Department: Biomedical Engineering (Engineering and Technology) ![[clear]](close-x.png "Remove this limiter")
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1.
Carlson, Grady E.
Dynamic Biochemical Tissue Analysis of L-selectin Ligands on Colon Cancer Tissues.
Degree: MS, Biomedical Engineering (Engineering and Technology), 2012, Ohio University
► Identification and characterization of molecular markers (MϺ) on cancerous tissue can lead…
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▼ Identification and characterization of molecular markers (MϺ) on cancerous tissue can lead to novel diagnostics and prognostics for cancer. Sialofucosylated MϺ, e.g., sialyl Lewis X and sialyl Lewis A, are over expressed in colon cancers and have been associated with poor cancer prognosis. Mounting evidence suggests sialofucosylated MϺ include E-, P- and L-selectin ligands that mediate cancer metastasis with their selectin counterparts. In this study, immunostaining, the current standard for analysis of MϺ on pathological tissue was employed to detect L-selectin/L-selectin ligand binding. However, immunostains did not engender the biophysical conditions requisite for detection of functional L-selectin/L-selectin ligand interactions. In stark contrast, a novel method of tissue analysis, termed dynamic biochemical tissue analysis (DBTA), probed colon cancer tissues for L-selectin ligands and detected the signature event of selectin/selectin ligand binding, i.e., rolling. Microsphere rolling velocities across defined levels of wall shear stress reflected the force-dependent nature of L-selectin/L-selectin ligand interactions, and revealed that in contrast to immunostains, DBTA provides a distinct detection of functional in situ L-selectin ligands on colon cancer tissues.
Advisors/Committee Members: Burdick, Monica.
Subjects: Biomedical Engineering
Keywords: DBTA; L-selectin; colon cancer
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2.
Gu, Mingyu.
Effect of Nitric Oxide on Myeloid Dendritic Cell Adhesion.
Degree: MS, Biomedical Engineering (Engineering and Technology), 2012, Ohio University
► Cell adhesion and motility are controlled by the interplay between the dynamics…
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▼ Cell adhesion and motility are controlled by the interplay between the dynamics of actin cytoskeleton and the formation/disassembly of cell-matrix adhesion area. Dendritic cells (DCs), known as the initiators and modulators of innate and adaptive immunities, can migrate from peripheral tissues to lymph nodes (LN) after antigen challenge. However, the mechanism of how DCs manage to leave the tissue sites is not fully understood. Some previous in vitro studies on bone marrow-derived myeloid DCs suggest (1) in static cell culture systems, cellular production of inducible nitric oxide (NO) by mature DCs plays a role in decreasing adherence between these cells to extracellular matrix components (ECM); (2) NO inhibition restores adhesion events, especially on fibronectin. In this thesis, we try to uncover the way in which DCs decrease adhesive property to ECM after encountering foreign antigens. We found NO is involved in regulating the distribution of cytoskeleton and the expression protein kinases at the focal adhesion sites, suggesting the capability of NO in decreasing the adhesive properties of DCs.
Advisors/Committee Members: Benencia, Fabian.
Keywords: dendritic cell; focal adhesion; cytoskeleton; nitric oxide; extra cellular matrix
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3.
Hata, Misako.
Comparison of a Novel Cell-based Reporter Assay and a Competitive Binding ELISA for the Detection of Thyrotropin-Receptor (TSHR) Autoantibodies (TRAb) in Graves’ Disease Patients.
