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- Genre: Masters Thesis
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Description
A synbody is a newly developed protein binding peptide which can be rapidly produced by chemical methods. The advantages of the synbody producing process make it a potential human proteome binding reagent. Most of the synbodies are designed to bind to specific proteins. The peptides incorporated in a synbody are discovered with peptide microarray technology. Nevertheless, the targets for unknown synbodies can also be discovered by searching through a protein mixture. The first part of this thesis mainly focuses on the process of target searching, which was performed with immunoprecipitation assays and mass spectrometry analysis. Proteins are pulled down from the cell lysate by certain synbodies, and then these proteins are identified using mass spectrometry. After excluding non-specific bindings, the interaction between a synbody and its real target(s) can be verified with affinity measurements. As a specific example, the binding between 1-4-KCap synbody and actin was discovered. This result proved the feasibility of the mass spectrometry based method and also suggested that a high throughput synbody discovery platform for the human proteome could be developed. Besides the application of synbody development, the peptide microarray technology can also be used for immunosignatures. The composition of all types of antibodies existing in one's blood is related to an individual's health condition. A method, called immunosignaturing, has been developed for early disease diagnosis based on this principle. CIM10K microarray slides work as a platform for blood antibody detection in immunosignaturing. During the analysis of an immunosignature, the data from these slides needs to be validated by using landing light peptides. The second part of this thesis focuses on the validation of the data. A biotinylated peptide was used as a landing light on the new CIM10K slides. The data was collected in several rounds of tests and indicated that the variation among landing lights was significantly reduced by using the newly prepared biotinylated peptide compared with old peptide mixture. Several suggestions for further landing light improvement are proposed based on the results.
ContributorsSun, Minyao (Author) / Johnston, Stephen Albert (Thesis advisor) / Diehnelt, Chris Wayne (Committee member) / Stafford, Phillip (Committee member) / Arizona State University (Publisher)
Created2011
Description
Advancements in computer vision and machine learning have added a new dimension to remote sensing applications with the aid of imagery analysis techniques. Applications such as autonomous navigation and terrain classification which make use of image classification techniques are challenging problems and research is still being carried out to find better solutions. In this thesis, a novel method is proposed which uses image registration techniques to provide better image classification. This method reduces the error rate of classification by performing image registration of the images with the previously obtained images before performing classification. The motivation behind this is the fact that images that are obtained in the same region which need to be classified will not differ significantly in characteristics. Hence, registration will provide an image that matches closer to the previously obtained image, thus providing better classification. To illustrate that the proposed method works, naïve Bayes and iterative closest point (ICP) algorithms are used for the image classification and registration stages respectively. This implementation was tested extensively in simulation using synthetic images and using a real life data set called the Defense Advanced Research Project Agency (DARPA) Learning Applied to Ground Robots (LAGR) dataset. The results show that the ICP algorithm does help in better classification with Naïve Bayes by reducing the error rate by an average of about 10% in the synthetic data and by about 7% on the actual datasets used.
ContributorsMuralidhar, Ashwini (Author) / Saripalli, Srikanth (Thesis advisor) / Papandreou-Suppappola, Antonia (Committee member) / Turaga, Pavan (Committee member) / Arizona State University (Publisher)
Created2011
Description
Natural products that target the DNA of cancer cells have been an important source of knowledge and understanding in the development of anticancer chemotherapeutic agents. Bleomycin (BLM) exemplifies this class of DNA damaging agent. The ability of BLM to chelate metal ions and effect oxidative damage of the deoxyribose sugar moiety of DNA has been studied extensively for four decades. Here, the study of BLM A5 was conducted using a previously isolated library of hairpin DNAs found to bind strongly to metal free BLM. The ability of BLM to effect single-stranded was then extensively characterized on both the 3′ and 5′-arms of the hairpin DNAs. The strongly bound DNAs were found to be efficient substrates for Fe·BLM A5-mediated cleavage. Surprisingly, the most prevalent site of damage by BLM was found to be a 5′-AT-3′ dinucleotide sequence. This dinucleotide sequence and others generally not cleaved by BLM when examined using arbitrarily chosen DNA substrate were found in examining the library of ten hairpin DNAs. In total, 111 sites of DNA damage were found to be produced by exposure of the hairpin DNA library to Fe·BLM A5. Also, an assay was developed with which to test the propensity of the hairpin DNAs to undergo double stranded DNA damage. Adapting methods previously described by the Povirk laboratory, one hairpin was characterized using this method. The results were in accordance with those previously reported.
