Engineering Commons^™

Mathematical Analysis Of Feedback Targets Of Bmp Signaling In Drosophila Embryonic Development, Yan Luo

Open Access Theses

Bone morphogenetic proteins (BMPs) drive a range of cellular processes especially in the early stages of embryonic development. This family of proteins acts as one of the most important extracellular signals in development pattern formation across the animal kingdom. Cells in embryos differentiate into different cell types in response to the concentration level of BMP. This complex process is regulated by multiple regulators that serve to tune the signal response.

Extensive experimental and computational research has been performed to analyze BMP regulation in Drosophila, a widely studied model organism, and has advanced our understanding of animal development. Because of …

Potential Applications For Halloysite Nanotubes Based Drug Delivery Systems, Lin Sun

Doctoral Dissertations

Drug delivery refers to approaches, formulations, technologies, and systems for transporting a drug in the body. The purpose is to enhance the drug efficacy and to reduce side reactions, which can significantly improve treatment outcomes. Halloysite is a naturally occurred alumino-silicate clay with a tubular structure. It is a biocompatible material with a big surface area which can be used for attachment of targeted molecules. Besides, loaded molecules can present a sustained release manner in solution. These properties make halloysite nanotubes (HNTs) a good option for drug delivery.

In this study, a drug delivery system was built based on halloysite …

Optical Dosimetry Tools And Monte Carlo Based Methods For Applications In Image Guided Optical Therapy In The Brain, Akshay N Prabhu Verleker

Open Access Dissertations

Purpose: The long-term goal of this research is to determine the feasibility of using near infra-red light to stimulate drug release in metastatic lesions within the brain. In this work, we focused on developing the tools needed to quantify and verify photon fluence distribution in biological tissue. To accomplish this task, an optical dosimetry probe and Monte Carlo based simulation code were fabricated, calibrated and developed to predict light transport in heterogeneous tissue phantoms of the skull and brain. Empirical model (EM) of photon transport using CT images as input were devised to provide real-time calculations capable of being translated …

Three-Dimensional Printing And Nanotechnology For Enhanced Implantable Materials, Karthik Kumar Tappa

Doctoral Dissertations

Orthopedic and oro-maxillofacial implants have revolutionized treatment of bone diseases and fractures. Currently available metallic implants have been in clinical use for more than 40 years and have proved medically efficacious. However, several drawbacks remain, such as excessive stiffness, accumulation of metal ions in surrounding tissue, growth restriction, required removal/revision surgery, inability to carry drugs, and susceptibility to infection. The need for additional revision surgery increases financial costs and prolongs recovery time for patients. These metallic implants are bulk manufactured and often do not meet patient's requirements. A surgeon must machine (cut, weld, trim or drill holes) them in order …

Influence Of The 3d Microenvironment On Glioblastoma Migration And Drug Response, Ruth Marisol Herrera Perez

Open Access Dissertations

Glioblastoma (GBM) is a highly invasive brain cancer characterized by poor prognosis. Despite significant efforts by the basic and clinical research community our understanding of GBM progression and recurrence has been incremental. Improvements in therapeutic response have been dismal, and GBM continues to be the deadliest tumor of the central nervous system, with patient average survival rate of 12 months. Synergistic relationships that the tumor cells establish with the brain microenvironment have been proven fundamental for successful tumor progression and maintenance. Yet, many in vitro GBM studies are performed in formats that fail to recapitulate the most essential component of …

Consonant Discrimination In The Inferior Colliculus Of Young And Aged Rats, Christopher S. Soverns

Open Access Theses

Complex acoustic stimuli are thoroughly encoded and processed along the primary auditory pathway to give reliable and relevant information about the environment, and elucidating the neural coding mechanisms is essential to informing clinical attempts to combat auditory dysfuntion. Receiving a uniquely diverse set of ascending and descending inputs, the inferior colliculus (IC) is a site of intricate temporal processing. In this work, natural and modified human speech is used to investigate discrimination of voice onset time (VOT) in the spiking output of IC neurons. A template-matching classification model is proposed in which single stimulus presentation responses are correlated with aggregate …

Densified Collagen-Fibril Biomaterials For Bone Tissue Engineering, Lauren E. Watkins

