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Cancer autoantibody biomarker discovery and validation using nucleic acid programmable protein array
Description
Currently in the US, many patients with cancer do not benefit from the population-based screening, due to challenges associated with the existing cancer screening scheme. Blood-based diagnostic assays have the potential to detect diseases in a non-invasive way. Proteins released from small early tumors may only be present intermittently and get diluted to tiny concentrations in the blood, making them difficult to use as biomarkers. However, they can induce autoantibody (AAb) responses, which can amplify the signal and persist in the blood even if the antigen is gone. Circulating autoantibodies is a promising class of molecules that have potential to serve as early detection biomarkers for cancers. This Ph.D thesis aims to screen for autoantibody biomarkers for the early detection of two deadly cancer, basal-like breast cancer and lung adenocarcinoma. First, a method was developed to display proteins in both native and denatured conformation on protein array. This method adopted a novel protein tag technology, called HaloTag, to covalently immobilize proteins on glass slide surface. The covalent attachment allowed these proteins to endure harsh treatment without getting dissociated from slide surface, which enabled the profiling of antibody responses against both conformational and linear epitopes. Next, a plasma screening protocol was optimized to significantly increase signal to noise ratio of protein array based AAb detection. Following this, the AAb responses in basal-like breast cancer were explored using nucleic acid programmable protein arrays (NAPPA) containing 10,000 full-length human proteins in 45 cases and 45 controls. After verification in a large sample set (145 basal-like breast cancer cases / 145 controls / 70 non-basal breast cancer) by ELISA, a 13-AAb classifier was developed to differentiate patients from controls with a sensitivity of 33% at 98% specificity. Similar approach was also applied to the lung cancer study to identify AAbs that distinguished lung cancer patients from computed-tomography positive benign pulmonary nodules (137 lung cancer cases, 127 smoker controls, 170 benign controls). In this study, two panels of AAbs were discovered that showed promising sensitivity and specificity. Six out of eight AAb targets were also found to have elevated mRNA level in lung adenocarcinoma patients using TCGA data. These projects as a whole provide novel insights on the association between AAbs and cancer, as well as general B cell antigenicity against self-proteins.
ContributorsWang, Jie (Author) / LaBaer, Joshua (Thesis advisor) / Anderson, Karen S (Committee member) / Lake, Douglas F (Committee member) / Chang, Yung (Committee member) / Arizona State University (Publisher)
Created2015
Description
One of the most remarkable outcomes resulting from the evolution of the web into Web 2.0, has been the propelling of blogging into a widely adopted and globally accepted phenomenon. While the unprecedented growth of the Blogosphere has added diversity and enriched the media, it has also added complexity. To cope with the relentless expansion, many enthusiastic bloggers have embarked on voluntarily writing, tagging, labeling, and cataloguing their posts in hopes of reaching the widest possible audience. Unbeknown to them, this reaching-for-others process triggers the generation of a new kind of collective wisdom, a result of shared collaboration, and the exchange of ideas, purpose, and objectives, through the formation of associations, links, and relations. Mastering an understanding of the Blogosphere can greatly help facilitate the needs of the ever growing number of these users, as well as producers, service providers, and advertisers into facilitation of the categorization and navigation of this vast environment. This work explores a novel method to leverage the collective wisdom from the infused label space for blog search and discovery. The work demonstrates that the wisdom space can provide a most unique and desirable framework to which to discover the highly sought after background information that could aid in the building of classifiers. This work incorporates this insight into the construction of a better clustering of blogs which boosts the performance of classifiers for identifying more relevant labels for blogs, and offers a mechanism that can be incorporated into replacing spurious labels and mislabels in a multi-labeled space.
