Les modèles actuels de perception de la parole suggèrent un couplage étroit entre les rythmes cérébraux, caractérisés par les oscillations neuronales, et le rythme de la parole, permettant de segmenter le flux verbal continu en unités linguistiques pertinentes pour la reconnaissance. En particulier, les modulations lentes d’amplitude de l’enveloppe temporelle de la parole, véhiculant l’information syllabique et prosodique, sont capables d’« entrainer » les oscillations corticales auditives dans la bande de fréquence thêta (4-7 Hz), échantillonnant le signal verbal en unités syllabiques. L’information temporelle qui caractérise la parole joue un rôle fondamental dans l’acquisition et le développement du langage ; un déficit de traitement des indices rythmiques de la parole a d’ailleurs été décrit dans les troubles développementaux du langage. L’objectif de ce travail de thèse était de mieux comprendre les processus neurocognitifs sous-tendant la perception du rythme de la parole naturelle chez l’enfant présentant un développement langagier typique ou atypique (dysphasie) dans trois études. Une première étude en magnétoencéphalographie (MEG) a permis de dévoiler la dynamique corticale oscillatoire chez des enfants francophones neurotypiques (8-13 ans) lors de l’écoute de phrases naturellement produites à un débit normal ou rapide. Nos résultats suggèrent l’existence de deux phénomènes d’« entrainment » des oscillations sur l’enveloppe temporelle de la parole à débit normal, l’un dans la bande thêta au sein des régions auditives droites, l’autre dans une bande centrée sur le débit syllabique moyen des stimuli dans les régions temporales antérieures gauches. Dans la condition de parole rapide, une synchronisation cortico-acoustique a été mise en évidence dans la bande thêta au sein des régions (pré)motrices gauches, reflétant le rôle de la voie dorsale d’intégration sensori-motrice dans les conditions d’écoute difficiles mais aussi dans le développement du langage oral. Les deux études suivantes ont été réalisées chez des enfants présentant une dysphasie expressive (8-13 ans) afin de tester l’hypothèse d’un trouble de traitement du rythme syllabique chez ces enfants, potentiellement sous-tendu par une dynamique corticale oscillatoire atypique. Dans une étude comportementale, nous avons évalué les capacités des enfants dysphasiques à décoder de la parole naturellement produite à débit normal ou rapide, ou accélérée artificiellement. Nous avons montré des performances réduites chez ces enfants, en regard d’enfants neurotypiques, pour traiter des phrases accélérées naturellement et artificiellement, suggérant un déficit d’extraction du rythme de la parole lorsque la fréquence des modulations de l’enveloppe temporelle augmente. Une étude en MEG, identique à celle réalisée chez les enfants neurotypiques, nous a permis d’apporter de premiers éléments en faveur de cette interprétation en révélant un traitement cortical atypique de l’information syllabique dans la dysphasie, qui pourrait rendre compte des troubles phonologiques et morpho-syntaxiques souvent décrits dans ce trouble neuro-développemental. Une synchronisation réduite des oscillations thêta du cortex auditif a ainsi été mise en évidence chez les enfants dysphasiques par rapport à leurs pairs lors de la perception de parole à débit normal. L’absence d’alignement de l’activité oscillatoire des régions prémotrices sur l’enveloppe temporelle des phrases à débit rapide nous a en outre conduit à émettre l’hypothèse d’un dysfonctionnement de la voie dorsale chez ces enfants. Dans l’ensemble, ce travail de thèse fournit donc, pour la première fois à notre connaissance, des preuves expérimentales (i) de la synchronisation entre rythmes corticaux et rythme de la parole naturelle chez les enfants à développement langagier typique et (ii) d’une dynamique oscillatoire atypique lors de la perception de parole à débit normal et rapide chez les enfants dysphasiques. / Current models of speech perception suggest a close correspondence between brain rhythms, characterized by neuronal oscillations, and speech rhythm, which would allow the brain to parse the incoming speech signal into relevant linguistic units for decoding. Slow amplitude modulations in speech temporal envelope, which convey syllabic and prosodic information, have been shown to entrain oscillatory activity of auditory cortex in the theta frequency band (4-7 Hz), sampling the acoustic signal into syllable-sized units. Temporal information in speech is a foundation for oral language acquisition and development; accordingly, deficits in processing speech rhythmic cues have been described in developmental language disorders. This thesis sought to throw light on the neurocognitive processes underlying the perception of natural speech in children with typical and atypical language development (Specific Language Impairment – SLI – or Developmental Language Disorder – DLD) in three experimental