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In an effort to begin validating the large number of discovered candidate biomarkers, proteomics is beginning to shift from shotgun proteomic experiments towards targeted proteomic approaches that provide solutions to automation and economic concerns. Such approaches to validate biomarkers necessitate the mass spectrometric analysis of hundreds to thousands of human samples. As this takes place, a serendipitous opportunity has become evident. By the virtue that as one narrows the focus towards "single" protein targets (instead of entire proteomes) using pan-antibody-based enrichment techniques, a discovery science has emerged, so to speak. This is due to the largely unknown context in which "single" proteins exist in blood (i.e. polymorphisms, transcript variants, and posttranslational modifications) and hence, targeted proteomics has applications for established biomarkers. Furthermore, besides protein heterogeneity accounting for interferences with conventional immunometric platforms, it is becoming evident that this formerly hidden dimension of structural information also contains rich-pathobiological information. Consequently, targeted proteomics studies that aim to ascertain a protein's genuine presentation within disease- stratified populations and serve as a stepping-stone within a biomarker translational pipeline are of clinical interest. Roughly 128 million Americans are pre-diabetic, diabetic, and/or have kidney disease and public and private spending for treating these diseases is in the hundreds of billions of dollars. In an effort to create new solutions for the early detection and management of these conditions, described herein is the design, development, and translation of mass spectrometric immunoassays targeted towards diabetes and kidney disease. Population proteomics experiments were performed for the following clinically relevant proteins: insulin, C-peptide, RANTES, and parathyroid hormone. At least thirty-eight protein isoforms were detected. Besides the numerous disease correlations confronted within the disease-stratified cohorts, certain isoforms also appeared to be causally related to the underlying pathophysiology and/or have therapeutic implications. Technical advancements include multiplexed isoform quantification as well a "dual- extraction" methodology for eliminating non-specific proteins while simultaneously validating isoforms. Industrial efforts towards widespread clinical adoption are also described. Consequently, this work lays a foundation for the translation of mass spectrometric immunoassays into the clinical arena and simultaneously presents the most recent advancements concerning the mass spectrometric immunoassay approach.
ContributorsOran, Paul (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Ros, Alexandra (Committee member) / Williams, Peter (Committee member) / Arizona State University (Publisher)
Created2011
Description
Signal processing techniques have been used extensively in many engineering problems and in recent years its application has extended to non-traditional research fields such as biological systems. Many of these applications require extraction of a signal or parameter of interest from degraded measurements. One such application is mass spectrometry immunoassay (MSIA) which has been one of the primary methods of biomarker discovery techniques. MSIA analyzes protein molecules as potential biomarkers using time of flight mass spectrometry (TOF-MS). Peak detection in TOF-MS is important for biomarker analysis and many other MS related application. Though many peak detection algorithms exist, most of them are based on heuristics models. One of the ways of detecting signal peaks is by deploying stochastic models of the signal and noise observations. Likelihood ratio test (LRT) detector, based on the Neyman-Pearson (NP) lemma, is an uniformly most powerful test to decision making in the form of a hypothesis test. The primary goal of this dissertation is to develop signal and noise models for the electrospray ionization (ESI) TOF-MS data. A new method is proposed for developing the signal model by employing first principles calculations based on device physics and molecular properties. The noise model is developed by analyzing MS data from careful experiments in the ESI mass spectrometer. A non-flat baseline in MS data is common. The reasons behind the formation of this baseline has not been fully comprehended. A new signal model explaining the presence of baseline is proposed, though detailed experiments are needed to further substantiate the model assumptions. Signal detection schemes based on these signal and noise models are proposed. A maximum likelihood (ML) method is introduced for estimating the signal peak amplitudes. The performance of the detection methods and ML estimation are evaluated with Monte Carlo simulation which shows promising results. An application of these methods is proposed for fractional abundance calculation for biomarker analysis, which is mathematically robust and fundamentally different than the current algorithms. Biomarker panels for type 2 diabetes and cardiovascular disease are analyzed using existing MS analysis algorithms. Finally, a support vector machine based multi-classification algorithm is developed for evaluating the biomarkers' effectiveness in discriminating type 2 diabetes and cardiovascular diseases and is shown to perform better than a linear discriminant analysis based classifier.
