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Description
Galaxies represent a fundamental catalyst in the ``lifecycle'' of matter in the Universe, and the study of galaxy assembly and evolution provides unique insight into the physical processes governing the transformation of matter from atoms to gas to stars. With the Hubble Space Telescope, the astrophysical community is able to

Galaxies represent a fundamental catalyst in the ``lifecycle'' of matter in the Universe, and the study of galaxy assembly and evolution provides unique insight into the physical processes governing the transformation of matter from atoms to gas to stars. With the Hubble Space Telescope, the astrophysical community is able to study the formation and evolution of galaxies, at an unrivaled spatial resolution, over more than 90% of cosmic time. Here, I present results from two complementary studies of galaxy evolution in the local and intermediate redshift Universe which used new and archival HST images. First, I use archival broad-band HST WFPC2 optical images of local (d<63 Mpc) Seyfert-type galaxies to test the observed correlation between visually-classified host galaxy dust morphology and AGN class. Using quantitative parameters for classifying galaxy morphology, I do not measure a strong correlation between the galaxy morphology and AGN class. This result could imply that the Unified Model of AGN provides a sufficient model for the observed diversity of AGN, but this result could also indicate the quantitative techniques are insufficient for characterizing the dust morphology of local galaxies. To address the latter, I develop a new automated method using an inverse unsharp masking technique coupled to Source Extractor to detect and measure dust morphology. I measure no strong trends with dust-morphology and AGN class using this method, and conclude that the Unified Model remains sufficient to explain the diversity of AGN. Second, I use new UV-optical-near IR broad-band images obtained with the HST WFC3 in the Early Release Science (ERS) program to study the evolution of massive, early-type galaxies. These galaxies were once considered to be ``red and dead'', as a class uniformly devoid of recent star formation, but observations of these galaxies in the local Universe at UV wavelengths have revealed a significant fraction (30%) of ETGs to have recently formed a small fraction (5-10%) of their stellar mass in young stars. I extend the study of recent star formation in ETGs to intermediate-redshift 0.35<1.5 with the ERS data. Comparing the mass fraction and age of young stellar populations identified in these ETGs from two-component SED analysis with the morphology of the ETG and the frequency of companions, I find that at this redshift many ETGs are likely to have experienced a minor burst of recent star formation. The mechanisms driving this recent star formation are varied, and evidence for both minor merger driven recent star formation as well as the evolution of transitioning ETGs is identified.
ContributorsRutkowski, Michael (Author) / Windhorst, Rogier A. (Thesis advisor) / Bowman, Judd (Committee member) / Butler, Nathaniel (Committee member) / Desch, Steven (Committee member) / Young, Patrick (Committee member) / Arizona State University (Publisher)
Created2013
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Description
V(D)J recombination is responsible for generating an enormous repertoire of immunoglobulins and T cell receptors, therefore it is a centerpiece to the formation of the adaptive immune system. The V(D)J recombination process proceeds through two steps, site-specific cleavage at RSS (Recombination Signal Sequence) site mediated by the RAG recombinase (RAG1/2)

