Engineering Commons^™

Selective Targeting Of Microglia By Quantum Dots And Green Synthesis Of Metal Organic Biohybrids; Applications In Dynamic Cell And Assay Systems, Navya Uppu

Doctoral Dissertations

Neurological disorders are the leading cause of physical and cognitive disability across the globe, currently affecting approximately 15% of the worldwide population. Part of the glioma microenvironment are microglia, resident immune cells of the CNS that were thought to be involved in the pathogenesis of diverse neurodegenerative diseases. Though it remains uncertain what triggers microglial activation in these disorders, targeting and tracking microglial functions using nanotools like Quantum Dots (QDs) could help us elucidate them in such neurological diseases. This research focuses on the comparative study of different QDs formulations and their selective uptake by brain microglia in primary cultures …

Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov

Doctoral Dissertations

Reactive chemistries for protein chemical modification play an instrumental role in chemical biology, proteomics, and therapeutics. Depending on the application, the selectivity of these modifications can range from precise modification of an amino acid sequence by genetic manipulation of protein expression machinery to a stochastic modification of lysine residues on the protein surface. Ligand-Directed (LD) chemistry is one of the few methods for targeted modification of endogenous proteins without genetic engineering. However, current LD strategies are limited by stringent amino acid selectivity. To bridge this gap, this thesis focuses on the development of highly reactive LD Triggerable Michael Acceptors (LD-TMAcs) …

Advanced Air Quality Management With Machine Learning, Cheng-Pin Kuo

Doctoral Dissertations

Air pollution has been a significant health risk factor at a regional and global scale. Although the present method can provide assessment indices like exposure risks or air pollutant concentrations for air quality management, the modeling estimations still remain non-negligible bias which could deviate from reality and limit the effectiveness of emission control strategies to reduce air pollution and derive health benefits. The current development in air quality management is still impeded by two major obstacles: (1) biased air quality concentrations from air quality models and (2) inaccurate exposure risk estimations

Inspired by more available and overwhelming data, machine learning …

Unobtrusive Assessment Of Upper-Limb Motor Impairment Using Wearable Inertial Sensors, Brandon R. Oubre

Doctoral Dissertations

Many neurological diseases cause motor impairments that limit autonomy and reduce health-related quality of life. Upper-limb motor impairments, in particular, significantly hamper the performance of essential activities of daily living, such as eating, bathing, and changing clothing. Assessment of impairment is necessary for tracking disease progression, measuring the efficacy of interventions, and informing clinical decision making. Impairment is currently assessed by trained clinicians using semi-quantitative rating scales that are limited by their reliance on subjective, visual assessments. Furthermore, existing scales are often burdensome to administer and do not capture patients' motor performance in home and community settings, resulting in a …

Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian

Doctoral Dissertations

The self-assembly of charged macromolecules forms the basis of all life on earth. From the synthesis and replication of nucleic acids, to the association of DNA to chromatin, to the targeting of RNA to various cellular compartments, to the astonishingly consistent folding of proteins, all life depends on the physics of the organization and dynamics of charged polymers. In this dissertation, I address several of the newest challenges in the assembly of these types of materials. First, I describe the exciting new physics of the complexation between polyzwitterions and polyelectrolytes. These materials open new questions and possibilities within the context …

Design And Development Of The Urban Population Health Observatory To Improve Disease Surveillance And Response, Whitney Brakefield

Doctoral Dissertations

Chronic and infectious diseases have a profound impact on the quality and length of life of populations that suffer from these conditions. Scientists, physicians, and health officials are seeking innovative approaches to decrease the morbidity and mortality of deadly diseases. Incorporating artificial intelligence and data science techniques across the health science domain could improve disease surveillance, intervention planning, and policymaking. In this dissertation, we describe the design and development of the Urban Population Health Observatory (UPHO), an explainable knowledge-based multimodal big data analytics platform. A common challenge for conducting multimodal big data analytics is integrating multidimensional heterogeneous data sources, which …

Decision-Analytic Models Using Reinforcement Learning To Inform Dynamic Sequential Decisions In Public Policy, Seyedeh Nazanin Khatami