Degree: MS, Biomedical Engineering (Engineering and Technology), 2010, Ohio University
► The pathogenesis factor of Graves’ Disease (GD) has been widely accepted as…
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▼ The pathogenesis factor of Graves’ Disease (GD) has been widely accepted as autoantibodies against thyrotropin receptor (TSHR) over-stimulating follicular cells to produce excess thyroid hormones. For the last few decades, the competitive binding assay for TSHR antibody (TRAb) has been the most commonly used assay for the differential diagnosis of GD. The competitive binding assay measures the heterogeneous mixture of TRAbs in the patients’ sera that prevent labeled thyroid stimulating hormone (TSH) or monoclonal stimulating TRAb from binding to the fixed human recombinant or porcine TSHRs. In this study, a new cell based reporter assay with chimeric human TSHR (Mc4) was evaluated against the third generation competitive binding Enzyme-Linked Immuno Sorbent Assay (ELISA). Mc4 utilizes its mechanism to detect only the simulating TRAbs in the patent sera that directly correlate with GD hyperthyroidism. Furthermore, a Mc4 predicate, a cell based reporter assay with human wild type (hWT) TSHR (CHO-Luc), was evaluated. This study conducted comparisons of these three assays on the same group of GD patients (n = 200) and healthy blood donors (HBD) (n = 40). Overall sensitivities given the sample provider’s diagnosis as the reference standard were similar with all three assays (84.0 – 73.4%). Mc4 had the second highest sensitivity (79.5%) without misdiagnosing normal controls (specificity = 100%). Sensitivity comparison was ambiguous since some of the 200 GD specimens had high TSH and might have been receiving antithyroid drug treatments which interfered with the assay results. When GD positive groups were divided with TSH levels, agreements of all the assay results were the highest within the very low TSH (TSH < 0.01 µIU/mL) group. Interpretation of TRAb ELISA gave different performance measures (sensitivity and specificity) within the same sample set.
Advisors/Committee Members: Goetz, Douglas.
Subjects: Biochemistry; Biomedical research; Engineering
Keywords: Graves’ Disease; Basedow’s Disease; GD; TSHR; thyrotropin receptor; TSHR autoantibodies; TRAb assay; TSAb assay; TRAb ELISA; Thyretain; TSI reporter bioassay; TSI assay; Diagnostic HYBRIDS; Diagnostic Test; Chimeric Receptor; Sensitivity
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4.
Henson, Karissa A.
A Study of Breast Cancer Cell Adhesion to Endothelium in Response to Cytokine Stimulus.
Degree: MS, Biomedical Engineering (Engineering and Technology), 2010, Ohio University
► Molecules present in the bone marrow microenvironment contribute to attraction, adhesion, and…
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▼ Molecules present in the bone marrow microenvironment contribute to attraction, adhesion, and infiltration of circulating breast cancer cells. Breast cancer stem cells, characterized as CD44+/CD24-/low, are implicated in progression of the disease. However, the specific mechanism used by breast cancer cells to metastasize is unknown. This study thus aimed to determine the role of breast cancer stem cells and microenvironmental factors in bone marrow metastasis, specifically in the adhesion of migrating cancer cells to bone marrow endothelium. The focal points of the study were E-selectin, SDF-1α, and their binding partners because of their integral roles in the cell adhesion and migration of other cell types to bone. Both stem cell-like and non stem cell-like breast cancer cells were found to express CXCR4 which binds SDF-1α. SDF-1α consistently enhanced E-selectin related adhesion of breast cancer cells to endothelium. Conversely, TGF-β1 induced epithelial mesenchymal transition to make cancer cells stem-like appeared to have no effect on this process. These results indicate that the breast cancer stem cell phenotype may not be necessary for E-selectin mediated cancer homing to the metastatic site, but may play a role in a unique homing method to bone marrow or in the formation of a new tumor upon bone marrow infiltration.
Advisors/Committee Members: Burdick, Monica M.
Subjects: Biomedical research
Keywords: Breast Cancer; Cancer Stem Cells; Metastasis; E-selectin; Cell Adhesion; SDF-1; TGF-beta
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5.
Nandigam, Harika.
Capability of the Tumor Microenvironment to Attract a Precursor of B-cells and Dendritic Cells from Bone Marrow.
Degree: MS, Biomedical Engineering (Engineering and Technology), 2011, Ohio University
► Bone marrow derived precursors are attracted by tumors [20]. Evidence shows that…
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▼ Bone marrow derived precursors are attracted by tumors [20]. Evidence shows that these bone marrow precursor cells can secrete factors that they will either modulate neovasculature or incorporate tissue vascularization [5, 24]. A bone marrow derived leukocyte population is seen in tumor vasculature, which expresses both hematopoietic and endothelial cell markers and was named as Vascular Leukocytes (VLCs) [3]. This population was not seen outside the tumor microenvironment [22]. In mouse ovarian models, experiments were performed, which showed that there was a dramatic decrease in the bone marrow precursors as tumor develops, particularly precursor B-cells and DCs (PBDs). Those leukocytes are believed to be attracted by subgroup of cytokines called chemokines. Experiments were conducted in ovarian tumors to reveal the profile of chemokines and their receptors, which might be responsible for migration of the PBDs. These results indicate that Exodus 2, RANTES and SDF-1 play a major role in migration of PBDs towards the tumor.
