Research

Current research in natural products has heavily focused on the identification of potent biologically active compounds, specifically for drug development. The project detailed in this thesis focuses on the extraction of compounds from marine invertebrates as well as defining the absolute configuration for a compound. Utilizing marine invertebrates, the sonications method developed in this thesis provides an alternative approach to rapidly extract compounds for primary screening. This method is viable compared to a traditional overnight extraction method, without suffering compound degredation... Previously, clathric acid was isolated from an unknown Clathria sp. This compound is a bibyblic C-21 terpenoid shown to have mild antimicrobial activity against gram positive bacteria. With only its relative configuration established, additional amounts of clathric acid were required to define the overall absolute configuration. Identifying the Clathria sp. to be Clathria compressa, through spicule analysis, additional sponge tissues were then collected off the coast of Boca Raton, Florida to isolate additional quatities of clathric acid. The absolulte configuration was determined through circular dichroism and the octant rule to establish a final configuration for clathric acid's four carbon stereocenters to be: (3S, 7S, 8R, and 12S).

Huntington's disease (HD) is caused by an expanded plyglutamine repeat in the huntingtin protein. In this study, I focused on the effect of the mutant huntingtin protein (mhtt) on the subcellular localization of glutamic acid decarboxylase (GAD), the enzyme responsible for synthesizing gama-aminobutyric acid (GABA). Subcellular distribution of GAD65 is significantly altered in two neuronal cell lines that express either the N-terminus or full length mhtt. GAD65 is predominantly associated with the Golgi membrane in cells expressing normal huntingtin (Htt). However, it diffuses in the cytosol of cells expressing mhtt. Palmitoylation of GAD65 is required for GAD65 trafficking, and I demonstrated the palmitoylation of GAD65 is reduced in the HD model. Overexpression of huntingtin-interacting protein 14 (HIP14), the enzyme that palmitoylates GAD65, rescues GAD65 palmitoylation and vesicle-associated trafficking. This data suggests that impairment of GAD65 palmitoylation by mhtt may alter its localization and lead to altered inhibitory neurotransmission in HD.

Brain glutamic acid decarboxylase 65 (GAD65) catalyzes the rate-limiting step in the biosynthesis of the major inhibitory neurotransmitter-amino butyric acid (GABA) from the substrate L-glutamic acid. Severe lapse in GABA neurotransmission is one of the etiologies documented in the manifestation of certain neurodegenerative diseases such as epilepsy, Parkinson's disease, Huntington's disease etc. Because GAD65 synthesizes GABA, any modulation of GAD65, therefore, has direct implications on the quanta of GABA released at the synapse. Hence, the major objective of this study was to focus on the regulation of GAD65, with special emphasis on investigating the proteolytic cleavage of fGAD65. Previously, we have shown in vitro that GAD65 was cleaved to form its truncated form (tGAD65), which was more active than the full length form (fGAD65). The enzyme responsible for cleavage was later identified as calpain. Calpain is known to cleave its substrates either under a transient physiologica l stimulus or upon a sustained pathological insult. However, the precise role of calpain cleavage of fGAD65 is poorly understood. In this study, we examined the cleavage of fGAD65 under a range of conditions encompassing both physiological and pathological aspects, including rats under ischemia/reperfusion insult, rat brain synaptosomes or primary neuronal cultures subjected to excitotoxic stimulation with KCl. It was observed that the formation of tGAD65 progressively increased with increasing stimulus concentration. More importantly, cleavage of synaptic vesicle (SV) - associated fGAD65 by calpain was demonstrated, and the resulting tGAD65 harboring the active site of the enzyme was detached from the SVs. Vesicular uptake of the newly synthesized GABA into the SVs was found to be reduced in calpain treated SVs. Furthermore, we also observed that the levels of tGAD65 in the focal cerebral ischemic rat brain tissue increased corresponding to the elevation of local glutamate indica

Bottlenose (Tursiops truncatus) and spotted (Stenella frontalis) dolphins are sympatric species, resident to Little Bahama Bank, Bahamas. A unique, dynamic methodology quantified how interspecific aggression changed over time in terms of the individuals participating, context, and behaviors used. The timing of human observation relative to the onset of aggression did not result in differences in the proportion of behaviors observed. Highly intense behaviors were used most often. The synchronous state of spotted dolphin groups, not the presence alone, was a crucial factor in determining the onset and progression of aggression. When synchronous, spotted dolphins successfully dominated the larger bottlenose dolphins. Two levels of dominance were observed. Within a single encounter ("encounter level"), one species did dominate the other. When all aggressive encounters were considered collectively over the long term ("gross level"), one species did not dominate the other. The combination of contextual factors best determined the dynamic of interspecific aggression.

The combustion process of a fuel is a challenging subject when it comes to analyze its performance and resultant emissions. The main task of this study is to optimize the selection of a hydrogen-rich fuel based on its performance and emissions. Computational Fluid Dynamics analysis is performed to test the combustion performance and emissions from the vortex trapped combustor when natural gas fuel (methane) is replaced with renewable and alternative fuels such as hydrogen and synthesis gas. Correlation graphs for the trapped vortex combustor performance and NOx, CO, and CO2 emissions for various types of fuels with different compositions and heat of combustion values were established. Methane, Hydrogen and 10 different syngas fuels were analyzed in this study using computational fluid dynamics numerical method. The trapped vortex combustor that represents an efficient and compact combustor for flame stability was investigated. The TVC consists of a fore body and two after body disks . These components are all encircled with a Pyrex tube. The purpose of the after body disks is to create the vortex wakes that will enhance the combustion process and minimize the NOx emissions. The TVC CFD model was validated by comparing the CFD model results using propane fuel with existing experimental results that were established in Rome, Italy. The static temperature distribution and NOx, CO emissions, combustor efficiency and total pressure drop results of the three dimensional CFD model were similar to the experimental data. Effects of H2/CO and H2/CH4 ratios and the mass fraction of each constituent of syngas fuels and Hydrogen-Methane fuel mixture on the TVC performance and emissions were investigated.

