Biomedical Engineering and Bioengineering Commons^™

The Role Of Death-Associated Protein Kinase In Endothelial Apoptosis Under Fluid Shear Stress, Keith R. Rennier

Open Access Dissertations

Endothelial cells are the interface between hemodynamic fluid flow and vascular tissue contact. They actively translate physical and chemical stimuli into intracellular signaling cascades which in turn regulate cell function, and endothelial dysfunction leads to inflammation and diseased conditions. For example, atherosclerosis, a chronic vascular disease, favorably develops in regions of disturbed fluid flow and low shear stress. Apoptosis, or programmed cell death, must be properly regulated to maintain homeostasis in the vascular wall. The loss of apoptosis control, as seen in low shear stress regions, is implicated in various diseases such as atherosclerosis and cancer. Death-associated protein kinase, DAPK …

The Pathological Role Of Acrolein In Experimental Autoimmune Encephalomyelitis And Multiple Sclerosis, Melissa A. Tully

Open Access Dissertations

Multiple sclerosis (MS) is an autoimmune demyelinating neuropathy that affects nearly 2.5 million people worldwide. Despite substantial efforts, few treatments are currently available largely due to limited knowledge of pathogenic mechanisms underlying the disease. The immune-inflammatory nature of the pathology has prompted investigation of the role of oxidative stress in disease development and progression; however targeting reactive oxygen species for neutralization has had marginal success therapeutically, suggesting that an alternate oxidative stress-related target would prove beneficial. Recently, our lab has implicated acrolein, a highly reactive aldehyde that is both a byproduct and catalyst of lipid peroxidation, as a potential therapeutic …

Surface Modification Of Traditional And Bioresorbable Metallic Implant Materials For Improved Biocompatibility, Emily Kristine Walker

Open Access Dissertations

Due to their strength, elasticity, and durability, a variety of metal alloys are commonly used in medical implants. Traditionally, corrosion-resistant metals have been preferred. These permanent materials can cause negative systemic and local tissue effects in the long-term. Permanent stenting can lead to late-stent thrombosis and in-stent restenosis. Metallic pins and screws for fracture fixation can corrode and fail, cause loss of bone mass, and contribute to inflammation and pain at the implant site, requiring reintervention. Corrodible metallic implants have the potential to prevent many of these complications by providing transient support to the affected tissue, dissolving at a rate …

A Three Constituent Mixture Theory Model Of Cutaneous And Subcutaneous Tissue In The Context Of Neonatal Pressure Ulcer Etiology And Prevention, Anne Dye Zakrajsek

Open Access Dissertations

Localized ischemia, impaired interstitial fluid flow, and sustained mechanical loading of cells have all been hypothesized as mechanisms of pressure ulcer (PrU) etiology. Time-varying loading has experimentally been shown to increase fluid flow in human skin in vivo. Towards the design of prophylactic protocols and treatment modalities for PrU management there is a need for an analytical model to investigate the local fluid flow characteristics of skin tissue under time-varying loading. In this study, a triphasic mixture theory model with constituents of extracellular matrix, interstitial fluid, and blood was calibrated and validated and used to investigate stress and fluid velocity …

Unveiling The Mechanical Behavior Of The Rod-Like Microstructure In The Radular Teeth Of Cryptochiton Stelleri, Enrique Escobar De Obaldia

Open Access Dissertations

Natural ceramics provided with high volume fractions of mineralized materials that are surrounded by a weak organic interface combine the stiff mechanical behavior of building blocks, like hydroxyapatite or aragonite, and the compliance of the organic surroundings. Unique mechanical properties (e.g. light density and toughness) distinguish bio-composites from common engineering materials. A key example is the highly mineralized shell of the radular teeth of the Crypochiton stelleri. Nature has provided the radular teeth with a highly oriented rod-like microstructure of nano-scale dimensions embedded in a matrix of chitin sheaths. Compared to other biological materials, the external iron oxide layer of …

