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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
231

Monitoring for Enhanced Gas and Liquids Recovery from a CO2 'Huff-and-Puff' Injection Test in a Horizontal Chattanooga Shale Well

Louk, Andrew Kyle 01 July 2015 (has links)
Permanently sequestering carbon dioxide (CO2) in gas-bearing shale formations is beneficial in that it can mitigate greenhouse gas emissions as well as enhance gas recovery in production wells. This is possible due to the sorption properties of the organic material within shales and their greater affinity for CO2 over methane. The phenomenon of preferentially adsorbing CO2 while desorbing methane has been proven in coalbed reservoirs successfully, and is feasible for shale formations. The objective of this thesis is to explore the potential for enhanced gas recovery from gas-bearing shale formations by injecting CO2 into a targeted shale formation. With the advancement of technologies in horizontal drilling combined with hydraulic fracturing, shale gas has become a significant source of energy throughout the United States. With over 6,000 trillion cubic feet (Tcf) of theoretical gas-in-place, Appalachia has proven a major basin for gas production from organic shales. With its extensive shale reserves and lack of conventional reservoirs typically used for CO2 storage, Appalachia's unconventional reservoirs are favorable candidates for CO2 storage with enhanced gas recovery. Enhancing gas recovery not only increases reserves, but extends the life of mature wells and fields throughout the basin. As part of this research, 510 tons of CO2 were successfully injected into a horizontal production well completed in the Chattanooga shale formation, a late Devonian shale, in Morgan County, Tennessee. An extensive monitoring program was implemented during the pre-injection baseline, injection, soaking, and flowback phases of the test. Multiple fluorinated tracers were used to monitor for potential CO2 breakthrough at offset production wells and to help account for the CO2 once the well was flowed back. Results from this test, once the well was put back into normal production state, confirm the injectivity and storage potential of CO2 in shale formations, as well as an increase in gas production rate and quality of gas produced. / Master of Science
232

Nitrogen release, tree uptake, and ecosystem retention in a mid-rotation loblolly pine plantation following fertilization with 15N-enriched enhanced efficiency fertilizers

Werner, Amy 11 June 2013 (has links)
Nitrogen is the most frequently limiting nutrient in southern pine plantations.  Previous studies found that only 10 to 25% of applied urea fertilizer N is taken up by trees.  Enhanced efficiency fertilizers could increase tree uptake efficiency by controlling the release of N and/or stabilize N.  Three enhanced efficiency fertilizers were selected as a representation of fertilizers that could be used in forestry: 1) NBPT treated urea (NBPT urea), 2) polymer coated urea (PC urea), and 3) monoammonium phosphate coated NBPT treated urea (MC NBPT urea). Urea, MC NBPT urea, and NBPT urea fertilizer treatments showed an extractable NH4+ spike 14 days after fertilization while the polymer coated urea showed a spike in NH4+ 49 days after fertilization. Total ecosystem recovery of fertilizer in each treatment was; MC NBPT urea, 51.29 g N; NBPT urea, 48.87 g N; urea, 45.09 g N; and PC urea, 31.30 g N which represents 78.7%, 74.7%, 72.1%, and 47.6% respectively of the total N applied.  For the MC NBPT urea, NBPT urea, and PC urea treatments the largest sinks for N were the forest floor and mineral soil.  The largest sink for fertilizer applied N in the urea treatment was in the tree.  The 2011 foliage cohort was the largest sinks for fertilizer N recovered by the tree.  N volatilization was around 20% for all fertilizer treatments except polymer coated fertilizer, which was 1.1%.  Urea preformed the same as the soluble enhanced efficiency fertilizers and better than the PC urea fertilizer.  The results emphasize the importance of climatic conditions on fertilizer release and effectiveness. / Master of Science
233

A City Stadium in a Stadium City

Ritchie, Colin Bradley 05 June 2018 (has links)
This thesis creates an improved fan experience creating the heart of a city through a design that the community can call home throughout the year. It extends the design of sports stadiums to include the fan experiences throughout the interior and the community experiences throughout the exterior to merge. By combining the stadium and city into experiential layering, the architectural decisions to form pedestrian streets and programmatic features can enhance the fan experiences and community experiences to merge through materials, structures, and spaces. The thesis creates an iconic entertainment hub that allows these experiences to expand into the city of Chicago, Illinois, USA. / Master of Architecture
234