ContributorsSegerman, Zachary (Author) / Hecht, Sidney M. (Thesis advisor) / Levitus, Marcia (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2011
Description
Mexican Americans have an increased risk for type 2 diabetes and premature cardiovascular disease (CVD). The association of hyperglycemia with traditional CVD risk factors in this population has been established, but there is limited data regarding other non-traditional CVD risk factors. Thus, this cross-sectional study was conducted to evaluate CVD risk among Mexican Americans by measuring concentrations of lipids, high-sensitivity C-reactive protein (hsCRP), and cholesterol in low-density-lipoprotein (LDL) and high-density-lipoprotein (HDL) subfractions. Eighty overweight/obese Mexican-American adults participating in the Maricopa Insulin Resistance Initiative were randomly selected from each of the following four groups (n = 20 per group): nomolipidemic
ormoglycemic controls (NC), dyslipidemic
ormoglycemic (DN), dyslipidemic/prediabetic (DPD) and dyslipidemic/diabetic (DD). Total cholesterol (TC) was 30% higher among DD than in NC participants (p<0.0001). The DPD group had 27% and 12% higher LDL-C concentrations than the NC and DN groups, respectively. Similarly, LDL-C was 29% and 13% higher in DD than in NC and DN participants (p=0.013). An increasing trend was observed in %10-year CVD risk with increasing degree of hyperglycemia (p<0.0001). The NC group had less cholesterol in sdLDL particles than dyslipidemic groups, regardless of glycemic status (p<0.0001). When hyperglycemia was part of the phenotype (DPD and DD), there was a greater proportion of total and HDL-C in sHDL particles in dyslipidemic individuals than in NC (p=0.023; p<0.0001; respectively). Percent 10-year CVD risk was positively correlated with triglyceride (TG) (r=0.384, p<0.0001), TC (r=0.340, p<0.05), cholesterol in sdLDL(r=0.247; p<0.05), and TC to HDL-C ratio (r=0.404, p<0.0001), and negatively correlated with HDL-C in intermediate and large HDL(r=-0.38, p=0.001; r=0.34, p=0.002, respectively). The TC/HDL-C was positively correlated with cholesterol in sdLDL particles (r=0.698, p<0.0001) and HDL-C in sHDL particles (r=0.602, p<0.0001), and negatively correlated with cholesterol in small (r=-0.35, p=0.002), intermediate (r=-0.91, p<0.0001) and large (r=-0.84, p<0.0001) HDL particles, and HDL-C in the large HDL particles (r=-0.562, p<0.0001). No significant association was found between %10-year CVD risk and hsCRP. Collectively, these results corroborate that dyslipidemic Mexican-American adults have higher CVD risk than normolipidemic individuals. Hyperglycemia may further affect CVD risk by modulating cholesterol in LDL and HDL subfractions.
ormoglycemic controls (NC), dyslipidemic
ormoglycemic (DN), dyslipidemic/prediabetic (DPD) and dyslipidemic/diabetic (DD). Total cholesterol (TC) was 30% higher among DD than in NC participants (p<0.0001). The DPD group had 27% and 12% higher LDL-C concentrations than the NC and DN groups, respectively. Similarly, LDL-C was 29% and 13% higher in DD than in NC and DN participants (p=0.013). An increasing trend was observed in %10-year CVD risk with increasing degree of hyperglycemia (p<0.0001). The NC group had less cholesterol in sdLDL particles than dyslipidemic groups, regardless of glycemic status (p<0.0001). When hyperglycemia was part of the phenotype (DPD and DD), there was a greater proportion of total and HDL-C in sHDL particles in dyslipidemic individuals than in NC (p=0.023; p<0.0001; respectively). Percent 10-year CVD risk was positively correlated with triglyceride (TG) (r=0.384, p<0.0001), TC (r=0.340, p<0.05), cholesterol in sdLDL(r=0.247; p<0.05), and TC to HDL-C ratio (r=0.404, p<0.0001), and negatively correlated with HDL-C in intermediate and large HDL(r=-0.38, p=0.001; r=0.34, p=0.002, respectively). The TC/HDL-C was positively correlated with cholesterol in sdLDL particles (r=0.698, p<0.0001) and HDL-C in sHDL particles (r=0.602, p<0.0001), and negatively correlated with cholesterol in small (r=-0.35, p=0.002), intermediate (r=-0.91, p<0.0001) and large (r=-0.84, p<0.0001) HDL particles, and HDL-C in the large HDL particles (r=-0.562, p<0.0001). No significant association was found between %10-year CVD risk and hsCRP. Collectively, these results corroborate that dyslipidemic Mexican-American adults have higher CVD risk than normolipidemic individuals. Hyperglycemia may further affect CVD risk by modulating cholesterol in LDL and HDL subfractions.