V(D)J recombination is responsible for generating an enormous repertoire of immunoglobulins and T cell receptors, therefore it is a centerpiece to the formation of the adaptive immune system. The V(D)J recombination process proceeds through two steps, site-specific cleavage at RSS (Recombination Signal Sequence) site mediated by the RAG recombinase (RAG1/2) and the subsequent imprecise resolution of the DNA ends, which is carried out by the ubiquitous non-homologous end joining pathway (NHEJ). The V(D)J recombination reaction is obliged to be tightly controlled under all circumstances, as it involves generations of DNA double strand breaks, which are considered the most dangerous lesion to a cell. Multifaceted regulatory mechanisms have been evolved to create great diversity of the antigen receptor repertoire while ensuring genome stability. The RAG-mediated cleavage reaction is stringently regulated at both the pre-cleavage stage and the post-cleavage stage. Specifically, RAG1/2 first forms a pre-cleavage complex assembled at the boarder of RSS and coding flank, which ensures the appropriate DNA targeting. Subsequently, this complex initiates site-specific cleavage, generating two types of double stranded DNA breaks, hairpin-ended coding ends (HP-CEs) and blunt signal ends (SEs). After the cleavage, RAG1/2 proteins bind and retain the recombination ends to form post-cleavage complexes (PCC), which collaborates with the NHEJ machinery for appropriate transfer of recombination ends to NHEJ for proper end resolution. However, little is known about the molecular basis of this collaboration, partly attributed to the lack of sensitive assays to reveal the interaction of PCC with HP-CEs. Here, for the first time, by using two complementary fluorescence-based techniques, fluorescence anisotropy and fluorescence resonance energy transfer (FRET), I managed to monitor the RAG1/2-catalyzed cleavage reaction in real time, from the pre-cleavage to the post-cleavage stages. By examining the dynamic fluorescence changes during the RAG-mediated cleavage reactions, and by manipulating the reaction conditions, I was able to characterize some fundamental properties of RAG-DNA interactions before and after cleavage. Firstly, Mg2+, known as a physiological cofactor at the excision step, also promotes the HP-CEs retention in the RAG complex after cleavage. Secondly, the structure of pre-cleavage complex may affect the subsequent collaborations with NHEJ for end resolution. Thirdly, the non-core region of RAG2 may have differential influences on the PCC retention of HP-CEs and SEs. Furthermore, I also provide the first evidence of RAG1-mediated regulation of RAG2. Our study provides important insights into the multilayered regulatory mechanisms, in modulating recombination events in developing lymphocytes and paves the way for possible development of detection and diagnotic markers for defective recombination events that are often associated immunodeficiency and/or lymphoid malignancy.
ContributorsWang, Guannan (Author) / Chang, Yung (Thesis advisor) / Levitus, Marcia (Committee member) / Misra, Rajeev (Committee member) / Anderson, Karen (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Intrinsic antibiotic resistance is of growing concern in modern medical treatment. The primary action of multidrug resistant strains is through over-expression of active transporters which recognize a broad range of antibiotics. In Escherichia coli, the TolC-AcrAB complex has become a model system to understand antibiotic efflux. While the structures of

Intrinsic antibiotic resistance is of growing concern in modern medical treatment. The primary action of multidrug resistant strains is through over-expression of active transporters which recognize a broad range of antibiotics. In Escherichia coli, the TolC-AcrAB complex has become a model system to understand antibiotic efflux. While the structures of these three proteins (and many of their homologs) are known, the exact mechanisms of interaction are still poorly understood. By mutational analysis of the TolC turn 1 residues, a drug hypersensitive mutant has been identified which is defective in functional interactions with AcrA and AcrB. Antibiotic resistant revertants carry alterations in both TolC and AcrA act by stabilizing functional complex assembly and opening of the TolC aperture, as monitored by stability of a labile TolC mutant and sensitivity to vancomycin, respectively. Alterations in the AcrB periplasmic hairpin loops lead to a similar antibiotic hypersensitivity phenotype and destabilized complex assembly. Likewise, alterations in TolC which constitutively open the aperture suppress this antibiotic sensitivity. Suppressor alterations in AcrA and AcrB partially restore antibiotic resistance by mediating stability of the complex. The AcrA suppressor alterations isolated in these studies map to the three crystallized domains and it is concluded they alter the AcrA conformation such that it is permanently fixed in an active state, which wild type only transiently goes through when activated by AcrB. Through this genetic evidence, a direct interaction between TolC and AcrB which is stabilized by AcrA has been proposed. In addition to stabilizing the interactions between TolC and AcrB, AcrA is also responsible for triggering opening of the TolC aperture by mediating energy flow from AcrB to TolC. By permanently altering the conformation of AcrA, suppressor mutants allow defective TolC or AcrB mutants to regain functional interactions lost by the initial mutations. The data provide the genetic proof for direct interaction between AcrB and that AcrA mediated opening of TolC requires AcrB as a scaffold.
ContributorsWeeks, Jon William (Author) / Misra, Rajeev (Thesis advisor) / Stout, Valerie (Committee member) / Shi, Yixin (Committee member) / Clark-Curtiss, Josephine (Committee member) / Arizona State University (Publisher)
Created2012
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Description
The discovery and development of novel antibacterial agents is essential to address the rising health concern over antibiotic resistant bacteria. This research investigated the antibacterial activity of a natural clay deposit near Crater Lake, Oregon, that is effective at killing antibiotic resistant human pathogens. The primary rock types in the