Uncertainty`s effect on test-enhanced learning

Brännäs, Lisa January 2019 (has links)
The purpose of this bachelor thesis was to evaluate the impact of uncertainty on test-enhanced learning. A within-groups experiment was designed to compare uncertainty under three study and retrieval conditions carried out in a single session; study-restudy-restudy, study-test-test with feedback and study-test-test without feedback. In this first session, 105 Swedish-Swahili word-pairs were presented to each participant. Participants then made judgments of learning on the word pairs. Subsequently, participants either re-studied the word-pair, were tested on the pair via cued recall and given feedback or tested without feedback. Participants were then tested in cued recall tests on the word pairs two hours and one week after the learning session, respectively. Ten participants were tested during three sessions which were administered on a web-based platform. The result indicate that no test-effect was found, and participants scored highest in the restudy condition at the cued recall tests. Judgment of learning score was a significant predictor of final cued recall scores on the final test. / I den här Kandidat uppsatsen görs ett försök att utvärdera hur känslan av osäkerhet att påverka test-effekten. Ett experiment designades för att utvärdera tre olika conditions, en studie-studie-studie, en studie-test-test med feedback och enstudie-test-test utan feedbacki en experimentell inom grupp design. Deltagarna ombads mellan delarna skatta sin skala av säkerhet på att kunna göra en framgångsrik återkallning efter en vecka. Allt deltagande var web baserat. Tio deltagare deltog i studien och de testades under tre olika tillfällen. Första tillfället med tre olika conditions, sedan med två uppföljande test tillfällen. Den första efter två timmar och ett avslutande test efter en vecka. Deltagarna testades på 105 ordpar Swahili-Svenska. Resultatet visar att ingen test-effekt uppnåddes och deltagarna nådde högst resultat på upprepad studie alternativet. Själv skattningen på deltagarnas skala av säkerhet var signifikant som indikator på korrekt återkallning efter en vecka i de två upprepad test delarna.
235

Enhancement of tomato resistance to Tuta absoluta by the expression of two barley proteinase inhibitors

