Engineering Commons^™

Antimicrobial Activity And Mechanism Of Amyloid Proteins And Synthetic Conjugated Polyelectrolytes, Fahimeh Maghsoodi

Nanoscience and Microsystems ETDs

Although the exact cause of Alzheimer’s disease (AD) is still unknown, it is widely considered that the accumulation of amyloid plaques composed of the amyloid-β (Aβ) peptide in the brain is linked to neurodegeneration. Co-localization of viral DNA with Aβ plaques, the association of brain infection and AD, and research indicating the protective effect of Aβ against bacteria and fungi in mice and human cells have led to the hypothesis that Aβ expression and deposition may be central to its function as an antimicrobial peptide (AMP). In my thesis research, we seek to elucidate how Aβ functions as an AMP …

Material Characterization And Comparison Of Sol-Gel Deposited And Rf Magnetron Deposited Lead Zirconate Titanate Thin Films, Katherine Lynne Miles

Mechanical Engineering ETDs

Lead zirconate titanate (PZT) has been a material of interest for sensor, actuator, and transducer applications in microelectromechanical systems (MEMS). This is due to their favorable piezoelectric, pyroelectric and ferroelectric properties. While various methods are available to deposit PZT thin films, radio frequency (RF) magnetron sputtering was selected to provide high quality PZT films with the added capability of batch processing. These sputter deposited PZT films were characterized to determine their internal film stress, Young’s modulus, composition, and structure. After characterization, the sputtered PZT samples were poled using corona poling and direct poling methods. As a means of comparison, commercially …

The Investigation Of Surface Structures On Various Pathogens And Their Interactions With The Human Immune System, Carmen M. Villalobos

Biomedical Engineering ETDs

The cell surface is the first interface the host immune system encounters and

its investigation has led to a better understanding of cellular biology and types of

pathways that pathogens target in a host cell. The cell surface has evolved to include

many functions such as manipulation of the cytoskeleton, cell signaling, membrane

trafficking, adhesion, and integration into host tissue. The pathogens of interest are

the pathogenic fungus, Candida albicans, and the parasite, Giardia lamblia and we

investigate the consequences of drug treatments on the cell surface, leading to

promising new targets.

Screening And Characterization Of A Pan-Gtpase Inhibitor, Leyla Akhadov

Biomedical Engineering ETDs

Abnormal functioning of small GTPases is implicated in a variety of diseases, ranging from neurological and developmental diseases to cancer. In fact, mutant GTPases are found in up to 30% of cancers. Thus, small GTPases are a highly relevant target in drug discovery and development. High-throughput targeted screening of small molecules is the most productive method of discovering compounds that can give insights into drug development. This thesis describes improvements made to a high-throughput GTPase-targeted screening method to minimize confounding systematic error. It also describes the follow-up characterization of a compound that was identified in a high-throughput screen. The compound …

Diagnostic Sequence Detection Against A Complex Background Using A Dna Molecular Computation Framework, Adan Leon Myers Y Gutierrez

Nanoscience and Microsystems ETDs

Diagnostic assays are designed to detect a unique analyte profile in a disease of interest. Nucleic acids contain an information-dense sequence, and thus are ideal candidates for unique analytes. The gold-standard of nucleic-acid-based detection is PCR which has high sensitivity, but involves time, expertise, and cost. DNA molecular logic technology holds much promise as an alternative molecular detection method due to the potential to save cost and expertise, while also achieving a high sensitivity. However, nucleic acid detection in biomedical applications carries with it the difficulty of choice of appropriate sequence and potential biological sample background.