Advisors/Committee Members: Benencia, Fabian.
Subjects: Biology; Biomedical Engineering; Biomedical Research; Immunology
Keywords: Bone marrow; chemokines; hematopoietic; VLCs; PBDs; HSCs; tumor microenvironment
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6.
O'Brien, John D.
The Effect of Small Organic Compounds on Triple Negative Breast Cancer Cells.
Degree: MS, Biomedical Engineering (Engineering and Technology), 2012, Ohio University
► The ability of small organic compounds to inhibit the expression of a…
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▼ The ability of small organic compounds to inhibit the expression of a cytokine by triple negative breast cancer cells was explored. In addition, the ability of the cytokine to exert an autocrine effect on the cancer cells was probed.
Advisors/Committee Members: Goetz, Douglas.
Subjects: Biomedical Engineering; Biomedical Research
Keywords: breast cancer; triple negative; phenylmethimazole; interleukin-6 (IL-6); interleukin 6 receptor
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7.
Schwartz, Anthony L.
A Novel Approach for the Treatment of Pancreatic Cancer.
Degree: MS, Biomedical Engineering (Engineering and Technology), 2009, Ohio University
► It is recognized that chronic inflammation is an important risk factor for…
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▼ It is recognized that chronic inflammation is an important risk factor for the development of cancer. The pro-inflammatory cytokine IL-6 is implicated in cancer via its role in the activation of STAT-3, a key regulator of cancer growth, survival, metastasis, and angiogenesis. We have shown that human pancreatic cancer cells express high levels of Toll-like receptor 3 (TLR3). We hypothesize that IL6/ STAT-3 activation, mediated by over-expressed TLR3 signaling, is important in the tumor growth process, increases Wnt5a signaling, and is associated with increased cellular growth and migration. Phenylmethimazole (C10), a novel inhibitor of pathologic TLR3 signaling, decreased IL-6, STAT-3 and Wnt5a, suppressed human pancreatic cancer cell growth and migration in vitro as well as growth in a syngeneic mouse model. These results suggest that inhibition of TLR3 expression and signaling may be a new therapeutic paradigm for the treatment of pancreatic cancer.
Advisors/Committee Members: McCall, Kelly D.
Subjects: Biomedical research
Keywords: Toll-like Receptors; phenylmethimazole; pancreatic cancer
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8.
Shi, Bibo.
Regularity-Guaranteed Transformation Estimation in Medical Image Registration.
Degree: MS, Biomedical Engineering (Engineering and Technology), 2011, Ohio University
► In addition to seeking geometric correspondence between the inputs, a legitimate medical…
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▼ In addition to seeking geometric correspondence between the inputs, a legitimate medical image registration algorithm should also keep the estimated transformation meaningful or regular. In this thesis, we present a mathematically sound formulation that explicitly controls the transformation to keep each grid in a meaningful shape over the entire geometric matching procedure. The deformation regularity conditions are enforced by maintaining all the moving neighbors as non-twist grids. In contrast to similar work, we differentiate and formulate the convex and concave folding cases under an efficient and straightforward point-to-line/surface orientation framework, and use equality constraints to guarantee grid regularity and prevent folding. The equality constrained optimization problem is efficiently solved using the augmented Lagrangian Mulplier method. Experiments on human brain MR images are presented to show the improvements made by our model over the popular Demon’s and DCT-based registration algorithms. Extension to develop a clinical registration package including the regularity guaranteed conditions is also explored.
Advisors/Committee Members: Liu, Jundong.
Subjects: Biomedical Engineering
Keywords: medical image; image registration; regularity
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9.
Snively, Eric.
Rigid Body Mechanics of Prey Capture in Large Carnivorous Dinosaurs.
