The inner ear is a complex sensory organ of interconnected chambers, each with a sensory epithelium comprised of hair cells and support cells for detection of sound and motion. This dissertation focuses on the development and regulation of sensory epithelia in zebrafish and utilizes loss of function, gain of function and laser ablation techniques. Hair cells and support cells develop from an equivalence group specified by proneural genes encoding bHLH transcription factors. The vertebrate Atoh1 bHLH transciption factor is a potential candidate for this role. However, data in mouse has led some researchers to conclude it does not have a proneural activity, but, rather, is involved in later stages of hair cell differentiation. In addition, the factors regulating Atoh1 are mostly unknown. We address these issues in zebrafish and show that the zebrafish homologs atoh1a and atoh1b are required during two developmental phases, first in the preotic placode and later in the otic vesicle. They interact with the Notch pathway and are necessary and sufficient for specification of sensory epithelia. Our data confirm atoh1 genes have proneural function. We also go on to show Atoh1 works in a complex network of factors, Pax2/5/8, Sox2, Fgf and Notch. Misexpression of atoh1 alters axial patterning and leads to expanded sensory epithelia, which is enhanced by misexpression of either fgf8 or sox2. Lastly, we examine the role of sox2 in sensory epithelia development and regeneration. Sox2 has been implicated in maintainence of pluripotent stem cells as well as cell differentiation. In the inner ear, Sox2 is initially expressed in the prosensory domain and is required for its formation. Eventually, Sox2 is downregulated in hair cells and maintained in support cells; however, its later role has not been determined. We show that in the zebrafish inner ear, sox2 is expressed after sensory epithelium development has begun and, like in mouse, expression is down regulated in hair cells and maintained in support cells. Our data demonstrate a role for sox2 in maintenance of hair cells and in transdifferentation of support cells into hair cells after laser ablation. Additionally, sox2 is regulated by Aoth1a/1b, Fgf, and Notch.

Vertebrates have evolved a unique way to sense their environment: placodallyderived sense organs. These sensory structures emerge from a crescent-shaped domain, the preplacodal domain, which surrounds the anterior neural plate and generates the paired sense organs as well as the cranial ganglia. For decades, embryologists have attempted to determine the tissue interactions required for induction of various placodal tissues. More recently, technological advances have allowed investigators to ask probing questions about the molecular nature of placodal development. In this dissertation I largely focus on development of the otic placode. I utilize loss-of-function techniques available in the zebrafish model system to demonstrate that two members of the fibroblast growth factors family of secreted ligands, Fgf3 and Fgf8, are redundantly required for otic placode induction. I go on to show that these factors are expressed in periotic tissues from the beginning of gastrulation. These findings are consistent with a model where Fgf3 and Fgf8 signal to preotic tissue to induce otic-specific gene expression. This model does not address other potential inducers in otic induction. A study using chick explant cultures suggests that a member of the Wnt family of secreted ligands also has a role in otic induction. I therefore test the relative roles of Wnt and Fgf in otic placode induction. The results demonstrate that Wnt functions primarily to correctly position the Fgf expression domain and that it is these Fgf factors which are directly received by future otic cells. Lastly, I examine the function of the muscle segment homeobox (msx) gene family expressed in the preplacodal domain. This study demonstrates that Msx proteins refine the boundary between the preplacodal domain and the neural plate. Further, msx genes function in the differentiation and survival of posterior placodal tissues (including the otic field), neural crest and dorsal neural cell types. Loss of Msx function results in precocious cell death and morphogenesis defects which may reflect perturbed BMP signaling.

Historically, the collared peccary (Tayassu tajacu) occurred throughout much of Texas including the northern portion of the Texas Hill Country. Remaining peccary populations were extirpated in much of their former range due to over harvest and habitat loss. In 2004, efforts to restore peccary populations to the Texas Hill Country began when Texas Parks and Wildlife Department biologists translocated 29 collared peccaries into the 2,157 ha, Mason Mountain Wildlife Management Area (MMWMA). I evaluated the success of peccary translocations for mixed and intact family groups by comparing survival, ranges, and dispersal of translocated, radio-tagged peccaries. In addition, I evaluated two release methods (soft versus hard) to determine differences in population demographics. I found that peccary ranges and dispersal patterns did not differ (P > 0.05) between intact and mixed groups or release method (soft versus hard). However, I did find that peccary fidelity to release sites was greater for soft releases of family groups. Individuals from the soft release group dispersed the shortest distance and stayed on MMWMA. Only 2 individuals from the hard releases stayed on MMWMA while the rest (19 individuals) dispersed 4-8 km. Future peccary translocations should emphasize the release method employed and family structure of individuals released to improve translocation effectiveness in establishing populations in target areas.