studies. In a first magnetoencephalography (MEG) study, we unraveled the oscillatory dynamics in a group of French-speaking typically-developing children aged 8 to 13 years old during listening to naturally-produced sentences either at a normal or fast rate. Our results suggested two types of entrainment of cortical oscillations on the temporal envelope of normal rate speech: the first one occurred in the theta band in right auditory cortex whereas the second one was found in a frequency band centered on the mean syllabic rate of our stimuli in left anterior temporal regions. As to the fast rate condition, we showed cortico-acoustic coupling in the theta band in left (pre)motor areas, reflecting the role of the sensorimotor dorsal pathway in challenging listening conditions as well as in language development. In two other studies, we tested the hypothesis of an impairment to process speech syllabic rhythm, potentially underpinned by atypical oscillatory cortical dynamics, in children with developmental language disorders mainly at the expressive level. In a behavioral study, we examined how French-speaking children with expressive DLD (8-13 years old) processed speech naturally produced at a normal or fast rate, or artificially accelerated. Our results showed poorer performance to decode fast sentences, either accelerated naturally or artificially, in these children as compared to their typically-developing peers, which suggests a deficit in extracting speech syllabic information with increased modulation frequency in the amplitude envelope. The last study, identical to the first one in MEG conducted in typically-developing children, provided the first piece of evidence in favor of this interpretation by showing atypical cortical processing of syllabic information in children with DLD, which may account for the phonological and morpho-syntactic deficits frequently described in this developmental disorder. Reduced alignment of theta oscillatory activity in auditory cortex to normal rate speech has indeed been evidenced in children with DLD as compared to typically-developing children. Lack of synchronization of oscillations in left (pre)motor regions to amplitude envelope of fast rate sentences was also observed, which we interpreted as potential dysfunction of the dorsal stream in this population. To the best of our knowledge, the findings obtained in this thesis therefore provide first experimental evidence for (i) coupling between brain rhythms and rhythm of naturally produced speech in typically-developing children and (ii) atypical oscillatory cortical dynamics underlying normal and fast rate speech in children with developmental language disorders.

As operárias de Melipona quadrifasciata exercem diferentes funções na colônia, segundo sua faixa etária. No interior da colônia, os indivíduos mais jovens, nutrizes, ficam localizados na região mais interna e aproximam-se progressivamente das regiões periféricas à medida que envelhecem. Os indivíduos mais velhos, forrageiras, saem da colônia diariamente. Ritmos biológicos estão presentes nas operárias de todas as idades, mas apenas os ritmos das forrageiras estão bem caracterizados. Neste trabalho, o objetivo foi detectar mudanças no sistema temporal que ocorrem ao longo do desenvolvimento ontogenético de abelhas operárias. O ritmo monitorado foi aquele de consumo de O2, empregando um ciclo claro/escuro como agente sincronizador. O consumo de O2 foi registrado em nutrizes com 24 horas de vida e em forrageiras, sendo que as nutrizes foram divididas em dois grupos: Nutri_BOD, indivíduos colocados em condições constantes de temperatura e iluminação assim que emergiam do favo, e NUTRI_Col, indivíduos devolvidos à colônia por 24 horas antes dos testes. O protocolo experimental foi dividido em três fases: Fase1, forrageiras e Nutriz_BOD eram mantidos em condição constante de iluminação e temperatura durante 24 horas. Nutriz_Col era devolvida a colônia de origem durante esse mesmo intervalo; Fase2, exposição a ciclo claro/escuro 12:12h durante 48 horas; Fase3, todos os indivíduos voltavam às condições ambientais constantes. Em Fase2 e Fase3 foram feitas as medidas de consumo de O2. Os resultados da Fase2 não mostraram arrastamento, período significativo do ritmo difere de 24h. A média de consumo na fotofase apresenta diferença significativa da média de consumo na escotofase, para o grupo das forrageiras e Nutri_Col, sendo o consumo maior na fotofase. Ritmos em livre curso foram encontrados em todas as forrageiras e em 25% das nutrizes de ambos os grupos. Os resultados indicam a existência de um processo de maturação do sistema circadiano, bem como na capacidade de lidar com a luz, que representa uma situação desfavorável à sobrevivência das nutrizes. Como os dois grupos de nutrizes apresentaram ritmos endógenos, o surgimento deles independe da influência da colônia. A colônia, porém, parece modular a velocidade do estabelecimento do ritmo