The main theme of the thesis is to examine the influence of alcohol on the speech apparatus and speech signal. The first part is focused on symptoms and detection of alcohol concentration in the human body. The following part describes somescientific publications and projects, which dealt witha a similar theme. Also the czech documentation to german database ALC was created. Based on phonetic knowledge, Czech text was compiled. Different speakers were reading this text so we go tour own database of alcoholic and sober speech. Samples from individual speakers are processed using linear prediction, formant and cepstral analysis in MATLAB and the effect of alcohol on selected parameters of speech signal is evaluated.

No description available.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has received more attention in recent years as a treatment option for regulating the symptoms of Parkinson's disease. Previous studies of DBS documented consistent improvements in motor function but more variability in speech outcomes. In the present study, six participants diagnosed with idiopathic Parkinson's disease who reported worsened speech with stimulation were recorded performing speech acoustic tasks with the stimulators on, and again with the stimulators off. Improvements were noted for most participants in measurements of formant slopes, long term average spectrum (LTAS) of a sustained vowel, and spirantization with stimulation on. Stimulation negatively affected most participants' vowel space area, verbal fluency, sequential motion rate, and LTAS while reading and describing a picture. Measures of stop gap duration, alternating motion rate, and voice onset time were within normal limits for most participants across both stimulation conditions.

本論文為以共振峰頻率資料來研究台灣華語母音音質之聲學研究。 本研究的受試者為六名生長在台灣台北市的男性華語母語使用者。本研究使用的測試字為70個包含所有韻母型態的單音節字。語音資料是利用KAY CSL 4100 (KAY Electronics)來錄製及分析。本研究所採用的資料為獨立發音且無聲母的測試字。 根據共振峰頻率資料本研究得到以下有關台灣華語母音音質的發現。首先研究的部分為音標所隱含的語音對比。在齒槽（alveolar）及後齒槽（post-alveolar）組的舌尖母音（apical vowels）間並沒有發現音質上的顯著差別，但統計及其它證據支持低母音裡的前後對比及中母音裡的半開（open-mid）及半閉（closed-mid）對比的存在。 其次，研究的結果也包括語音環境中的音段對於母音音質的影響。結果發現韻母中的元素，包含母音前介音、母音後介音、及韻尾鼻音，都對母音有不同的語音制約（conditioning）。另外，本研究發現順同化（progressive assimilation）比逆同化（regressive assimilation）對於低母音音質有較大的影響。 第三，本研究藉由與之前聲學研究的結果作比較來討論台灣母音音質的改變。結果發現硬顎及後硬顎組的舌尖母音間的音質差異隨著時間縮小終至於消失。此外，研究發現半閉母音及半開母音在母音高度及母音前後相對位置出現反轉。共振峰頻率的比較顯示這種反轉的原因為半閉母音[e]在音質上的改變。然而，我們需要進一步的研究才能對這些音質的改變有合理的解釋。 最後，本研究以共振峰頻率的形式描述及紀錄了當代台灣華語表層母音的音質。希望這些資料能對台灣華語母音的研究有所貢獻。 / This thesis is an acoustic study that investigates the vowel quality of Taiwan Mandarin vowels with formant frequency data. The subjects of this study included six male native Mandarin speakers born and raised in Taipei city, Taiwan. Testing items used in this study were 70 syllables that involve all combinations of segment in the syllable final. The speech data were recorded and analyzed with KAY CSL 4100 (KAY Electronics). The data discussed in this study were testing items produced in citation form without initial consonant. The vowel qualities of Taiwan Mandarin surface vowel were measured and analyzed. Several results concerning the vowel quality of Taiwan Mandarin surface vowel phones were reported based on the formant frequency data. Firstly, the distinction between vowel phones implied by their transcription was examined. The difference in vowel quality was not observed in the alveolar and post-alveolar groups of apical vowels, while the front-back distinction in low vowels and the open-mid and closed-mid distinction in mid vowels were found with statistic and other evidence. Secondly, the conditioning of segments in the neighboring environments on the vowel quality was investigated. It is found that elements in the syllable final, including pre-nuclear, post-nuclear glide and coda nasals, generally have different types of conditioning on the vowel. In addition, the progressive assimilation was found have greater influence on the vowel quality of low vowel phones than the regressive assimilation. Thirdly, the change in vowel quality was discussed through the comparison with results in previous acoustic studies. The difference in vowel backness between the alveolar and post-alveolar groups of apical vowels were found to be decreasing and eventually disappeared. Besides, the relative vowel height and backness of closed-mid and open-mid vowel were found to be in reverse compared with that in the literature. Comparison in formant frequencies showed that this reverse lay in the change of vowel quality in the close-mid [e]. However, further investigations were needed to offer reasonable explanations for the change. Finally, the vowel qualities of present Taiwan Mandarin surface vowel phones were described and recorded as the formant frequency data presented in this study. Hopefully, the data could contribute to the study of vowels in Taiwan Mandarin.