The discovery and development of novel antibacterial agents is essential to address the rising health concern over antibiotic resistant bacteria. This research investigated the antibacterial activity of a natural clay deposit near Crater Lake, Oregon, that is effective at killing antibiotic resistant human pathogens. The primary rock types in the deposit are andesitic pyroclastic materials, which have been hydrothermally altered into argillic clay zones. High-sulfidation (acidic) alteration produced clay zones with elevated pyrite (18%), illite-smectite (I-S) (70% illite), elemental sulfur, kaolinite and carbonates. Low-sulfidation alteration at neutral pH generated clay zones with lower pyrite concentrations pyrite (4-6%), the mixed-layered I-S clay rectorite (R1, I-S) and quartz.

Antibacterial susceptibility testing reveals that hydrated clays containing pyrite and I-S are effective at killing (100%) of the model pathogens tested (E. coli and S. epidermidis) when pH (< 4.2) and Eh (> 450 mV) promote pyrite oxidation and mineral dissolution, releasing > 1 mM concentrations of Fe2+, Fe3+ and Al3+. However, certain oxidized clay zones containing no pyrite still inhibited bacterial growth. These clays buffered solutions to low pH (< 4.7) and oxidizing Eh (> 400 mV) conditions, releasing lower amounts (< 1 mM) of Fe and Al. The presence of carbonate in the clays eliminated antibacterial activity due to increases in pH, which lower pyrite oxidation and mineral dissolution rates.

The antibacterial mechanism of these natural clays was explored using metal toxicity and genetic assays, along with advanced bioimaging techniques. Antibacterial clays provide a continuous reservoir of Fe2+, Fe3+ and Al3+ that synergistically attack pathogens while generating hydrogen peroxide (H2O¬2). Results show that dissolved Fe2+ and Al3+ are adsorbed to bacterial envelopes, causing protein misfolding and oxidation in the outer membrane. Only Fe2+ is taken up by the cells, generating oxidative stress that damages DNA and proteins. Excess Fe2+ oxidizes inside the cell and precipitates Fe3+-oxides, marking the sites of hydroxyl radical (•OH) generation. Recognition of this novel geochemical antibacterial process should inform designs of new mineral based antibacterial agents and could provide a new economic industry for such clays.
ContributorsMorrison, Keith D (Author) / Williams, Lynda B (Thesis advisor) / Williams, Stanley N (Thesis advisor) / Misra, Rajeev (Committee member) / Shock, Everett (Committee member) / Anbar, Ariel (Committee member) / Arizona State University (Publisher)
Created2015
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Description
The Milky Way galaxy is a powerful dynamic system that is highly efficient at recycling material. Stars are born out of intergalactic gas and dust, fuse light elements into heavier elements in their cores, then upon stellar death spread material throughout the galaxy, either by diffusion of planetary nebula or

The Milky Way galaxy is a powerful dynamic system that is highly efficient at recycling material. Stars are born out of intergalactic gas and dust, fuse light elements into heavier elements in their cores, then upon stellar death spread material throughout the galaxy, either by diffusion of planetary nebula or by explosive events for high mass stars, and that gas must cool and condense to form stellar nurseries. Though the stellar lifecycle has been studied in detail, relatively little is known about the processes by which hot, diffuse gas ejected by dying stars cools and conglomerates in the interstellar medium (ISM). Much of this mystery arises because only recently have instruments with sufficient spatial and spectral resolution, sensitivity, and bandwidth become available in the terahertz (THz) frequency spectrum where these clouds peak in either thermal or line emission. In this dissertation, I will demonstrate technology advancement of instruments in this frequency regime with new characterization techniques, machining strategies, and scientific models of the spectral behavior of gas species targeted by these instruments.

