Matching Items (38)
Description
Rewired biological pathways and/or rewired microRNA (miRNA)-mRNA interactions might also influence the activity of biological pathways. Here, rewired biological pathways is defined as differential (rewiring) effect of genes on the topology of biological pathways between controls and cases. Similarly, rewired miRNA-mRNA interactions are defined as the differential (rewiring) effects of miRNAs on the topology of biological pathways between controls and cases. In the dissertation, it is discussed that how rewired biological pathways (Chapter 1) and/or rewired miRNA-mRNA interactions (Chapter 2) aberrantly influence the activity of biological pathways and their association with disease.
This dissertation proposes two PageRank-based analytical methods, Pathways of Topological Rank Analysis (PoTRA) and miR2Pathway, discussed in Chapter 1 and Chapter 2, respectively. PoTRA focuses on detecting pathways with an altered number of hub genes in corresponding pathways between two phenotypes. The basis for PoTRA is that the loss of connectivity is a common topological trait of cancer networks, as well as the prior knowledge that a normal biological network is a scale-free network whose degree distribution follows a power law where a small number of nodes are hubs and a large number of nodes are non-hubs. However, from normal to cancer, the process of the network losing connectivity might be the process of disrupting the scale-free structure of the network, namely, the number of hub genes might be altered in cancer compared to that in normal samples. Hence, it is hypothesized that if the number of hub genes is different in a pathway between normal and cancer, this pathway might be involved in cancer. MiR2Pathway focuses on quantifying the differential effects of miRNAs on the activity of a biological pathway when miRNA-mRNA connections are altered from normal to disease and rank disease risk of rewired miRNA-mediated biological pathways. This dissertation explores how rewired gene-gene interactions and rewired miRNA-mRNA interactions lead to aberrant activity of biological pathways, and rank pathways for their disease risk. The two methods proposed here can be used to complement existing genomics analysis methods to facilitate the study of biological mechanisms behind disease at the systems-level.
This dissertation proposes two PageRank-based analytical methods, Pathways of Topological Rank Analysis (PoTRA) and miR2Pathway, discussed in Chapter 1 and Chapter 2, respectively. PoTRA focuses on detecting pathways with an altered number of hub genes in corresponding pathways between two phenotypes. The basis for PoTRA is that the loss of connectivity is a common topological trait of cancer networks, as well as the prior knowledge that a normal biological network is a scale-free network whose degree distribution follows a power law where a small number of nodes are hubs and a large number of nodes are non-hubs. However, from normal to cancer, the process of the network losing connectivity might be the process of disrupting the scale-free structure of the network, namely, the number of hub genes might be altered in cancer compared to that in normal samples. Hence, it is hypothesized that if the number of hub genes is different in a pathway between normal and cancer, this pathway might be involved in cancer. MiR2Pathway focuses on quantifying the differential effects of miRNAs on the activity of a biological pathway when miRNA-mRNA connections are altered from normal to disease and rank disease risk of rewired miRNA-mediated biological pathways. This dissertation explores how rewired gene-gene interactions and rewired miRNA-mRNA interactions lead to aberrant activity of biological pathways, and rank pathways for their disease risk. The two methods proposed here can be used to complement existing genomics analysis methods to facilitate the study of biological mechanisms behind disease at the systems-level.
ContributorsLi, Chaoxing (Author) / Dinu, Valentin (Thesis advisor) / Kuang, Yang (Thesis advisor) / Liu, Li (Committee member) / Wang, Xiao (Committee member) / Arizona State University (Publisher)
Created2017
Description
Two different techniques utilizing vocalization in clarinet performance were examined through a research study in which one subject (the author) played several tasks utilizing each technique with different played pitches, vocalized pitches, and dynamic levels for each task. The first technique was singing while playing, which is also sometimes referred to as growling. This technique is produced by engaging the vocal folds during regular clarinet performance to create a second vocalized pitch that resonates in the oral cavity and exits through the mouthpiece as part of the same air stream as that used by the vibrating reed. The second technique studied was a much more recently pioneered technique that the author has labelled humming while playing due to its similarity to traditional humming in vocal pedagogy. This technique is produced by filling the oral cavity with air, sealing it off from the rest of the vocal tract using the tongue and soft palate, and humming through the nasal cavity. The cheeks are simultaneously used to squeeze air into the mouthpiece to maintain the clarinet pitch, much like in the technique of circular breathing.