Open Access Theses

Millions of craniofacial bone defects occur annually as a result of trauma, congenital defects, disease, or tooth extraction. When present in the oral cavity, these defects are associated with adverse impacts on speech, mastication, and aesthetics. Thus, there is a clinical need for interventional strategies to restore and preserve alveolar bone mass to improve the success of future treatment options intended to reestablish functionality and aesthetics. Guided bone regeneration using bone grafts and a membrane represent the current standard of care for repairing alveolar bone defects, but face a number of limitations related to resorption time and structural integrity. Improvements …

Nanoformulation For Anticancer Drug Delivery: Enhanced Pharmacokinetics And Circulation, Gaurav Parekh

Doctoral Dissertations

In this study, we have explored the application of the Layer-by-Layer (LbL) assembly technique for improving injectable drug delivery systems of low soluble anticancer drugs (e.g. Camptothecin (CPT), Paclitaxel (PTX) or Doxorubicin (DOX)). For this study, a polyelectrolyte shell encapsulates different types of drug nanocores (e.g. soft core, nanomicelle or solid lipid nanocores).The low soluble drugs tend to crystallize and precipitate in an aqueous medium. This is the reason they cannot be injected and may have low concentrations and low circulation time in the blood. Even though these drugs when present in the cancer microenvironment have high anti-tumor inhibition, the …

Nanotechnology And Additive Manufacturing Platforms For Clinical Medicine: An Investigation Of 3d Printing Bioactive Constructs And Halloysite Nanotubes For Drug Delivery And Biomaterials, Jeffery A. Weisman

Doctoral Dissertations

Personalized medicine requires the development of new technologies for controlled or targeted drug delivery. Three-dimensional (3D) printing and additive manufacturing techniques can be used to generate customized constructs for bioactive compound delivery. Nanotechnology in the form of nanoparticles, used as a stand-alone construct or for material enhancements, can significantly improve established biomaterials such as PMMA based bone cements or enable new technology to have enhanced capabilities. Combinations of the technologies can be used in such applications as infectious disease treatments, chemotherapeutic targeted drug delivery or targeted delivery of nearly any bioactive compound.

Chemotherapeutic or antibiotic enhanced 3D printing filaments were …

Feasibility Of Pulsed Proton Induced Acoustics For 3d Dosimetry, Fahed M. Alsanea

Open Access Theses

Proton therapy has the potential to deposit its energy in tissue with high conformity to the tumor and significantly reduced integral dose to normal tissue compared to conventional radiation, such as x-rays. As a result, local control can be enhanced while reducing side-effects and secondary cancers. This is due to the way charged Particles deposit their energy or dose, where protons form a Bragg peak and establish a well-defined distal edge as a function of depth (range). To date, the dose delivered to a patient from proton therapy remains uncertain, in particular the positioning of the distal edge of the …

Developing A Hardware Platform For A Low-Power, Low-Cost, Size-Constrained Biomechanical Telemetry System, Aditya Balasubramanian

Open Access Theses

As sport-related traumatic brain injuries face increasing attention from the media and the general public, the need to be able to detect brain injury quickly, inexpensively and accurately is more important than ever. Commercially-available event-based systems exist that claim to achieve this goal; however, they collect little to no continuous-time data and primarily indicate when a pre-determined acceleration threshold has been exceeded under the unvalidated assumption that a potentially concussive blow has occurred. Recent findings by the Purdue Neurotrauma Group (PNG) have indicated that repeated exposure to both concussive and subconcussive blows can result in cumulative trauma disorder. To track …

Biomechanics And Relaxivity For Functional Imaging Of Articular Cartilage Injury And Degradation, Kateri Elizabeth Fites

Open Access Theses

Osteoarthritis (OA) is a major debilitating health concern and economic burden worldwide, affecting 27 million people in the United States alone. OA often follows tissue injury, and is marked by changes in the structure and biomechanical function of cartilage, including breakdown of extracellular matrix molecules, loss of bulk tissue stiffness, and increase in articular surface friction and wear. Unlike bone and many other tissues, cartilage lacks an intrinsic capacity for regeneration. Advanced OA is typically diagnosed by patient symptoms (e.g. joint pain) and confirmed by radiographic evaluation of joint space narrowing. However, the application of functional imaging to assess cartilage …

Controlling Protein Release Using Biodegradable Microparticles, Benjamin Patrick Kline