De nouvelles sondes oligonucléotidiques fluorescentes spécifiques des structures d'acides nucléiques en double brin ont été obtenues. Ces oligonucléotides formant des triples hélices, sont liés par leurs extrémités 5'-ou/et 3' à une série de marqueurs fluorescents de la famille des cyanines monométhines possédant des propriétés intercalantes, par des bras polyméthylène de longueur variable. Dans tous les cas, l'hybridation des sondes avec les cibles en double brin s'accompagne d'une forte augmentation de l'intensité du signal fluorescent émis qui dépend de la structure de la cyanine et des paramètres de sa liaison aux oligonucléotides (longueur du bras de liaison et sa position de fixation sur les oligonucléotides et sur les marqueurs). En présence d'une cible simple brin, les modifications du signal ne sont pas significatives. La présence du marqueur stabilise les triples hélices. Les sondes comportant le thiazole orange, attaché par le noyau benzothiazole via un bras de liaison à huit méthylènes, présente le meilleur compromis en termes de stabilisation, d'intensité de fluorescence et d'augmentation d'intensité de fluorescence lors de l'hybridation.<br />Dans le but d'obtenir de nouvelles sondes utilisables en milieu cellulaire et in vivo, de nouveaux marqueurs fluorescents de type squaraine ont été synthétisés et couplés pour la première fois, à notre connaissance, à des oligonucléotides. Les conjugués correspondant émettent un signal fluorescent détectable au-delà de 650 nm et possèdent des rendements quantiques de fluorescence élevés. La photostabilité des marqueurs et des conjugués, en milieu acide faible et à 37 °C a été fortement augmentée après incorporation d'atomes de fluor sur le squaraine.

During musical performance and recording, there are a variety of techniques and electronic effects available to transform the singing voice. The particular effect examined in this dissertation is breathiness, where artificial noise is added to a voice to simulate aspiration noise. The typical problem with this effect is that artificial noise does not effectively blend into voices that exhibit high vocal effort. The existing breathy effect does not reduce the perceived effort; breathy voices exhibit low effort. A typical approach to synthesizing breathiness is to separate the voice into a filter representing the vocal tract and a source representing the excitation of the vocal folds. Artificial noise is added to the source to simulate aspiration noise. The modified source is then fed through the vocal tract filter to synthesize a new voice. The resulting voice sounds like the original voice plus noise. Listening experiments were carried out. These listening experiments demonstrated that constant pre-emphasis linear prediction (LP) results in an estimated vocal tract filter that retains the perception of vocal effort. It was hypothesized that reducing the perception of vocal effort in the estimated vocal tract filter may improve the breathy effect. This dissertation presents adaptive pre-emphasis LP (APLP) as a technique to more appropriately model the spectral envelope of the voice. The APLP algorithm results in a more consistent vocal tract filter and an estimated voice source that varies more appropriately with changes in vocal effort. This dissertation describes how APLP estimates a spectral emphasis filter that can transform the spectral envelope of the voice, thereby reducing the perception of vocal effort. A listening experiment was carried out to determine whether APLP is able to transform high effort voices into breathy voices more effectively than constant pre-emphasis LP. The experiment demonstrates that APLP is able to reduce the perceived effort in the voice. In addition, the voices transformed using APLP sound less artificial than the same voices transformed using constant pre-emphasis LP. This indicates that APLP is able to more effectively transform high-effort voices into breathy voices.

