Digital Commons Network^™

Specific Thiazolidinediones Inhibit Ovarian Cancer Cell Line Proliferation And Cause Cell Cycle Arrest In A Pparγ Independent Manner, Linah Al-Alem, R. Chase Southard, Michael W. Kilgore, Thomas E. Curry

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Peroxisome Proliferator Activated Receptor gamma (PPARγ) agonists, such as the thiazolinediones (TZDs), have been studied for their potential use as cancer therapeutic agents. We investigated the effect of four TZDs--Rosiglitazone (Rosi), Ciglitazone (CGZ), Troglitazone (TGZ), and Pioglitazone (Pio)--on ovarian cancer cell proliferation, PPARγ expression and PPAR luciferase reporter activity. We explored whether TZDs act in a PPARγ dependent or independent manner by utilizing molecular approaches to inhibit or overexpress PPARγ activity.

PRINCIPAL FINDINGS: Treatment with CGZ or TGZ for 24 hours decreased proliferation in three ovarian cancer cell lines, Ovcar3, CaOv3, and Skov3, whereas Rosi and Pio had no …

Analysis Of The Proteome Of Human Airway Epithelial Secretions., Mehboob Ali, Erik P Lillehoj, Yongsung Park, Yoshiyuki Kyo, K Chul Kim

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Airway surface liquid, often referred to as mucus, is a thin layer of fluid covering the luminal surface that plays an important defensive role against foreign particles and chemicals entering the lungs. Airway mucus contains various macromolecules, the most abundant being mucin glycoproteins, which contribute to its defensive function. Airway epithelial cells cultured in vitro secrete mucins and nonmucin proteins from their apical surface that mimics mucus production in vivo. The current study was undertaken to identify the polypeptide constituents of human airway epithelial cell secretions to gain a better understanding of the protein composition of respiratory mucus.

RESULTS: …

Steroids Up-Regulate P66shc Longevity Protein In Growth Regulation By Inhibiting Its Ubiquitination., Santosh Kumar, Satyendra Kumar, Mythilypriya Rajendran, Syed Mahfuzul Alam, Fen-Fen Lin, Pi-Wan Cheng, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: p66Shc, an isoform of Shc adaptor proteins, mediates diverse signals, including cellular stress and mouse longevity. p66Shc protein level is elevated in several carcinomas and steroid-treated human cancer cells. Several lines of evidence indicate that p66Shc plays a critical role in steroid-related carcinogenesis, and steroids play a role in its elevated levels in those cells without known mechanism.

METHODS AND FINDINGS: In this study, we investigated the molecular mechanism by which steroid hormones up-regulate p66Shc protein level. In steroid-treated human prostate and ovarian cancer cells, p66Shc protein levels were elevated, correlating with increased cell proliferation. These steroid effects on …

Gene Expression In Cardiac Tissues From Infants With Idiopathic Conotruncal Defects., Douglas C. Bittel, Merlin G. Butler, Nataliya Kibiryeva, Jennifer A. Marshall, Jie Chen, Gary K. Lofland, James E. O'Brien

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Tetralogy of Fallot (TOF) is the most commonly observed conotruncal congenital heart defect. Treatment of these patients has evolved dramatically in the last few decades, yet a genetic explanation is lacking for the failure of cardiac development for the majority of children with TOF. Our goal was to perform genome wide analyses and characterize expression patterns in cardiovascular tissue (right ventricle, pulmonary valve and pulmonary artery) obtained at the time of reconstructive surgery from 19 children with tetralogy of Fallot.

METHODS: We employed genome wide gene expression microarrays to characterize cardiovascular tissue (right ventricle, pulmonary valve and pulmonary artery) …

The Roles Of Conserved And Nonconserved Cysteinyl Residues In The Oligomerization And Function Of Mammalian Prestin, Benjamin Currall, Danielle Rossino, Heather Jensen Smith, Richard Hallworth

Journal Articles: Eppley Institute

The creation of several prestin knockout and knockin mouse lines has demonstrated the importance of the intrinsic outer hair cell membrane protein prestin to mammalian hearing. However, the structure of prestin remains largely unknown, with even its major features in dispute. Several studies have suggested that prestin forms homo-oligomers that may be stabilized by disulfide bonds. Our phylogenetic analysis of prestin sequences across chordate classes suggested that the cysteinyl residues could be divided into three groups, depending on the extent of their conservation between prestin orthologs and paralogs or homologs. An alanine scan functional analysis was performed of all nine …