In 2000 and 2001,The Financial Institution Merger Act and Financial Holding Act were legislated in Taiwan. There are 15 financial holding companies established till now. Financial holding companies hope to diversify financial commodities to investors through joint-marketing and gain cost-saving and risk-control and improve financial performance. It expects to pursue and promote broad business scope. Cathay Financial Holding company, one of the financial holding companies, is the biggest financial holding company except the Taiwan Financial Holding company. Cathay Financial Holding company has total assets exceeding NTD 3.68 trillion. The subsidiaries of Cathay Financial Holding company include Cathay Life Insurance, Cathay United Bank, Cathay Century Insurance, Cathay Securities, and Cathay Venture Capital. The financial performance of subsidiaries of financial holding company becomes more sensitive due to competition of financial liberalization and macroeconomic variables changed. The research not only uses a multiple-regression model and reported here was trying to examine the macroeconomic variables that determine the financial performance of subsidiaries of Cathay Financial Holding company, but also uses a managing capital method EAR to discuss the risk-control of Cathay Financial Holding company. Keywords : Financial Holding company, financial performance, macroeconomic variables, managing capital, EAR

Engineers and physicians alike are impressed by the micromechanics of the human hearing organ with its broad dynamic range. Sound waves which pass the external ear are transformed into mechanical vibrations in the middle ear and than transferred to the inner ear fluid. The vibrations of the inner ear structures lead to an evoked nerve potential which stimulates the hearing areas in the brain. Nowadays, vibration patterns in the nanometre range are detectable in the smallest middle and inner ear structures by laser Doppler vibrometry measurements. This paper demonstrates how multidisciplinary research at the Technische Universität Dresden has furthered knowledge of the mechanical dynamic processes in the hearing organ. The results influence also clinical investigations concerning new middle and inner ear implants. / Das menschliche Hörorgan ist für Mediziner und Ingenieure gleichermaßen ein mikromechanisches Wunderwerk mit großem Dynamikbereich. Schallwellen werden vom äußeren Ohr aufgenommen, im Mittelohr in mechanische Schwingungen umgewandelt und an das flüssigkeitsgefüllte Innenohr weitergeleitet. Erst dort erfolgt die Umwandlung der Schwingungsprozesse in ein elektrisches Signal, welches mehrfach verarbeitet an das Gehirn weitergeleitet wird. In den letzten Jahren ist es gelungen, Schwingformen des Mittel- und Innenohres im Nanometerbereich nach akustischer Anregung sichtbar zu machen. Als entscheidendes Messinstrument ist dabei das Laser-Doppler- Vibrometer zum Einsatz gekommen. Die vorliegende Arbeit zeigt beispielhaft, wie sich anhand dieser an der TU Dresden interdisziplinär durchgeführten Untersuchungen das bisherige Bild von den mechanischen Vorgängen des Ohres verändert hat und wie diese Erkenntnisse direkt in die klinische Medizin und Implantatentwicklung übernommen werden konnten.