Doctoral Dissertations

We developed decision-analytic models specifically suited for long-term sequential decision-making in the context of large-scale dynamic stochastic systems, focusing on public policy investment decisions. We found that while machine learning and artificial intelligence algorithms provide the most suitable frameworks for such analyses, multiple challenges arise in its successful adaptation. We address three specific challenges in two public sectors, public health and climate policy, through the following three essays. In Essay I, we developed a reinforcement learning (RL) model to identify optimal sequence of testing and retention-in-care interventions to inform the national strategic plan “Ending the HIV Epidemic in the US”. …

Qualitative And Quantitative Improvements For Positron Emission Tomography Using Different Motion Correction Methodologies, Tasmia Rahman Tumpa

Doctoral Dissertations

Positron Emission Tomography (PET) data suffers from low image quality and quantitative accuracy due to different kinds of motion of patients during imaging. Hardware-based motion correction is currently the standard; however, is limited by several constraints, the most important of which is retroactive data correction. Data-driven techniques to perform motion correction in this regard are active areas of research. The motivation behind this work lies in developing a complete data-driven approach to address both motion detection and correction. The work first presents an algorithm based on the positron emission particle tracking (PEPT) technique and makes use of time-of-flight (TOF) information …

Engineered Nanoparticles For Site-Specific Bioorthogonal Catalysis: Imaging And Therapy, Riddha Das

Doctoral Dissertations

Bioorthogonal catalysis offers a strategy for chemical transformations complementary to bioprocesses and has proven to be a powerful tool in biochemistry and medical sciences. Transition metal catalysts (TMCs) have emerged as a powerful tool to execute selective chemical transformations, however, lack of biocompatibility and stability limits their use in biological applications. Incorporation of TMCs into nanoparticle monolayers provides a versatile strategy for the generation of bioorthogonal nanocatalysts known as “nanozymes”. We have fabricated a family of nanozymes using gold nanoparticles (AuNPs) as scaffolds featuring diverse chemical functional groups for controlled localization of nanozymes in biological environments, providing unique strategies for …

Investigation On Nanoparticle Based Combination Therapy For Targeted Cancer Treatment, Muhammad Raisul Abedin

Doctoral Dissertations

“The current treatment methods in cancer are associated with toxicity in healthy tissues, partial therapeutic response, drug resistance and finally recurrence of the disease. The cancer drugs are challenged by non-specific binding, undesired toxicity in healthy cells, low therapeutic index and finally poor therapeutic outcome. In this work, a targeted nanoscale therapeutic system Antibody Drug Nanoparticle (ADN) was engineered to selectively inhibit the breast cancer cell growth with reduced toxicity in healthy cells. The ADNs were designed by synthesizing rod shaped anoparticles using pure chemotherapeutic drug and covalently conjugating a therapeutic monoclonal antibody (mAb) on the surface of the drug …

Engineering Nanomaterials For Imaging And Therapy Of Bacteria And Biofilm-Associated Infections, Akash Gupta

Doctoral Dissertations

Infections caused by multidrug-resistant (MDR) bacteria pose a serious global burden of mortality, causing thousands of deaths each year. The “superbug” risk is further exacerbated by chronic infections generated from antibiotic-resistant biofilms that are highly resistant to available treatments. Synthetic macromolecules such as polymers and nanoparticles have emerged as promising antimicrobials. Moreover, ability to modulate nanomaterial interaction with bacterial cellular systems plays a pivotal role in improving the efficacy of the strategy. In the initial studies on engineering nanoparticle surface chemistry, I investigated the role played by surface ligands in determining the antimicrobial activity of the nanoparticles. In further study, …

Three Essays On Data-Driven Optimization For Scheduling In Manufacturing And Healthcare, Ekin Koker

Doctoral Dissertations

This dissertation consists of three essays on data-driven optimization for scheduling in manufacturing and healthcare. In Chapter 1, we briefly introduce the optimization problems tackled in these essays. The first of these essays deals with machine scheduling problems. In Chapter 2, we compare the effectiveness of direct positional variables against relative positional variables computationally in a variety of machine scheduling problems and we present our results. The second essay deals with a scheduling problem in healthcare: the team primary care practice. In Chapter 3, we build upon the two-stage stochastic integer programming model introduced by Alvarez Oh (2015) to solve …

Combining Human Factors And Data Science Methods To Evaluate The Use Of Free Text Communication Orders In Electronic Health Records, Swaminathan Kandaswamy