Prerequisites In Behavioral Science And Business: Opportunities For Dental Education., David G. Dunning, Brian M. Lange, Robert D. Madden, Koko K. Tacha

Journal Articles: College of Dentistry

There is increasing pressure on recent dental school graduates to understand and successfully utilize patient management and business management strategies to run a productive dental office. Dental schools are faced with the dilemma to either add more credit hours in their already crowded curriculum or adjust predental school requirements. All fifty-nine U.S. dental schools were assessed online to determine admission requirements in the areas of behavioral science and business education. Results show that only 11.9 percent of the schools require prerequisite course work in behavioral science and no school requires prerequisite course work in business. However, 64.4 percent and 30.5 …

Prehypertension And Endothelial Progenitor Cell Function., Oj Maceneaney, C A Desouza, B R Weil, E J Kushner, Gary Van Guilder, M L Mestek, J J Greiner, B L Stauffer

Health and Nutritional Sciences Faculty Publications

Prehypertension is associated with significant damage to the coronary vasculature and increased rates of adverse cardiovascular events. Circulating endothelial progenitor cells (EPCs) are critical to vascular repair and the formation of new blood vessels. We tested the hypothesis that prehypertension is associated with EPC dysfunction. Peripheral blood samples were collected from 83 middle-aged and older adults (51 M/32 F): 40 normotensive (age 53±2 yr; BP 111/74±1/1 mmHg) and 43 prehypertensive (54±2; 128/77±1/1 mmHg). EPCs were isolated from peripheral blood and EPC colony-forming capacity (colony-forming unit assay), migratory activity (Boyden chamber) and apoptotic susceptibility (active caspase-3 concentrations) were determined. There were …

Differentiation Of Embryonic Stem Cells Into Fibroblast-Like Cells In Three-Dimensional Type I Collagen Gel Cultures, Shinsaku Togo, Tadashi Sato, Hisatoshi Sugiura, Xingqi Wang, Hesham Basma, Amy J. Nelson, Xiangde Liu, Tom W. Bargar, J. Graham Sharp, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

Fibroblasts are heterogeneous mesenchymal cells that play important roles in the production and maintenance of extracellular matrix. Although their heterogeneity is recognized, progenitor progeny relationships among fibroblasts and the factors that control fibroblast differentiation are poorly defined. The current study was designed to develop a reliable method that would permit in vitro differentiation of fibroblast-like cells from human and murine embryonic stem cells (ESCs). Undifferentiated ESCs were differentiated into embryoid bodies (EBs) with differentiation media. EBs were then cast into type I collagen gels and cultured for 21 d with basal media. The spindle-shaped cells that subsequently grew from the …

Potential For Interdependent Development Of Trna Determinants For Aminoacylation And Ribosome Decoding., Cuiping Liu, Howard Gamper, Hanqing Liu, Barry S Cooperman, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Although the nucleotides in tRNA required for aminoacylation are conserved in evolution, bacterial aminoacyl-transfer RNA synthetases are unable to acylate eukaryotic tRNA. The cross-species barrier may be due to the absence of eukaryote-specific domains from bacterial aminoacyl-transfer RNA synthetases. Here we show that whereas Escherichia coli CysRS cannot acylate human tRNA(Cys), the fusion of a eukaryote-specific domain of human CysRS overcomes the cross-species barrier in human tRNA(Cys). In addition to enabling recognition of the sequence differences in the tertiary core of tRNA(Cys), the fused eukaryotic domain redirects the specificity of E. coli CysRS from the A37 present in bacterial tRNA(Cys) …

Animal Models For Periodontal Disease, Helieh S. Oz, David A. Puleo

Center for Oral Health Research Faculty Publications

Animal models and cell cultures have contributed new knowledge in biological sciences, including periodontology. Although cultured cells can be used to study physiological processes that occur during the pathogenesis of periodontitis, the complex host response fundamentally responsible for this disease cannot be reproduced in vitro. Among the animal kingdom, rodents, rabbits, pigs, dogs, and nonhuman primates have been used to model human periodontitis, each with advantages and disadvantages. Periodontitis commonly has been induced by placing a bacterial plaque retentive ligature in the gingival sulcus around the molar teeth. In addition, alveolar bone loss has been induced by inoculation or …

