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Recent data suggests that olfactory input is important for antennal lobe development in honey bees. Chronic association of a single odor to food resources during crucial stages of development results in delayed antennal lobe development for mature foraging bees. The antennal lobes of these bees instead closely resemble an immature network observed in young, newly emerged bees. Using an odor stimuli variance assay, learning and memory tests can be used to explore how well honey bees discriminate single odors within complex odor mixtures. Here we are validating two different odor mixtures, a Brassica rapa floral blend and a second replicate mixture composed of common molecularly dissimilar odors. Odors in each mixture are either held constant or varied in concentration over 16 conditioning trials. Subsequent memory tests are performed two hours later to observe the ability of bees to distinguish and recognize specific odor components in each mixture. So far in our assay we find high rates of generalization for both odor mixtures. In general, more bees responded to all odors in the replicate treatment group over the Brassica treatment group. Additionally, bees in the Brassica treatment group did not respond to the target odor. More data is being collected to validate this assay. In future studies, I propose to apply this behavioral assay to bees with an altered olfactory developmental in order to see the functional impacts of this chronic odor association treatment.
ContributorsHalby, Rachael (Author) / Smith, Brian (Thesis director) / Jernigan, Christopher (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Asperger's syndrome is a high-functioning subset of Autism Spectrum Disorders (ASD). Diagnosed patients often lack refined social skills but possess a normal level of cognitive skills without delay in language development. These deficient social skills can impact the ability to find and maintain a job, which can be burdensome for all individuals involved in the patient's life. Although the causes of this condition are largely unknown, a wide variety of social and cognitive therapies have been used to reduce symptom severity, one of which is Mindfulness-Based Stress Reduction (MBSR). Mindfulness is the act of being aware on purpose to whatever is being experienced in the present moment with non-judgment and receptivity. MBSR has been used to bring greater awareness to sensations, thoughts and emotions with the result being reduced reactivity and increased purposeful responsiveness. It is therefore the aim of this study to address the use of an 8-week Mindfulness-Based Stress Reduction in adolescents with clinical Asperger's Syndrome to reduce reactive tendencies. This study will utilize a randomized control group of waitlisted participants given MBSR informational material and a practicing MBSR group. Post-MBSR Parent Global Impressions-III (PGI-III) and Social Responsiveness Scale scores are hypothesized to be improved in MBSR group and unaffected in the control for behavioral markers with no change in core autistic symptoms. Daily average cortisol response is also expected to decrease in the experimental group with unaffected levels in the control.
ContributorsBrzezinski, Molly Alexandra (Author) / Smith, Brian (Thesis director) / Sebren, Ann (Committee member) / School of Music (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
The mammalian olfactory system is commonly studied by using the mouse as a model system. Odor habituation is used to investigate odor perception and learning processes. Most previous experimental preparations have been tedious, requiring a researcher to manually change odorants, record investigation time and duration at each odorant, or physical alteration on the mice to enable video tracking. These limitations were overcame by creating an odorized hole-board to allow for systematic and automatic recording of olfactory behavior in mice. A cohort of five male mice were utilized in these experiments and the responses to the odor of strawberries, a diet staple of wile mice, were examined. Experiment 1 showed that free-feeding mice exhibit a preference to locations with strawberry (over control locations), even when these locations can only be identified using olfaction. This preference habituates within a trial but not across days. Experiment 2 showed that strawberry odor without reward causes habituation or extinction to the odor both within trials and across days. From these experiments, it can be concluded that mice innately explore strawberry odor and this can be exploited to the study odor habituation using an odorized hole-board.
ContributorsMa, Jason (Author) / Smith, Brian (Thesis director) / Gerkin, Richard (Committee member) / Oddo, Salvatore (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Animals must learn to ignore stimuli that are irrelevant to survival, a process referred to as latent inhibition. The Amtyr1 gene has been shown through quantitative trait loci mapping to be linked to strong latent inhibition in honey bees. Here we implicate this G-protein coupled receptor for the biogenic amine tyramine as an important factor underlying this form of learning in honey bees. We show that dsRNA targeted to disrupt the tyramine receptors, specifically affects latent inhibition but not excitatory associative conditioning. Our results therefore identify a distinct reinforcement pathway for latent inhibition in insects.