本論文為以共振峰頻率資料來研究海陸腔客語母音音質之聲學研究。 語言學的文獻中，以共振峰頻率資料來研究世界上各種語言的母音的音質已經有相當豐富的文獻，在過去五十年來，前人在客語的語音及音韻系統上已經有豐富的研究成果。但以聲學資料來對海陸客語做描述的文獻相當缺乏。 本研究的受試者為居住在新竹縣新埔鎮，六位以海陸腔客家話為母語的人士，其中有三名男性及三名女性。本研究使用了32個測試字，包含了單元音、雙合元音及三合元音。語音資料是利用KAY CSL 4100 (KAY Electronics)來做分析。本研究測試字包含的音節結構有:CV, CVV, CVVC, CVC, 以及CVVV。測試字在實驗的過程中，被受試者單獨發音，或是放在句子中間。在實驗資料完成分析後，我們以Origin 6.0軟體繪出海陸腔客語母音的聲學空間圖。 根據供振峰研究資料，本研究得到以下有關海陸腔客語母音音質的表現。首先關於單元音，海陸腔客語共有六個單元音: [i], [e], [ɨ], [a], [o], 以及 [u]。其次，海陸腔客語共有十一個雙元音: [ie], [ia], [io], [iu], [eu], [ai], [au], [oi], [ui], [ue], 以及 [ua]。我們比較單元音及雙元音的聲學空間圖(vowel space)後，發現相同的母音在雙母音的環境下，由於受到鄰近母音發音位置的影響，在聲學空間上，比起在單母音的時候，變的更高低，或更前或後。第三，三母音[iai], [iau]和[uai]在聲譜圖上的表現，第一個母音[i]和[u]都比其後的兩個母音，長度來的相對的短一些，表現很像是滑音[j]和[w]。 最後，本研究以共振峰聲學頻率的形式描述及記錄了當代海陸腔客語母音的音質，前人的研究中，以楊時逢(1952)最能說明本研究所提供的聲學資料。希望這些資料能對海陸腔客語母音的研究有所貢獻。 / This thesis is an acoustic study that investigates the vowel quality of Hai-lu Hakka vowels with formant frequency data. The acoustic method has been widely applied to the study of vowel quality of languages worldwide. In the past 50 years, Hakka researchers have yielded rich results in phonological system and phonetic description of Hakka, but there are relatively fewer research focus on the acoustic properties and characteristics of vowel phones in Hai-lu Hakka. The subjects of this study included three male and three female native Hai-lu Hakka speakers. Testing items used in this study were 32 syllables that involve monophthongs, diphthongs, and triphthongs. The speech data were analyzed by using KAY CSL 4100 (KAY Electronics). The data discussed in this study were testing items produced in citation form and sentence form, including the following syllable structures: CV, CVC, CVV, CVVC, and CVVV. The vowel qualities of Hai-lu Hakka vowels were measured and analyzed, and the acoustic vowel space of Hai-lu Hakka is plotted by the software Origin 6.0. Several results concerning the vowel quality of Hai-lu Hakka vowels were reported based on the formant frequency data. Firstly, there are six monophthongs in the vowel system of Hailu Hakka: [i], [e], [ɨ], [a], [o], and [u]. Secondly, there are eleven diphthongs in the vowel system of Hai-lu Hakka : [ie], [ia], [io], [iu], [eu], [ai], [au], [oi], [ui], [ue], and [ua]. By comparing the relative position of the vowel in a diphthong and the corresponding vowel as in a monophthong, we found that the second vowel in a diphthong tend to be higher or lower, more fontal or back, and it is possibly due to the coarticulatory influence of the adjacent phones.the Thirdly, as shown in the spectrogram of the three tripthongs [iai], [iau] and [uai], the duration of [i] in [iai55], [i] in [tʰiau55] and [u] in [kuai55] are relatively shorter than the rest two vowels in the same syllable, as [ai] in [iai55], [au] in [tʰiau55] and [ai] in [kuai55]. In these CVVV syllables, [u] and [i] are similar to glides or so-called semi-vowels, or approximants [j] and [w] as shown in the spectrogram. Finally, the vowel system in Yang (1957) is more suitable for accounting for the data in this study. Hopefully, the vowel formant data presented in this study will contribute to the study of vowels in Hakka.

