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Membrane proteins are very important for all living cells, being involved in respiration, photosynthesis, cellular uptake and signal transduction, amongst other vital functions. However, less than 300 unique membrane protein structures have been determined to date, often due to difficulties associated with the growth of sufficiently large and well-ordered crystals.

Membrane proteins are very important for all living cells, being involved in respiration, photosynthesis, cellular uptake and signal transduction, amongst other vital functions. However, less than 300 unique membrane protein structures have been determined to date, often due to difficulties associated with the growth of sufficiently large and well-ordered crystals. This work has been focused on showing the first proof of concept for using membrane protein nanocrystals and microcrystals for high-resolution structure determination. Upon determining that crystals of the membrane protein Photosystem I, which is the largest and most complex membrane protein crystallized to date, exist with only a hundred unit cells with sizes of less than 200 nm on an edge, work was done to develop a technique that could exploit the growth of the Photosystem I nanocrystals and microcrystals. Femtosecond X-ray protein nanocrystallography was developed for use at the first high-energy X-ray free electron laser, the LCLS at SLAC National Accelerator Laboratory, in which a liquid jet would bring fully hydrated Photosystem I nanocrystals into the interaction region of the pulsed X-ray source. Diffraction patterns were recorded from millions of individual PSI nanocrystals and data from thousands of different, randomly oriented crystallites were integrated using Monte Carlo integration of the peak intensities. The short pulses ( 70 fs) provided by the LCLS allowed the possibility to collect the diffraction data before the onset of radiation damage, exploiting the diffract-before-destroy principle. At the initial experiments at the AMO beamline using 6.9- Å wavelength, Bragg peaks were recorded to 8.5- Å resolution, and an electron-density map was determined that did not show any effects of X-ray-induced radiation damage. Recently, femtosecond X-ray protein nanocrystallography experiments were done at the CXI beamline of the LCLS using 1.3- Å wavelength, and Bragg reflections were recorded to 3- Å resolution; the data are currently being processed. Many additional techniques still need to be developed to explore the femtosecond nanocrystallography technique for experimental phasing and time-resolved X-ray crystallography experiments. The first proof-of-principle results for the femtosecond nanocrystallography technique indicate the incredible potential of the technique to offer a new route to the structure determination of membrane proteins.
ContributorsHunter, Mark (Author) / Fromme, Petra (Thesis advisor) / Wolf, George (Committee member) / Levitus, Marcia (Committee member) / Arizona State University (Publisher)
Created2011
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Description
Molybdenum (Mo) is a key trace nutrient for biological assimilation of nitrogen, either as nitrogen gas (N2) or nitrate (NO3-). Although Mo is the most abundant metal in seawater (105 nM), its concentration is low (<5 nM) in most freshwaters today, and it was scarce in the ocean before 600