Structure Of Cards Toxin, A Unique Adp-Ribosylating And Vacuolating Cytotoxin From Mycoplasma Pneumoniae, Argentina Becker, T. R. Kannan, Alexander B. Taylor, Olga N. Pakhomova, Yanfeng Zhang, Sudha R. Somarajan, Ahmad Galaleldeen, Stephen P. Holloway, Joel B. Baseman, P. John Hart

Bioelectrics Publications

Mycoplasma pneumoniae (Mp) infections cause tracheobronchitis and "walking" pneumonia, and are linked to asthma and other reactive airway diseases. As part of the infectious process, the bacterium expresses a 591-aa virulence factor with both mono-ADP ribosyltransferase (mART) and vacuolating activities known as Community-Acquired Respiratory Distress Syndrome Toxin (CARDS TX). CARDS TX binds to human surfactant protein A and annexin A2 on airway epithelial cells and is internalized, leading to a range of pathogenetic events. Here we present the structure of CARDS TX, a triangular molecule in which N-terminal mART and C-terminal tandem beta-trefoil domains associate to form an overall architecture …

Diffusion Imaging In The Rat Cervical Spinal Cord, Elizabeth Zakszewski, Brian D. Schmit, Shekar N. Kurpad, Matthew D. Budde

Biomedical Engineering Faculty Research and Publications

Magnetic resonance imaging (MRI) is the state of the art approach for assessing the status of the spinal cord noninvasively, and can be used as a diagnostic and prognostic tool in cases of disease or injury. Diffusion weighted imaging (DWI), is sensitive to the thermal motion of water molecules and allows for inferences of tissue microstructure. This report describes a protocol to acquire and analyze DWI of the rat cervical spinal cord on a small-bore animal system. It demonstrates an imaging setup for the live anesthetized animal and recommends a DWI acquisition protocol for high-quality imaging, which includes stabilization of …

Temporal Evolution Of Both Premotor And Motor Cortical Tuning Properties Reflect Changes In Limb Biomechanics, Aaron J. Suminski, Philip Mardoum, Timothy P. Lillicrap, Nicholas G. Hatsopoulos

Biomedical Engineering Faculty Research and Publications

A prevailing theory in the cortical control of limb movement posits that premotor cortex initiates a high-level motor plan that is transformed by the primary motor cortex (MI) into a low-level motor command to be executed. This theory implies that the premotor cortex is shielded from the motor periphery and therefore its activity should not represent the low-level features of movement. Contrary to this theory, we show that both dorsal (PMd) and ventral premotor (PMv) cortices exhibit population-level tuning properties that reflect the biomechanical properties of the periphery similar to those observed in M1. We recorded single-unit activity from M1, …

Cardiovascular Magnetic Resonance Imaging-Based Computational Fluid Dynamics/Fluid-Structure Interaction Pilot Study To Detect Early Vascular Changes In Pediatric Patients With Type 1 Diabetes, Margaret M. Samyn, Ronak Jashwant Dholakia, Hongfeng Wang, Jennifer Co-Vu, Ke Yan, Michael E. Widlansky, John F. Ladisa Jr., Pippa Simpson, Ramin Alemzadeh

Biomedical Engineering Faculty Research and Publications

We hypothesized that pediatric patients with type 1 diabetes have cardiac magnetic resonance (CMR) detectable differences in thoracic aortic wall properties and hemodynamics leading to significant local differences in indices of wall shear stress, when compared with age-matched control subjects without diabetes. Pediatric patients with type 1 diabetes were recruited from Children’s Hospital of Wisconsin and compared with controls. All underwent morning CMR scanning, 4-limb blood pressure, brachial artery reactivity testing, and venipuncture. Patient-specific computational fluid dynamics modeling with fluid–structure interaction, based on CMR data, determined regional time-averaged wall shear stress (TAWSS) and oscillatory shear index (OSI). Twenty type 1 …

Sagittal Subtalar And Talocrural Joint Assessment With Weight-Bearing Fluoroscopy During Barefoot Ambulation, Ben Mchenry, Emily L. Exten, Jason Long, Brian Law, Richard Marks, Gerald F. Harris

Biomedical Engineering Faculty Research and Publications

Background: Identifying talar position during ambulation has proved difficult as the talus lacks palpable landmarks for skin marker placement and more invasive methodologies such as bone pins are not practical for most clinical subjects. A fluoroscopic motion system was used to track the talus and calcaneus, allowing kinematic analysis of the talocrural and subtalar joints.