Medical Encounter Characteristics Of Hiv Seroconverters In The Us Army And Air Force, 2000–2004, Shilpa Hakre, David Brett-Major, Darrell E. Singer, Robert J. O'Connell, Warren B. Sateren, Jose L. Sanchez, Brian K. Agan, Nelson L. Michael, Paul T. Scott

Journal Articles: Epidemiology

BACKGROUND AND METHODS: Active duty US Army and Air Force military personnel undergo mandatory biennial HIV antibody screening. We compared pre- and post-HIV seroconversion health status by conducting a case-control study, which evaluated all medical encounters and sociodemographic factors among incident HIV seroconverters and HIV-negative controls from June 2000 through February 2004.

RESULTS: A total of 274 HIV seroconverters and 6205 HIV-negative personnel were included. In multivariate analysis restricted to male personnel (cases = 261, controls = 5801), single marital status (adjusted odds ratio [AOR] = 14.37), clinical indicators or symptoms within four years of HIV diagnosis (AOR = 6.22), …

The Cardiac Atlas Project--An Imaging Database For Computational Modeling And Statistical Atlases Of The Heart, Carissa G. Fonseca, Michael Backhaus, David A. Bluemke, Randall D. Britten, Jae Do Chung, Brett R. Cowan, Alan H. Kadish

Office of the President Publications and Research

MOTIVATION: Integrative mathematical and statistical models of cardiac anatomy and physiology can play a vital role in understanding cardiac disease phenotype and planning therapeutic strategies. However, the accuracy and predictive power of such models is dependent upon the breadth and depth of noninvasive imaging datasets. The Cardiac Atlas Project (CAP) has established a large-scale database of cardiac imaging examinations and associated clinical data in order to develop a shareable, web-accessible, structural and functional atlas of the normal and pathological heart for clinical, research and educational purposes. A goal of CAP is to facilitate collaborative statistical analysis of regional heart shape …

Capturing Changes In Gene Expression Dynamics By Gene Set Differential Coordination Analysis, Tianwei Yu, Yun Bai

PCOM Scholarly Works

Analyzing gene expression data at the gene set level greatly improves feature extraction and data interpretation. Currently most efforts in gene set analysis are focused on differential expression analysis - finding gene sets whose genes show first-order relationship with the clinical outcome. However the regulation of the biological system is complex, and much of the change in gene expression dynamics do not manifest in the form of differential expression. At the gene set level, capturing the change in expression dynamics is difficult due to the complexity and heterogeneity of the gene sets. Here we report a systematic approach to detect …

Improving Gene Expression Data Interpretation By Finding Latent Factors That Co-Regulate Gene Modules With Clinical Factors, Tianwei Yu, Yun Bai

PCOM Scholarly Works

Background: In the analysis of high-throughput data with a clinical outcome, researchers mostly focus on genes/proteins that show first-order relations with the clinical outcome. While this approach yields biomarkers and biological mechanisms that are easily interpretable, it may miss information that is important to the understanding of disease mechanism and/or treatment response. Here we test the hypothesis that unobserved factors can be mobilized by the living system to coordinate the response to the clinical factors.Results: We developed a computational method named Guided Latent Factor Discovery (GLFD) to identify hidden factors that act in combination with the observed clinical factors to …

Cardiac Dysfunction After Cancer Treatment, Michael S Ewer, Sandra M Swain, Daniela Cardinale, Anecita Fadol, Thomas M Suter

The Texas Heart Institute Journal

Onco-cardiology is an evolving discipline that requires the consideration of cardiotoxicity in preclinical, clinical,and therapeutic aspects of protocol development,treatment, and surveillance of patients who have undergone interventions using cardiotoxic agents. Only then can we foster new ways to maximize survival while keeping cardiac damage within acceptable limits. It is to this end that our working together has brought us to our present understanding. In the future, we may expect onco-cardiology to play an even greater role in the care of cancer patients.