Doctoral Dissertations

Medication errors are a leading cause of death in the United States. Electronic Health Records (EHR) along with Computerized Provider Order Entry (CPOE) are considered promising ways to reduce these errors. However, EHR systems have not eliminated medication errors. Moreover, in some cases they have facilitated errors due to issues such as poor usability and negative effects on clinical workflows. The use of unexpected free text within a CPOE system can serve as a marker that the system does not adequately support clinical workflow. Prior studies have looked at the use of free text within medication orders, but the inclusion …

Direct Printing Of Conductive Inks For Organic Electronics And Wearable Microfluidics, Aditi Naik

Doctoral Dissertations

This dissertation examines the direct printing of conductive inks on polymeric substrates for applications in organic electronics, microfluidic valving systems, and wearable sweat sensors. The inexpensive production of solution-based electrodes with high electrical conductivity is necessary to enable the next-generation of printed, flexible, and organic electronics. Specifically, the optimization and printing of liquid-phase graphene ink and nanoparticle-based silver ink by soft nanoimprint lithography and inkjet-printing is discussed to achieve printed functional devices. Using scalable low-cost patterning systems, these flexible applications are compatible with roll-to-roll processing, enabling large-scale manufacturing. This research expands the knowledge of high-resolution printing optimization for the direct …

Engineered Coating Of Natural Fibers And Oil-Water Interfaces With Self-Assembly Of Clay Nanotubes, Abhishek Panchal

Doctoral Dissertations

Taking into consideration two different types of surfaces, this dissertation proposes techniques to coat the surface of natural fibers and oil-water interfaces by spontaneous self-assembly of halloysite clay nanotubes. The material of choice, halloysite clay, is a widely available natural resource and can be used after minimal processing. In regards to chemical composition, halloysite clay resembles aluminosilicate mineral kaolin; physically, a defect in the crystal structure ordering causes the sheets of kaolinite to roll into halloysite nanotubes. The dimensions of halloysite nanotubes are dependent on the source, but generally vary from 200 nm to 3 µm in length, 100-150 nm …

Role Of Rigidity And Flexibility Of Functional Groups Within The Interior Of Supramolecular Assemblies And Their Implications, Oyuntuya Munkhbat

Doctoral Dissertations

Engineering of supramolecular assemblies at molecular level renders functional nanomaterials that present explicit response to certain environmental changes. Systematic structure-property correlation studies will unravel the fundamental design constraints of these functional nanomaterials that fulfill the emergent need. This dissertation will primarily focus on understanding the role of rigidity and flexibility of functional groups within amphiphilic assemblies and employing this basic concept in drug delivery and diagnostics applications. Supramolecular assemblies formed by amphiphilic dendrimers and polymers are preferred for this study as they exhibit high thermodynamic stability and structural flexibility. The role of aromatic interaction on the unimer-aggregate dynamic equilibrium was …

Atomic Layer Deposition Prepared Nanostructured Materials For Various Catalytic Reactions, Xiaofeng Wang

Doctoral Dissertations

"Atomic layer deposition (ALD) has been widely used for thin film coating and metal nanoparticles (NPs) preparation. In this report, the applications of ALD prepared nanostructured materials in catalysis were examined.

Highly dispersed Pt monometallic catalysts with different substrates and multi-walled carbon nanotubes (MWCNTs) supported Pt-Co bimetallic catalysts were synthesized by ALD for selective hydrogenation of α, β-unsaturated aldehydes to unsaturated alcohols (UA). Pt/MWCNTs showed the highest selectivity of UA in selective hydrogenation of citral, as compared to Pt/SiO₂, Pt/ALD-Al₂O₃, and Pt/γ-Al₂O₃. After adding Co, the highest selectivity was achieved …

Evaluation Of Increased Targeted Enforcement And Community-Based Outreach And Education Programs To Increase Nighttime Seatbelt Use In East Tennessee, Kwaku Frimpong Boakye

Doctoral Dissertations

According to the National Highway Traffic Safety Administration (NHTSA), motor vehicle crashes are the leading cause of death among people aged 1-54 in the United Sates. In 2015, the number of motor-vehicle deaths on U.S. roadways totaled 35,092, a 7% increase from 2014 (32,744). Though lower gas prices and increased vehicle mileage combined with risky driving behaviors (e.g. speeding, driving while texting) account for the increased fatality rate, seatbelt non-use has been a significant contributory factor. It is estimated that nearly half (48%) of passenger vehicle occupants involved in fatal crashes each year are unrestrained.

