Physical Sciences and Mathematics Commons^™

Structural Insights Into The Cl-Par-4 Protein: Ionic Requirements, Conformational Transitions, And Interaction With Cisplatin, Krishna Kumar Raut

Chemistry & Biochemistry Theses & Dissertations

Cancer continues to be the leading global cause of death, with challenges in early diagnosis, drug resistance, non-specific drug targeting, and cancer recurrence and metastasis posing formidable obstacles in cancer therapy. In this context, Prostate Apoptosis Response-4 (Par-4), a pro-apoptotic tumor suppressor protein, emerged as a promising therapeutic target due to its ability to selectively induce apoptosis in cancer cells, thereby minimizing the drug-associated adverse effects. However, a comprehensive understanding of the structural features of Par-4, specifically the caspase-cleaved fragment (cl-Par-4), is crucial for therapeutic advancements.

This dissertation investigated the effects of various ions, both monovalent and divalent, on the …

Utilization Of Finite Element Analysis Techniques For Adolescent Idiopathic Scoliosis Surgical Planning, Michael A. Polanco

Mechanical & Aerospace Engineering Theses & Dissertations

Adolescent Idiopathic Scoliosis, a three-dimensional deformity of the thoracolumbar spine, affects approximately 1-3% of patients ages 10-18. Surgical correction and treatment of the spinal column is a costly and high-risk task that is consistently complicated by factors such as patient-specific spinal deformities, curve flexibility, and surgeon experience. The following dissertation utilizes finite element analysis to develop a cost-effective, building-block approach by which surgical procedures and kinematic evaluations may be investigated. All studies conducted are based off a volumetric, thoracolumbar finite element (FE) model developed from computer-aided design (CAD) anatomy whose components are kinematically validated with in-vitro data. Spinal ligament stiffness …

Biophysical Characterization Of The Par-4 Tumor Suppressor: Evidence Of Structure Outside The Coiled Coil Domain And Interactions With Platinum Chemotherapeutics, Andrea Megan Clark

Chemistry & Biochemistry Theses & Dissertations

Prostate apoptosis response-4 (Par-4) is an apoptosis-inducing tumor suppressor protein. Full-length Par-4 has previously been shown to be a predominantly intrinsically disordered protein (IDP) under neutral conditions, with significant regular secondary structure evident only within the C-terminal coiled coil domain. However, IDPs can gain ordered structure through the process of induced folding, which often occurs under non-neutral conditions. Previous work has shown that the Par-4 leucine zipper, which is a subset of the C-terminal coiled coil domain, is disordered under neutral conditions, but forms a dimeric coiled coil at acidic pH. Increase in ionic strength was also shown to increase …

Characterizing The Activity Of Antimicrobial Peptides Against The Pathogenic Bacterium Clostridium Difficile In An Anaerobic Environment, Adenrele Mojeed Oludiran

Chemistry & Biochemistry Theses & Dissertations

Clostridium difficile is an anaerobic Gram-positive pathogen with high treatment costs and mortality and very high antibiotic tolerance. Antimicrobial host-defense peptides (HDPs) produced naturally by animal immune systems are promising candidates to develop novel therapies for bacterial infection because they cause oxidative stress that damages multiple targets in bacterial cells, so it is difficult for bacteria to evolve resistance to these attacks.

Piscidins, fish-derived HDPs that can also form complexes with copper (Cu) to enhance their activities, are very active against multiple bacterial species in an aerobic environment. We examined their activity against C. difficile and other species in an …

Computational Modeling For Abnormal Brain Tissue Segmentation, Brain Tumor Tracking, And Grading, Syed Mohammad Shamin Reza

Electrical & Computer Engineering Theses & Dissertations

This dissertation proposes novel texture feature-based computational models for quantitative analysis of abnormal tissues in two neurological disorders: brain tumor and stroke. Brain tumors are the cells with uncontrolled growth in the brain tissues and one of the major causes of death due to cancer. On the other hand, brain strokes occur due to the sudden interruption of the blood supply which damages the normal brain tissues and frequently causes death or persistent disability. Clinical management of these brain tumors and stroke lesions critically depends on robust quantitative analysis using different imaging modalities including Magnetic Resonance (MR) and Digital Pathology …

Mobile Cloud Computing Based Non Rigid Registration For Image Guided Surgery, Arun Brahmavar Vishwanatha

