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While teleoperation of technical highly sophisticated systems has already been a wide field of research, especially for space and robotics applications, the automation industry has not yet benefited from its results. Besides the established fields of application, also production lines with industrial robots and the surrounding plant components are in need of being remotely accessible. This is especially critical for maintenance or if an unexpected problem cannot be solved by the local specialists.
Special machine manufacturers, especially robotics companies, sell their technology worldwide. Some factories, for example in emerging economies, lack qualified personnel for repair and maintenance tasks. When a severe failure occurs, an expert of the manufacturer needs to fly there, which leads to long down times of the machine or even the whole production line. With the development of data networks, a huge part of those travels can be omitted, if appropriate teleoperation equipment is provided.
This thesis describes the development of a telemaintenance system, which was established in an active production line for research purposes. The customer production site of Braun in Marktheidenfeld, a factory which belongs to Procter & Gamble, consists of a six-axis cartesian industrial robot by KUKA Industries, a two-component injection molding system and an assembly unit. The plant produces plastic parts for electric toothbrushes.
In the research projects "MainTelRob" and "Bayern.digital", during which this plant was utilised, the Zentrum für Telematik e.V. (ZfT) and its project partners develop novel technical approaches and procedures for modern telemaintenance. The term "telemaintenance" hereby refers to the integration of computer science and communication technologies into the maintenance strategy. It is particularly interesting for high-grade capital-intensive goods like industrial robots. Typical telemaintenance tasks are for example the analysis of a robot failure or difficult repair operations. The service department of KUKA Industries is responsible for the worldwide distributed customers who own more than one robot. Currently such tasks are offered via phone support and service staff which travels abroad. They want to expand their service activities on telemaintenance and struggle with the high demands of teleoperation especially regarding security infrastructure. In addition, the facility in Marktheidenfeld has to keep up with the high international standards of Procter & Gamble and wants to minimize machine downtimes. Like 71.6 % of all German companies, P&G sees a huge potential for early information on their production system, but complains about the insufficient quality and the lack of currentness of data.
The main research focus of this work lies on the human machine interface for all human tasks in a telemaintenance setup. This thesis provides own work in the use of a mobile device in context of maintenance, describes new tools on asynchronous remote analysis and puts all parts together in an integrated telemaintenance infrastructure. With the help of Augmented Reality, the user performance and satisfaction could be raised. A special regard is put upon the situation awareness of the remote expert realized by different camera viewpoints. In detail the work consists of:
- Support of maintenance tasks with a mobile device
- Development and evaluation of a context-aware inspection tool
- Comparison of a new touch-based mobile robot programming device to the former teach pendant
- Study on Augmented Reality support for repair tasks with a mobile device
- Condition monitoring for a specific plant with industrial robot
- Human computer interaction for remote analysis of a single plant cycle
- A big data analysis tool for a multitude of cycles and similar plants
- 3D process visualization for a specific plant cycle with additional virtual information
- Network architecture in hardware, software and network infrastructure
- Mobile device computer supported collaborative work for telemaintenance
- Motor exchange telemaintenance example in running production environment
- Augmented reality supported remote plant visualization for better situation awareness
Telemedicine uses telecommunication and information technology to provide health care services over spatial distances. In the upcoming demographic changes towards an older average population age, especially rural areas suffer from a decreasing doctor to patient ratio as well as a limited amount of available medical specialists in acceptable distance. These areas could benefit the most from telemedicine applications as they are known to improve access to medical services, medical expertise and can also help to mitigate critical or emergency situations. Although the possibilities of telemedicine applications exist in the entire range of healthcare, current systems focus on one specific disease while using dedicated hardware to connect the patient with the supervising telemedicine center.
This thesis describes the development of a telemedical system which follows a new generic design approach. This bridges the gap of existing approaches that only tackle one specific application. The proposed system on the contrary aims at supporting as many diseases and use cases as possible by taking all the stakeholders into account at the same time. To address the usability and acceptance of the system it is designed to use standardized hardware like commercial medical sensors and smartphones for collecting medical data of the patients and transmitting them to the telemedical center. The smartphone can also act as interface to the patient for health questionnaires or feedback.