Usefulness Of The Echocardiographic Multi-Parameter Score (Emps) In Evaluating Left Ventricular Global Heart Function, Bingyuan Zhou, Junhua Yang, Xiangjun Yang, Yongming He, Caiming Zhao, Sudan Xu, Huifeng Wang

The Texas Heart Institute Journal

In this study, we established a new index by combining several echocardiographic parameters to quantify heart failure. We selected 233 consecutive patients who underwent both echocardiographic and plasma B-type natriuretic peptide (BNP) tests within 24 hours after referral for suspected heart failure. The echocardiographic parameters included systolic function, diastolic function, left ventricular chamber remodeling, valvular lesions, systolic pulmonary arterial pressure, and regional wall-motion abnormality. Each factor was scored from 1 to 3 points according to its severity. The total point from these 6 factors is the echocardiographic multi-parameter score (EMPS).

The EMPS for 37, 51, 77, and 38 patients from …

Rosuvastatin Therapy Does Not Affect Serum Mmp-13 Or Timp-1 Levels In Hypercholesterolemic Patients, Cihan Cevik, Kenneth Nugent, Gary Meyerrose, Mohammad Otahbachi, Cemil Izgi, Mark Lyte, R David Fish

The Texas Heart Institute Journal

Matrix metalloproteinases degrade the collagen content of atherosclerotic plaque and reduce plaque stability. In tissue sections of atherosclerotic plaque, the expression of matrix metalloproteinases is increased. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) decrease the tissue expression of matrix metalloproteinases-1, -2, -3, and -9 in atheromatous plaque by attenuating the inflammatory process that leads to increased expression. However, it is not known whether statins decrease levels of matrix metalloproteinase-13—an enzyme crucial to the initiation of collagen degradation—as part of their plaque-stabilizing effect.

We prospectively examined the effect of statin therapy on serum levels of matrix metalloproteinase-13, tissue inhibitor of metalloproteinase-1, and …

Cd34-Positive Stem Cells In The Treatment Of Heart And Vascular Disease In Human Beings, Alexander R Mackie, Douglas W Losordo

The Texas Heart Institute Journal

Bone marrow-derived CD34(+) cells are a well-characterized population of stem cells that have traditionally been used clinically to reconstitute the hematopoietic system after radiation or chemotherapy. More recently, CD34(+) cells have also been shown to induce therapeutic angiogenesis in animal models of myocardial, peripheral, and cerebral ischemia. The mechanism by which CD34(+) cells promote therapeutic angiogenesis is not completely understood, although evidence supports both direct incorporation of the cells into the expanding vasculature and paracrine secretion of angiogenic growth factors that support the developing microvasculature. Phase I and phase II clinical trials have explored the usefulness of CD34(+) cells in …

Prehypertension: A Meta-Analysis Of The Epidemiology, Risk Factors, And Predictors Of Progression, Xiaofan Guo, Liling Zou, Xingang Zhang, Jue Li, Liqiang Zheng, Zhaoqing Sun, Jian Hu, Nathan D Wong, Yingxian Sun

The Texas Heart Institute Journal

We investigated the prevalence and risk factors of prehypertension, as well as the predictors of progression from prehypertension to hypertension. To do this, we performed a systematic review and meta-analysis of cross-sectional and longitudinal studies, after unrestricted searches of PubMed and The Cochrane Library through September 2010. In addition, we reviewed references, major textbooks, and review articles. Pooled prevalence, standardized mean differences, and odds ratios were estimated by using a random-effects model.

Twenty-six articles met our inclusion criteria; these included 20 cross-sectional and 6 longitudinal studies, with a total sample of 250,741 individuals. The overall pooled prevalence of prehypertension was …

Heart Disease And Hormones, Stephanie A Coulter

The Texas Heart Institute Journal

Results from more than 40 observational studies conducted in women over 3 decades have repeatedly indicated the cardioprotective effects of postmenopausal hormone replacement therapy (HRT). Women taking estrogen in these observational trials experienced a consistent 30% to 50% reduction in cardiovascular (CV) events. The biologic benefit of estrogen has been attributed to improvements in lipid profiles and endothelial function.

Mechanical Behavior Of Fully Expanded Commercially Available Endovascular Coronary Stents, Josip Tambaca, Suncica Canic, Mate Kosor, R David Fish, David Paniagua

The Texas Heart Institute Journal

The mechanical behavior of endovascular coronary stents influences their therapeutic efficacy. Through computational studies, researchers can analyze device performance and improve designs. We developed a 1-dimensional finite element method, net-based algorithm and used it to analyze the effects of radial loading and bending in commercially available stents. Our computational study included designs modeled on the Express, Cypher, Xience, and Palmaz stents.