This work describes the …

Assessment Of The Biocompatibilty, Stability, And Suitability Of Natural And Synthetic Polymers And Drugs In The Fda Approval Process, Phuong Anh Hoang Nguyen

Biomedical Engineering ETDs

Regulation of the development, production, marketing, and sales of medical pharmaceuticals and devices in the United States fall under the regulatory functions of the Food and Drug Administration (FDA). The current FDA approval process takes an average of 10 years from start to completion, and costs over $100 million. As a result, companies use many different methods to find additional use of their drugs through marketing directly to the physician, or recycling of previously approved drug moieties. In this work, an evaluation of the in vitro and ex vivo biocompatibility of polymers and drugs in different phases of FDA approval …

Detection And Remodeling Of Toxic Amyloid Aggregates By Novel Conjugated Polyelectrolytes, Adeline Marianne Fanni

Biomedical Engineering ETDs

The abnormal misfolding and aggregation of intrinsically disordered proteins into ordered fibrillar amyloid aggregates is recognized as a common pathological event in neurodegenerative disorders (ND) such as Alzheimer’s and Parkinson’s diseases. The key role of fibrillar and pre-fibrillar aggregates in ND makes them ideal biomarkers to better understand disease progression but also for early disease detection and therapeutic intervention. The work described herein was conducted to gain a better understanding of amyloid interaction to lipid membrane and its role in peptide toxicity. This research was also focused on evaluating the fluorescent probe, oligomeric p-phenylene ethynylene (OPE), as an amyloid …

Computational Investigation Of The Interactions Between Bioactive Compounds And Biological Assemblies, Tye D. Martin

Biomedical Engineering ETDs

Small, biologically active molecules with unique properties and applications are potential solutions to a wide range of threats to global health including infectious agents and neurodegenerative disease. Experimental studies on a class of oligomeric p-phenylene ethynylenes (OPEs) have shown potential both as bioactive antimicrobials and fluorescent sensing agents for tracking amyloid-β (Aβ) aggregates found in Alzheimer’s Disease (AD). A second type of small molecule with potential applications in AD therapy, curcumin, has been found to interfere with Aβ fibril growth. Curcumin also attenuates Aβ-membrane interactions and Aβ toxicity. Our goal has been to use computational techniques to better understand the …

A Microfluidics-Based Cross-Flow Filtration Platform For Rapid Processing Of Amphiphilic Biomarkers From Blood, Kiersten D. Lenz

Biomedical Engineering ETDs

Early and accurate detection of bacterial infections can help save lives, prevent the spread of disease, and decrease the overuse of antibiotics. Our team at the Los Alamos National Laboratory has developed novel assays to detect bacterial biomarkers from patient blood at the point-of-care in order to facilitate a universal diagnostic platform. However, these biomarkers are amphiphilic in nature, and this biochemical property causes them to be sequestered by high-density and low-density lipoproteins (HDL and LDL) in the host’s blood. Extraction of the bacterial biomarkers from the lipoprotein complexes is thereby required for the development and deployment of a diagnostic …

Development Of Biomimetic Membrane Assemblies On Microspheres For High-Throughput And Multiplexable Studies, Nadiezda P. Fernandez Oropeza

Biomedical Engineering ETDs

Membranes and membrane-associated components are the target of approximately 60% of the current drugs, of synthetic materials, such as polymers, which are used for drug delivery purposes and of other biomolecules, such as endotoxins, which gain entry into the cell by disrupting the membrane. Therefore, the development of biomimetic membrane assemblies allows the study of different biological processes in which cell membranes play an important role, and the characterization and screening of drug delivery tools and other membrane-bound components.

Since its development, membrane assemblies on planar silica surfaces have been the method of choice to study membrane-associated and membrane-bound components. …

A Multiscale Modeling Study Of The Mammary Gland, Joseph D. Butner

Biomedical Engineering ETDs

Multiscale, hybrid computer modeling has emerged as a valuable tool in the fields of computational systems biology and mathematical oncology. In this work, we present an overview of the motivations for, and development and implementation of, three hybrid multiscale models of the mammary gland system and early stage ductal carcinoma in situ (DCIS) in the gland. Pubertal mammary gland development was described first using a two-dimensional, lattice-based hybrid agent-based model description of the mammary terminal end bud (TEB), and then with a three-dimensional lattice-free TEB model. Both models implement a discrete, agent-based description of the cell scale, and a continuum, …