Dissertations / Theses on the topic 'Cell synchronization'

Saccharomyces cerevisiae ist ein bekanntester Modellorganismen in der Systembiologie, der häufig zur Untersuchung des mitotischen Zellzyklus eukaryotischer Zellen verwendet wird. Des Zellzyklus wird durch Cycline, Cyclin-abhängige Kinasen (CDK) und CDK-Inhibitoren (CKI) reguliert. Der wichtigste Kontrollpunkt innerhalb des Zellzyklus reguliert den Übergang von der G1 in die S Phase und wird START genannt. Im dieser Arbeit verwenden wir einen stochastischen Modellierungsansatz, um die Auswirkungen verschiedener Synchronisationsmethoden auf den Zellzyklus zu untersuchen. Um Modellparameter zu schätzen, kombinieren wir Phasen aufgelöste mRNA-Verteilungen unsynchronisierter Einzelzellen und Protein-Zeitreihen synchronisierter Zellpopulationen. Somit können wir mRNA-Dynamiken für ausgewählte Synchronisationsmethoden vorhersagen. In einem zweistufigen Optimierungsansatz unterscheiden wir zwischen mRNA- und Protein-Ebene. Die Parameterschätzung basiert auf der Maximum-Likelihood-Methode. Die Phasen aufgelösten mRNA-Verteilungen wurden mithilfe der smFISH-Technik für SIC1, CLN2 und CLB5 gemessen. Die Protein-Zeitreihen wurden mithilfe von Western Blots für entsprechenden Proteine gemessen. Die gemessenen Moleküle sind die Hauptregulatoren des G1-S Phasenübergangs, welche die Komponenten unseres Zellzyklusmodells darstellen. Durch die erfolgreiche Integration von qualitativ unterschiedlichen Datentypen in der Parameterschätzung konnten wir eine systematische Analyse von Synchronisationseffekten auf den Zellzyklus durchführen. Der zeitlicher Ablauf des Zellzyklus ist dabei maßgeblich beeinflusst. Die stärksten zeitlichen Veränderungen weist die Synchronisation mit alpha-Faktor auf. Elutrierte Zellen sind den unsynchronisierten Zellen trotz verlängerter G1 Phase am ähnlichsten. Wir zeigen in dieser Arbeit, dass synchronisierte Zellpopulationen unzureichend sind, um Rückschlüsse auf den Zellzyklus unsynchronisierter Zellen zu ziehen.
cell cycle, G1/S transition, stochastic modeling, parameter estimation, smFISH, singel cells, Western blotting, cell populations Saccharomyces cerevisiae is a famous model organism in systems biology to study the mitotic cell cycle in eukaryotic cells. The cell cycle is a highly controlled process which is regulated by cyclins, cycline-dependent kinases (CDK) and cyclin-dependent kinase inhibitors (CKI). The main kinase involved in cell cycle regulation is Cdc28. START is the most important check point and controls the G1 to S phase transition. At this point, cells decide if they enter a new cell division cycle or not. In this study, we analyze influences of different synchronization methods on the cell cycle and differences between unsynchronized and synchronized cells by using a stochastic modeling approach. We combine phase-resolved mRNA distributions of unsynchronized single cells and protein time courses of synchronized cell populations to estimate model parameters and to predict synchronization specific mRNA dynamics. Parameter estimation is based on a maximum likelihood approach and performed in a 2-step-optimization in which we differentiate between mRNA and protein level. We measured phase-resolved mRNA distributions of mRNA species SIC1, CLN2 and CLB5 by smFISH and protein time courses of protein species Sic1, Cln2 and Clb5 by Western blotting. These molecules are key regulators of the G1 to S phase transition and represent components of our cell cycle model. By integrating qualitatively different data types in parameter estimation, we come up with a systematic analysis of synchronization effects on the cell cycle. Cell cycle timing is mainly responsible for differences between unsynchronized and synchronized cells and is mostly affected in alpha-factor synchronized cells. Ignoring the prolongation of the G1 phase, elutriated cells are most similar to unsynchronized cells. We show that synchronized cell populations are insufficient to derive general cell cycle behavior of unsynchronized cells.

Narrowband Internet-of-Things (NB-IoT) is a new wireless technology designed to support cellular networks with wide coverage for a massive number of very cheap low power user devices. Studies have been initiated for deployment of NB-IoT in unlicensed frequency bands, some of which demand the use of a frequency-hopping scheme with a short channel dwell time. In order for a device to connect to a cell, it must synchronize well within the dwell time in order to decode the frequency-hopping pattern. Due to the significant path loss, the narrow bandwidth and the device characteristics, decreasing the synchronization time is a challenge. This thesis studies different methods to decrease the synchronization time for NB-IoT without increasing the demands on the user device. The study shows how artificial fast fading can be combined with denser reference signalling in order to achieve improvements to the cell acquisition and synchronization procedure sufficient for enabling unlicensed operation of NB-IoT.
Narrowband Internet-of-Things (NB-IoT) är en ny trådlös teknik som är designad för att hantera mobilnät med vidsträckt täckning för ett massivt antal mycket billiga och strömsnåla användarenheter. Studier har inletts för att operera NB-IoT i olicensierade frekvensband, varav några kräver att frekvenshoppande spridningsspektrum, med kort uppehållstid per kanal, används. För att en användarenhet ska kunna ansluta till en basstation måste den slutföra synkronisingsfasen inom uppehållstiden, så att basstationens hoppmönster kan avkodas. På grund utav den stora signalförsvagningen, den smala bandbredden och användarenhetens egenskaper är det en stor utmaning att förkorta synkroniseringstiden. Detta examensarbete studerar olika metoder för att förkorta synkroniseringstiden i NB-IoT utan att öka kraven på användarenheten. Arbetet visar att artificiell snabb-fädning kan kombineras med tätare referenssignalering för att uppnå förbättringar i synkroniseringsprocessen som är tillräckliga för att möjliggöra operation av NB-IoT i olicensierade frekvensband.

What is flagellar swimming? Cilia and flagella are whip-like cell appendages that can exhibit regular bending waves. This active process emerges from the non-equilibrium dynamics of molecular motors distributed along the length of cilia and flagella. Eukaryotic cells can possess many cilia and flagella that beat in a coordinated fashion, thus transporting fluids, as in mammalian airways or the ventricular system inside the brain. Many unicellular organisms posses just one or two flagella, rendering them microswimmers that are propelled through fluids by the flagellar beat including sperm cells and the biflagellate green alga Chlamydomonas. Objectives. In this thesis in theoretical biological physics, we seek to understand the nonlinear dynamics of flagellar swimming and synchronization. We investigate the flow fields induced by beating flagella and how in turn external hydrodynamic flows change speed and shape of the flagellar beat. This flagellar load-response is a prerequisite for flagellar synchronization. We want to find the physical principals underlying stable synchronization of the two flagella of Chlamydomonas cells. Results. First, we employed realistic hydrodynamic simulations of flagellar swimming based on experimentally measured beat patterns. For this, we developed analysis tools to extract flagellar shapes from high-speed videoscopy data. Flow-signatures of flagellated swimmers are analysed and their effect on a neighboring swimmer is compared to the effect of active noise of the flagellar beat. We were able to estimate a chemomechanical energy efficiency of the flagellar beat and determine its waveform compliance by comparing findings from experiments, in which a clamped Chlamydomonas is exposed to external flow, to predictions from an effective theory that we designed. These mechanical properties have interesting consequences for the synchronization dynamics of Chlamydomonas, which are revealed by computer simulations. We propose that direct elastic coupling between the two flagella of Chlamydomonas, as suggested by recent experiments, in combination with waveform compliance is crucial to facilitate in-phase synchronization of the two flagella of Chlamydomonas.

Micronúcleos são estruturas constituídas por material cromatínico contido por um envoltório nuclear e menores que o núcleo principal. Apesar do amplo uso do teste do micronúcleo na avaliação do potencial genotóxico de diversas substâncias, os trabalhos cujas preocupações sejam elucidar o mecanismo de formação dessas estruturas, seu conteúdo e a fase do ciclo celular em que surgem, são raros. O objetivo do presente trabalho foi estudar a cinética de surgimento de micronúcleos em células A549, provenientes de carcinoma de pulmão humano, submetidas à sincronização. Após duplo bloqueio por ausência de soro fetal bovino e adição de vincristina ao meio, o surgimento de micronúcleos foi acompanhado com o auxílio de um marcador para fase S. Os resultados obtidos indicam que micronúcleos podem surgir tanto durante a mitose quanto na intérfase e possuem capacidade de replicação de DNA, independentemente do núcleo principal. A capacidade de escapar ao duplo bloqueio permite sugerir que o ponto de checagem de ligação ao fuso mitótico em A549 não é funcional. Também foram observadas seqüências amplificadas de EGFR no interior dos micronúcleos. A interpretação do significado dos micronúcleos é importante para a definição de sua relação com a expulsão de oncogenes em células tumorais ou de outras seqüências amplificadas.
Micronuclei are structures composed by chromatin material contained in the nuclear envelope and smaller than the main nucleus. Micronucleus test has been widely used in the genotoxic potential evaluation of different compounds. Although a few report concerning on the mechanism of micronucleus genesis, its DNA sequences content and the cell cycle phase when they arise. The aim of this work was to analyze the kinetic of micronuclei in A549 cells from human lung carcinoma submitted to cell cycle synchronization. After double blocking by fetal bovine serum deprivation and vincristine treatment, micronucleus formation was monitored with a S-phase marker. The results have showed that both in the mitosis and in the interphasic phase, micronuclei may arise and they were able to replicate its DNA. This process seemed to be independent of main nucleus. Cellular ability to escape from double blocking suggests that mitotic spindle checkpoint in A549 is not functional. Moreover, EGFR sequences were detected into the micronucleus. It is important to elucidate the micronucleus meaning to describe precisely its association with elimination of oncogene or other amplified sequences from the tumor cells.