In a recent 2014 report …

Total Organic Iodine Quantification And Occurrence In Drinking Water, And Toxicity Assessment Of Iodinated Disinfection By-Products, Rassil El Sayess

Doctoral Dissertations

The focus of this work has been placed is on iodinated DBPs (I-DBPs), measured using total organic iodine (TOI), a surrogate measure of iodinated organics. This is due to the growing toxicity literature that places I-DBPs among the most toxic of all DBPs. To measure TOI in water, a new method was developed. This method combines adsorption, combustion, and trapping of combustion products, with an offline inductively coupled plasma/mass spectrometer (ICP-MS) for iodide detection. Three factors were varied across two levels each in order to optimize the method. The chosen method used a sample pH of less than 1 prior …

Real-Time Diesel Particulate Matter Monitoring In Underground Mine Atmospheres, Association With The Standard Method And Related Challenges, Muhammad Usman Khan

Doctoral Dissertations

"Diesel-powered equipment is a significant component of underground mining operations. Miners' exposure to diesel exhaust is harmful. The standard Diesel Particulate Matter (DPM) monitoring method (NIOSH 5040 method) has limitations that preclude rapid DPM estimation and detailed understanding of DPM variations over time. However, real-time DPM monitors do not inherit these limitations. Biodiesel is often used as a substitute for regular petroleum-diesel because of its ability to emit less DPM. However, accuracy of available real-time DPM monitors has not been determined in mines using 70% to 99% (high-percent) biodiesel. The present research addresses this need by rigorous testing of a …

Elucidating The Effects Of Metabolic State On Nanoparticle Distribution In Mice And In Vitro Uptake, Kevin James Quigley

Doctoral Dissertations

Since almost 70% of the U.S. population over 20 years old is overweight and 30% is obese, with much of the western world following suit, many patients that will potentially be administered circulating nanoparticles designed to localize to tumors and avoid non-target areas will have significant amounts of white adipose tissue (WAT), enlarged livers, and additional metabolic complications such as type 2 diabetes. However, studies on nanoparticle biodistribution and efficacy take place almost without exception in lean rodents with healthy metabolic states. In this work, I determined the biodistribution of model nanoparticles – neutral filomicelles and polystyrene spheres both carrying …

The Effect Of Interruptions On Primary Task Performance In Safety-Critical Environments, Cheryl Ann Nicholas

Doctoral Dissertations

Safety critical systems in medicine utilize alarms to signal potentially life threatening situations to professionals and patients. In particular, in the medical field multiple alarms from equipment are activated daily and often simultaneously. There are a number of alarms which require caregivers to take breaks in complex, primary tasks to attend to the interruption task which is signaled by the alarm. The motivation for this research is the knowledge that, in general, interrupting tasks can have a potentially negative impact on performance and outcomes of the primary task. The focus of this research is on the effect of an interrupting …

Multi-Classifier Fusion Strategy For Activity And Intent Recognition Of Torso Movements, Abhijit Kadrolkar

Doctoral Dissertations

As assistive, wearable robotic devices are being developed to physically assist their users, it has become crucial to develop safe, reliable methods to coordinate the device with the intentions and motions of the wearer. This dissertation investigates the recognition of user intent during flexion and extension of the human torso in the sagittal plane to be used for control of an assistive exoskeleton for the human torso. A multi-sensor intent recognition approach is developed that combines information from surface electromyogram (sEMG) signals from the user’s muscles and inertial sensors mounted on the user’s body. Intent recognition is implemented by following …

Design, Implementation, And Evaluation Of A User Training Program For Integrating Health Information Technology Into Clinical Processes, Ze He

Doctoral Dissertations

Health information technology (IT) implementation can be costly, and remains a challenging problem with mixed outcomes on patient safety and quality of care. Systems engineering and IT management experts have advocated the use of sociotechnical models to understand the impact of health IT on user and organizational factors. Sociotechnical models suggest the need for user-centered implementation approaches, such as user training and support, and focus on processes to mitigate the negative impact and facilitate optimal IT use during training. The training design and development should also follow systematic processes guided by instructional development models. It should take into account of …

