Research

Male C7BL/6J mice were implanted with bilateral dorsal CA1 guide cannulae. After confirming that intrahippocampal microinfusion of muscimol impaired hippocampal function, demonstrated by impaired performance in the Morris water maze, the influence of intrahippocampal muscimol was tested in the Novel Object Recognition paradigm. During a test session 24 h after the last habituation/sample session, mice were presented with one familiar object and one novel object. Successful retention of object memory was inferred if mice spent more time exploring the novel object than the familiar object. Results demonstrate that muscimol infused into dorsal CA1 region prior to the test session eliminates novel object preference, indicating that the hippocampus is necessary for the retrieval of this non-spatial memory - a topic that has garnered much debate. Understanding the similarities between rodent and human hippocampal function could enable future animal studies to effectively answer questions about diseases and disorders affecting human learning and memory.

A method for modeling and simulating neural action potential (AP) propagation along the length of an axon containing a number of Ranvier nodes is proposed in this dissertation. A system identification approach is adopted to represent node of Ranvier (NR) response to current pulse stimulus in the form of transfer function representations for NR excitability. Segments of myelinated internodal (IN) and NR regions are cascaded, representing the remaining downstream axon after a site-of-stimulus introduction of an external current pulse. This cascading network is used to simulate "cable" properties and signal propagation along the length of the axon. This work proposes possible solutions to attenuation losses inherited in the classical myelinated cable models and accounts for neuronal AP velocity as well as introducing signal attenuation and transient delays associated with internodal demyelination. This model could aide as a predictive tool for the diagnosis and analysis of axonal signal integrity associated with demyelination pathology. Possible applications could include functional stimulation control methodologies for axon bundles that may exhibit signal fidelity issues associated with demyelination. It is further proposed that this model may serve as an instructive tool for further development and incorporation of other axon dynamic behaviors such as: relative refractory periods of AP generation, NR AP recovery mechanisms and responses to varied current stimulus input.

This thesis proposes a Power Management Model (PMM) for optimization of several green power generation systems. A Photovoltaic/Fuel cell Hybrid Energy System (PFHES) consisting of solar cells, electrolyzer and fuel cell stack is utilized to meet a specific DC load bank for various applications. The Photovoltaic system is the primary power source to take advantage of renewable energy. The electrolyzer-fuel cell integration is used as a backup and as a hydrogen storage system with the different energy sources integrated through a DC link bus. An overall power management strategy is designed for the optimization of the power flows among the different energy sources. Extensive simulation experiments have been carried out to verify the system performance under PMM governing strategy. The simulation results indeed demonstrate the effectiveness of the proposed approach.

Provision of complete and responsive solution to healthcare services requires a multi-tired health delivery system. One of the aspects of healthcare hierarchy is the need for nursing care of the patient. Nursing care and observation provide basis for nurses to communicate with other aspects of healthcare system. The ability of capturing and managing nursing practice is essential to the quality of human care. The thesis proposes knowledge based decision making and analyzing system for the nurses to capture and manage the nursing practice. Moreover it allows them to monitor nursing care quality, as well as to test an aspect of an electronic healthcare record for recording and reporting nursing practice. The framework used for this system is based on nursing theory and is coupled with the quantitative analysis of qualitative data. It allows us to quantify the qualitative raw natural nursing language data. The results are summarized in the graph that shows the relative importance of those attributes with respect to each other at different instances of nurse-patient encounter. Research has been conducted by the Department of Computer and Electrical Engineering and Computer Science for the College of Nursing.

Small conductance calcium-activated potassium (SK) channels are found ubiquitously throughout the brain and modulate the encoding of learning and memory. Systemic injection of 1-ethyl-2-benzimidalzolinoe (EBIO), a SK channel activator, impairs the encoding of novel object memory and locomotion but spares fear memory encoding in C57BL/6NHsd mice. The memory impairments discovered were not due to non-cognitive performance confounds such as ataxia, anxiety, attention or analgesia. Further investigation with intra-hippocampal application of EBIO revealed SK channels in dorsal CA1 contribute to the encoding deficits seen systemically, but do not account for the full extent of the impairment. Concentrated activation of dorsal CA1 SK channels do not influence fear memory encoding or locomotor impairments. Taken together, these data indicate SK channels, especially in the dorsal hippocampus, have a modulatory role on novel object memory encoding, but not retrieval; however, pharmacological activation of hippocampal SK channels does not appear to influence fear memory encoding.

