Biomedical Engineering and Bioengineering Commons^™

Hif-1 Alpha: A Master Regulator Of Trophoblast Differentiation And Placental Development, Kashmira Kulkarni

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Early embryonic development occurs under low oxygen levels. The placenta is an organ transiently formed during pregnancy and plays a crucial role during development of the embryo. Alterations in the placental structure or function have been associated with the pathologies such as preeclampsia in humans. In mammals, the hypoxia inducible factor (HIF) transcription factors have been identified as the major regulators of cellular responses in low oxygen. In the current study, we investigated the effects of low oxygen on the differentiation of trophoblast stem cells, lineage committed trophoblast giant cells and labyrinthine lineage-committed cells. We examined the effects of an …

Central Mechanisms Regulating Pituitary-Adrenal Activity In Infant Guinea Pigs (Cavia Porcellus) During Exposure To Psychological Stressors: Independent And Combined Effects Of Maternal Separation And Novelty, Deborah Suzanne Maken

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Separation from the maternal attachment figure, particularly when it occurs in a novel or threatening environment, reliably increases pituitary-adrenal activity in a number of species, and is thought to increase later susceptibility to psychopathology in humans. However, little is known about the central mechanisms mediating these effects. Therefore, I investigated cortisol and ACTH levels in plasma, corticotropin-releasing factor (CRF) mRNA expression in the hypothalamic paraventricular nucleus (PVN), and c-Fos activity in a circuit [medial amygdala (MeA)- bed nucleus of the stria terminalus (BNST)] thought to drive pituitary-adrenal activity during exposure to psychological stressors, as well as in the PVN. Measurements …

Genetic Differentiation In Ambystomatid Salamanders Across A Fragmented Landscape, Joseph E. Bartoszek

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It is generally recognized that amphibian populations declining across the globe. Habitat loss is the primary cause of decline. The salamander family Ambystomatidae has experienced significantly more rapid decline than the average for amphibians. Coefficients of Conservatism (CoC) have been developed for amphibians in Ohio. These are based primarily on habitat requirements with high CoCs for amphibians with stringent habitat requirements (e.g. vernal pools associated with large, intact, undisturbed forest), and low CoCs for amphibians with less stringent habitat requirements. Genetic diversity in five species and one hybrid complex of ambystomatid salamander in southwest Ohio were examined and compared to …

Characterization Of Excitatory Amino Acid Neurotransmitters At Motoneuron Synapses Contacting Renshaw Cells, Dannette Shanon Richards

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Motoneurons are among the best studied neurons in the central nervous system. The motoneuron synapses have been well characterized in the periphery where they release acetylcholine at the neuromuscular junction. However excitatory amino acids also seem to be released from motoneuron terminals in the periphery, and centrally at their synapses contacting Renshaw cells. Although excitatory amino acids are suggested to be released from motoneuron synapses it is not known which excitatory amino acids (either aspartate or glutamate) are released, nor is the mechanism for their release known. To examine the presence and mechanism of release for aspartate and glutamate at …

The Effects Of Chronic Hypoxia And Substance P On The Chemosensitive Response Of Individual Nucleus Tractus Solitarius (Nts) Neurons From Adult Rats, Nicole L. Nichols

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The chemosensitive responses of individual nucleus tractus solitarius (NTS) neurons from neonatal rats have been extensively studied, but few studies have examined the chemosensitive responses of NTS neurons from adult rats. In addition, environmental conditions have been used to mimic respiratory diseases/disorders in rats to study how the cellular responses of individual neurons change to regulate breathing during pathological conditions. Lastly, it has been shown that substance P release increases in response to hypoxia from peripheral afferents that primarily terminate in the caudal NTS. We studied the effect of chronic hypoxia (CHx) and substance P on the response to hypercapnia …

Novel Redox And Dna-Dependent Conformational Changes In Human Ku, A Dna-Double Strand Break Repair Protein, Jason Alexander Lehman

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Ionizing radiation (IR) and radiomimetic drugs used in cancer chemotherapy cause DNA double-strand breaks which are repaired by the nonhomologous end joining (NHEJ) pathway. Ku is a heterodimeric protein comprised of 70 and 80 kDa subunits and recognizes free DNA ends. Once Ku is bound to DNA, it binds to the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and forms a heterotrimeric DNA-PK complex for repair and damage signaling.