e sua capacidade de sincronizar-se com o ciclo claro/escuro ambiental. / The workers of the stingless bee, Melipona quadrifasciata, assume different tasks during their adult life. Newly emerged individuals - nurses - remain inside the nest, without contact with the external environment. As the workers mature, they migrate to more peripheral regions but only the oldest - foragers - leave the nest. Foragers have strong daily rhythms. Biological rhythms have already been detected in all the workers, but only the rhythms of foragers are well characterized. This work aimed to detect changes in temporal biological system during post-embryonic development. For this, the rhythm of oxygen consumption was measured and light/dark cycle was used as the synchronizing agent. Oxygen consumption was monitored in foragers and in nurses 24 hours after the emergence. The nurses were divided into two groups: 1-Nutri_BOD: the bees were kept in constant conditions of temperature and illumination. 2- NUTRI_Col: newly emerged workers were transferred back to the colony for 24 hours before the experiment. The experimental protocol was divided into three parts: 1- Forager and Nutriz_BOD were kept in constant conditions of illumination and temperature for 24 hours. Nutriz_Col were returned to the colony during the same interval. 2- Animals were exposed to a light/dark cycle, 12:12h, for 48 hours. 3- All the bees returned to constant conditions, for 4 days. Mesurements of O2 consumption were taken during the second and third parts of the experiment. There was not entrainment of the individual\'s rhythms. The period was different from 24h. In foragers and Nutri_Col there were significant differences between the average consumption in the photophase and the average consumption in the scotophase. A free running rhythm was present in all foragers and in 25% of Nutri_Col and Nutri_BOD. Results indicate the existence of a process of maturation running in the circadian system, and an increasing ability to respond to light. Presence of light is a non-permissive condition for the nurses\' survival. Endogenous rhythms are present in both groups of nurses. The presence of the colony is not necessary to the development of the rhythm. However, the colony seems to modulate the rate of to the development and the ability to synchronize with the light/dark cycle.

Chute aerators are widely used in spillways to avoid cavitation damage. When the water flow passes the aerator, two jets form – upper and lower jet. The purpose of this thesis has been to study the effects from the aerator by conducting experiments in a model with a flow depth large enough to ensure that the upper and lower jet remain separated. This means that the effects from the self-aeration at the upper surface has no effect on the process in the lower jet, thus making it possible to quantify the effects from the aerator. This thesis has also provided information of the bubble formation in the lower jet to aid in the ongoing research at Sichuan University. The following questions were set up for this thesis: • What is cavitation and how is it harmful? • What is the working principle of an aerator? • How is air concentration and bubble frequency distributed in the flow? • How well do the experimental results coincide with theoretical calculations? • How are air bubbles formed and transported within the flow? The effects from the aerator have been quantified by measuring the air concentration and bubble frequency throughout the cavity zone. The model was modified and the velocity was varied between the experiments to study how different parameters effected the aeration. The results indicate that much air is being entrapped in the lower surface, but only a small amount of the entrapped air is being entrained into the flow and that the bubble frequency increases with both distance from the aerator and with an increased flow velocity. No difference in behaviour was noticed between the different modifications of the model. The bubble formation was studied by recording the flow with a high-speed camera. These recordings were used to obtain data about important parameters for the ongoing research at Sichuan University.

The purpose of this study is to summarize theoretical and practical knowledge of frost resistance of concrete. It suggests, that there are numerous factors affecting the freeze-thaw resistence of concrete. These are especially raw materials, production technology, time and method of curing. The influence of addition, air entrainment and air void structure is complied and evaluated experimentally. The testing method is crucial for the evaluation of durability of concrete. Hence, this thesis includes a research of methods used around the world and practical comparison of some of them. This thesis is valuable because of implementation of the requirement in the standard ČSN EN 206 (2014) for the frost resistence of concrete in exposure classes XF1 and XF3.