Subject of study: Cilia and flagella are slender appendages of eukaryotic cells. They are actively bending structures and display regular bending waves. These active flagellar bending waves drive fluid flows on cell surfaces like in the case of the ciliated trachea or propels single cell micro-swimmers like sperm or alga. Objective: The axoneme is the evolutionarily conserved mechanical apparatus within cilia and flagella. It is comprised of a cylindrical arrangement of microtubule doublets, which are the elastic elements and dyneins, which are the force generating elements in the axonemal structure. Dyneins collectively bend the axoneme and must be specifically regulated to generate symmetric and highly asymmetric waveforms. In this thesis, I address the question of the molecular origin of the asymmetric waveform and test different theoretical descriptions for motor regulation. Approach: I introduce the isolated and reactivated Chlamydomonas axoneme as an experimental model for the symmetric and asymmetric flagellar beat. This system allows to study the beat in a controlled and cell free environment. I use high-speed microscopy to record shapes with high spatial and temporal resolution. Through image analysis and shape parameterization I extract a minimal set of parameters that describe the flagellar waveform. Using Chlamydomonas, I make use of different structural and motor mutants to study their effect on the shape in different reactivation conditions. Although the isolated axoneme system has many advantages compared to the cell-bound flagellum, to my knowledge, it has not been characterized yet. Results: I present a shape parameterization of the asymmetric beat using Fourier decomposition methods and find, that the asymmetric waveform can be understood as a sinusoidal beat around a circular arc. This reveals the similarities of the two different beat types: the symmetric and the asymmetric beat. I investigate the origin of the beat-asymmetry and find evidence for a specific dynein motor to be responsible for the asymmetry. I furthermore find experimental evidence for a strong sliding restriction at the basal end of the axoneme, which is important to establish a static bend. In collaboration with P. Sartori and F. Jülicher, I compare theoretical descriptions of different motor control mechanisms and find that a curvature controlled motor-regulation mechanism describes the experimental data best. We furthermore find, that in the dynamic case an additional sliding restriction at the base is unnecessary. By comparing the waveforms of intact cells and isolated reactivated axonemes, I reveal the effect of hydrodynamic loading, and the influence of boundary conditions on the shape of the beating flagella.

Subject of study: Cilia and flagella are slender appendages of eukaryotic cells. They are actively bending structures and display regular bending waves. These active flagellar bending waves drive fluid flows on cell surfaces like in the case of the ciliated trachea or propels single cell micro-swimmers like sperm or alga. Objective: The axoneme is the evolutionarily conserved mechanical apparatus within cilia and flagella. It is comprised of a cylindrical arrangement of microtubule doublets, which are the elastic elements and dyneins, which are the force generating elements in the axonemal structure. Dyneins collectively bend the axoneme and must be specifically regulated to generate symmetric and highly asymmetric waveforms. In this thesis, I address the question of the molecular origin of the asymmetric waveform and test different theoretical descriptions for motor regulation. Approach: I introduce the isolated and reactivated Chlamydomonas axoneme as an experimental model for the symmetric and asymmetric flagellar beat. This system allows to study the beat in a controlled and cell free environment. I use high-speed microscopy to record shapes with high spatial and temporal resolution. Through image analysis and shape parameterization I extract a minimal set of parameters that describe the flagellar waveform. Using Chlamydomonas, I make use of different structural and motor mutants to study their effect on the shape in different reactivation conditions. Although the isolated axoneme system has many advantages compared to the cell-bound flagellum, to my knowledge, it has not been characterized yet. Results: I present a shape parameterization of the asymmetric beat using Fourier decomposition methods and find, that the asymmetric waveform can be understood as a sinusoidal beat around a circular arc. This reveals the similarities of the two different beat types: the symmetric and the asymmetric beat. I investigate the origin of the beat-asymmetry and find evidence for a specific dynein motor to be responsible for the asymmetry. I furthermore find experimental evidence for a strong sliding restriction at the basal end of the axoneme, which is important to establish a static bend. In collaboration with P. Sartori and F. Jülicher, I compare theoretical descriptions of different motor control mechanisms and find that a curvature controlled motor-regulation mechanism describes the experimental data best. We furthermore find, that in the dynamic case an additional sliding restriction at the base is unnecessary. By comparing the waveforms of intact cells and isolated reactivated axonemes, I reveal the effect of hydrodynamic loading, and the influence of boundary conditions on the shape of the beating flagella.:Contents 1 Introduction. . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.1 Biology of Cilia and Flagella . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.1.1 The dimensions of flagellated micro-swimmers . . . . . . . . . . . . . . . . . 4 1.1.2 The symmetric and the asymmetric beat . . . . . . . . .. . . . . . . . . . . . 5 1.1.3 Chlamydomonas reinhardtii as a flagella model . . . . . . . . . . 5 1.2 The axoneme is the internal structure in eukaryotic cilia and flagella . . 6 1.3 Structure and function of microtubules and dyneins . . . . . . . . . . . 9 1.3.1 Microtubules: The structural elements in the axoneme . . . . . . 9 1.3.2 Dyneins: The force generators that drive the axonemal beat . . . 10 1.3.3 The asymmetries in the axoneme and consequences for the beat 17 1.4 Axonemal waveform models and mechanisms: from sliding to bending to beating . . . . . . . . . . . . . . 20 1.5 Geometrical representation and parameterization of the axonemal beat . . . . . . . . . . . . . . . 23 2 Questions addressed in this thesis . . . . . . . . . . . . . . 27 3 Material and Methods . . . . . . . . . . . . . . 29 3.1 Chlamydomonas cells: Axoneme preparation and motility assays . . . . 29 3.1.1 Culturing of Chlamydomonas reinhardtii cells . . . . . . . . . . . 29 3.1.2 Isolation, demembranation and storage of axonemes . . . . . . . 33 3.1.3 Reactivation of axonemes in controlled conditions . . . . . . . . . 35 3.1.4 Axoneme gliding assay using kinesin 1 . . . . . . . . . . . . . . . 36 3.2 Imaging and image processing . . . . . . . . . . . . . . . . . . . . . . . . 38 3.2.1 High-speed imaging of the flagella and axonemes . . . . . . . . . 38 3.2.2 Precise tracking of isolated axonemes and the flagella of cells . . 42 3.2.3 High throughput frequency evaluation of isolated axonemes . . . 47 3.2.4 Beat frequency characterization of the reactivated WT axoneme . . . . . . . . . . . . . . 49 4 Results and Discussion . . . . . . . . . . . . . . 53 4.1 The beat of the axoneme propagates from base to tip . . . . . . . . . . . 53 4.1.1 TEM study reveals no sliding at the base of a bend axoneme . . 53 4.1.2 The direction of wave propagation is directly determined from the reactivation of polarity marked axonemes . . . . . . . . . . 57 4.1.3 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 4.2 The asymmetric beat is the superposition of a static semi-circular arc and a sinusoidal beat . . . . . . .. . . . . . . . . . . . . . . . . 61 4.2.1 The waveform is parameterized by Fourier decomposition in time . . . . . . . . . . . . . . 61 4.2.2 The 0th and 1st Fourier modes describe the axonemal waveform . . . . . . . . . . . . . . 65 4.2.3 General dependence of shape parameters on axoneme length and beat frequency. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 4.2.4 The isolated axoneme is a good model for the intact flagellum . .. . . . . . . . . . . . . . 71 4.2.5 Summary: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 4.3 The circular motion is a consequence of the axonemal waveform . . . . . . . . . . . . . . . . . . . 79 4.3.1 Hydrodynamic relations for small amplitude waves explain the relation between swimming and shape of axonemes . . . . 79 4.3.2 The swimming path can be reconstructed using shape information and a hydrodynamic model . . . . . . . . . . . . . . . . 83 4.3.3 Motor mutations alter the direction of rotation of reactivated axonemes. . . . . . . . . . . . . . . . . . . . . . . . 84 4.3.4 Summary: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 4.4 The molecular origin of the circular mean shape. . . . . . . . . . . . . . 89 4.4.1 Motor Mutations do not abolish the mean shape, a structural mutation does . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 4.4.2 The axoneme is straight in absence of ATP but bend at low ATP concentrations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 4.4.3 Viscous load decreases the mean curvature . . . . . . . . . . . . 99 4.4.4 Summary: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 4.5 Curvature-dependent dynein activation accounts for the shape of the beat of the isolated axoneme . . . . . . . . . . . . . . . . 103 5 Conclusions and Outlook . . . . . . . . . . . . . . . . 109 5.1 Summary of the results . . . . . . . . . . . . . . . . . . . . . . . . . . . 109 5.2 Future directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110 Abbreviations . . . . . . . . . . . . . . . . 111 List of figures . . . . . . . . . . . . . . . . 116 List of tables . . . . . . . . . . . . . . . . 118 Bibliography

