Adaptive Gray Box Reinforcement Learning Methods to Support Therapeutic Research: From Product design to Manufacturing

190990-Thumbnail Image.png
Description
This thesis is developed in the context of biomanufacturing of modern products that have the following properties: require short design to manufacturing time, they have high variability due to a high desired level of patient personalization, and, as a result,

This thesis is developed in the context of biomanufacturing of modern products that have the following properties: require short design to manufacturing time, they have high variability due to a high desired level of patient personalization, and, as a result, may be manufactured in low volumes. This area at the intersection of therapeutics and biomanufacturing has become increasingly important: (i) a huge push toward the design of new RNA nanoparticles has revolutionized the science of vaccines due to the COVID-19 pandemic; (ii) while the technology to produce personalized cancer medications is available, efficient design and operation of manufacturing systems is not yet agreed upon. In this work, the focus is on operations research methodologies that can support faster design of novel products, specifically RNA; and methods for the enabling of personalization in biomanufacturing, and will specifically look at the problem of cancer therapy manufacturing. Across both areas, methods are presented attempting to embed pre-existing knowledge (e.g., constraints characterizing good molecules, comparison between structures) as well as learn problem structure (e.g., the landscape of the rewards function while synthesizing the control for a single use bioreactor). This thesis produced three key outcomes: (i) ExpertRNA for the prediction of the structure of an RNA molecule given a sequence. RNA structure is fundamental in determining its function. Therefore, having efficient tools for such prediction can make all the difference for a scientist trying to understand optimal molecule configuration. For the first time, the algorithm allows expert evaluation in the loop to judge the partial predictions that the tool produces; (ii) BioMAN, a discrete event simulation tool for the study of single-use biomanufacturing of personalized cancer therapies. The discrete event simulation engine was designed tailored to handle the efficient scheduling of many parallel events which is cause by the presence of single use resources. This is the first simulator of this type for individual therapies; (iii) Part-MCTS, a novel sequential decision-making algorithm to support the control of single use systems. This tool integrates for the first-time simulation, monte-carlo tree search and optimal computing budget allocation for managing the computational effort.
Date Created
2023
Agent

Understanding Metabolic Health and Substrate Utilization In the Human Body

190969-Thumbnail Image.png
Description
Obesity has consistently presented a significant challenge, with excess body fat contributing to the development of numerous severe conditions such as diabetes, cardiovascular disease, cancer, and various musculoskeletal disorders. In this study, different methods are proposed to study substrate utilization

Obesity has consistently presented a significant challenge, with excess body fat contributing to the development of numerous severe conditions such as diabetes, cardiovascular disease, cancer, and various musculoskeletal disorders. In this study, different methods are proposed to study substrate utilization (carbohydrates, proteins, and fats) in the human body and validate the biomarkers enabling to investigation of weight management and monitor metabolic health. The first technique to study was Indirect calorimetry, which assessed Resting Energy Expenditure (REE) and measured parameters like oxygen consumption (VO2) and carbon dioxide production (VCO2). A validation study was conducted to study the effectiveness of the medical device Breezing Med determining REE, VO2, and VCO2. The results were compared with correlation slopes and regression coefficients close to 1. Indirect Calorimetry can be used to determine carbohydrate and fat utilization but it requires additional correction for protein utilization. Protein utilization can be studied by analyzing urinary nitrogen. Therefore, a secondary technique was studied for identifying urea and ammonia concentration in human urine samples. Along this line two methods for detecting urea were explored, a colorimetric technique and it was validated against the Ion-Selective method. The results were then compared by correlation analysis of urine samples measured with both methods simultaneously curves. The equations for fat, carb, and protein oxidation, involving VO2, VCO2 consumption, and urinary nitrogen were implemented and validated, using the above-described methods in a human subject study with 16 subjects. The measurements included diverse diets (normal vs. high fat/protein) in normal energy balance and pre-/post interventions of exercise, fasting, and a high-fat meal. It can be concluded that the indirect calorimetry portable method in conjunction with urine urea methods are important to help the understanding of substrate utilization in human subjects, and therefore, excellent tools to contribute to the treatments and interventions of obesity and overweighted populations.
Date Created
2023
Agent