Drop impact is a canonical problem in fluid mechanics, with numerous applications in industrial as well as natural phenomena. The extremely simple initial configuration of the experiment can produce a very large variety of fast and complex dynamics. Scientific progress was made in parallel with major improvements in imaging and computational technologies. Most recently, high-speed imaging video cameras have opened the exploration of new phenomena occurring at the micro-second scale, and parallel computing allowed realistic direct numerical simulations of drop impacts. We combine these tools to bring a new understanding of two fundamental aspects of drop impacts: splashing and air entrapment. The early dynamics of a drop impacting on a liquid pool at high velocity produces an ejecta sheet, emerging horizontally in the neck between the drop and the pool. We show how the interaction of this thin liquid sheet with the air, the drop or the pool, can produce micro-droplets and bubble rings. Then we detail how the breakup of the air film stretched between the drop and the pool for lower impact velocities can produce a myriad of micro-bubbles.

Purpose: We investigated motor-respiratory coordination (MRC) in visually guided forearm tracking movements focusing on two main questions: (1) Does attentional demand, training or complexity of the tracking task have an effect on the degree of MRC? (2) Does MRC impair the precision of those movements? We hypothesized that (1) enhanced attention to the tracking task and training increase the degree of MRC while higher task complexity would reduce it, and (2) MRC impairs tracking precision. Methods: Thirty-five volunteers performed eight tracking trials with several conditions: positive (direct) signal–response relation (SRR), negative (inverse) SRR to increase task complexity, specific instruction for enhanced attention to maximize tracking precision (“strict” instruction), and specific instruction that tracking precision would not be evaluated (“relaxed” instruction). The trials with positive and negative SRR were performed three times each to study training effects. Results: While the degree of MRC remained in the same range throughout all experimental conditions, a switch in phase-coupling pattern was observed. In conditions with positive SRR or with relaxed instruction, we found one preferred phase-relationship per period. With higher task complexity (negative SRR) or increased attentional demand (strict instruction), a tighter coupling pattern with two preferred phase-relationships per period was adopted. Our main result was that MRC improved tracking precision in all conditions except for that with relaxed instruction. Reduction of amplitude errors mainly contributed to this precision improvement. Conclusion: These results suggest that attention devoted to a precision movement intensifies its phase-coupling with breathing and enhances MRC-related improvement of tracking precision.

This study was designed to determine if impingement and entrainment by cooling water intake at the Comanche Peak Steam Electric Station have an adverse impact upon the Squaw Creek Reservoir fish population. The yearly impingement of fish was estimated to be 262,994 of 14 species. The threadfin shad (Dorosoma petenense) accounted for 96% of this total. Entrainment of eggs and larvae for a five month period was estimated to be 15,989,987 and 42,448,794 respectively. Two fish population studies were performed on Squaw Creek Reservoir to help assess impact. It was determined that the losses due to impingement and entrainment have no adverse impact upon the fish population of Squaw Creek Reservoir.

