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An Improved Polynomial Chaos Expansion Based Response Surface Method And Its Applications On Frame And Spring Engineering Based Structures, Mhd A. Hafez

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In engineering fields, computational models provide a tool that can simulate a real world response and enhance our understanding of physical phenomenas. However, such models are often computationally expensive with multiple sources of uncertainty related to the model’s input/assumptions. For example, the literature indicates that ligament’s material properties and its insertion site locations have a significant effect on the performance of knee joint models, which makes addressing uncertainty related to them a crucial step to make the computational model more representative of reality. However, previous sensitivity studies were limited due to the computational expense of the models. The high computational …

Targeting Heat Shock 27 Kda Protein Induces Androgen Receptor Degradation, Yaxin Li

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Glioblastoma (GBM) is the most common and aggressive brain tumor, with very poor prognosis. Androgen receptor (AR) plays a significant role in the progression of GBM, and anti-androgen agents have the potential to be used for the treatment of GBM. However, AR mutation commonly happens in GBM, which makes the anti-androgen agents less effective. Heat shock 27 kDa protein (HSP27) is a well-documented chaperone protein to stabilize AR. Inhibition of HSP27 results in AR degradation regardless the mutation status of AR, which makes HSP27 a good target to abolish AR in GBM. Identified compound I ((N-(3-((2,5-dimethoxybenzyl)oxy)-4-(methylsulfonamido) phenyl)-4-methoxybenzamide) inhibits GBM cell …

Development And Analysis Of Next-Generation Polymeric And Bio-Ceramic Based Orthopedic Scaffolds By Advanced Manufacturing Techniques, Sudeep K. Gummadi

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Gliomas express mutant isocitrate dehydrogenases producing excessive amounts of D 2-hydroxyglutarate (D2HG) and releasing some of it into the environment. The immune surveillance is reduced as a result, however, the mechanisms behind lymphocyte suppression by the D2HG stereoisomer remain unknown. I incubated Jurkat T cells with D2HG at concentrations present within and surrounding gliomas, or its obverse L2HG stereoisomer, and quantified 2HG isomers within washed cells by TSPC derivatization with stable isotope-labeled D2HG and L2HG internal standards, HPLC separation, and mass spectrometry. D2HG was found in quiescent cells in double the amount of L2HG. External D2HG or L2HG increased the …

Measurement Of Red Blood Cell Oxygenation State By Magnetophoresis, Nina A. Smith

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Magnetophoresis of red blood cells (RBCs) at varying partial pressures of oxygen (pO2) is hypothesized to rejuvenate stored blood to be utilized beyond the FDA regulated 42-day storage time. Magnetophoresis is a particle or cells motion induced by an applied magnetic field in a viscous media. The average magnetophoretic mobility of an oxygenated RBC is -0.126x10-6 mm3-s/kg, and a deoxygenated RBC is 3.66x10-6 mm3-s/kg, presenting magnetophoresis as a resource for RBC rejuvenation in hopes of storing it longer than 42 days. The main objective of this paper was to determine if controlling the pO2 within an RBC suspension, can singly- …

Feasibility Of Using An Equilibrium Point Strategy To Control Reaching Movements Of Paralyzed Arms With Functional Electrical Stimulation, Matthew Huffman

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Functional electrical stimulation (FES) is a technology capable of improving the quality of life for those with the loss of limb movement related to spinal cord injuries. Individuals with high-level tetraplegia, in particular, have lost all movement capabilities below the neck. FES has shown promise in bypassing spinal cord damage by sending electrical impulses directly to a nerve or muscle to trigger a desired function. Despite advancements in FES, full-arm reaching motions have not been achieved, leaving patients unable to perform fundamental tasks such as eating and grooming. To overcome the inability in current FES models to achieve multi-joint coordination, …

Evaluation Of A Small Molecule Agonist Of Epha2 Receptor Tyrosine Kinase And Copalic Acid Analogs As Prostate Cancer Therapeutics, Nethrie Idippily