ContributorsBuddi, Sai (Author) / Taylor, Thomas (Thesis advisor) / Cochran, Douglas (Thesis advisor) / Nelson, Randall (Committee member) / Duman, Tolga (Committee member) / Arizona State University (Publisher)
Created2012
Description
Infectious diseases have been a major threat to survival throughout human history. Humans have developed a behavioral immune system to prevent infection by causing individuals to avoid people, food, and objects that could be contaminated. This current project investigates how ambient temperature affects the activation of this system. Because temperature is positively correlated with the prevalence of many deadly diseases, I predict that temperature moderates the behavioral immune system, such that a disease prime will have a stronger effect in a hot environment compared to a neutral environment and one's avoidant behaviors will be more extreme. Participants were placed in a hot room (M = 85F) or a neutral room (M = 77F) and shown a disease prime slide show or a neutral slide show. Disgust sensitivity and perceived vulnerability surveys were used to measure an increased perceived risk to disease. A taste test between a disgusting food item (gummy bugs) and a neutral food item (gummy animals) measured food avoidance. There was no significant avoidance of the gummy and no significant difference in ratings of disgust sensitivity or perceived vulnerability as a function of temperature conditions. There were no significant interactions between temperature and disease. The conclusion is that this study did not provide evidence that temperature moderates the effect of disease cues on behavior.
ContributorsOsborne, Elizabeth (Author) / Cohen, Adam B. (Thesis advisor) / Kwan, Sau (Committee member) / Neuberg, Steven (Committee member) / Arizona State University (Publisher)
Created2012
Description
Cancer claims hundreds of thousands of lives every year in US alone. Finding ways for early detection of cancer onset is crucial for better management and treatment of cancer. Thus, biomarkers especially protein biomarkers, being the functional units which reflect dynamic physiological changes, need to be discovered. Though important, there are only a few approved protein cancer biomarkers till date. To accelerate this process, fast, comprehensive and affordable assays are required which can be applied to large population studies. For this, these assays should be able to comprehensively characterize and explore the molecular diversity of nominally "single" proteins across populations. This information is usually unavailable with commonly used immunoassays such as ELISA (enzyme linked immunosorbent assay) which either ignore protein microheterogeneity, or are confounded by it. To this end, mass spectrometric immuno assays (MSIA) for three different human plasma proteins have been developed. These proteins viz. IGF-1, hemopexin and tetranectin have been found in reported literature to show correlations with many diseases along with several carcinomas. Developed assays were used to extract entire proteins from plasma samples and subsequently analyzed on mass spectrometric platforms. Matrix assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) mass spectrometric techniques where used due to their availability and suitability for the analysis. This resulted in visibility of different structural forms of these proteins showing their structural micro-heterogeneity which is invisible to commonly used immunoassays. These assays are fast, comprehensive and can be applied in large sample studies to analyze proteins for biomarker discovery.
ContributorsRai, Samita (Author) / Nelson, Randall (Thesis advisor) / Hayes, Mark (Thesis advisor) / Borges, Chad (Committee member) / Ros, Alexandra (Committee member) / Arizona State University (Publisher)
Created2012
Description
The present study explored the relationship between desired purchasing behavior and individual differences using two nationally-representative, longitudinal samples of the U.S. population early in the COVID-19 pandemic. Past research has shown that individual differences provide information about how one might respond to threat. Therefore, we predicted changes in desired purchasing behavior across different sociodemographic variables that might reflect those differences. Specifically, we investigated hypotheses related to political orientation, age, sexual orientation, socioeconomic status, and whether or not the participant had children. We measured participants’ reported desired purchasing behavior across eleven categories of goods and investigated the connection between specific demographic variables and desired purchasing behavior. We found that conservatives desired to purchase more basic protection goods (guns/ammunition, cash, gas) and that older people desired to purchase more cleaning supplies and toiletries. These findings illustrate possible explanations for purchasing behavior during the COVID-19 pandemic and reveal directions for marketing designed to influence purchasing behavior.
