor) / Calhoun, Ronald (Committee member) / Huang, Huei-Ping (Committee member) / Kostelich, Eric (Committee member) / Mahalov, Alex (Committee member) / Arizona State University (Publisher)
Created2018
Description
Despite the safe and effective use of attenuated vaccines for over fifty years, measles virus (MV) remains an insidious threat to global health. Problematically, infants less than one year of age, who are the most prone to severe infection and death by measles, cannot be immunized using current MV vaccines. For this dissertation, I generated and performed preclinical evaluation of two novel MV vaccine candidates. Based on data from clinical trials that showed increasing the dosage of current MV vaccines improved antibody responses in six-month-old recipients, I hypothesized that increasing the relevant antigenic stimulus of a standard titer dose would allow safe and effective immunization at a younger age. I generated two modified MVs with increased expression of the hemagglutinin (H) protein, the most important viral antigen for inducing protective neutralizing immunity, in the background of a current vaccine-equivalent. One virus, MVvac2-H2, expressed higher levels of full-length H, resulting in a three-fold increase in H incorporation into virions, while the second, MVvac2-Hsol, expressed and secreted truncated, soluble H protein to its extracellular environment. The alteration to the virion envelope of MVvac2-H2 conferred upon that virus a measurable resistance to in vitro neutralization. In initial screening in adult mouse models of vaccination, both modified MVs proved more immunogenic than their parental strain in outbred mice, while MVvac2-H2 additionally proved more immunogenic in the gold standard MV-susceptible mouse model. Remarkably, MVvac2-H2 better induced protective immunity in the presence of low levels of artificially introduced passive immunity that mimic the passive maternal immunity that currently limits vaccination of young infants, and that strongly inhibited responses to the current vaccine-equivalent. Finally, I developed a more physiological infant-like mouse model for MV vaccine testing, in which MV-susceptible dams vaccinated with the current vaccine-equivalent transfer passive immunity to their pups. This model will allow additional preclinical evaluation of the performance of MVvac2-H2 in pups of immune dams. Altogether, in this dissertation I identify a promising candidate, MVvac2-H2, for a next generation measles vaccine.
ContributorsJulik, Emily (Author) / Reyes del Valle, Jorge (Thesis advisor) / Chang, Yung (Committee member) / Blattman, Joseph (Committee member) / Hogue, Brenda (Committee member) / Nickerson, Cheryl (Committee member) / Arizona State University (Publisher)
Created2016
Description
The role of environmental factors that influence atmospheric propagation of sound originating from freeway noise sources is studied with a combination of field experiments and numerical simulations. Acoustic propagation models are developed and adapted for refractive index depending upon meteorological conditions. A high-resolution multi-nested environmental forecasting model forced by coarse global analysis is applied to predict real meteorological profiles at fine scales. These profiles are then used as input for the acoustic models. Numerical methods for producing higher resolution acoustic refractive index fields are proposed. These include spatial and temporal nested meteorological simulations with vertical grid refinement. It is shown that vertical nesting can improve the prediction of finer structures in near-ground temperature and velocity profiles, such as morning temperature inversions and low level jet-like features. Accurate representation of these features is shown to be important for modeling sound refraction phenomena and for enabling accurate noise assessment. Comparisons are made using the acoustic model for predictions with profiles derived from meteorological simulations and from field experiment observations in Phoenix, Arizona. The challenges faced in simulating accurate meteorological profiles at high resolution for sound propagation applications are highlighted and areas for possible improvement are discussed.
A detailed evaluation of the environmental forecast is conducted by investigating the Surface Energy Balance (SEB) obtained from observations made with an eddy-covariance flux tower compared with SEB from simulations using several physical parameterizations of urban effects and planetary boundary layer schemes. Diurnal variation in SEB constituent fluxes are examined in relation to surface layer stability and modeled diagnostic variables. Improvement is found when adapting parameterizations for Phoenix with reduced errors in the SEB components. Finer model resolution (to 333 m) is seen to have insignificant ($<1\sigma$) influence on mean absolute percent difference of 30-minute diurnal mean SEB terms. A new method of representing inhomogeneous urban development density derived from observations of impervious surfaces with sub-grid scale resolution is then proposed for mesoscale applications. This method was implemented and evaluated within the environmental modeling framework. Finally, a new semi-implicit scheme based on Leapfrog and a fourth-order implicit time-filter is developed.
A detailed evaluation of the environmental forecast is conducted by investigating the Surface Energy Balance (SEB) obtained from observations made with an eddy-covariance flux tower compared with SEB from simulations using several physical parameterizations of urban effects and planetary boundary layer schemes. Diurnal variation in SEB constituent fluxes are examined in relation to surface layer stability and modeled diagnostic variables. Improvement is found when adapting parameterizations for Phoenix with reduced errors in the SEB components. Finer model resolution (to 333 m) is seen to have insignificant ($<1\sigma$) influence on mean absolute percent difference of 30-minute diurnal mean SEB terms. A new method of representing inhomogeneous urban development density derived from observations of impervious surfaces with sub-grid scale resolution is then proposed for mesoscale applications. This method was implemented and evaluated within the environmental modeling framework. Finally, a new semi-implicit scheme based on Leapfrog and a fourth-order implicit time-filter is developed.
ContributorsShaffer, Stephen R. (Author) / Moustaoui, Mohamed (Thesis advisor) / Mahalov, Alex (Committee member) / Fernando, Harindra J.S. (Committee member) / Ovenden, Nicholas C. (Committee member) / Huang, Huei-Ping (Committee member) / Calhoun, Ronald (Committee member) / Arizona State University (Publisher)
Created2014