The thesis deals with the recognition of Parkinson's disease from the speech signal. The first part refers to the principles of speech signals and speech signals by patients suffering from Parkinson's disease. Further, it continues to describe the issues of speech signals processing, basic symptoms used for diagnosis of Parkinson's disease (e. g. VAI, VSA, FCR, VOT etc.) and reduction of these symptoms. The next part focuses on a block diagram of the program for the diagnosis of Parkinson's disease. The main objective of this thesis is comparison of two methods of feature selection (mRMR and SFFS). For classification have selected two different methods were used. The first method is classification kNN and second method of classification is Gaussian mixture model (GMM).

This diploma thesis deals with creating of finite element model for the analysis of acustic waves radiation through human vocal tract and through the head surrounding space. The thesis contains a short overview of the anatomy of relevant parts and a short overview of formerly published models relevant to the topic. Then the process of creating the 3D model of human head, including the vocal tract, based on CT scans, and the mesh itself follows. This is succeeded by the computational solution taking in the acount the acoustic absorption of the vocal tract walls and radiation into the open space. The results gained are compared to relevant literature on this topic. The changes in frequency spectra in specific nodes of the mesh are reviewed and compared to relevant literature on the topic. The results could be used as basis of eventual frequention corrections of microphones used for voice diagnosis or registration in general, eg of speach or singing.

Le développement de nouveaux systèmes pour l’administration de médicaments par la voie transcutanée ne cesse de susciter un intérêt croissant pour élaborer de nouvelles stratégies visant à traverser la barrière du stratum corneum et transporter efficacement les agents thérapeutiques à travers la peau. Bien que l’administration par voie orale soit la plus favorable chez les patients, une faible biodisponibilité est souvent rencontrée pour certains médicaments et notamment pour les produits biopharmaceutiques. Ainsi, la peau représente un site accessible et pratique pour l’absorption de médicaments, mais détient un potentiel encore sous-estimé comme voie alternative à l’administration par voie orale. La conception de systèmes d'administration parentérale prolongée de médicaments capables de contrôler la libération du médicament au long terme et réduire la fréquence d’administration des médicaments pourrait présenter une option de traitement attrayante. Parmi les systèmes d’implants se formant in situ, les implants d’organogel offrent de nombreux avantages pour libérer au long terme une grande variété de molécules médicamenteuses et notamment des substances actives lipophiles piégées dans les huiles gélifiées. Cependant si l’objectif visé est une administration minimalement invasive et rapide de substances actives, les timbres de microaiguilles dissolvant dans la peau seraient d’un grand intérêt en raison de leur auto-administration, leur sécurité d’emploi et leur capacité à administrer des médicaments à base de peptides. Malgré les effets bénéfiques de ces deux nouveaux systèmes d’administration, les rôles exacts de la composition des organogels et des paramètres géométriques des microaiguilles hydrosolubles sur la libération de médicaments restent peu explorés. Le premier objectif principal de cette thèse était de déterminer l’effet de la composition des organogels se formant in situ par rapport au pourcentage massique en organogélifiant de bas poids moléculaire (acide 12-hydroxystéarique, 12-HSA) et de l’ajout de tensioactif (polysorbate 80) dans le système sur le taux de libération de substances actives hydrophile (acyclovir) et lipophile (clotrimazole). De plus, l'influence des paramètres de composition de ces organogels sur l'induction d'effets toxiques au niveau des fibroblastes de prépuce humain a également été étudiée. Pour ce faire, des systèmes d’organogel formant un dépôt sous-cutané à base de 12-HSA ont été développés en utilisant une faible quantité de solvant organique miscible à l’eau (N-méthyl-2-pyrrolidone) en tant qu’agent