ContributorsNeupane, Srijana (Author) / Vega-Lopez, Sonia (Thesis advisor) / Shaibi, Gabriel Q (Committee member) / Johnston, Carol S (Committee member) / Arizona State University (Publisher)
Created2011
Description
Studies have demonstrated that anthocyanins can function as antioxidants, reduce inflammation, and improve dyslipidemia. Tart cherries are anthocyanin-rich, making them particularly attractive as a functional food to improve cardiovascular disease (CVD) risk. There have been few published studies to date examining the impact of tart cherries on biomarkers of dyslipidemia and inflammation, particularly in overweight and obese individuals at high risk for these conditions. This study evaluated the effect of consuming 100% tart cherry juice daily on blood lipids including total cholesterol, low-density lipoprotein cholesterol (LDL-C), calculated very low density lipoprotein cholesterol (VLDL-C), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), and the CVD risk ratios, as well as the inflammatory biomarkers interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), monocyte chemotactic protein-1 (MCP-1), and erythrocyte sedimentation rate (ESR) following a 4-week period. Based on the high anthocyanin content of tart cherries, it was hypothesized that the lipid and inflammatory profiles would be significantly improved following the intervention. A total of 26 men and women completed this 4-week randomized, single-blind, placebo-controlled, crossover study. Participants were randomized to drink either 8 ounces of placebo beverage or tart cherry juice daily for 4 weeks. Following a 4-week washout period, the alternate beverage was consumed. Ultimately, this investigation demonstrated no statistically significant alterations in any of the lipid or inflammatory biomarkers when analyzed across time and between interventions (p > 0.05). As expected, glucose and insulin parameters remained stable over the duration of the study, as well as self-reported physical activity level, total calorie consumption, and macronutrient intake. However, trans-fat was reported to be significantly higher during the cherry arm of the study as compared to the placebo arm (p < 0.05), potentially confounding other results. Although the results of this study were equivocal, it is feasible that a higher dose, longer treatment duration, or more susceptible target population may be required to elicit significant effects. Consequently, further investigation is necessary to clarify this research.
ContributorsColes, Katie (Author) / Martin, Keith R. (Thesis advisor) / Traustadottir, Tinna (Committee member) / Vega-Lopez, Sonia (Committee member) / Arizona State University (Publisher)
Created2012
Description
A potential new class of cancer chemotherapeutic agents has been synthesized by varying the 2 position of a benzimidazole based extended amidine. Compounds 6-amino-2-chloromethyl-4-imino-1-(2-methansulfonoxyethyl)-5-methyl-1H-benzimidazole-7-one (1A) and 6-amino-2-hydroxypropyl-4-imino-1-(2-methansulfonoxyethyl)-5-methyl-1H-benzimidazole-7-one (1B) were assayed at the National Cancer Institute's (NCI) Developmental Therapeutic Program (DTP) and found to be cytotoxic at sub-micromolar concentrations, and have shown between a 100 and a 1000-fold increase in specificity towards lung, colon, CNS, and melanoma cell lines. These ATP mimics have been found to correlate with sequestosome 1 (SQSTM1), a protein implicated in drug resistance and cell survival in various cancer cell lines. Using the DTP COMPARE algorithm, compounds 1A and 1B were shown to correlate to each other at 77%, but failed to correlate with other benzimidazole based extended amidines previously synthesized in this laboratory suggesting they operate through a different biological mechanism.
ContributorsDarzi, Evan (Author) / Skibo, Edward (Thesis advisor) / Gould, Ian (Committee member) / Francisco, Wilson (Committee member) / Arizona State University (Publisher)
Created2011
Description
As robots are increasingly migrating out of factories and research laboratories and into our everyday lives, they should move and act in environments designed for humans. For this reason, the need of anthropomorphic movements is of utmost importance. The objective of this thesis is to solve the inverse kinematics problem of redundant robot arms that results to anthropomorphic configurations. The swivel angle of the elbow was used as a human arm motion parameter for the robot arm to mimic. The swivel angle is defined as the rotation angle of the plane defined by the upper and lower arm around a virtual axis that connects the shoulder and wrist joints. Using kinematic data recorded from human subjects during every-day life tasks, the linear sensorimotor transformation model was validated and used to estimate the swivel angle, given the desired end-effector position. Defining the desired swivel angle simplifies the kinematic redundancy of the robot arm. The proposed method was tested with an anthropomorphic redundant robot arm and the computed motion profiles were compared to the ones of the human subjects. This thesis shows that the method computes anthropomorphic configurations for the robot arm, even if the robot arm has different link lengths than the human arm and starts its motion at random configurations.