Tinnitus is a conscious perception of phantom sounds in the absence of external acoustic stimuli, and masking is one of the popular ways to treat it. Due to the variation in the perceived tinnitus sound from patient to patient, the usefulness of masking therapy cannot be generalized. Thus, it is important to first determine the feasibility of masking therapy on a particular patient, by quantifying the tinnitus sound, and then generate an appropriate masking signal. This paper aims to achieve this kind of individual profiling by developing interactive software -Tinnitus Analyzer, based on clinical approach. The developed software has been proposed to be used in place of traditional clinical methods and this software (as a part of the future work) will be implemented in the practical scenario involving real tinnitus patients.

Mammalian neurons exhibit extreme sensitivity to oxygen deprivation and undergo rapid and irreversible degeneration when oxygen supply is curtailed. Though several neuroprotective pathways are activated during oxygen deprivation, their analyses are masked by the complex series of pathological events which are triggered simultaneously. Such events can be analyzed in the anoxia tolerant fresh water turtle, which can inherently survive the conditions of oxygen deprivation and post-anoxic reoxygenation without brain damage. It is likely in such a model that modulation of a particular molecular pathway is adaptive rather than pathological. The major objective behind this study was to analyze the intracellular signaling pathways mediating the protective effects of adenosine, a potential neuromodulator, and its effect on cell survival by influencing the key prosurvival proteins that prevent apoptosis. In vivo and in vitro studies have shown that adenosine acts as a neuroprotective metabolite and its action can be duplicated or abrogated using specific agonist and antagonists. Stimulating the adenosine receptors using selective A1 receptor agonist N6-cyclopentyladenosine (CPA) activated the presumed prosurvival ERK and P13-K/AKT cascade promoting cell survival, and suppression of the receptor using the selective antagonist DPCPX (8- cyclopentyl-1,3-dipropylxanthine) activated the prodeath JNK and P38 pathways. The complex regulation of the MAPK's/AKT signaling cascades was also analyzed using their specific inhibitors. The inhibiton of the ERK and AKT pathway increased cell death, indicating a prosurvival role, whereas inhibiton of the JNK and p38 pathway increased cell survival in this model. In vitro studies have also shown a high Bcl-2/BAX ratio during anoxia and reoxygenation, indicating a strong resistance to cell death via apoptosis.

This experiment investigated an individual's memory of specific motion events, unique actor, intrinsic motion, and extrinsic motion combination. Intrinsic motions involve the movement of an individual's body parts in a specific manner to move around, while extrinsic motions specify a path in reference to an external object. Participants viewed video clips, each depicting an actor performing a unique extrinsic and intrinsic motion combination. One week later, they viewed a different series of retrieval video clips consisting of old (identical to encoding), extrinsic conjunction (extrinsic motion previously performed by different actor), intrinsic conjunction (intrinsic motion previously performed by different actor), and new (novel extrinsic or intrinsic motion) video clips. Participants responded "yes" to viewing the old video clips the most often, followed by conjunction video clips, and then new video clips. Furthermore, there were a greater number of "yes" event memory recognition responses for extrinsic conjunction items than intrinsic conjunction items.

Tumor cells interact with basement membrane collagen at the site of extravasation through distinct cellular receptors, including the α2β1 and α3β1integrins. These receptors are known to be differentially expressed in metastatic tumors, relative to the normal cells, depending on tumor type and stage of progression. The binding sites within type IV collagen for the α2β1 andα3β1 integrins have been identified. Since both of the integinspecific sequences possess at least one glycosylated Hyl residue, we questioned whether glycosylation could modulate integrin binding. Triple-helical peptides with and without Lys substituted by glycosylated Hyl for Lys543 and Lys540 from the human a1(IV)531-543 gene sequence (α3β integrin-specific) and Lys393 from the human a1(IV)382-393 gene sequence (α2β1 integrin-specific) were synthesized and utilized in the present study.

Microarray expression data which contains the expression levels of a large number of simultaneously observed genes have been used in many scientific research and clinical studies. Due to its high dimensionalities, selecting a small number of genes has shown to be beneficial for many tasks such as building prediction models from the microarray expression data or gene regulatory network discovery. Traditional gene selection methods, however, fail to take the class distribution into the selection process. In biomedical science, it is very common to have microarray expression data which is severely biased with one class of examples (e.g., diseased samples) significantly less than other classes (e.g., normal samples). These sample sets with biased distributions require special attention from researchers for identification of genes responsible for a particular disease. In this thesis, we propose three filtering techniques, Higher Weight ReliefF, ReliefF with Differential Minority Repeat and ReliefF with Balanced Minority Repeat to identify genes responsible for fatal diseases from biased microarray expression data. Our solutions are evaluated on five well-known microarray datasets, Colon, Central Nervous System, DLBCL Tumor, Lymphoma and ECML Pancreas. Experimental comparisons with the traditional ReliefF filtering method demonstrate the effectiveness of the proposed methods in selecting informative genes from microarray expression data with biased sample distributions.