The system can handle the collection and transport of medical data, analysis and visualization of the data as well as providing a real time communication with video and audio between the users.
On top of the generic telemedical framework the issue of scalability is addressed by integrating a rule-based analysis tool for the medical data. Rules can be easily created by medical personnel via a visual editor and can be personalized for each patient. The rule-based analysis tool is extended by multiple options for visualization of the data, mechanisms to handle complex rules and options for performing actions like raising alarms or sending automated messages.
It is sometimes hard for the medical experts to formulate their knowledge into rules and there may be information in the medical data that is not yet known. This is why a machine learning module was integrated into the system. It uses the incoming medical data of the patients to learn new rules that are then presented to the medical personnel for inspection. This is in line with European legislation where the human still needs to be in charge of such decisions.
Overall, we were able to show the benefit of the generic approach by evaluating it in three completely different medical use cases derived from specific application needs: monitoring of COPD (chronic obstructive pulmonary disease) patients, support of patients performing dialysis at home and councils of intensive-care experts. In addition the system was used for a non-medical use case: monitoring and optimization of industrial machines and robots. In all of the mentioned cases, we were able to prove the robustness of the generic approach with real users of the corresponding domain. This is why we can propose this approach for future development of telemedical systems.
The attitude and orbit control system of pico- and nano-satellites to date is one of the bottle necks for future scientific and commercial applications. A performance increase while keeping with the satellites’ restrictions will enable new space missions especially for the smallest of the CubeSat classes. This work addresses methods to measure and improve the satellite’s attitude pointing and orbit control performance based on advanced sensor data analysis and optimized on-board software concepts. These methods are applied to spaceborne satellites and future CubeSat missions to demonstrate their validity. An in-orbit calibration procedure for a typical CubeSat attitude sensor suite is developed and applied to the UWE-3 satellite in space. Subsequently, a method to estimate the attitude determination accuracy without the help of an external reference sensor is developed. Using this method, it is shown that the UWE-3 satellite achieves an in-orbit attitude determination accuracy of about 2°.
An advanced data analysis of the attitude motion of a miniature satellite is used in order to estimate the main attitude disturbance torque in orbit. It is shown, that the magnetic disturbance is by far the most significant contribution for miniature satellites and a method to estimate the residual magnetic dipole moment of a satellite is developed. Its application to three CubeSats currently in orbit reveals that magnetic disturbances are a common issue for this class of satellites. The dipole moments measured are between 23.1mAm² and 137.2mAm². In order to autonomously estimate and counteract this disturbance in future missions an on-board magnetic dipole estimation algorithm is developed.
The autonomous neutralization of such disturbance torques together with the simplification of attitude control for the satellite operator is the focus of a novel on-board attitude control software architecture. It incorporates disturbance torques acting on the satellite and automatically optimizes the control output. Its application is demonstrated in space on board of the UWE-3 satellite through various attitude control experiments of which the results are presented here.
The integration of a miniaturized electric propulsion system will enable CubeSats to perform orbit control and, thus, open up new application scenarios. The in-orbit characterization, however, poses the problem of precisely measuring very low thrust levels in the order of µN. A method to measure this thrust based on the attitude dynamics of the satellite is developed and evaluated in simulation. It is shown, that the demonstrator mission UWE-4 will be able to measure these thrust levels with a high accuracy of 1% for thrust levels higher than 1µN.
The orbit control capabilities of UWE-4 using its electric propulsion system are evaluated and a hybrid attitude control system making use of the satellite’s magnetorquers and the electric propulsion system is developed. It is based on the flexible attitude control architecture mentioned before and thrust vector pointing accuracies of better than 2° can be achieved. This results in a thrust delivery of more than 99% of the desired acceleration in the target direction.