ContributorsZeider, Justyn (Author) / Varnum, Michael (Thesis director) / Neuberg, Steven (Committee member) / Department of Psychology (Contributor) / School of International Letters and Cultures (Contributor) / School of Social Transformation (Contributor) / Sandra Day O'Connor College of Law (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Regular instances of employee and petty theft seem to suggest that stealing is common. Certain situations make stealing an advantageous opportunity, and studies show that most people will steal under the right conditions. However, these "right conditions" vary widely among individuals and are a combination of biological, social, psychological, and situational factors. In an attempt to better understand the rationality of stealing, our research team applied evolutionary psychology principles to a social experiment involving gift card theft. To find trends in how people will steal when given the opportunity, we attempted to create these "right conditions" (which we believed would encourage theft by minimizing cost) so that we could measure how a random sample of subjects (male students on the Tempe campus of Arizona State University) responded to variation in benefit. We predicted that if the cost was kept low, and if some gift cards conferred greater advantages than others (by possession greater value or utility), then the more advantageous gift cards would be stolen at a higher frequency from the sample pool than less advantageous ones. The results show that our assumptions were wrong. Theft almost never occurred and the few cards that were stolen were not the more "rational" choices as predicted. The experimental design indicates a flawed understanding of how the subjects weighed the benefits and costs of stealing gift cards. One major issue is that we failed to consider pro-social behavior as the norm. We also neglected the evolutionary benefits of cooperative behavior while overemphasizing the evolutionary benefits of theft. A more thorough and nuanced examination of the literature must be performed to avoid these fundamental flaws in the experiment in the future. The experiment also suffered from issues which might have inadvertently discouraged theft including the location, population, presence of other students, and time given to contemplate theft. If we wish to truly examine trends in theft to see if there is a trend towards the rational theft model we proposed, we must work with a population in which individuals already have a propensity to steal, the benefit is sufficiently high, and social pressures to be cooperative are low.
ContributorsKumar, Davina Sangitha (Author) / Angilletta, Michael (Thesis director) / Neuberg, Steven (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Contextual cues can impact how statements are perceived. Specifically, they may be perceived as more aggressive than they otherwise would be. For the study, both medium of communication (in-person versus online) as well as how competitive the context was (non-competitive or competitive) were examined, with a bit of focus on gender. 130 Arizona State University students enrolled in Psychology 101 were surveyed; the mean age was 19.32 (SD = 1.43). A 2x2 factorial design was used, consisting of four possible conditions: In-person/Competitive, Online/Competitive, In-person/Non-Competitive, and Online/Non-Competitive. Participants read two scenarios, each featuring a target character who says an ambiguous statement, and each scenario with one of the four conditions at random. One scenario involved earning a promotion, and the other involved trying to win a voucher via mini-golf. After, participants answered questions regarding how they felt about the intent of the ambiguous statement, how the participant would feel in the scenario, and what kind of person the participant felt the target character was. Exploratory Factor Analysis with Principal Axis Factoring and Direct Oblimin Rotation was used to find outcome variables. We hypothesized that Perceived Aggression and Participant Negative Emotion would be higher in both the competitive condition as well as the online condition, and that Perceived Agreeableness would be higher in both the non-competitive condition as well as the in-person condition; this applied for both scenarios. The results were mostly not statistically significant, and contrary to the hypotheses, Perceived Aggression and Participant Negative Emotion were higher in the in-person condition than the online condition. However, as predicted, Perceived Agreeableness was higher for the in-person condition, and the competitive led to higher levels of Perceived Aggression and Participant Negative Emotion, along with lower levels of Perceived Agreeableness, as opposed to the non-competitive condition. Limitations included a small age range and only one type of online communication (instant messaging), along with the fact that the study was a survey. Future studies are needed to examine what factors affect perception of aggression, as very few have been conducted.