inhibant partiellement la gélation, favorisant ainsi l’injection des formulations. Au contact du milieu aqueux, les molécules de 12-HSA ont précipité en immobilisant simultanément l’huile et la substance active en son sein. Une augmentation du pourcentage massique en 12-HSA a conduit à une augmentation de la résistance du gel à la déformation grâce à la formation d’une structure de réseau en trois dimensions complexe. Cependant, l’ajout de polysorbate 80 dans le système a conduit à une structure plus fluide (de faible résistance) diminuant la capacité d’injectabilité des formulations et augmentant l’érosion du gel en surface. Ce dernier phénomène étant amplifié avec un plus faible pourcentage massique en 12-HSA. Les organogels de 12-HSA ont montré diminuer significativement les taux de libération au long terme de l’acyclovir comparé aux formulations de clotrimazole in vitro et ex vivo à travers la peau de porc excisé. La toxicité cellulaire était dépendante du pourcentage massique en 12-HSA et du type de culture cellulaire utilisée. En effet, les effets cytotoxiques étaient plus élevés en augmentant la quantité de 12-HSA dans l’implant pour une sensibilité plus élevée dans la culture cellulaire tridimensionnelle que dans celle bidimensionnelle. Ces résultats semblent néanmoins influencés par le type d’huile utilisé et son potentiel cytotoxique. Le deuxième objectif principal de cette thèse était de déterminer l’effet de la hauteur des microaiguilles en forme de pyramide et solubles dans l’eau sur le taux de libération d’un peptide modèle, le growth hormone-releasing peptide-6 (GHRP-6). À cet effet, les microaiguilles ont été préparées par micro-moulage à l’aide de deux polymères biocompatibles hydrosolubles approuvés par la Food and Drug Agency (FDA), l’alcool polyvinylique (PVA) et polyvinylpyrrolidone (PVP). Les timbres de microaiguilles ainsi développés permettaient de pénétrer efficacement dans la peau de porc tout en libérant la molécule encapsulée à l’interface entre l’épiderme et le derme supérieur. La quantification du GHRP-6 dans différentes matrices (peau, microaiguilles, plasma) a pu être réalisée grâce à une méthode analytique robuste et sensible utilisant la chromatographie liquide ultra performance couplée à la spectrométrie de masse en tandem. Les études de libération du GHRP-6 ex vivo sur la peau de porc ont montré que le taux de libération du GHRP-6 était plus élevé au long terme pour une hauteur en aiguille plus grande (800 µm contre 500 µm) tout en permettant d’augmenter l’encapsulation du GHRP-6 dans le système. En conclusion, ces résultats suggèrent que les organogels de 12-HSA pourraient constituer une approche prometteuse pour l’administration prolongée de substance active et notamment celles hydrophiles. Toutefois, les formulations développées devront être efficaces in vivo tout en minimisant les effets toxiques par l’utilisation d’huiles plus biocompatibles. Pour une libération rapide de substances actives, les timbres de microaiguilles représentent une avenue très prometteuse notamment pour les médicaments innovants de nature peptidique. Leur efficacité pour la libération de GHRP-6 et de leurs dérivés azapeptides devra être confirmée lors d’études in vivo (pharmacocinétique, pharmacodynamique, biodistribution), ce qui pourrait constituer une avancée dans l’administration de thérapie à base de peptides pour la gestion de l’inflammation chronique. / The development of novel transcutaneous drug delivery systems has gained increasing interest, with the focus on overcoming the stratum corneum barrier and efficiently transport therapeutic agents through the skin. Although oral administration is the most favorable route for patients, low bioavailability is often reported for certain drugs and especially for biopharmaceuticals. Accordingly, the skin represents an accessible and convenient site for drug absorption, but has yet to fully achieve its potential as an alternative to oral delivery. The design of parenteral sustained drug delivery systems capable of controlling long-term delivery of drugs and reducing the frequency of drug administration could present an attractive treatment option. Among in situ forming implants, in situ forming organogels offer many advantages such as controlled-release of a wide variety of drug