Three-Dimensional Printing And Nanotechnology For Enhanced Implantable Materials, Karthik Kumar Tappa

Doctoral Dissertations

Orthopedic and oro-maxillofacial implants have revolutionized treatment of bone diseases and fractures. Currently available metallic implants have been in clinical use for more than 40 years and have proved medically efficacious. However, several drawbacks remain, such as excessive stiffness, accumulation of metal ions in surrounding tissue, growth restriction, required removal/revision surgery, inability to carry drugs, and susceptibility to infection. The need for additional revision surgery increases financial costs and prolongs recovery time for patients. These metallic implants are bulk manufactured and often do not meet patient's requirements. A surgeon must machine (cut, weld, trim or drill holes) them in order …

High Reliability Organizational Suggestions To Reduce The Risk Of Hospital-Associated Infections, Sandra Catrice Affare

Doctoral Dissertations

Over 1.7 million hospital-associated infections (HAIs), resulting in 99,000 deaths, occur each year in the United States. HAIs are defined as infections that occur within 48 hours of hospital admission without evidence of the infection being present or incubating at the time of admission. HAIs are a major concern to the medical community due to the potential loss of life and high costs. Healthcare providers should be accountable for reducing the rates of HAIs and society needs to hold them accountable for the safe implementation and outcomes of the services they provide.

A high-reliability organization (HRO) is commonly described as …

Detecting, Segmenting And Tracking Bio-Medical Objects, Mingzhong Li

Doctoral Dissertations

"Studying the behavior patterns of biomedical objects helps scientists understand the underlying mechanisms. With computer vision techniques, automated monitoring can be implemented for efficient and effective analysis in biomedical studies. Promising applications have been carried out in various research topics, including insect group monitoring, malignant cell detection and segmentation, human organ segmentation and nano-particle tracking.

In general, applications of computer vision techniques in monitoring biomedical objects include the following stages: detection, segmentation and tracking. Challenges in each stage will potentially lead to unsatisfactory results of automated monitoring. These challenges include different foreground-background contrast, fast motion blur, clutter, object overlap and …

Mimicking The Arterial Microenvironment With Peg-Pc To Investigate The Roles Of Physicochemical Stimuli In Smc Phenotype And Behavior, William G. Herrick

Doctoral Dissertations

The goal of this dissertation was to parse the roles of physical, mechanical and chemical cues in the phenotype plasticity of smooth muscle cells (SMCs) in atherosclerosis. We first developed and characterized a novel synthetic hydrogel with desirable traits for studying mechanotransduction in vitro. This hydrogel, PEG-PC, is a co-polymer of poly(ethylene glycol) and phosphorylcholine with an incredible range of Young’s moduli (~1 kPa - 9 MPa) that enables reproduction of nearly any tissue stiffness, exceptional optical and anti-fouling properties, and support for covalent attachment of extracellular matrix (ECM) proteins. To our knowledge, this combination of mechanical range, low …

Guidelines For Scheduling In Primary Care: An Empirically Driven Mathematical Programming Approach, Hyun Jung Alvarez Oh

Doctoral Dissertations

Primary care practices play a vital role in healthcare delivery since they are the first point of contact for most patients, and provide health prevention, counseling, education, diagnosis and treatment. Practices, however, face a complex appointment scheduling problem because of the variety of patient conditions, the mix of appointment types, the uncertain service times with providers and non-provider staff (nurses/medical assistants), and no-show rates which all compound into a highly variable and unpredictable flow of patients. The end result is an imbalance between provider idle time and patient waiting time. To understand the realities of the scheduling problem we analyze …

Developing An Optimal Model For Infant Home Visitation, Isaac Atuahene

Doctoral Dissertations

The United States, Great Britain, Denmark, Canada and many other countries have accepted home visitation (HV) as a promising strategy for interventions for infants after births and for their mothers. Prior HV studies have focused on theoretical foundations, evaluations of programs, cost/benefit analysis and cost estimation by using hospital/payer/insurance data to prove its effectiveness and high cost. As governments and private organizations continue to fund HVs, it is an opportune time to develop and formulate operations research (OR) models of HV coverage, quality and cost so they might be used in program implementation as done for adult home healthcare (HHC) …