Accessing the inner ear presents a significant challenge for the diagnosis and treatment of inner ear diseases. Many existing techniques to access the inner ear are invasive and can cause permanent damage to the cochlea. Recently, a novel microneedle has been fabricated to perforate the round window membrane (RWM) – a membrane sealing one of the two openings in the cochlea. These perforations enhance drug delivery into the inner ear, potentially improving the efficacy of therapeutics. Furthermore, they allow for the aspiration of perilymph samples, which is essential for diagnosing inner ear diseases. However, owing to limited knowledge about the mechanical properties of the RWM, certain technical aspects remain unexplored. Specifically, the interaction between the RWM and the microneedle during perforation is yet to be examined. This investigation is pivotal for the optimal design of microneedles — those robust enough to perforate RWMs yet delicate enough to minimize damage. In this thesis, we conduct a thorough examination of the guinea pig RWM, encompassing its geometry and its mechanical responses to pressures from the middle ear and inner ear. Additionally, we also formulate a comprehensive constitutive law for the guinea pig RWM. Our exploration begins with the creation of a U-Net model tailored to automatically segment the RWM. Despite the presence of other structures in the same image—such as bone, the basilar membrane, and ambient noise—the model proved invaluable for efficiently and automatically segmenting the RWM. To enhance accuracy, post-processing techniques like connected component analysis and majority voting were incorporated. Using this 3D model, we proceeded to study the RWM’s geometry. Recognizing the shrinkage observed in fixed RWMs, we integrated fresh RWM data to estimate the shrinkage ratio. Subsequently, we analyzed both the overall RWM thickness and that of the middle connective tissue layer—crucial metrics for future RWM modeling. Next, we proposed a method to evaluate the in-plane deformation of the RWM due to applied pressure. This involved using a bulge test system to pressurize and deform the RWM, combined with confocal microscopy to track stained nuclei or pre-introduced fluorescent beads on the RWM. We then utilized the coherent point drift (CPD) algorithm to measure the displacement of beads and nuclei. Results indicated that both markers could be successfully used to measure the RWM’s displacement. Further analysis revealed the in-plane Lagrangian strain of the RWM, with a significant observation being that the direction of maximum in-plane Lagrangian strain is perpendicular to the fiber direction. This underscores the crucial role of collagen fibers in determining the RWM’s mechanical properties. To conclude our study, we devised a constitutive law for the RWM, conceptualizing it as a combination of the ground substance and a family of dispersed fibers. This model was integrated into a FEBioStudio plugin, facilitating simulations of the RWM’s mechanical reactions to different pressures. Although our simulations closely aligned with experimental findings, some discrepancies were noted, likely stemming from an incomplete understanding of fiber dispersions. Nevertheless, our constitutive law reinforces the notion that fibers primarily govern the RWM’s mechanical characteristics.

Inner ear hair cells have been identified as the sites of mechanoelectrical transduction from a mechanical event (e.g. hearing, motion) to an electrical event (e.g. neural response). Deflection of bundles of hair-like stereocilia extending from these cells has been associated with the transduction process. Stereocilia bundle structure and stiffness controls deflection and thus the fundamental sensitivity of the transduction process. The finite-element method was used along with analytical techniques to characterize individual stereocilium and stereocilia bundle stiffnesses. A three ‘stack’ bundle with a Young’s modulus of 3 GPa (F-actin protein) and Poisson’s ratio of 0.4 (nearly incompressible) resulted in a stiffness of K = 2.1 x 10⁻³ N/m. This value is within the range of experimentally determined stiffmesses. Tip-link and subapical band interconnecting structures each contribute significantly to bundle stiffness and each could act as the gating-spring in transduction models, which propose gating structures as a means of regulating ionic activity and therefore neural activity. Stiffness depends most strongly on individual stereocilium geometry and material description, tip-link orientation and material description, and stereocilia bundle width. Stiffness depends least on stereocilia height variations and subapical bands configuration. Linear analysis was reliable up to deflections of 3.5 um, the upper limit of physical response. Preliminary dynamic response indicates a natural frequency of 382 kHz for the vibration mode resembling physical deformation behavior. Future models should include hexagonal bundle arrangements, transversely isotropic stereocilia material descriptions, and viscoelastic tip-link behavior. / Master of Science

京都大学 / 新制・課程博士 / 博士(医学) / 甲第25494号 / 医博第5094号 / 新制||医||1073(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 藤田 恭之, 教授 羽賀 博典, 教授 妹尾 浩 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