Computer Science Theses & Dissertations

In this thesis we present the design and implementation of a Mobile Cloud computing platform for non-rigid registration required in Image Guided Surgery (MCIGS). MCIGS contributes in flexible, portable and accurate alignment of pre-operative brain data with intra-operative MRI, for image guided diagnosis and therapy and endoscopic skull base surgery. Improved precision of image guided therapy and specifically neurosurgery procedures is known to result in the improved prognosis for brain tumor patients. MCI GS system is tested with Physics Based Non-Rigid Registration method form ITK. Our preliminary results for brain images indicate that the proposed system over Wi-Fi can be …

Multi-Surface Simplex Spine Segmentation For Spine Surgery Simulation And Planning, Rabia Haq

Computational Modeling & Simulation Engineering Theses & Dissertations

This research proposes to develop a knowledge-based multi-surface simplex deformable model for segmentation of healthy as well as pathological lumbar spine data. It aims to provide a more accurate and robust segmentation scheme for identification of intervertebral disc pathologies to assist with spine surgery planning. A robust technique that combines multi-surface and shape statistics-aware variants of the deformable simplex model is presented. Statistical shape variation within the dataset has been captured by application of principal component analysis and incorporated during the segmentation process to refine results. In the case where shape statistics hinder detection of the pathological region, user-assistance is …

Meshless Mechanics And Point-Based Visualization Methods For Surgical Simulations, Rifat Aras

Computational Modeling & Simulation Engineering Theses & Dissertations

Computer-based modeling and simulation practices have become an integral part of the medical education field. For surgical simulation applications, realistic constitutive modeling of soft tissue is considered to be one of the most challenging aspects of the problem, because biomechanical soft-tissue models need to reflect the correct elastic response, have to be efficient in order to run at interactive simulation rates, and be able to support operations such as cuts and sutures.

Mesh-based solutions, where the connections between the individual degrees of freedom (DoF) are defined explicitly, have been the traditional choice to approach these problems. However, when the problem …

An Extensible Mathematical Model Of Glucose Metabolism, Caleb L. Adams

Mathematics & Statistics Theses & Dissertations

The American Diabetes Association reports that diabetes is the fifth leading cause of death by disease in the United States. An estimated 23.6 million individuals, or seven percent of the population, have diabetes. Nearly one-third are unaware that they have the disease. The total of the direct and indirect medical costs associated with diabetes in 2007 was projected to be $174 billion, or approximately one out of every ten health care dollars.

One must understand the glucose regulatory system of the healthy body to understand diabetes. Blood glucose concentration returns to a constant level after eating and is maintained during …

Mathematical Models Of Tumors And Their Remote Metastases, Carryn Bellomo

Mathematics & Statistics Theses & Dissertations

Clinical observations and indications in the literature have led us to investigate several models of tumors. For example, it has been shown that a tumor has the ability to send out anti-growth factors, or inhibitors, to keep its remote metastases from growing. Thus, we model the depleting effect of such a growth inhibitor after the removal of the primary tumor (thus removing the source) as a function of time t and distance from the original tumor r.

It has also been shown clinically that oxygen and glucose are nutrients critical to the survival and growth of tumors. Thus, we model …

Reaction-Diffusion Models Of Cancer Dispersion, Kim Yvette Ward

Mathematics & Statistics Theses & Dissertations

The phenomenological modeling of the spatial distribution and temporal evolution of one-dimensional models of cancer dispersion are studied. The models discussed pertain primarily to the transition of a tumor from an initial neoplasm to the dormant avascular state, i.e. just prior to the vascular state, whenever that may occur. Initiating the study is the mathematical analysis of a reaction-diffusion model describing the interaction between cancer cells, normal cells and growth inhibitor. The model leads to several predictions, some of which are supported by experimental data and clinical observations $\lbrack25\rbrack$. We will examine the effects of additional terms on these characteristics. …

Mathematical Models Of Chemotherapy, John Carl Panetta

Mathematics & Statistics Theses & Dissertations

Several mathematical models are developed to describe the effects of chemotherapy on both cancerous and normal tissue. Each model is defined by either a single homogeneous equation or a system of heterogeneous equations which describe the states of the normal and/or cancer cells. Periodic terms are added to model the effects of the chemotherapy. What we obtain are regions, in parameter space (dose and period), of acceptable drug regimens.

The models take into account various aspects of chemotherapy. These include, interactions between the cancer and normal tissue, cell specific chemotherapeutic drug, the use of non-constant parameters to aid in modeling …