Object six Degrees of Freedom (6DOF) pose estimation is a fundamental problem in many practical robotic applications, where the target or an obstacle with a simple or complex shape can move fast in cluttered environments. In this thesis, a 6DOF pose estimation algorithm is developed based on the fused data from a time-of-flight camera and a color camera. The algorithm is divided into two stages, an annealed particle filter based coarse pose estimation stage and a gradient decent based accurate pose optimization stage. In the first stage, each particle is evaluated with sparse representation. In this stage, the large inter-frame motion of the target can be well handled. In the second stage, the range data based conventional Iterative Closest Point is extended by incorporating the target appearance information and used for calculating the accurate pose by refining the coarse estimate from the first stage. For dealing with significant illumination variations during the tracking, spherical harmonic illumination modeling is investigated and integrated into both stages. The robustness and accuracy of the proposed algorithm are demonstrated through experiments on various objects in both indoor and outdoor environments. Moreover, real-time performance can be achieved with graphics processing unit acceleration.
This dissertation presents controller design methodologies for a formation of cooperative mobile robots to perform trajectory tracking and convoy protection tasks. Two major problems related to multi-agent formation control are addressed, namely the time-delay and optimality problems. For the task of trajectory tracking, a leader-follower based system structure is adopted for the controller design, where the selection criteria for controller parameters are derived through analyses of characteristic polynomials. The resulting parameters ensure the stability of the system and overcome the steady-state error as well as the oscillation behavior under time-delay effect. In the convoy protection scenario, a decentralized coordination strategy for balanced deployment of mobile robots is first proposed. Based on this coordination scheme, optimal controller parameters are generated in both centralized and decentralized fashion to achieve dynamic convoy protection in a unified framework, where distributed optimization technique is applied in the decentralized strategy. This unified framework takes into account the motion of the target to be protected, and the desired system performance, for instance, minimal energy to spend, equal inter-vehicle distance to keep, etc.
Both trajectory tracking and convoy protection tasks are demonstrated through simulations and real-world hardware experiments based on the robotic equipment at Department of Computer Science VII, University of Würzburg.
In this work, a novel method for estimating the relative pose of a known object is presented, which relies on an application-specific data fusion process. A PMD-sensor in conjunction with a CCD-sensor is used to perform the pose estimation. Furthermore, the work provides a method for extending the measurement range of the PMD sensor along with the necessary calibration methodology. Finally, extensive measurements on a very accurate Rendezvous and Docking testbed are made to evaluate the performance, what includes a detailed discussion of lighting conditions.
Im metastasierten Melanom sind bei Vorhandensein einer BRAF V600 Mutation zielgerichtete Therapien mit BRAF+MEK-Inhibitoren sowie Immuntherapien (ICB), die Immuncheckpoints wie PD-1 blockieren, zugelassen. Aktuell gibt es keine evidenzbasierte Empfehlung welche Therapie in der Erstlinie im BRAF V600 mutierten Melanom eingesetzt werden sollte. Bis jetzt wurde der Stellenwert PD-1 basierter Immuncheckpoint Blockade in der Zweitlinie nach Progress unter BRAF+MEK-Inhibition nicht beschrieben. Es ist auch unklar, ob die Kombinations-ICB (PD-1 plus CTLA-4 Blockade) mit einer Verbesserung des Ansprechens und Überlebens gegenüber einer PD-1 Monotherapie assoziiert ist, wie für das therapie-naive Melanom beschrieben. Wir haben eine retrospektive, multizentrische Studie durchgeführt um die Wirksamkeit von PD-1 basierten Immuntherapien nach Progress unter zielgerichteter Therapie zu explorieren. In unserer Untersuchung zeigten PD-1 Monotherapie und die kombinierte PD-1 plus CTLA-4 Blockade eine ähnliche Wirksamkeit in Patienten mit BRAFi+MEKi-Resistenz. Die Kombinationstherapie war dagegen mit einem deutlich höheren Risiko für schwerwiegende immunvermittelte Nebenwirkungen im Vergleich zu PD-1 Monotherapie assoziiert. Unsere Daten indizieren, dass eine PD-1 Blockade einer Kombinations-ICB in der Zweitlinie nach Progress unter zielgerichteter Therapie im fortgeschrittenen BRAF V600 mutierten Melanom vorzuziehen ist.
