In the recent years, a rapidly increasing amount of experimental data has been generated by high-throughput technologies. Despite of these large quantities of protein-related data and the development of computational prediction methods, the function of many proteins is still unknown. In the human proteome, at least 20% of the annotated proteins are not characterized. Thus, the question, how to predict protein function from its amino acid sequence, remains to be answered for many proteins. Classical bioinformatics approaches for function prediction are based on inferring function from well-characterized homologs, which are identified based on sequence similarity. However, these methods fail to identify distant homologs with low sequence similarity. As protein structure is more conserved than sequence in protein families, structure-based methods (e.g. fold recognition) may recognize possible structural similarities even at low sequence similarity and therefore provide information for function inference. These fold recognition methods have already been proven to be successful for individual proteins, but their automation for high-throughput application is difficult due to intrinsic challenges of these techniques, mainly caused by a high false positive rate. Automated identification of remote homologs based on fold recognition methods would allow a signi cant improvement in functional annotation of proteins. My approach was to combine structure-based computational prediction methods with experimental data from genome-wide RNAi screens to support the establishment of functional hypotheses by improving the analysis of protein structure prediction results. In the first part of my thesis, I characterized proteins from the Ska complex by computational methods. I showed the benefit of including experimental information to identify remote homologs: Integration of functional data helped to reduce the number of false positives in fold recognition results and made it possible to establish interesting functional hypotheses based on high con dence structural predictions. Based on the structural hypothesis of a GLEBS motif in c13orf3 (Ska3), I could derive a potential molecular mechanism that could explain the observed phenotype. In the second part of my thesis, my goal was to develop computational tools and automated analysis techniques to be able to perform structure-based functional annotation in a high-throughput way. I designed and implemented key tools that were successfully integrated into a computational platform, called StrAnno, which I set up together with my colleagues. These novel computational modules include a domain prediction algorithm and a graphical overview that facilitates and accelerates the analysis of results. StrAnno can be seen as a first step towards automatic functional annotation of proteins by structure-based methods. First, the analysis of long hit lists to identify promising candidates for further analysis is substantially facilitated by integration and combination of various sequence-based computational tools and data from functional databases. Second, the developed post-processing tools accelerate the evaluation of structural and functional hypotheses. False positives from the threading result lists are removed by various filters, and analysis of the possible true positives is greatly enhanced by the graphical overview. With these two essential benefits, fold recognition techniques are applicable to large-scale approaches. By applying this developed methodology to hits from a genome-wide cell cycle RNAi screen and evaluating structural hypotheses by molecular modeling techniques, I aimed to associate biological functions to human proteins and link the RNAi phenotype to a molecular function. For two selected human proteins, c20orf43 and HJURP, I could establish interesting structural and functional hypotheses. These predictions were based on templates with low sequence identity (10-20%). The uncharacterized human protein c20orf43 might be a E3 SUMO-ligase that could be involved either in DNA repair or rRNA regulatory processes. Based on the structural hypotheses of two domains of HJURP, I predicted a potential link to ubiquitylation processes and direct DNA binding. In addition, I substantiated the cell cycle arrest phenotype of these two genes upon RNAi knockdown. Fold recognition methods are a promising alternative for functional annotation of proteins that escape sequence-based annotation due to their low sequence identity to well-characterized protein families. The structural and functional hypotheses I established in my thesis open the door to investigate the molecular mechanisms of previously uncharacterized proteins, which may provide new insights into cellular mechanisms.

Physical interaction with textiles is generally found through the purpose of the textiles; for clothing, or interior use. We engage not just for the textiles, but primarily for it’s function. Within Dynamic Folding Knits, the purpose of the material is purely interaction focused. To encourage and to entice the visitor to play, and thus creating a new focus to the material. One that focuses on the materiality before the function. Described through practical based research, knitted materials have been explored to investigate and encourage the physical interaction between the viewer and textiles. Folding methods have been developed that increase the tactility of the material, and integrate intricate form. Both these qualities have been shown to increase curiosity to interact and explore the textiles due to the materials tactility. Working within three main categories of folding methods; The Strict Fold, The Soft Fold and An Amalgamation of Folds, the results provide a vast range of folding textiles, through strict geometry set into the structure of the material, to the softer accumulation of fabric that builds and forms. All of these are then offered to visitors to interact with through touch and play, to experience the movement, the textures the folds and the forms.

Microcirculation plays an essential and functional role in the human body and reflects people’s physical status with microscopic detail. For peripheral microcirculation, nail-fold microscopy is a convenient and non-invasive tool since the capillaries in the nail-fold are well arranged and parallel to the skin, which is advantageous for microscopic visualization. Further, nail-fold capillaroscopy information is widely useful. In diagnosis, various diseases such as systemic lupus erythematosus and cardiac diseases can be detected and predicted at an early stage with capillaroscopic patterns and capillary blood velocity. For medical experiments, capillaroscopic information can be used to monitor drug effects and other medical treatments. Though nail-fold capillaroscopy is of significant convenience, it is not widely used. Currently, there is no commercial product with those functions due to the limitations of the equipment, such as microscope resolution and lens magnification. Besides, there is no concrete standard for measurement procedures or objective rules for quantitive data analysis. This thesis proposes a reliable system estimating nail-fold capillary blood flow velocity. It is tested and applied to the microscope from Optilia. In this work, various image and video processing methods are discussed in detail and tested in practice. Taking computational load and equipment limitations into consideration, the system applies frame enhancement and video stabilization. It uses dual-window and correlation methods to estimate the velocity of red blood cells in nail-fold capillaries. In order to test the reliability of the system, the obtained results are compared with the outcome of direct observation. It turns out that the chosen methods employed in the system provide rational results within 5 pixel bias.