Hamza, Rim 14 December 2017 (has links)
Evolution has provided vast genetic diversity, enabling plants to surmount many biotic pressures. Plants have evolved various morphological and biochemical adaptations to cope with herbivores attacks. Despite that, yearly, around 40 % of worldwide crop production is lost due to pests and pathogens, with 13 % due to insects. Tuta absoluta has become a major pest threatening tomato crops worldwide and without the appropriated management it can cause production losses between 80 to 100 %. To cope with this threat, we need to strengthen plant defense arsenals. The incorporation to plants of defensive genes like proteinase inhibitors by means of genetic engineering is a promising alternative. In the first chapter of this work we investigated the inhibitory activity of two trypsin inhibitors from barley; BTI-CMe and BTI-CMc. Besides, we succeeded to increase the BTI-CMc in vitro inhibitory activity by introducing a single mutation in its putative reactive site. In the second chapter, we investigated the in vivo effect of (a serine proteinase inhibitor) BTI-CMe and a (cysteine proteinase inhibitor) Hv-CPI2 isolated from barley on Tuta absoluta and we examined the effect of their expression on the tomato defensive response. We found that larvae fed on the double transgenic plants showed a notable reduction in weight. Moreover, only 56% of the larvae reached the adult stage. The emerged adults showed wings deformities and reduced fertility. We also investigated the effect of proteinase inhibitors ingestion on the insect digestive enzymes. Our results showed a decrease in larval trypsin activity. Proteinase inhibitors had no harmful effect on Nesidiocoris tenuis; a predator of Tuta absoluta, despite transgenic tomato plants attracted the mirid. We investigated whether or not plant defensive mechanisms were activated in the transgenic tomato plants and found that, interestingly, the expression of the barley cysteine proteinase inhibitor promoted plant defense, inducing the tomato endogenous wound inducible proteinase inhibitor 2 (Pin2) gene. Moreover, glandular trichomes production was increased and the emission of volatile organic compounds was altered. Our results demonstrate the usefulness of the co-expression of different proteinase inhibitors for the enhancement of plant resistance to pests. / La evolución ha proporcionado una gran diversidad genética, permitiendo a las plantas superar muchas presiones bióticas. Las plantas han desarrollado diversas adaptaciones morfológicas y bioquímicas para hacer frente a los ataques de los herbívoros. A pesar de ello, anualmente, alrededor del 40 % de la producción mundial de cultivos se pierde debido a plagas y patógenos, siendo un 13 % debido a insectos. Tuta absoluta se ha convertido en una de las principales plagas que amenazan los cultivos de tomate en todo el mundo y sin la gestión adecuada puede causar pérdidas de producción entre el 80 y el 100 %. Para hacer frente a esta amenaza, necesitamos fortalecer los arsenales de defensa de las plantas. La incorporación a las plantas, mediante ingeniería genética, de genes defensivos como los inhibidores de proteinasas es una alternativa prometedora. En el primer capítulo de este trabajo se investigó la actividad inhibitoria de dos inhibidores de tripsina procedentes de cebada; BTI-CMe y BTI-CMc. Además, se logró aumentar la actividad inhibitoria in vitro de BTI-CMc mediante la introducción de una única mutación en su putativo centro reactivo. En el segundo capítulo, se investigó el efecto in vivo de un inhibidor de serin proteinasa (BTI-CMe) y un inhibidor de cisteín proteinasa (Hv-CPI2) aislado de cebada en Tuta absoluta y se examinó el efecto de su expresión en la respuesta defensiva del tomate. Se encontró que las larvas alimentadas con las plantas transgénicas dobles mostraron una notable reducción de peso. Además, sólo el 56 % de las larvas alcanzó la etapa adulta. Los adultos emergentes mostraron deformidades de las alas y reducción de la fertilidad. También se investigó el efecto de la ingesta de inhibidores de proteinasa en las enzimas digestivas de los insectos. Nuestros resultados mostraron una disminución en la actividad tripsina larvaria. Los inhibidores de proteinasas no tuvieron efectos nocivos sobre Nesidiocoris tenuis(depredador de Tuta absoluta) a pesar de que las plantas transgénicas de tomate atrajeron al mirido. Se investigó si los mecanismos defensivos de las plantas se activaban en las plantas de tomate transgénico y se encontró que, curiosamente, la expresión de la cistatina de cebada promovía la defensa de la planta, induciendo el gen del inhibidor de proteasa 2 endógeno del tomate, inducible por herida (Pin2). Además, aumentó la producción de tricomas glandulares y se alteró la emisión de compuestos orgánicos volátiles. Nuestros resultados demuestran la utilidad de la co-expresión de diferentes inhibidores de proteinasas para el aumento de la resistencia de las plantas a plagas. / L'evolució ha proporcionat una gran diversitat genètica, permetent a les plantes superar moltes pressions biòtiques. Les plantes han desenvolupat diverses adaptacions morfològiques i bioquímiques per fer front als atacs dels herbívors. Tot i això, anualment, al voltant del 40 % de la producció mundial de cultius es perd a causa de plagues i patògens, amb un 13 % a causa de insectes. Tuta absoluta s'ha convertit en una de les principals plagues que amenacen els cultius de tomaca a tot el món i sense la gestió adequada pot causar pèrdues de producció entre el 80 i el 100 %. Per fer front a aquesta amenaça, necessitem enfortir els arsenals de defensa de les plantes. La incorporació a les plantes de gens defensius com els inhibidors de proteïnases per mitjà de l'enginyeria genètica és una alternativa prometedora. En el primer capítol d'aquest treball es va investigar l'activitat inhibitòria de dos inhibidors de tripsina aïllats a partir d'ordi; BTI-CMe i BTI-CMC. A més, es va aconseguir augmentar l'activitat inhibitòria in vitro de BTI-CMC mitjançant la introducció d'una única mutació en el seu lloc reactiu putatiu. En el segon capítol, es va investigar l'efecte in vivo d'un inhibidor de serin proteinasa (BTI-CMe) i un inhibidor de cisteïn proteinasa (Hv-CPI2) aïllats d'ordi en Tuta absoluta i es va examinar l'efecte de la seva expressió en la resposta defensiva del tomaca. Es va trobar que les larves alimentades amb les plantes transgèniques dobles van mostrar una notable reducció de pes. A més, només el 56 % de les larves va aconseguir l'etapa adulta. Els adults emergents van mostrar deformitats de les ales i reducció de la fertilitat. També es va investigar l'efecte de la ingesta d'inhibidors de proteinasa en els enzims digestius dels insectes. Els nostres resultats van mostrar una disminució en l'activitat tripsina larvària. Els inhibidors de proteïnases no van tenir efectes nocius sobre Nesidiocoris tenuis, un depredador de Tuta absoluta, tot i les plantes transgèniques de tomaca van atreure al mirid. Es va investigar si els mecanismes defensius de les plantes s'activaven a les plantes de tomaca transgènic i es va trobar que, curiosament, l'expressió de cistatina d'ordi promovia la defensa de la planta, induint el gen de l'inhibidor de proteasa 2 endogen de la tomaca, induïble per ferida (Pin2). A més, va augmentar la producció de tricomes glandulars i es va alterar l'emissió de compostos orgànics volàtils. Els nostres resultats demostren la utilitat de la co-expressió de diferents inhibidors de proteïnases per a l'augment de la resistència de les plantes a plagues. / Hamza, R. (2017). Enhancement of tomato resistance to Tuta absoluta by the expression of two barley proteinase inhibitors [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/92723
236