We have analyzed the Ku protein using multiple biochemical techniques and uncovered a novel reversible redox change (Andrews, Lehman and Turchi, (2006) JBC 281(19):13596-603). From this data, we hypothesized that a redox-dependent …

Performance Analysis Of Quantitative Bone Measurement With Spiral, Multi-Detector Ct Scanners, Shruti Gupta

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The measure of bone strength and fracture risk assessment is based primarily on bone mineral density (BMD). Computed tomography (CT), a frequently used radiographic technique that provides cross-sectional images, can be used for BMD quantification. Called quantitative computed tomography (QCT), it determines true volumetric density and also differentiates between trabecular and cortical bone. As a result, QCT improves the ability to detect early changes in trabecular BMD accurately and precisely.

The introduction of helical CT for quantitative analysis introduces new complexities. Even though using multi-detector helical CT for BMD assessment is being suggested, a detailed analysis of its validity is …

Histogram-Based Template Matching Object Detection In Images With Varying Brightness And Contrast, Christina Da-Wann Schrider

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Our challenge was to develop a semi-automatic target detection algorithm to aid human operators in locating potential targets within images. In contrast to currently available methods, our approach is relatively insensitive to image brightness, image contrast and object orientation. Working on overlapping image blocks, we used a sliding difference method of histogram matching. Incrementally sliding the histograms of the known object template and the image region of interest (ROI) together, the sum of absolute histogram differences was calculated. The minimum of the resultant array was stored in the corresponding spatial position of a response surface matrix. Local minima of the …

Biomechanical Evaluation Of Locked And Non-Locked Constructs Under Axial And Torsion Loading, Vinit A. Patel

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Locking compression plates are proven to be safe for use in open reduction and internal fixation (ORIF). The ORIF is a procedure performed to treat fractures. It has various combination of holes, the system provides more options for clinicians to use either locking screw or non-locking screws. This thesis investigates and determines the best construct with special locking and non-locking screws under both axial and torsion loading. Twenty femur constructs were assembled with 2 cm osteotomy gap between femur shaft and condyle, bridged with 4.5 mm - 10 holes condyle plates. Femurs were divided in to 4 groups according to …

Motion-Control System Of Bench-Top Ct Scanner, Tarpit Kaushikbhai Patel

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Computed Tomography (CT) imaging has found applications in many areas such as diagnostic visualization, quantitative estimation, and therapeutic verification. In this wide range of applications, a CT scanner that can provide the data collection schemes of both second- and third-generation data-collection geometries will be an asset for laboratory research. In this thesis project, we developed a mechanical design and constructed a dual-generation CT scanner that provides flexibility in accommodating a wide range of object sizes with minimum scan time. Using 3-D graphical design software, models of the current second-generation CT scanner and possible solutions for modification were simulated. Based on …

Finite Element Optimization Of Hip Implant Geometrical Parameters To Determine Safe Zones And Resist Dislocation, Himanshu K. Bhatt

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A computational study was performed using finite element analysis (FEA) of three dimensional solid hip implant models. Twelve different hip implant models were designed to investigate the performance of geometrical parameters affecting hip stability. The parameters examined were head diameter, neck diameter, head-to-neck ratio, neck angle and acetabular liner thickness. Component orientations included cup anatomical inclination and cup anteversion, which should be accounted for during total hip implant design as well as in the practice of arthroplasties. A static analysis was performed for all 12 hip designs using stainless steel 316L. von Mises stress, contact stress, contact penetration, and sliding …

Automated Analysis Of Metacarpal Cortical Thickness In Serial Hand Radiographs, Aarti Raheja

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To understand the roles of various genes that influence skeletal bone accumulation and loss, accurate measurement of bone mineralization is needed. However, it is a challenging task to accurately assess bone growth over a person's lifetime. Traditionally, manual analysis of hand radiographs has been used to quantify bone growth, but these measurements are tedious and may be impractical for a large-scale growth study. The aim of this project was to develop a tool to automate the measurement of metacarpal cortical bone thickness in standard hand-wrist radiographs of humans aged 3 months to 70+ years that would be more accurate, precise …

Detection Of Aortic Calcification During Vertebral Fracture Assessment (Vfa) Compared To Digital Radiography, John T. Schousboe, Kevin E. Wilson, Thomas N. Hangartner

Biomedical, Industrial & Human Factors Engineering Faculty Publications

Background: Cardiovascular disease is the most common cause of mortality among post-menopausal women. Our objective was to determine whether or not lateral spine images obtained on a bone densitometer to detect prevalent vertebral fracture can also accurately detect radiographic abdominal aortic calcification (AAC), an important risk factor for cardiovascular disease independent of clinical risk factors.