Open Access Theses

Research in the field of protein therapeutics has exploded over the past decade and continues to grow in both academia and in industry. Protein drugs have advantages of being highly specific and highly active making them coveted targets for high profile disease states like cancer and multiple sclerosis. Unfortunately, their many advantages are complemented by their obstacles. Because proteins are highly active and highly specific, the window between efficacy and toxicity is very narrow and drug development can be long and arduous. In addition, protein activity is dependent on its specific folding conformation that is easily disrupted by a variety …

Characteristics Of Fibrous Tissue At High Rates Of Tensile Loading, Benjamin J. Claus

Open Access Theses

The mechanical behavior of fibrous tissue is generally characterized at very low strain rates. However, many injuries occur at high rates of loading, such as those encountered in sporting events or vehicle accidents. An understanding of injury behavior requires the injury process to be recorded at high strain rates. Even at low rates of loading, the injury/failure within tissues occurs quickly. Furthermore, using conventional imaging systems, the surface of a specimen may be well documented throughout an experiment. However, damage formation does not necessarily begin at the surface of the specimen or even on the surface exposed to a camera. …

Low Soluble Drug Encapsulation Based On Architecture Of Layer-By-Layer Assembly For Longer Circulation Time And Targeted Therapy, Pravin Pattekari

Doctoral Dissertations

A combined effect of sonication and layer-by-layer assembly (LbL) enhances the solubility of many poorly soluble inorganic and organic materials by forming stable particles with ca. 200 nm size and up to 90 wt% of loading. The entire method is reproducible, easy-to-handle, and flexible for varying surface properties according to the application of the materials. The method develops good colloidal stability of materials in buffers and maintains architecture for future improvement. A top-down approach, with a combined effect of sonication and LbL assembly, ruptures the material and allows adsorption of oppositely charged polyelectrolytes simultaneously. Thus, the approach is applicable for …

The Effect Of Network Transitions On Spontaneous Activity And Sycnhrony In Devloping Neural Networks, Jude P. J. Savarraj

Doctoral Dissertations

Connectivity patterns of developing neural circuits and the effects of its dynamics on network behavior, particularly the emergence of spontaneous activity and synchrony, are not clear. We attempt to quantify anatomical connectivity patterns of rat cortical cultures during different stages of development. By culturing the networks on dishes embedded with micro electrode arrays, we simultaneously record electrical activity from multiple regions of the developing network and monitor its electrical behavior, particularly its tendency to fire spontaneously and to synchronize under certain conditions. We investigate possible correlations between changes in the network connectivity patterns and spontaneous electrical activity and synchrony. Cocultures …

A Watershed Scale Evaluation Of Selected Second Generation Biofeedstocks On Water Quality, Gurdeep Singh

Graduate Theses and Dissertations

This study compares a novel simulation approach to the conventional Soil and Water Assessment Tool (SWAT) modeler's approach for targeting biofuel crop production on marginal lands. In conventional SWAT modeling approach, non-spatial definition of hydrological response units (HRUs) results in the simulation of biofuel crops on both marginal and non-marginal land. This study provides an alternative approach in which a marginal-land raster was integrated into the land use and land cover (LULC) raster in such a way that the land uses were divided into marginal and non-marginal components. This modified LULC was used for model setup which resulted in marginal …

Evaluation Of Autonomous Robotic Milling Methodology For Natural Tooth-Shaped Implants Based On Sko Optimization, Yongki Yoon

Mechanical & Aerospace Engineering Theses & Dissertations

Robotic surgery is one of the most demanding and challenging applications in the field of automatic control. One of the conventional surgeries, the dental implantation, is the standard methodology to place the artificial tooth root composed of titanium material into the upper or lower jawbone. During the dental implant surgery, mechanical removal of the bone material is the most critical procedure because it may affect the patient's safety including damage to the mandibular canal nerve and/or piercing the maxillary sinus. With this problem, even though short term survival rates are greater than 95%, long term success rate of the surgery …

Effects Of Diabetes And Aging On Posture And Acceleration Thresholds During Lateral Translations, Samantha Jean Richerson

Doctoral Dissertations

Research objectives. One source of falls in the elderly may be an inability to sufficiently adjust to transient postural perturbations or slips. Identifying useful predictors of fall potential, as well as factors that affect the ability of an individual to detect a movement of the standing support surface may provide insight into postural stability and methods to increase stability in elders. To do this, acceleration thresholds to short, precise, lateral platform translations and the resultant psychophysical responses of adults with early Type 2 diabetes to age-matched controls and young adults were measured.