The implantable cardioverter defibrillator (ICD) is an electronic medical device that was invented by Dr. Michael Mirowski and his team in 1980. The purpose of the ICD, which is implanted in a person's chest, is to sense and shock the heart when detecting a lethal cardiac arrhythmia into a rhythm that can sustain life. While the ICD saves lives, it also has the potential to deliver painful shocks when it is activated. The ICD was initially inserted in people who had survived a sudden cardiac arrest; the device is now being implanted in older adults with heart failure and no known history of cardiac arrhythmias. When talking with patients and personal family members who had an ICD, it was unclear what influenced their decision to have an ICD implanted. Understanding the experience of decision-making for older adults who had an ICD has added to nursing knowledge, practice, and education when working with people who had an ICD inserted. To understand the lived experience, the researcher conducted a phenomenological research study, guided by the theoretical lens of Paterson and Zderad's (1976/1988) humanistic nursing and analyzed the data as outlined by Giorgi (2009). The results of the study indicated the participants' lived experience of decision-making for older adults who had an implantable cardioverter defibrillator inserted was influenced by the following : trust in their physician's decision; accepting the device was necessary; the decision was easy to make; and hope and desire to live longer.

MicroRNAs (miRNAs) may serve as diagnostic and predictive biomarkers for cancer. The aim of this study was to identify novel cancer biomarkers from miRNA datasets, in addition to those already known. Three published miRNA cancer datasets (liver, breast, and brain) were evaluated, and the performance of the entire feature set was compared to the performance of individual feature filters, an ensemble of those filters, and a support vector machine (SVM) wrapper. In addition to confirming many known biomarkers, the main contribution of this study is that seven miRNAs have been newly identified by our ensemble methodology as possible important biomarkers for hepatocellular carcinoma or breast cancer, pending wet lab confirmation. These biomarkers were identified from miRNA expression datasets by combining multiple feature selection techniques (i.e., creating an ensemble) or by the SVM-wrapper, and then classified by different learners. Generally speaking, creating a subset of features by selecting only the highest ranking features (miRNAs) improved upon results generated when using all the miRNAs, and the ensemble and SVM-wrapper approaches outperformed individual feature selection methods. Finally, an algorithm to determine the number of top-ranked features to include in the creation of feature subsets was developed. This algorithm takes into account the performance improvement gained by adding additional features compared to the cost of adding those features.

Economic game theory has been a challenge to traditional models of selfish human nature. Resource acquisition games, such as the dictator game, which have been primarily played by adults, have revealed that humans are inclined to share even when it is not in their best interest to do so. Few studies have been conducted on the development of resource distribution in children, and fewer still have explored the effect of context and level of involvement of a second player in such games. In the current study, 179 children from kindergarten, first, and second grades participated in a modified dictator game with another player. Children were randomly assigned to one of four conditions; a control condition, where they played individually with an anonymous player, or one of three experimental conditions with two players who each played with varying levels of involvement with the second player. It was found that kindergarteners shared significantly less across conditions than first and second graders, with first and second graders sharing similar amounts. The presence of another player significantly increased the amount of sharing for all grades. Additionally, second players shared significantly less than first players. Developmental and contextual patterns of sharing are discussed.

The efforts addressed in this thesis refer to applying nonlinear risk predictive techniques based on logistic regression to medical diagnostic test data. This study is motivated and pursued to address the following: 1. To extend logistic regression model of biostatistics to medical informatics 2. Computational preemptive and predictive testing to determine the probability of occurrence (p) of an event by fitting a data set to a (logit function) logistic curve: Finding upper and lower bounds on p based on stochastical considerations 3. Using the model developed on available (clinical) data to illustrate the bounds-limited performance of the prediction. Relevant analytical methods, computational efforts and simulated results are presented. Using the results compiled, the risk evaluation in medical diagnostics is discussed with real-world examples. Conclusions are enumerated and inferences are made with directions for future studies.

Previous research suggests that self-reports of the frequency of events can vary dramatically. Minor changes in question format can result in major changes in the obtained results. The purpose of this study is to examine how changes in reference period, memory cue, and measurement scale affect participants' self-reports of conflict frequency. Additionally, the role of cognitive effort was examined to gain insight into the recall strategy used for different measures of conflict. Participants include 175 college undergraduates between the ages of 18-24, enrolled in psychology courses at Florida Atlantic University. Results indicate that reference period and memory cue form a significant interaction to create changes in reports of conflict frequency. Both reference period and memory cue act differently within the different conflict measurement scales. In the 0-10 or more scale, memory cue was statistically significant with higher rates of conflict reported in the cued condition than the uncued. In the open (fill in the blank) scale, there was a significant interaction between reference period and memory cue with the highest amount of conflict being reported in the one day/cued condition. The Likert scale behaved differently than the other two absolute frequency scales. Within the Likert scale there was a significant interaction between reference period and memory cue, however, the highest amount of conflict reported was in the two weeks/uncued condition. Finally, cognitive effort varied as a product of reference period, within both the 0-10 or more scale and the open scale with the two weeks condition eliciting higher reports of effort than the one day condition. These cognitive effort findings suggest that participants used enumeration as a recall strategy for the absolute frequency scales and estimation for the Likert scale.