For people with hearing impairments, attending to a single speaker in a multi-talker background can be very difficult and something which the current hearing aids can barely help with. Recent studies have shown that the audio stream a human focuses on can be found among the surrounding audio streams, using EEG and linear models. With this rises the possibility of using EEG to unconsciously control future hearing aids such that the attuned sounds get enhanced, while the rest are damped. For such hearing aids to be useful for every day usage it better be using something other than a motion sensitive, precisely placed EEG cap. This could possibly be archived by placing the electrodes together with the hearing aid in the ear. One of the leading hearing aid manufacturer Oticon and its research lab Erikholm Research Center have recorded an EEG data set of people listening to sentences and in which electrodes were placed in and closely around the ears. We have analyzed the data set by applying a range of signal processing approaches, mainly in the context of audio estimation from EEG. Two different types of linear sparse models based on L1-regularized least squares are formulated and evaluated, providing automatic dimensionality reduction in that they significantly reduce the number of channels needed. The first model is based on linear combinations of spectrograms and the second is based on linear temporal filtering. We have investigated the usefulness of the in-ear electrodes and found some positive indications. All models explored consider the in-ear electrodes to be the most important, or among the more important, of the 128 electrodes in the EEG cap.This could be a positive indication of the future possibility of using only electrodes in the ears for future hearing aids.

Thesis (M.Sc.)--University of Stellenbosch, 2005. / ENGLISH ABSTRACT: Current technological development has a strong impact on education. Students normally have free access to computers and the internet. Computer-based instruction is more frequently available in classrooms and reinforces the traditional educational systems. The purpose of this study was to determine whether a computer-based program, Auralia 2.1, can be used effectively in the Music Certificate Course of the University Stellenbosch. Due to limited time during lessons as well as time-constraints for individual practising by the students, the researcher investigated the efficacy of Auralia 2.1 for use in the classroom. Students are able to practise individually during lessons as well as on their own. The problem to find a peer to practise aural training is therefore avoided as the computer fulfills this function. The researcher administered Auralia 2.1 on a group of eight Certificate students from the University Stellenbosch. The evaluation period consisted of two semesters of fourteen weeks each. The researcher used the traditional method of aural training in the first semester and she used Auralia 2.1-sessions in the second semester. The researcher compared the two semesters to each other to ensure the integrity of the results of the research. The researcher systematically held record of observations as well as the progress of the students. Questionnaires were completed and interviews were held as part of the evaluation process. Suggestions are made in this thesis on how Auralia 2.1 can be used effectively for educational aims. / AFRIKAANSE OPSOMMING: Die hedendaagse ontwikkeling in tegnologie het ‘n sterk invloed op opvoeding. Studente het oor die algemeen vrye toegang tot rekenaars en die internet. Rekenaargesteunde onderrig kom toenemend in klaskamers voor en word ter versterking van die tradisionele onderwysstelsel gebruik. Die doelstelling van hierdie navorsing was om te bepaal of ‘n rekenaargesteunde onderrigprogram, naamlik Auralia 2.1, effektief benut kan word in die musiekoorbruggingsprogram (Sertifikaatkursus) van die Universiteit Stellenbosch. Weens beperkte klastyd en ‘n gebrek by Sertifikaatstudente aan noodsaaklike tyd vir gehooropleidingsoefeninge, het die navorser ondersoek ingestel na die effektiwiteit van Auralia 2.1, vir gebruik in die klas. Die studente kon met behulp van die rekenaar individueel tydens asook buite klastyd oefen. Probleme om ‘n “oefenmaat” vir gehoor te vind is dus uitgeskakel aangesien die rekenaar daardie funksie vervul het. Die navorser het die program Auralia 2.1 op ‘n groep van agt Sertifikaatstudente van die Universiteit Stellenbosch toegepas. Die evaluering het oor twee semesters van veertien weke elk gestrek. Die navorser het in die eerste semester ‘n tradisionele metode van gehooropleiding gevolg en in die tweede semester het sy gebruik gemaak van Auralia 2.1-sessies. Die navorser het die twee semesters met mekaar vergelyk om sodoende die integriteit van die navorsingsresultate te verseker. Daar is tydens die navorser se studie sistematies verslag van die waarnemings en die studente se vordering gehou. Vraelyste is voltooi en onderhoude gevoer as deel van die evalueringsproses. In hierdie tesis word daar ook voorstelle gemaak oor hoe Auralia 2.1 effektief gebruik kan word vir opvoedkundige doeleindes.