I begin this work with a description of radiation pattern measurements and their use in astronomical instrument characterization. I will introduce a novel technique to measure complex (phase-sensitive) field patterns using direct detectors. I successfully demonstrate the technique with a single pixel microwave inductance detectors (MKID) experiment. I expand that work by measuring the APEX MKID (A-MKID) focal plane array of 880 pixel detectors centered at 350 GHz. In both chapters I discuss the development of an analysis pipeline to take advantage of all information provided by complex field mapping. I then discuss the design, simulation, fabrication processes, and characterization of a circular-to-rectangular waveguide transformer module integrated into a circularly symmetric feedhorn block. I conclude with a summary of this work and how to advance these technologies for future ISM studies.
ContributorsDavis, Kristina (Author) / Groppi, Christopher E (Thesis advisor) / Bowman, Judd (Committee member) / Mauskopf, Philip (Committee member) / Jellema, Willem (Committee member) / Pan, George (Committee member) / Trichopoulos, Georgios (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Lignocellulosic biomass represents a renewable domestic feedstock that can support large-scale biochemical production processes for fuels and specialty chemicals. However, cost-effective conversion of lignocellulosic sugars into valuable chemicals by microorganisms still remains a challenge. Biomass recalcitrance to saccharification, microbial substrate utilization, bioproduct titer toxicity, and toxic chemicals associated with chemical

Lignocellulosic biomass represents a renewable domestic feedstock that can support large-scale biochemical production processes for fuels and specialty chemicals. However, cost-effective conversion of lignocellulosic sugars into valuable chemicals by microorganisms still remains a challenge. Biomass recalcitrance to saccharification, microbial substrate utilization, bioproduct titer toxicity, and toxic chemicals associated with chemical pretreatments are at the center of the bottlenecks limiting further commercialization of lignocellulose conversion. Genetic and metabolic engineering has allowed researchers to manipulate microorganisms to overcome some of these challenges, but new innovative approaches are needed to make the process more commercially viable. Transport proteins represent an underexplored target in genetic engineering that can potentially help to control the input of lignocellulosic substrate and output of products/toxins in microbial biocatalysts. In this work, I characterize and explore the use of transport systems to increase substrate utilization, conserve energy, increase tolerance, and enhance biocatalyst performance.
ContributorsKurgan, Gavin (Author) / Wang, Xuan (Thesis advisor) / Nielsen, David (Committee member) / Misra, Rajeev (Committee member) / Nannenga, Brent (Committee member) / Arizona State University (Publisher)
Created2018
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Description
The Cosmic Microwave Background (CMB) has provided precise information on the evolution of the Universe and the current cosmological paradigm. The CMB has not yet provided definitive information on the origin and strength of any primordial magnetic fields or how they affect the presence of magnetic fields observed throughout the

The Cosmic Microwave Background (CMB) has provided precise information on the evolution of the Universe and the current cosmological paradigm. The CMB has not yet provided definitive information on the origin and strength of any primordial magnetic fields or how they affect the presence of magnetic fields observed throughout the cosmos. This work outlines an alternative method to investigating and identifying the presence of cosmic magnetic fields. This method searches for Faraday Rotation (FR) and specifically uses polarized CMB photons as back-light. I find that current generation CMB experiments may be not sensitive enough to detect FR but next generation experiments should be able to make highly significant detections. Identifying FR with the CMB will provide information on the component of magnetic fields along the line of sight of observation.

The 21cm emission from the hyperfine splitting of neutral Hydrogen in the early universe is predicted to provide precise information about the formation and evolution of cosmic structure, complementing the wealth of knowledge gained from the CMB.