Vocal fold models are valuable for studying voice production. They provide an alternative method of studying the mechanics of the voice that does not require in vivo experimentation or the use of excised human or animal tissue. In this thesis, a new method of creating vocal fold models through additive manufacturing is described. The purpose of this research was to reduce model fabrication time, to decrease the number of model failures during manufacturing, and to lay the foundation for creating models with more lifelike geometric and material properties. This research was conducted in four stages. First, a suitable silicone additive manufacturing technique using a UV-curable silicone was chosen. The technique chosen was called freeform reversible embedding (FRE) and involved embedding liquid silicone material into a gel-like medium named organogel. The UV-curable silicone's material properties were identified to confirm its utility in vocal fold model design. Second, an open-source, fused deposition modeling slicing software was selected to create g-code for the printer. Applicable software settings were tuned through qualitative printing tests to find their optimal values for use in FRE printing. Third, 3D-printed cubes were used in tensile tests to characterize the material properties of FRE-printed, silicone material. The cubes were found to be anisotropic, exhibiting different modulus values corresponding to the layer orientation of the printed material. Fourth, vocal fold models were FRE-printed in two different layer orientations and were used in phonation tests to gather data for onset pressure, vibratory frequency, amplitude, and flow rate. The printed models self-oscillated and withstood the strains induced by phonation. These tests showed that layer direction affects the phonation properties of the models, demonstrating that models with layers in the coronal plane had slightly lower frequencies and onset pressures than models with layers in the sagittal plane. The models' onset pressures were higher than what is found in human vocal folds. However, their frequencies were within a comparable range. These tests showed the effectiveness of additive manufacturing in the application of vocal fold fabrication, reducing production effort by allowing researchers to go directly from model design to fabrication in a single manufacturing step. It is anticipated that this method will be modified to incorporate printing of multiple stiffnesses of silicone to better mimic the material properties of vocal fold tissue, and that the anisotropy of 3D-printed material will be leveraged to model the anisotropy of human vocal folds. This work also has potential application areas outside of voice research.

Philosophiae Doctor - PhD / Mountainous areas are important water sources in many landscapes. An understanding of how mountainous catchments function is important particularly in semi-arid areas, where water shortages are prevalent. In addition to climate and physiographic factors, the hydrological responses of mountainous catchments can be influenced by land uses and land cover types. Although the general effects of land use and land cover types on hydrological processes are known, prediction of the specific effects in a given catchment is still problematic. This study characterized flowpaths, and hydrological responses to different land cover types in a semi-arid, mountainous Kromme River catchment (Eastern Cape province of South Africa), located in the Cape Fold Mountains of the Table Mountain Group (TMG) geological region.

Final publication is available at http://onlinelibrary.wiley.com/doi/10.1002/term.2060/abstract;jsessionid=F0849D98381EEF9E83401A02B9042F4D.f04t02 / 京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19602号 / 医博第4109号 / 新制||医||1014(附属図書館) / 32638 / 京都大学大学院医学研究科医学専攻 / (主査)教授 別所 和久, 教授 伊佐 正, 教授 川口 義弥 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20235号 / 医博第4194号 / 新制||医||1019(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 別所 和久, 教授 鈴木 茂彦, 教授 渡邊 直樹 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

Purpose: This study examined voice onset time (VOT) in children with and without vocal fold nodules (VFN). The purpose of this study was to provide further evidence regarding the need for individualized research and treatment dedicated to the pediatric population. The pediatric population has a distinctly different laryngeal mechanism than adults, as they are still developing. Although the pediatric system is anatomically different from that of a fully mature adult system, treatment for children with VFN is largely based on adult research. This study examined the VOTs of voiceless consonants, as the transition from the voiceless consonant to the subsequent vowel requires significant vocal and articulatory control and coordination. Measures of VOT change throughout the maturation as VOT follows a significant developmental pattern. Children with and without VFN were enlisted in order to examine the effects VFN have on VOT. Hypotheses: We hypothesize that children with VFN would have differences in 1) average VOT values compared to the control group, with no prediction for direction of difference (shorter and longer), and 2) between-word variability of VOT values compared to the control group, with no prediction for direction of difference (more variable and less variable). Methods: Participant data were retrospectively collected and included children between 6 and 12 years old with VFN and age- and sex-matched controls. Participants were recorded producing the six CAPE-V sentences. Four voiceless consonants were selected for VOT analysis. Praat was utilized to manually mark the vocal onset of the stop consonant by the current researcher. A previous researcher identified the vocal offset, and each placement was confirmed by the current researcher. VOT was calculated as the time between the stop consonant burst and the vocal onset of the vowel. Results: There was no significant difference between the VFN and the control groups in average VOT or VOT variability. Within the VFN group, participants who were more dysphonic (lower cepstral peak prominence (CPP) values) had more variable VOT values. Participants in the VFN group had lower CPP values than the control group, suggesting that CPP measures are a reliable indicator of dysphonia. Additionally, within the VFN group, male children had lower CPP values than female children. Conclusion: Although no group difference was found, the within-group analyses indicated that VFNs impacted productions. Children with VFN who were more dysphonic had increased VOT variability. This may suggest that VFN impact a child’s ability to phonate therefore causing more variability within productions. Future research is needed to study the impact dysphonia treatment for children with VFN may have on VOT values. Additionally, a longitudinal study of the impact of VFNs on VOT values during developmental stages may be warranted. / Public Health

No description available.