Engineering Commons^™

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 …

Tauopathies, Novel Optogenetic Tools, And The Future Of Artificial Intellience In Medicine., Jessica L. Binder

Biomedical Sciences ETDs

To this day, there is no cure for Alzheimer’s disease (AD) and related dementias (ADRD). With the daunting rise at an exponential rate of ADRD burden and related deaths, the necessity to find a new line of attack is vital. Pathological accumulation of microtubule associated protein tau in neurons is a major neuropathological hallmark of Alzheimer’s disease (AD) and related tauopathies. Attempts have been made to promote clearance of pathological tau (p-Tau) from neurons via autophagy. Transcription factor EB (TFEB) has shown to clear p-Tau from neurons via autophagy. However, sustained TFEB activation and autophagy can create burden on cellular …

Large Scale Electronic Health Record Data And Echocardiography Video Analysis For Mortality Risk Prediction, Alvaro Emilio Ulloa Cerna

Electrical and Computer Engineering ETDs

Electronic health records contain the clinical history of patients. The enormous potential for discovery in such a rich dataset is hampered by their complexity. We hypothesize that machine learning models trained on EHR data can predict future clinical events significantly better than current models. We analyze an EHR database of 594,862 Echocardiography studies from 272,280 unique patients with both unsupervised and supervised machine learning techniques.

In the unsupervised approach, we first develop a simulation framework to evaluate a family of different clustering pipelines. We apply the optimized approach to 41,645 patients with heart failure without providing any survival information to …

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 …

Cellular Modification And Artificial Cell Construction, Jimin Guo

Chemical and Biological Engineering ETDs

With all its complexities and different biofunctionalities, a cell is the basic structural and functional unit of all living organisms with the exception of viruses. In this dissertation, I demonstrated gain of function strategies of modifying mammalian cells using silicification and modular nanoparticle (NP) exoskeletons. In addition, I used a modular design concept to build a multifunctional artificial RBC system which can mimic the unique characteristics (e.g. shape, flexibility, the ability to carry oxygen, and long circulation times) of the native RBCs. Together, these cell modification or artificial cell construction strategies are expected to generate new mammalian cell-like structures with …

Developing A Synthetic Model Of The Candida Albicans Cell Wall Using Self-Assembled Monolayers To Host Beta-Glucan As Ligands, Ushnik Ghosh

Biomedical Engineering ETDs

The goal of this investigation is to study mechanisms the immune cell receptor, Dectin-1, uses to identify the fungal cell species, Candida albicans. Dectin-1 identifies extracellular matrix polysaccharides that Candida albicans express known as β-glucan. To study the interaction of β-glucan – Dectin-1 at the nanoscopic scale, the investigators of this project have endeavored to model the Candida albicans cell wall with engineered Self-Assembled Monolayers presenting β-glucan as a ligand for immobilized Dectin-1 receptors. By engineering a simplified ex-vivo model of the Candida albicans cell wall, the investigators of this study aim to gain precise control of the composition …

Incorporation Of Egfr And Ron Receptors Into Nanodiscs, Cristina Flores-Cadengo

Biomedical Engineering ETDs

Understanding the structure-function relationship of membrane receptors is essential to comprehend the crosstalk between key signaling pathways. Aberrant trans-activation between receptors can lead to tumorigenesis. Two of these receptors known to be involved in cancer development are receptor tyrosine kinases (RTKs), RON (Recepteur d'Origine Nantais) and EGFR (Epidermal Growth Factor Receptor). There has been evidence of heterodimerization and crosstalk between these two receptors based on co-immunoprecipitation, however the structural requirements behind these interactions remain unknown. Structural studies could provide insights into these RTKs’ modes of dimerization and structure-function relationship. However, structural studies of full-length membrane proteins are often difficult due …

The Effect Of Defects And Surface Modification On Biomolecular Assembly And Transport, Haneen Martinez

Nanoscience and Microsystems ETDs

Nanoscale transport using the kinesin-microtubule (MT) biomolecular system has been successfully used in a wide range of nanotechnological applications including self-assembly, nanofluidic transport, and biosensing. Most of these applications use the ‘gliding motility geometry’, in which surface-adhered kinesin motors attach and propel MT filaments across the surface, a process driven by ATP hydrolysis. It has been demonstrated that active assembly facilitated by these biomolecular motors results in complex, non-equilibrium nanostructures currently unattainable through conventional self-assembly methods. In particular, MTs functionalized with biotin assemble into rings and spools upon introduction of streptavidin and/or streptavidin-coated nanoparticles. Upon closer examination of these structures …