Matching Items (173)
Description
Cell-cell interactions in a microenvironment under stress conditions play a critical role in pathogenesis and pre-malignant progression. Hypoxia is a central factor in carcinogenesis, which induces selective pressure in this process. Understanding the role of intercellular communications and cellular adaptation to hypoxia can help discover new cancer biosignatures and more effective diagnostic and therapeutic strategies. This dissertation presents a study on transcriptomic and metabolic profiling of pre-malignant progression of Barrett's esophagus. It encompasses two methodology developments and experimental findings of two related studies. To integrate phenotype and genotype measurements, a minimally invasive method was developed for selectively retrieving single adherent cells from cell cultures. Selected single cells can be harvested by a combination of mechanical force and biochemical treatment after phenotype measurements and used for end-point assays. Furthermore, a method was developed for analyzing expression levels of ten genes in individual mammalian cells with high sensitivity and reproducibility without the need of pre-amplifying cDNA. It is inexpensive and compatible with most of commercially available RT-qPCR systems, which warrants a wide applicability of the method to gene expression analysis in single cells. In the first study, the effect of intercellular interactions was investigated between normal esophageal epithelial and dysplastic Barrett's esophagus cells on gene expression levels and cellular functions. As a result, gene expression levels in dysplastic cells were found to be affected to a significantly larger extent than in the normal esophageal epithelial cells. These differentially expressed genes are enriched in cellular movement, TGFβ and EGF signaling networks. Heterotypic interactions between normal and dysplastic cells can change cellular motility and inhibit proliferation in both normal and dysplastic cells. In the second study, alterations in gene transcription levels and metabolic phenotypes between hypoxia-adapted cells and age-matched normoxic controls representing four different stages of pre-malignant progression in Barrett's esophagus were investigated. Through differential gene expression analysis and mitochondrial membrane potential measurements, evidence of clonal evolution induced by hypoxia selection pressure in metaplastic and high-grade dysplastic cells was found. These discoveries on cell-cell interactions and hypoxia adaptations provide a deeper insight into the dynamic evolutionary process in pre-malignant progression of Barrett's esophagus.
ContributorsZeng, Jia (Author) / Meldrum, Deirdre R (Thesis advisor) / Kelbauskas, Laimonas (Committee member) / Barrett, Michael T (Committee member) / Bussey, Kimberly J (Committee member) / Zhang, Weiwen (Committee member) / Arizona State University (Publisher)
Created2014
Description
Cellular heterogeneity is a key factor in various cellular processes as well as in disease development, especially associated with immune response and cancer progression. Cell-to-cell variability is considered to be one of the major obstacles in early detection and successful treatment of cancer. Most present technologies are based on bulk cell analysis, which results in averaging out the results acquired from a group of cells and hence missing important information about individual cells and their behavior. Understanding the cellular behavior at the single-cell level can help in obtaining a complete profile of the cell and to get a more in-depth knowledge of cellular processes. For example, measuring transmembrane fluxes oxygen can provide a direct readout of the cell metabolism.
The goal of this thesis is to design, optimize and implement a device that can measure the oxygen consumption rate (OCR) of live single cells. A microfluidic device has been designed with the ability to rapidly seal and unseal microchambers containing individual cells and an extracellular optical oxygen sensor for measuring the OCR of live single cells. The device consists of two parts, one with the sensor in microwells (top half) and the other with channels and cells trapped in Pachinko-type micro-traps (bottom half). When the two parts of the device are placed together the wells enclose each cell. Oil is flown in through the channels of the device to produce isolated and sealed microchamber around each cell. Different fluids can be flowed in and out of the device, alternating with oil, to rapidly switch between sealed and unsealed microenvironment around each cell. A fluorescent ratiometric dual pH and oxygen sensor is placed in each well. The thesis focuses on measuring changes in the oxygen consumption rate of each cell within a well. Live and dead cells are identified using a fluorescent live/dead cell assay. Finally, the technology is designed to be scalable for high-throughput applications by controlling the flow rate of the system and increasing the cell array density.
The goal of this thesis is to design, optimize and implement a device that can measure the oxygen consumption rate (OCR) of live single cells. A microfluidic device has been designed with the ability to rapidly seal and unseal microchambers containing individual cells and an extracellular optical oxygen sensor for measuring the OCR of live single cells. The device consists of two parts, one with the sensor in microwells (top half) and the other with channels and cells trapped in Pachinko-type micro-traps (bottom half). When the two parts of the device are placed together the wells enclose each cell. Oil is flown in through the channels of the device to produce isolated and sealed microchamber around each cell. Different fluids can be flowed in and out of the device, alternating with oil, to rapidly switch between sealed and unsealed microenvironment around each cell. A fluorescent ratiometric dual pH and oxygen sensor is placed in each well. The thesis focuses on measuring changes in the oxygen consumption rate of each cell within a well. Live and dead cells are identified using a fluorescent live/dead cell assay. Finally, the technology is designed to be scalable for high-throughput applications by controlling the flow rate of the system and increasing the cell array density.