Effects of Metallic Nanoalloys on Dye Fluorescence

Dorcéna, Cassandre Jenny 15 October 2007 (has links)
Metallic nanoparticles (NPs) are exploited for their ability to interact with organic compounds and to increase significantly the fluorescence intensity and the photostability of many fluorescent dye molecules. Metal enhanced fluorescence (MEF) is therefore widely investigated for biosensing applications. When used in immunoassays, silver island films (SIFs) could augment the fluorescence intensity of fluorescein by a factor of seventeen; SIFs were also able to double or triple the emission intensity of cyanine dyes which are commonly used in (deoxyribonucleic acid) DNA microarrays. The emission intensity of indocyanine green — widely used as a contrast agent in medical imaging — was about twenty times higher in the proximity of SIFs. This enhancement phenomenon — due to the surface plasmon polaritons associated with the metallic NPs — can be explained by energy transfer from the metal NPs to the fluorescent dye molecules or by a modified local electromagnetic field experienced by the fluorophores in the vicinity of metal surfaces. Our research focused on the optical characterization of colloidal gold-silver alloy NPs containing different ratios of gold and silver (Au<sub>1.00</sub>-Ag<sub>0.00</sub>, Au<sub>0.75</sub>-Ag<sub>0.25</sub>, Au<sub>0.50</sub>-Ag<sub>0.50</sub>, and Au<sub>0.25</sub>-Ag<sub>0.75</sub>), as well as their interaction with three fluorophores: rose bengal, rhodamine B, and fluorescein sodium. Depending upon the dye quantum yield and its concentration in solution, enhancement or quenching of fluorescence was obtained. Thus, a three to five times increase in fluorescence intensity was observed in a 2.0 mM solution of rose bengal with all nanoalloys, a slight enhancement of fluorescence (1.2 – 1.6 times) was noticed in a 0.13 mM solution of rhodamine B with all four types of NPs, and fluorescence quenching occurred in all the fluorescein-NP solutions regardless of the dye concentration. / Master of Science
237

An evaluation of students' and lecturers' use of technologies: an engineering case study.

Sheriff, Ray E. 17 August 2012 (has links)
Yes / The introduction in the early 1990s of the world wide web was a significant factor in the creation of a global information society, allowing new possibilities to work, entertain and communicate, from home, at the workplace or on the move. In recent years, there have been significant advances in information technology (IT), while a new generation of applications that are able to harness the power of the world wide web has been introduced under the banner of Web 2.0. The increased capabilities of IT and the nature of Web 2.0 applications have attracted interest from the academic community as a means of enhancing the delivery of higher education. This paper considers the implications of introducing technology into the higher education sector from the perspectives of academic staff and students, with particular emphasis on the use of technology and Web 2.0 applications, and the relationship between technology and teaching and learning.
238