Degree: MS, Biomedical Engineering (Engineering and Technology), 2012, Ohio University
► Rigid body mechanics enables testing hypotheses of feeding in predatory theropod dinosaurs.…
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▼ Rigid body mechanics enables testing hypotheses of feeding in predatory theropod dinosaurs. This thesis presents two analyses: (a) calculation and comparison of theropod rotational moments of inertia about a vertical axis (Iy), and (b) simulation of head movements in the theropod Allosaurus. (a). Tyrannosaurids were unique as the only theropods in their habitats. I calculated mass and Iy by representing theropod bodies as superelliptical frustra, and derived indices for relative agility from Iy and leg muscle forces and moments. Tyrannosaurids (especially juveniles) had higher agility indices than other theropods of the same mass. Estimates of mass and Iy agree closely with those from other methods. (b). Allosaurus had an apparently flexible neck. I constructed a musculoskeletal model of Allosaurus in Solid Edge and MSC.Adams, to simulate kinematics and dynamics of its head and neck. Allosaurus could move its head at higher angular accelerations than could Tyrannosaurus. Unique muscle attachments substantially augmented head ventroflexion, and alternate reconstructions of the muscle m. complexus would both rapidly lateroflex the head.
Advisors/Committee Members: Cotton, John.
Subjects: Biomedical Research; Paleontology
Keywords: Dinosauria, biomechanics, Theropoda, feeding
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10.
Sprague, Leslee W.
Dendritic Cell Culture With 2D and 3D Collagen Substrates.
Degree: MS, Biomedical Engineering (Engineering and Technology), 2011, Ohio University
► Dendritic cells (DCs) are professional antigen presenting cells (APCs) which play a…
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▼ Dendritic cells (DCs) are professional antigen presenting cells (APCs) which play a major role in signaling and directing immune responses. DCs are primarily found in peripheral tissues where they phagocytose, process, and present pathogen derived peptides to T lymphocytes through major histocompatibility complex (MHC) molecules I and II (Signal I). In addition to antigen presentation with MHC I and II molecules, APCs express co-stimulatory molecules that can induce or suppress specific T cell activity and differentiation (Signal II). The presence of DC derived cytokines provides the next signal for the adaptation of a specific adaptive immune response (Signal III). However, previous studies conducted in our lab have shown that in addition to cytokine signaling, the extracellular microenvironment where DCs encounter pathogen and interact with other immune cells may define their ability to activate or suppress specific adaptive immune responses (Signal III). The extracellular matrix components can sometimes even lead to an immunosuppressive and angiogenic DC phenotype. Here, we outline the in vitro study of murine bone marrow derived myeloid DCs cultured in a two-dimensional (2D) or three-dimensional (3D) culture substrates of collagen type I in the presence of GM-CSF. We have found that DCs can differentially express angiogenic factors when cultured in 3D arrangement when compared with the 2D arrangement. RNA extracts were taken after fourteen days of culture to analyze DC production of angiogenic and immunogenic factors at the RNA level and protein level. Angiogenic factors were analyzed at the mRNA level by real time quantitative PCR (qPCR) using a murine angiogenesis PCR array. Immunogenic factors at the protein level were analyzed using flow cytometry and cytokine multiplex analysis.
Advisors/Committee Members: Benencia, Fabian.
Subjects: Biology; Biomedical Research; Cellular Biology; Immunology; Molecular Biology
Keywords: dendritic cells; angiogenesis; immunology; cytokines; chemokines; pcr
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11.
Starkey, Michael M.
Investigation of Capstan Friction and its Potential Use as a Mechanical Amplifier.
Degree: MS, Biomedical Engineering (Engineering and Technology), 2010, Ohio University
► Actuation is one of the fundamental aspects of robots. Optimization of a…
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▼ Actuation is one of the fundamental aspects of robots. Optimization of a robotic system poses a complex problem for engineers. For developing robots that mimic biological systems, the robot actuation problem becomes more complicated because of stringent limitations on space and power output. It is hypothesized that a system can be designed which would allow a rotating capstan to act as a mechanical amplifier when a flexible member such as a cord or rope is wrapped around it. When a tension is applied to the end of the cord pointing in the direction of the capstan's rotation, friction will be transferred to the cord and the tension will effectively be amplified. Experimentation was performed to validate a traditional assumption for how the dynamics of the system should work. The capstan equation was found to be only a rough estimation of the behavior of the system. A new equation was formed by combining known curves and fitting them to the data. Simulation of the new equation provides an initial insight into the behavior of a combined capstan amplifier system.