We found that stents that did not fully expand were less rigid than the fully expanded stents and, therefore, exhibited larger displacement. Stents with an open-cell design, such as Express-like or Xience-like stents, had a higher bending flexibility. Stents …

Cardiac Surgery: A Century Of Progress, Allen B Weisse

The Texas Heart Institute Journal

Well into the first decades of the 20th century, medical opinion held that any surgical attempts to treat heart disease were not only misguided, but unethical. Despite such reservations, innovative surgeons showed that heart wounds could be successfully repaired. Then, extracardiac procedures were performed to correct patent ductus arteriosus, coarctation of the aorta, and tetralogy of Fallot. Direct surgery on the heart was accomplished with closed commissurotomy for mitral stenosis. The introduction of the heart-lung machine and cardiopulmonary bypass enabled the surgical treatment of other congenital and acquired heart diseases. Advances in aortic surgery paralleled these successes. The development of …

Tdp-43 Potentiates Alpha-Synuclein Toxicity To Dopaminergic Neurons In Transgenic Mice., Tian Tian, Cao Huang, Jianbin Tong, Ming Yang, Hongxia Zhou, Xugang Xia

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

TDP-43 and α-synuclein are two disease proteins involved in a wide range of neurodegenerative diseases. While TDP-43 proteinopathy is considered a pathologic hallmark of sporadic amyotrophic lateral sclerosis and frontotemporal lobe degeneration, α-synuclein is a major component of Lewy body characteristic of Parkinson's disease. Intriguingly, TDP-43 proteinopathy also coexists with Lewy body and with synucleinopathy in certain disease conditions. Here we reported the effects of TDP-43 on α-synuclein neurotoxicity in transgenic mice. Overexpression of mutant TDP-43 (M337V substitution) in mice caused early death in transgenic founders, but overexpression of normal TDP-43 only induced a moderate loss of cortical neurons in …

Mitochondrial Genome Sequence Analysis: A Custom Bioinformatics Pipeline Substantially Improves Affymetrix Mitochip V2.0 Call Rate And Accuracy., Hongbo M Xie, Juan C Perin, Theodore G Schurr, Matthew C Dulik, Sergey I Zhadanov, Joseph A Baur, Michael P King, Emily Place, Colleen Clarke, Michael Grauer, Jonathan Schug, Avni Santani, Anthony Albano, Cecilia Kim, Vincent Procaccio, Hakon Hakonarson, Xiaowu Gai, Marni J Falk

Department of Biochemistry and Molecular Biology Faculty Papers

BACKGROUND: Mitochondrial genome sequence analysis is critical to the diagnostic evaluation of mitochondrial disease. Existing methodologies differ widely in throughput, complexity, cost efficiency, and sensitivity of heteroplasmy detection. Affymetrix MitoChip v2.0, which uses a sequencing-by-genotyping technology, allows potentially accurate and high-throughput sequencing of the entire human mitochondrial genome to be completed in a cost-effective fashion. However, the relatively low call rate achieved using existing software tools has limited the wide adoption of this platform for either clinical or research applications. Here, we report the design and development of a custom bioinformatics software pipeline that achieves a much improved call rate …

Measuring The Symptom Burden Of Lung Cancer: The Validity And Utility Of The Lung Cancer Module Of The M D Anderson Symptom Inventory, Tito R Mendoza, Xin Shelley Wang, Charles Lu, Guadalupe R Palos, Zhongxing Liao, Gary M Mobley, Shitij Kapoor, Charles S Cleeland

Faculty, Staff and Student Publications

We conducted a study to establish the psychometric properties of a module of the M. D. Anderson Symptom Inventory (MDASI) developed specifically for patients with lung cancer (MDASI-LC). The MDASI measures 13 common "core" symptoms of cancer and its treatment. The MDASI-LC includes the 13 core MDASI symptom items and three lung cancer-specific items: coughing, constipation, and sore throat. MDASI-LC items were administered to three cohorts of patients with lung cancer undergoing either chemotherapy or chemoradiotherapy. Known-group validity and criterion (concurrent) validity of the MDASI-LC were evaluated using the Eastern Cooperative Oncology Group performance status and the 12-item Short-Form Health …