ContributorsRodrigues, Meryl (Author) / Meldrum, Deirdre (Thesis advisor) / Kelbauskas, Laimonas (Committee member) / LaBelle, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2014
Description
This research compares shifts in a SuperSpec titanium nitride (TiN) kinetic inductance detector's (KID's) resonant frequency with accepted models for other KIDs. SuperSpec, which is being developed at the University of Colorado Boulder, is an on-chip spectrometer designed with a multiplexed readout with multiple KIDs that is set up for a broadband transmission of these measurements. It is useful for detecting radiation in the mm and sub mm wavelengths which is significant since absorption and reemission of photons by dust causes radiation from distant objects to reach us in infrared and far-infrared bands. In preparation for testing, our team installed stages designed previously by Paul Abers and his group into our cryostat and designed and installed other parts necessary for the cryostat to be able to test devices on the 250 mK stage. This work included the design and construction of additional parts, a new setup for the wiring in the cryostat, the assembly, testing, and installation of several stainless steel coaxial cables for the measurements through the devices, and other cryogenic and low pressure considerations. The SuperSpec KID was successfully tested on this 250 mK stage thus confirming that the new setup is functional. Our results are in agreement with existing models which suggest that the breaking of cooper pairs in the detector's superconductor which occurs in response to temperature, optical load, and readout power will decrease the resonant frequencies. A negative linear relationship in our results appears, as expected, since the parameters are varied only slightly so that a linear approximation is appropriate. We compared the rate at which the resonant frequency responded to temperature and found it to be close to the expected value.
ContributorsDiaz, Heriberto Chacon (Author) / Mauskopf, Philip (Thesis director) / McCartney, Martha (Committee member) / Department of Physics (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Supernovae are vital to supplying necessary elements to forming bodies in our solar systems. This project studies the creation of a subset of these necessary elements, called short-lived radionuclides (SLRs). SLRs are isotopes with relatively short half-lives and can serve as heat sources for forming planetary bodies, and their traces can be used to date stellar events. Computational models of asymmetric supernovae provide opportunities to study the effect of explosion geometry on the SLR yields. We are most interested in the production of \iso{Al}{26}, \iso{Fe}{60}, and \iso{Ca}{41}, whose decayed products are found in our own solar system. To study the effect of explosion asymmetries in supernovae, we use TYCHO stellar evolution code, SNSHP smooth particle hydrodynamics code for 3D explosion simulations, Burn code for nucleosythesis post-processing, and Python code written to analyze the output of the post-processing code.
ContributorsJohnson, Charlotte (Author) / Young, Patrick (Thesis director) / Lunardini, Cecilia (Committee member) / Department of Physics (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
We hypothesized that recurrent exposure to a temporal discounting task would habitize participants, so that they become insensitive to framing effects. Temporal discounting is a behavioral trend which describes how people discount the value of a reward dependent on the time until receipt. Participants completed a temporal discounting task weekly for five weeks, to promote formation of a habitual decision strategy. Concomitant with this, we expected that people would shift their decision process from a deliberate, goal-oriented approach that is sensitive to changes in reward outcomes and environmental context, to a simplified, automatic approach that minimizes cognitive effort. We expected that this shift in decision strategy would be evident in a reduced influence of contextual effects on choice outcomes. We tested this hypothesis by leveraging two framing effects \u2014 the date/delay effect and the decimal effect. Consistent with our hypothesis, we find that the date/delay effect is significant on week 1, shows significant changes in week 1 to week 5, and is no longer significant on week 5. The results for the decimal effects were not significant. We discuss these results with respect to the cognitive processes that underlie temporal discounting and self-control.
ContributorsSt Amand, Jesse Dean (Author) / McClure, Samuel (Thesis director) / Sanabria, Federico (Committee member) / School of Molecular Sciences (Contributor) / Department of Physics (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
A problem of interest in theoretical physics is the issue of the evaporation of black holes via Hawking radiation subject to a fixed background. We approach this problem by considering an electromagnetic analogue, where we have substituted Hawking radiation with the Schwinger effect. We treat the case of massless QED in 1+1 dimensions with the path integral approach to quantum field theory, and discuss the resulting Feynman diagrams from our analysis. The results from this thesis may be useful to find a version of the Schwinger effect that can be solved exactly and perturbatively, as this version may provide insights to the gravitational problem of Hawking radiation.