Methods. Using an innovative SLIP-FALLS platform, …

Modular Machine Learning Methods For Computer-Aided Diagnosis Of Breast Cancer, Mia Kathleen Markey '94

Doctoral Dissertations

The purpose of this study was to improve breast cancer diagnosis by reducing the number of benign biopsies performed. To this end, we investigated modular and ensemble systems of machine learning methods for computer-aided diagnosis (CAD) of breast cancer. A modular system partitions the input space into smaller domains, each of which is handled by a local model. An ensemble system uses multiple models for the same cases and combines the models' predictions.

Five supervised machine learning techniques (LDA, SVM, BP-ANN, CBR, CART) were trained to predict the biopsy outcome from mammographic findings (BIRADS™) and patient age based on a …

Postural Balance And Acceleration Threshold Detection For Anterior Horizontal Translation In Diabetic And Non-Diabetic Elderly, Venkatesh Balasubramanian

Doctoral Dissertations

Slips and falls, and even the fear of failing, can represent a major medical and functional deterrent to living independently, especially among the elderly population. Various groups of elders are at known risk for falling including, but not limited to, those with vestibular dysfunction, those with low visual acuity including visual neuropathies, and those with peripheral neuropathies. The first two groups are fairly well studied, but the relationship between the level of peripheral neuropathy and extent of falling has received relatively less attention.

In this study, using sliding linear investigative platform for analyzing lower limb stability (SLIP-FALLS), the psychophysical thresholds …

Nitric Oxide Production: A Mechanism For Inhibition Of Chlamydia Trachomatis Replication, Bojun Chen

Electronic Theses and Dissertations

Chlamydia trachomatis (CT) replicates in macrophages, but is inhibited by IFN-$\gamma$ or LPS. IFN-$\gamma$ and/or LPS induced nitrite production in mouse peritoneal macrophages, macrophage cell lines (RAW264.7 and J774A.1) and McCoy cells. Kinetic studies indicated that peak production occurred 48 hours post-treatment. CT infection itself was insufficient to induce nitrite production, but resulted in enhancement of nitrite production in IFN-$\gamma$-treated cells. Treatment with IFN-$\gamma$ or LPS resulted in significant inhibition of CT replication in these cells. Strong correlation between nitrite production and inhibition of CT replication was observed in RAW264.7 and J774A.1 cells (correlation coefficients: $-$0.93 and $-$0.94, p $<$ 0.001). N$\sp{\rm g}$- monomethyl-L-arginine (L-NMMA) specifically inhibited nitrite production and partially reversed inhibition of CT replication in macrophage cell lines. NOS mRNA was measured in RAW264.7 cells by Northern blot and Dot blot hybridization. Strong correlation between NOS mRNA expression and inhibition of CT replication (correlation coefficient: $-$0.97, p $<$ 0.05) was observed. Anti-TNF-$\alpha$ antibody completely neutralized the biological activity of TNF-$\alpha$ secreted by LPS-treated RAW264.7 cells, yet the antibody neither reduced nitrite production nor restored CT replication. Combination of the antibody and L-NMMA significantly enhanced restoration of CT replication. In peritoneal macrophages, inhibition of CT replication induced by IFN-$\gamma$ was partially restored by L-NMMA or anti-TNF-$\alpha$ antibody. In McCoy cells, inhibition of CT replication induced by IFN-$\gamma$ and LPS was not significantly restored by L-NMMA. Great restoration of CT replication by 1 mM L-NMMA was observed in LPS-treated J774A.1 cells (31%), but not in IFN-$\gamma$-treated cells (5%). Our data indicate that (1) NO production is one of the mechanisms for inhibition of CT replication in IFN-$\gamma$-activated peritoneal macrophages and RAW264.7 cells; (2) NO plays a significant role in CT inhibition in LPS-treated macrophage cell lines, but not peritoneal macrophages; (3) TNF-$\alpha$ may be associated with inhibition, but the mechanism(s) may not involve NO production; (4) NO production may not be the mechanism for CT inhibition in McCoy cells treated with IFN-$\gamma$ and LPS.