Ludwig-Maximilians-Universität München

Digitale Hochschulschriften der LMU
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    Avian sleep

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    Sleep is not a uniform brain state but undergoes developmental changes and local variations. This thesis explores both aspects in zebra finches using multi-channel EEG and LFP recordings. First, we show that sleep patterns change with age: juveniles spend more time in intermediate sleep (IS), especially males engaged in vocal learning, while adults exhibit more SWS and REM sleep. Functional connectivity matures over time, with adults showing fewer but stronger EEG networks. Second, we demonstrate that sleep stages are not synchronized across the avian pallium. Unlike prior studies linking local sleep to prior wake activity, our findings reveal spontaneous regional differences, with deeper brain areas playing a key role in synchrony. These results highlight sleep’s complexity in birds and challenge the traditional view of sleep as a global state

    Therapeutische Wirkungen und Nebenwirkungen der Strahlentherapie niedrig-maligner Non-Hodgkin Lymphome der Orbita

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    Tensor network impurity solvers

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    Transition metal oxides (TMOs) and other quantum materials recently attracted immense interest due to their plethora of functional properties. These properties are often the result of strong electronic correlation effects at low temperatures, rendering their theoretical description challenging. The current state-of-the-art method for the simulation of such materials is dynamical mean field theory (DMFT), which provides an exact description of the kinetic part of the system while approximating the Coulomb interaction as local. In this thesis, we present advances in tensor network based impurity solvers, which we use to simulate intricate TMOs at low temperatures within the DMFT approximation. We discuss both methodological and conceptual developments that result in significant improvements in runtime and accuracy. We introduce a tree tensor network structure, the MT3N, specifically tailored to optimally represent the intricate correlation structure of multi\hyp orbital impurity models. A significant advantage of tensor network based impurity solvers is their ability to compute Green's functions both on the Matsubara axis and directly on the real frequency axis. We developed a new analytic continuation algorithm, MinKL, that allows us to combine those Green's functions to significantly stabilize the procedure and improve its accuracy compared to prevalent algorithms. Additionally, we introduce a novel concept of time evolution by evolving systems along complex time contours. By shifting time evolution away from the real time axis, we significantly curtail entanglement growth, enabling substantial improvements in accuracy and efficiency. We present several complex time contours along with multiple post\hyp processing methods that analytically continue our results back to the real frequency axis. These advancements enable us to resolve the Fermi liquid behavior of a multi-orbital system down to ~0.002 eV. Finally, we use these developments in the study of the transition metal oxide LiV2_2O4_4. This material has captivated researchers due to its heavy quasiparticle mass at low temperatures, a rare occurrence outside f\hyp orbital materials. Our algorithmic advancements allow us to propose a new theory describing this compound's emerging heavy fermion regime

    The molecular basis of motion detection in Drosophila Melanogaster

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    Suitability of digitally recorded data for automatic lameness detection on dairy farms

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    Role of hemostasis for immune cell trafficking into malignant tumors

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    Investigating pericytes heterogeneity in glioblastoma vasculature

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    A novel paradigm to investigate the role of the retrosplenial cortex in spatial learning and memory in freely behaving mice

