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Full-Text Articles in Biomedical Engineering and Bioengineering

Computational Protein Design For Peptide-Directed Bioconjugation, Joseph Gabriel Plaks Jan 2019

Computational Protein Design For Peptide-Directed Bioconjugation, Joseph Gabriel Plaks

Chemical & Biological Engineering Graduate Theses & Dissertations

Proteins enable living organisms to perform many of their critical functions, having been applied over evolutionary time to solve problems of overwhelming diversity and complexity. Protein engineering seeks to deploy these versatile molecules in addressing problems of human concern and would benefit from innovations that improve protein utilization in unnatural environments as well as from increased predictive capability in protein design.

Bioconjugation facilitates the use of proteins in unnatural environments by permitting the attachment of molecules, such as polymers, that can modulate protein stability, solubility, and activity and by mediating protein immobilization. We initially explored this propensity of bioconjugation by ...


Development Of Novel Crispr-Based Methods For Transcriptional Control Over Bacterial Gene Expression, Katia Tarasava Jan 2019

Development Of Novel Crispr-Based Methods For Transcriptional Control Over Bacterial Gene Expression, Katia Tarasava

Materials Science & Engineering Graduate Theses & Dissertations

One of the challenges of the 21st century is creating a sustainable economy that is able to serve the needs of a growing population with the decreasing supply of natural resources. In addition to alternative energy sources, renewable economy concerns production of materials and chemicals. The chemical and polymer industries rely heavily on petroleum for manufacturing consumer goods. Many of these chemicals can be produced from renewable resources using microorganisms. However, the amounts produced are often not enough to make the process commercially viable. By rewiring cellular metabolism and regulation, it is possible to redirect metabolic flux to increase the ...


Nanoscale Stiffness Cues Influence Valvular Interstitial Cell Activation To Myofibroblasts, Michaela Wenning Jan 2019

Nanoscale Stiffness Cues Influence Valvular Interstitial Cell Activation To Myofibroblasts, Michaela Wenning

Undergraduate Honors Theses

Surgery is currently the primary treatment option for aortic valve stenosis (AVS) patients, many of whom are ineligible for surgery and are left untreated. AVS is progression is known to differ between males and females, and an understanding of sex-specific mechanisms of disease progression is imperative in developing accurate treatment options for men and women. The development of a nonsurgical therapy for AVS patients requires a deeper understanding of the molecular and cellular mechanisms of AVS progression. Currently, the role of calcium phosphate nanoparticles detected in the aortic valve during early stages of AVS in influencing disease progression and valvular ...


Feasibility And Analysis Of A Hybrid Spacesuit Architecture For Planetary Surface Exploration, Roger Huerta I Lluch Jan 2019

Feasibility And Analysis Of A Hybrid Spacesuit Architecture For Planetary Surface Exploration, Roger Huerta I Lluch

Aerospace Engineering Sciences Graduate Theses & Dissertations

This Thesis presents a novel hybrid spacesuit architecture concept to enable planetary exploration by combining mechanical counterpressure (MCP) with gas-pressurization (GP). This conceptual design has the potential to offer a quantifiable increase in mobility, increases in safety through pressure layer redundancy, and decreased pre-breathe time to improve operational efficiency.

The Thesis performs an engineering study on the concept. First, to assess the feasibility and benefit of implementing two separate pressure layers in the spacesuit, a trade analysis of the design space was performed by numerically modelling different spacesuit-related parameters. The analysis is done considering the combined system performance across different ...


Engineering Bacterial Gene Expression: Applications Towards Biofuels And Antibiotic Resistance, Peter Britton Otoupal Jan 2018

Engineering Bacterial Gene Expression: Applications Towards Biofuels And Antibiotic Resistance, Peter Britton Otoupal

Chemical & Biological Engineering Graduate Theses & Dissertations

Nature is rarely static. Organisms live in diverse and stressful environments that necessitate rapid response strategies for survival. Microorganisms have responded to this by evolving bet-hedging, wherein they exhibit constitutively heterogeneous gene expression to maximize fitness across numerous background. The goal of this thesis is to “hijack” this phenomenon using novel gene expression engineering techniques to alter how bacteria respond to their environments, in order to address pressing societal concerns.