molecules over a longer period of time, including lipophilic active substances trapped within gelled oil solutions. However, if the objective is the rapid administration of active substances, minimally invasive, dissolving microneedle patches would be of great interest due to their self-administration, their safety and their ability to deliver peptide-based drugs. Despite the beneficial effects of these two new delivery systems, the exact roles of the composition of organogels and geometrical parameters of microneedles on drug delivery are largely understudied. The first main objective of this thesis was to determine the effect of the composition of in situ forming organogels with respect to the organogelator concentration (12-hydroxystearic acid, 12-HSA) and the addition of a nonionic surfactant (polysorbate 80) to the system on the release rate of a hydrophilic (acyclovir) and a lipophilic (clotrimazole) active substances. In addition, the toxic effects of these organogels of different compositions on human foreskin fibroblasts were also studied. To do so, 12-HSA-based organogel systems forming a depot in the subcutaneous tissue have been developed using a small amount of water-miscible organic solvent (N-methyl-2-pyrrolidone) as an agent that can partially inhibit gelation, thus enhancing injectability of the formulations. Upon contact with aqueous medium, 12-HSA molecules precipitated simultaneously immobilizing the oil and the active substance therein. An increase in the concentration of 12-HSA led to an increase in the resistance of the gel to deformation thanks to the formation of a complex three-dimensional network structure. However, the addition of polysorbate 80 to the system resulted in fluid-matrix organogel (weak gel) decreasing the syringability of the formulations while increasing the erosion of the gel on the surface. The latter phenomenon is also intensified with a lower concentration of 12-HSA. 12-HSA organogels have been shown to significantly decrease acyclovir release rates for a longer time period in vitro and ex vivo through excised pig skin compared to clotrimazole formulations. Cellular cytotoxicity was dependent on the concentration of 12-HSA and the type of cell culture used. Indeed, the cytotoxic effects were higher by increasing the concentration of 12-HSA in the implant for a higher sensitivity in the three-dimensional cell culture than in the two-dimensional one. However, these results seem to be influenced by the type of oil used and its cytotoxic potential. The second main objective of this thesis was to determine the effect of dissolving pyramidal microneedles height on the release rate of a model peptide, the growth hormone-releasing peptide-6 (GHRP-6). For this purpose, the microneedles were prepared by micromolding process using two water-soluble biocompatible polymers approved by the Food and Drug Agency (FDA), poly(vinyl alcohol) (PVA) and polyvinylpyrrolidone (PVP). The microneedle patches allowed the microneedles to efficiently penetrate pig skin while releasing the encapsulated molecule at the interface between the epidermis and upper dermis. The quantification of GHRP-6 in different matrices (skin, microneedles, plasma) was achieved using a robust and sensitive analytical method using ultra performance liquid chromatography - tandem mass spectrometry. Ex vivo GHRP-6 release studies on pig skin showed that the release rate of GHRP-6 was higher over time for high-height microneedle (800 µm vs. 500 µm) while increasing the amount of GHRP-6 loaded in microneedles. In conclusion, these results suggest that 12-HSA organogels could constitute a promising approach as a sustained-release dosage form of active substances and in particular hydrophilic ones. However, the formulations developed must be effective in vivo while minimizing toxic effects through the use of more biocompatible oils. For a rapid release of drugs, microneedle patches represent a very promising avenue, in particular for emerging peptide drugs. Their efficacy for the release of GHRP-6 and azapeptide derivatives of GHRP-6 needs to be confirmed using in vivo studies (pharmacokinetic, pharmacodynamic, biodistribution), which may represent a breakthrough in the transdermal delivery of therapeutic peptides for the management of chronic inflammation.