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(1 - 9 of 9)
- Title
- Deciphering the Role of Adrenergic Hormones in Embryonic Cardiac Calcium Signaling and Metabolism.
- Creator
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Peoples, Jessica, Ebert, Steven, Davidson, Victor, Phanstiel, Otto, Yooseph, Shibu, University of Central Florida
- Abstract / Description
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The adrenergic hormones norepinephrine (NE) and epinephrine (EPI) are critical regulators of mammalian cardiovascular physiology. NE and EPI mediate stress responses to enhance cardiovascular function, however dysregulation of adrenergic signaling leads to heart failure, congenital heart malformations, and sudden cardiac death. Adrenergic hormone-expressing cells were found in the early embryonic heart, and NE has been determined essential for embryonic cardiac development. Despite extensive...
Show moreThe adrenergic hormones norepinephrine (NE) and epinephrine (EPI) are critical regulators of mammalian cardiovascular physiology. NE and EPI mediate stress responses to enhance cardiovascular function, however dysregulation of adrenergic signaling leads to heart failure, congenital heart malformations, and sudden cardiac death. Adrenergic hormone-expressing cells were found in the early embryonic heart, and NE has been determined essential for embryonic cardiac development. Despite extensive work in adults, the regulatory roles and adrenergic targets of these hormones during embryonic cardiac development have not yet been fully determined. Prior transcriptomic studies from our lab showed that expression of signal transduction and metabolic genes in embryos lacking adrenergic hormones were by far the most affected categories of genes. Thus, we hypothesized that adrenergic hormones stimulate early calcium signaling, and are required for sufficient supply of energy substrates for the metabolic shift from anaerobic glycolysis to aerobic respiration during heart development. We utilized the dopamine ?-hydroxylase knock-out (Dbh-/-) mouse model to examine effects of adrenergic-deficiency on calcium signaling and metabolism during heart development. Using calcium-imaging and patch-clamp techniques, we found that calcium transients, voltage-gated calcium channels, and L-type calcium currents in adrenergic-deficient embryonic hearts were not affected relative to controls indicating adrenergic stimulation did not influence early calcium signaling. Metabolomics analyses of adrenergic-deficient hearts revealed disruption in glycolytic and pentose-phosphate pathways as well as reduced activity of respective regulatory enzymes, glyceraldehyde 3-phosphate dehydrogenase and glucose 6-phosphate dehydrogenase indicating compromised glucose metabolism. Addition of pyruvate to embryonic hearts led to significant recovery of ATP concentrations and oxygen consumption rates, thereby supporting the hypothesis that adrenergic-deficient hearts are (")starved(") of metabolic substrates required for transitions from anaerobic glycolysis to aerobic metabolism. Overall, we showed that adrenergic hormones are not necessary for calcium signaling in the embryonic heart, but are essential regulators ensuring sufficient metabolic substrate and boosting enzymatic activities to fuel aerobic metabolism.
Show less - Date Issued
- 2018
- Identifier
- CFE0007233, ucf:52223
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0007233
- Title
- THE ENDOCYTIC PROTEIN NUMB REGULATES APP METABOLISM AND NOTCH SIGNALING: IMPLICATIONS FOR ALZHEIMER'S DISEASE.
- Creator
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Kyriazis, George, Chan, Sic, University of Central Florida
- Abstract / Description
-
Increased production of amyloid beta (A-beta) peptide, via altered proteolytic cleavage of amyloid protein precursor (APP), and abnormalities in neuronal calcium homeostasis play central roles in the pathogenesis of Alzheimer's disease (AD). Notch1, a membrane receptor that controls cell fate decisions during development of the nervous system, has been linked to AD because it is a substrate for the gamma-secretase protein complex in which mutations cause early-onset inherited AD. Numb is...