Methodology/Principal Findings: One hundred seventy four postmenopausal women had bone densitometry, lateral spine densitometry imaging (called vertebral fracture assessment, or VFA), and lateral spine digital radiographs. Radiographs and VFA images were scored for AAC using a previously validated 24 point scale and a simplified, …

Loss Of Hdmx Leads To Alterations In Gene Expression And Inhibition Of Cell Growth In Tumor Cells With Wild-Type P53, Katherine Ann Heminger

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Mutations in the p53 tumor suppressor gene are among the most prevalent molecular abnormalities in human cancer. While half of all human tumors possess p53 mutations, inactivation of wild-type p53 can also occur through a variety of mechanisms that do not involve p53 gene mutation or deletion. This dissertation focuses on human tumor cell lines harboring wild-type p53 protein and elevated levels of HdmX and/or Hdm2, two critical negative regulators of p53 function. My hypothesis is that loss of HdmX in tumor cells with wild-type p53 and over-expressed HdmX, will activate p53 and induce p53 target genes leading to growth …

Optimal Eeg Channels And Rhythm Selection For Task Classification, Vikramvarun Kannan Adikarapatti

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The Primary Objective of this research is to implement an automatic method for selecting the most optimal EEG channels for task classification purposes. The secondary objective of this research is to choose the most optimal EEG rhythm from which the optimal EEG channels would be selected automatically. The automatic selection of the optimal channels is enabled by implementing the Common Spatial Patterns algorithm (CSP). Common spatial analysis is performed on the data recorded. By choosing the channels with high spatial pattern values the optimal channels are chosen. The optimal frequency bands are chosen by splitting the data from a single …

Structural And Signaling Elements Important For The Efficient Degradation Of Bhmt Through Macroautophagy, Carol A. Mercer

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Healthy cells maintain a dynamic and responsive intracellular environment that is marked by the synthesis and degradation of proteins, complex macromolecules and organelles. Autophagy, literally "self-eating," is a mechanism that delivers cellular cargo to the lytic compartment for digestion. Defects in the regulation of autophagy have been implicated in pathologies such as cancer and neurodegenerative disease, making the study of its regulation compelling. However, few studies have looked at the regulation of mammalian autophagy as a function of a specific cargo protein. Previous studies had indicated that the metabolic enzyme betaine homocysteine methyltransferase (BHMT) is degraded through an autophagic mechanism. …

Biochemical Characterization Of Htrf1 And Htep1, Two Proteins Involved In Telomere Maintenance, Kambiz Tahmaseb

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Telomeres are the structures that protect the ends of linear chromosomes from fusion and degradation. The telomere consists of tandem repeated DNA sequences that can range from hundreds of bases to kilo-bases depending on the organism. As the cells of an organism replicate their DNA, these repeats are lost due to the end replication problem, where the ends of linear DNA cannot be fully replicated. As the telomeres are shortened through each round of replication, they eventually reach a critical point. Once the telomeres are too short and the cell risks losing coding sequences, a signaling pathway is initiated that …

Investigating The Role Of Subunit Iii In The Structure And Function Of Rhodobacter Sphaeroides Cytochrome C Oxidase, R. Ryan Geyer

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The role of subunit III (SIII) in cytochrome c oxidase structure and function was investigated using enzyme isolated from the bacterium Rhodobacter sphaeroides. Energy minimization calculations suggested that in the absence of SIII, subunit I (SI) adopted a more open conformation. This observation was tested through the use of limited proteolysis using, á-chymotrypsin. The results showed that in the absence of SIII the solution structures of wild-type and I/II oxidase were not significantly different, and that proteolysis occurred exclusively at the N and C-termini of SI. Upon inactivation of I/II oxidase by catalytic turnover, and subsequent digestion with the protease …