Team Workload in Action Teams

190910-Thumbnail Image.png
Description
A key contribution of human factors engineering is the concept of workload: a construct that represents the relationship between an operator’s cognitive resources, the demands of their task, and performance. Understanding workload can lead to improvements in safety and performance

A key contribution of human factors engineering is the concept of workload: a construct that represents the relationship between an operator’s cognitive resources, the demands of their task, and performance. Understanding workload can lead to improvements in safety and performance for people working in critical environments, particularly within action teams. Recently, there has been interest in considering how the workload of a team as a whole may differ from that of an individual, prompting investigation into team workload as a distinct team-level construct. In empirical research, team-level workload is often considered as the sum or average of individual team members' workloads. However, the intrinsic characteristics of action teams—such as interdependence and heterogeneity—challenge this assumption, and traditional methods of measuring team workload might be unsuitable. This dissertation delves into this issue with a review of empirical work in action teams, pinpointing several gaps. Next, the development of a testbed is described and used to address two pressing gaps regarding the impact of interdependence and how team communications relate to team workload states and performance. An experiment was conducted with forty 3-person teams collaborating in an action team task. Results of this experiment suggest that the traditional way of measuring workload in action teams via subjective questionnaires averaged at the team level has some major shortcomings, particularly when demands are elevated, and action teams are highly interdependent. The results also suggested that several communication measures are associated with increases in demands, laying the groundwork for team-level communication-based measures of team workload. The results are synthesized with findings from the literature to provide a way forward for conceptualizing and measuring team workload in action teams.
Date Created
2023
Agent

Embodied Wearables: The Role of Proprioception in Exoskeleton Design.

190848-Thumbnail Image.png
Description
This work endeavors to lay a solid foundation for the exploration and the considerations of exoskeletons, exosuits, and medical devices concerning proprioceptive feedback. This investigation is situated at the nexus of engineering, neuroscience, and rehabilitation medicine, striving to cultivate a

This work endeavors to lay a solid foundation for the exploration and the considerations of exoskeletons, exosuits, and medical devices concerning proprioceptive feedback. This investigation is situated at the nexus of engineering, neuroscience, and rehabilitation medicine, striving to cultivate a holistic understanding of how mechanical augmentation, interfaced synergistically with human proprioception, can foster enhanced mobility and safety. This is especially pertinent for individuals with compromised motor functions.British Neurologist Oliver Wolf Sacks in 1985 published “The Man who Mistook His Wife for a Hat” a series of his most memorable neurological case describing the brain's strangest pathways. One of these cases is “The Disembodied Lady”, Christina a 27-year-old woman that lost entirely the sense of proprioception due to polyneuropathy. This caused her to not be able to control her body, and she declares that “I feel the wind on my arms and face, and then I know, faintly, I have arms and a face. It’s not the real thing, but it’s something—it lifts this horrible, dead veil for a while. ” Finally, she was able to control her body using vision alone. Dr. Sacks introduced, for the first time, the importance of proprioception, as the sense of position of body parts relative to other parts of the body, to western culture. This document’s mission is to identify unexplored concepts in the literature regarding exoskeletons, wearables and assistive technology and a user’s proprioception, embodiment and utilization when wearing devices. Dr. Philipp Beckerle suggests the need to research the connections between wearable hardware and human sense of proprioception. He also emphasizes the need for functional assessment protocols for wearables devices and the role of embodiment. He criticizes the current commercially available upper-limb prostheses since they only restore limited functions and therefore impede embodiment. This document’s goal is to identify operative solutions through the adaptation of existing technologies and to use effective solutions to improve the quality of life of people suffering from pathologies or traumatic injuries.
Date Created
2023
Agent

An Android-Enabled Modular Self-Interference Cancellation System for Standalone Simultaneous Transmit and Receive Multichannel Magnetic Resonance Imaging at 1.5T