Sox10 is a high mobility group (HMG) domain transcription factor which is an important regulator for neural crest development. SOX10 mutations have been identified in Waardenburg-Shah syndrome type 4 (WS4) patients who suffer from sensorineural deafness. However, the mechanisms underlying the hearing defect of SOX10-mediated WS4 are unclear. The aim of this study is to elucidate the function of Sox10 during mouse inner ear development using a mutant mouse model, in order to reveal the underlying basis for SOX10 mutation associated sensorineural deafness in WS4 patients. The mammalian inner ear originates from the otic placode epithelium as well as neural crest cells (NCCs). To understand the role of Sox10 in inner development, I investigated the contribution of cranial NCCs to the cochleovestibular ganglion (CVG) by lineage tracing analysis, using Wnt1-cre;ZEG mice in which all NCCs were marked by GFP. Co-expression of GFP-positive cells with the glial marker BFABP suggested that glial cells in the CVG were derived from NCCs. Furthermore, Sox10-expressing NCCs were found to invade the CVG at 30-somite stage. These results suggest a role of Sox10 in regulating cranial NCCs contribution to CVG glia. In our laboratory we have generated a mouse mutant Sox10EGFP in which the Sox10 N-terminal domain was fused to the EGFP reporter. To investigate the function of Sox10 in NCCs invasion and gliogenesis of CVG, phenotypic analysis of Sox10NGFP mutant mouse were performed. EGFP expression in the CVG and inner ear epithelium of Sox10NGFP/+ embryos recapitulated the dynamic expression pattern of Sox10. Sox10NGFP/NGFP mutants displayed a reduced number of migrating NCCs and lacked NCCs or glia in their CVG. Moreover, loss of glial cell in the developing spiral ganglia of Sox10NGFP/NGFP mice led to disorganized fasciculation and degeneration of axonal filaments. These data suggest that Sox10 is required for maintaining the cranial NC stem cell pool, and is also essential for CVG gliogenesis and normal growth and innervation of spiral ganglion neurons. To study the function of Sox10 in regulating cochlear morphogenesis, morphological and histological analysis of mutant cochlear were performed. As illustrated by paint-filling analysis, Sox10NGFP/NGFP mice developed a shortened cochlear duct, reduced cochlear turning and enlarged endolymph lumen. Sensory hair cell patterning in the organ of Corti was normal in the Sox10 mutant as shown by immunohistochemistry analysis, suggesting that cochlear lumen enlargement was not due to disrupted planar cell polarity (PCP) pathway. To explore the molecular basis of Sox10-mediated cochlear morphogenic defect, expression of genes related to cochlear development were examined by qRT-PCR. Candidate genes included those involved in fluid homeostasis, which are known to affect the size of cochlear lumen. Up-regulated expression of Aquaporin 3, a water channel protein in the cochlear epithelium that facilitates water transport across the cell membrane, was observed in Sox10NGFP/NGFP cochlear. These results suggest that Sox10 may regulate cochlear morphogenesis by controlling endolymph homeostasis. In conclusion, Sox10 is required in multiple processes during inner ear development including NCC invasion, gliogenesis and cochlear morphogenesis, and their abnormal development can lead to sensorineural deafness in WS4 syndrome. / published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

Ecological momentary assessment provides a unique way of studying quality of life factors of colorectal cancer patients. It has yet to be used to study the behavioral expression of distress or depression by colorectal cancer patients. The current study utilized the Electronically Activated Recorder (EAR) technology to capture the daily activities and conversations of forty-eight adults with colorectal cancer. The study had two purposes: 1) to test the feasibility of the EAR with colorectal cancer patients; 2) to examine separate (self-report and behavioral) indicators of physical functioning, coping, and social support for their relationship to depression. Study participants wore the EAR, a portable digital recorder, for two consecutive days as the EAR recorded 30 seconds every 12.5 minutes. The EAR digital data were transcribed and analyzed for behavioral and linguistic indicators of physical functioning, coping, and social support. The acoustic data were analyzed using the standardized coding system Social Environment Coding of Sound Inventory (SECSI) and the Linguistic Inquiry and Word Count (LIWC2007) computer program. The results provided preliminary evidence that the EAR operated as a feasible and non-disruptive tool for gathering naturalistic data about colorectal patients’ lives. The EAR data revealed information about both the colorectal patients’ internal emotional world as well as their external world which was characterized by solitary acts of daily living. Study subjects were more likely to accept and receive tangible support from others than directly discuss their cancer with others. Analysis of language found that personal disclosure to others was associated with coping through emotional support while causation words (e.g., because, effect, hence) were significantly related with self-report cognitive scales. Furthermore, the study found that first-person singular pronouns were associated not only with depression, but with appraisal of social support. Lastly, a predictive model was tested to see whether self-reported tangible and emotional support and behavioral coding of emotional support each contributed uniquely to the prediction of depression. Only self-reported tangible support was found to significantly predict depression. / text

published_or_final_version / Surgery / Master / Master of Surgery

published_or_final_version / abstract / toc / Speech and Hearing Sciences / Master / Master of Science in Audiology

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