ContributorsDhumuntarao, Aditya (Author) / Parikh, Maulik (Thesis director) / Davies, Paul C. W. (Committee member) / Department of Physics (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Observations of four times ionized iron and nickel (Fe V & Ni V) in the G191-B2B white dwarf spectrum have been used to test for variations in the fine structure constant, α, in the presence of strong gravitational fields. The laboratory wavelengths for these ions were thought to be the cause of inconsistent conclusions regarding the
variation of α as observed through the white dwarf spectrum. This thesis presents 129 revised Fe V wavelengths (1200 Å to 1600 Å) and 161 revised Ni V wavelengths (1200 Å to 1400 Å) with uncertainties of approximately 3 mÅ. A systematic calibration error
is identified in the previous Ni V wavelengths and is corrected in this work. The evaluation of the fine structure variation is significantly improved with the results
found in this thesis.
variation of α as observed through the white dwarf spectrum. This thesis presents 129 revised Fe V wavelengths (1200 Å to 1600 Å) and 161 revised Ni V wavelengths (1200 Å to 1400 Å) with uncertainties of approximately 3 mÅ. A systematic calibration error
is identified in the previous Ni V wavelengths and is corrected in this work. The evaluation of the fine structure variation is significantly improved with the results
found in this thesis.
ContributorsWard, Jacob Wolfgang (Author) / Treacy, Michael (Thesis director) / Alarcon, Ricardo (Committee member) / Nave, Gillian (Committee member) / Department of Physics (Contributor) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
In fan fiction, fans utilize different elements in an original work and incorporate them into their fanfics; elements such as the characters and setting of an original work are frequently used in fan fiction. A different element is investigated: time travel. The physics behind time travel is not yet understood, so authors have to create their own time travel physics in their works to account for this lack of understanding. Therefore, for fan authors to incorporate time travel into their fanfic, they must study the time travel physics in the original work the same way that characters from an original work are studied. Three original works and three fanfics are examined: the television show My Little Pony: Friendship is Magic and its fanfic "The Fall and Rise of the Alicorn", the Harry Potter book series and its fanfic "Back to the Time of the Unknown", and the webcomic Homestuck and its fanfic "Like a Bug on a Windshield".
ContributorsClark, Michael Robert (Author) / Ingram-Waters, Mary (Thesis director) / Scott, Suzanne (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Physics (Contributor)
Created2014-05
Description
The influence of mix design on the structural properties of FAU-type (faujasite) zeolite was studied. Samples were synthesized in a forced convection oven using various proportions of coal fly ash, sodium hydroxide (NaOH), and sodium chloride (NaCl). Three faujasite varieties, labeled X, P and S, were prepared for each mix design. Samples were characterized using Fourier transform infrared (FT-IR) spectroscopy and thermo-gravimetric analysis (TGA). Mercury intrusion porosimetry (MIP) was used to obtain porosity information on the samples. Mechanical strength testing was performed on solid blocks of the zeolite samples prepared in a mold. It was found that the S variety in mix design (iv) had the most desirable balance of porosity and strength for engineering applications.
ContributorsRuta, Francesco Luigi (Author) / Neithalath, Narayanan (Thesis director) / Ramakrishna, Bindiganavale (Committee member) / Civil, Environmental and Sustainable Engineering Programs (Contributor) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Physics (Contributor)
Created2015-05
Description
We develop the mathematical tools necessary to describe the interaction between a resonant pole and a threshold energy. Using these tools, we analyze the properties an opening threshold has on the resonant pole mass (the "cusp effect"), leading to an effect called "pole-dragging." We consider two models for resonances: a molecular, mesonic model, and a color-nonsinglet diquark plus antidiquark model. Then, we compare the pole-dragging effect due to these models on the masses of the f0(980), the X(3872), and the Zb(10610) and compare the effect's magnitude. We find that, while for lower masses, such as the f 0 (980), the pole-dragging effect that arises from the molecular model is more significant, the diquark model's pole-dragging effect becomes dominant at higher masses such as those of the X(3872) and the Z b (10610). This indicates that for lower threshold energies, diquark models may have less significant effects on predicted resonant masses than mesonic models, but for higher threshold energies, it is necessary to include the pole-dragging effect due to a diquark threshold in high-precision QCD calculations.
ContributorsBlitz, Samuel Harris (Author) / Richard, Lebed (Thesis director) / Comfort, Joseph (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / Department of Physics (Contributor) / Barrett, The Honors College (Contributor)
Created2015-05