This begins with a systematic exploration of how bacterial gene expression naturally responds to antibiotics and biofuels. This reveals promising gene candidates for targeted manipulation, for which a library of ...


Development And Characterization Of Improved Red Fluorescent Protein Variants, Premashis Manna Jan 2018

Development And Characterization Of Improved Red Fluorescent Protein Variants, Premashis Manna

Chemistry & Biochemistry Graduate Theses & Dissertations (1986-2018)

Aequorea victoria-based green fluorescent proteins and their blue, cyan and red counterparts offer unprecedented advantage as biological markers owing to their genetic encodability and straightforward expression in different organisms. Fluorescent proteins are characterized with complex photo-kinetics due to the presence of light-induced non-fluorescent or dark states which are responsible for their fluorescence intermittency or 'blinking'. We developed time- and frequency-domain techniques for probing the kinetics involving dark state conversion (DSC) and ground state recovery (GSR) in red fluorescent proteins (RFPs). Ensemble-level DSC and GSR kinetics in FPs were presented in the context of their single molecule fluorescence behaviors. Although ...


In Situ Designer Lipid Production: Integration Of Novel Characteristics And Behaviors Into Synthetic Cell Membranes, Danielle S. Konetski Jan 2018

In Situ Designer Lipid Production: Integration Of Novel Characteristics And Behaviors Into Synthetic Cell Membranes, Danielle S. Konetski

Chemical & Biological Engineering Graduate Theses & Dissertations

This thesis investigated the coupling of lysolipids and functionalized tails for in situ formation of synthetic liposomes designed to enable specific characteristics or behaviors in applications ranging from drug delivery to the advancement of artificial cell development. Copper-catalyzed Azide-Alkyne Cycloaddition (CuAAC) mediated lipid coupling was improved via incorporation of a photoinitiation system. Here, photo-CuAAC enabled spatiotemporal control over liposome assembly, an over 400-fold increase in formation density, and control over the maximal cross-sectional area of the liposomes formed.

Thiol-Michael mediated lipid coupling was enabled using thiol-functionalized lysolipids and acrylate tails where phospholipids were produced over 48 hours with approximate 90 ...


Modeling And Designing Genetic Devices Using Transcriptional Interference In Escherichia Coli, Antoni Escalas Bordoy Jan 2018

Modeling And Designing Genetic Devices Using Transcriptional Interference In Escherichia Coli, Antoni Escalas Bordoy

Chemical & Biological Engineering Graduate Theses & Dissertations

Microorganisms inhabit every extreme location of our planet. In their journey through the ages, they have been able to incredibly adapt to a myriad of different environmental conditions. A key mechanism for their success has been their ability to respond to environmental and nutritional changes through regulatory programs primarily encoded at the transcriptional level. This adaptability to new environments is what encourages scientists to believe in engineering a biological revolution that will transform our lives due to its potential to result in innovative approaches for bioremediation, sustainable energy production, and biomedical therapies. This thesis explores the potential of the phenomenon ...


Connecting Protein Structure And Dynamics On Biomaterials With The Foreign Body Response, David Faulon Marruecos Jan 2018

Connecting Protein Structure And Dynamics On Biomaterials With The Foreign Body Response, David Faulon Marruecos

Chemical & Biological Engineering Graduate Theses & Dissertations

The harsh environment of the foreign body response (FBR) has the potential to negatively impact the implantations of biomaterials in the body. The FBR is initiated by inflammatory cells that recognize the material as foreign through surface-adsorbed proteins. When proteins interact with surfaces, they can unfold and expose epitopes that may be recognized by immune cells and trigger a series of reactions. Importantly, the presentation of unfolded proteins is directly influenced by the highly dynamic and heterogeneous behavior of proteins in near-surface environments, as well as by the physicochemical features of the underlying surface. Such behavior is the result of ...