Produktionssysteme mit Industrierobotern werden zunehmend komplex; waren deren Arbeitsbereiche früher noch statisch und abgeschirmt, und die programmierten Abläufe gleichbleibend, so sind die Anforderungen an moderne Robotik-Produktionsanlagen gestiegen: Diese sollen sich jetzt mithilfe von intelligenter Sensorik auch in unstrukturierten Umgebungen einsetzen lassen, sich bei sinkenden Losgrößen aufgrund individualisierter Produkte und häufig ändernden Produktionsaufgaben leicht rekonfigurieren lassen, und sogar eine direkte Zusammenarbeit zwischen Mensch und Roboter ermöglichen. Gerade auch bei dieser Mensch-Roboter-Kollaboration wird es damit notwendig, dass der Mensch die Daten und Aktionen des Roboters leicht verstehen kann. Aufgrund der gestiegenen Anforderungen müssen somit auch die Bedienerschnittstellen dieser Systeme verbessert werden. Als Grundlage für diese neuen Benutzerschnittstellen bietet sich Augmented Reality (AR) als eine Technologie an, mit der sich komplexe räumliche Daten für den Bediener leicht verständlich darstellen lassen. Komplexe Informationen werden dabei in der Arbeitsumgebung der Nutzer visualisiert und als virtuelle Einblendungen sichtbar gemacht, und so auf einen Blick verständlich. Die diversen existierenden AR-Anzeigetechniken sind für verschiedene Anwendungsfelder unterschiedlich gut geeignet, und sollten daher flexibel kombinier- und einsetzbar sein. Auch sollen diese AR-Systeme schnell und einfach auf verschiedenartiger Hardware in den unterschiedlichen Arbeitsumgebungen in Betrieb genommen werden können. In dieser Arbeit wird ein Framework für Augmented Reality Systeme vorgestellt, mit dem sich die genannten Anforderungen umsetzen lassen, ohne dass dafür spezialisierte AR-Hardware notwendig wird. Das Flexible AR-Framework kombiniert und bündelt dafür verschiedene Softwarefunktionen für die grundlegenden AR-Anzeigeberechnungen, für die Kalibrierung der notwendigen Hardware, Algorithmen zur Umgebungserfassung mittels Structured Light sowie generische ARVisualisierungen und erlaubt es dadurch, verschiedene AR-Anzeigesysteme schnell und flexibel in Betrieb zu nehmen und parallel zu betreiben. Im ersten Teil der Arbeit werden Standard-Hardware für verschiedene AR-Visualisierungsformen sowie die notwendigen Algorithmen vorgestellt, um diese flexibel zu einem AR-System zu kombinieren. Dabei müssen die einzelnen verwendeten Geräte präzise kalibriert werden; hierfür werden verschiedene Möglichkeiten vorgestellt, und die mit ihnen dann erreichbaren typischen Anzeige- Genauigkeiten in einer Evaluation charakterisiert. Nach der Vorstellung der grundlegenden ARSysteme des Flexiblen AR-Frameworks wird dann eine Reihe von Anwendungen vorgestellt, bei denen das entwickelte System in konkreten Praxis-Realisierungen als AR-Benutzerschnittstelle zum Einsatz kam, unter anderem zur Überwachung von, Zusammenarbeit mit und einfachen Programmierung von Industrierobotern, aber auch zur Visualisierung von komplexen Sensordaten oder zur Fernwartung. Im Verlauf der Arbeit werden dadurch die Vorteile, die sich durch Verwendung der AR-Technologie in komplexen Produktionssystemen ergeben, herausgearbeitet und in Nutzerstudien belegt.
Since the first CubeSat launch in 2003, the hardware and software complexity of the nanosatellites was continuosly increasing.
To keep up with the continuously increasing mission complexity and to retain the primary advantages of a CubeSat mission, a new approach for the overall space and ground software architecture and protocol configuration is elaborated in this work.
The aim of this thesis is to propose a uniform software and protocol architecture as a basis for software development, test, simulation and operation of multiple pico-/nanosatellites based on ultra-low power components.
