Matching Items (192)
Description
Within the last decade there has been remarkable interest in single-cell metabolic analysis as a key technology for understanding cellular heterogeneity, disease initiation, progression, and drug resistance. Technologies have been developed for oxygen consumption rate (OCR) measurements using various configurations of microfluidic devices. The technical challenges of current approaches include: (1) deposition of multiple sensors for multi-parameter metabolic measurements, e.g. oxygen, pH, etc.; (2) tedious and labor-intensive microwell array fabrication processes; (3) low yield of hermetic sealing between two rigid fused silica parts, even with a compliance layer of PDMS or Parylene-C. In this thesis, several improved microfabrication technologies are developed and demonstrated for analyzing multiple metabolic parameters from single cells, including (1) a modified "lid-on-top" configuration with a multiple sensor trapping (MST) lid which spatially confines multiple sensors to micro-pockets enclosed by lips for hermetic sealing of wells; (2) a multiple step photo-polymerization method for patterning three optical sensors (oxygen, pH and reference) on fused silica and on a polyethylene terephthalate (PET) surface; (3) a photo-polymerization method for patterning tri-color (oxygen, pH and reference) optical sensors on both fused silica and on the PET surface; (4) improved KMPR/SU-8 microfabrication protocols for fabricating microwell arrays that can withstand cell culture conditions. Implementation of these improved microfabrication methods should address the aforementioned challenges and provide a high throughput and multi-parameter single cell metabolic analysis platform.
ContributorsSong, Ganquan (Author) / Meldrum, Deirdre R (Thesis advisor) / Goryll, Michael (Committee member) / Wang, Hong (Committee member) / Tian, Yanqing (Committee member) / Arizona State University (Publisher)
Created2014
Description
Traumatic brain injury (TBI) is a leading cause of disability worldwide with 1.7 million TBIs reported annually in the United States. Broadly, TBI can be classified into focal injury, associated with cerebral contusion, and diffuse injury, a widespread injury pathology. TBI results in a host of pathological alterations and may lead to a transient blood-brain-barrier (BBB) breakdown. Although the BBB dysfunction after TBI may provide a window for therapeutic delivery, the current drug delivery approaches remains largely inefficient due to rapid clearance, inactivation and degradation. One potential strategy to address the current therapeutic limitations is to employ nanoparticle (NP)-based technology to archive greater efficacy and reduced clearance compared to standard drug administration. However, NP application for TBI is challenging not only due to the transient temporal resolution of the BBB breakdown, but also due to the heterogeneous (focal/diffuse) aspect of the disease itself. Furthermore, recent literature suggests sex of the animal influences neuroinflammation/outcome after TBI; yet, the influence of sex on BBB integrity following TBI and subsequent NP delivery has not been previously investigated. The overarching hypothesis for this thesis is that TBI-induced compromised BBB and leaky vasculature will enable delivery of systemically injected NPs to the injury penumbra. This study specifically explored the feasibility and the temporal accumulation of NPs in preclinical mouse models of focal and diffuse TBI. Key findings from these studies include the following. (1) After focal TBI, NPs ranging from 20-500nm exhibited peak accumulation within the injury penumbra acutely (1h) post-injury. (2) A smaller delayed peak of NP accumulation (40nm) was observed sub-acutely (3d) after focal brain injury. (3) Mild diffuse TBI simulated with a mild closed head injury model did not display any measurable NP accumulation after 1h post-injury. (4) In contrast, a moderate diffuse model (fluid percussion injury) demonstrated peak accumulation at 3h post-injury with up to 500 nm size NPs accumulating in cortical tissue. (5) Robust NP accumulation (40nm) was found in female mice compared to the males at 24h and 3d following focal brain injury. Taken together, these results demonstrate the potential for NP delivery at acute and sub-acute time points after TBI by exploiting the compromised BBB. Results also reveal a potential sex dependent component of BBB disruption leading to altered NP accumulation. The applications of this research are far-reaching ranging from theranostic delivery to personalized NP delivery for effective therapeutic outcome.