Molybdenum (Mo) is a key trace nutrient for biological assimilation of nitrogen, either as nitrogen gas (N2) or nitrate (NO3-). Although Mo is the most abundant metal in seawater (105 nM), its concentration is low (<5 nM) in most freshwaters today, and it was scarce in the ocean before 600 million years ago. The use of Mo for nitrogen assimilation can be understood in terms of the changing Mo availability through time; for instance, the higher Mo content of eukaryotic vs. prokaryotic nitrate reductase may have stalled proliferation of eukaryotes in low-Mo Proterozoic oceans. Field and laboratory experiments were performed to study Mo requirements for NO3- assimilation and N2 fixation, respectively. Molybdenum-nitrate addition experiments at Castle Lake, California revealed interannual and depth variability in plankton community response, perhaps resulting from differences in species composition and/or ammonium availability. Furthermore, lake sediments were elevated in Mo compared to soils and bedrock in the watershed. Box modeling suggested that the largest source of Mo to the lake was particulate matter from the watershed. Month-long laboratory experiments with heterocystous cyanobacteria (HC) showed that <1 nM Mo led to low N2 fixation rates, while 10 nM Mo was sufficient for optimal rates. At 1500 nM Mo, freshwater HC hyperaccumulated Mo intercellularly, whereas coastal HC did not. These differences in storage capacity were likely due to the presence in freshwater HC of the small molybdate-binding protein, Mop, and its absence in coastal and marine cyanobacterial species. Expression of the mop gene was regulated by Mo availability in the freshwater HC species Nostoc sp. PCC 7120. Under low Mo (<1 nM) conditions, mop gene expression was up-regulated compared to higher Mo (150 and 3000 nM) treatments, but the subunit composition of the Mop protein changed, suggesting that Mop does not bind Mo in the same manner at <1 nM Mo that it can at higher Mo concentrations. These findings support a role for Mop as a Mo storage protein in HC and suggest that freshwater HC control Mo cellular homeostasis at the post-translational level. Mop's widespread distribution in prokaryotes lends support to the theory that it may be an ancient protein inherited from low-Mo Precambrian oceans.
ContributorsGlass, Jennifer (Author) / Anbar, Ariel D (Thesis advisor) / Shock, Everett L (Committee member) / Jones, Anne K (Committee member) / Hartnett, Hilairy E (Committee member) / Elser, James J (Committee member) / Fromme, Petra (Committee member) / Arizona State University (Publisher)
Created2011
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Description
Anti-retroviral drugs and AIDS prevention programs have helped to decrease the rate of new HIV-1 infections in some communities, however, a prophylactic vaccine is still needed to control the epidemic world-wide. Despite over two decades of research, a vaccine against HIV-1 remains elusive, although recent clinical trials have shown promising

Anti-retroviral drugs and AIDS prevention programs have helped to decrease the rate of new HIV-1 infections in some communities, however, a prophylactic vaccine is still needed to control the epidemic world-wide. Despite over two decades of research, a vaccine against HIV-1 remains elusive, although recent clinical trials have shown promising results. Recent successes have focused on highly conserved, mucosally-targeted antigens within HIV-1 such as the membrane proximal external region (MPER) of the envelope protein, gp41. MPER has been shown to play critical roles in the viral mucosal transmission, though this peptide is not immunogenic on its own. Gag is a structural protein configuring the enveloped virus particles, and has been suggested to constitute a target of the cellular immunity potentially controlling the viral load. It was hypothesized that HIV-1 enveloped virus-like particles (VLPs) consisting of Gag and a deconstructed form of gp41 comprising the MPER, transmembrane, and cytoplasmic domains (dgp41) could be expressed in plants. Plant-optimized HIV-1 genes were constructed and expressed in Nicotiana benthamiana by stable transformation, or transiently using a tobacco mosaic virus-based expression system or a combination of both. Results of biophysical, biochemical and electron microscopy characterization demonstrated that plant cells could support not only the formation of HIV-1 Gag VLPs, but also the accumulation of VLPs that incorporated dgp41. These particles were purified and utilized in mice immunization experiments. Prime-boost strategies combining systemic and mucosal priming with systemic boosting using two different vaccine candidates (VLPs and CTB-MPR - a fusion of MPER and the B-subunit of cholera toxin) were administered to BALB/c mice. Serum antibody responses against both the Gag and gp41 antigens could be elicited in mice systemically primed with VLPs and these responses could be recalled following systemic boosting with VLPs. In addition, mucosal priming with VLPs allowed for a robust boosting response against Gag and gp41 when boosted with either candidate. Functional assays of these antibodies are in progress to test the antibodies' effectiveness in neutralizing and preventing mucosal transmission of HIV-1. This immunogenicity of plant-based Gag/dgp41 VLPs represents an important milestone on the road towards a broadly-efficacious and inexpensive subunit vaccine against HIV-1.
ContributorsKessans, Sarah (Author) / Mor, Tsafrir S (Thesis advisor) / Matoba, Nobuyuki (Committee member) / Mason, Hugh (Committee member) / Hogue, Brenda (Committee member) / Fromme, Petra (Committee member) / Arizona State University (Publisher)
Created2011
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Description