21cm cosmology is a relatively new field, and precise measurements of the Epoch of Reionization (EoR) have not yet been achieved. In this work I present 2σ upper limits on the power spectrum of 21cm fluctuations (Δ²(k)) probed at the cosmological wave number k from the Donald C. Backer Precision Array for Probing the Epoch of Reionization (PAPER) 64 element deployment. I find upper limits on Δ²(k) in the range 0.3 < k < 0.6 h/Mpc to be (650 mK)², (450 mK)², (390 mK)², (250 mK)², (280mK)², (250 mK)² at redshifts z = 10.87, 9.93, 8.91, 8.37, 8.13 and 7.48 respectively

Building on the power spectrum analysis, I identify a major limiting factor in detecting the 21cm power spectrum.

This work is concluded by outlining a metric to evaluate the predisposition of redshifted 21cm interferometers to foreground contamination in power spectrum estimation. This will help inform the construction of future arrays and enable high fidelity imaging and

cross-correlation analysis with other high redshift cosmic probes like the CMB and other upcoming all sky surveys. I find future

arrays with uniform (u,v) coverage and small spectral evolution of their response in the (u,v,f) cube can minimize foreground leakage while pursuing 21cm imaging.
ContributorsKolopanis, Matthew John (Author) / Bowman, Judd (Thesis advisor) / Mauskopf, Philip (Thesis advisor) / Lunardini, Cecilia (Committee member) / Chamberlin, Ralph (Committee member) / Vachaspati, Tanmay (Committee member) / Arizona State University (Publisher)
Created2018
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Description
This thesis contains an overview, as well as the history of optical interferometers. A new approach to interferometric measurements of stars is proposed and explored. Modern updates to the classic techniques are described along with some theoretical derivations showing why the method of single photon counting shows significant promise relative

This thesis contains an overview, as well as the history of optical interferometers. A new approach to interferometric measurements of stars is proposed and explored. Modern updates to the classic techniques are described along with some theoretical derivations showing why the method of single photon counting shows significant promise relative to the currently used amplitude interferometry.

Description of a modular intensity interferometer system using commercially available single-photon detectors is given. Calculations on the sensitivity and \emph{uv}-plane coverage using these modules mounted on existing telescopes on Kitt Peak, Arizona is presented.

Determining fundamental stellar properties is essential for testing models of stellar evolution as well as for deriving physical properties of transiting exoplanets. The proposed method shows great promise in measuring the angular size of stars. Simulations indicate that it is possible to measure stellar diameters of bright stars with AB magnitude <6 with a precision of >5% in a single night of observation.

Additionally, a description is given of a custom time-to-digital converter designed to time tag individual photons from multiple single-photon detectors with high count rate, continuous data logging, and low systematics. The instrument utilizes a tapped-delay line approach on an FPGA chip which allows for sub-clock resolution of <100 ps. The TDC is implemented on a Re-configurable Open Architecture Computing Hardware Revision 2 (ROACH2) board which allows for continuous data streaming and time tagging of up to 20 million events per second. The functioning prototype is currently set-up to work with up to ten independent channels. Laboratory characterization of the system, including RF, pick up and mitigation, as well as measurement of in-lab photon correlations from an incoherent light source (artificial star), are presented. Additional improvements to the TDC will also be discussed, such as improving the data transfer rate by a factor of 10 via an SDP+ Mezzanine card and PCIe 2SFP+ 10 Gb card, as well as scaling to 64 independent channels.

Furthermore, a modified nulling interferometer with image inversion is proposed, for direct imaging of exoplanets below the canonical Rayleigh resolution limit. Image inversion interferometry relies on splitting incoming radiation from a source, either spatially rotating or reflecting the electric field from one arm of the interferometer before recombining the signals and detecting the resulting images in the two output ports with an array of high-speed single-photon detectors. Sources of incoming radiation that have cylindrical symmetry and are centered on the rotation axis will cancel in one of the output ports and add in the other output port. The ability to suppress light from a host star, as well as the ability to resolve past the Rayleigh limit, enables sensitive detection of exoplanets from a stable environment without the need for a coronagraph. The expected number of photons and the corresponding variance in the measurement for different initial contrast ratios are shown, with some first-order theoretical instrumental errors.