Methods: Thirteen male subjects (mean age 22.9 ± 3.0 years) previously screened for normal gait were tested. A fluoroscopy unit was used to collect images at 120 fps during stance. Sagittal motion of the talocrural and subtalar joints were analyzed.

Results: The intersubject mean and …

Ablation Of Cardiac Tissue With Nanosecond Pulsed Electric Fields: Experiments And Numerical Simulations, Fei Xie

Biomedical Engineering Theses & Dissertations

Cardiac ablation for the treatment of cardiac arrhythmia is usually performed by heating tissue with radio-frequency (RF) electrical currents to create conduction-blocking lesions in order to stop the propagation of electrical waves. Problems associated with RF ablation are recurrence of arrhythmias after successful treatments, tissue loss beyond the targeted tissue, long duration of the ablation procedure, and thermal side effects including thrombus formation that may lead to stroke. Here, we propose a new, non-thermal ablation method using nanosecond pulsed electric fields (nsPEFs) with better-controlled ablation volume, shorter procedure time, and no thermal side effects. We demonstrate that we can create …

Plasma Activated Air Mediates Gene Transfer, Chelsea M. Edelblute

Biological Sciences Theses & Dissertations

Cold plasma is produced when strong applied electric fields accelerate free electrons, which dissociate, excite, or ionize gaseous molecules [1]. The deposition of ions from the plasma source is dependent on power generation, input gas composition, and gas flow rate. In the presence of reactive species, the membrane of eukaryotic cells is compromised allowing for otherwise impermeant molecules, such as DNA, to enter the inner-cell milieu [2].

The efficacy of a novel cold plasma reactor based on shielded sliding discharge for the delivery of plasmid DNA was assessed. The device is entirely non-contact, wherein the plasma never directly touches the …

Multichannel Characterization Of Brain Activity In Neurological Impairments, Yalda Shahriari

Biomedical Engineering Theses & Dissertations

Hundreds of millions of people worldwide suffer from various neurological and psychiatric disorders. A better understanding of the underlying neurophysiology and mechanisms for these disorders can lead to improved diagnostic techniques and treatments. The objective of this dissertation is to create a novel characterization of multichannel EEG activity for selected neurological and psychiatric disorders based on available datasets. Specifically, this work provides spatial, spectral, and temporal characterizations of brain activity differences between patients/animal models and healthy controls, with focus on modern techniques that quantify cortical connectivity, which is widely believed to be abnormal in such disorders. Exploring the functional brain …

Raman Spectroscopy As A Tool For Single Circulating Tumor Cell (Ctc) Detection And Imaging, Zeid A. Nima

Theses and Dissertations

Breast cancer is the most common type of cancers in the United States. It is imperative that a quick and reliable method for the early detection of circulating tumor cells (CTCs) be identified and tested. In this research several new detection and imaging techniques based on using Raman spectroscopy have been invented. Raman active nano-complex agents based on single-walled carbon nanotubes (SWCNTs) were prepared and used for the swift and specific detection of breast cancer cells. SWCNTs are functionalized with the anti-epithelial cell adhesion molecule (anti-EpCAM) antibody, were able to detect CTCs within 30 min and discriminate few CTCs among …

A Ten-Year Search For Synchronous Cells: Obstacles, Solutions, And Practical Applications, Charles E. Helmstetter

Biomedical Engineering and Sciences Faculty Publications

My effort to use synchronously dividing cultures to examine the Escherichia coli cell cycle involved a 10-year struggle with failure after failure punctuated by a few gratifying successes, especially at the end. In this essay, I recount my personal journey in this obsessive experimental pursuit. That narrative is followed by a description of a simplified version of the "baby machine," a technique that was developed to obtain minimally disturbed, synchronously growing E. coli cells. Subsequent studies with this methodology led to an understanding of the basic properties of the relationship between chromosome replication and cell division. Accordingly, I end this …