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    Spatial cognition is vital for the survival of many species, enabling mice and other animals to navigate their environment, locate food resources, and escape from threats. Meanwhile, spatial learning and memory allow an individual to acquire, retain, and recall spatial information. The retrosplenial cortex (RSC) has recently gained attention for its role in spatial cognition and memory, integrating sensory and spatial signals. Despite extensive research on the neural circuits involved in spatial learning through employment of various spatial memory tasks, the specific contributions of the rodent RSC to spatial memory are not fully understood. This gap in knowledge emphasises the need for innovative behavioural paradigms to address previous spatial memory tasks’ limitations. In this thesis, I present a novel behavioural paradigm designed to explore the role of the RSC to spatial learning and memory. The task I developed investigates mechanisms of spatial memory formation, retrieval, and reversal learning in rodents, wherein mice learn the locations of hidden trigger zones within a circular arena. This spatial memory task stands out for its ability to track mice, their behaviour, and task performance in a three-dimensional environment without any physical constraints on head or body movement. This allows for naturalistic animal behaviour and the simultaneous use of portable neuronal recording devices during training. In this study, I identified key task metrics for quantifying behaviour in the spatial memory task, including error angles and active task engagement, to assess learning and task performance. Using these parameters, I demonstrate that the goal-directed navigational strategies employed by mice vary significantly whether they are guided by vision or memory. Specifically, mice resort to memory-guided navigation exclusively in the absence of visual landmark cues. Through manipulations of the external landmarks within the animals' environment during spatial memory training, I demonstrate that mice develop a comprehensive cognitive map of the arena and the surrounding space, using allocentric navigation strategies to locate previously learnt goal locations. The results of this study further show that mice can form robust allocentric spatial memories quickly and efficiently, even under conditions where RSC activity is inhibited. Chemogenetic experiments show that inactivating RSC neuronal activity does not impede the formation or retrieval of spatial memories in this task. Taken together, these findings highlight the effectiveness of this task for investigating allocentric spatial learning and memory in mice. Characterized by rapid acquisition of task proficiency, high trial rates, reliable memory formation and recall, brief pre-training periods, and unrestricted, natural mouse behaviour, this paradigm opens up new avenues for advanced research into the neural substrates of spatial learning and memory with broad applications in RSC research and beyond

    Das Reproduktionssystem der Lanzenfliegen (Diptera: Lonchopteridae)

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    Diese aus insgesamt drei Publikationen bzw. Kapiteln bestehende Dissertation soll zum allgemeinen Verständnis der Mechanismen der postkopulatorischen sexuellen Selektion beitragen, die zur Entstehung von Riesenspermien geführt haben. Zu diesem Zweck wurde das Fortpflanzungssystem der Lanzenfliegen (Diptera: Lonchopteridae) eingehender untersucht. Bei den Vertretern dieser Familie gibt es hierbei bemerkenswerte Unterschiede, wobei einige Arten Riesenspermien produzieren und die entsprechenden Weibchen extrem lange Spermatheken besitzen. Mit einer Länge von 7.500 µm und einer Dicke von 1,3 µm gehört das Spermium von Lonchoptera fallax zu den größten bisher bekannten überhaupt. Die Weibchen dieser Art besitzen Spermatheken mit einer Gesamtlänge von etwa 14.000 µm, womit diese etwa viermal so lang wie deren Körper sind. Anhand von 3D-Rekonstruktionen und Erkenntnissen aus der Elektronenmikroskopie wird in Kapitel I die Morphologie und Ultrastruktur der Spermien der nahe verwandten Art Lonchoptera lutea näher beschrieben. Mit einer Länge von 2.200 μm und einer Dicke von 1,4 μm sind diese zwar deutlich kleiner als die von L. fallax, können aber dennoch als riesig bezeichnet werden. Anders als die typischen Spermien anderer Fliegen haben sie einen stark asymmetrischen Querschnitt mit nur einem, wenn auch sehr großen Mitochondrienderivat und einem Paar massiver akzessorischer Körper, von denen sich aber nur einer über die gesamte Länge des Flagellums erstreckt. Um die Entstehung von Riesenspermien in dieser Fliegen-Familie näher zu erforschen, wurden für Kapitel II die Körpergröße, die Hodengröße, die Spermiengröße und die Anzahl der Spermien pro Bündel und pro Hoden bei insgesamt elf Lonchoptera-Arten untersucht. Anhand dieser Ergebnisse wird diskutiert, wie diese Merkmale miteinander in Beziehung stehen und wie ihre Entwicklung die Ressourcenverteilung unter den Spermien beeinflusst. Auf Grundlage der Spermienmerkmale und unterstützt durch einen aus DNA-Barcodes abgeleiteten molekularen Stammbaum wird zudem eine phylogenetische Hypothese für die Gattung Lonchoptera formuliert. Um die postkopulatorischen Prozesse zu verstehen, die zur Entstehung von riesigen Spermien bei Lonchopteridae geführt haben, wurden für Kapitel III die Abmessungen der Spermatheken, die wiederum in vier morphologisch, histologisch und funktionell unterschiedliche Abschnitte unterteilt werden können, bei elf Lonchoptera-Arten untersucht und mit den Maßen der entsprechenden Spermien ins Verhältnis gesetzt. 3D-Rekonstruktionen machten es zudem möglich, das Volumen in diese Überlegungen mit einzubeziehen, was einen neuen Ansatz in diesem Kontext darstellt. Die Ergebnisse zeigen, dass die Spermatheken immer deutlich länger sind als die entsprechenden Spermien und dass ein hochsignifikanter, positiv linearer Zusammenhang zwischen beiden Größen besteht, was auf einen zugrundeliegenden koevolutiven Prozess hindeutet. Auf Grundlage aller Ergebnisse werden einige evolutive Szenarien inklusive eines neuen Ansatzes zu den selektiven Vorteilen längerer Spermien aufgezeigt, um zu diskutieren, wie Spermien- und Spermathekenlänge bei Lonchopteridae abhängig voneinander entstanden sein könnten

