Indiana University-Purdue University Indianapolis (IUPUI) / Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive loss of motor function resulting from dopaminergic neuronal death in the substantia nigra pars compacta leading to subsequent decreased striatal dopamine levels. The majority of PD cases are diagnosed as sporadic in nature, however 10% - 15% of patients show a positive family history of the disease. While many genes have been found to be implicated in the familial form of PD, early-onset autosomal recessive PD has been associated with mutations in PARK7, a gene which codes for the protein DJ-1. While there are many proposed roles of DJ-1 across numerous systems, the function of DJ-1 in relation to the development and progression of PD remains largely unclear. A first step towards determining this function is the creation of biologically relevant cell models of PD. The goal of this work was to design a representative cell model of DJ-1-associated PD in order to further study DJ-1 with the intention of elucidating its relevant function in relation of PD pathogenesis.

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Self-reactive CD4+ helper T cells (Th) are key causal agents in the pathogenesis of many autoimmune diseases. Experimental autoimmune encephalomyelitis (EAE) is a CD4+T cell model of the demyelinating autoimmune disease multiple sclerosis (MS). It has been shown that EAE is caused by CD4+ T-cells that produce pro-inflammatory cytokines IFN-γ (Th1) and IL-17 (Th17). As such, understanding how these Th cells are generated and controlled is essential. There is debate as to whether Th1 and Th17 cells act independently in EAE or if there is plasticity between these two subtypes, and whether the capacity to switch from Th1 to Th17 confers pathogenic capacity. T-bet was first described as the master transcription factor for Th1 cells, and is thought to have a critical role in EAE even though IFN-γ, the Th1 archetypal cytokine, has been shown to be redundant. More recent work has shown that T-bet is expressed in multiple immune cell types, and it remains unclear in what cells the expression of T-bet is required for EAE. Considerable efforts have been put into understanding the role of T-bet in EAE pathogenesis, with a view to modulate cells expressing T-bet for therapy. The hypothesis of this work was that T-bet has multifaceted roles in EAE, in initiating and directing an immune response in innate antigen presenting cells such as dendritic cells (DC) as well as programming pathogenic effector CD4+ T cell (Teff) response to antigen. T-bet-/- mice were studied using different models of EAE to dissect the role of T-bet in disease pathogenesis. Active immunisation of C57BL/6 mice with the immunodominant peptide from myelin oligodendrocyte glycoprotein (MOG35-55) showed that T-bet-/- mice developed EAE with an IL-17 dominated profile and critically, T-bet-/- mice were able to produce GM-CSF which has recently been described as a key cytokine for EAE. T-bet-/- cells were not able to transfer EAE in a model of passive transfer EAE, where CD4+ T cells were polarised towards a Th1 profile in vitro. Illustrating that T-bet is required in CD4+ T cells for Th1 mediated EAE. DC driven EAE showed that T-bet-/- DC were able to activate CD4+ T cells in vitro and cause EAE upon co-transfer into host mice with transgenic CD4+ T cells. Thus, it has been shown that T-bet is not required in EAE. This work represents a step further towards understanding the disease mechanisms involved in EAE and suggests T-bet is not an appropriate therapeutic target for the treatment of MS.

Many modeling studies have been carried out to simulate the current distribution across the channel and shoulder direction in a proton exchange membrane (PEM) fuel cell. However the modeling results do not show agreement on the current density distribution. At the same time, no experimental measurement result of current density distribution across the channel and the shoulder direction is available to testify the modeling studies. Hence in this work, an experiment was conducted to separately measure the current densities under the channel and the shoulder in a PEM fuel cell by using the specially designed membrane electrode assemblies. The experimental results show that the current density under the channel is lower than that under the shoulder except when the fuel cell load is high. Afterwards two more experiments were carried out to find out the reason causing the higher current density under the shoulder. The effects of the electric resistance of gas diffusion layer (GDL) in the lateral and through-plane directions on the current density distribution were studied respectively. The experimental results show that it is the through-plane electric resistance that leads to the higher current density under the shoulder. Moreover, a three-dimensional fuel cell model is developed using FORTRAN. A new method of combining the thin-film model and homogeneous model is utilized to model the catalyst layer. The model is validated by the experimental data. The distribution of current density, oxygen concentration, membrane phase potential, solid phase potential and overpotential in a PEM fuel cell have been studied by the model. The modeling results show that the new modeling method provides better simulations to the actual transport processes and chemical reaction in the catalyst layer of a PEM fuel cell.