Lastly, preliminary results from a sizeable photometric survey are presented. This survey is used to derive bolometric flux alongside from angular size measurements and the effective stellar temperatures.
ContributorsPilyavsky, Genady (Author) / Mauskopf, Philip (Thesis advisor) / Groppi, Christopher (Committee member) / Butler, Nathaniel (Committee member) / Bowman, Judd (Committee member) / Scowen, Paul (Committee member) / Arizona State University (Publisher)
Created2018
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Description
The purpose of this study was to observe the effectiveness of the phenylalanyl arginine β-naphthylamide dihydrochloride inhibitor and Tween 20 when combined with an antibiotic against Escherichia. coli. As antibiotic resistance becomes more and more prevalent it is necessary to think outside the box and do more than just increase

The purpose of this study was to observe the effectiveness of the phenylalanyl arginine β-naphthylamide dihydrochloride inhibitor and Tween 20 when combined with an antibiotic against Escherichia. coli. As antibiotic resistance becomes more and more prevalent it is necessary to think outside the box and do more than just increase the dosage of currently prescribed antibiotics. This study attempted to combat two forms of antibiotic resistance. The first is the AcrAB efflux pump which is able to pump antibiotics out of the cell. The second is the biofilms that E. coli can form. By using an inhibitor, the pump should be unable to rid itself of an antibiotic. On the other hand, using Tween allows for biofilm formation to either be disrupted or for the biofilm to be dissolved. By combining these two chemicals with an antibiotic that the efflux pump is known to expel, low concentrations of each chemical should result in an equivalent or greater effect on bacteria compared to any one chemical in higher concentrations. To test this hypothesis a 96 well plate BEC screen test was performed. A range of antibiotics were used at various concentrations and with varying concentrations of both Tween and the inhibitor to find a starting point. Following this, Erythromycin and Ciprofloxacin were picked as the best candidates and the optimum range of the antibiotic, Tween, and inhibitor were established. Finally, all three chemicals were combined to observe the effects they had together as opposed to individually or paired together. From the results of this experiment several conclusions were made. First, the inhibitor did in fact increase the effectiveness of the antibiotic as less antibiotic was needed if the inhibitor was present. Second, Tween showed an ability to prevent recovery in the MBEC reading, showing that it has the ability to disrupt or dissolve biofilms. However, Tween also showed a noticeable decrease in effectiveness in the overall treatment. This negative interaction was unable to be compensated for when using the inhibitor and so the hypothesis was proven false as combining the three chemicals led to a less effective treatment method.
ContributorsPetrovich Flynn, Chandler James (Author) / Misra, Rajeev (Thesis director) / Bean, Heather (Committee member) / Perkins, Kim (Committee member) / Mechanical and Aerospace Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
The inherent risk in testing drugs has been hotly debated since the government first started regulating the drug industry in the early 1900s. Who can assume the risks associated with trying new pharmaceuticals is unclear when looked at through society's lens. In the mid twentieth century, the US Food and

The inherent risk in testing drugs has been hotly debated since the government first started regulating the drug industry in the early 1900s. Who can assume the risks associated with trying new pharmaceuticals is unclear when looked at through society's lens. In the mid twentieth century, the US Food and Drug Administration (FDA) published several guidance documents encouraging researchers to exclude women from early clinical drug research. The motivation to publish those documents and the subsequent guidance documents in which the FDA and other regulatory offices established their standpoints on women in drug research may have been connected to current events at the time. The problem of whether women should be involved in drug research is a question of who can assume risk and who is responsible for disseminating what specific kinds of information. The problem tends to be framed as one that juxtaposes the health of women and fetuses and sets their health as in opposition. That opposition, coupled with the inherent uncertainty in testing drugs, provides for a complex set of issues surrounding consent and access to information.
ContributorsMeek, Caroline Jane (Author) / Maienschein, Jane (Thesis director) / Brian, Jennifer (Committee member) / School of Life Sciences (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05