Bacterial proliferation has been studied for more than 100 years, but our knowledge of the mechanisms that control its dynamical aspects is still very limited. In this Thesis we have studied, at both singlecell and population levels, different aspects of the main regulators of bacterial proliferation, namely the cell cycle, biomass production and membrane stability. Our goal has been to shed light on how perturbation of these regulators affects their dynamical responses in a variety of situations. Specifically, we show that the periodic doubling of genes through the bacterial cell cycle partially entrains a genetic oscillator, but that significant coupling only arises when the oscillator is fed back to cell cycle. We have also studied perturbations in the ability of cells to produce biomass, for instance through antibiotics that affect ribosomal function. Our results suggest that survival in the presence of these antibiotics is determined by the ability of the cells to incorporate magnesium ions, which can be captured by membrane potential changes. Finally, we show that interplay between different bacterial species with diverse sensitivities to membrane-targeting antibiotics can have an unexpected outcome in co-culture, which can be explained in a simple manner by the sharing of the antibiotic between the two species.
La proliferació bacteriana ha estat estudiada durant més de 100 anys, però el nostre coneixement dels mecanismes que controlen els aspectes dinàmics d’aquesta encara són molt limitats. En aquesta Tesi hem estudiat, tant en cèl.lules individuals com a nivell poblacional, diferents aspectes dels principals reguladors de la proliferació cel.lular, concretament el cicle cel.lular, la producció de biomassa i la estabilitat de la membrana. El nostre objectiu ha estat ajudar a explicar com pertorbacions en aquests reguladors afecten la dinàmica de les seves respostes en una varietat de situacions. Específicament, mostrem que el doblament periòdic de gens a través del cicle cel.lular bacterià entrena parcialment un oscil.lador genètic, però aquest acoblament només és significatiu quan l’oscil.lador retorna la resposta al cicle cel.lular. Tamée hem estudiat pertorbacions en l’habilitat de les cèl.lules de produir biomassa, per exemple a través d’antibiòtics que afecten la funció ribosomal. Els nostres resultats suggereixen que la supervivència sota l’efecte d’aquests antibiòtics ve determinada per l’habilitat de les cèl.lules d’incorporar ions de magnesi, la qual pot ser capturada a través de canvis en el potencial de membrana. Finalment, mostrem que les interaccions entre diferents espècies bacterianes amb diverses sensitivitats a antibiòtics que afecten la membrana cel.lular poden donar lloc a resultats inesperats quan es troben en co-cultiu, els quals poden ser explicats de forma senzilla a partir del compartiment de l’antibiòtic entre les dues espècies.

Le diadenosine tetraphosphate (ap**(4)a) est le principal produit de la reaction d'aminoacylation catalysee par certaines aminoacyl-trna synthetases. L'ap**(4)a est une molecule "signal" s'accumulant a l'interphase g1/5 du cycle cellulaire des cellules eucarydes declenchant ainsi la synthese du dna precedant la division cellulaire. Quantification du contenu cellulaire en ap**(4)a et en atp apres synchronisation des cellules (hepertome de rat, fibroblaste de souris) en culture par l'aphidicoline agent bloquant les cellules en phase s et par privation de serum qui arrete la croissance en mi-phase g. Mise au point d'un modele de reparation, dans les ovocytes ou les oeufs non fecondes de xenopus laevis, du plasmute pbr322 modifie par l'acetylaminofluorene. L'effet de l'ap**(4)a sur la reparation est etudie

La modélisation, l’analyse et le contrôle des oscillations, notamment des rythmes biologiques ont été étudiés dans cette thèse. La thèse est divisée en deux parties. Dans la première partie, motivée par un problème pratique de la surveillance de l'environnement côtier, cette thèse considère les rythmes biologiques des huîtres. En utilisant les informations des rythmes biologiques, une solution de surveillance environnementale indirecte en utilisant les huîtres comme bio-capteur a été proposé. La solution proposée se base sur l'estimation de la perturbation par la modélisation du rythme biologique des huîtres par un oscillateur de Van der Pol. Une limite inhérente de cette approche est que celle-ci fonctionne uniquement grâce à la détection des comportements anormaux. Cependant les comportements anormaux ne sont pas tous liés à la pollution. Nous considérons donc la détection d'un type particulier de comportement oscillatoire anormal à savoir la ponte, qui est un phénomène naturel et non lié à la pollution. Le premier problème de la deuxième partie est la robustesse des oscillations dans la division cellulaire. Les oscillations persistent dans les oscillateurs génétiques après la division cellulaire. Dans cette thèse, nous fournissons des conditions d'analyse qui garantissent la synchronisation de phase après la division cellulaire. Enfin, nous considérons le problème de la synchronisation des systèmes multi-stables en utilisant l’Input-to-State Stability (ISS). En utilisant une généralisation récente de la théorie de l'ISS pour les systèmes multi-stables, nous proposons des conditions suffisantes pour la synchronisation des systèmes multi-stables
Modeling, analysis and control of oscillations, notably biological rhythms have been studied in this thesis. The thesis is divided into two parts. In part-I, motivated by a practical problem of environmental monitoring of coastal environment, this thesis considers the biological rhythms of oysters. Using the information of biological rhythms, an indirect environmental monitoring solution using oysters as bio-sensor has been proposed. The proposed solution works on estimating the perturbation by modeling the biological rhythm of oysters through Van der Pol oscillator model. An inherent limit of this approach is that it works through detecting abnormal behavior only. However abnormal behaviors are not all related to pollution. So, we consider the detection of a particular type of abnormal oscillatory behavior i.e. spawning (behavior during reproduction) which is a natural phenomenon and not related to pollution. In part-II, oscillations are studied from a theoretical point of view. The first problem of this part is the robustness of oscillations under cell division. Oscillations persist in genetic oscillators after cell division. In this thesis, we provide analytical conditions that guarantee phase synchronization after cell division using Phase Response Curve (PRC) formalism. Finally we consider the problem of synchronization of multi-stable systems using Input-to-State (ISS) stability tool. Using a recent generalization of ISS theory for multi-stable systems, we propose sufficient conditions for the synchronization of multi-stable systems. As a side result, this work has been applied for the global synchronization of the Brockett oscillator

Following the discovery of the one-dimensional sequence of human DNA, much focus has been directed on microscopy and molecular techniques to learn about the spatial organization of chromatin in a 3D cell. The development of these powerful tools has enabled high-resolution, genome-wide analysis of chromosome structure under many different conditions. In this thesis, I focus on how the organization of interphase chromatin is established and maintained following mitosis. Mitotic chromosomes are folded into helical loop arrays creating short and condensed chromosomes, while interphase chromosomes are decondensed and folded into a number of structures at different length scales ranging from loops between CTCF sites, enhancers and promoters to topologically associating domains (TADs), and larger compartments. While the chromatin organization at these two very different states is well defined, the transition from a mitotic to interphase chromatin state is not well understood. The aim of this thesis is to determine how interphase chromatin is organized following mitotic chromosome decondensation and to interrogate factors potentially responsible for driving the transition. First, I determine the temporal order with which CTCF-loops, TADs, and compartments reform as cells exit mitosis, revealing a unique structure at the anaphase-telophase transition never observed before. Second, I test the role of transcription in reformation of 3D chromosome structure and show that active transcription is not required for the formation of most interphase chromatin features; instead, I propose that transcription relies on the proper formation of these structures. Finally, I show that RNA in the interphase nucleus can be degraded with only slight consequences on the overall chromatin organization, suggesting that once interphase chromatin structures are achieved, the structures are stable and RNA is only required to reduce the mixing of active and inactive compartments. Together, these studies further our understanding of how interphase structures form, how these structures relate to functional activities of the interphase cell, and the stability of chromatin structures over time.

The aim of this master thesis is to introduce a new technique for the design of cellular automata which will provide a better possibilities for the implementation and solving given problems in an environment of non-uniform automata. In this work, the theoretical foundations of cellular automata have been summarized and the possibilities of their design were examined using two evolutionary principles that have commonly been used - genetic algorithm and cellular programming. Two principally different issues were selected on which the possibilities and capabilities of these techniques were proven: the synchronization problem and the system of implementation of logic gates in an environment of cellular automata. Based on a review of the implementation properties and the initial results of usage of these methods a new design method for cellular automata was created - cellular evolution. The cellular evolution with its method of "prediction of the future state of surrounding cells" provides new possibilities in the design of cellular automata since it operates with structured genes which allow the gene to be active for a variety of cellular surroundings. In the conclusion of this work, all three methods were compared on two selected problems and their abilities were summarized in a detailed overview.