Show moreIncreased production of amyloid beta (A-beta) peptide, via altered proteolytic cleavage of amyloid protein precursor (APP), and abnormalities in neuronal calcium homeostasis play central roles in the pathogenesis of Alzheimer's disease (AD). Notch1, a membrane receptor that controls cell fate decisions during development of the nervous system, has been linked to AD because it is a substrate for the gamma-secretase protein complex in which mutations cause early-onset inherited AD. Numb is an evolutionarily conserved endocytic adapter involved in the internalization of transmembrane receptors. Mammals produce four Numb isoforms that differ in two functional domains, a phosphotyrosine-binding domain (PTB) and a proline-rich region (PRR). Recent studies showed that the PTB domain of Numb interacts with the cytoplasmic tails of APP and Notch but the functional relevance of these interactions with respect to AD pathogenesis is not clear. In the current studies, we proposed to investigate the biological consequences of the interaction of the Numb proteins with APP and Notch in neural cells stably overexpressing each of the four human Numb proteins. In the first part of our studies, we found that expression of the Numb isoforms lacking the insert in the PTB (SPTB-Numb) caused the abnormal accumulation of cellular APP in the early endosomes, and increased the levels of C-terminal APP fragments and A-beta. By contrast, expression of the Numb isoforms with the insert in PTB (LPTB-Numb) leads to the depletion of cellular APP and coincides with significantly lower production of APP derivatives and A-beta. The contrasting effects of the Numb isoforms on APP metabolism were not attributed to differences in the expression of APP nor the activities of the various APP-processing secretases. In the second part of our studies, we found that expression of SPTB-Numb protein enhances neuronal vulnerability to serum deprivation-induced cell death by a mechanism involving the dysregulation of cellular calcium homeostasis. Neural cells expressing SPTB-Numb exhibited enhanced Notch activity, which markedly upregulated the expression of transient receptor potential canonical 6 (TRPC6) channels enhancing calcium entry in response to store depletion. We also found that serum deprivation increased TRPC6 expression, mediating the serum deprivation-induced death in neural cells. Interestingly, expression of LPTB-Numb protein suppressed serum deprivation-induced activation of Notch and the subsequent upregulation of TRPC6 and cell death. Finally, we showed that the Numb proteins differentially impact Notch activation by altering the endocytic trafficking and processing of Notch. Taken together, these studies demonstrate that aberrant expression of the Numb proteins may influence APP metabolism and Notch-mediated cellular responses to injury by altering their endocytic trafficking and processing.
Show less - Date Issued
- 2008
- Identifier
- CFE0002233, ucf:47917
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0002233
- Title
- Use of Accelerated Calcite Precipitation Method to Investigate Calcium Carbonate Precipitation from Recycled Concrete for Drainage System Applications.
- Creator
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McCulloch, Toni, Nam, Boo Hyun, Chopra, Manoj, Arboleda Monsalve, Luis, An, Jin Woo, Filler, Dennis, University of Central Florida
- Abstract / Description
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Recycled concrete aggregate (RCA) is a sustainable construction material that is a viable option for use in drainage systems by replacing virgin aggregate. Replacing virgin aggregate with RCA is beneficial from both economic and environmental perspectives. However, the use of RCA as pipe backfill materials may cause a long-term performance issue such as potential clogging due to fines accumulation and calcite precipitation on filter fabric. Previous studies investigated the long-term...
Show moreRecycled concrete aggregate (RCA) is a sustainable construction material that is a viable option for use in drainage systems by replacing virgin aggregate. Replacing virgin aggregate with RCA is beneficial from both economic and environmental perspectives. However, the use of RCA as pipe backfill materials may cause a long-term performance issue such as potential clogging due to fines accumulation and calcite precipitation on filter fabric. Previous studies investigated the long-term performance of RCA regarding flow rate. Therefore, this study investigated calcite precipitation potential of RCA. The Accelerated Calcite Precipitation (ACP) procedure was devised and used to estimate (")life-time(") calcite precipitation of RCA for French Drains. The ACP procedure was studied further and improved to optimize the calcite precipitation procedure. The enhanced method was used to compare the calcite precipitation of limestone and RCA samples - sources with varying chemistry and history. Key findings are (1) the clogging due to calcite precipitation of RCA is not as significant as clogging due to the existing and/or accumulated fines, (2) the calcite precipitation can be increased with a temperature of 75(&)deg;C and 17-hour heating time, and (3) the potential for calcite precipitation from RCA is not as significant as limestone for Type I underdrain gradation.