    Investigations on multilateration of ionoacoustic signals for localisation of the bragg peak in pre-clinical research

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    Radiation therapy is one of the most typically used treatments in cancer care, with around 60% of patients undergoing this form of treatment. While X-rays and gamma rays (photon therapy) are the standard approach, proton therapy has emerged as a valuable alternative. Proton therapy is renowned for its ability to provide a more conformal dose delivery. Proton therapy’s superiority over photon therapy is due to protons depositing their maximum energy directly within the tumour while sparing surrounding healthy tissues. However, proton therapy is highly sensitive to range uncertainties. Range uncertainties in proton therapy arise primarily because we cannot precisely determine where the proton beam will stop, leading to the risk of overshooting or undershooting the target. Thus, there is a need for in vivo range verification methods to reduce range uncertainties. The two methods nearing routine clinical use are positron emission tomography (PET) and prompt gamma imaging (PGI). Range verification relies on monitoring nuclear reaction products along proton beams for these methods. However, PET and PGI methods do not directly correlate the measurable signal, beam range, or Bragg peak (BP) position. Additionally, their equipment is bulky and not cost-effective. Therefore, the research conducted during this work proposes a range verification method that is both cost-effective and establishes a direct correlation between the proton beam and ionoacoustic (IA) signals. At present, only two commercial platforms support small animal photon radiotherapy, though their imaging systems can be adapted for research beamlines. Proton therapy offers distinct advantages over photon therapy, which led to the development of the Small Animal Proton Irradiator for Research in Molecular Image-guided Radiation-Oncology (SIRMIO) project. It was led by Prof. Dr. Katia Parodi at Ludwig Maximilians-Universit¨at (LMU) Munich and funded by the European Research Council (ERC) under grant agreement 725539. SIRMIO aimed to create the first portable, imageguided research platform for small animal proton therapy. As part of this effort, different range verification methods are investigated. One of these methods is the one studied in this thesis, which is based on localising the BP using IA signals. The research presented here investigates BP localisation using IA signals, aiming to determine the BP position in both two-dimensional (2D) and three-dimensional (3D) space. The localisation was performed in homogenous and heterogenous media via time-of-flight (ToF) estimation from different sensor spatial locations. The localisation of the BP was assessed using a technique called multilateration. The initial studies were performed in-silico, using ideal point sources that emulated the BP position and evaluated the robustness of two numerical optimisation algorithms: Nelder-Mead Simplex and Levenberg Marquardt. Secondly, the robustness of the multilateration technique was assessed for two localisation methods: time-of-arrival (TOA) and time-difference-of-arrival (TDOA). By modelling random and systematic uncertainties in the geometrical ToF, the robustness of both TOA and TDOA was evaluated. Random uncertainties aimed to model the speed of sound variations, inaccurate knowledge of the sensor spatial location and errors on the ToF. On the other hand, the objective of modelling systematic uncertainties was to simulate the inaccurate knowledge of the measurement starting time from a proton beam accelerator. After fully understanding the numerical optimisation methods and the impact of uncertainties on TOA and TDOA, the localisation focus was addressed to a realistic simulation case using a pre-clinical beam with an energy of 20 MeV. The multilateration of the BP position was performed with a sensor network of 843 ideal point sensors arranged in a semi-circular configuration with a diameter of 60 mm. Similarly, the impact of different ToF extraction methods on BP localisation was evaluated. Moreover, the studies