ContributorsPetersen, Mary Margaret (Author) / Smith, Brian (Thesis director) / Wang, Ying (Committee member) / Sinakevitch, Irina (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Almost every form of cancer deregulates the expression and activity of anabolic glycosyltransferase (GT) enzymes, which incorporate particular monosaccharides in a donor acceptor as well as linkage- and anomer-specific manner to assemble complex and diverse glycans that significantly affect numerous cellular events, including tumorigenesis and metastasis. Because glycosylation is not template-driven, GT deregulation yields heterogeneous arrays of aberrant intact glycan products, some in undetectable quantities in clinical bio-fluids (e.g., blood plasma). Numerous glycan features (e.g., 6 sialylation, β-1,6-branching, and core fucosylation) stem from approximately 25 glycan “nodes:” unique linkage specific monosaccharides at particular glycan branch points that collectively confer distinguishing features upon glycan products. For each node, changes in normalized abundance (Figure 1) may serve as nearly 1:1 surrogate measure of activity for culpable GTs and may correlate with particular stages of carcinogenesis. Complementary to traditional top down glycomics, the novel bottom-up technique applied herein condenses each glycan node and feature into a single analytical signal, quantified by two GC-MS instruments: GCT (time-of-flight analyzer) and GCMSD (transmission quadrupole analyzers). Bottom-up analysis of stage 3 and 4 breast cancer cases revealed better overall precision for GCMSD yet comparable clinical performance of both GC MS instruments and identified two downregulated glycan nodes as excellent breast cancer biomarker candidates: t-Gal and 4,6-GlcNAc (ROC AUC ≈ 0.80, p < 0.05). Resulting from the activity of multiple GTs, t-Gal had the highest ROC AUC (0.88) and lowest ROC p‑value (0.001) among all analyzed nodes. Representing core-fucosylation, glycan node 4,6-GlcNAc is a nearly 1:1 molecular surrogate for the activity of α-(1,6)-fucosyltransferase—a potential target for cancer therapy. To validate these results, future projects can analyze larger sample sets, find correlations between breast cancer stage and changes in t-Gal and 4,6-GlcNAc levels, gauge the specificity of these nodes for breast cancer and their potential role in other cancer types, and develop clinical tests for reliable breast cancer diagnosis and treatment monitoring based on t-Gal and 4,6-GlcNAc.
ContributorsZaare, Sahba (Author) / Borges, Chad (Thesis director) / LaBaer, Joshua (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Aberrant glycosylation has been shown to be linked to specific cancers, and using this idea, it was proposed that the levels of glycans in the blood could predict stage I adenocarcinoma. To track this glycosylation, glycan were broken down into glycan nodes via methylation analysis. This analysis utilized information from N-, O-, and lipid linked glycans detected from gas chromatography-mass spectrometry. The resulting glycan node-ratios represent the initial quantitative data that were used in this experiment.
For this experiment, two Sets of 50 µl blood plasma samples were provided by NYU Medical School. These samples were then analyzed by Dr. Borges’s lab so that they contained normalized biomarker levels from patients with stage 1 adenocarcinoma and control patients with matched age, smoking status, and gender were examined. An ROC curve was constructed under individual and paired conditions and AUC calculated in Wolfram Mathematica 10.2. Methods such as increasing size of training set, using hard vs. soft margins, and processing biomarkers together and individually were used in order to increase the AUC. Using a soft margin for this particular data set was proved to be most useful compared to the initial set hard margin, raising the AUC from 0.6013 to 0.6585. In regards to which biomarkers yielded the better value, 6-Glc/6-Man and 3,6-Gal glycan node ratios had the best with 0.7687 AUC and a sensitivity of .7684 and specificity of .6051. While this is not enough accuracy to become a primary diagnostic tool for diagnosing stage I adenocarcinoma, the methods examined in the paper should be evaluated further. . By comparison, the current clinical standard blood test for prostate cancer that has an AUC of only 0.67.
For this experiment, two Sets of 50 µl blood plasma samples were provided by NYU Medical School. These samples were then analyzed by Dr. Borges’s lab so that they contained normalized biomarker levels from patients with stage 1 adenocarcinoma and control patients with matched age, smoking status, and gender were examined. An ROC curve was constructed under individual and paired conditions and AUC calculated in Wolfram Mathematica 10.2. Methods such as increasing size of training set, using hard vs. soft margins, and processing biomarkers together and individually were used in order to increase the AUC. Using a soft margin for this particular data set was proved to be most useful compared to the initial set hard margin, raising the AUC from 0.6013 to 0.6585. In regards to which biomarkers yielded the better value, 6-Glc/6-Man and 3,6-Gal glycan node ratios had the best with 0.7687 AUC and a sensitivity of .7684 and specificity of .6051. While this is not enough accuracy to become a primary diagnostic tool for diagnosing stage I adenocarcinoma, the methods examined in the paper should be evaluated further. . By comparison, the current clinical standard blood test for prostate cancer that has an AUC of only 0.67.
ContributorsDe Jesus, Celine Spicer (Author) / Taylor, Thomas (Thesis director) / Borges, Chad (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
In Apis mellifera, gustatory responsiveness to sucrose is a good indicator of learning ability \u2014 in that individuals with high sucrose responsiveness will typically form faster, longer-lasting associations with conditioned stimulus than individuals with a low sucrose responsiveness. The purpose of this study was to determine whether experience with olfactory conditioning had lasting effects on gustatory responsiveness. Groups were placed in an environment that would facilitate association of an odor to a sucrose reward, tested for retention, then tested for gustatory responsiveness. Control groups underwent the same testing schedule, but were not exposed to odor in the first environment. There was no significant difference in gustatory responsiveness between the two groups. Mann-Whitney tests were used to analyze the results, and though the mean GRS score was lower among the treatment group there was no significant trend, possibly due to small sample sizes.