Opus cui titulus est "Carthago Indiarum obsessa sed non expugnata" est carmen divulgatum sine nomine auctoris saeculo duodevicesimo ad celebrandam vic- toriam quam Hispani a Britannis Carthagenae Indiarum anno 1741 in bello auris illius Ienkins (vulgo, the War of Jenkins’ Ear) reportaverunt. In hac thesi tractantur modo satis compendiario res gestae huius proelii quo melius lectores carmen ipsum possint intellegere. Necnon hic inveniuntur ea quae spectant ad huius opusculi genus, indolem et momentum litterarium. Postremo, praebetur hic editio critica, paraphra- sis Latina, commentarius in hoc carmen scriptus. Ex hoc carmine potest conspici quomodo litterarum Latinarum patrimonium pertineat ad omnes aetates, ad omnes gentes, ad omnes patrias. The work Carthago Indiarum obsessa, sed non expugnata ("Cartagena de Indias, Assailed but not Captured") is an eighteenth century anonymous poem that celebrates the Spanish victory over the English at Cartagena de Indias during the War of Jenkins’ Ear in 1741. This thesis presents a summary of the battle in order to contextualize the significance of the poem. It further presents a literary analysis of the poem’s genre, characteristics, and literary importance, as well as a critical edi-tion, a paraphrase in Latin prose, and a commentary. From analyzing this poem, one can see some ways in which the Latin literary patrimony brought from the ancients pertains to all ages, peoples, and nations.

published_or_final_version / abstract / Biochemistry / Doctoral / Doctor of Philosophy

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

The morphological diversity of the external and internal surfaces of the petrosal bone, which contains the structures of the inner ear, across a broad range of therian mammals is documented, and patterns of variation across taxa are identified. One pattern of variation is the result of ontogenetic changes in the ear region, as described for the external surface morphology of a sample of isolated petrosal bones referred to Proboscidea from Pleistocene deposits in central Texas. The morphology of the aquaeductus Fallopii for passage of the greater petrosal branch of the facial nerve supports an ontogenetic explanation for some variation within the proboscidean sample, and a sequence of ossification surrounding the aquaeductus Fallopii is hypothesized. Further ontogenetic patterns are investigated using digital endocasts of the bony labyrinth (preserved on the internal surfaces of the petrosal) constructed from CT data across a growth series of the opossum Monodelphis domestica. Strong correlation between skull length and age is found, but from 27 days after birth onward, there is no correlation with age among most dimensions of the inner ear. Adult dimensions of several of the inner ear structures are achieved before the inner ear is functional in M. domestica. Morphological variation within the inner ear of several eutherian mammals from the Cretaceous of Asia, including zhelestids from the Bissekty Formation of Uzbekistan, is described. The variation within the fossil sample is compared to that observed within extant species of placental mammals, and it is determined that the amount of variation within the Bissekty zhelestid population is within the range of that measured for extant species. Additional evolutionary and physiological patterns preserved within the walls of the bony labyrinth are identified through a high level anatomical comparison of the inner ear cavities across Placentalia as a whole. In particular, features of the inner ear support monophyly of Cetacea, Carnivora, Primatomorpha, and caviomorph Rodentia. The volumetric percentage of the vestibular apparatus (vestibule plus semicircular canals) of aquatic mammals is smaller than that calculated for terrestrial relatives of comparable body size. Thus, aspects of the bony labyrinth are both phylogenetically and physiologically informative. / text

I det här arbetet har jag undersökt hur fiollärare med förankring i folkmusiken undervisar samt vilka eventuella områden som de lägger vikt vid och varför. Jag valde att göra en kvalitativ intervju med fem informanter. Mitt mål var att välja fiollärare med utbildning från musikhögskola, men för övrigt med så varierande bakgrund som möjligt. Jag har ställt intervjusvaren mot några klassiska fiolmetoder. Jag har inte kommit fram till några nya perspektiv eller infallsvinklar i folkmusikundervisningen. Jag ser istället likheter mellan informanternas undervisning och de klassiska metoderna. Momentens syfte kan dock variera. I folkmusikundervisningen används gehörsundervisning i alla åldrar. Informanterna tycker det är viktigt att eleverna tycker det är kul att spela fiol och musicera och att man lättare når fram till musicerandet om man utgå från gehöret. / In this study, I will examine how violin teachers with roots in folk music teach, and if there are any areas which they prioritize and why. I chose to make a qualitative interview with five interviewees. My goal was to choose violin teachers who had studied at a colleges of music, but also with as varied a background as possible. I have set interview responses against some classical violin methods. I have not reached any new perspective or angles in folk music teaching. Instead, I see similarities between the interviewees’ teaching and the classical methods. The aim for the methods may vary. In folk music, ear training is used among all ages. The interviewees think it is important that students enjoy playing the violin and to make music. It is easier to understand and grasp the music if you begin with ear training.