Pendant le développement du cervelet, les progéniteurs des neurones granulaires (PNG) nécessitent la présence du cil primaire pour proliférer en réponse à Sonic Hedgehog (SHH). En effet, la prolifération dérégulée des PNGs peut conduire à la formation d'une tumeur pédiatrique maligne appelée SHH-médulloblastome (MB), de ce fait comprendre comment le cil primaire est régulé dans les PNGs est crucial.Nous montrons que le facteur de transcription Atoh1 contrôle la présence du cil primaire dans les PNGs in vitro et in vivo. En particulier, la suppression du cil primaire par l’inactivation génétique de gènes impliqués dans la ciliogenèse (par exemple, Kif3a ou Ift88) empêche Atoh1 de maintenir les PNGs en prolifération, ce qui indique qu’Atoh1 favorise l’expansion des PNGs en maintenant la présence du cil primaire. D’un point de vue moléculaire, Atoh1 contrôle la formation du cil primaire en régulant le bon positionnement peri-centrosomal des satellites centriolaires (SC), complexes protéiques essentiels pour la ciliogenèse. L'inactivation de Atoh1 dans les PNGs perturbe en effet la distribution subcellulaire des SCs, altérant ainsi inévitablement la ciliogenèse. Cette nouvelle fonction de Atoh1 est gouvernée par la régulation transcriptionnelle directe d'un composant clé des SCs, Cep131. L’expression ectopique de Cep131 dans les PNGs restore les effets liés à l'inactivation d'Atoh1, rétablissant la localisation correcte du SC et comme conséquence la présence d’un cil primaire.De plus, nous avons montré que cette voie Atoh1-SC-cil primaire-SHH contrôlant la prolifération des PNGs est également conservée dans le contexte du SHH-MB, où Atoh1 est surexprimée et essentielle pour sa formation et sa maintenance.Ces données révèlent un mécanisme par lequel la ciliogenèse est régulée dans des progéniteurs de neurones, offrant de nouvelles informations sur la neurogenèse dans le cervelet et sur la pathogenèse du SHH-MB. / Cerebellar granule neuron progenitors (GNPs) require the primary cilium to proliferate in response to Sonic Hedgehog (SHH) during cerebellar development. As aberrant proliferation of GNPs may lead to SHH-type medulloblastoma (SHH-MB), a pediatric brain tumor, understanding which mechanisms control ciliogenesis in GNPs represents a major interest in the field. Here, we show that the proneural bHLH transcription factor Atoh1 controls the presence of primary cilia in GNPs both in vitro and in vivo, thus maintaining GNPs responsive to the mitogenic effects of SHH. Indeed, loss of primary cilia induced via knockdown of specific ciliary components (e.g. Kif3a and Ift88) abolishes the ability of Atoh1 to keep GNPs in proliferation in vivo. Mechanistically, Atoh1 controls ciliogenesis by regulating the proper peri-centrosomal clustering of centriolar satellites (CS), large multiprotein complexes working as essential machineries for ciliogenesis. Knockdown of Atoh1 in GNPs perturbs CS subcellular distribution, leading to impairment of ciliogenesis. Luciferase reporter assays and chromatin immunoprecipitation experiments indicate that Atoh1 can directly regulate the expression of Cep131, a key CS core component. Importantly, ectopic expression of Cep131 in GNPs depleted of Atoh1, is sufficient to restore proper CS localization and consequent primary cilia formation, indicating that the Atoh1-Cep131-CS axis is responsible for ciliogenesis in GNPs.In addition, we further demonstrated that these functions of Atoh1 are conserved in the context of SHH-MB, where Atoh1 is typically overexpressed and acts as a lineage-dependent transcription factor.These data reveal a mechanism whereby ciliogenesis is regulated in neuron progenitors providing novel insights into cerebellar neurogenesis and pathogenesis of SHH-MB.