Functional Interplay Between Subthreshold Ion Channels In Preautonomic Neurons Of The Hypothalamic Paraventricular Nucleus In Health And Disease Conditions, Patrick M. Sonner

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Under normal conditions, blood pressure is tightly regulated through autonomic tonic and reflex mechanisms. However, when the set-point for blood pressure is chronically elevated, hypertension occurs. Hypertension if untreated can lead to further complications including heart failure, stroke and kidney failure. Elevated sympathetic outflow is known to contribute to the development and/or maintenance of hypertension, and while the hypothalamic paraventricular nucleus (PVN), a preautonomic center, has been implicated in the elevation of sympathetic activity during hypertension, the precise pathophysiological mechanisms underlying sympathoexcitation remain unclear. Subthreshold ion channels, including the A-type K ⁺(I _A) and the T-type Ca ^{2+ …}

Fabrication And Testing Of Scaffolds For Cell Growth From Ionic Liquid Solubilized Fibroin, Maneesh Kumar Gupta

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The advent of tissue engineering has spurred research into developing materials to act as scaffolds for tissue growth. These scaffolds require materials capable of mimicking the in vivo conditions so that tissues can be grown effectively in vitro. Silk is an attractive biomaterial for use in tissue engineering applications because of its slow degradation, excellent mechanical properties, and biocompatibility. The major objective of the research in this thesis is to demonstrate a simple method to cast films directly from silk fibroin dissolved in an ionic liquid. The films cast from the silk ionic liquid solution were found to support normal …

Regulation Of Dna Replication Initiation By Histone Acetylation And The Dna Unwinding Element Binding Protein Due-B, Michael George Kemp

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Duplication of the genome during S phase of the mitotic cell cycle begins at thousands of sites along chromosomes termed origins of replication. Although many of the essential protein components catalyzing events at these sites are known and are conserved throughout eukaryotes, the likelihood or efficiency of initiation of DNA synthesis at any given genomic site is expected to be influenced by other novel factors, including aspects of chromatin and DNA structure.

Here I show that increased histone H4 acetylation at replication origin loci occurs after treatment with the histone deacetylase inhibitor TSA and coincides with a loss of specific …

Methodology For Quantifying Biomechanical Bone Movement Of Transtibial Amputations, Johanna C. Bell

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A controversy has long existed about an alternate below knee amputation procedure that may be more beneficial than the traditional transtibial amputation. The proponents of this alternate procedure that stabilizes the distal tibia and fibula claim it reduces excessive movement of the fibula relative to the tibia that occurs with common movements, such as walking. The purpose of this study is to develop a methodology for quantifying excessive movement of the fibula bone relative to the tibia bone in traditional below the knee amputations. The methodology will measure the movement and rotation of the fibula relative to the tibia. These …

Overview Of Metal-On-Polyethylene, Metal-On-Metal, And Ceramic Hip Wear Mechanisms, A. Buford, Tarun Goswami

Biomedical, Industrial & Human Factors Engineering Faculty Publications

Premature failure of orthopaedic hip implants caused by multiple wear mechanisms is the primary failure mode of prosthetic hips. Wearing of the implants may lead to aseptic loosening, biological incompatibilities, and mechanical failure of the implant. In order to prevent or restrict the effects of the wear mechanisms, multiple laboratory studies are being conducted in order to determine each mechanism and its contribution to increased wear rates. This paper combines previous laboratory studies related to the wear of metal-onpolyethylene, metal-on-metal, and ceramic materials. The bulk quantity materials discussed include cobalt chromium alloys, stainless steels, zirconium oxide ceramics, and polyethylene materials …

Wear Mechanisms In Ceramic Hip Implants, M. Slonaker

Biomedical, Industrial & Human Factors Engineering Faculty Publications

The wear in hip implants is one of the main causes for premature hip replacements. The wear affects the potential life of the prosthesis and subsequent removals of in-vivo implants. Therefore, the objective of this article is to review various joints that show lower wear rates and consequently higher life. Ceramics are used in hip implants and have been found to produce lower wear rates. This article discusses the advantages and disadvantages of ceramics compared to other implant materials. Different types of ceramics that are being used are reviewed in terms of the wear characteristics, debris released, and their size …