Show less - Date Issued
- 2018
- Identifier
- CFE0007321, ucf:52132
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0007321
- Title
- Evaluating the Use of Recycled Concrete Aggregate in French Drain Applications.
- Creator
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Behring, Zachary, Nam, Boo Hyun, Chopra, Manoj, Behzadan, Amir, Kim, Jin-Young, University of Central Florida
- Abstract / Description
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Recycled concrete aggregate (RCA) is often used as a replacement of virgin aggregate in road foundations (base course), embankments, hot-mix asphalt, and Portland cement concrete. However, the use of RCA in exfiltration drainage systems, such as French drains, is currently prohibited in many states of the U.S. The French drain system collects water runoff from the road pavement and transfers to slotted pipes underground and then filters through coarse aggregate and geotextile. The primary...
Show moreRecycled concrete aggregate (RCA) is often used as a replacement of virgin aggregate in road foundations (base course), embankments, hot-mix asphalt, and Portland cement concrete. However, the use of RCA in exfiltration drainage systems, such as French drains, is currently prohibited in many states of the U.S. The French drain system collects water runoff from the road pavement and transfers to slotted pipes underground and then filters through coarse aggregate and geotextile. The primary concerns with using RCA as a drainage media are the fines content and the precipitation of calcium carbonate to cause a reducing in filter fabric permittivity. Additional concerns include the potential for rehydration of RCA fines.The performance of RCA as drainage material has not been evaluated by many researchers and the limited information limits its use. A literature review has been conducted on the available information related to RCA as drainage material. A survey was issued to the Departments of Transportation across the nation in regards to using RCA particularly in French drains. Some state highway agencies have reported the use of RCA as base course; however, no state reports the use of RCA in exfiltration drainage systems. This thesis describes the investigations on the performance of RCA as backfill material in French drains.RCA was tested for its physical properties including, specific gravity, unit weight, percent voids, absorption, and abrasion resistance. RCA cleaning/washing methods were also applied to evaluate the fines removal processes. The potential for RCA rehydration was evaluated by means of heat of hydration, pH, compressive strength, and setting time. The permeability of RCA was tested using the No. 4 gradation. Long term permeability testing was conducted to evaluate the tendency for geotextile clogging from RCA fines. Calcium carbonate precipitation was also evaluated and a procedure to accelerate the precipitation process was developed.The results show that RCA has a high abrasion value, that is, it is very susceptible to break down from abrasion during aggregate handling such as transportation, stockpiling, or placing. The most effective cleaning method was found to be pressure washing with agitation. RCA has not demonstrated the tendency to rehydrate and harden when mixed with water. The permeability test results show that the No. 4 gradation does not restrict the flow of water; the flow rate is highly dependent on the hydraulic system itself, however excessive fines can cause large reductions in permeability over time. It has been determined that No. 4 gradation of RCA can provide a suitable drainage media providing the RCA is properly treated before its use.
Show less - Date Issued
- 2013
- Identifier
- CFE0004974, ucf:49595
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0004974
- Title
- Dairy calcium advertising awareness, attitudes and behavior : a survey of 13-17 year-old females.
- Creator
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Cooper, Michele, Davis, Robert H., Arts and Sciences
- Abstract / Description
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University of Central Florida College of Arts and Sciences Thesis; In April 1984, at a conference convened by the National Institutes of Health, a panel of experts issued a statement listing calcium as a "mainstay in the prevention and management of osteoporosis." Osteoporosis, or "brittle bone disease," affects one out of every four American women over 5 0 and is the 12th leading cause of death in the United States. In January 1985, the National Dairy Promotion and Research Board began...