Advantages of electrochemical wastewater treatment over conventional wastewater treatment include its smaller footprint, modularity, and ability to meet increasingly stringent government regulations. A power supply that can be packaged with an electrochemical stack could make electrochemical wastewater treatment more cost-effective and scalable. For this application, the series and series-parallel resonant converters are suitable power converter candidates. With an output current specification of 100A, the series-parallel resonant converter (SPRC) is superior due to its simpler output stage. The thesis presents the design of a 500W SPRC for a wastewater treatment cell stack. A rudimentary cell model is derived experimentally. The closed loop analysis, controller design and simulation results are presented. The output voltage and current are estimated using sensed quantities extracted from the high voltage, low current primary side. Low voltage experimental results verify the operation of the power stage and voltage estimation circuitry in open loop pulsed operation.

Advantages of electrochemical wastewater treatment over conventional wastewater treatment include its smaller footprint, modularity, and ability to meet increasingly stringent government regulations. A power supply that can be packaged with an electrochemical stack could make electrochemical wastewater treatment more cost-effective and scalable. For this application, the series and series-parallel resonant converters are suitable power converter candidates. With an output current specification of 100A, the series-parallel resonant converter (SPRC) is superior due to its simpler output stage. The thesis presents the design of a 500W SPRC for a wastewater treatment cell stack. A rudimentary cell model is derived experimentally. The closed loop analysis, controller design and simulation results are presented. The output voltage and current are estimated using sensed quantities extracted from the high voltage, low current primary side. Low voltage experimental results verify the operation of the power stage and voltage estimation circuitry in open loop pulsed operation.

Many speech enhancement algorithms suffer from musical noise - an estimation residue noise consisting of music-like varying tones. To reduce this annoying noise, some speech enhancement algorithms require post-processing. However, a lack of auditory perception theories about musical noise limits the effectiveness of musical noise reduction methods. Scientists now have some understanding of the human auditory system, thanks to the advances in hearing research across multiple disciplines - anatomy, physiology, psychology, and neurophysiology. Auditory models, such as the gammatone filter bank and the Meddis inner hair cell model, have been developed to simulate the acoustic to neuron transduction process. The auditory models generate the neuron firing signals called the cochleagram. Cochleagram analysis is a powerful tool to investigate musical noise. We use auditory perception theories in our musical noise investigations. Some auditory perception theories (e.g., volley theory and auditory scene analysis theories) suggest that speech perception is an auditory grouping process. Temporal properties of neuron firing signals, such as period and rhythm, play important roles in the grouping process. The grouping process generates a foreground speech stream, a background noise stream, and possibly additional streams. We assume that musical noise is the result of grouping to the background stream the neuron firing signals whose temporal properties are different from the ones grouped to the foreground stream. Based on this hypothesis, we believe that a musical noise reduction method should increase the probability of grouping the enhanced neuron firing signals to the foreground speech stream, or decrease the probability of grouping them into the background stream. We propose a post-processing musical noise reduction method for the auditory Wiener filter speech enhancement method, in which we employ a proposed complex gammatone filter bank for the cochlear decomposition. The results of a subjective listening test of our speech enhancement system show that the proposed musical noise reduction method is effective. / Thesis (Master, Electrical & Computer Engineering) -- Queen's University, 2008-05-28 16:11:28.374