The Electoral College, the current electoral system in the U.S., operates on a Winner-Take-All or First Past the Post (FPTP) principle, where the candidate with the most votes wins. Despite the Electoral College being the current system, it is problematic. According to Lani Guinier in Tyranny of the Majority, “the

The Electoral College, the current electoral system in the U.S., operates on a Winner-Take-All or First Past the Post (FPTP) principle, where the candidate with the most votes wins. Despite the Electoral College being the current system, it is problematic. According to Lani Guinier in Tyranny of the Majority, “the winner-take-all principle invariably wastes some votes” (121). This means that the majority group gets all of the power in an election while the votes of the minority groups are completely wasted and hold little to no significance. Additionally, FPTP systems reinforce a two-party system in which neither candidate could satisfy the majority of the electorate’s needs and issues, yet forces them to choose between the two dominant parties. Moreover, voting for a third party candidate only hurts the voter since it takes votes away from the party they might otherwise support and gives the victory to the party they prefer the least, ensuring that the two party system is inescapable. Therefore, a winner-take-all system does not provide the electorate with fair or proportional representation and creates voter disenfranchisement: it offers them very few choices that appeal to their needs and forces them to choose a candidate they dislike. There are, however, alternative voting systems that remedy these issues, such as a Ranked voting system, in which voters can rank their candidate choices in the order they prefer them, or a Proportional voting system, in which a political party acquires a number of seats based on the proportion of votes they receive from the voter base. Given these alternatives, we will implement a software simulation of one of these systems to demonstrate how they work in contrast to FPTP systems, and therefore provide evidence of how these alternative systems could work in practice and in place of the current electoral system.

ContributorsSummers, Jack Gillespie (Co-author) / Martin, Autumn (Co-author) / Burger, Kevin (Thesis director) / Voorhees, Matthew (Committee member) / Computer Science and Engineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

System and software verification is a vital component in the development and reliability of cyber-physical systems - especially in critical domains where the margin of error is minimal. In the case of autonomous driving systems (ADS), the vision perception subsystem is a necessity to ensure correct maneuvering of the environment

System and software verification is a vital component in the development and reliability of cyber-physical systems - especially in critical domains where the margin of error is minimal. In the case of autonomous driving systems (ADS), the vision perception subsystem is a necessity to ensure correct maneuvering of the environment and identification of objects. The challenge posed in perception systems involves verifying the accuracy and rigidity of detections. The use of Spatio-Temporal Perception Logic (STPL) enables the user to express requirements for the perception system to verify, validate, and ensure its behavior; however, a drawback to STPL involves its accessibility. It is limited to individuals with an expert or higher-level knowledge of temporal and spatial logics, and the formal-written requirements become quite verbose with more restrictions imposed. In this thesis, I propose a domain-specific language (DSL) catered to Spatio-Temporal Perception Logic to enable non-expert users the ability to capture requirements for perception subsystems while reducing the necessity to have an experienced background in said logic. The domain-specific language for the Spatio-Temporal Perception Logic is built upon the formal language with two abstractions. The main abstraction captures simple programming statements that are translated to a lower-level STPL expression accepted by the testing monitor. The STPL DSL provides a seamless interface to writing formal expressions while maintaining the power and expressiveness of STPL. These translated equivalent expressions are capable of directing a standard for perception systems to ensure the safety and reduce the risks involved in ill-formed detections.