The Application Of Biomedical Engineering Techniques To The Diagnosis And Management Of Tropical Diseases: A Review, Fatimah Ibrahim, Tzer Hwai Gilbert Thio, Tarig Faisal, Michael Neuman

Michigan Tech Publications, Part 1

This paper reviews a number of biomedical engineering approaches to help aid in the detection and treatment of tropical diseases such as dengue, malaria, cholera, schistosomiasis, lymphatic filariasis, ebola, leprosy, leishmaniasis, and American trypanosomiasis (Chagas). Many different forms of non-invasive approaches such as ultrasound, echocardiography and electrocardiography, bioelectrical impedance, optical detection, simplified and rapid serological tests such as lab-on-chip and micro-/nano-fluidic platforms and medical support systems such as artificial intelligence clinical support systems are discussed. The paper also reviewed the novel clinical diagnosis and management systems using artificial intelligence and bioelectrical impedance techniques for dengue clinical applications.

Continual Cell Deformation Induced Via Attachment To Oriented Fibers Enhances Fibroblast Cell Migration, Sisi Qin, Vincent Ricotta, Marcia Simon, Richard A. F. Clark, Miriam Rafailovich

Department of Biomedical Engineering Faculty Publications

Fibroblast migration is critical to the wound healing process. In vivo, migration occurs on fibrillar substrates, and previous observations have shown that a significant time lag exists before the onset of granulation tissue. We therefore conducted a series of experiments to understand the impact of both fibrillar morphology and migration time. Substrate topography was first shown to have a profound influence. Fibroblasts preferentially attach to fibrillar surfaces, and orient their cytoplasm for maximal contact with the fiber edge. In the case of en-mass cell migration out of an agarose droplet, fibroblasts on flat surfaces emerged with an enhanced velocity, v …

Differential Effects Of Buffer Ph On Ca2+-Induced Ros Emission With Inhibited Mitochondrial Complexes I And Iii, Daniel P. Lindsay, Amadou K. S. Camara, David F. Stowe, Mohammed Aldakkak, Ryan Lubbe

Biomedical Engineering Faculty Research and Publications

Excessive mitochondrial reactive oxygen species (ROS) emission is a critical component in the etiology of ischemic injury. Complex I and complex III of the electron transport chain are considered the primary sources of ROS emission during cardiac ischemia and reperfusion (IR) injury. Several factors modulate ischemic ROS emission, such as an increase in extra-matrix Ca²⁺, a decrease in extra-matrix pH, and a change in substrate utilization. Here we examined the combined effects of these factors on ROS emission from respiratory complexes I and III under conditions of simulated IR injury. Guinea pig heart mitochondria were suspended in experimental …

P-08 Paper-Based Biosensor For Colorimetric Detection Of Psa Biomarker, Alyson E. Drew

Honors Scholars & Undergraduate Research Poster Symposium Programs

Prostate cancer is detected by excess PSA in the bloodstream, a protein the prostate overproduces when tumors are present. In this paper, we designed an origami paper analytical device, specific to PSA using gold nanoparticles which provide a colorimetric, qualitative, inexpensive, disposable design to detect PSA. Our device separates the sample laterally to prevent back-mixing and vertically to enable addition of novel particles. The design was optimized for channel thickness, size, proper heating, type of paper involved, and amount of sample solution needed. We are currently concept-testing of PSA qualitative detection via sandwich assay to target detection levels < 100ng/mL.

Microscale Magnetic Field Modulation For Enhanced Capture And Distribution Of Rare Circulating Tumor Cells, Peng Chen, Yu-Yen Huang, Kazunori Hoshino, John X.J Zhang

Dartmouth Scholarship

Immunomagnetic assay combines the powers of the magnetic separation and biomarker recognition and has been an effective tool to perform rare Circulating Tumor Cells detection. Key factors associated with immunomagnetic assay include the capture rate, which indicates the sensitivity of the system, and distributions of target cells after capture, which impact the cell integrity and other biological properties that are critical to downstream analyses. Here we present a theoretical framework and technical approach to implement a microscale magnetic immunoassay through modulating local magnetic field towards enhanced capture and distribution of rare cancer cells. Through the design of a two-dimensional micromagnet …