The Coordination Of Movement From Motor Units To Muscle Synergies, Daniel Francis Feeney Jan 2018

The Coordination Of Movement From Motor Units To Muscle Synergies, Daniel Francis Feeney

Integrative Physiology Graduate Theses & Dissertations

This dissertation comprises computational and experimental studies that examined the neuromuscular factors underlying differences in manual dexterity and mobility in health and disease.

The first two studies developed models of motor unit force production. The first model used a Proportional-Integral-Derivative (PID) control algorithm to activate a pool of motor units to simulate the force trajectory during force-matching tasks. The second model comprised a probabilistic state-space model to estimate the common synaptic input to motor neurons based on the discharge times of action potentials by activated motor units. The state-space model demonstrated superior sensitivity compared with previous models.

The next three ...


Crispr-Assisted Interrogation And Engineering Of Metabolic Pathways, Marcelo Colika Bassalo Jan 2018

Crispr-Assisted Interrogation And Engineering Of Metabolic Pathways, Marcelo Colika Bassalo

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Since Mendel’s work established the basis of inheritance in the late 1800s, multiple decades of research characterized monogenic traits across all domains of life. Yet, we still have a fairly limited knowledge on the genotype behind the vast majority of phenotypes. It is now evident that discrete biological functions can rarely be linked to a single gene. Further, these multigenic traits are often interconnected via a sophisticated and robust metabolic and regulatory network, selected by evolution in order to optimally distribute resources. The complexity of these multigenic traits challenges traditional genetic tools, broadly limiting our capability to understand and ...


Skeletal Muscle Metabolism: From Tissue To Stem Cell, Katherine Elise Gadek Jan 2018

Skeletal Muscle Metabolism: From Tissue To Stem Cell, Katherine Elise Gadek

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Excessive circulating triglycerides due to reduction or loss of lipoprotein lipase (LPL) activity contribute to hypertriglyceridemia and increased risk for pancreatitis. The only gene therapy treatment for LPL deficiency decreases pancreatitis but minimally reduces hypertriglyceridemia. Synthesized in striated muscle and adipose tissue, LPL is then trafficked to blood vessel endothelial cells where it hydrolyzes triglycerides into free fatty acids. We conditionally knocked out LPL in differentiated striated muscle tissue lowering striated muscle LPL activity and causing hypertriglyceridemia. We crossed these LPL knockout mice with mice possessing a conditional avian retroviral receptor gene and infected mice with human LPL or mCherry ...


Modeling Hypertrophic Cardiomyopathy In Neonatal Cardiomyocytes In Cultured In 3d, Esther Choi Jan 2018

Modeling Hypertrophic Cardiomyopathy In Neonatal Cardiomyocytes In Cultured In 3d, Esther Choi

Undergraduate Honors Theses

Heart disease continues to be the leading cause of death in both men and women. It is accompanied with cellular- and organ- level remodeling that cannot be mimicked or recaptured by cells on standard culture platforms. Polyethylene glycol hydrogels bridge this gap by providing user-defined tunability for cell culture. A novel 3D cell culture system was developed to encapsulate neonatal rat ventricular cardiomyocytes (NRVMs) in a single plane, and cell health was assessed. In parallel, recombinant adenoviruses containing the mutations responsible for human hypertrophic cardiomyopathy (HCM) in the beta myosin gene (R403Q and R453C) were generated and used as a ...