Detonation waves are highly unstable and possesses three-dimensional cellular structure. They are believed to correlate with the detonation length, or hydrodynamic thickness, in the direction of propagation. The hydrodynamic thickness is considered an acceptable, or true, length scale for cellular detonations. The hydrodynamic thickness is defined as the distance from the leading shock, to the Chapman-Jouguet (CJ) surface, or sonic surface, behind the detonation front. The sonic surface is the location behind the shock where the flow transitions from supersonic to subsonic. The location of the sonic surface is paramount in characterizing a length scale for detonation-based propulsion and power generation technology. A better understanding of this length scale will greatly influence the ability to characterize and maintain sustained detonations. It is of importance to note that there is a lack of experimental data supporting current hydrodynamic theories. The current study plans to produce such experimental data by determining the location of the sonic surface by detonating hydrogen-air mixtures in a Pulsed Detonation Engine (PDE) and Rotating Detonation Engine (RDE) facility. Velocity and temperature profiles are constructed, for both cases, in order to create a spatial evolution of the Mach number profile for the identification of the sonic surface. The hydrodynamic thickness for both cases is revealed and compared to current detonation theories.

Non-intrusive acoustic instruments that measure fluid velocity and temperature have been restricted to low subsonic Mach number applications due to increased complexities associated with acoustic refraction, low signal-to-noise ratios, and a limited range of practical applications. In the current work, the use of acoustics for non-intrusive flow monitoring in compressible flows is explored and a novel sonic anemometry and thermometry (SAT) technique is developed. Using multiple arrangements of SAT equipment, a compressible acoustic tomography technique was also developed to resolve flow non-uniformities. Three validation experiments were used to investigate the novel SAT technique performance, and a fourth validation experiment was used to explore compressible flow tomography capabilities. In the first experiment, an unheated jet was used to verify that the acoustic technique could measure fluid velocities in high subsonic Mach number flows. The application demonstrated velocity root mean square (RMS) errors of 9 m/s in unheated jet flows up to Mach 0.83. Next, a heated jet facility was used to assess the impact of fluid temperature on measurement accuracy. Using jet Mach numbers up to 0.7 and total temperatures up to 700 K, RMS velocity and static temperature errors up to 8.5 m/s (2.4% of maximum jet velocity) and 23.3 K (3.3% of total temperature) were observed. Finally, the acoustic technique was implemented at the exhaust of a JT15D-1A turbofan engine to investigate technique sensitivity to bypass engine conditions. A mass flow rate and thrust estimation approach was developed and RMS errors of 1.1 kg/s and 200 N were observed in conditions up to an exhaust Mach number of 0.48. Since modern acoustic tomography techniques require an incompressible flow assumption for velocity detection, advancements were made to extend acoustic tomography methods to compressible flow scenarios for the final experiment. The approach was tested in the heated jet operating at Mach 0.48 and 0.72 (total temperature of 675 K, approximately 2.25 times the ambient) and numerical simulations were used to identify technique sensitivity to input variables and system design. This research marks the first time an acoustic method has been used to estimate compressible flow velocities and temperatures. / Ph. D.

Commercial aircraft are subject to noise regulations imposed by the Federal Aviation Administration. Currently, the FAA limits overland flight of supersonic airplanes due to the negative effect of the sonic boom on communities. The annoyance produced by the impulsive signature of sonic booms, particularly indoors, cannot exceed that of the broadband, low-overpressure noise produced by subsonic airplanes for the restriction to be lifted. Therefore, the ability to understand and accurately reproduce the acoustic response of a sonic boom is important for psychoacoustic classification of their tolerability within residences. This thesis presents and interprets results of the propagation and transmission of simulated sonic booms incident on wood-framed structures. The testing environment, sonic boom simulation method, and associated instrumentation are described. The effects of the traveling blast on the structure are investigated through pressure loading and structural response measurements. The ensuing interior acoustic responses for several different configurations are presented, including the effects of room cavity interaction and exposure of the room cavities to the traveling wave through an open door. Calculated transfer functions between the interior acoustic response and the free-field incident wave are computed to assess the extent to which wood-framed buildings transmit energy to their cavities. In all cases tested, significant transmission of the sonic boom's low frequency content into the structures was apparent through direct apertures and the excitation of structural components. The data show that sonic booms provide significant excitation of structural and acoustic modes that drives the interior acoustic response in residential structures. / Master of Science