Zincor, a refinery in South Africa, uses the conventional roast-leachelectrowinning process to produce zinc metal. The roasting process of ZnS concentrate makes use of four Lurgi fluidized bed roasters to produce calcine (contains ZnO and ZnFe2O4 as zinc products) and SO2 gas. The roasting plant consists of two 18 m2 and two 35 m2 cross sectional area roasters. Prior to 1996, Zincor utilized air as the only oxidant and fluidizing medium in its roasters. The maximum dry feed rates that the roasters could process were 6.5 t/d.m2. In an attempt to increase production, oxygen enrichment was first trialled and then introduced into the fluidizing air. The ability of oxygen enrichment to increase the rate of the ZnS oxidation reaction allowed higher feed rates to the roasters. This was successful and oxygen enrichment was permanently implemented. That enabled dry feed rates to be maintained at 7.0 t/d.m2 and 7.3 t/d.m2 for the small and big roasters respectively. Oxygen enrichment up to 26% in the fluidizing air is utilized. Due to the highly competitive nature of the zinc industry, innovative processing techniques are necessary to be competitive. The aim of this study is to determine whether oxygen enriched air can be reduced by introducing micro-pelletized concentrate into the roaster feed blend, whilst maintaining current roaster feed rates and calcine quality. This study was executed in four parts. Firstly, the role entrainment played in influencing average particle residence time. Secondly, a study of production methods for stable micro-pellets. Thirdly, a study of the influence of oxygen enrichment and particle size on the roasting of micropellets. The fourth part of the study was introduction of micro-pellets into the Zincor roasters to determine whether oxygen enrichment could be reduced. The particle size distribution of a blend of feed concentrate to the roasters is 50% passing approximately 48 μm. This leads to entrainment values between 87% and 91%. The micro-pelletization process reduces the –500 μm fraction from 87% to 10%, which degrades to 30% during roasting. This requires that approximately 48% of the concentrate needs to be micro-pelletized to restore the 70% designed entrainment target. It was determined that entrained particles spend on average 0.46 hr to 2.44 hr in the bed compared to particles in the overflow that have residence times between 3.93 and 4.00 hr. The calculated times for entrainable particles are somewhat higher and for the bed overflow lower compared to the values measured by Spira, 1970. The required reaction time for micropellets was found to be far below their residence time inside a Zincor roaster. With a load of 20% micro-pellets introduced into the feed concentrate, the oxygen enrichment could be reduced by 60%. The quality of the calcine produced was maintained above the target of 98.8% ZnS to ZnO conversion. The results of this study have shown that the use of micro-pelletization of concentrate at Zincor reduces entrainment of particles successfully. Manipulation of entrainment through micro-pelletization can be used successfully to reduce oxygen enrichment, whilst improving production and maintaining quality at Zincor. Copyright / Dissertation (MEng)--University of Pretoria, 2009. / Materials Science and Metallurgical Engineering / unrestricted

This dissertation deals with instabilities of thin liquid films up to entrainment of drops. Four types of instabilities have been classified depending on the type of structure and process on the liquid film surface: two-dimensional slow waves, two-dimensional fast waves, three-dimensional waves, solitary waves and entrainment of drops from the film surface. This thesis analyzes the physical principles of instabilities and deals with the mathematical formulation of the problem. Shear and pressure forces acting on the surface of the liquid film are identified as the cause of instabilities. Mathematical models for predicting instabilities are demonstrated using approaches based on solving the Orr-Sommerfeld equation and the equations of motion in integral form. Models of shear and pressure forces acting on the surface of the film and selected models of film thickness are presented. The work is focused on the prediction of the initiation of two-dimensional waves using the integral approach. Shear stress and pressure forces acting on the liquid film surface have been modeled using the simulation of air flow over a solid surface. Finally, criteria for drop entrainment are presented with their dependence on air velocity and film thickness.