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Project I: Chemotherapeutic drugs have many side effects that are undesirable and are highly toxic. Therefore, there is a growing need for the development of drugs with enhanced efficacy, specificity, and potency to provide cancer patients with a better prognosis. It was discovered that a member of the Receptor Tyrosine Kinase family, EphA2, may prove to be a viable target in developing anti-cancer agents. In the presence of its ligand, EphA2 receptor is responsible for apoptotic and anti-migratory activity. However, in the absence of ligand, EphA2 is able to stimulate cell migration and therefore tumorigenic activity. These conflicting roles of …

Modeling Liver Diseases Using Hepatic Cell Microarrays, Alexander David Roth

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Hepatocellular carcinoma (HCC) is an invasive and aggressive cancer of the liver that arises due to chronic cirrhosis. Research into understanding HCC has focused on two-dimensional (2D) and three-dimensional (3D) technologies to simulate the liver microenvironment and use animal models to model how HCC affects the rest of the body. 3D hydrogel models are desired because they can mimic the transport behavior observed in vivo by structurally mimicking the extracellular matrix (ECM) without the ethical concerns of animal models. However, hydrogels can be toxic to cells and require optimal procedures for appropriate handling. In this study, we created 3D models …

Advanced Manufacturing Of Titanium Alloys For Biomedical Applications, Nicholas C. Mavros

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In metallurgy, Titanium has been a staple for biomedical purposes. Its low toxicity and alloying versatility make it an attractive choice for medical applications. However, studies have shown the difference in elastic modulus between Titanium alloys (116 GPa) and human bone (40-60 GPa) contribute to long term issues with loose hardware fixation. Additionally, long term studies have shown elements such as Vanadium and Aluminum, which are commonly used in Ti-6Al-4V biomedical alloys, have been linked to neurodegenerative diseases like Alzheimers and Parkinsons. Alternative metals known to be less toxic are being explored as replacements for alloying elements in Titanium alloys. …

Determination Of Novel Metabolites Of Therapeutic Agents Used In The Treatment Of Castration-Resistant Prostate Cancer, Mohammad Alyamani

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Despite an array of improved treatment options over the past decade, prostate cancer remains the second leading cause of cancer mortality for men in the United States. Abiraterone and galeterone are oral steroidal compounds that are used to treat metastatic castration-resistant prostate cancer (CRPC). Abiraterone blocks 17a-hydroxylase/17,20-lyase (CYP17A1), an enzyme required for androgen synthesis. Galeteron inhibits CYP17A1, blocks the androgen receptor (AR), and decreases AR protein levels. Both drugs share the same structure with endogenous androgens such as dehydroepiandrosterone, which are substrates for the enzyme, 3ß-hydroxysteroid dehydrogenase (3ßHSD). Metabolites of 3ßHSD undergo further metabolism to produce the AR ligand, testosterone …

The Regulatory Role Of Interleukin-1 Receptor Associated Kinase M In Toll-Like Receptor Signaling, Hao Zhou

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Toll-like receptors (TLRs) are one of the major groups of pattern recognition receptors. TLRs are able to recognize the pathogen-associated molecular patterns and transduce their signals through the adaptor molecule MyD88 and members of the IL-1R-associated kinase family (IRAK1, 2, M and 4). IRAKM was previously known to function as a negative regulator that prevents the dissociation of IRAKs from MyD88, thereby inhibiting downstream signaling. However, we now found that IRAKM was also able to interact with MyD88-IRAK4 to form IRAKM Myddosome to mediate TLR7-induced MEKK3-dependent second wave NF¿B activation. As a result, the IRAKM-dependent pathway only induced expression of …

The Synthesis And Characterization Of Multifunctional Nanoparticles Of Elastin-Like Polypeptides For Theranostic Applications, James T. Cole