Suture or bone anchors are used to reattach a tendon or ligament after it has been torn away from the bone. Anchors provide secure attachments to bone during trauma or reconstructive surgery, holding the ligament or tendon in place and potentially allowing greater mobility during recovery. Computer modelling techniques are used to investigate both established bone anchor technology, such as threaded implants, and emerging technologies such as cement augmentation or sonic-fusion. Sonic fusion is an ultrasound-assisted anchoring method which has recently been introduced in low load maxillofacial applications, and is expected to be used in other low load applications such as hallux valgus alignment procedures and suture attachment. Threaded anchors were examined using two Finite Element (FE) models of human cancellous bone, representing both “normal” and “weaker” bone. Simulation and analysis revealed the critical nature of modelling the microstructure of bone. Changing the direction of loading in the model leads to significant changes in the response of the construct, and this cannot be represented in continuum models, or in physical models using artificial cancellous bone. Rapid prototyping (RP) using 3d printing was used for validation of the FE models. While this method has previously been implemented to create physical bone models, testing an assembly model and comparing it to FE results for inclined loading had not been attempted. RP models were created of the threaded anchor in both “normal” and “weaker” bone, and a sonic fusion model in the normal bone was also created. These models were then subjected to mechanical testing. Results produced from the simulation correlated with the physical results. The importance of a cortical layer was re-confirmed. At the apparent densities simulated, engagement with the cortical layer increases pull-out force dramatically. Engaging the anchor even with a thin cortical layer can produce a significant improvement to pull-out strength. Novel sonic fusion FE models were created from a CT scan of animal bone, and the geometry for both the sonic-fusion pin and bone were taken from the CT scan. Computer generated geometry was used to build pin concepts of varying shapes. It was shown that if good engagement is made with bone, as in the case of all of the concepts created, then sonic fusion can produce a good holding power - comparable with that of a threaded anchor. The results showed that sonic-fusion requires less drill penetration into the bone, meaning less of the inherent bone structure is removed – vital for patients with poor bone quality. Bone cement models were investigated. Bone augmentation models were created, and the addition of cement demonstrated an improvement in anchor holding power. The research showed that there are benefits to using FEA as a tool to evaluate the mechanical aspects of cement distribution. The results proved the hypothesis that augmentation will likely increase the holding power of anchor, and its distribution will affect pull-out significantly. This work has created a method for modelling and evaluating both established and novel bone anchor technology in CT bone geometry, a procedure which could be expanded to other bone implants. It has been validated using the innovative approach of rapid prototyping.

During embryogenesis, airway epithelial cells possess primary cilia, and HH signaling guides lung development. As epithelial cells mature, they produce hundreds of motile cilia and continue to produce the sonic hedgehog (SHH) ligand, which is found apically in the thin layer of liquid covering airways. However, whether ciliated airway cells express apical HH signaling components and what their function might be have remained unknown. Here we show that motile cilia are enriched for HH signaling proteins, including patched 1 and smoothened. These cilia are also enriched for proteins affecting cAMP-dependent signaling, including Gαi and adenylyl cyclase 5/6. Surprisingly, SHH in differentiated airway epithelia did not elicit the canonical SHH signaling pathway that regulates transcription during development. But instead, activating HH signaling decreases intracellular levels of cAMP, which reduces ciliary beat frequency and airway surface liquid pH, similar to changes that have been observed in the airway of people with chronic obstructive pulmonary disease (COPD). Furthermore, we observed that significant increase of SHH ligand expression in differentiated airway epithelia with COPD, suggesting a potential role of SHH signaling in the pathogenesis of airway disease. Collectively, our study indicates that airway cilia detect apical SHH to mediate airway physiology through noncanonical HH signaling. SHH may dampen defenses at the contact point between the environment and the lung, perhaps counterbalancing processes that stimulate airway defenses. This may suggest a potential role of SHH signaling in the pathogenesis of airway disease, such as COPD.