Zonal Articular Cartilage Possesses Complex Mechanical Behavior Spanning Multiple Length Scales: Dependence On Chemical Heterogeneity, Anisotropy, And Microstructure, Joseph Anders Wahlquist Jan 2017

Zonal Articular Cartilage Possesses Complex Mechanical Behavior Spanning Multiple Length Scales: Dependence On Chemical Heterogeneity, Anisotropy, And Microstructure, Joseph Anders Wahlquist

Mechanical Engineering Graduate Theses & Dissertations

This work focused on characterizing the mechanical behavior of biological material in physiologically relevant conditions and at sub millimeter length scales. Elucidating the time, length scale, and directionally dependent mechanical behavior of cartilage and other biological materials is critical to adequately recapitulate native mechanosensory cues for cells, create computational models that mimic native tissue behavior, and assess disease progression. This work focused on three broad aspects of characterizing the mechanical behavior of articular cartilage. First, we sought to reveal the causes of time-dependent deformation and variation of mechanical properties with distance from the articular surface. Second, we investigated size dependence ...


Zonal Articular Cartilage Possesses Complex Mechanical Behavior Spanning Multiple Length Scales: Dependence On Chemical Heterogeneity, Anisotropy, And Microstructure, Joseph Anders Wahlquist Jan 2017

Zonal Articular Cartilage Possesses Complex Mechanical Behavior Spanning Multiple Length Scales: Dependence On Chemical Heterogeneity, Anisotropy, And Microstructure, Joseph Anders Wahlquist

Mechanical Engineering Graduate Theses & Dissertations

This work focused on characterizing the mechanical behavior of biological material in physiologically relevant conditions and at sub millimeter length scales. Elucidating the time, length scale, and directionally dependent mechanical behavior of cartilage and other biological materials is critical to adequately recapitulate native mechanosensory cues for cells, create computational models that mimic native tissue behavior, and assess disease progression. This work focused on three broad aspects of characterizing the mechanical behavior of articular cartilage. First, we sought to reveal the causes of time-dependent deformation and variation of mechanical properties with distance from the articular surface. Second, we investigated size dependence ...


Understanding The Mechanics Of Tissue Growth In Engineered Scaffolds: Case Of Cartilage Tissue, Umut Akalp Jan 2017

Understanding The Mechanics Of Tissue Growth In Engineered Scaffolds: Case Of Cartilage Tissue, Umut Akalp

Civil Engineering Graduate Theses & Dissertations

Tissue failure due to aging or diseases reduces the quality of life for individuals. In the case of cartilage tissue, the current solution is to use implants to fulfill the functional duties of native tissue. However, this approach has limitations, such as periodic replacement and number of the required operations. Tissue engineering provides an alternative approach in which the aim is to regenerate the native tissue by a population of cells encapsulated in a scaffold (i.e. hydrogels). Although this approach is promising, there are several limitations regarding the design of these scaffolds which can be overcome only by the ...


Epithelial-Mesenchymal Crosstalk Influences Cancer-Related Cell Behavior: A 3d Lung Alveolus-Fibroblast Co-Culture System, Jessica Kole Hall Jan 2017

Epithelial-Mesenchymal Crosstalk Influences Cancer-Related Cell Behavior: A 3d Lung Alveolus-Fibroblast Co-Culture System, Jessica Kole Hall

Undergraduate Honors Theses

Lung cancer is a devastating disease that kills more individuals in the United States than any other cancer. The tumor microenvironment is increasingly recognized as playing a major role in the progression of cancer. Thus, studying the interactions among lung cancer cells, non-malignant cells and the surrounding matrix is critical for understanding and treating lung cancer. Three-dimensional in vitro co-culture systems allow for tissue-relevant platforms that better recapitulate the native cell environment. In this work, we employed a cyst templating technique to culture alveolar epithelial cells on photodegradable microspheres and subsequently encapsulated the cell-covered spheres within poly(ethylene glycol) (PEG ...


An Inquiry Into The Electro-Physiology Of Bacteria, Prasanth Prahladan Apr 2016

An Inquiry Into The Electro-Physiology Of Bacteria, Prasanth Prahladan

Electrical, Computer & Energy Engineering Graduate Theses & Dissertations

This thesis documents the exploration of tools and techniques which were used to determine the existence of patterns within and relationships between the voltage and calcium measurements from individual bacterial cells. The research lies in the broad domain of bacterial electro-physiology.