For the study, audio, nasalance, and intraoral pressure data were collected and analyzed. Audio was analyzed using spectrograms and root mean square measurements of sound pressure for intensity (IRMS). Analysis of the nasalance data confirmed the description of the physiological mechanisms used to generate the humming while playing technique, with nasalance values for this technique far exceeding those for both singing while playing and regular playing. Intraoral pressure data showed significant spikes in pressure during the transitions from the regular air stream to air stored in the oral cavity when humming while playing. Audio analysis showed that the dynamic range of each technique is similar to that of regular playing, and that each technique produces very different and distinct aural effects.
This information was then used to help create a method to assist performers in learning how to produce both singing and humming while playing and a resource to help educate composers about the possibilities and limitations of each technique.
For the study, audio, nasalance, and intraoral pressure data were collected and analyzed. Audio was analyzed using spectrograms and root mean square measurements of sound pressure for intensity (IRMS). Analysis of the nasalance data confirmed the description of the physiological mechanisms used to generate the humming while playing technique, with nasalance values for this technique far exceeding those for both singing while playing and regular playing. Intraoral pressure data showed significant spikes in pressure during the transitions from the regular air stream to air stored in the oral cavity when humming while playing. Audio analysis showed that the dynamic range of each technique is similar to that of regular playing, and that each technique produces very different and distinct aural effects.
This information was then used to help create a method to assist performers in learning how to produce both singing and humming while playing and a resource to help educate composers about the possibilities and limitations of each technique.
ContributorsRuth, Jeremy Larkham (Author) / Gardner, Joshua T (Thesis advisor) / Spring, Robert S (Thesis advisor) / Schmelz, Peter J (Committee member) / Weinhold, Juliet (Committee member) / Arizona State University (Publisher)
Created2019
Description
Childhood Apraxia of Speech (CAS) is a severe motor speech disorder that is difficult to diagnose as there is currently no gold-standard measurement to differentiate between CAS and other speech disorders. In the present study, we investigate underlying biomarkers associated with CAS in addition to enhanced phenotyping through behavioral testing. Cortical electrophysiological measures were utilized to investigate differences in neural activation in response to native and non-native vowel contrasts between children with CAS and typically developing peers. Genetic analysis included full exome sequencing of a child with CAS and his unaffected parents in order to uncover underlying genetic variation that may be causal to the child’s severely impaired speech and language. Enhanced phenotyping was completed through extensive behavioral testing, including speech, language, reading, spelling, phonological awareness, gross/fine motor, and oral and hand motor tasks. Results from cortical electrophysiological measures are consistent with previous evidence of a heightened neural response to non-native sounds in CAS, potentially indicating over specified phonological representations in this population. Results of exome sequencing suggest multiple genetic variations contributing to the severely affected phenotype in the child and provide further evidence of heterogeneous genomic pathways associated with CAS. Finally, results of behavioral testing demonstrate significant impairments evident across tasks in CAS, suggesting underlying sequential processing deficits in multiple domains. Overall, these results have the potential to delineate functional pathways from genetic variations to the brain to observable behavioral phenotypes and motivate the development of preventative and targeted treatment approaches.
ContributorsVose, Caitlin (Author) / Peter, Beate (Thesis advisor) / Liu, Li (Committee member) / Brewer, Gene (Committee member) / Arizona State University (Publisher)
Created2018
Description
Circular RNAs (circRNAs) are a class of endogenous, non-coding RNAs that are formed when exons back-splice to each other and represent a new area of transcriptomics research. Numerous RNA sequencing (RNAseq) studies since 2012 have revealed that circRNAs are pervasively expressed in eukaryotes, especially in the mammalian brain. While their functional role and impact remains to be clarified, circRNAs have been found to regulate micro-RNAs (miRNAs) as well as parental gene transcription and may thus have key roles in transcriptional regulation. Although circRNAs have continued to gain attention, our understanding of their expression in a cell-, tissue- , and brain region-specific context remains limited. Further, computational algorithms produce varied results in terms of what circRNAs are detected. This thesis aims to advance current knowledge of circRNA expression in a region specific context focusing on the human brain, as well as address computational challenges.
The overarching goal of my research unfolds over three aims: (i) evaluating circRNAs and their predicted impact on transcriptional regulatory networks in cell-specific RNAseq data; (ii) developing a novel solution for de novo detection of full length circRNAs as well as in silico validation of selected circRNA junctions using assembly; and (iii) application of these assembly based detection and validation workflows, and integrating existing tools, to systematically identify and characterize circRNAs in functionally distinct human brain regions. To this end, I have developed novel bioinformatics workflows that are applicable to non-polyA selected RNAseq datasets and can be used to characterize circRNA expression across various sample types and diseases. Further, I establish a reference dataset of circRNA expression profiles and regulatory networks in a brain region-specific manner. This resource along with existing databases such as circBase will be invaluable in advancing circRNA research as well as improving our understanding of their role in transcriptional regulation and various neurological conditions.