<p>Omfattande forskning har gjorts på hur genus framställs i medier. Undersökningarna som har genomförts har fokuserat på hur genusframställningen ser ut i bland annat nyhetsmedier och livsstilsmagasin. Genusforskning på medietexter har visat klara skillnader i hur män och kvinnor framställs i text och bild.</p><p>Denna uppsats berör ett hittills outforskat område, popjournalistik. Vi undersöker hur genus framställs av manliga och kvinnliga artister, om det förekommer stereotyper och hur dessa i sådana fall ser ut. Vår tes är att det förekommer klara stereotyper. Vi undersöker även hur artisterna framställs i bilder och om det finns några skillnader beroende på genustillhörighet. Våra analyser baseras på material från poptidskriften Sonic Magazine, som är en av Sveriges största tidskrifter på det här området.</p><p>Den teoretiska ramen för denna uppsats utgår från identitet, stereotyper och representation. För att kunna urskilja tendenser i hur framställningen av manliga och kvinnliga artister ser ut, utgår vi från ovannämnd teori.</p><p>Som metod har vi använt oss av kvalitativa analyser. Vi har hämtat inspiration från den retoriska textanalysen och den semiotiska bildanalysen. Vårt material utgår från de senaste fem numren av Sonic Magazine som fanns att tillgå. Vi koncentrerar vår analys på fyra manliga och fyra kvinnliga personporträtt.</p><p>Med utgångspunkt i vår teoretiska ram har vi kommit fram till att det förekommer stereotypiska skildringar av både manliga och kvinnliga artister, i texterna till personporträtten. I personporträtten om de manliga artisterna är stereotypen ”konstnärssjälen” ofta förekommande. Vår tes är således stärkt. Dock är dessa stereotyper snarare kopplade till artisternas yrkesroll framför deras genustillhörighet. Vad gäller framställningen av manliga och kvinnliga artister i bilder ser vi en tendens att de kvinnliga artisterna skildras på ett sätt som är mer kopplat till deras genustillhörighet än de manliga artisterna.</p>

Omfattande forskning har gjorts på hur genus framställs i medier. Undersökningarna som har genomförts har fokuserat på hur genusframställningen ser ut i bland annat nyhetsmedier och livsstilsmagasin. Genusforskning på medietexter har visat klara skillnader i hur män och kvinnor framställs i text och bild. Denna uppsats berör ett hittills outforskat område, popjournalistik. Vi undersöker hur genus framställs av manliga och kvinnliga artister, om det förekommer stereotyper och hur dessa i sådana fall ser ut. Vår tes är att det förekommer klara stereotyper. Vi undersöker även hur artisterna framställs i bilder och om det finns några skillnader beroende på genustillhörighet. Våra analyser baseras på material från poptidskriften Sonic Magazine, som är en av Sveriges största tidskrifter på det här området. Den teoretiska ramen för denna uppsats utgår från identitet, stereotyper och representation. För att kunna urskilja tendenser i hur framställningen av manliga och kvinnliga artister ser ut, utgår vi från ovannämnd teori. Som metod har vi använt oss av kvalitativa analyser. Vi har hämtat inspiration från den retoriska textanalysen och den semiotiska bildanalysen. Vårt material utgår från de senaste fem numren av Sonic Magazine som fanns att tillgå. Vi koncentrerar vår analys på fyra manliga och fyra kvinnliga personporträtt. Med utgångspunkt i vår teoretiska ram har vi kommit fram till att det förekommer stereotypiska skildringar av både manliga och kvinnliga artister, i texterna till personporträtten. I personporträtten om de manliga artisterna är stereotypen ”konstnärssjälen” ofta förekommande. Vår tes är således stärkt. Dock är dessa stereotyper snarare kopplade till artisternas yrkesroll framför deras genustillhörighet. Vad gäller framställningen av manliga och kvinnliga artister i bilder ser vi en tendens att de kvinnliga artisterna skildras på ett sätt som är mer kopplat till deras genustillhörighet än de manliga artisterna.