Engineering Of Filamentous Bacteriophage For Protein Sensing, Michael David Brasino Jan 2016

Engineering Of Filamentous Bacteriophage For Protein Sensing, Michael David Brasino

Materials Science & Engineering Graduate Theses & Dissertations

Methods of high throughput, sensitive and cost effective quantification of proteins enables personalized medicine by allowing healthcare professionals to better monitor patient condition and response to treatment. My doctoral research has attempted to advance these methods through the use of filamentous bacteriophage (phage). These bacterial viruses are particularly amenable to both genetic and chemical engineering and can be produced efficiently in large amounts. Here, I discuss several strategies for modifying phage for use in protein sensing assays. These include the expression of bio-orthogonal conjugation handles on the phage coat, the incorporation of specific recognition sequences within the phage genome, and ...


Sensorimotor Adaptation In Whole-Body Postural Control, Alison Pienciak-Siewert Jan 2016

Sensorimotor Adaptation In Whole-Body Postural Control, Alison Pienciak-Siewert

Mechanical Engineering Graduate Theses & Dissertations

The ability to maintain stable, upright standing is a critical component of our daily activities. This ability requires that we generate appropriate postural control when making voluntary movements and when responding to perturbations, and appropriately adapt that control to compensate for changing conditions. Despite this, adaptation of whole-body postural control is not well understood.

This dissertation investigates the control strategies involved in the adaptation of whole-body postural control and how well this learning transfers to different environments. We used an experimental paradigm in which subjects made reaching movements while standing and holding the handle of a force-generating robotic arm that ...


The Effects Of Weak Static And Pulsed Magnetic Fields On Fibroblast And Fibrosarcoma Cells Under A Controlled Magnetic Environment, Julian Brandon Cyrus Apr 2015

The Effects Of Weak Static And Pulsed Magnetic Fields On Fibroblast And Fibrosarcoma Cells Under A Controlled Magnetic Environment, Julian Brandon Cyrus

Electrical, Computer & Energy Engineering Graduate Theses & Dissertations

This thesis provides evidence supporting the claim that weak static and pulsed magnetic fields have measureable effects upon fibrosarcoma cells. Fibroblast and fibrosarcoma cell lines were exposed to 0, 100, and 200μT fields, with a static 45μT field as the control. Each exposure intensity, other than 0μT, was conducted at a 20 sec pulse repetition rate, as well as the normal static conditions. The cells were tested for variations in oxidative stress, membrane potential, and cell viability. The fibrosarcoma cells were also tested for cell count. The trials were conducted using an electromagnetic system that provided a controlled magnetic environment ...


Optimization And Control Of An Active Helmet Design For Head Injury Prevention, Chadi S. Abdel-Samad Apr 2015

Optimization And Control Of An Active Helmet Design For Head Injury Prevention, Chadi S. Abdel-Samad

Electrical, Computer & Energy Engineering Graduate Theses & Dissertations

Thousands of mild traumatic brain injuries (mBTIs) occur in US football each year. In some instances, injuries are quite serious and life-threatening. New NFL rules being enforced by the league are an attempt to address this problem. Of interest is whether an active helmet design, employing feedback, can also reduce the incidence of mBTIs in football. Medical evidence and research suggests that peak center of gravity (CG) head acceleration is well correlated with the onset and severity of mBTI. In this dissertation, an active helmet design is introduced, dynamically modeled, and explored from the perspective of using control to reduce ...


Improved Methods For Understanding Sparse, Multi-Dimensional, High Throughput Sequencing Data, Sophie J. Weiss Jan 2015

Improved Methods For Understanding Sparse, Multi-Dimensional, High Throughput Sequencing Data, Sophie J. Weiss

Chemical & Biological Engineering Graduate Theses & Dissertations

Tremendous advances in genetic and sequencing technology are enabling unprecedented insight into human disease, forensics, and cellular mechanisms, to name a few. Conclusions drawn from these studies are strongly influenced by the interpretation of their associated massive data sets. The goal of this thesis is to understand, develop, and apply algorithms to help overcome common ecological and biological sequencing study challenges: contamination, differences in sampling efforts, a very large amount of zeroes, and compositionality.