Show moreUniversity of Central Florida College of Arts and Sciences Thesis; In April 1984, at a conference convened by the National Institutes of Health, a panel of experts issued a statement listing calcium as a "mainstay in the prevention and management of osteoporosis." Osteoporosis, or "brittle bone disease," affects one out of every four American women over 5 0 and is the 12th leading cause of death in the United States. In January 1985, the National Dairy Promotion and Research Board began emphasizing dietary calcium in the promotion of milk and dairy products. Television commercials and print advertising were developed which focused on the calcium contained in dairy products and stressed the importance of this nutrient to a woman's diet. Recent consumer research conducted by Market Facts, Inc. of Chicago indicates that this positive calcium message designed to increase dairy product intake may not be effectively reaching the 13-24 year old female. The study shows that subjects in this age group report that they are doing less about their calcium deficiencies than subjects who were studied prior to the time that the dietary calcium advertising began. In addition, the research indicates that those women who are taking steps to increase calcium intake are less likely to use dairy products. Teenage females offer the dairy industry a challenging opportunity. While average male milk consumption jumps dramatically during the ages of 13-19, average female milk consumption experiences only a slight increase. Reaching this audience at this habit-forming age end changing their attitudes and behavior could provide lifelong use of dairy products. The purpose of this study is to determine the efficacy of past dairy calcium advertising messages in affecting the health attitudes and dietary behavior of 13-17 year old women in Florida.
Show less - Date Issued
- 1987
- Identifier
- CFR0004326, ucf:52991
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFR0004326
- Title
- Evaluation of an On-Line Device to Monitor Scale Formation in a Brackish Water Reverse Osmosis Membrane Process.
- Creator
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Roque, Jennifer, Duranceau, Steven, Randall, Andrew, Zhang, Husen, University of Central Florida
- Abstract / Description
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A modified two-element membrane pressure vessel assembly has been used to monitor process operational changes in a full-scale reverse osmosis (RO) water treatment plant (WTP). This study evaluated the effectiveness of the assembly as an on-line monitoring device intended to detect scale formation conditions when connected to an operating RO process train. This study was implemented to support the requirements of a larger University of Central Florida (UCF) research project ongoing at the city...
Show moreA modified two-element membrane pressure vessel assembly has been used to monitor process operational changes in a full-scale reverse osmosis (RO) water treatment plant (WTP). This study evaluated the effectiveness of the assembly as an on-line monitoring device intended to detect scale formation conditions when connected to an operating RO process train. This study was implemented to support the requirements of a larger University of Central Florida (UCF) research project ongoing at the city of Sarasota's Public Works and Utilities (City) water treatment facilities located in Sarasota, Florida. During the time-frame of this study, the City was in the process of eliminating their sulfuric acid feed from the pretreatment system of their existing 4.5 million gallon per day (MGD) RO membrane process. The City was motivated to eliminate its dependence on sulfuric acid to reduce operating costs as well as reduce operation health and safety risks associated with the use of the acid as a pretreatment chemical. Because the City was concerned with secondary process impacts associated with acid elimination, additional measures were desired in order to protect the full-scale process.This thesis reports on the design, fabrication and installation of a third-stage two membrane element pressure vessel (")canary(") sentinel monitoring device (Canary), its effectiveness as an on-line scaling monitor during full-scale acid elimination, and presents the results of the study. The Canary sentinel device was controlled using the normalized specific flux of the two membrane elements fed by a portion of the second stage concentrate of one of the City's full-scale RO process skids. Although the Canary demonstrated the ability to detect changes in an RO process operation, scaling did not occur under the conditions evaluated in this study. An autopsy of one of the Canary elements revealed that no scaling had occurred during the acid elimination process. Therefore, the Canary was found to be useful in its function as a sentinel, even though no scaling was detected by the device after acid elimination at the City's full-scale plant had been accomplished.
Show less - Date Issued
- 2012
- Identifier
- CFE0004433, ucf:49353
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0004433
- Title
- Mechanisms of Alpha-Synuclein-Induced Neurodegenertaion in Parkinson's Disease and Stroke.