The overarching goal of my research unfolds over three aims: (i) evaluating circRNAs and their predicted impact on transcriptional regulatory networks in cell-specific RNAseq data; (ii) developing a novel solution for de novo detection of full length circRNAs as well as in silico validation of selected circRNA junctions using assembly; and (iii) application of these assembly based detection and validation workflows, and integrating existing tools, to systematically identify and characterize circRNAs in functionally distinct human brain regions. To this end, I have developed novel bioinformatics workflows that are applicable to non-polyA selected RNAseq datasets and can be used to characterize circRNA expression across various sample types and diseases. Further, I establish a reference dataset of circRNA expression profiles and regulatory networks in a brain region-specific manner. This resource along with existing databases such as circBase will be invaluable in advancing circRNA research as well as improving our understanding of their role in transcriptional regulation and various neurological conditions.
ContributorsSekar, Shobana (Author) / Liang, Winnie S (Thesis advisor) / Dinu, Valentin (Thesis advisor) / Craig, David (Committee member) / Liu, Li (Committee member) / Arizona State University (Publisher)
Created2018
Description
The purpose of this study was to examine swallowing patterns using ultrasound technology subsequent to the implementation of two therapeutic interventions. Baseline swallow patterns were compared to swallows after implementation of therapeutic interventions common in both feeding therapy (FT) and orofacial myofunctional therapy (OMT). The interventions consist of stimulation of the tongue by z-vibe and tongue pops. Changes in swallowing patterns are described, and similarities of interventions across the two professions are discussed. Ultrasound research in the realm of swallowing is sparse despite having potential clinical application in both professions. In using ultrasound, this study outlines a protocol for utilization of a hand-held probe and reinforces a particular protocol described in the literature. Real-time ultrasound recordings of swallows for 19 adult female subjects were made. Participants with orofacial myofunctional disorder are compared to a group with typical swallowing and differences in swallowing patterns are described. Three stages of the oral phase of the swallow were assigned based on ultrasonic observation of the tongue shape. Analysis involves total duration of the swallow, duration of the three stages in relation to the total duration of the swallow, and the number of swallows required for the bolus to be cleared from the oral cavity. No significant effects of either intervention were found. Swallowing patterns showed a general trend to become faster in total duration subsequent to each intervention. An unexpected finding showed significant changes in the relationship between the bolus preparation stage and the bolus transportation stage when comparing the group classified as having a single swallow and the group classified as having multiple swallows.
ContributorsMckay, Michelle Diane (Author) / Weinhold, Juliet (Thesis director) / Scherer, Nancy (Committee member) / Department of Speech and Hearing Science (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Research in the last decade has indicated that collaboration between speech-language pathologists (SLP) and general education teachers is a necessary component for effective instruction. Students that have language difficulties should have the necessary support to help them succeed in the general education classroom. Despite the overwhelming evidence that supports that collaboration is the best practice, it does not take place due to lack of training, time, and funding. My creative project includes a template and website that allows SLPs and teachers to collaborate to enrich instruction targeted towards third grade students diagnosed with a language disorder. This template is designed for the SLP to contribute specific language-based strategies that they implement during their therapy sessions. In turn, the general educator can access the template and easily integrate those strategies into her lessons to support the language skills of her students so that the student has more opportunities to generalize their skills. The template is formatted around the IEP goals of the students and aligned to the Common Core standards. The purpose of the template is to provide SLPs and general education teachers a means to collaborate without having to take additional time from each other's limited schedules and eliminates the need for in-person training to implement these strategies to effectively support students with language disabilities struggling in the general education classroom.
ContributorsJagelka, Daniella (Author) / Weinhold, Juliet (Thesis director) / Mitchell, Jennifer (Committee member) / Division of Teacher Preparation (Contributor) / Department of Speech and Hearing Science (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
The purpose of this paper is to evaluate the effectiveness of a craft book used for stimulation therapy on the phonetic sounds /ŋ/, /r/, /s/, /ʃ/, /tʃ/, and /θ/. The book is specifically geared toward children who do not qualify for speech remediation services but who may be at risk of a speech sound disorder. Four children participated in the study with ages ranging from 4;3-7;6. The study lasted for four weeks in which data was collected on a weekly basis via Likert Scale surveys in accordance with two conversational speech samples. The speech samples were phonetically transcribed with minimal differences pre and post use of the craft book. Data from the surveys give insight to the children’s favorite crafts, the level of difficulty of each craft, and the likelihood of the craft book to be used as part of a remediation program. The study had limitations in sample size, duration, and number of craft activities. Future revisions should include increasing the number of crafts available per chapter and incorporating into the introduction an educational component for parents.