ContributorsSeemann, J. H. (Author) / Amdam, Gro (Thesis director) / Smith, Brian (Committee member) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Disturbances in the protein interactome often play a large role in cancer progression. Investigation of protein-protein interactions (PPI) can increase our understanding of cancer pathways and will disclose unknown targets involved in cancer disease biology. Although numerous methods are available to study protein interactions, most platforms suffer from drawbacks including high false positive rates, low throughput, and lack of quantification. Moreover, most methods are not compatible for use in a clinical setting. To address these limitations, we have developed a multiplexed, in-solution protein microarray (MISPA) platform with broad applications in proteomics. MISPA can be used to quantitatively profile PPIs and as a robust technology for early detection of cancers. This method utilizes unique DNA barcoding of individual proteins coupled with next generation sequencing to quantitatively assess interactions via barcode enrichment. We have tested the feasibility of this technology in the detection of patient immune responses to oropharyngeal carcinomas and in the discovery of novel PPIs in the B-cell receptor (BCR) pathway. To achieve this goal, 96 human papillomavirus (HPV) antigen genes were cloned into pJFT7-cHalo (99% success) and pJFT7-n3xFlag-Halo (100% success) expression vectors. These libraries were expressed via a cell-free in vitro transcription-translation system with 93% and 96% success, respectively. A small-scale study of patient serum interactions with barcoded HPV16 antigens was performed and a HPV proteome-wide study will follow using additional patient samples. In addition, 15 query proteins were cloned into pJFT7_nGST expression vectors, expressed, and purified with 93% success to probe a library of 100 BCR pathway proteins and detect novel PPIs.
ContributorsRinaldi, Capria Lakshmi (Author) / LaBaer, Joshua (Thesis director) / Mangone, Marco (Committee member) / Borges, Chad (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Microfluidic platforms have been exploited extensively as a tool for the separation of particles by electric field manipulation. Microfluidic devices can facilitate the manipulation of particles by dielectrophoresis. Separation of particles by size and type has been demonstrated by insulator-based dielectrophoresis in a microfluidic device. Thus, manipulating particles by size has been widely studied throughout the years. It has been shown that size-heterogeneity in organelles has been linked to multiple diseases from abnormal organelle size. Here, a mixture of two sizes of polystyrene beads (0.28 and 0.87 μm) was separated by a ratchet migration mechanism under a continuous flow (20 nL/min). Furthermore, to achieve high-throughput separation, different ratchet devices were designed to achieve high-volume separation. Recently, enormous efforts have been made to manipulate small size DNA and proteins. Here, a microfluidic device comprising of multiple valves acting as insulating constrictions when a potential is applied is presented. The tunability of the electric field gradient is evaluated by a COMSOL model, indicating that high electric field gradients can be reached by deflecting the valve at a certain distance. Experimentally, the tunability of the dynamic constriction was demonstrated by conducting a pressure study to estimate the gap distance between the valve and the substrate at different applied pressures. Finally, as a proof of principle, 0.87 μm polystyrene beads were manipulated by dielectrophoresis. These microfluidic platforms will aid in the understanding of size-heterogeneity of organelles for biomolecular assessment and achieve separation of nanometer-size DNA and proteins by dielectrophoresis.
ContributorsOrtiz, Ricardo (Author) / Ros, Alexandra (Thesis advisor) / Hayes, Mark (Committee member) / Borges, Chad (Committee member) / Arizona State University (Publisher)
Created2021
Description
Traditional Reinforcement Learning (RL) assumes to learn policies with respect to reward available from the environment but sometimes learning in a complex domain requires wisdom which comes from a wide range of experience. In behavior based robotics, it is observed that a complex behavior can be described by a combination of simpler behaviors. It is tempting to apply similar idea such that simpler behaviors can be combined in a meaningful way to tailor the complex combination. Such an approach would enable faster learning and modular design of behaviors. Complex behaviors can be combined with other behaviors to create even more advanced behaviors resulting in a rich set of possibilities. Similar to RL, combined behavior can keep evolving by interacting with the environment. The requirement of this method is to specify a reasonable set of simple behaviors. In this research, I present an algorithm that aims at combining behavior such that the resulting behavior has characteristics of each individual behavior. This approach has been inspired by behavior based robotics, such as the subsumption architecture and motor schema-based design. The combination algorithm outputs n weights to combine behaviors linearly. The weights are state dependent and change dynamically at every step in an episode. This idea is tested on discrete and continuous environments like OpenAI’s “Lunar Lander” and “Biped Walker”. Results are compared with related domains like Multi-objective RL, Hierarchical RL, Transfer learning, and basic RL. It is observed that the combination of behaviors is a novel way of learning which helps the agent achieve required characteristics. A combination is learned for a given state and so the agent is able to learn faster in an efficient manner compared to other similar approaches. Agent beautifully demonstrates characteristics of multiple behaviors which helps the agent to learn and adapt to the environment. Future directions are also suggested as possible extensions to this research.
ContributorsVora, Kevin Jatin (Author) / Zhang, Yu (Thesis advisor) / Yang, Yezhou (Committee member) / Praharaj, Sarbeswar (Committee member) / Arizona State University (Publisher)
Created2021