Cyanobakterien zŠhlen zu den Šltesten Lebewesen auf der Erde. Diese Bakterien, auch Blaualgen genannt, trugen wesentlich zur Sauerstoffanreicherung der Erde bei, da sie eine ausgeprŠgte FŠhigkeit zur Photosynthese besitzen. Der produzerte Sauerstoff der Photosynthese hemmt jedoch eine weitere AktivitŠt von Cyanobakterien, die Stickstofffixierung. Um die Hemmung zu vermeiden, werden diese AktivitŠten zeitlich getrennt und optimal dem tŠglichen Hell-Dunkel-Rhythmus angepasst. Ein evolutionŠrer Vorteil wird erzielt, wenn der Organismus diesen Rhythmus antizipiert und sich darauf vorbereitet. Aus diesem Grund haben Cyanobakterien eine innere Uhr entwickelt, deren Rhythmus zirkadian ist, ãzirka diemÒ bedeutet ãungefŠhr ein TagÒ. Cyanobakterien der Spezies Synechococcus elongatus PCC 7942 haben sich als Modellorganismus etabliert, weil in ihnen die ersten bakteriellen zirkadianen Oszillationen auf molekularer Ebene entdeckt worden sind. Ihre zirkadiane Uhr entspringt dreier, auf der DNS beieinanderliegenden, Gene (kaiA, kaiB, kaiC) und ihrer dazugehšrigen Proteine. Phosphorylierte KaiC-Proteine Ÿben eine RŸckkopplung auf die Transkription von kaiB und kaiC aus, wodurch die AktivitŠt des kaiBC-Promotors zirkadian oszilliert. Eines der wichtigsten Experimente der letzten Jahre hat gezeigt, dass dieser Transkriptions-Translations-Oszillator mit einem weiteren Oszillator gekoppelt ist, der nicht von Transkription und Translation abhŠngt. Das Experiment des Kondo Labors rekonstruiert zirkadiane Oszillationen mit nur drei Proteinen KaiA, KaiB, KaiC und ATP. Die Proteine bilden Komplexe verschiedener Stoichiometrie, die durchschnittliche Phosphorylierung des Proteins KaiC zeigt stabile Oszillationen mit einer zirkadianen Periode. Da ein Entfernen von einem der Proteine zum Verlust der Oszillationen fŸhrt, wird dieser Post-Translations-Oszillator auch als Kernoszillator bezeichnet. Der Phosphorylierungszyklus von KaiC wird bestimmt durch fortlaufende Phosphorylierung und Dephosphorylierung an zwei Positionen des Proteins, den AminosŠuren Serin 431 und Threonin 432. Die Phase des Kernoszillators kann an der Verteilung der vier PhosphorylierungszustŠnde (nicht-, serin-, threonin- und doppeltphosphoryliert) abgelesen werden. KaiC wechselwirkt mit KaiA und KaiB, damit verschieden phosphorylierte KaiC synchronisieren und die Uhr Ÿber mehrere Tage konstante Oszillationen zeigt. Die Details dieser Wechselwirkung sind jedoch unbekannt. In dieser Dissertation erstelle ich ein mathematisches Modell des Kernoszillators und simuliere die vorliegenden Experimente des O''Shea Labors. Die Simulation reproduziert den KaiC Phosphorylierungszyklus der Uhr quantitativ. Um die wichtigsten experimentellen Nebenbedingungen zu erfŸllen, muss das theoretische Modell zwei molekulare Eigenschaften von KaiC berŸcksichtigen, wodurch ich wichtige Vorhersagen treffe. Die erste Nebenbedingung ist durch die Robustheit des Systems gegeben. Die KaiC-Phosphorylierung Šndert sich nicht, wenn die Gesamtkonzentrationen der drei Proteine in gleicher Weise variiert werden. Um diese Bedingung zu erfŸllen, muss das Modell zwei verschiedenartige Komplexe von KaiA und KaiC berŸcksichtigen. ZusŠtzlich zu einem KaiAC Komplex, der die Autophosphorylierung von KaiC unterstŸtzt, muss KaiC den grš§ten Teil von KaiA unabhŠngig vom Phosphorylierungszustand sequestrieren. Diese zweite Bindestelle ist meine erste theoretische Vorhersage. Die zweite Nebenbedingung ist durch das Ÿbergangsverhalten nach Hinzugabe von KaiB gegeben. KaiB induziert eine Dephosphorylierung von KaiC, die abhŠngig vom Phosphorylierungsniveau ist. Ein Umschalten zwischen phosphoylierendem und dephosphorylierendem KaiC ist deshalb nur in bestimmten Zeitfenstern mšglich. Um die gemessenen Zeitfenster in der Simulation zu reproduzieren, postuliere ich im Modell, dass sechsfach Serin phosphorylierte KaiBC Komplexe KaiA inaktivieren. Diese hochgradig nichtlineare RŸckkopplung ist meine zweite theoretische Vorhersage. Die beiden Vorhersagen werden anschlie§end experimentell ŸberprŸft. HierfŸr werden aufgereinigte Kai-Proteine mit ATP gemischt. Proben an ausgewŠhlten Zeitpunkten werden mit der nativen Massenspektrometrie untersucht. Diese ist eine neuartige Methode, die es erlaubt, intakte Proteinkomplexe zu untersuchen. Die Spektren bestŠtigen sowohl die zweite KaiAC-Bindestelle