ContributorsGalan, Magdiel F (Author) / Liu, Huan (Thesis advisor) / Davulcu, Hasan (Committee member) / Ye, Jieping (Committee member) / Li, Baoxin (Committee member) / Arizona State University (Publisher)
Created2015
Description
A process plan is an instruction set for the manufacture of parts generated from detailed design drawings or CAD models. While these plans are highly detailed about machines, tools, fixtures and operation parameters; tolerances typically show up in less formal manner in such plans, if at all. It is not uncommon to see only dimensional plus/minus values on rough sketches accompanying the instructions. On the other hand, design drawings use standard GD&T (Geometrical Dimensioning and tolerancing) symbols with datums and DRFs (Datum Reference Frames) clearly specified. This is not to say that process planners do not consider tolerances; they are implied by way of choices of fixtures, tools, machines, and operations. When converting design tolerances to the manufacturing datum flow, process planners do tolerance charting, that is based on operation sequence but the resulting plans cannot be audited for conformance to design specification.
In this thesis, I will present a framework for explicating the GD&T schema implied by machining process plans. The first step is to derive the DRFs from the fixturing method in each set-up. Then basic dimensions for the features to be machined in each set up are determined with respect to the extracted DRF. Using shop data for the machines and operations involved, the range of possible geometric variations are estimated for each type of tolerances (form, size, orientation, and position). The sequence of manufacturing operations determines the datum flow chain. Once we have a formal manufacturing GD&T schema, we can analyze and compare it to tolerance specifications from design using the T-map math model. Since the model is based on the manufacturing process plan, it is called resulting T-map or m-map. Then the process plan can be validated by adjusting parameters so that the m-map lies within the T-map created for the design drawing. How the m-map is created to be compared with the T-map is the focus of this research.
In this thesis, I will present a framework for explicating the GD&T schema implied by machining process plans. The first step is to derive the DRFs from the fixturing method in each set-up. Then basic dimensions for the features to be machined in each set up are determined with respect to the extracted DRF. Using shop data for the machines and operations involved, the range of possible geometric variations are estimated for each type of tolerances (form, size, orientation, and position). The sequence of manufacturing operations determines the datum flow chain. Once we have a formal manufacturing GD&T schema, we can analyze and compare it to tolerance specifications from design using the T-map math model. Since the model is based on the manufacturing process plan, it is called resulting T-map or m-map. Then the process plan can be validated by adjusting parameters so that the m-map lies within the T-map created for the design drawing. How the m-map is created to be compared with the T-map is the focus of this research.
ContributorsHaghighi, Payam (Author) / Shah, Jami J. (Thesis advisor) / Davidson, Joseph K. (Committee member) / Ren, Yi (Committee member) / Arizona State University (Publisher)
Created2015
Description
Stroke accounts for high rates of mortality and disability in the United States. It levies great economic burden on the affected subjects, their family and the society at large. Motor impairments after stroke mainly manifest themselves as hemiplegia or hemiparesis in the upper and lower limbs. Motor recovery is highly variable but can be enhanced through motor rehabilitation with sufficient movement repetition and intensity. Cost effective assistive devices that can augment therapy by increasing movement repetition both at home and in the clinic may facilitate recovery. This thesis aims to develop a Smart Glove that can enhance motor recovery by providing feedback to both the therapist and the patient on the number of hand movements (wrist and finger extensions) performed during therapy. The design implements resistive flex sensors for detecting the extensions and processes the information using the Lightblue bean microcontroller mounted on the wrist. Communication between the processing unit and display module is wireless and executes Bluetooth 4.0 communication protocol. The capacity for the glove to measure and record hand movements was tested on three stroke and one traumatic brain injured patient while performing a box and blocks test. During testing many design flaws were noted and several were adapted during testing to improve the function of the glove. Results of the testing showed that the glove could detect wrist and finger extensions but that the sensitivity had to be calibrated for each patient. It also allowed both the therapist and patient to know whether the patient was actually performing the task in the manner requested by the therapist. Further work will reveal whether this feedback can enhance recovery of hand function in neurologically impaired patients.
ContributorsSasidharan, Smrithi (Author) / Kleim, Jeffrey A. (Thesis advisor) / Santello, Marco (Committee member) / Buneo, Christopher A. (Committee member) / Arizona State University (Publisher)
Created2015
Description
Complex human controls is a topic of much interest in the fields of robotics, manufacturing, space exploration and many others. Even simple tasks that humans perform with ease can be extremely complicated when observed from a controls and complex systems perspective. One such simple task is that of a human carrying and moving a coffee cup. Though this may be a mundane task for humans, when this task is modelled and analyzed, the system may be quite chaotic in nature. Understanding such systems is key to the development robots and autonomous systems that can perform these tasks themselves.