- Creator
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Belal, Cherine, Chan, Sic, Ebert, Steven, Self, William, Teter, Kenneth, University of Central Florida
- Abstract / Description
-
Parkinson's disease (PD) is a debilitating neurodegenerative disorder affecting one million Americans. Despite its social and economic impact, the pathological cascades that lead to neuron dysfunction and degeneration in PD are poorly understood. Endoplasmic reticulum (ER) stress has been implicated as an initiator or contributing factor in neurodegenerative diseases including PD. The ER is an organelle central to protein folding and intracellular Ca2+ homeostasis. Perturbations of these...
Show moreParkinson's disease (PD) is a debilitating neurodegenerative disorder affecting one million Americans. Despite its social and economic impact, the pathological cascades that lead to neuron dysfunction and degeneration in PD are poorly understood. Endoplasmic reticulum (ER) stress has been implicated as an initiator or contributing factor in neurodegenerative diseases including PD. The ER is an organelle central to protein folding and intracellular Ca2+ homeostasis. Perturbations of these functions result in ER stress and upregulation of ER stress proteins, of which some have been implicated in counteracting ER stress-induced cell death. The mechanisms that lead to ER stress and how ER stress proteins contribute to the degenerative cascades remain unclear but their understanding is critical to devising effective therapies for PD. Both the accumulation of mutant a-synuclein (aSyn), which causes an inherited form of PD, and the inhibition of mitochondrial complex I function by PD-inducing neurotoxin lead to ER stress. The critical involvement of ER stress in experimental models of PD supports its potential relevance to PD pathogenesis and led us to test the hypothesis whether the homocysteine-inducible ER protein (Herp), an ubiquitin-like domain (UBD) containing ER-resident protein, can counteract mutant Alpha Syn- and neurotoxin- induced pathological cascades.
Show less - Date Issued
- 2011
- Identifier
- CFE0004470, ucf:49310
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0004470
- Title
- Synthesis of Fluorescent Molecules and their Applications as Viscosity Sensors, Metal Ion Indicators, and Near-Infrared Probes.
- Creator
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Wang, Mengyuan, Belfield, Kevin, Campiglia, Andres, Miles, Delbert, Frazer, Andrew, Cheng, Zixi, University of Central Florida
- Abstract / Description
-
The primary focus of this dissertation is the development of novel fluorescent near-infrared molecules for various applications. In Chapter 1, a compound dU-BZ synthesized via Sonogashira coupling reaction methodology is described. A deoxyuridine building block was introduced to enhance hydrophilic properties and reduce toxicity, while an alkynylated benzothiazolium dye was incorporated for near-IR emission and reduce photodamage and phototoxicity that is characteristic of common fluorphores...
Show moreThe primary focus of this dissertation is the development of novel fluorescent near-infrared molecules for various applications. In Chapter 1, a compound dU-BZ synthesized via Sonogashira coupling reaction methodology is described. A deoxyuridine building block was introduced to enhance hydrophilic properties and reduce toxicity, while an alkynylated benzothiazolium dye was incorporated for near-IR emission and reduce photodamage and phototoxicity that is characteristic of common fluorphores that are excited by UV or visible light. A 30-fold enhancement of fluorescence intensity of dU-BZ was achieved in a viscous environment. Values of fluorescence quantum yields in 99% glycerol/1% methanol (v/v) of varying temperature from 293 K to 343 K, together with fluorescence quantum yields, radiative and nonradiative rate constants and fluorescence lifetimes in glycerol/methanol solutions of varying viscosities from 4.8 to 950 cP were determined. It was found that both fluorescence quantum yields and fluorescence lifetimes increased with increasing viscosity, which is consistent with results predicted by theory. This suggests that the newly designed compound dU-BZ is capable of functioning as a probe of local microviscosity, and was later confirmed by in vitro bioimaging experiments.In Chapter 2, a new BAPTA (O,O'-bis(2-aminophenyl)ethyleneglycol-N,N,N',N'-tetra acetic acid) and BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene)-based calcium indicator, BAPBO-3, is reported. A new synthetic route was employed to simplify both synthesis and purification, which tend to be low yielding and cumbersome for BAPTA derivatives. Upon excitation, a 1.5-fold increase in fluorescence intensity in buffer containing 39 ?? Ca2+ and a 3-fold increase in fluorescence intensity in buffer containing 1 M Ca2+ was observed; modest but promising fluorescence turn-on enhancements.In Chapter 3, a newly-designed unsymmetrical squaraine dye, SQ3, was synthesized. A one-pot synthesis was employed resulting in a 10% yield, a result that is generally quite favorable for the creation of unsymmetrical squaraines Photophysical and photochemical characterization was conducted in various solvents, and a 678 nm absorption maximum and a 692 nm emission maximum were recorded in DMSO solution with a fluorescence quantum yield of 0.32. In vitro cell studies demonstrated that SQ3 can be used as a near-IR probe for bioimaging.