ContributorsAnderson, Jacob (Author) / Fainekos, Georgios (Thesis director) / Yezhou, Yang (Committee member) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description

The market for searching for food online is exploding. According to one expert at Google, “there are over 1 billion restaurant searches on Google every month” (Kelso, 2020). To capture this market and ride the general digital trend of internet personalization (as evidenced by Google search results, ads, YouTube and

The market for searching for food online is exploding. According to one expert at Google, “there are over 1 billion restaurant searches on Google every month” (Kelso, 2020). To capture this market and ride the general digital trend of internet personalization (as evidenced by Google search results, ads, YouTube and social media algorithms, etc), we created Munch to be an algorithm meant to help people find food they’ll love. <br/><br/>Munch offers the ability to search for food by restaurant or even as specific as a menu item (ex: search for the best Pad Thai). The best part? It is customized to your preferences based on a quiz you take when you open the app and from that point continuously learns from your behavior.<br/><br/>This thesis documents the journey of the team who founded Munch, what progress we made and the reasoning behind our decisions, where this idea fits in a competitive marketplace, how much it could be worth, branding, and our recommendations for a successful app in the future.

ContributorsInocencio, Phillippe Adriane (Co-author) / Rajan, Megha (Co-author) / Krug, Hayden (Co-author) / Byrne, Jared (Thesis director) / Sebold, Brent (Committee member) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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CubeSats can encounter a myriad of difficulties in space like cosmic rays, temperature<br/>issues, and loss of control. By creating better, more reliable software, these problems can be<br/>mitigated and increase the chance of success for the mission. This research sets out to answer the<br/>question: how do we create reliable flight software

CubeSats can encounter a myriad of difficulties in space like cosmic rays, temperature<br/>issues, and loss of control. By creating better, more reliable software, these problems can be<br/>mitigated and increase the chance of success for the mission. This research sets out to answer the<br/>question: how do we create reliable flight software for CubeSats? by providing a concentrated<br/>list of the best flight software development practices. The CubeSat used in this research is the<br/>Deployable Optical Receiver Aperture (DORA) CubeSat, which is a 3U CubeSat that seeks to<br/>demonstrate optical communication data rates of 1 Gbps over long distances. We present an<br/>analysis over many of the flight software development practices currently in use in the industry,<br/>from industry leads NASA, and identify three key flight software development areas of focus:<br/>memory, concurrency, and error handling. Within each of these areas, the best practices were<br/>defined for how to approach the area. These practices were also developed using experience<br/>from the creation of flight software for the DORA CubeSat in order to drive the design and<br/>testing of the system. We analyze DORA’s effectiveness in the three areas of focus, as well as<br/>discuss how following the best practices identified helped to create a more reliable flight<br/>software system for the DORA CubeSat.

ContributorsHoffmann, Zachary Christian (Author) / Chavez-Echeagaray, Maria Elena (Thesis director) / Jacobs, Daniel (Committee member) / Computer Science and Engineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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"No civil discourse, no cooperation; misinformation, mistruth." These were the words of former Facebook Vice President Chamath Palihapitiya who publicly expressed his regret in a 2017 interview over his role in co-creating Facebook. Palihapitiya shared that social media is ripping apart the social fabric of society and he also sounded