ContributorsRobins, Alexander Eric (Author) / Shiota, Michelle (Lani) (Thesis director) / Neuberg, Steven (Committee member) / Danvers, Alexander (Committee member) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
In the current study, the author investigated whether sociosexual orientation interacted with an experimental manipulation of sex ratios previously used by Li et al. (2010) which showed that men and women report greater religiosity after viewing profiles of attractive members of their own sex. The author predicted that only people of restricted sociosexual orientation would be reporting greater religiosity after viewing profiles of attractive members of their own sex. A sample of 171 undergraduate students (85 men, Mage = 19.5) from a large Southwestern university participated in the study for course credit. Participants were first administered the Sociosexual Orientation Index (Simpson & Gangestad, 1991). Then, under the pretense of assisting psychology faculty in designing a dating website for incoming students, participants viewed a set of profiles (photo and description) of either attractive men or attractive women, after which they answered a series of questions on a religiosity scale developed for the current study. Results showed that sociosexual orientation did not interact significantly with the experimental manipulation. Additionally, the results of the current study failed to replicate those of Li et al. (2010). The author discusses possibilities for why the results of the current study failed to replicate the results of Li et al., and for alternative explanations of the potential role of sociosexual orientation in responding to shifting sex ratios.
ContributorsCottengaim, Isaiah John (Author) / Cohen, Adam (Thesis director) / Neuberg, Steven (Committee member) / Barrett, The Honors College (Contributor) / School of Social and Behavioral Sciences (Contributor)
Created2014-05
Description
The aim of this thesis was to explore whether major life changes can have a visual, perceptible impact on facial changes. The proposed mediation model suggested that changes in personality serve as a mediating factor between life experiences and facial changes throughout the lifetime. The proposed model was tested by examining (1) perceived personality changes, (2) perceived physical changes, and (3) major life changes in photos of individuals' old-aged faces compared to their respective younger faces. Participants in the current study viewed old and young photos of 29 Miss America pageant winners and rated how much each older face changed from its respective younger face on the following criteria: age change, overall change, personality change, and physical change. Responses were aggregated across participants for each target, and personality and physical items were separately composited into single measures of overall perceived personality change and overall perceived physical change. Results did not support the proposed model; however, some marginally significant correlations were found between the number of times the targets experienced a change in marital status and the appearance of being calm, feminine, and less changed in older age. However, these correlations were in the reverse direction from what was expected; further research is needed to understand how marital changes influence, and are influenced by, personality and physical changes. As a form of face perception, the processes underlying the proposed model are discussed in terms of possible social consequences. Further research is needed to explore whether changes in life events, such as the ones presented here, are related to specific facets of personality and physical changes, and how these perceptions translate to important social outcomes. Suggestions for future research pertaining to these issues are discussed.
ContributorsMichael, Kendra (Author) / Kwan, Virginia (Thesis director) / Knight, George (Committee member) / Neuberg, Steven (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12
Description
What characteristics do people prefer in potential mates? Previous studies have explored this question, discovering that preferred characteristics vary by people's sex and sexual strategy, but have implied that these preferences remain constant across the lifespan. We suggest, however, that systematic variation exists in individuals' mate preferences across the lifespan, as they shift their investments from mating toward parenting. We suggest that the characteristics of a potential mate can be viewed as affordances that assist or hinder an individual in achieving certain fundamental goals. Incorporating the framework of Life History Theory with this affordance-management approach to social behavior, we propose that an individual's life stage, sex, and life history strategy together serve as the basis for these goals and thereby shape the characteristics people seek in potential mates. Using data collected from participants aged 18-45 recruited on Amazon's Mechanical Turk, we tested a range of hypotheses derived from our approach. In general, results provide mixed support for a role of life stage in shaping mate preferences. For example, nurturance and social competence were viewed as more necessary characteristics in a mate by participants invested in parenting. Moreover, as their investment in mating increased, females expressed a greater preference for ambition in their potential mates, but males did not. Other predictions were not borne out, however, suggesting that there is still much to be learned from investigating the relationship between life stage and mate preferences.
ContributorsKalina, Catherine Ellen (Author) / Neuberg, Steven (Thesis director) / Glenberg, Arthur (Committee member) / Gangestad, Steven (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / Graduate College (Contributor)
Created2014-05