The coffee cup system can be simplified and modeled by a cart-and-pendulum system. Bazzi et al. and Maurice et al. present two different cart-and-pendulum systems to represent the coffee cup system [1],[2]. The purpose of this project was to build upon these systems and to gain a better understanding of the coffee cup system and to determine where chaos existed within the system. The honors thesis team first worked with their senior design group to develop a mathematical model for the cart-and-pendulum system based on the Bazzi and Maurice papers [1],[2]. This system was analyzed and then built upon by the honors thesis team to build a cart-and-two-pendulum model to represent the coffee cup system more accurately.
Analysis of the single pendulum model showed that there exists a low frequency region where the pendulum and the cart remain in phase with each other and a high frequency region where the cart and pendulum have a π phase difference between them. The transition point of the low and high frequency region is determined by the resonant frequency of the pendulum. The analysis of the two-pendulum system also confirmed this result and revealed that differences in length between the pendulum cause the pendulums to transition to the high frequency regions at separate frequency. The pendulums have different resonance frequencies and transition into the high frequency region based on their own resonant frequency. This causes a range of frequencies where the pendulums are out of phase from each other. After both pendulums have transitioned, they remain in phase with each other and out of phase from the cart.
However, if the length of the pendulum is decreased too much, the system starts to exhibit chaotic behavior. The short pendulum starts to act in a chaotic manner and the phase relationship between the pendulums and the carts is no longer maintained. Since the pendulum length represents the distance between the particle of coffee and the top of the cup, this implies that coffee near the top of the cup would cause the system to act chaotically. Further analysis would be needed to determine the reason why the length affects the system in this way.
The coffee cup system can be simplified and modeled by a cart-and-pendulum system. Bazzi et al. and Maurice et al. present two different cart-and-pendulum systems to represent the coffee cup system [1],[2]. The purpose of this project was to build upon these systems and to gain a better understanding of the coffee cup system and to determine where chaos existed within the system. The honors thesis team first worked with their senior design group to develop a mathematical model for the cart-and-pendulum system based on the Bazzi and Maurice papers [1],[2]. This system was analyzed and then built upon by the honors thesis team to build a cart-and-two-pendulum model to represent the coffee cup system more accurately.
Analysis of the single pendulum model showed that there exists a low frequency region where the pendulum and the cart remain in phase with each other and a high frequency region where the cart and pendulum have a π phase difference between them. The transition point of the low and high frequency region is determined by the resonant frequency of the pendulum. The analysis of the two-pendulum system also confirmed this result and revealed that differences in length between the pendulum cause the pendulums to transition to the high frequency regions at separate frequency. The pendulums have different resonance frequencies and transition into the high frequency region based on their own resonant frequency. This causes a range of frequencies where the pendulums are out of phase from each other. After both pendulums have transitioned, they remain in phase with each other and out of phase from the cart.
However, if the length of the pendulum is decreased too much, the system starts to exhibit chaotic behavior. The short pendulum starts to act in a chaotic manner and the phase relationship between the pendulums and the carts is no longer maintained. Since the pendulum length represents the distance between the particle of coffee and the top of the cup, this implies that coffee near the top of the cup would cause the system to act chaotically. Further analysis would be needed to determine the reason why the length affects the system in this way.