ContributorsWang, Yuting (Author) / Artemiadis, Panagiotis (Thesis advisor) / Mignolet, Marc (Committee member) / Santos, Veronica J (Committee member) / Arizona State University (Publisher)
Created2013
Description
With robots being used extensively in various areas, a certain degree of robot autonomy has always been found desirable. In applications like planetary exploration, autonomous path planning and navigation are considered essential. But every now and then, a need to modify the robot's operation arises, a need for a human to provide it some supervisory parameters that modify the degree of autonomy or allocate extra tasks to the robot. In this regard, this thesis presents an approach to include a provision to accept and incorporate such human inputs and modify the navigation functions of the robot accordingly. Concepts such as applying kinematical constraints while planning paths, traversing of unknown areas with an intent of maximizing field of view, performing complex tasks on command etc. have been examined and implemented. The approaches have been tested in Robot Operating System (ROS), using robots such as the iRobot Create, Personal Robotics (PR2) etc. Simulations and experimental demonstrations have proved that this approach is feasible for solving some of the existing problems and that it certainly can pave way to further research for enhancing functionality.
ContributorsVemprala, Sai Hemachandra (Author) / Saripalli, Srikanth (Thesis advisor) / Fainekos, Georgios (Committee member) / Turaga, Pavan (Committee member) / Arizona State University (Publisher)
Created2013
Description
Electromyogram (EMG)-based control interfaces are increasingly used in robot teleoperation, prosthetic devices control and also in controlling robotic exoskeletons. Over the last two decades researchers have come up with a plethora of decoding functions to map myoelectric signals to robot motions. However, this requires a lot of training and validation data sets, while the parameters of the decoding function are specific for each subject. In this thesis we propose a new methodology that doesn't require training and is not user-specific. The main idea is to supplement the decoding functional error with the human ability to learn inverse model of an arbitrary mapping function. We have shown that the subjects gradually learned the control strategy and their learning rates improved. We also worked on identifying an optimized control scheme that would be even more effective and easy to learn for the subjects. Optimization was done by taking into account that muscles act in synergies while performing a motion task. The low-dimensional representation of the neural activity was used to control a two-dimensional task. Results showed that in the case of reduced dimensionality mapping, the subjects were able to learn to control the device in a slower pace, however they were able to reach and retain the same level of controllability. To summarize, we were able to build an EMG-based controller for robot devices that would work for any subject, without any training or decoding function, suggesting human-embedded controllers for robotic devices.
ContributorsAntuvan, Chris Wilson (Author) / Artemiadis, Panagiotis (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / Santos, Veronica J (Committee member) / Arizona State University (Publisher)
Created2013
Description
Linear Temporal Logic is gaining increasing popularity as a high level specification language for robot motion planning due to its expressive power and scalability of LTL control synthesis algorithms. This formalism, however, requires expert knowledge and makes it inaccessible to non-expert users. This thesis introduces a graphical specification environment to create high level motion plans to control robots in the field by converting a visual representation of the motion/task plan into a Linear Temporal Logic (LTL) specification. The visual interface is built on the Android tablet platform and provides functionality to create task plans through a set of well defined gestures and on screen controls. It uses the notion of waypoints to quickly and efficiently describe the motion plan and enables a variety of complex Linear Temporal Logic specifications to be described succinctly and intuitively by the user without the need for the knowledge and understanding of LTL specification. Thus, it opens avenues for its use by personnel in military, warehouse management, and search and rescue missions. This thesis describes the construction of LTL for various scenarios used for robot navigation using the visual interface developed and leverages the use of existing LTL based motion planners to carry out the task plan by a robot.
ContributorsSrinivas, Shashank (Author) / Fainekos, Georgios (Thesis advisor) / Baral, Chitta (Committee member) / Burleson, Winslow (Committee member) / Arizona State University (Publisher)
Created2013