Le cycle de division cellulaire et l'horloge circadienne sont deux processus fondamentaux de la régulation cellulaire qui génèrent une expression rythmique des gènes et des protéines. Dans les cellules mammifères, les mécanismes qui sous-tendent les interactions entre le cycle cellulaire et l'horloge restent très mal connus. Dans cette thèse, nous étudions ces deux oscillateurs biologiques, à la fois individuellement et en tant que système couplé, pour comprendre et reproduire leurs principales propriétés dynamiques, détecter les composants essentiels du cycle cellulaire et de l'horloge, et identifier les mécanismes de couplage. Chaque oscillateur biologique est modélisé par un système d'équations différentielles ordinaires non linéaires et ses paramètres sont calibrés par rapport à des données expérimentales: le modèle du cycle cellulaire se base sur les modifications post-traductionnelles du complexe Cdk1-CycB et mène à un oscillateur de relaxation dont la dynamique et la période sont contrôlés par les facteurs de croissance; le modèle de l'horloge circadienne reproduit l'oscillation antiphasique BMAL1/PER:CRY et l'adaptation de la durée des états d'activation et répression par rapport à deux signaux d’entrée hormonaux déphasés. Pour analyser les interactions entre les deux oscillateurs nous étudions la synchronisation des deux rythmes pour des régimes de couplage uni- ou bi-directionnels. Les simulations numériques reproduisent les ratios entre les périodes de l'horloge et du cycle cellulaire, tels que 1:1, 3:2 et 5:4. Notre étude suggère des mécanismes pour le ralentissement du cycle cellulaire avec des implications pour la conception de nouvelles chronothérapies
The cell division cycle and the circadian clock are two fundamental processes of cellular control that generate cyclic patterns of gene activation and protein expression, which tend to be synchronous in healthy cells. In mammalian cells, the mechanisms that govern the interactions between cell cycle and clock are still not well identified. In this thesis we analyze these two biological oscillators, both separately and as a coupled system, to understand and reproduce their main dynamical properties, uncover essential cell cycle and clock components, and identify coupling mechanisms. Each biological oscillator is first modeled by a system of non-linear ordinary differential equations and its parameters calibrated against experimental data: the cell cycle model is based on post-translational modifications of the mitosis promoting factor and results in a relaxation oscillator whose dynamics and period are controlled by growth factor; the circadian clock model is transcription-based, recovers antiphasic BMAL1/PER:CRY oscillation and relates clock phases to metabolic states. This model shows how the relative duration of activating and repressing molecular clock states is adjusted in response to two out-of-phase hormonal inputs. Finally, we explore the interactions between the two oscillators by investigating the control of synchronization under uni- or bi-directional coupling schemes. Simulations of experimental protocols replicate the oscillators’ period-lock response and recover observed clock to cell cycle period ratios such as 1:1, 3:2 and 5:4. Our analysis suggests mechanisms for slowing down the cell cycle with implications for the design of new chronotherapies

Imagine a world where someone’s personal information is constantly compromised, where federal government entities AKA Big Brother always knows what anyone is Googling, who an individual is texting, and their emoticons on Twitter. Government entities have been doing this for years; they never cared if they were breaking the law or their moral compass of human dignity. Every day the Federal government blatantly siphons data with programs from the original ECHELON to the new series like PRISM and Xkeyscore so they can keep their tabs on issues that are none of their business; namely, the personal lives of millions. Our allies are taking note; some are learning our bad habits, from Government Communications Headquarters’ (GCHQ) mass shadowing sharing plan to America’s Russian inspiration, SORM. Some countries are following the United States’ poster child pose of a Brave New World like order of global events. Others like Germany are showing their resolve in their disdain for the rise of tyranny. Soon, these new found surveillance troubles will test the resolve of the American Constitution and its nation’s strong love and tradition of liberty. Courts are currently at work to resolve how current concepts of liberty and privacy apply to the current conditions facing the privacy of society. It remains to be determined how liberty will be affected as well; liberty for the United States of America, for the European Union, the Russian Federation and for the people of the World in regards to the extent of privacy in today’s blurred privacy expectations.
B.S.
Bachelors
Health and Public Affairs
Legal Studies

The present habilitation thesis in theoretical biological physics addresses two central dynamical processes in cells and organisms: (i) active motility and motility control and (ii) self-organized pattern formation. The unifying theme is the nonlinear dynamics of biological function and its robustness in the presence of strong fluctuations, structural variations, and external perturbations. We theoretically investigate motility control at the cellular scale, using cilia and flagella as ideal model system. Cilia and flagella are highly conserved slender cell appendages that exhibit spontaneous bending waves. This flagellar beat represents a prime example of a chemo-mechanical oscillator, which is driven by the collective dynamics of molecular motors inside the flagellar axoneme. We study the nonlinear dynamics of flagellar swimming, steering, and synchronization, which encompasses shape control of the flagellar beat by chemical signals and mechanical forces. Mechanical forces can synchronize collections of flagella to beat at a common frequency, despite active motor noise that tends to randomize flagellar synchrony. In Chapter 2, we present a new physical mechanism for flagellar synchronization by mechanical self-stabilization that applies to free-swimming flagellated cells. This new mechanism is independent of direct hydrodynamic interactions between flagella. Comparison with experimental data provided by experimental collaboration partners in the laboratory of J. Howard (Yale, New Haven) confirmed our new mechanism in the model organism of the unicellular green alga Chlamydomonas. Further, we characterize the beating flagellum as a noisy oscillator. Using a minimal model of collective motor dynamics, we argue that measured non-equilibrium fluctuations of the flagellar beat result from stochastic motor dynamics at the molecular scale. Noise and mechanical coupling are antagonists for flagellar synchronization. In addition to the control of the flagellar beat by mechanical forces, we study the control of the flagellar beat by chemical signals in the context of sperm chemotaxis. We characterize a fundamental paradigm for navigation in external concentration gradients that relies on active swimming along helical paths. In this helical chemotaxis, the direction of a spatial concentration gradient becomes encoded in the phase of an oscillatory chemical signal. Helical chemotaxis represents a distinct gradient-sensing strategy, which is different from bacterial chemotaxis. Helical chemotaxis is employed, for example, by sperm cells from marine invertebrates with external fertilization. We present a theory of sensorimotor control, which combines hydrodynamic simulations of chiral flagellar swimming with a dynamic regulation of flagellar beat shape in response to chemical signals perceived by the cell. Our theory is compared to three-dimensional tracking experiments of sperm chemotaxis performed by the laboratory of U. B. Kaupp (CAESAR, Bonn). In addition to motility control, we investigate in Chapter 3 self-organized pattern formation in two selected biological systems at the cell and organism scale, respectively. On the cellular scale, we present a minimal physical mechanism for the spontaneous self-assembly of periodic cytoskeletal patterns, as observed in myofibrils in striated muscle cells. This minimal mechanism relies on the interplay of a passive coarsening process of crosslinked actin clusters and active cytoskeletal forces. This mechanism of cytoskeletal pattern formation exemplifies how local interactions can generate large-scale spatial order in active systems. On the organism scale, we present an extension of Turing’s framework for self-organized pattern formation that is capable of a proportionate scaling of steady-state patterns with system size. This new mechanism does not require any pre-pattering clues and can restore proportional patterns in regeneration scenarios. We analytically derive the hierarchy of steady-state patterns and analyze their stability and basins of attraction. We demonstrate that this scaling mechanism is structurally robust. Applications to the growth and regeneration dynamics in flatworms are discussed (experiments by J. Rink, MPI CBG, Dresden)
Das Thema der vorliegenden Habilitationsschrift in Theoretischer Biologischer Physik ist die nichtlineare Dynamik funktionaler biologischer Systeme und deren Robustheit gegenüber Fluktuationen und äußeren Störungen. Wir entwickeln hierzu theoretische Beschreibungen für zwei grundlegende biologische Prozesse: (i) die zell-autonome Kontrolle aktiver Bewegung, sowie (ii) selbstorganisierte Musterbildung in Zellen und Organismen. In Kapitel 2, untersuchen wir Bewegungskontrolle auf zellulärer Ebene am Modelsystem von Zilien und Geißeln. Spontane Biegewellen dieser dünnen Zellfortsätze ermöglichen es eukaryotischen Zellen, in einer Flüssigkeit zu schwimmen. Wir beschreiben einen neuen physikalischen Mechanismus für die Synchronisation zweier schlagender Geißeln, unabhängig von direkten hydrodynamischen Wechselwirkungen. Der Vergleich mit experimentellen Daten, zur Verfügung gestellt von unseren experimentellen Kooperationspartnern im Labor von J. Howard (Yale, New Haven), bestätigt diesen neuen Mechanismus im Modellorganismus der einzelligen Grünalge Chlamydomonas. Der Gegenspieler dieser Synchronisation durch mechanische Kopplung sind Fluktuationen. Wir bestimmen erstmals Nichtgleichgewichts-Fluktuationen des Geißel-Schlags direkt, wofür wir eine neue Analyse-Methode der Grenzzykel-Rekonstruktion entwickeln. Die von uns gemessenen Fluktuationen entstehen mutmaßlich durch die stochastische Dynamik molekularen Motoren im Innern der Geißeln, welche auch den Geißelschlag antreiben. Um die statistische Physik dieser Nichtgleichgewichts-Fluktuationen zu verstehen, entwickeln wir eine analytische Theorie der Fluktuationen in einem minimalen Modell kollektiver Motor-Dynamik. Zusätzlich zur Regulation des Geißelschlags durch mechanische Kräfte untersuchen wir dessen Regulation durch chemische Signale am Modell der Chemotaxis von Spermien-Zellen. Dabei charakterisieren wir einen grundlegenden Mechanismus für die Navigation in externen Konzentrationsgradienten. Dieser Mechanismus beruht auf dem aktiven Schwimmen entlang von Spiralbahnen, wodurch ein räumlicher Konzentrationsgradient in der Phase eines oszillierenden chemischen Signals kodiert wird. Dieser Chemotaxis-Mechanismus unterscheidet sich grundlegend vom bekannten Chemotaxis-Mechanismus von Bakterien. Wir entwickeln eine Theorie der senso-motorischen Steuerung des Geißelschlags während der Spermien-Chemotaxis. Vorhersagen dieser Theorie werden durch Experimente der Gruppe von U.B. Kaupp (CAESAR, Bonn) quantitativ bestätigt. In Kapitel 3, untersuchen wir selbstorganisierte Strukturbildung in zwei ausgewählten biologischen Systemen. Auf zellulärer Ebene schlagen wir einen einfachen physikalischen Mechanismus vor für die spontane Selbstorganisation von periodischen Zellskelett-Strukturen, wie sie sich z.B. in den Myofibrillen gestreifter Muskelzellen finden. Dieser Mechanismus zeigt exemplarisch auf, wie allein durch lokale Wechselwirkungen räumliche Ordnung auf größeren Längenskalen in einem Nichtgleichgewichtssystem entstehen kann. Auf der Ebene des Organismus stellen wir eine Erweiterung der Turingschen Theorie für selbstorganisierte Musterbildung vor. Wir beschreiben eine neue Klasse von Musterbildungssystemen, welche selbst-organisierte Muster erzeugt, die mit der Systemgröße skalieren. Dieser neue Mechanismus erfordert weder eine vorgegebene Kompartimentalisierung des Systems noch spezielle Randbedingungen. Insbesondere kann dieser Mechanismus proportionale Muster wiederherstellen, wenn Teile des Systems amputiert werden. Wir bestimmen analytisch die Hierarchie aller stationären Muster und analysieren deren Stabilität und Einzugsgebiete. Damit können wir zeigen, dass dieser Skalierungs-Mechanismus strukturell robust ist bezüglich Variationen von Parametern und sogar funktionalen Beziehungen zwischen dynamischen Variablen. Zusammen mit Kollaborationspartnern im Labor von J. Rink (MPI CBG, Dresden) diskutieren wir Anwendungen auf das Wachstum von Plattwürmern und deren Regeneration in Amputations-Experimenten