ContributorsZindani, Abdul Rahman (Co-author) / Crane, Kari (Co-author) / Lai, Ying-Cheng (Thesis director) / Jiang, Junjie (Committee member) / Electrical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-12
Description
Pasta is a staple food for many people and understanding how the process of making it at a homemade level and industrial level should be examined. Pasta is a large and growing market due to growing populations and new products, therefore, researching the pasta has many benefits. The goal of the research is to determine a consistent way to make homemade pasta and compare it to the industrial method. The comparisons that will be examined are the costs and the process to make the pasta. From there it can be determined where homemade pasta can fit in the market. Through experimentation, an optimal ratio of 1.65 grams of flour to 1 gram of egg was found to create pasta dough that would consistently make pasta easy to work with. Different methods of storage were tested to find a viable method to store fresh pasta. It was found that storing the pasta in an enclosed bag with a condensed shape in the freezer was the best method because it created the most durable pasta out of all the trials and it could be cooked. The industrial method for making pasta differed in some aspects to the homemade pasta method. The biggest changes were the use of an extruder and a drying machine which makes it easier to mass produce uniform pasta. The cost per kilogram based off ingredient prices to make homemade pasta was 0.92 dollars while the industrial pasta cost 0.89 dollars per kilogram. The biggest changes in cost comes from the method of storage of homemade pasta. It was determined that following the drying process of the industrial method would be best because then the price difference is dependent on the price of ingredients. This led to multiple possibilities where homemade pasta could enter the market, for example, as a part of premade meals. Overall, it is possible to create a better quality pasta that can be supplied to a wide arrange of demographics.
ContributorsKupres, Matthew David (Author) / Taylor, David (Thesis director) / Schoepf, Jared (Committee member) / Economics Program in CLAS (Contributor) / Chemical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-12
Description
In a society that is becoming more technologically driven, it is important to have people to design, test, and build new things in order for society to progress. This is oftentimes the role of an engineer. However, engineering school is not easy, and engineering students don’t always make it all the way through school to get an engineering job. This thesis is an in-depth analysis of an engineering student’s path - from choosing engineering as a major to ultimately transitioning into a full-time engineering job. It will do this by covering (1) what engineering is and what career opportunities exist within the discipline, (2) common pitfalls that students may encounter while going through engineering school, (3) how to get an engineering job in industry, and (4) how to appropriately transition into an industry job using the skills from engineering school. While talking about what engineering is and what career opportunities exist, this thesis will discuss engineering as a profession, the ABET accreditation board, and careers in industry vs academia. As part of common pitfalls that engineering students face, this thesis will discuss tenure track, theory vs reality, cooperative learning, and misconceptions about engineering. In order to talk about how to get an industry job, this thesis will discuss the impact of grades, relevant experience, communication, personal branding, and industry options. Finally, while talking about effectively transitioning into industry, this thesis will discuss understanding the skills gained from engineering school, the different roles in industry, and how to appropriately apply those skills. Ultimately this thesis aims to be a resource for students interested in engineering so that they can understand how to successfully make it through school and move into the work force effectively.
ContributorsJordan, Arminta Claire (Author) / Takahashi, Timothy (Thesis director) / Zhu, Haolin (Committee member) / Mechanical and Aerospace Engineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
An understanding of aerodynamics is crucial for automobile performance and efficiency. There are many types of “add-on” aerodynamic devices for cars including wings, splitters, and vortex generators. While these have been studied extensively, rear spoilers have not, and their effects are not as widely known. A Computational Fluid Dynamics (CFD) and wind tunnel study was performed to study the effects of spoilers on vehicle aerodynamics and performance. Vehicle aerodynamics is geometry dependent, meaning what applies to one car may or may not apply on another. So, the Scion FRS was chosen as the test vehicle because it is has the “classic” sports car configuration with a long hood, short rear, and 2+2 passenger cabin while also being widely sold with a plethora of aftermarket aerodynamic modifications available. Due to computing and licensing restrictions, only a 2D CFD simulation was performed in ANSYS Fluent 19.1. A surface model of the centerline of the car was created in SolidWorks and imported into ANSYS, where the domain was created. A mesh convergence study was run to determine the optimum mesh size, and Realizable k-epsilon was the chosen physics model. The wind tunnel lacked equipment to record quantifiable data, so the wind tunnel was utilized for flow visualization on a 1/24 scale car model to compare with the CFD.