als auch die nichtlineare RŸckkopplung. Das mathematische Modell erlaubt es au§erdem, die drei definierenden Prinzipien von zirkadianen Uhren fŸr den Kernoszillator zu erklŠren. Erstens sichern konstante Phosphorylierungs- und Dephosphorylierungsraten von KaiC und ein pŸnktliches Umschalten zwischen beiden Phasen den Freilauf des Oszillators. Dieser Freilauf bewirkt, dass die zirkadiane Uhr auch unter konstanten Bedingungen, vor allem gleichbleibenden LichtverhŠltnissen, weiterlaufen kann. Zweitens muss die Periodendauer des Oszillators zu unterschiedlichen Šu§eren Bedingungen erhalten bleiben (Temperaturkompensation). Diese Bedingung wird realisiert, indem temperaturabhŠngige Dissoziationskonstanten von KaiAC und KaiBC Komplexen Phasenverschiebungen erzeugen, die sich gegenseitig kompensieren. Drittens muss die Phase des Oszillators sich dem Tagesrhythmus anpassen kšnnen. Diese Anpassung folgt aus einem Šu§eren Warm-Kalt-Rhythmus, der die drei temperaturabhŠngigen Phasenverschiebungen nur zum Teil einschaltet und damit die Kompensation verhindert. Eine in silico Evolutionsanalyse zeigt, dass eine zweite phosphorylierbare AminosŠure einen evolutionŠren Vorteil bringt und die Verteilung der PhosphorylierungszustŠnde optimiert ist, um eindeutig die Zeit zu bestimmen. Das Ergebnis weist darauf hin, dass diese Verteilung die physiologisch wichtige Ausgangsgrš§e der Uhr ist und die vier PhosphroylierungszustŠnde die Funktionen der zirkadianen Uhr von Cyanobakterien sichern. / Biological activities in cyanobacteria are coordinated by an internal clock. The rhythm of the cyanobacterium Synechococcus elongatus PCC 7942 originates from the kai gene cluster and its corresponding proteins. In a test tube, the proteins KaiA, KaiB and KaiC form complexes of various stoichiometry and the average phosphorylation level of KaiC exhibits robust circadian oscillations in the presence of ATP. The characteristic cycle of individual KaiC proteins is determined by phosphorylation of serine 431 and threonine 432. Differently phosphorylated KaiC synchronize due to an interaction with KaiA and KaiB. However, the details of this interaction are unknown. Here, I quantitatively investigate the experimentally observed characteristic phosphorylation cycle of the KaiABC clockwork using mathematical modeling. I thereby predict the binding properties of KaiA to both KaiC and KaiBC complexes by analyzing the two most important experimental constraints for the model. In order to reproduce the KaiB-induced dephosphorylation of KaiC a highly non-linear feedback loop has been identified. This feedback originates from KaiBC complexes, which are exclusively phosphorylated at the serine residue. The observed robustness of the KaiC phosphorylation level to concerted changes of the total protein concentrations demands an inclusion of two KaiC binding sites to KaiA in the mathematical model. Besides the formation of KaiAC complexes enhancing the autophosphorylation activity of KaiC, the model accounts for a KaiC binding site, which constantly sequestrates a large fraction of free KaiA. These theoretical predictions have been confirmed by the novel method of native mass spectrometry, which was applied in collaboration with the Heck laboratory. The mathematical model elucidates the mechanism by which the circadian clock satisfies three defining principles. First, the highly non-linear feedback loop assures a rapid and punctual switch to dephosphorylation which is essential for a precise period of approximately 24 h (free-running rhythm). Second, the dissociation of the protein complexes increases with increasing temperatures. These perturbations induce opposing phase shifts, which exactly compensate during one period (temperature compensation). Third, a shifted external rhythm of low and high temperature affects only a part of the three compensating phase perturbations, which leads to phase shifts (phase entrainment). An in silico evolution analysis shows that the existing second phosphorylatable residue of KaiC is not necessary for the existence of sustained oscillations but provides an evolutionary benefit. The analysis demonstrates that the distribution of four phosphorylated states of KaiC is optimized in order for the organism to uniquely distinguish between dusk and dawn. Consequently, this thesis emphasizes the importance of the four phosphorylated states of KaiC, which assure the outstanding performance of the core oscillator.