ContributorsKolaz, Chloe Ann (Author) / Weinhold, Juliet (Thesis director) / Azuma, Tamiko (Committee member) / Barrett, The Honors College (Contributor) / Department of Speech and Hearing Science (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor)
Created2014-05
Description
Research on /r/ production previously used formant analysis as the primary acoustic analysis, with particular focus on the low third formant in the speech signal. Prior imaging of speech used X-Ray, MRI, and electromagnetic midsagittal articulometer systems. More recently, the signal processing technique of Mel-log spectral plots has been used to study /r/ production in children and female adults. Ultrasound imaging of the tongue also has been used to image the tongue during speech production in both clinical and research settings. The current study attempts to describe /r/ production in three different allophonic contexts; vocalic, prevocalic, and postvocalic positions. Ultrasound analysis, formant analysis, Mel-log spectral plots, and /r/ duration were measured for /r/ production in 29 adult speakers (10 male, 19 female). A possible relationship between these variables was also explored. Results showed that the amount of superior constriction in the postvocalic /r/ allophone was significantly lower than the other /r/ allophones. Formant two was significantly lower and the distance between formant two and three was significantly higher for the prevocalic /r/ allophone. Vocalic /r/ had the longest average duration, while prevocalic /r/ had the shortest duration. Signal processing results revealed candidate Mel-bin values for accurate /r/ production for each allophone of /r/. The results indicate that allophones of /r/ can be distinguished based the different analyses. However, relationships between these analyses are still unclear. Future research is needed in order to gather more data on /r/ acoustics and articulation in order to find possible relationships between the analyses for /r/ production.
ContributorsHirsch, Megan Elizabeth (Author) / Weinhold, Juliet (Thesis director) / Gardner, Joshua (Committee member) / Department of Speech and Hearing Science (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Phylogenetic analyses that were conducted in the past didn't have the ability or functionality to inform and implement useful public health decisions while using clustering. Models can be constructed to conduct any further analyses for the result of meaningful data to be used in the future of public health informatics. A phylogenetic tree is considered one of the best ways for researchers to visualize and analyze the evolutionary history of a certain virus. The focus of this study was to research HIV phylodynamic and phylogenetic methods. This involved identifying the fast growing HIV transmission clusters and rates for certain risk groups in the US. In order to achieve these results an HIV database was required to retrieve real-time data for implementation, alignment software for multiple sequence alignment, Bayesian analysis software for the development and manipulation of models, and graphical tools for visualizing the output from the models created. This study began by conducting a literature review on HIV phylogeographies and phylodynamics. Sequence data was then obtained from a sequence database to be run in a multiple alignment software. The sequence that was obtained was unaligned which is why the alignment was required. Once the alignment was performed, the same file was loaded into a Bayesian analysis software for model creation of a phylogenetic tree. When the model was created, the tree was edited in a tree visualization software for the user to easily interpret. From this study the output of the tree resulted the way it did, due to a distant homology or the mixing of certain parameters. For a further continuation of this study, it would be interesting to use the same aligned sequence and use different model parameter selections for the initial creation of the model to see how the output changes. This is because one small change for the model parameter could greatly affect the output of the phylogenetic tree.
ContributorsNandan, Meghana (Author) / Scotch, Matthew (Thesis director) / Liu, Li (Committee member) / Biomedical Informatics Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Cancer is the second leading cause of death in the United States. Cancer is a serious, complex disease which causes cells to grow uncontrollably, causing millions of deaths per year [1]. Cancer is usually caused by a combination of environmental variables and biological pathways. The pathways have a very robust structure normally, but are altered because of cancer, resulting in a loss of connectivity between pathways. In order detect these pathways, a PageRank-based method called Pathways of Topological Rank Analysis (PoTRA) was created, which measures the relative rankings of the genes in each pathway. Applying this algorithm will allow us to figure out what pathways differed significantly in areas with cancer and areas without cancer. This would allow scientists to focus on specific pathways in order to learn more about the cancer and find more effective ways to treat it. So far, analysis using PoTRA has been successfully conducted on hepatocellular carcinoma (HCC) and its subtypes, resulting in all significant pathways found being cancer-associated. Now, using the TCGA data stored in Google Cloud's BigQuery, we created a pipeline to apply PoTRA to other cancer data sets and see how well it cross-applies to other cancers. The results show that even though some modification may need to be made to adapt to other datasets, many significant pathways were found for both HCC and breast cancer.
ContributorsMahesh, Sunny Nishant (Author) / Valentin, Dinu (Thesis director) / Liu, Li (Committee member) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05