Association Of Retinoic Acid Receptor Genes With Meningomyelocele, Phong X Tran, Kit Sing Au, Alanna C Morrison, Jack M Fletcher, Kathryn K Ostermaier, Gayle H Tyerman, Hope Northrup

Faculty, Staff and Student Publications

BACKGROUND: Neural tube defects (NTDs) occur in as many as 0.5-2 per 1000 live births in the United States. One of the most common and severe neural tube defects is meningomyelocele (MM) resulting from failed closure of the caudal end of the neural tube. MM has been induced by retinoic acid teratogenicity in rodent models. We hypothesized that genetic variants influencing retinoic acid (RA) induction via retinoic acid receptors (RARs) may be associated with risk for MM.

METHODS: We analyzed 47 single nucleotide polymorphisms (SNPs) that span across the three retinoic acid receptor genes using the SNPlex genotyping platform. Our …

Autophagy In Antigen-Presenting Cells Results In Presentation Of Citrullinated Peptides To Cd4 T Cells, Jamie M. Ireland, Emil R. Unanue

Open Access Publications

Antibody responses to citrullinated self-proteins are found in autoimmunities, particularly in rheumatoid arthritis, where they serve as a diagnostic indicator. We show here that processing of the protein hen egg-white lysozyme (HEL) resulted in citrullination of peptides presented on class II MHC molecules by antigen-presenting cells. The presentation of the citrullinated peptides but not of the unmodified peptides was associated with autophagy. Dendritic cells (DCs), macrophages, and thymic DCs presented citrullinated peptides constitutively. Their treatment with 3-methyladenine (3MA) blocked presentation of citrullinated HEL peptides, but presentation of unmodified peptides was not affected. Presentation of citrullinated peptides was not detected on …

Barth Syndrome Mutations That Cause Tafazzin Complex Lability, Steven M. Claypool, Kevin Whited, Santi Srijumnong, Xianlin Han, Carla M. Koehler

Open Access Publications

Deficits in mitochondrial function result in many human diseases. The X-linked disease Barth syndrome (BTHS) is caused by mutations in the tafazzin gene TAZ1. Its product, Taz1p, participates in the metabolism of cardiolipin, the signature phospholipid of mitochondria. In this paper, a yeast BTHS mutant tafazzin panel is established, and 18 of the 21 tested BTHS missense mutations cannot functionally replace endogenous tafazzin. Four BTHS mutant tafazzins expressed at low levels are degraded by the intermembrane space AAA (i-AAA) protease, suggesting misfolding of the mutant polypeptides. Paradoxically, each of these mutant tafazzins assembles in normal protein complexes. Furthermore, in the …

Changes In Iron-Regulatory Gene Expression Occur In Human Cell Culture Models Of Parkinson's Disease., C. B. Carroll, M. L. Zeissler, N. Chadborn, K. Gibson, G. Williams, J. P. Zajicek, K. E. Morrison, C. O. Hanemann

Peninsula Medical School

BACKGROUND: Neuronal iron accumulation is thought to be relevant to the pathogenesis of Parkinson's disease (PD), although the mechanism remains elusive. We hypothesized that neuronal iron uptake may be stimulated by functional mitochondrial iron deficiency. OBJECTIVE: To determine firstly whether the mitochondrial toxin, 1-methyl-4-phenylpyridinium iodide (MPP(+)), results in upregulation of iron-import proteins and transporters of iron into the mitochondria, and secondly whether similar changes in expression are induced by toxins with different mechanisms of action. METHODS: We used quantitative PCR and Western blotting to investigate expression of the iron importers, divalent metal transporter, transferrin receptor 1 and 2 (TfR1 and …

Modeling The Development Of Pronunciation In Infant Speech Acquisition., Is Howard, P Messum

School of Engineering, Computing and Mathematics

Pronunciation is an important part of speech acquisition, but little attention has been given to the mechanism or mechanisms by which it develops. Speech sound qualities, for example, have just been assumed to develop by simple imitation. In most accounts this is then assumed to be by acoustic matching, with the infant comparing his output to that of his caregiver. There are theoretical and empirical problems with both of these assumptions, and we present a computational model- Elija-that does not learn to pronounce speech sounds this way. Elija starts by exploring the sound making capabilities of his vocal apparatus. Then …