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- Title
- VALIDATING DRUG TARGETS THROUGH INHIBITION OF PROTEIN-PROTEIN INTERACTIONS IN MYCOBACTERIUM TUBERCULOSIS.
- Creator
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Driscoll, Erin C, Rohde, Kyle, University of Central Florida
- Abstract / Description
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Tuberculosis is the leading cause of death by single infectious disease worldwide; novel antibiotics are needed to continue to treat this disease. To goal of this project is to provide proof-of-principle support for the idea that targeting protein-protein interactions (PPI) is an appropriate course for the discovery of new drugs. This study optimized the M-PFC assay, which allows detection of PPI in Mycobacteria, through the use of stronger promoters and inducible expression of a peptide...
Show moreTuberculosis is the leading cause of death by single infectious disease worldwide; novel antibiotics are needed to continue to treat this disease. To goal of this project is to provide proof-of-principle support for the idea that targeting protein-protein interactions (PPI) is an appropriate course for the discovery of new drugs. This study optimized the M-PFC assay, which allows detection of PPI in Mycobacteria, through the use of stronger promoters and inducible expression of a peptide blocker by riboswitch. To accomplish this, promoter induction studies were used to find stronger promoters for the M-PFC, optimization of the riboswitch as a method for inducible protein expression within this system, and the addition of both elements to the existing version of the M-PFC. This M-PFC targets DosR homodimerization; this process is known to be essential for survival within the host. This study optimizes a system that may be used to screen for drugs that are capable of interrupting this interaction.
Show less - Date Issued
- 2017
- Identifier
- CFH2000190, ucf:46030
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFH2000190
- Title
- DEVELOPMENT OF NOVEL FLUORESCENT TOOLS FOR INVESTIGATING VIRULENCE FACTORS AND DRUG SUSCEPTIBILITY IN MYCOBACTERIUM TUBERCULOSIS.
- Creator
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Wilburn, Kaley, Rohde, Kyle, University of Central Florida
- Abstract / Description
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Mycobacterium tuberculosis (Mtb) is the causative agent of Tuberculosis (TB), a life-threatening disease primarily affecting the lungs that infects about one third of the world's population and causes 1.3 million deaths annually. It is estimated that TB has been infecting humans for around 70,000 years and has killed more people than any other infectious disease. The highly effective, persistent, and multifaceted virulence strategies that have allowed Mtb to continue to spread and thrive for...
Show moreMycobacterium tuberculosis (Mtb) is the causative agent of Tuberculosis (TB), a life-threatening disease primarily affecting the lungs that infects about one third of the world's population and causes 1.3 million deaths annually. It is estimated that TB has been infecting humans for around 70,000 years and has killed more people than any other infectious disease. The highly effective, persistent, and multifaceted virulence strategies that have allowed Mtb to continue to spread and thrive for so long are still poorly understood at the molecular level. This lack of knowledge contributes to ongoing challenges to curing TB. Although drugs capable of killing Mtb exist, even strains that are susceptible to these drugs remain so difficult to treat that stringent six- to nine-month courses of four-drug cocktails are required. Practical difficulties in administering full treatments and patient noncompliance have contributed to a rise in drug-resistant TB cases globally. To combat this increasing world health problem, new antibiotic treatments that kill Mtb and drug-resistant Mtb more effectively via new mechanisms of action are necessary. Discovering these antibiotics expediently requires that innovative Mtb-specific drug-screening assays are developed. An ideal and innovative TB drug screening method would target validated protein-protein interactions (PPI) essential to Mtb's pathogenesis and would be performed on whole Mtb cells under relevant in vivo-like conditions. This project focused on engineering several tools relevant to creating an ideal TB drug screen. A protein fragment complementation assay capable of studying PPI of the TB gyrase complex was created, and this assay was assessed for future HTS applications. To streamline the readout, this assay was re-engineered to include green fluorescent protein. Modifications to the red fluorescent protein mCherry, including the creation of a large Stokes shift mutant mCherry and an mCherry bimolecular fluorescence complementation assay, were also engineered and investigated.
Show less - Date Issued
- 2015
- Identifier
- CFH0004843, ucf:45473
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFH0004843
- Title
- REALIZATION OF POWER FACTOR CORRECTION AND MAXIMUM POWER POINT TRACKING FOR LOW POWER WIND TURBINES.
- Creator
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Gamboa, Gustavo, Batarseh, Issa, University of Central Florida
- Abstract / Description
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In recent years, wind energy technology has become one of the top areas of interest for energy harvesting in the power electronics world. This interest has especially peaked recently due to the increasing demand for a reliable source of renewable energy. In a recent study, the American Wind Energy Association (AWEA) ranked the U.S as the leading competitor in wind energy harvesting followed by Germany and Spain. Although the United States is the leading competitor in this area, no one has...