Wear Mechanisms In Ceramic Hip Implants, M. Slonaker, Tarun Goswami

Biomedical, Industrial & Human Factors Engineering Faculty Publications

The wear in hip implants is one of the main causes for premature hip replacements. The wear affects the potential life of the prosthesis and subsequent removals of in-vivo implants. Therefore, the objective of this article is to review various joints that show lower wear rates and consequently higher life. Ceramics are used in hip implants and have been found to produce lower wear rates. This article discusses the advantages and disadvantages of ceramics compared to other implant materials. Different types of ceramics that are being used are reviewed in terms of the wear characteristics, debris released, and their size …

General Creep-Fatigue Life Prediction Models, J. Toland, Tarun Goswami

Biomedical, Industrial & Human Factors Engineering Faculty Publications

This paper presents a data bank that was compiled from published and unpublished sources. Using these data, low cycle fatigue curves were generated under a range of test conditions showing the effect of test parameters on the Coffin-Manson behavior of steel alloys. Generic equations have been developed in this paper to predict the creep-fatigue life of high temperature materials. Several new multivariate equations were developed to predict the creep-fatigue life of following alloy groups; I) Cr-Mo steels, 2) stainless steels and 3) generic materials involving the materials from the following alloy groups, solder, copper, steels, titanium, tantalum, and nickel based …

Feasibility Of Radiographic Absorptiometry Of The Mandible As An Osteoporosis Screening Method, Julie A. Skipper

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The purpose of this work was to develop and evaluate single- and dual-energy radiographic absorptiometry (RA) for the measurement of mandibular bone mineral density (BMD), using standard dental equipment, that would allow for inexpensive and widespread osteoporosis screening. Accurately measured x-ray tube spectra are important for validating the simulations used in the design of the method. A constrained least-squares deconvolution technique for reducing the detector-induced blurring of the energy spectrum was developed. Application of this analytic correction to spectra acquired with a NaI-photomultiplier detector improved the measured data by 20-60%. Implementation of the screening method is accomplished by simultaneously acquiring …

Weibull Model Development For Fatigue Crack Growth, Bobby Day, Tarun Goswami

Biomedical, Industrial & Human Factors Engineering Faculty Publications

This effort is an attempt to "Weibullize" fatigue crack growth rate data as a function of stress intensity range (ΔΚ). It is not a classical Weibull application in that it does not address a population but rather treats rate of crack growth as a fraction of the highest rate of crack growth rate in the data set (usually the final data point of the set) as the "failed fraction of a population." All da/dN values are converted to a percentage or fraction of the 100% data value, processed into a linear relationship and plotted against the natural log of the …

A Review Of Nanotechnology Applications, Nick Ledbetter, Tarun Goswami

Biomedical, Industrial & Human Factors Engineering Faculty Publications

A review of current technology research efforts has been conducted in this paper. In nanoscience, objects are measured in nanometers, 1 billionth of a meter. For comparison, a human hair is approximately 100,000 nanometers thick and the smallest feature on current computer chips measures about 200 nanometers. Since nanotechnology has a wide range of applications from computer chip manufacturing, new materials, renewable energy, interconnection technology to mount the nano-chips, and in medical science, this review presents a broad summary of development efforts in the government and private sector laboratories. Therefore this project on the one hand prepares a review of …

Effect Of Exposure Time On The Fatigue Crack Growth Behavior Of Aircraft Skin Material, Kathryn Lemasters, Tarun Goswami

Biomedical, Industrial & Human Factors Engineering Faculty Publications

The objective of this research project is to identify the effects of service exposure on aircraft materials. The senior author participated in the KC-135 Corrosion Prevention Program conducted by the University of Utah, Salt Lake City. Data from this research program was analyzed to compare the fatigue crack growth rates of aged aircraft materials with those of virgin materials. 2024-T3(clad) Middle Tension (M(T)) specimens were machined from the fuselage and upper wing skins of a retired aircraft. Fatigue crack growth rate (da/dN) and mode 1 stress intensity factor range (Δ K) plots were generated for both sets of data. The …