"No civil discourse, no cooperation; misinformation, mistruth." These were the words of former Facebook Vice President Chamath Palihapitiya who publicly expressed his regret in a 2017 interview over his role in co-creating Facebook. Palihapitiya shared that social media is ripping apart the social fabric of society and he also sounded the alarm regarding social media’s unavoidable global impact. He is only one of social media’s countless critics. The more disturbing issue resides in the empirical evidence supporting such notions. At least 95% of adolescents own a smartphone and spend an average time of two to four hours a day on social media. Moreover, 91% of 16-24-year-olds use social media, yet youth rate Instagram, Facebook, and Twitter as the worst social media platforms. However, the social, clinical, and neurodevelopment ramifications of using social media regularly are only beginning to emerge in research. Early research findings show that social media platforms trigger anxiety, depression, low self-esteem, and other negative mental health effects. These negative mental health symptoms are commonly reported by individuals from of 18-25-years old, a unique period of human development known as emerging adulthood. Although emerging adulthood is characterized by identity exploration, unbounded optimism, and freedom from most responsibilities, it also serves as a high-risk period for the onset of most psychological disorders. Despite social media’s adverse impacts, it retains its utility as it facilitates identity exploration and virtual socialization for emerging adults. Investigating the “user-centered” design and neuroscience underlying social media platforms can help reveal, and potentially mitigate, the onset of negative mental health consequences among emerging adults. Effectively deconstructing the Facebook, Twitter, and Instagram (i.e., hereafter referred to as “The Big Three”) will require an extensive analysis into common features across platforms. A few examples of these design features include: like and reaction counters, perpetual news feeds, and omnipresent banners and notifications surrounding the user’s viewport. Such social media features are inherently designed to stimulate specific neurotransmitters and hormones such as dopamine, serotonin, and cortisol. Identifying such predacious social media features that unknowingly manipulate and highjack emerging adults’ brain chemistry will serve as a first step in mitigating the negative mental health effects of today’s social media platforms. A second concrete step will involve altering or eliminating said features by creating a social media platform that supports and even enhances mental well-being.

ContributorsGupta, Anay (Author) / Flores, Valerie (Thesis director) / Carrasquilla, Christina (Committee member) / Barnett, Jessica (Committee member) / The Sidney Poitier New American Film School (Contributor) / Computer Science and Engineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

Over the years, advances in research have continued to decrease the size of computers from the size of<br/>a room to a small device that could fit in one’s palm. However, if an application does not require extensive<br/>computation power nor accessories such as a screen, the corresponding machine could be microscopic,<br/>only

Over the years, advances in research have continued to decrease the size of computers from the size of<br/>a room to a small device that could fit in one’s palm. However, if an application does not require extensive<br/>computation power nor accessories such as a screen, the corresponding machine could be microscopic,<br/>only a few nanometers big. Researchers at MIT have successfully created Syncells, which are micro-<br/>scale robots with limited computation power and memory that can communicate locally to achieve<br/>complex collective tasks. In order to control these Syncells for a desired outcome, they must each run a<br/>simple distributed algorithm. As they are only capable of local communication, Syncells cannot receive<br/>commands from a control center, so their algorithms cannot be centralized. In this work, we created a<br/>distributed algorithm that each Syncell can execute so that the system of Syncells is able to find and<br/>converge to a specific target within the environment. The most direct applications of this problem are in<br/>medicine. Such a system could be used as a safer alternative to invasive surgery or could be used to treat<br/>internal bleeding or tumors. We tested and analyzed our algorithm through simulation and visualization<br/>in Python. Overall, our algorithm successfully caused the system of particles to converge on a specific<br/>target present within the environment.

ContributorsMartin, Rebecca Clare (Author) / Richa, Andréa (Thesis director) / Lee, Heewook (Committee member) / Computer Science and Engineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

In this Barrett Honors Thesis, I developed a model to quantify the complexity of Sankey diagrams, which are a type of visualization technique that shows flow between groups. To do this, I created a carefully controlled dataset of synthetic Sankey diagrams of varying sizes as study stimuli. Then, a pair

In this Barrett Honors Thesis, I developed a model to quantify the complexity of Sankey diagrams, which are a type of visualization technique that shows flow between groups. To do this, I created a carefully controlled dataset of synthetic Sankey diagrams of varying sizes as study stimuli. Then, a pair of online crowdsourced user studies were conducted and analyzed. User performance for Sankey diagrams of varying size and features (number of groups, number of timesteps, and number of flow crossings) were algorithmically modeled as a formula to quantify the complexity of these diagrams. Model accuracy was measured based on the performance of users in the second crowdsourced study. The results of my experiment conclusively demonstrates that the algorithmic complexity formula I created closely models the visual complexity of the Sankey Diagrams in the dataset.

ContributorsGinjpalli, Shashank (Author) / Bryan, Chris (Thesis director) / Hsiao, Sharon (Committee member) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05