Evaluation of an advanced fine coal cleaning circuit

Venkatraman, Parthasarathy 06 June 2008 (has links)
A new fine-coal cleaning circuit, with potential near-term applications, has been evaluated for treating fine coal (i.e., 28 mesh x 0). This circuit combines a surface-based separator known as Microcel™ column flotation with an enhanced gravity separator known as the Multi-Gravity Separator (MGS). The synergistic effect of combining both processes in a single circuit resulted in improved ash and pyritic sulfur rejection with minimal losses in energy recovery. In addition, technical and economic analyses of this processing scheme suggest it compares favorably with existing post-combustion desulfurization techniques. A detailed study of the MGS included the development of a model based on fundamental principles of fluid mechanics and mineral processing. The theoretical analyses identified drum speed as the most important MGS operating parameter. To validate these findings, a detailed parametric test program was conducted using coal samples from the Pittsburgh No. 8 and Illinois No. 6 seams. A statistical analysis of the test data also showed that drum speed was the most important variable in controlling the performance of the MGS. The other controlling parameters, i.e., feed percent solids, feed rate and wash-water addition rate, were found to be of lesser importance. The experimental test results were found to be in good agreement with the theoretical predictions obtained using the model. / Ph. D.
239

Maximizing Local Access to Therapeutic Deliveries in Glioblastoma: Evaluating the utility and mechanisms of potential adverse events for minimally invasive diagnostic two novel therapeutic techniques for brain tumors