The accumulation of carbon dioxide gas (CO2) in the atmosphere is considered be the main cause of global warming effects. These emissions can be reduced substantially by capturing and storing the CO2. The CO2SINK project started in April 2004 in the northeast German Basin (NEGB) at the town of Ketzin near Berlin, Germany. Uppsala University is one of the main participants in the seismic part of the CO2SINK project. Full waveform sonic data were acquired in the Ktzi-201 injection well at the Ketzin CO2 storage site. The mode of logging was monopole logging. The target was the Stuttgart Formation, a saline sandstone aquifer at the depth of 500-700m. A total of 1210 shots were conducted and data were recorded on 13 channels. Receiver spacing was 6 inches (15.24 cm). The focus of the CO2SINK project was to develop the basis for the CCS technique by injecting CO2 into a saline aquifer and monitoring of the injected CO2 in the aquifer as a pilot study for future geological storage of CO2 in Europe. The objective of this study is to calculate P-wave &amp; S-wave velocities from full waveform sonic data recorded in Ktzi-201 injection well. In hard formations, shear wave velocities can be determined directly from full waveform sonic data recorded in monopole logging. However, in slow formations like Stuttgart Formation as in the Ketzin CO2SINK project, shear wave arrivals are absent in full waveform sonic data recorded in monopole logging. In this case, shear wave velocities can be determined from Stoneley wave velocities provided that one knows the P-wave velocity in the borehole fluid. P-wave velocities were calculated by picking the P-wave arrivals on full waveform sonic data. Due to the absence of shear wave arrivals, the shear wave velocities were estimated from the larger amplitude Stoneley waves. The estimated S-wave velocities from Stoneley waves were less than the fluid wave velocity in the borehole, confirming the mode of logging was monopole and the formation is a slow formation. The reliability of shear wave velocities estimated from Stoneley waves also depends on five other parameters such as formation permeability, borehole fluid property, tool diameter, borehole radius etc.

Batrachoididae, one of the most well-studied soniferous fishes, are typical examples of fish using intrinsic sonic muscles to excite vibration of swim bladder to emit sound. Most fishes possess a single swim bladder including the Batrachoididae. However, the grunting toadfish (Allenbatrachus grunniens) was found to have two separated swim bladders located in the dorsal part of the abdominal cavity; the size of the swim bladders were quite similar. Sonic muscles were firmly attached to the lateral side of each swim bladder. The aims of this study were to (1) investigate the specialized swimbladder morphology and the acoustic signals of the grunting toadfish (A. grunniens), (2) to falsify the hypothesis that this unique form of swim bladder is a synapomorphic character, and species that possess this character are sister groups. The vocal repertoire in grunting toadfish can generally divided into two types ¡V grunt and boatwhistle. Grunts were harmonic signals with shorter call duration, and could be emitted alone as single grunt (i.e., hand-held grunt) or in series (known as grunt train). Boatwhistles were also hamonic but much longer in call duration and usually appeared in succession. A small portion of signals were found to have acoustic beats, which was previously described in the three-spined toadfish (Batrachomoeus trispinosus), which also possess a pair of swim bladders. Therefore, signals with acoustic beats may be a key character for generating sound by two separated swim bladders. Comparing the morphological measurements of swim bladders indicated that there were no significant differences between swim bladders on different sides. However, comparisons between genders showed that the width, thickness, and weight of sonic muscle in females were significantly higher than males. Less wide sonic muscles with shorter sonic muscle fibers may enables the muscle to contract at a higher velocity in male fishes. However, females were found to have thicker sonic muscle, which indicated that the vocal ability in females may be higher than it was expected. The sonic muscle fibers of females have a larger myofibrillar region compared with males, which have a relatively larger central core. These characters may increase the fatigue-resistance of sonic muscle in males, which can contract at a relatively higher rate for a longer duration. Species with two separated swim bladders were found to be sister group in the molecular phylogenetic tree, implying that this specialized morphological character is synapomorphy.