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OPEN FAU

Online publication system of Friedrich-Alexander-Universität Erlangen-Nürnberg

The online publication system OPEN FAU is the central publication platform for Open Access publishing for all members of Friedrich-Alexander-Universität. Qualified works from research and teaching may be published here free of charge, either as a primary or secondary publication. The full texts are permanently available worldwide and are findable and citable via catalogues and search engines.


To search for documents in OPEN FAU, please select "Search" (via the magnifying glass at the top right); this will provide you with various search options. If you want to publish a document, go to "Login" and "My Publications". Then drag you document into the field provided and enter the metadata. In just a few steps, you can submit your document. Please note our guidelines, the publication contract and FAQs.

 

Recent Submissions

Doctoral thesis
Open Access
High-Throughput Viscoelastic Characterization of Cells in Microchannels
(2024) Reichel, Felix
Extensive research has showcased the potential of cell viscoelastic properties as intrinsic markers of cell state, functionality, and disease. While various techniques have been developed to measure cell viscoelasticity, most lack the throughput required for clinical diagnostics. Microfluidic techniques were designed to enhance throughput, but available designs lead to intricate stress distributions on the cell surface, complicating the analysis of a stress-strain relation. This thesis aims to bridge this gap by presenting a high-throughput framework offering a straightforward stress-strain relation for a direct derivation of viscoelastic properties. Microfluidic cell deformability techniques frequently employ a carrier solution of methyl cellulose (MC). These solutions exhibit complex stresses in flow and a complete description of shear and normal stresses at high shear rates was not reported before. In a comprehensive study, the shear rheology of MC solutions was measured at shear rates up to 150 000 1/s, providing the first results at these shear rates and revealing the viscoelastic nature of these solutions. I analyzed these measurements to derive constitutive equations for calculating the stresses of MC solutions in microchannel flow. These results were employed to model the flow in real-time deformability cytometry (RT-DC), a prominent microfluidic technique for measuring cell elasticity. I developed a protocol and analysis pipeline to extend RT-DC for viscoelasticity measurements. Simultaneously, simulations were created to match experimental conditions, revealing discrepancies between simulation and experiment. The main reason for the mismatch was identified as an incomplete modeling of the viscoelastic contributions of the MC solutions. Furthermore, the simulations unveiled a complex stress-strain relation for RT-DC experiments. To address this, I proposed a hyperbolic channel design to create a well-defined and constant stress along the flow axis, simplifying the viscoelastic analysis. I validated this approach by determining deformation timescales through measurements on oil droplets with varying viscosities and the stiffness of mechanical calibration particles from polyacrylamide (PAAm) microgels. Subsequently, the hyperbolic channels were then employed on human leukemia cell line HL60 cells, demonstrating that changes in cell viscoelasticity due to interference with the cytoskeleton could be measured. This showcases the approach as a streamlined and time-efficient solution for assessing the viscoelastic properties of large cell populations and other microscale soft particles. The concepts outlined here are already routinely used for the analysis of RT-DC experiments. The results presented in this thesis offer valuable insights for the fields of cell mechanics, deformability cytometry, and fluid mechanics of complex liquids, with wide-ranging applications in cell research or diagnostics.
Doctoral thesis
Open Access
Der Verlust von Polyzystin-1 führt zu einem cAMP-abhängigen Umschalten von Tubulogenese auf Zystenbildung
(2024) Scholz, Julia Katharina
Hintergrund: Die autosomal dominante polyzystische Nierenerkrankung (ADPKD) ist die häufigste zu terminaler Niereninsuffizienz führende monogenetische Erkrankung und wird in einer Mehrzahl der Fälle durch eine Mutation im Polyzystin-1 kodierenden PKD1-Gen verursacht. In der Folge bilden sich multiple renale Zysten, deren kontinuierliches Wachstum durch Druck auf umliegende Nephrone zu einem Verlust der Nierenfunktion führt. Als gesichert gilt die Annahme, dass das Wachstum dieser Nierenzysten von dem second Messenger zyklisches Adenosinmonophosphat (cAMP) abhängig ist. Die Rolle von cAMP in der Entstehung der Nierenzysten ist jedoch noch nicht geklärt. Methoden: In der vorliegenden Publikation „Loss of Polycystin-1 causes cAMP-dependent switch from tubule to cyst formation“ wurde der Einfluss von cAMP auf die Organisation von renalen Tubulusepithelzellen im Kontext einer Polyzystin-1-Defizienz untersucht. Mit Hilfe von genetischer Modifikation mittels CRISPR/Cas9 wurde ein Polyzystin-1-defizientes Tubuluszellmodell etabliert. Die Auswirkung dieses Polyzystin-1-Verlusts auf Migration und Zellpolarität wurde in vitro in 2D-Modellen analysiert. Dessen Folge auf die Morphologie und das Migrationsverhalten von Sphäroiden wurde ergänzend in einem 3D-Kollagenmodell untersucht. Zudem wurde der Einfluss von