190806-Thumbnail Image.png
Description
In 1946 Felix Bloch first demonstrated the phenomenon of nuclear magnetic resonance using continuous-wave signal generation and acquisition. Shortly after in 1966, Richard R. Ernst demonstrated the breakthrough that nuclear magnetic resonance needed to develop into magnetic resonance imaging: the

In 1946 Felix Bloch first demonstrated the phenomenon of nuclear magnetic resonance using continuous-wave signal generation and acquisition. Shortly after in 1966, Richard R. Ernst demonstrated the breakthrough that nuclear magnetic resonance needed to develop into magnetic resonance imaging: the application of Fourier transforms for sensitive pulsed imaging. Upon this discovery, the world of research began to develop high power radio amplifiers and fast radio switches for pulsed experimentation. Consequently, continuous-wave imaging placed on the backburner.Although high power pulses are dominant in clinical imaging, there are unique advantages to low power, continuous-wave pulse sequences that transmit and receive signals simultaneously. Primarily, tissues or materials with short T2 time constants can be imaged and the peak radio power required is drastically reduced. The fundamental problem with this lies in its nature; the transmitter leaks a strong leakage signal into the receiver, thus saturating the receiver and the intended nuclear magnetic resonance signal is lost noise. Demonstrated in this dissertation is a multichannel standalone simultaneous transmit and receive (STAR) system with remote user-control that enables continuous- wave full-duplex imaging. STAR calibrates cancellation signals through vector modulators that match the leakage signal of each receiver in amplitude but opposite in phase, therefore destructively interfering the leakage signals. STAR does not require specific imaging coils or console inputs for calibration. It was designed to be general- purpose, therefore integrating into any imaging system. To begin, the user uses an Android tablet to tune STAR to match the Larmor frequency in the bore. Then, the user tells STAR to begin calibration. After self-calibrating, the user may fine-tune the calibration state of the system before enabling a low-power mode for system electronics and imaging may commence. STAR was demonstrated to isolate two receiver coils upwards of 70 dB from the transmit coil and is readily upgradable to enable the use of four receive coils. Some primary concerns of STAR are the removal of transceivers for multichannel operation, digital circuit noise, external noise, calibration speed, upgradability, and the isolation introduced; all of which are addressed in the proceeding thesis.
Date Created
2023
Agent

Soft Skills, the Other Half of Success

Description
The interpersonal, subjective, and communication skills we carry with us are crucial to our professional successes, sometimes even more crucial than the technical skills we use to execute tasks. The engineering industry is wildly technical and competitive in order to

The interpersonal, subjective, and communication skills we carry with us are crucial to our professional successes, sometimes even more crucial than the technical skills we use to execute tasks. The engineering industry is wildly technical and competitive in order to define a better tomorrow for the human population. However, such a technical field often neglects the use of these soft skills, both originating from students, employees, and companies. In this thesis, I delve into the importance and various applications of soft skills within the engineering industry, the presence of a gap among engineers' expected versus actual soft skill usage, and if anything can be done to mend that gap.
Date Created
2023-12
Agent

The Future of Space Exploration: A look into how modern generations examine humanity's future investment into the cosmos

Description
For this study, my overarching goal was to understand the possibilities of humanity’s future in space exploration. Addressing the future of space exploration not only opens doors for a multitude of discoveries but may answer questions that can be essential

For this study, my overarching goal was to understand the possibilities of humanity’s future in space exploration. Addressing the future of space exploration not only opens doors for a multitude of discoveries but may answer questions that can be essential to our survival on Earth. This study, more specifically, aimed to determine how college students at Arizona State University, engineering and astronomy students in particular, visualize the future of space exploration, as in the future, they will become the leading experts at the forefront of all space-related developments. The method through which I have conducted this study is a short survey, consisting of a variety of questions, designed to encourage students to develop their own unique interpretations of space exploration and ultimately, its imminent future. The results ultimately demonstrated that most participants in the study believed that political obstacles were the most prevalent concern in the further development of space exploration. There also appeared to be a moderate outlook on the future success and vitality of space exploration among student scientists and engineers. From a statistical standpoint, there appeared to be no alarming difference of opinion between these two ASU student groups.
Date Created
2023-12
Agent