La chronothérapie des cancers administre les médicaments anticancéreux à des moments précis de la journée afin d’en optimiser la tolérance et l’efficacité. Cependant le système circadien qui règle sur 24 h la prolifération et le métabolisme cellulaires peut être altéré par un décalage horaire chronique, la mutation d’un gène de l’horloge, ou un traitement, favorisant ainsi la survenue de pathologies métaboliques, comportementales ou malignes. La disparité des profils circadiens de température corporelle des patients cancéreux ainsi que leurs modifications sous chimiothérapie fournit les bases d’une personnalisation de la chronothérapeutique. La capacité d’un cycle thermique à entraîner sur 24 h l’horloge circadienne de cellules d’hépatocarcinome en culture indique que ce biomarqueur est aussi un effecteur de la synchronisation des cellules cancéreuses, et constitue un repère circadien pour la chronothérapeutique in vitro et in vivo
Chronotherapy delivers anticancer drugs at specific times of the day to optimize tolerability and efficacy. However, the circadian system that controls cell proliferation and metabolism over 24 h, can be altered by a chronic jet lag, a clock gene mutation, or a xeniobiotic treatment, thus favoring the occurrence of metabolic, behavioral or malignancies. The disparity of circadian body temperature patterns of cancer patients as well as its disruption during the treatment provides a clincher for chronotherapy personalization. The ability of a thermal cycle to drive the circadian clock in cultured hepatocarcinoma cells of 24 h indicates that this biomarker is also an effector of the synchronization of cancer cells, as well as a marker for the circadian in vitro and in vivo chronotherapeutic

碩士
國立交通大學
電信工程研究所
101
In a macro/femtocell overlay network, multi-cell interference (MCI) would make synchronization more difficult than that in conventional single-cell environments. Therefore how to reduce the MCI is crucial. In this research we propose a set of synchronization sequences which have not only good autocorrelation property but also more robust to the MCI. Our simulation results show that the MCI is sufficiently mitigated by applying the proposed synchronization sequences as well as the cell detection performance is improved. Moreover, since OFDM system is sensitive to the carrier frequency offset (CFO), CFO estimation and compensation is also important in multi-cell scenario. Simulation results depict that, with the proposal CFO estimation method, our propose sequences have significantly better CFO detection accuracy than the primary sequence used in LTE standard.

碩士
元智大學
通訊工程學系
97
In this thesis, we first construct the downlink (DL) preamble structure and signal model with carrier frequency offset (CFO) for IEEE 802.16e orthogonal frequency division multiplexing access (OFDMA) systems. In order to achieve the truly initial synchronization, several methods for packet/symbol timing, frequency synchronization, and cell ID search are introduced, improve, and analyzed by using DL preamble properties and the derived received signal model. In addition, when the mobile device receives the preamble signals from multiple basestations, these signals will cause synchronization errors and interfere with each other which is called multi-cell interference. For this special case, we also propose some effective multi-cell cancellation schemes in frequency domain and in space-frequency domain to mitigate the multi-cell interference and to avoid the synchronization errors before using the proposed initial synchronization algorithms. Finally, from analytic and computer simulation results, we show that the proposed overall initial synchronization algorithm achieves high efficiency and performance, making it suitable for practical applications.

碩士
國立中山大學
通訊工程研究所
99
Long Term Evolution (LTE) developed by Third Generation Partnership Project (3GPP) is expected to be the standard of the Fourth-Generation (4G) of wireless communication system. LTE supports Frequency Division Duplex (FDD) and Time Division Duplex (TDD), and both of them are based on Orthogonal Frequency Division Multiplexing (OFDM) system in downlink. OFDM systems are sensitive to timing and frequency offset. Therefore, synchronization plays an important role in OFDM systems. In this thesis, we study synchronization problems of a LTE FDD baseband receiver. Particularly, we develop a complete procedure to deal with the synchronization problems. The basic design concept and procedure are as follows: The receiver estimates and compensates the timing and frequency offset by using the repetition property of the cyclic prefix. In the meanwhile, the receiver also detects cyclic prefix mode (or the length of the cyclic prefix). After the frequency offset has been compensated, the receiver then processes cell search. To this end, we multiply each subcarrier by the synchronization sequence provided by LTE specification and transform them into time domain. We then estimate the channel energy in time domain to detect the Cell Identity (Cell ID). Using computer simulations, we verify that the designed receiver performs well.

碩士
國立成功大學
電腦與通信工程研究所
98
In cellular communication systems the mobile station (MS) must perform initial synchronization and search for a base station to set up the downlink access. This process is the so-called initial cell search. To accomplish the operations mentioned above, two synchronization signals, the primary synchronization signal (PSS) and the secondary synchronization signal (SSS), are periodically transmitted from base station in the 3GPP LTE (Long Term Evolution) system. It is announced OFDM signal is applied to downlink transmission in the LTE cellular network. However, OFDM signal is sensitive to synchronization error, such as carrier frequency offset (CFO). CFO, which exists between the transmitter and the receiver, causes loss of orthogonality among subcarriers and inter-carrier interference (ICI) and degrade the system performance. In this thesis all the procedures of synchronization and initial cell search are specified. Two Innovative processing algorithms for PSS, including the theoretical analysis and deduction, are provided. Most important, the proposed schemes are able to evaluate the ICFO more accurately and improve the error rate effectively. Comparisons between the proposed schemes and the existing ones are illustrated in the simulation results. Furthermore, the proposed schemes also reduce the computational complexity.

博士
國立成功大學
電腦與通信工程研究所
100
In cellular communication systems the mobile station (MS) must perform initial synchronization and search for a base station with best signal quality to set up the downlink access. This process is the well-known initial cell search. The 3.9G mobile wireless wideband technology consists of the Worldwide Interoperability for Microwave Access (WiMAX) and the Long Term Evolution (LTE). IEEE 802.16e is the specifications designed for the WiMAX system in applications of mobile environments. Its time-domain preamble does not have the perfect periodicity for time synchronization. Two synchronization signals, the primary synchronization signal (PSS) and the secondary synchronization signal (SSS), are periodically emitted from the base station in the 3GPP LTE system. In this dissertation all the procedures of synchronization and the initial cell search, including the theoretical analysis and deduction, are provided. Secondly, several innovative algorithms are proposed and their simulations are compared with those of the existing ones. The results confirm that the proposed algorithms are able to reduce the error rates of cell search. Moreover, they can estimate ICFO more accurately and efficiently. Finally, the proposed schemes also reduce the computational complexity. In order to achieve robust performance, one of the most important steps is the channel estimation based on the limited number of pilot signals. Owing to the channel’s time variant characteristics caused by user’s mobility and the irregular arrangement of the pilot signals, the exact channel estimation is more difficult to achieve for the 802.16e system. In this dissertation a DFT-based Channel Estimation is proposed to apply to the WiMAX system. The proposed scheme is capable of providing excellent system performances under various channel environments.

碩士
國立成功大學
電腦與通信工程研究所
97
For broadband wireless access, it is very important that the mobile station (MS) has to perform initial synchronization and cell search when setting up the downlink transmission. The IEEE 802.16e OFDMA system is different from conventional OFDM systems like WLAN. Its time-domain preamble does not have perfect periodicity for time synchronization. And the complexity of the conventional Cell ID identification method is very high due to a large number of long preamble PN codes. In this paper, we utilize the property of its preamble’s frequency-domain structure and that of an OFDM signal to achieve frame detection and Cell ID identification. Meanwhile we also estimate the integer and fractional frequency offset, thus accomplishing the frequency synchronization. This method can reduce the complexity in Cell ID identification and improve the frame detection accuracy.

碩士
國立臺北科技大學
電子工程系
106
With the evolution of 5G communication, to enable users to achieve better communication quality and signal coverage, telecom operators and users may install more small cells in the indoor region. However, the small cells would suffer severe inter-cell interference due to denser deployment. The thesis explores the implementation issues of enhanced inter-cell interference (eICIC) coordination among small cells. The time-domain based eICIC, namely almost blank subframe (ABS), is utilized to avoid the concurrent transmission among the neighbor cells. According to the literature, the time synchronization requirement should be within 1$mu$s. Moreover, although the major part of each subframe, i.e., the data transmission interference through the physical downlink shared channel (PDSCH), is coordinated, the other portion of the subframe such as the synchronization signals and the physical broadcast channel (PBCH) would still interfere others. The subframe shifting among neighbor cells is further considered to improve the performance. We implement using OpenAirInterface (OAI) with universal software radio peripherals (USRP). To study the impact of time synchronization on the performance of eICIC, we utilize a packet-based protocol IEEE 1588 and compare with the clock source device OctoClock-G. In the experiments, three USRPs are installed to serve as two small cells and one user. One small cell transmits data to the user, and the other transmits as the interference source. We verified that the throughput of the time synchronization case could increase up to 28% compared to the asynchronous case, and the further consideration of subframe offset scheme will increase by 40% in total, which shows that user can get guarantee data transmission in the dense small cell.