cAMP auf die Tubuli von an Embryonal-Tag 13,5 entnommenen und ex vivo kultivierten Mausembryonieren untersucht. Ergebnisse: Der Verlust von Polyzystin-1 führte zu einem signifikanten Anstieg von intrazellulärem cAMP in den untersuchten Nierentubuluszellen. Der Anstieg von cAMP beeinträchtigte dabei sowohl die Polarität, das Migrationsverhalten als auch die Morphologie der renalen Tubuluszellen in vitro. In den Mausembryonieren führte der cAMP-Anstieg zu einer gestörten Orientierung der Tubulusepithelzellen. Schlussfolgerung: Die vorliegenden Ergebnisse zeigen, dass der Verlust von Polyzystin-1 zu einem Anstieg von cAMP in renalen Tubuluszellen führt. Die dadurch verursachten zellulären Störungen bekräftigen den vermuteten Einfluss von cAMP auf die Bildung renaler Zysten, die sich von den bisher bekannten cAMP-abhängigen Mechanismen beim Zystenwachstum deutlich unterscheiden.
Doctoral thesis
Open Access
Coupling methods of topology and shape optimization for geometrically exact design
Schriftenreihe Technische Mechanik : 54, (2024) Stankiewicz, Gabriel
Structural optimization offers automated tools to design structures based on user-defined objectives and constraints. Various structural optimization types excel in specific fields of application, Among which, density-based topology optimization is the most versatile one and is capable of generating complex geometries without any initial design guess. Nevertheless, it lacks accurate and smooth boundary representation. On the other hand, node-based shape optimization deals with an explicit boundary but does not possess the capability to undertake substantial design alterations. A modification to the standard, explicitly meshed shape optimization involves the embedding domain discretization (EDD) method. EDD-based shape optimization offers larger design updates, simpler regularization and most importantly, the structure is represented in a comparable manner to density-based topology optimization. The objective of this work is to develop methods that merge density-based topology optimization with EDD-based shape optimization to create smooth, optimal structures that are production-ready without the need for an initial design guess, regardless of the geometric complexity. To achieve this, two coupling methods are proposed and evaluated. First, a novel simultaneous coupling approach is proposed by merging topology optimization and EDD-based shape optimization into a single problem. To realize this, pseudo-densities are introduced into the EDD formulation, thereby expanding the design space with a second set of design variables. Secondly, the widely-used sequential approach is modified to meet the requirements of EDD-based shape optimization, thereby streamlining the transition from topology to EDD-based representation, as compared to generating the standard, explicit mesh. The performance of the simultaneously coupled approach is evaluated for linear elastic problems. The sequential approach is typically applied to highly complex problems, specifically those involving geometrically nonlinear compliant mechanisms and piezoelectric metamaterials. The inclusion of an explicit boundary during the shape optimization process allows for the consideration of boundary-specific constraints. In order to enhance both durability and manufacturability, a novel formulation of a curvature constraint is presented, which is integrated into the sensitivity regularization method by means of a traction method. The traction method is adapted for the specifics of EDD such that it is formulated directly on the embedded boundary and addresses both sensitivity smoothing and geometrical constraints. Furthermore, adaptive domain and shape refinement strategies have been revised to improve accuracy in critical regions and at the same time lowering the computational effort.
Doctoral thesis
Open Access
Learning Visuomotor Policies for Cooperative Robot-Assisted Surgery
(2024) Scheikl, Paul Maria
An ageing population and increasing urbanization have led to a shortage of medical personnel, which impacts patient care, especially in surgery. Minimally invasive surgery of the abdomen, laparoscopy, has advantages over open surgery, such as less bleeding and infection risk, shorter hospital stays, and reduced pain. However, the complexity of laparoscopic procedures demands a high level of skill and coordination among surgical staff, exacerbating personnel shortages. Although developments in Robot-Assisted Surgery (RAS) have eased the physical and mental strain on surgeons and enabled solo-surgery to partly address the personnel shortage, these systems lack autonomy and are mostly controlled directly by surgeons. Automation of repetitive tasks and cooperative assistive systems could further reduce the strain on surgical staff and improve patient care. The complexity of laparoscopic tasks, cooperation among team members with distinct roles, and the intricacies of the surgical environment underscore the demand for decentralized artificial agents to cooperatively solve tasks in RAS. This thesis focuses on advancing RAS by learning visuomotor policies that are able to cooperate with human surgeons. It addresses a variety of challenges in laparoscopic surgery, such as the need for precision in manipulating deformable objects, reacting to changes and uncertainties in the environment, and flexibly cooperating with human surgeons. The contributions of this thesis encompass five topics. 