ContributorsBharadwaj, Vimala Nagabhushana (Author) / Stabenfeldt, Sarah E (Thesis advisor) / Kodibagkar, Vikram D (Thesis advisor) / Kleim, Jeffrey (Committee member) / Tian, Yanqing (Committee member) / Lifshitz, Jonathan (Committee member) / Anderson, Trent R (Committee member) / Arizona State University (Publisher)
Created2018
Description
A series of mitochondria targeting probes was synthesized for the purpose of exploring the feasibility of a mitochondria targeting fluorescent sensor. Of the probes, the probe with a two carbon spacer showed the best co-localization from staining with the established MitoTracker Red® FM, indicating a potential development of the probe into mitochondria targeting sensor. However, cytotoxicity was observed for the probe with a six carbon spacer. Three additional mitochondria targeting fluorescent probes of longer spacer groups were synthesized, but the cytotoxicity was not observed to be as high as that of the probe with a two carbon spacer. The cytotoxicity was characterized to be that of caspase dependent cell death. To screen for a possible effect on apoptosis due to the mitochondrial probe, three fluorescent fusion proteins binding the anti-apoptotic proteins were designed and expressed. Each purified fusion protein was then incubated with the cytotoxic mitochondrial probe, and the mixture was isolated by running an affinity column. The fluorescence analysis of eluted fractions showed preliminary data of possible interaction between the protein and the mitochondrial probe.
ContributorsLee, Fred (Author) / Meldrum, Deirdre R. (Thesis director) / Tian, Yanqing (Committee member) / Zhang, Liqiang (Committee member) / Barrett, The Honors College (Contributor) / Chemical Engineering Program (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-12
Description
An in-depth analysis of Homeview Realty and Homeview Financial was conducted. A marketing plan for both companies was prepared for this project. Homeview Realty and Homeview Financial are in the midst of dynamic industries. The landscape of doing business in the real estate and mortgage industries are constantly changing and evolving. Thus, it is vital for Homeview Realty and Homeview Financial to constantly be knowledgeable in these fields. With this dynamic aspect, the landscape for marketing has also changed; it became digital in nature. Thus, it is important to analyze Homeview Realty and Homeview Financial currently and create a live marketing plan that can be updated when needed. With a marketing plan in hand, Homeview will be able understand its business model, mission, goals, and objectives and in turn be able to create marketing campaigns compatible with the companies objectives and strategic directions.
ContributorsCrowley, Rachel Victoria (Author) / Ostrom, Lonnie (Thesis director) / Montoya, Detra (Committee member) / Mirshak, Paul (Committee member) / Barrett, The Honors College (Contributor) / Department of Marketing (Contributor) / Department of Supply Chain Management (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Department of Finance (Contributor) / School of Accountancy (Contributor)
Created2014-05
Description
Repeating tiles made of DNA were used to try to form an indefinitely large structure. Both the tiles and structure were 2D. Two different patterns were tested, one corrugated and one not. Corrugation means that the tiles alternated between facing up and facing down, canceling out any curvature to the tile and creating a slightly corrugated but largely 2D pattern. Annealing methods were also experimented with. Annealing the structure in two, separate steps as opposed to one was tested. Another experiment was comparing cyclic versus linear annealing. A linear decrease in temperatures defines the linear annealing, and a cyclic method involved a linear drop to a certain temperature, followed by a slight increase in temperature and cooling back down again. This cycle is done several times before it continues linear cool down. It was seen that both corrugated and non-corrugated structures could be made. In both cases tiles that make up a larger section of the overall pattern were more successful. This is especially important for the non-corrugated pattern. Linear and 2step annealing methods seem to yield the best results.
ContributorsHunt, Ashley Elizabeth (Author) / Yan, Liu (Thesis director) / Yan, Hao (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05
Description
Lung cancer is the leading cause of cancer-related deaths in the US. Low-dose computed tomography (LDCT) scans are speculated to reduce lung cancer mortality. However LDCT scans impose multiple risks including false-negative results, false- positive results, overdiagnosis, and cancer due to repeated exposure to radiation. Immunosignaturing is a new method proposed to screen and detect lung cancer, eliminating the risks associated with LDCT scans. Known and blinded primary blood sera from participants with lung cancer and no cancer were run on peptide microarrays and analyzed. Immunosignatures for each known sample collectively indicated 120 peptides unique to lung cancer and non-cancer participants. These 120 peptides were used to determine the status of the blinded samples. Verification of the results from Vanderbilt is pending.