Show moreIn recent years, wind energy technology has become one of the top areas of interest for energy harvesting in the power electronics world. This interest has especially peaked recently due to the increasing demand for a reliable source of renewable energy. In a recent study, the American Wind Energy Association (AWEA) ranked the U.S as the leading competitor in wind energy harvesting followed by Germany and Spain. Although the United States is the leading competitor in this area, no one has been able successfully develop an efficient, low-cost AC/DC convertor for low power turbines to be used by the average American consumer. There has been very little research in low power AC/DC converters for low to medium power wind energy turbines for battery charging applications. Due to the low power coefficient of wind turbines, power converters are required to transfer the maximum available power at the highest efficiency. Power factor correction (PFC) and maximum power point tracking (MPPT) algorithms have been proposed for high power wind turbines. These turbines are out of the price range of what a common household can afford. They also occupy a large amount of space, which is not practical for use in one's home. A low cost AC/DC converter with efficient power transfer is needed in order to promote the use of cheaper low power wind turbines. Only MPPT is implemented in most of these low power wind turbine power converters. The concept of power factor correction with MPPT has not been completely adapted just yet. The research conducted involved analyzing the effect of power factor correction and maximum power point tracking algorithm in AC/DC converters for wind turbine applications. Although maximum power to the load is always desired, most converters only take electrical efficiency into consideration. However, not only the electrical efficiency must be considered, but the mechanical energy as well. If the converter is designed to look like a purely resistive load and not a switched load, a wind turbine is able to supply the maximum power with lower conduction loss at the input side due to high current spikes. Two power converters, VIENNA with buck converter and a Buck-boost converter, were designed and experimentally analyzed. A unique approach of controlling the MPPT algorithm through a conductance G for PFC is proposed and applied in the VIENNA topology. On the other hand, the Buck-boost only operates MPPT. With the same wind profile applied for both converters, an increase in power drawn from the input increased when PFC was used even when the power level was low. Both topologies present their own unique advantages. The main advantage for the VIENNA converter is that PFC allowed more power extraction from the turbine, increasing both electrical and mechanical efficiency. The buck-boost converter, on the other hand, presents a very low component count which decreases the overall cost and volume. Therefore, a small, cost-effective converter that maximizes the power transfer from a small power wind turbine to a DC load, can motivate consumers to utilize the power available from the wind.
Show less - Date Issued
- 2009
- Identifier
- CFE0002730, ucf:48158
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0002730
- Title
- DEVELOPMENT OF A FLUORESCENT DRUG SCREENING PLATFORM FOR INHIBITORS OF MYCOBACTERIUM TUBERCULOSIS PROTEIN-PROTEIN INTERACTIONS.
- Creator
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Versfeld, Zina, Rohde, Kyle, University of Central Florida
- Abstract / Description
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Tuberculosis (TB) is a respiratory disease caused by Mycobacterium tuberculosis (Mtb) that kills around 1.3 million people annually. Multi-drug resistant TB (MDR-TB) strains are increasingly encountered, in part resulting from shortcomings of current TB drug regimens that last between six to nine months. Patients may stop taking the antibiotics during their allotted regimen, leading to drug resistant TB strains. Novel drug screening platforms are therefore necessary to find drugs effective...
Show moreTuberculosis (TB) is a respiratory disease caused by Mycobacterium tuberculosis (Mtb) that kills around 1.3 million people annually. Multi-drug resistant TB (MDR-TB) strains are increasingly encountered, in part resulting from shortcomings of current TB drug regimens that last between six to nine months. Patients may stop taking the antibiotics during their allotted regimen, leading to drug resistant TB strains. Novel drug screening platforms are therefore necessary to find drugs effective against MDR-TB. In order to discover compounds that target under-exploited pathways that may be essential only in vivo, the proposed screening platform will use a novel approach to drug discovery by blocking essential protein-protein interactions (PPI). In Mtb, PPI can be monitored by mycobacterial protein fragment complementation (M-PFC). This project will re-engineer the M-PFC assay to include the red fluorescent mCherry reporter for increased efficiency and sensitivity in high-throughput screening applications. To optimize the mCherry assay, we have developed fluorescent M-PFC reporter strains to monitor distinct PPI required for Mtb virulence: homodimerization of the dormancy regulator DosR. A drug screen will then identify novel compounds that inhibit this essential PPI. The screen will involve positional-scanning combinatorial synthetic libraries, which are made up of chemical compounds with varying side chains. This work will develop novel tools for TB drug discovery that could identify new treatments for the emerging world threat of MDR-TB.
Show less - Date Issued
- 2015
- Identifier
- CFH0004785, ucf:45369
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFH0004785
- Title
- EVALUATING COMPETITION BETWEEN VERBAL AND IMPLICIT SYSTEMS WITH FUNCTIONAL NEAR-INFRARED SPECTROSCOPY.
- Creator
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Schiebel, Troy A, Bohil, Corey, University of Central Florida
- Abstract / Description
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In category learning, explicit processes function through the prefrontal cortex (PFC) and implicit processes function through the basal ganglia. Research suggested that these two systems compete with each other. The goal of this study was to shed light on this theory. 15 undergraduate subjects took part in an event-related experiment that required them to categorize computer-generated line-stimuli, which varied in length and/or angle depending on condition. Subjects participated in an...
Show moreIn category learning, explicit processes function through the prefrontal cortex (PFC) and implicit processes function through the basal ganglia. Research suggested that these two systems compete with each other. The goal of this study was to shed light on this theory. 15 undergraduate subjects took part in an event-related experiment that required them to categorize computer-generated line-stimuli, which varied in length and/or angle depending on condition. Subjects participated in an explicit "rule-based" (RB) condition and an implicit "information-integration" (II) condition while connected to a functional near-infrared spectroscopy (fNIRS) apparatus, which measured the hemodynamic response (HR) in their PFC. Each condition contained 2 blocks. We hypothesized that the competition between explicit and implicit systems (COVIS) would be demonstrated if, by block 2, task-accuracy was approximately equal across conditions with PFC activity being comparatively higher in the II condition. This would indicate that subjects could learn the categorization task in both conditions but were only able to decipher an explicit rule in the RB condition; their PFC would struggle to do so in the II condition, resulting in perpetually high activation. In accordance with predictions, results revealed no difference in accuracy across conditions with significant difference in channel activation. There were channel trends (p<.1) which showed PFC activation decrease in the RB condition and increase in the II condition by block 2. While these results support our predictions, they are largely nonsignificant, which could be attributed to the event-related design. Future research should utilize a larger samples size for improved statistical power.
Show less - Date Issued
- 2016
- Identifier
- CFH2000086, ucf:45502
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFH2000086