Kani Kani, Yukitaka Steve 29 September 2022 (has links)
Glioblastoma (GBM) is the most common adult malignant glioma (MG) variant, and the median survival of persons with GBM is about 2 years, even with aggressive treatments. Dogs and humans are the only species in which brain tumors commonly develop spontaneously, with an estimated post-mortem frequency of primary brain tumors approximating 2% in both species. Gliomas represent about 35% of all canine primary brain tumors, with high-grade oligodendroglioma and astrocytoma phenotypes accounting for about 70% of all canine gliomas. Canine gliomas are also treated using surgical, radiotherapeutic, and chemotherapeutic regimens similar to those used in humans. The efficacy of these therapies in dogs with MG is also poor, with median survival times ranging from 3-8 months, which closely mirrors the dismal prognosis associated with human GBM. Thus, treatment of MG represents a current and critically unmet need in both human and veterinary medicine. In this work, we investigate minimally invasive methods to access the brain for the purposes of ultimately improving the diagnosis and treatment of malignant brain tumors. Chapter 1 reviews the current clinical challenges associated with the treatment of GBM, highlights the value of using the spontaneous canine glioma model in translational brain tumor studies, and introduces High-Frequency Irreversible Electroporation (H-FIRE) and Convection Enhanced Delivery (CED), which are two novel treatment platforms for GBM being developed in our lab. In Chapter 2, we demonstrate that definitive diagnosis of brain tumors, a critical first step in patient management, can be safely and accurately performed in dogs with naturally occurring brain tumors using a stereotactic brain biopsy procedure. Chapter 3 evaluates the in vivo safety and biocompatibility of fiberoptic microneedle devices, a major technical component of our convection-enhanced thermotherapy catheter system (CETCS), chronically implanted in the rodent brain. The CETCS is a novel technology being developed and used in our laboratory to improve the delivery of drugs to brain tumors using CED. This study provides regulatory data fundamental to the commercialization of the CETCS device for brain tumor treatment by illustrating that the device did not cause clinically significant neurological complications and resulted in mild pathologic changes in brain tissue, similar to other types of devices designed and approved for use in the brain. In Chapters 4 and 5 we explore possible bystander effects of H-FIRE on glutamate metabolism in the brain. H-FIRE has been shown to be able to both ablate brain tumors as well as disrupt the blood-brain barrier (BBB). As these therapeutic effects of H-FIRE are dependent on applying electrical fields to the tissue that either reversibly permeabilize the cell membrane, allowing treated cells to survive, or permanently disrupt the structure of the cell membrane, causing cell death, we hypothesized that altering the membrane permeability with HFIRE would increase the extracellular glutamate concentrations and contribute to excitotoxic brain tissue damage. Chapters 4 used in vitro brain cell culture systems and in vivo experiments in normal and glioma-bearing rat brains to determine if glutamate release in the brain occurs as a bystander effect following H-FIRE treatment, identify concentrations of glutamate necessary to induce death of cells or BBB disruption, and characterize glutamatergic gene expression in response to H-FIRE treatment. Chapter 5 describes the use of magnetic resonance spectroscopic and spatial transcriptomic methods to further quantify the in vivo effects of H-FIRE treatment on glutamate release and metabolism in dogs with spontaneous brain tumors. The in vitro results indicated that the magnitude of glutamate release following H-FIRE is insufficient to induce cytotoxicity in normal or neoplastic brain cell lines, and also did not increase the permeability of the BBB. In our in vivo model systems, we documented significant, transient post-H-FIRE increases in glutamate to concentrations previously associated with excitotoxicty, with upregulation of the expression of genes involved with ionotropic and metabotropic glutamatergic receptor signaling. A contemporaneous upregulation of genes associated with glutamate uptake and recycling were also noted, indicating an adaptive, protective response to the glutamate release. Our work summarily demonstrates that the diagnosis and potential treatment of malignant brain tumors can be achieved through the use of minimally invasive techniques that provide local access to brain tissue. While complications will always be possible anytime the brain is manipulated surgically, and further investigations are required to characterize the spectrum and mechanisms of adverse events that can occur following CETCS CED and H-FIRE treatment, our results support the continued development of these novel therapeutic platforms for the treatment of GBM. / Doctor of Philosophy / Glioblastoma (GBM) is the most common adult malignant glioma (MG) variant, and the median survival of persons with GBM is about 2 years, even with aggressive treatments. Dogs and humans are the only species in which brain tumors commonly develop spontaneously, with an estimated post-mortem frequency of primary brain tumors approximating 2% in both species. Gliomas represent about 35% of all canine primary brain tumors, with high-grade oligodendroglioma and astrocytoma phenotypes accounting for about 70% of all canine gliomas. Canine gliomas are also treated using surgical, radiotherapeutic, and chemotherapeutic regimens similar to those used in humans. The efficacy of these therapies in dogs with MG is also poor, with median survival times ranging from 3-8 months, which closely mirrors the dismal prognosis associated with human GBM. Thus, treatment of MG represents a current and critically unmet need in both human and veterinary medicine. In this work, we investigate minimally invasive methods to access the brain for the purposes of ultimately improving the diagnosis and treatment of malignant brain tumors. Chapter 1 reviews the current clinical challenges associated with the treatment of GBM, highlights the value of using the spontaneous canine glioma model in translational brain tumor studies, and introduces High-Frequency Irreversible Electroporation (H-FIRE) and Convection Enhanced Delivery (CED), which are two novel treatment platforms for GBM being developed in our lab. In Chapter 2, we demonstrate that definitive diagnosis of brain tumors, a critical first step in patient management, can be safely and accurately performed in dogs with naturally occurring brain tumors using a stereotactic brain biopsy procedure. Chapter 3 evaluates the in vivo safety and biocompatibility of fiberoptic microneedle devices, a major technical component of our convection-enhanced thermotherapy catheter system (CETCS), chronically implanted in the rodent brain. The CETCS is a novel technology being developed and used in our laboratory to improve the delivery of drugs to brain tumors using CED. This study provides regulatory data fundamental to the commercialization of the CETCS device for brain tumor treatment by illustrating that the device did not cause clinically significant neurological complications and resulted in mild pathologic changes in brain tissue, similar to other types of devices designed and approved for use in the brain. In Chapters 4 and 5 we explore possible bystander effects of H-FIRE on glutamate metabolism in the brain. H-FIRE has been shown to be able to both ablate brain tumors as well as disrupt the blood-brain barrier (BBB). As these therapeutic effects of H-FIRE are dependent on applying electrical fields to the tissue that either reversibly permeabilize the cell membrane, allowing treated cells to survive, or permanently disrupt the structure of the cell membrane, causing cell death, we hypothesized that altering the membrane permeability with HFIRE would increase the extracellular glutamate concentrations and contribute to excitotoxic brain tissue damage. Chapters 4 used in vitro brain cell culture systems and in vivo experiments in normal and glioma-bearing rat brains to determine if glutamate release in the brain occurs as a bystander effect following H-FIRE treatment, identify concentrations of glutamate necessary to induce death of cells or BBB disruption, and characterize glutamatergic gene expression in response to H-FIRE treatment. Chapter 5 describes the use of magnetic resonance spectroscopic and spatial transcriptomic methods to further quantify the in vivo effects of H-FIRE treatment on glutamate release and metabolism in dogs with spontaneous brain tumors. The in vitro results indicated that the magnitude of glutamate release following H-FIRE is insufficient to induce cytotoxicity in normal or neoplastic brain cell lines, and also did not increase the permeability of the BBB. In our in vivo model systems, we documented significant, transient post-H-FIRE increases in glutamate to concentrations previously associated with excitotoxicty, with upregulation of the expression of genes involved with ionotropic and metabotropic glutamatergic receptor signaling. A contemporaneous upregulation of genes associated with glutamate uptake and recycling were also noted, indicating an adaptive, protective response to the glutamate release. Our work summarily demonstrates that the diagnosis and potential treatment of malignant brain tumors can be achieved through the use of minimally invasive techniques that provide local access to brain tissue. While complications will always be possible anytime the brain is manipulated surgically, and further investigations are required to characterize the spectrum and mechanisms of adverse events that can occur following CETCS CED and H-FIRE treatment, our results support the continued development of these novel therapeutic platforms for the treatment of GBM.
240