0° spoilers reduced the wake area behind the car, decreasing pressure drag but also decreasing underbody flow, causing a reduction in drag and downforce. Angled spoilers increased the wake area behind the car, increasing pressure drag but also increasing underbody flow, causing an increase in drag and downforce. Longer spoilers increased these effects compared to shorter spoilers, and short spoilers at different angles did not create significantly different effects. 0° spoilers would be best suited for cases that prioritize fuel economy or straight-line acceleration and speed due to the drag reduction, while angled spoilers would be best suited for cars requiring downforce. The angle and length of spoiler would depend on the downforce needed, which is dependent on the track.
0° spoilers reduced the wake area behind the car, decreasing pressure drag but also decreasing underbody flow, causing a reduction in drag and downforce. Angled spoilers increased the wake area behind the car, increasing pressure drag but also increasing underbody flow, causing an increase in drag and downforce. Longer spoilers increased these effects compared to shorter spoilers, and short spoilers at different angles did not create significantly different effects. 0° spoilers would be best suited for cases that prioritize fuel economy or straight-line acceleration and speed due to the drag reduction, while angled spoilers would be best suited for cars requiring downforce. The angle and length of spoiler would depend on the downforce needed, which is dependent on the track.
ContributorsNie, Alexander (Author) / Wells, Valana (Thesis director) / Huang, Huei-Ping (Committee member) / Mechanical and Aerospace Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-12
Description
This creative project is a children’s book designed to teach young readers about engineering through a fictional story about a group of children creating a robot for their school’s show-and-tell. The story aims to teach engineering principles to children in a lighthearted and entertaining form, narrating notions such as the design process, prototyping, specialty fields, and repurposing. Other principles such as learning patience, compromise and teamwork are also conveyed throughout the plot details. Small life lessons that transcend the realm of engineering are also embodied throughout. The plot of the story is a young girl who goes to visit her grandfather who is a garage tinkerer with a love of spare parts. He tells her about his job as a robotics engineer, and she loves it. She goes and tells her friends who decide they want to make a robot for show-and-tell at school. The grandfather agrees to help them build a robot and thus the group of kids are walked through the engineering design process, learning new things (and specialization) along the way. The story ends by revealing that the whole story was a flashback the main character was having as she is about to start her first day at an engineering firm.
ContributorsReed, Shelby Marie (Author) / Oberle, Eric (Thesis director) / Williams, Wendy (Committee member) / Engineering Programs (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
This project report contains the design of a low-cost structural model of a residential structure in the City of Phoenix, AZ. The structural unit will be part of a residential area in Ahwatukee Foothills Village located just south of South Mountain. The residential structure is 3600 square feet and consists of three bedrooms (including the master bedroom), two bathrooms (including the master bathroom), a 2-car garage, laundry room, kitchen, dining room, and a living room. There are two elevation options (A & B) for the roof framing plan. Elevation A includes a straight forward truss package consisting of two truss designs with no hip or girder trusses. Elevation B includes a more complex truss package which includes girder trusses, hip trusses, and corner jacks. Within both elevations, the trusses run perpendicular to the ridge of the structure as displayed in the Architectural Floor Plan (see Figure 4) with the exception of the hip trusses and corner jacks in Elevation B.
The design objective is to meet all safety specifications while minimizing the total cost of members and member connections. The design also aims to streamline the construction time and resources by using standard member cross section dimensions. This residential building report is carried out in accordance with the City of Phoenix standards and follows the ASCE7-10 code for the dead and live load combinations and wind pressures. This report also references the National Design Specifications (NDS) 2005 for the column design. HT Consulting Group is excited to create a safe and sustainable development for the residents within Ahwatukee Foothills Village.
The design objective is to meet all safety specifications while minimizing the total cost of members and member connections. The design also aims to streamline the construction time and resources by using standard member cross section dimensions. This residential building report is carried out in accordance with the City of Phoenix standards and follows the ASCE7-10 code for the dead and live load combinations and wind pressures. This report also references the National Design Specifications (NDS) 2005 for the column design. HT Consulting Group is excited to create a safe and sustainable development for the residents within Ahwatukee Foothills Village.
ContributorsHerrera-Theut, Joseph James (Author) / Ward, Kristen (Thesis director) / Morgan, John (Committee member) / Civil, Environmental and Sustainable Eng Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05