碩士
國立交通大學
電子研究所
99
The invent is a method of a new timing synchronization method and 3rd Generation Partnership Project (3GPP) Long Tern Evolution (LTE) cell search procedure is proposed. The procedure can be divided into four steps. Firstly, received signal has passed a low-pass filter to remove other data which are not synchronization signals. Secondly, timing synchronization is performed by Secondary synchronization signal’s conjugate symmetry that is immune to carrier frequency offsets (CFO). The property can raise the timing synchronization accuracy. Thirdly, in time or in frequency domain, use detected SSS starting position and perform joint of blind cyclic prefix (CP) detection and primary synchronization signal (PSS) detection to find out CP length, PSS position, and . The CFO problem can be also solved in this step. Finally, secondary synchronization signal (SSS) detection is adopted. After going through procedure we can get physical-layer cell identity (Cell-ID) and cell search is accomplished.

碩士
國立臺灣海洋大學
通訊與導航工程學系
103
This thesis focuses on the LTE-A system synchronization, cell identification (cell-ID) and channel estimation in the time-dispersive multipath channel environment. Synchronization can be grouped into two parts, one part is time offset (TO) and the other is carrier frequency offset (CFO). When it comes to CFO, it is separated into two parts: integer carrier frequency offset (ICFO) and fractional carrier frequency offset (FCFO). In LTE-A , there are two synchronization signals can be utilized to detect TO and CFO - Primary Synchronization Signal (PSS) and Secondary Synchronization Signal (SSS). The cell-ID consists of Cell-ID1 and Cell-ID2. The information of Cell-ID2 is within the PSS, and both Cell-ID1 and Cell-ID2 information are contained in SSS. The proposed schemes in this thesis use PSS properties to detect TO, FCFO, joint detection cell-ID2 and ICFO and channel response. In the multipath channel, lots of PSS symmetric property will be destroyed. The new proposed schemes dedicate to reduce and ease the channel effect, and finally estimate the channel response. Compared with the conventional detection schemes, the proposed schemes have better performance and lower computational complexity advantage in time-dispersive channel scenarios.

Establishing a definitive cell cycle progression has been one of the fundamental aims of cellular biology. Its importance lies in gaining insight into the basic processes of life as well as the functions of mutant cell cycle pathways in promoting cancer by replication deficiencies and loss of checkpoint control. Currently used methods to control cell cycle and synchronize cells, function by halting cell cycle progression. Such harsh methods are detrimental to the cell and insufficient to provide an accurate reflection of the cell cycle. This study focused on replicating and confirming the efficiency of a technique developed by Helmstetter, called the “Baby Machine,” that can produce new born cells with little to no perturbations. Using this in conjunction with a short pulse RNA labelling technique, called Bru-seq, allowed the capture and RNA sequencing of synchronized cells and its nascent RNA. Here we show the first glimpse into the transcriptional profile of newly divided cells as well as novel rapid exon splicing and transcription read-through processes.

碩士
國立臺灣海洋大學
通訊與導航工程學系
101
Because of the increasing demand of the transmission data rate for a wireless access service, the development of the fourth generation (4G) wireless communication system becomes more and more urgent and important. The Long Term Evolution Advanced (LTE-A) is the most popular candidate for the future 4G system, and it has some issues need to be investigated, such as Synchronization, Inter-cell interference, Channel Estimation (CE), etc. In this thesis, the synchronization and inter-cell interference problems are discussed. LTE-A adopts the PSSs and SSSs that transmit every 5ms for the synchronization. Several low-complexity schemes are provided to conduct the Timing Offset (TO) estimation via the time-domain symmetric property of PSS and conjugated symmetric property of SSS in this thesis. Computer simulations show that the proposed synchronization methods have not only the good Mean Square Error (MSE) performance but also the low computation complexity advantage. Besides, a sectorized Coordinated Multi-Point (CoMP) resource planning method is provided to avoid the macro cell to macro cell inter-cell interference. The proposed sectorized CoMP is compared with the traditional Inter-Cell Interference Coordination (ICIC) methods and results shows that the proposed method has better performance of system frequency efficiency and user capacity. Finally, a modified greedy method is also provided to achieve the fair resource allocation purpose for the UEs in this thesis.

What is flagellar swimming? Cilia and flagella are whip-like cell appendages that can exhibit regular bending waves. This active process emerges from the non-equilibrium dynamics of molecular motors distributed along the length of cilia and flagella. Eukaryotic cells can possess many cilia and flagella that beat in a coordinated fashion, thus transporting fluids, as in mammalian airways or the ventricular system inside the brain. Many unicellular organisms posses just one or two flagella, rendering them microswimmers that are propelled through fluids by the flagellar beat including sperm cells and the biflagellate green alga Chlamydomonas. Objectives. In this thesis in theoretical biological physics, we seek to understand the nonlinear dynamics of flagellar swimming and synchronization. We investigate the flow fields induced by beating flagella and how in turn external hydrodynamic flows change speed and shape of the flagellar beat. This flagellar load-response is a prerequisite for flagellar synchronization. We want to find the physical principals underlying stable synchronization of the two flagella of Chlamydomonas cells. Results. First, we employed realistic hydrodynamic simulations of flagellar swimming based on experimentally measured beat patterns. For this, we developed analysis tools to extract flagellar shapes from high-speed videoscopy data. Flow-signatures of flagellated swimmers are analysed and their effect on a neighboring swimmer is compared to the effect of active noise of the flagellar beat. We were able to estimate a chemomechanical energy efficiency of the flagellar beat and determine its waveform compliance by comparing findings from experiments, in which a clamped Chlamydomonas is exposed to external flow, to predictions from an effective theory that we designed. These mechanical properties have interesting consequences for the synchronization dynamics of Chlamydomonas, which are revealed by computer simulations. We propose that direct elastic coupling between the two flagella of Chlamydomonas, as suggested by recent experiments, in combination with waveform compliance is crucial to facilitate in-phase synchronization of the two flagella of Chlamydomonas.:1 Introduction 1.1 Physics of cell motility: flagellated swimmers as model system 2 1.1.1 Tissue cells and unicellular eukaryotic organisms have cilia and flagella 2 1.1.2 The conserved architecture of flagella 3 1.1.3 Synchronization in collections of flagella 5 1.2 Hydrodynamics at the microscale 9 1.2.1 Navier-Stokes equation 10 1.2.2 The limit of low Reynolds number 10 1.2.3 Multipole expansion of flow fields 11 1.3 Self-propulsion by viscous forces 13 1.3.1 Self propulsion requires broken symmetries 13 1.3.2 Signatures of flowfields: pusher & puller 15 1.4 Overview of the thesis 16 2 Flow signatures of flagellar swimming 2.1 Self-propulsion of flagellated swimmers 20 2.1.1 Representation of flagellar shapes 20 2.1.2 Computation of hydrodynamic friction forces 21 2.1.3 Material frame and rigid-body transformations 22 2.1.4 The grand friction matrix 23 2.1.5 Dynamics of swimming 23 2.2 The hydrodynamic far field: pusher and puller 26 2.2.1 The flow generated by a swimmer 26 2.2.2 Force dipole characterization 27 2.2.3 Flagellated swimmers alternate between pusher and puller 29 2.2.4 Implications for two interacting Chlamydomonas cells 31 2.3 Inertial screening of oscillatory flows 32 2.3.1 Convection and oscillatory acceleration 33 2.3.2 The oscilet: fundamental solution of unsteady flow 35 2.3.3 Screening length of oscillatory flows 35 2.4 Energetics of flagellar self-propulsion 36 2.4.1 Impact of inertial screening on hydrodynamic dissipation 37 2.4.2 Case study: the green alga Chlamydomonas 38 2.4.3 Discussion: evolutionary optimization and the number of molecular motors 38 2.5 Summary 39 3 The load-response of the flagellar beat 3.1 Experimental collaboration: flagellated swimmers exposed to flows 41 3.1.1 Description of the experimental setup 42 3.1.2 Computed flow profile in the micro-fluidic device 43 3.1.3 Image processing and flagellar tracking 43 3.1.4 Mode decomposition and limit-cycle reconstruction 47 3.1.5 Changes of limit-cycle dynamics: deformation, translation, acceleration 49 3.2 An effective theory of flagellar oscillations 50 3.2.1 A balance of generalized forces 50 3.2.2 Hydrodynamic friction in generalized coordinates 51 3.2.3 Intra-flagellar friction 52 3.2.4 Calibration of active flagellar driving forces 52 3.2.5 Stability of the limit cycle of the flagellar beat 53 3.2.6 Equations of motion 55 3.3 Comparison of theory and experiment 56 3.3.1 Flagellar mean curvature 57 3.3.2 Susceptibilities of phase speed and amplitude 57 3.3.3 Higher modes and stalling of the flagellar beat at high external load 59 3.3.4 Non-isochrony of flagellar oscillations 63 3.4 Summary 63 4 Flagellar load-response facilitates synchronization 4.1 Synchronization to external driving 65 4.2 Inter-flagellar synchronization in the green alga Chlamydomonas 67 4.2.1 Equations of motion for inter-flagellar synchronization 68 4.2.2 Synchronization strength for free-swimming and clamped cells 70 4.2.3 The synchronization strength depends on energy efficiency and waveform compliance 73 4.2.4 The case of an elastically clamped cell 74 4.2.5 Basal body coupling facilitates in-phase synchronization 75 4.2.6 Predictions for experiments 78 4.3 Summary 80 5 Active flagellar fluctuations 5.1 Effective description of flagellar oscillations 84 5.2 Measuring flagellar noise 84 5.2.1 Active phase fluctuations are much larger than thermal noise 84 5.2.2 Amplitude fluctuations are correlated 85 5.3 Active flagellar fluctuations result in noisy swimming paths 86 5.3.1 Effective diffusion of swimming circles of sperm cell 86 5.3.2 Comparison of the effect of noise and hydrodynamic interactions 87 5.4 Summary 88 6 Summary and outlook 6.1 Summary of our results 89 6.2 Outlook on future work 90 A Solving the Stokes equation A.1 Multipole expansion 95 A.2 Resistive-force theory 96 A.3 Fast multipole boundary element method 97 B Linearized Navier-Stokes equation B.1 Linearized Navier-Stokes equation 101 B.2 The case of an oscillating sphere 102 B.3 The small radius limit 103 B.4 Greens function 104 C Hydrodynamic friction C.1 A passive particle 107 C.2 Multiple Particles 107 C.3 Generalized coordinates 108 D Data analysis methods D.1 Nematic filter 111 D.1.1 Nemat 111 D.1.2 Nematic correlation 111 D.2 Principal-component analysis 112 D.3 The quality of the limit-cycle projections of experimental data 113 E Adler equation F Sensitivity analysis for computational results F.1 The distance function of basal coupling 117 F.2 Computed synchronization strength for alternative waveform 118 F.3 Insensitivity of computed load-response to amplitude correlation time 118 List of Symbols List of Figures Bibliography