The Engineers That Built Today

Description
This creative project details 5 engineers who made contributions to the ways that we live life today, yet have received little to no recognition for their efforts. The 5 engineers presented are Gottfried Wilhelm Leibniz, George Stephenson, Charles Babbage, David

This creative project details 5 engineers who made contributions to the ways that we live life today, yet have received little to no recognition for their efforts. The 5 engineers presented are Gottfried Wilhelm Leibniz, George Stephenson, Charles Babbage, David Alter, and Nikola Tesla. Each engineer is detailed via a portrait and a biography that covers a little bit of their life and the contributions that they made.
Date Created
2023-12
Agent

Development of Pervaporation Membranes and Integration Into System Design for Space Flight Wastewater Management

189407-Thumbnail Image.png
Description
Pervaporation is a membrane process suited to complex and highly contaminated wastewaters. Pervaporation desalination is an emerging area of study where the development of high-performance membranes is necessary to propel the field forward. This research demonstrated that sulfonated block polymer

Pervaporation is a membrane process suited to complex and highly contaminated wastewaters. Pervaporation desalination is an emerging area of study where the development of high-performance membranes is necessary to propel the field forward. This research demonstrated that sulfonated block polymer membranes (Nexar™)show excellent permeance (water passage normalized by driving force) of as much as 135.5 ± 29 kg m-2 hr-1 bar-1, with salt removal values consistently equal to or greater than 99.5%. Another challenging water management scenario is in spaceflight situations, such as on the International Space Station (ISS). Spaceflight wastewaters are highly complex, with low pH values, and high levels of contaminants. Current processes produce 70% wastewater recovery, necessitating the handling and processing of concentrated brines. Since recoveries of 85% are desired moving forward, further efforts in water recovery are desirable. An area of concern in these ISS water treatment systems is scalant deposition, especially of divalent ions such as calcium species. Zwitterions are molecules with localized positive and negative charges, but an overall neutral charge. Zwitterions have been used to modify the surface of membranes have shown to decrease fouling. Building a copolymer between zwitterions and other polymers, creates zwitterion layer on top of previously studied Nexar™ membranes. This coating demonstrates great promise to combat scaling, as it increases the hydrophilicity of the membrane surface measured via contact angle. The zwitterion membranes experienced reduced scaling, with the greatest difference being between 1617 ± 241 wt% on control membranes, to 317 ± 87 wt% on zwitterion coated membranes in the presence of CaCl2. In treating spaceflight wastewater, these zwitterion membranes are effective at retaining the acid in the feed, going from a pH value of 2 to 7 and reducing the contamination level of the feed, with a removal value of 99.3 ± 0.4%, measured through conductivity. These membranes also perform well in separation processes that do not require extreme vacuum and can be operated passively. By optimizing both membrane material properties and process conditions, achieving increased high levels of water recovery from spaceflight wastewaters is attainable.
Date Created
2023
Agent

Talent Acquisition in Scientific and Engineering Disciplines: A Case Study of National Laboratory

189400-Thumbnail Image.png
Description
Identifying the hindrances to performing effective talent acquisition within the science, technology, engineering, and mathematics field is an important topic for technical hiring managers. Top candidates have multiple options during highly competitive market conditions requiring managers to look for unique

Identifying the hindrances to performing effective talent acquisition within the science, technology, engineering, and mathematics field is an important topic for technical hiring managers. Top candidates have multiple options during highly competitive market conditions requiring managers to look for unique solutions which diverge from competition. Prior to this study there has been very little research considering national laboratory research and development challenges from a technical hiring manager’s talent acquisition perspective. Utilizing a unique combination of national laboratory multi-organization survey, pilot study, Human Resource (HR) tracking data and trust based business strategy to enhance partnering this research finds hiring managers can leverage out of the box techniques to improve internal processes while developing industry support to target highly qualified individuals. This methodology could be utilized by technical hiring managers across federal national laboratory enterprise to effectively capture next generation staff and leadership talent who align with their organization professionally as well as social culture.
Date Created
2023
Agent