Environmental Analysis at the Nanoscale: From Sensor Development to Full Scale Data Processing

Willner, Marjorie Rose 26 April 2018 (has links)
Raman spectroscopy is an extremely versatile technique with molecular sensitivity and fingerprint specificity. However, the translation of this tool into a deployable technology has been stymied by irreproducibility in sample preparation and the lack of complex data analysis tools. In this dissertation, a droplet microfluidic platform was prototyped to address both sample-to-sample variation and to introduce a level of quantitation to surface enhanced Raman spectroscopy (SERS). Shifting the SERS workflow from a cell-to-cell mapping routine to the mapping of tens to hundreds of cells demanded the development of an automated processing tool to perform basic SERS analyses such as baseline correction, peak feature selection, and SERS map generation. The analysis tool was subsequently expanded for use with a multitude of diverse SERS applications. Specifically, a two-dimensional SERS assay for the detection of sialic acid residues on the cell membrane was translated into a live cell assay by utilizing a droplet microfluidic device. Combining single-cell encapsulation with a chamber array to hold and immobilize droplets allowed for the interrogation of hundreds of droplets. Our novel application of computer vision algorithms to SERS maps revealed that sialic sugars on cancer cell membranes are found in small clusters, or islands, and that these islands typically occupy less than 30% of the cell surface area. Employing an opportunistic mindset for the application of the data processing platform, a number of smaller projects were pursued. Biodegradable aliphatic-aromatic copolyesters with varying aromatic content were characterized using Raman spectroscopy and principal component analysis (PCA). The six different samples could successfully be distinguished from one another and the tool was able to identify spectral feature changes resulting from an increasing number of aryl esters. Uniquely, PCA was performed on the 3,125 spectra collected from each sample to investigate point-to-point heterogeneities. A third set of projects evaluated the ability of the data processing tool to calculate spectral ratios in an automated fashion and were exploited for use with nano-pH probes and Rayleigh hot-spot normalization. / Ph. D. / How can we understand the dynamic behavior of the cell membrane? Do certain polymeric structures in biodegradable plastic favor bacterial growth and subsequent degradation? To answer these and other intriguing scientific questions, techniques and technologies must be borrowed from a diverse array of fields and combined with fundamental understanding to create innovative solutions. In this dissertation, a two-dimensional surface enhanced Raman spectroscopy (SERS) assay was translated into a live cell assay by utilizing a droplet microfluidic device. Combining single-cell encapsulation with a chamber array to hold and immobilize droplets allowed for the interrogation of hundreds of droplets. Shifting the SERS workflow from a manual cell-to-cell mapping routine to the mapping of tens to hundreds of cells demanded the development of an automated processing tool to perform basic SERS analyses such as baseline correction, peak feature selection, and SERS map generation. Our novel application of computer vision algorithms to SERS maps was able to reveal that sialic sugars on cancer cell membranes are found in small clusters, or islands, and that these islands typically occupy less than 30% of the cell surface area. With an opportunistic mindset, several smaller projects that combine Raman and SERS with extensive data analysis were also pursued. Biodegradable plastics of varying content were studied with Raman spectroscopy. The aliphatic and aromatic polymeric units within these plastics both contain esters, but it is hypothesized that enzymatic hydrolysis occurs at the units asymmetrically. For each of six different samples, five maps were collected, processed using the analysis tool, and then analyzed using a multivariate analysis toolbox. Principal component analysis (PCA) was used to distinguish the polymers and to identify spectral feature changes resulting from an increasing v number of aryl esters. Uniquely, PCA was performed on the 3,125 spectra collected from each sample to investigate point-to-point heterogeneities. A third set of projects evaluated the ability of the data processing tool to calculate spectral ratios in an automated fashion and it was exploited for use with nano-pH probes and Rayleigh hot-spot normalization

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