碩士
國立交通大學
電子研究所
99
To ensure good transmission quality, a mobile user has to establish connection with a base station before transmitting or receiving any data. Cell search is the procedure that helps a user identify the nearest base station, and then a number of steps will be taken to enter the network via the base station. However, searching all possible base stations to find the nearest one requires high computation complexity as well as the execution time. This thesis focuses on low complexity designs of cell search based on BPSK-modulated signals. There have been a lot of techniques focusing on the same topic as this thesis. Most of them reduce the computation complexity at the price of performance loss. In this thesis, several low-complexity techniques for cell search without performance loss are proposed. The Grouping method and the Level-shifted method are the most important methods among all the proposed methods. In the Grouping method, an efficient multiplexing scheme is derived to achieve low-complexity realizations of the existing cell search methods. In the Level-shifted method, a new metric for cell search is derived by employing the binary characteristic of BPSK-modulated synchronization signals. The effect of timing offset on cell search is also investigated in this thesis. When timing errors exist, the conventional cell search algorithm is robust to timing errors and no performance loss results. If the symbol timing can be acquired to reasonable accuracy, the conventional cell search method can be further simplified.

碩士
國立清華大學
生命科學系
89
The DNA-damaging agent mitomycin C ( MMC ) was found to induce B-phase cell cycle arrest ( equivalent to G1 arrest in eukaryotes ) in the radiation-resistant bacterium Deinococcus radiodurans IR. The arrested cells were able to grow in a synchronous fashion when they washed followed by incubating in a fresh medium. D. radiodurans IR cells synchronized at different cell cycle phases exhibited different UV and MMC resistance , with a decreasing order of B> C> D (C and D are equivalent to S and G2 phase of eukaryotes , respectively ). Similar decreasing resistance does not occur when synchronized IR cells subjected to heat killing. Synchronized cultures were also subjected to cell volume determination by using Coulter size analyzer. The results showed that a newly born daughter cell grows in the B phase with increasing about 30﹪of its original volume, 40﹪in the C phase and 30﹪in the D phase. This is the first attempt to apply flow cytometry (FCM) in studying D. radiodurans and to apply both of Coulter size analyzer and FCM in studying cell cycle characteristics of a microorganism. 2. 英文摘要………………………………………………...…..2 3. 緒言…………………………………………………………3 4. 材料與方法…………………………………………………..5 5. 結果…………………………………………………………...8 6. 討論………………………………………………………….15 7. 參考文獻…………………………………………………….20 8. 圖………………………………………………………………i 9. 附錄………………………………………………………..xiii

碩士
國立交通大學
電信工程研究所
104
In the 5G cellular system, there exists the problem of synchronization and cell search when the mobile boots up. In this thesis, we propose a new method to execute synchronization and cell search. The cell search procedure is discussed and is divided into four different stages in the 5G cellular system. The users' data signals are transmitted in the time domain and we execute cell search according to control signals transmitted in the frequency domain at the same time. In the first stage, we use the received signal with the proposed algorithm to estimate symbol timing and fractional carrier frequency offset (FCFO) in the time domain, this method does not require any additional preamble to do cross correlation. In the second stage, we use a primary control tone to detect integer carrier frequency offset (ICFO) in the frequency domain. In the third phase, we use the secondary control tones to obtain cell ID after adjustment of ICFO. In the fourth stage, we use the control data, which is carried by the secondary control tones, to detect frame header by differential detection. The cell search procedure ends when the above four stages are completed. In our simulation results, we show that the proposed joint symbol timing, FCFO estimation, cell ID detection, and frame header detection algorithms have superior performances even with the interference of users' data.

Circadian rhythms are ∼24 hour cycles in behavioral and physiological responses observed in a wide range of organisms. The role of this central clock lies in its ability to recognize different environmental stimuli and adapt the behavior of organisms accordingly. This response is critical for an organism's survival and evolution as it allows for the anticipation of environmental cues. The circadian pacemaker of mammalian organisms is located in the brain region of the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN produces self-sustained oscillations and further controls a number of metabolic processes across distinct organs. This thesis has focused on the mathematical modeling of the SCN to investigate mechanisms responsible for the generation and synchronization of daily signals across the circadian network. For this purpose, we developed several multicellular models of the mammalian circadian clock characterized by a high degree of heterogeneity with respect to single cell periodicity and behavior (intrinsic and driven oscillators), neurotransmitter release (vasoactive intestinal peptide (VIP), γ-aminobutyric acid (GABA) and glutamate synthesis) and spatial organization (long range versus short range connectivity). A firing rate code model was further developed to incorporate known electrophysiological properties of SCN pacemakers that give rise to the electrical firing of individual neurons. In this model, daily changes in ion conductances, ion concentrations and membrane properties (such as membrane resistance) were integrated to produce circadian changes in the action potential frequency of SCN neurons. Intracellular signaling pathways, initiated by cytosolic calcium and VIP, were also included as the putative link between electrical firing and gene expression. The developed model predicted a direct relationship between firing frequency and gene expression amplitudes, demonstrated the importance of intracellular pathways for circadian behavior and synchrony and provided a novel multiscale framework which captured characteristics of the SCN at both the electrophysiological and gene regulatory levels. We further attempted to mimic the structural organization of the SCN and utilize experimentally derived connectivity schemes to simulate the SCN’s ventrolateral and dorsomedial subdivisions. The model predicted that sufficient connectivity between the two separate regions, associated with distinct circadian functions, was responsible for the expression of sustained circadian behavior.

Amoebae of the genus Acanthamoeba spp. are free-living unicellular organisms found in disparate ecosystems all over the world. Due to their ability to invade human body, evade its defensive mechanisms and cause extensive tissue damage, Acanthamoeba infection can lead to serious, if rare, diseases, affecting most commonly the eye and the central nervous system. Specific therapy for Acanthamoeba infections is not available. A major reason for therapeutic failure in ameobiasis is the ability of the protist to differentiate into resistant stages. These are cysts, known to be formed under prolonged unfavorable conditions, both in the environment and the infected tissues, and the pseudocysts, less durable but rapidly formed under acute stress. The present thesis focuses on as yet unexplored mechanisms of resistance of cysts and pseudocysts. Moreover, further characteristics distinguishing cysts and pseudocysts as well as the processes involved in their formation are investigated. One of the issues addressed is a presence of protective carbohydrate compounds mannitol and trehalose that participate in defensive reactions against abiotic stress in many organisms. Although putative genes for enzymes of the trehalose and mannitol synthetic pathways are present in the genome of Acanthamoeba, only one of the...

碩士
國立高雄師範大學
數學研究所
102
We study the synchronization behavior in nonlinearly coupled identical cells with distributed time delays. Using the idea of ”sequential contracting”, delay-dependent and delay-independent conditions that ensure the coupled dynamical network to be globally synchronized will be provided. These conditions do not include one another and can be applied to not only regular networks, but also complex ones. Several examples with numerical simulations are given to demonstrate the results.