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Theranostics is a promising field that aims to combine therapeutics and diagnostics into single multifunctional formulations. This field is driven by advancements in nanotechnology and specifically in the creation of multifunctional nanoparticles capable of providing the necessary functionalities. Elastin-like polypeptides (ELPs) are a class of environmentally responsive biopolymers that are known to undergo a transition in response to various stimuli. The organic nature of ELPs along with the ability to control their design at the gene level and the aforementioned responsive behavior make them a promising candidate for use in theranostic systems. The system presented here is one of the …

Decitabine-Loaded Nanogel Treatment To Reverse Cancer Drug Resistance, Samantha A. Cramer

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Cancers in which epigenetic changes, such as hypermethylation of DNA, lead to drug resistance cause the cancer to become unresponsive to existing chemotherapeutic treatments. The epigenetic drug – 5-aza-2’-deoxycytidine (decitabine, DAC) – is a potent hypomethylating agent, but its effect is transient due to its instability. Previous studies have shown that loading DAC into nanogel significantly enhances its antiproliferative effect (compared to DAC in solution) in drug-resistant breast cancer cells (MCF-7/ADR). Further, the previous studies demonstrated changes in the membrane lipid profile of resistant cells following treatment with DAC either as solution or in nanogels. The objective of the present …

Development Of A Testicular Cancer Vaccine, Roberto Aguilar Iii

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Testicular cancer mainly affects men between the ages of 20 and 35 but is the most common male neoplasm between the ages of 15 and 34. The National Cancer Institute (NCI) states that localized testicular cancer has a recurrence rate of 15-20% and tumors that are Sertoli or Leydig cell derived fail to respond to chemotherapy or radiation treatments. The recurrence rate may increase to 32% if at diagnosis the tumor is greater than 4 cm in size with invasion of the rete testes. To improve therapy for testicular cancer, we examined the usefulness of a testicular cancer vaccine. We …

Sex-Bias In Lupus-Prone (Nzbxnzw)F1 Mice: The Interplay Of Gr1+Cd11b+ Cells, Testosterone And Genetics, Abhishek Trigunaite

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Systemic Lupus Erythematosus (SLE) is a prototypic systemic autoimmune disorder predominantly (9:1) targeting females. Currently, there is no cure for SLE and also there is a lack of disease predicting biomarkers. The major aim of my research is to determine the cellular basis of the sex bias in SLE and subsequently facilitate the development of better therapeutics and biomarkers for the disease. In (NZBxNZW) F1 mice a similar female bias is observed as in humans and testosterone is shown to be protective against lupus-like disease development, but the mechanism is not well understood.

We found higher levels of Gr1hiCD11b+ myeloid …

A Robotic Neuro-Musculoskeletal Simulator For Spine Research, Robb W. Colbrunn

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An influential conceptual framework advanced by Panjabi represents the living spine as a complex neuromusculoskeletal system whose biomechanical functioning is rather finely dependent upon the interactions among and between three principal subsystems: the passive musculoskeletal subsystem (osteoligamentous spine plus passive mechanical contributions of the muscles), the active musculoskeletal subsystem (muscles and tendons), and the neural and feedback subsystem (neural control centers and feedback elements such as mechanoreceptors located in the soft tissues) [1]. The interplay between subsystems readily encourages "thought experiments" of how pathologic changes in one subsystem might influence another--for example, prompting one to speculate how painful arthritic changes …

In Vitro Biomechanical Testing And Computational: Modeling In Spine, Mageswaran Prasath

ETD Archive

Two separate in vitro biomechanical studies were conducted on human cadaveric spines (Lumbar) to evaluate the stability following the implantation of two different spinal fixation devices interspinous fixation device (ISD) and Hybrid dynamic stabilizers. ISD was evaluated as a stand-alone and in combination with unilateral pedicle rod system. The results were compared against the gold standard, spinal fusion (bilateral pedicle rod system). The second study involving the hybrid dynamic system, evaluated the effect on adjacent levels using a hybrid testing protocol. A robotic spine testing system was used to conduct the biomechanical tests. This system has the ability to apply …