We use simulations and experimental data to understand how different matrix normalization strategies mitigate the effects of the aforementioned challenges on downstream analyses, particularly principal coordinate ...


The Role Of Matrix Properties In Directing Valvular Interstitial Cell Phenotype, Kelly Marie Pollock Mabry Jan 2015

The Role Of Matrix Properties In Directing Valvular Interstitial Cell Phenotype, Kelly Marie Pollock Mabry

Chemical & Biological Engineering Graduate Theses & Dissertations

This thesis presents the development of hydrogel platforms to study the fibroblast-to-myofibroblast transition in valvular interstitial cells (VICs). These systems were used to characterize the effects of extracellular matrix cues on VICs, as well as the synergies between mechanical and biochemical signals. First, the impact of culture platform on VIC phenotype was assessed by culturing VICs in peptide-functionalized poly(ethylene glycol) hydrogels (2D and 3D) and comparing them to those cultured on tissue culture polystyrene (TCPS). Expression of the myofibroblast marker α-smooth muscle actin (αSMA), as well as by a global analysis of the transcriptional profiles1 demonstrated that TCPS ...


Real-Time Single-Molecule Observations Of Proteins At The Solid-Liquid Interface, Blake Brianna Langdon Jan 2014

Real-Time Single-Molecule Observations Of Proteins At The Solid-Liquid Interface, Blake Brianna Langdon

Chemical & Biological Engineering Graduate Theses & Dissertations

Non-specific protein adsorption to solid surfaces is pervasive and observed across a broad spectrum of applications including biomaterials, separations, pharmaceuticals, and biosensing. Despite great interest in and considerable literature dedicated to the phenomena, a mechanistic understanding of this complex phenomena is lacking and remains controversial, partially due to the limits of ensemble-averaging techniques used to study it. Single-molecule tracking (SMT) methods allow us to study distinct protein dynamics (e.g. adsorption, desorption, diffusion, and intermolecular associations) on a molecule-by-molecule basis revealing the protein population and spatial heterogeneity inherent in protein interfacial behavior. By employing single-molecule total internal reflection fluorescence microscopy ...


A Novel Selection Technology For The Discovery Of High-Affinity Human Proteins, David Busha Jan 2014

A Novel Selection Technology For The Discovery Of High-Affinity Human Proteins, David Busha

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Proteins that bind with high-affinity to cellular targets can be useful therapeutic treatments. High-throughput affinity screening of large protein libraries is often more successful at discovering novel high-affinity proteins than rational-design approaches. Display techniques such and phage and yeast display are commonly used in this screening process. However, bacteria and yeast cells can misfold or otherwise inappropriately express mammalian and human proteins due to differences in codon usage, protein folding machinery and post-translational modifications. Therefore, a display system that is entirely based in human cells could aid in the discovery of novel, high-affinity proteins. No such system has been described ...


The Effects Of Matrix Elasticity, Composition, And Exogenous Growth Factors On The Vascular Differentiation Of Mesenchymal Stem Cells, Kathryn Anne Wingate Jan 2013

The Effects Of Matrix Elasticity, Composition, And Exogenous Growth Factors On The Vascular Differentiation Of Mesenchymal Stem Cells, Kathryn Anne Wingate

Mechanical Engineering Graduate Theses & Dissertations

Cardiovascular diseases are the leading cause of death in the western world. Regeneration of functional vascular tissue remains a critical barrier to successful treatment of these diseases. Attempts to produce functional vascular tissue with autogenous vascular cells have limited success due to the need for invasive surgery. Mesenchymal stem cells (MSCs) are a powerful cellular alternative for vascular regeneration as they are easily obtainable, multipotent, and thrombo-resistant. Currently, the mechanisms that drive MSC differentiation to healthy or diseased vascular phenotypes are not well understood. There is a critical need to define the factors in the cellular microenvironment that guide MSC ...