The present habilitation thesis in theoretical biological physics addresses two central dynamical processes in cells and organisms: (i) active motility and motility control and (ii) self-organized pattern formation. The unifying theme is the nonlinear dynamics of biological function and its robustness in the presence of strong fluctuations, structural variations, and external perturbations. We theoretically investigate motility control at the cellular scale, using cilia and flagella as ideal model system. Cilia and flagella are highly conserved slender cell appendages that exhibit spontaneous bending waves. This flagellar beat represents a prime example of a chemo-mechanical oscillator, which is driven by the collective dynamics of molecular motors inside the flagellar axoneme. We study the nonlinear dynamics of flagellar swimming, steering, and synchronization, which encompasses shape control of the flagellar beat by chemical signals and mechanical forces. Mechanical forces can synchronize collections of flagella to beat at a common frequency, despite active motor noise that tends to randomize flagellar synchrony. In Chapter 2, we present a new physical mechanism for flagellar synchronization by mechanical self-stabilization that applies to free-swimming flagellated cells. This new mechanism is independent of direct hydrodynamic interactions between flagella. Comparison with experimental data provided by experimental collaboration partners in the laboratory of J. Howard (Yale, New Haven) confirmed our new mechanism in the model organism of the unicellular green alga Chlamydomonas. Further, we characterize the beating flagellum as a noisy oscillator. Using a minimal model of collective motor dynamics, we argue that measured non-equilibrium fluctuations of the flagellar beat result from stochastic motor dynamics at the molecular scale. Noise and mechanical coupling are antagonists for flagellar synchronization. In addition to the control of the flagellar beat by mechanical forces, we study the control of the flagellar beat by chemical signals in the context of sperm chemotaxis. We characterize a fundamental paradigm for navigation in external concentration gradients that relies on active swimming along helical paths. In this helical chemotaxis, the direction of a spatial concentration gradient becomes encoded in the phase of an oscillatory chemical signal. Helical chemotaxis represents a distinct gradient-sensing strategy, which is different from bacterial chemotaxis. Helical chemotaxis is employed, for example, by sperm cells from marine invertebrates with external fertilization. We present a theory of sensorimotor control, which combines hydrodynamic simulations of chiral flagellar swimming with a dynamic regulation of flagellar beat shape in response to chemical signals perceived by the cell. Our theory is compared to three-dimensional tracking experiments of sperm chemotaxis performed by the laboratory of U. B. Kaupp (CAESAR, Bonn). In addition to motility control, we investigate in Chapter 3 self-organized pattern formation in two selected biological systems at the cell and organism scale, respectively. On the cellular scale, we present a minimal physical mechanism for the spontaneous self-assembly of periodic cytoskeletal patterns, as observed in myofibrils in striated muscle cells. This minimal mechanism relies on the interplay of a passive coarsening process of crosslinked actin clusters and active cytoskeletal forces. This mechanism of cytoskeletal pattern formation exemplifies how local interactions can generate large-scale spatial order in active systems. On the organism scale, we present an extension of Turing’s framework for self-organized pattern formation that is capable of a proportionate scaling of steady-state patterns with system size. This new mechanism does not require any pre-pattering clues and can restore proportional patterns in regeneration scenarios. We analytically derive the hierarchy of steady-state patterns and analyze their stability and basins of attraction. We demonstrate that this scaling mechanism is structurally robust. Applications to the growth and regeneration dynamics in flatworms are discussed (experiments by J. Rink, MPI CBG, Dresden).:1 Introduction 10 1.1 Overview of the thesis 10 1.2 What is biological physics? 12 1.3 Nonlinear dynamics and control 14 1.3.1 Mechanisms of cell motility 16 1.3.2 Self-organized pattern formation in cells and tissues 28 1.4 Fluctuations and biological robustness 34 1.4.1 Sources of fluctuations in biological systems 34 1.4.2 Example of stochastic dynamics: synchronization of noisy oscillators 36 1.4.3 Cellular navigation strategies reveal adaptation to noise 39 2 Selected publications: Cell motility and motility control 56 2.1 “Flagellar synchronization independent of hydrodynamic interactions” 56 2.2 “Cell body rocking is a dominant mechanism for flagellar synchronization” 57 2.3 “Active phase and amplitude fluctuations of the flagellar beat” 58 2.4 “Sperm navigation in 3D chemoattractant landscapes” 59 3 Selected publications: Self-organized pattern formation in cells and tissues 60 3.1 “Sarcomeric pattern formation by actin cluster coalescence” 60 3.2 “Scaling and regeneration of self-organized patterns” 61 4 Contribution of the author in collaborative publications 62 5 Eidesstattliche Versicherung 64 6 Appendix: Reprints of publications 66
Das Thema der vorliegenden Habilitationsschrift in Theoretischer Biologischer Physik ist die nichtlineare Dynamik funktionaler biologischer Systeme und deren Robustheit gegenüber Fluktuationen und äußeren Störungen. Wir entwickeln hierzu theoretische Beschreibungen für zwei grundlegende biologische Prozesse: (i) die zell-autonome Kontrolle aktiver Bewegung, sowie (ii) selbstorganisierte Musterbildung in Zellen und Organismen. In Kapitel 2, untersuchen wir Bewegungskontrolle auf zellulärer Ebene am Modelsystem von Zilien und Geißeln. Spontane Biegewellen dieser dünnen Zellfortsätze ermöglichen es eukaryotischen Zellen, in einer Flüssigkeit zu schwimmen. Wir beschreiben einen neuen physikalischen Mechanismus für die Synchronisation zweier schlagender Geißeln, unabhängig von direkten hydrodynamischen Wechselwirkungen. Der Vergleich mit experimentellen Daten, zur Verfügung gestellt von unseren experimentellen Kooperationspartnern im Labor von J. Howard (Yale, New Haven), bestätigt diesen neuen Mechanismus im Modellorganismus der einzelligen Grünalge Chlamydomonas. Der Gegenspieler dieser Synchronisation durch mechanische Kopplung sind Fluktuationen. Wir bestimmen erstmals Nichtgleichgewichts-Fluktuationen des Geißel-Schlags direkt, wofür wir eine neue Analyse-Methode der Grenzzykel-Rekonstruktion entwickeln. Die von uns gemessenen Fluktuationen entstehen mutmaßlich durch die stochastische Dynamik molekularen Motoren im Innern der Geißeln, welche auch den Geißelschlag antreiben. Um die statistische Physik dieser Nichtgleichgewichts-Fluktuationen zu verstehen, entwickeln wir eine analytische Theorie der Fluktuationen in einem minimalen Modell kollektiver Motor-Dynamik. Zusätzlich zur Regulation des Geißelschlags durch mechanische Kräfte untersuchen wir dessen Regulation durch chemische Signale am Modell der Chemotaxis von Spermien-Zellen. Dabei charakterisieren wir einen grundlegenden Mechanismus für die Navigation in externen Konzentrationsgradienten. Dieser Mechanismus beruht auf dem aktiven Schwimmen entlang von Spiralbahnen, wodurch ein räumlicher Konzentrationsgradient in der Phase eines oszillierenden chemischen Signals kodiert wird. Dieser Chemotaxis-Mechanismus unterscheidet sich grundlegend vom bekannten Chemotaxis-Mechanismus von Bakterien. Wir entwickeln eine Theorie der senso-motorischen Steuerung des Geißelschlags während der Spermien-Chemotaxis. Vorhersagen dieser Theorie werden durch Experimente der Gruppe von U.B. Kaupp (CAESAR, Bonn) quantitativ bestätigt. In Kapitel 3, untersuchen wir selbstorganisierte Strukturbildung in zwei ausgewählten biologischen Systemen. Auf zellulärer Ebene schlagen wir einen einfachen physikalischen Mechanismus vor für die spontane Selbstorganisation von periodischen Zellskelett-Strukturen, wie sie sich z.B. in den Myofibrillen gestreifter Muskelzellen finden. Dieser Mechanismus zeigt exemplarisch auf, wie allein durch lokale Wechselwirkungen räumliche Ordnung auf größeren Längenskalen in einem Nichtgleichgewichtssystem entstehen kann. Auf der Ebene des Organismus stellen wir eine Erweiterung der Turingschen Theorie für selbstorganisierte Musterbildung vor. Wir beschreiben eine neue Klasse von Musterbildungssystemen, welche selbst-organisierte Muster erzeugt, die mit der Systemgröße skalieren. Dieser neue Mechanismus erfordert weder eine vorgegebene Kompartimentalisierung des Systems noch spezielle Randbedingungen. Insbesondere kann dieser Mechanismus proportionale Muster wiederherstellen, wenn Teile des Systems amputiert werden. Wir bestimmen analytisch die Hierarchie aller stationären Muster und analysieren deren Stabilität und Einzugsgebiete. Damit können wir zeigen, dass dieser Skalierungs-Mechanismus strukturell robust ist bezüglich Variationen von Parametern und sogar funktionalen Beziehungen zwischen dynamischen Variablen. Zusammen mit Kollaborationspartnern im Labor von J. Rink (MPI CBG, Dresden) diskutieren wir Anwendungen auf das Wachstum von Plattwürmern und deren Regeneration in Amputations-Experimenten.:1 Introduction 10 1.1 Overview of the thesis 10 1.2 What is biological physics? 12 1.3 Nonlinear dynamics and control 14 1.3.1 Mechanisms of cell motility 16 1.3.2 Self-organized pattern formation in cells and tissues 28 1.4 Fluctuations and biological robustness 34 1.4.1 Sources of fluctuations in biological systems 34 1.4.2 Example of stochastic dynamics: synchronization of noisy oscillators 36 1.4.3 Cellular navigation strategies reveal adaptation to noise 39 2 Selected publications: Cell motility and motility control 56 2.1 “Flagellar synchronization independent of hydrodynamic interactions” 56 2.2 “Cell body rocking is a dominant mechanism for flagellar synchronization” 57 2.3 “Active phase and amplitude fluctuations of the flagellar beat” 58 2.4 “Sperm navigation in 3D chemoattractant landscapes” 59 3 Selected publications: Self-organized pattern formation in cells and tissues 60 3.1 “Sarcomeric pattern formation by actin cluster coalescence” 60 3.2 “Scaling and regeneration of self-organized patterns” 61 4 Contribution of the author in collaborative publications 62 5 Eidesstattliche Versicherung 64 6 Appendix: Reprints of publications 66