were further expanded to investigate the impact of the number of sensors on the ToF estimation and, consequently, their impact on the accuracy of the BP localisation. Experimental campaigns were conducted to benchmark the localisation of the BP using pre-knowledge gained from the simulation studies. These experimental studies retrieved the BP position in the Tandem accelerator with two different beam energies (20 and 22 MeV). The first experimental campaign aimed to localise the BP using 3 transducers. Furthermore, two different techniques were implemented to localise the spatial location of the transducers. The second experimental campaign aimed to localise the BP using 5 transducers. Moreover, the spatial locations of the transducers were estimated experimental using a single approach based on the measurement performed with an optical tracking system. For the SIRMIO case, a dedicated localisation setup with a 50 MeV beam energy was considered. This setup aimed to localise the BP under various conditions, including different proton beam time profiles, beam spatial locations, and numbers of sensors. The first step involved studying the error in ToF as a function of the proton time profiles and then assessing multilateration accuracy based on thesame proton time profiles. After identifying the optimal proton time profile, the BP was localised by keeping the proton time profile constant while varying the number of sensors. For the numerical methods, the Levenberg-Marquardt method demonstrated greater robustness compared to the Nelder-Mead Simplex method, with failure rates (FR) of 0.22% and 0% when localising the emulated BP positions with TOA and 1.12% and 4.85% when localising the source with TDOA, respectively. Considering ideal point sources, both localisation methods were equivalent in 2D. A mean error in localisation of 7.4×10^−4 mm and 7.8×10^−4 mm for TOA and TDOA was obtained. In 3D, the localisation error varied from 7.8×10^−4 mm and 1.0×10^−3 mm for TOA and TDOA. The speed of sound varies in vivo depending on the tissue type, which is expected to reduce the BP localisation accuracy. With a conservative assumption of a 5% error in the average speed of sound along the acoustic path (modelled by random uncertainties), it was observed that the localisation error after multilateration increased by around 2 mm for the examined geometry. The lowest error on the ToF estimation is obtained for the maximum-envelope extraction method when considering IA signals. Therefore, through optimal sensor positioning to minimise ToF errors, the BP could be localised in-silico with an accuracy exceeding 90 μm (equivalent to a 2% error). The BP was localised for the first experimental setup with errors ranging from 0.43 mm to 0.48 mm, depending on the sensor arrangement. The localisation was performed with a total dose of 1.69 Gy with a single shot. In the second experimental setup, the localisation was performed with 50 IA signals and a total dose of 29 Gy, achieving a localisation error of 1 mm. For both setups, the primary sources of localisation errors were inaccuracies in sensor positioning and low signal-to-noise ratio (SNR) due to the weak and directional nature of the IA emissions. The studies conducted for the SIRMIO beamline demonstrated that the proton time profile significantly impacts the ToF estimation, influencing the accuracy of BP localisation. The optimal localisation accuracy was achieved with proton time profiles ranging from 1 μs to 4 μs. In this setup, the BP was localised for different beam offsets along the x,y, and z axes. When applying offsets along the beam axis (x-axis), the maximum error was found to be 0.48 mm. Conversely, a maximum error of 1.23 mm was obtained for a transverse beam offset (z-axis). In conclusion, this work introduces a range verification method using IA signals within the framework of the SIRMIO project. Additionally, further discussions explore the potential for transitioning the studies presented in this thesis toward real-time range verification applications

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    Digitale Hochschulschriften der LMU
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