abstract: This research investigated using impedance as a minimally invasive oral cancer-screening tool by modeling healthy and diseased tissue. This research developed an ultra-structurally based tissue model for oral mucosa that is versatile enough to be easily modified to mimic the passive electrical impedance responses of multiple benign and cancerous tissue types. This new model provides answers to biologically meaningful questions related to the impedance response of healthy and diseased tissues. This model breaks away from the old empirical top down "black box" Thèvinin equivalent model. The new tissue model developed here was created from a bottom up perspective resulting in a model that is analogous to having a "Transparent Box" where each network element relating to a specific structural component is known. This new model was developed starting with sub cellular ultra-structural components such as membranes, proteins and electrolytes. These components formed the basic network elements and topology of the organelles. The organelle networks combine to form the cell networks. The cell networks combine to make networks of cell layers and the cell layers were combined into tissue networks. This produced the complete "Transparent Box" model for normal tissue. This normal tissue model was modified for disease based on the ultra-structural pathology of each disease. The diseased tissues evaluated include cancers type one through type three; necrotic-inflammation, hyperkeratosis and the compound condition of hyperkeratosis over cancer type two. The impedance responses for each of the disease were compared side by side with the response of normal healthy tissue. Comparative evidence from the models showed the structural changes in cancer produce a unique identifiable impedance "finger print." The evaluation of the "Transparent Box" model for normal tissues and diseased tissues show clear support for using comparative impedance measurements as a clinical tool for oral cancer screening. / Dissertation/Thesis / normal oral mucosal tissue model / cancer type 1 oral mucosal tissue model / cancer type 2 oral mucosal tissue model / cancer type 3 oral mucosal tissue model / hyperkeratosis oral mucosal tissue model / hyperkeratosis over cancer type 2 oral mucosal tissue / necrotic inflammation oral tissue model / Ph.D. Electrical Engineering 2012

Doctor of Philosophy / Department of Human Nutrition / Brian Lindshield / Fortified blended foods (FBFs), in particular, corn-soybean blend (CSB), are food aid commodities widely used in infant and young children supplementary feeding programs. A United States Agency for International Development (USAID) Food Aid Quality Review report recommended developing novel FBFs using local alternative commodities such as sorghum and improving the nutritional quality of FBFs using extrusion processing. Extruded sorghum-cowpea, sorghum-soy and corn-soy FBFs were developed and compared with the non-extruded FBFs corn-soy blend 13 (CSB13) and corn-soy blend plus (CSB+) using the in-vitro digestion/Caco-2 cell model. Dry FBFs’ iron and vitamin A content ranged from 8.0 to 31.8 mg/100g and 0.54 to 1.67 mg/100g, respectively. Following in-vitro digestion, bioavailable iron and vitamin A levels were determined by measuring Caco-2 cell ferritin and vitamin A levels in response to 12-hour and 4-hour treatments, respectively, with aqueous fractions collected from digested FBFs. Most extruded FBFs’ aqueous fraction iron levels were 2- to 7-fold higher (p<0.05) than CSB13 and CSB+. However, Caco-2 cell ferritin and vitamin A levels were not significantly different among FBFs. These results suggest that consumption of newly developed extruded sorghum-cowpea, sorghum-soy and corn-soy FBFs will result in bioavailable iron and vitamin A levels comparable to traditional non-extruded CSB13 and CSB+. Thus, extruded sorghum-cowpea FBF may be a suitable alternative to corn-soybean based FBFs. Saw palmetto supplements are one of the most commonly consumed products by men with prostate cancer and/or benign prostatic hyperplasia (BPH). Some studies have found significant improvements in BPH with saw palmetto supplementation, whereas others found no benefits. The variation in the efficacy in these trials may be a result of differences in the putative active components, fatty acids and phytosterols, of the saw palmetto supplements. We quantified fatty acids and phytosterols in 20 commercially available liquid, powder, dried berry, and tincture saw palmetto supplements. Liquid saw palmetto supplements contained significantly higher (p<0.05) concentrations of total fatty acids (908.5 mg/g), individual fatty acids, total phytosterols (2.04 mg/g), and individual phytosterols, than the other supplement categories. Our findings suggest that liquid saw palmetto supplements may be the best choice for individuals who want to take a saw palmetto supplement.

This diploma thesis focuses on computational modeling of the cell mechanical tests. The goal of this thesis is to build a cell model and to simulate compression test on this model. If necessary, the model should be adjusted so the model reflects real cell behavior. It was created the cell model reflecting cytoplasm, nucleus, membrane and cell cytoskeleton. Cytoskeleton was modeled as tensegrity structure. After this, the pressure test was simulated on this model. The behavior of the cell model and real cell was compared using the stress force. The stress force - cell deformation curve was markedly different for the cell model and the real cell. For this reason, the cytoplasm material model was adjusted. The difference between the curves was acceptable after this modification. It was found during computations that the cytoskeleton model influence on the cell load is minimal. These results does not reflects real cell behavior, which means that the model is considered inadequate for performing stress load simulation.