1) Standardized Learning Environments: Establishes benchmark environments for comparable RAS research and identifies challenges for Reinforcement Learning (RL) in this domain. 2) Semantic Segmentation: Compares various architectures and training strategies for semantic segmentation in laparoscopic surgery, crucial for generating semantically rich observations as policy inputs. 3) Human-Robot Cooperation: Applies Multi-Agent RL in RAS, simplifying coordination in multi-instrument control and laying the foundation for cooperative autonomous surgical assistants. 4) Sim-to-Real Transfer of Visuomotor Policies: Demonstrates data-efficient transfer of visuomotor policies from simulation to real systems, focusing on deformable object manipulation. 5) Gentle Manipulation of Deformable Objects: Introduces a novel method integrating diffusion-based Imitation Learning (IL) and Probabilistic Dynamic Movement Primitives (ProDMPs) for data-efficient and robust policies in deformable object manipulation. The research contributes to cognitive surgical robotics, aiming to enhance patient care and surgical efficiency, emphasizing the synergy of human expertise and robotic precision.
Doctoral thesis
Open Access
Untersuchung eines Zusammenhangs zwischen dem sagittalen Wirbelsäulenprofil und der obstruktiven Schlafapnoe
(2024) Granderath, Verena, geb. Hundt
Hintergrund und Ziele Die Ätiologie der obstruktiven Schlafapnoe (OSA) ist bis dato nur unzureichend verstanden. Zahlreiche Studien konzentrieren sich bei dem Nachweis von Ursa-chen und Folgen der OSA auf den Kopf-Hals-Bereich. Die induktive Argumenta-tionskette der Autorin dieser Arbeit sah durch eine kompensatorische Hyper-lordosierung der Halswirbelsäule bei betonter Brustwirbelkyphose eine Änderung der Zugrichtung der Muskulatur infra- sowie suprahyoidal vor. Aus dieser Hal-tungsveränderung soll eine Forward Head Posture (FHP) folgen, welche nach-weislich einen kompromittierenden Einfluss auf die oberen Atemwege hat und damit zu OSA führt. Das Ziel der hier vorliegenden Arbeit war nun die Analyse eines denkbaren Ein-flusses des sagittalen Wirbelsäulenprofils sowie der Wirbelsäulenbeweglichkeit auf den Schweregrad der OSA. Zudem wurde eine Geschlechterdifferenz aller Parameter untersucht. Methoden In dieser prospektiven Studie wurden 50 OSA-Patienten mittels standardisierter Polysomnografie (PSG) im Schlaflabor untersucht. Die Patienten wurden nach ihrem Geschlecht eingeteilt. Der Schweregrad der OSA wurde über den Apnoe-Hypopnoe-Index (AHI) ermittelt. Die orthopädische Dokumentation umfasste Längen- und Umfangsmessungen von Hals, Brust, Bauch und Becken sowie Messungen von Bewegungsparametern nach der Neutral-Null-Methode der zer-vikalen und thorako-lumbalen Wirbelsäulenabschnitte. Aus den Bewegungspa-rametern wurde ein Beweglichkeitsprofil der Wirbelsäule erstellt. Weiter wurde der Body-Mass-Index (BMI) ermittelt. Die statistische Analyse potenzieller Un-terschiede erfolgte mit dem Mann-Whitney-U-Test. Eventuelle Zusammenhänge zwischen verschiedenen Parametern wurden mit der Korrelationsanalyse nach Pearson analysiert. Ergebnisse Bis auf den Halsumfang zeigten die männlichen und weiblichen Patienten keine signifikanten Unterschiede bezüglich der gemessenen anatomischen Daten. Es bestand kein signifikanter Zusammenhang zwischen dem Schweregrad der OSA und dem Beweglichkeitsprofil der Wirbelsäule sowie einzelnen Parametern der Wirbelsäulenbeweglichkeit. Der Schweregrad der OSA korrelierte lediglich mit dem BMI und dem Halsumfang. Schlussfolgerung Die gewonnenen Daten legen nahe, dass das sagittale Profil der Wirbelsäule sowie die Wirbelsäulenbeweglichkeit keinen eindeutigen Einfluss auf den Schwe-regrad der OSA besitzen. In diesen Parametern bestehen keine geschlechter-spezifischen Unterschiede.   2. Abstract The pathogenesis of obstructive sleep apnea is not jet known in its details. Men suffer more often than women of the narrowing and/or obstruction of the upper airways. The author itself suggested that a hyperlordosis of the cervical spine is caused by a hyperkyphosis of the thoracal spine and changes the supra- and infrahyoidal musculature. These changes follows a Forward Head Posture, which has a negative, compromising effect on the upper airway and leads to OSA. However, the objective of this study was to analyze the sagittal profile of the col-umn in men and women and its effects on the severity of OSA. Methods A sample of 50 adults was studied by standardized overnight polysomnography. The severity of OSA was determined via the apnea-hypopnea score. The clinical orthopedic examination included measurements of length and circumference of the neck, chest, abdomen, and the pelvis. Furthermore, the mobility of the cervi-cal and the thoraco-lumbal sections of the spine column was examined by the neutral-zero-method. A so called „profile of the spinemobility“was calculated from these parameters. In addition, the BMI was determined. The statistical analysis of potential correlations or differences was determined via Mann-Whitney-U-test and Pearson-Test. Results Despite the neck circumference there are no significant differences in men and women. Furthermore, there is neither a significant correlation between the sever-ity of OSA and the single parameters nor the determined “profile of spinemobili-ty”. Only the BMI and the neck circumference showed a correlation with the se-verity of OSA. Conclusion The Data obtained demonstrate that there is no significant influence of the sagit-tal profile of the spine on the severity of the obstructive sleep apnea.