Show less - Date Issued
- 2014
- Identifier
- CFE0005900, ucf:50863
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0005900
- Title
- Synchrotron X-Ray Diffraction and Piezospectroscopy used for the Investigation of Individual Mechanical Effects from Environmental Contaminants and Oxide Layer Undulations in Thermal Barrier Coatings.
- Creator
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Siddiqui, Sanna, Raghavan, Seetha, Bai, Yuanli, Gordon, Ali, University of Central Florida
- Abstract / Description
-
The durability of Thermal Barrier Coatings (TBCs) used on the turbine blades of aircraft and power generation engines has been known to be affected by sand particle ingression comprised of Calcium-Magnesium-Alumina-Silicate (CMAS). Previous studies have shown that these effects present themselves through variations in the thermomechanical and thermochemical properties of the coating. This study investigated the impact of CMAS ingression on the Yttria Stabilized Zirconia Topcoat (YSZ) and...
Show moreThe durability of Thermal Barrier Coatings (TBCs) used on the turbine blades of aircraft and power generation engines has been known to be affected by sand particle ingression comprised of Calcium-Magnesium-Alumina-Silicate (CMAS). Previous studies have shown that these effects present themselves through variations in the thermomechanical and thermochemical properties of the coating. This study investigated the impact of CMAS ingression on the Yttria Stabilized Zirconia Topcoat (YSZ) and Thermally Grown Oxide (TGO) strain in sprayed Thermal Barrier Coating (TBC) samples of varying porosity with and without CMAS ingression. In-Situ Synchrotron X-ray Diffraction measurements were taken on the sample under thermal loading conditions from which the YSZ and TGO peaks were identified and biaxial strain calculations were determined at high temperature. Quantitative strain results are presented for the YSZ and TGO during a thermal cycle. In-plane strain results for YSZ near the TGO interface for a complete thermal cycle are presented, for a 6% porous superdense sample with CMAS infiltration. The outcomes from this study can be used to understand the role of CMAS on the strain tolerance of the TBC coating.It is well known that under engine operational conditions the development of the TGO layer, with large critical stresses, has been linked to failure of the coating. The growth of the TGO manifests as undulations in a series of peaks and troughs. Understanding the mechanics of the oxide layer at these locations provides significant information with respect to the failure mechanisms of the TBC coating. This study investigated the stress at the peak and trough of a TGO undulation for a cycled Dense Vertically Cracked (DVC) plasma sprayed TBC sample through photo-luminescence (PL) spectroscopy. High resolution nanoscale stress maps were taken nondestructively in the undulation of the TGO. Preliminary results from first line mapping of TGO peak and trough scan, at a resolution of 200 nm, have shown a non-uniform TGO stress variation. The results obtained from this study can be used to understand the stress variation in the peak and trough of a DVC sample's TGO undulation and how it contributes to the life of the TBC coating.
Show less - Date Issued
- 2014
- Identifier
- CFE0005712, ucf:50136
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0005712