Advisors/Committee Members: Williams, Robert.
Subjects: Mechanical engineering; Robots
Keywords: capstan; unidrive; cable actuation; control motor; mechanical amplifier; mechanical amplification
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12.
Venkatesh, Amritha K.
Toll-like Receptor 3 Signaling in Breast Cancer Cells and the Recruitment of Leukocytes to the Tumor Microenvironment.
Degree: MS, Biomedical Engineering (Engineering and Technology), 2012, Ohio University
► Advanced stages of breast cancer are often associated with chronic inflammation in…
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▼ Advanced stages of breast cancer are often associated with chronic inflammation in the tumor microenvironment that in turn attracts proangiogenic factors, resulting in neoangiogenesis. The upstream signaling that triggers this chronic inflammation is poorly understood. Toll-like receptors are a group of proteins involved in innate immunity and it was hypothesized that the over-stimulation of downstream TLR3 signaling could lead to the production of chemokines that cause leukocyte infiltration into the tumor microenvironment. In vitro stimulation of TLR3 using poly(I:C) and poly(A:U) yielded supportive results, showing an increase in the expression of RANTES, IL-6 and MIP-2 in both mouse mammary tumor cell line 4T1 and human breast cancer cell line MCF7. Further, treated 4T1 cell samples caused a greater percentage of migration of mouse dendritic cells and macrophages as compared to untreated samples in vitro. Lastly, TLR3 expression was knocked down by using siRNA. In the future, TLR3 knock down studies in vivo will help understand the effectiveness of targeting TLR3 in drug development.
Advisors/Committee Members: Benencia, Fabian.
Subjects: Biomedical Engineering; Biomedical Research; Molecular Biology
Keywords: breast cancer; TLR3; toll like receptor; leukocyte infiltration; tumor microenvironment; poly(I:C); poly(A:U); TLR3 signaling
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13.
Wood, S. Matthew.
A Study of Head and Neck Squamous Cell Carcinoma Adhesion Mediated by Glycosphingolipids.
Degree: MS, Biomedical Engineering (Engineering and Technology), 2011, Ohio University
► Cancer metastasis is the leading cause of cancer related deaths. It is…
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▼ Cancer metastasis is the leading cause of cancer related deaths. It is a multistep process caused by cancer cells breaking away from the primary site and traveling through the lymphatic system or bloodstream, adhering to the endothelium and migrating through the endothelium to a new site. The molecular mechanisms concerning how cancer cells metastasize are not fully understood, with many gaps in the available information. It has been theorized that cancer cells may mimic and exploit similar mechanisms used by leukocytes in response to cytokine stimulation. Using the leukocyte adhesion cascade as a model, it is hypothesized that E-selectin a cell adhesion molecule (CAM) on endothelium and its ligands on cancer cells play a major role in metastasis of head and neck squamous cell carcinoma (HNSCC). Much research has been devoted to the study of sialofucosylated proteins as ligands for E-selectin; this study elucidates the role of sialofucosylated glycosphingolipids as a ligand for E-selectin. All HNSCC cells bound to human umbilical vein endothelial cells (HUVECs) in an E-selectin dependent manner, as treatment of HUVECs with anti-E-selectin monoclonal antibody eliminated tethering. Treatment of HNSCC cells with the protease bromelain led to decreased rolling velocities on HUVECs compared to untreated HNSCC cells, without reducing tethering. HNSCC polar lipid extracts (PLE, i.e. glycosphingolipids) were found to possess sialofucosylated E-selectin ligands, as adhesion of E-selectin transfected cells to immobilized HNSCC cell PLE was eradicated after treatment with sialidase and fucosidase. Moreover, polystyrene microspheres coated with PLE (mimicking cellular presentation) tethered and rolled on HUVECs under flow, while negative control microspheres did not. These results taken together implicate that siaolofucosylated glycosphingolipids are the major E-selectin ligands expressed on HNSCC cells.
Advisors/Committee Members: Burdick, Monica.
Subjects: Biomedical Engineering
Keywords: HNSCC; glycosphingolipids; E-selectin
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