ContributorsNguyen, Geneva Trieu (Author) / Woodbury, Neal (Thesis director) / Zhao, Zhan-Gong (Committee member) / Stafford, Phillip (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Department of Psychology (Contributor)
Created2015-05
Description
The purpose of this project was to identify proteins associated with the migration and invasion of non-transformed MCF10A mammary epithelial cells with ectopically expressed missense mutations in p53. Because of the prevalence of TP53 missense mutations in basal-like and triple-negative breast cancer tumors, understanding the effect of TP53 mutations on the phenotypic expression of human mammary epithelial cells may offer new therapeutic targets for those currently lacking in treatment options. As such, MCF10A mammary epithelial cells ectopically overexpressing structural mutations (G245S, H179R, R175H, Y163C, Y220C, and Y234C) and DNA-binding mutations (R248Q, R248W, R273C, and R273H) in the DNA-binding domain were selected for use in this project. Overexpression of p53 in the mutant cell lines was confirmed by western blot and q-PCR analysis targeting the V5 epitope tag present in the pLenti4 vector used to transduce TP53 into the mutant cell lines. Characterization of the invasion and migration phenotypes resulting from the overexpression of p53 in the mutant cell lines was achieved using transwell invasion and migration assays with Boyden chambers. Statistical analysis showed that three cell lines—DNA-contact mutants R248W and R273C and structural mutant Y220C—were consistently more migratory and invasive and demonstrated a relationship between the migration and invasion properties of the mutant cell lines. Two families of proteins were then explored: those involved in the Epithelial-Mesenchymal Transition (EMT) and matrix metalloproteinases (MMPs). Results of q-PCR and immunofluorescence analysis of epithelial marker E-cadherin and mesenchymal proteins Slug and Vimentin did not show a clear relationship between mRNA and protein expression levels with the migration and invasiveness phenotypes observed in the transwell studies. Results of western blotting, q-PCR, and zymography of MMP-2 and MMP-9 also did not show any consistent results indicating a definite relationship between MMPs and the overall invasiveness of the cells. Finally, two drugs were tested as possible treatments inhibiting invasiveness: ebselen and SBI-183. These drugs were tested on only the most invasive of the MCF10A p53 mutant cell lines (R248W, R273C, and Y220C). Results of invasion assay following 30 μM treatment with ebselen and SBI-183 showed that ebselen does not inhibit invasiveness; SBI-183, however, did inhibit invasiveness in all three cell lines tested. As such, SBI-183 will be an important compound to study in the future as a treatment that could potentially serve to benefit triple-negative or basal-like breast cancer patients who currently lack therapeutic treatment options.
ContributorsZhang, Kathie Q (Author) / LaBaer, Joshua (Thesis director) / Anderson, Karen (Committee member) / Gonzalez, Laura (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05
Description
This study assessed the effects of running an eating prevention program on body image satisfaction/behavior and the leadership skills of collegiate women. The sample included a group of 43 undergraduate women who voluntarily chose to become peer-educators in the eating prevention program called the Body Project. Self-report questionnaires evaluating both the preoccupation with personal body image and general leadership skills were distributed and collected electronically. The results were analyzed to determine that being a peer leader in the Body project did not increase eating disorder symptoms but actually decreased the symptoms. It was also determined that being a peer educator had no effect on leadership skills. Therefore, being a peer leader is beneficial for reducing eating disorder symptoms, but not for advancing leadership skills.
ContributorsCamiliere, Taylor Marie (Author) / Perez, Marisol (Thesis director) / Cavanaugh Toft, Carolyn (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Department of Psychology (Contributor)
Created2015-05
Description
Smartphone-based healthcare. It's becoming more real as technology advances, adding value to healthcare and opening the doors to more personalized medicine. The Medical Pal is a smartphone application that can track symptoms and analyze trends in the severity of those symptoms, alerting healthcare providers when there is a significant increase in the symptom severity. This is especially directed to the palliative patient, whose care is focused on managing symptoms and providing comfort. The HIPAA-compliant server used for the smartphone application was Catalyze.io and 40 Mayo Clinic Arizona palliative patients were surveyed on their smartphone usage to test the acceptance of this app in a clinical setting. A trial involving 9 simulated patients was conducted over a two week period to test the functionality of the app. A majority of surveyed patients (85%) expressed favor for the idea of a mobile ESAS, and the app was functioning, with the capability of displaying patient data on a healthcare provider's account. This project is intentionally a door-opener to an open field of opportunity for mobile health, symptom observation, and improvements in healthcare delivery.
ContributorsDao, Lelan Diep (Author) / Cortese, Denis (Thesis director) / Lipinski, Christopher (Committee member) / Fitch, Tom (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05
Description
The field of art conservation has evolved parallel to scientific advancements and in response to changing social conditions. Methods have expanded from dusting the surface of a work to bombarding an image with x-rays in an effort to fulfill the ultimate goal of restoration: to return a piece of art to the state originally created by the artist. The process has become much easier and more complex with the introduction of analytical equipment that shifted the focus of the field away from maintenance towards academic study. This work illustrates the changes the field and demonstrates the application of scientific techniques to specific works.
ContributorsSanders, Hailey Jane (Author) / Fahlman, Besty (Thesis director) / Codell, Julie (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05