In contrast to single-CubeSat missions, current and upcoming nanosatellite formation missions require faster and more straightforward development, pre-flight testing and calibration procedures as well as simultaneous operation of multiple satellites.
A dynamic and decentral Compass mission network was established in multiple active CubeSat missions, consisting of uniformly accessible nodes.
Compass middleware was elaborated to unify the communication and functional interfaces between all involved mission-related software and hardware components.
All systems can access each other via dynamic routes to perform service-based M2M communication.
With the proposed model-based communication approach, all states, abilities and functionalities of a system are accessed in a uniform way.
The Tiny scripting language was designed to allow dynamic code execution on ultra-low power components as a basis for constraint-based in-orbit scheduler and experiment execution.
The implemented Compass Operations front-end enables far-reaching monitoring and control capabilities of all ground and space systems.
Its integrated constraint-based operations task scheduler allows the recording of complex satellite operations, which are conducted automatically during the overpasses.
The outcome of this thesis became an enabling technology for UWE-3, UWE-4 and NetSat CubeSat missions.
Miniaturized satellites on a nanosatellite scale below 10kg of total mass contribute most to the number of launched satellites into Low Earth Orbit today. This results from the potential to design, integrate and launch these space missions within months at very low costs. In the past decade, the reliability in the fields of system design, communication, and attitude control have matured to allow for competitive applications in Earth observation, communication services, and science missions. The capability of orbit control is an important next step in this development, enabling operators to adjust orbits according to current mission needs and small satellite formation flight, which promotes new measurements in various fields of space science. Moreover, this ability makes missions with altitudes above the ISS comply with planned regulations regarding collision avoidance maneuvering.
This dissertation presents the successful implementation of orbit control capabilities on the pico-satellite class for the first time. This pioneering achievement is demonstrated on the 1U CubeSat UWE–4. A focus is on the integration and operation of an electric propulsion system on miniaturized satellites. Besides limitations in size, mass, and power of a pico-satellite, the choice of a suitable electric propulsion system was driven by electromagnetic cleanliness and the use as a combined attitude and orbit control system. Moreover, the integration of the propulsion system leaves the valuable space at the outer faces of the CubeSat structure unoccupied for future use by payloads. The used NanoFEEP propulsion system consists of four thruster heads, two neutralizers and two Power Processing Units (PPUs).
The thrusters can be used continuously for 50 minutes per orbit after the liquefaction of the propellant by dedicated heaters. The power consumption of a PPU with one activated thruster, its heater and a neutralizer at emitter current levels of 30-60μA or thrust levels of 2.6-5.5μN, respectively, is in the range of 430-1050mW. Two thruster heads were activated within the scope of in-orbit experiments. The thrust direction was determined using a novel algorithm within 15.7° and 13.2° of the mounting direction. Despite limited controllability of the remaining thrusters, thrust vector pointing was achieved using the magnetic actuators of the Attitude and Orbit Control System.
In mid 2020, several orbit control maneuvers changed the altitude of UWE–4, a first for pico-satellites. During the orbit lowering scenario with a duration of ten days, a single thruster head was activated in 78 orbits for 5:40 minutes per orbit. This resulted in a reduction of the orbit altitude by about 98.3m and applied a Delta v of 5.4cm/s to UWE–4. The same thruster was activated in another experiment during 44 orbits within five days for an average duration of 7:00 minutes per orbit. The altitude of UWE–4 was increased by about 81.2m and a Delta v of 4.4cm/s was applied. Additionally, a collision avoidance maneuver was executed in July 2020, which increased the distance of closest approach to the object by more than 5000m.
Small satellites contribute significantly in the rapidly evolving innovation in space engineering, in particular in distributed space systems for global Earth observation and communication services. Significant mass reduction by miniaturization, increased utilization of commercial high-tech components, and in particular standardization are the key drivers for modern miniature space technology.
This thesis addresses key fields in research and development on miniature satellite technology regarding efficiency, flexibility, and robustness. Here, these challenges are addressed by the University of Wuerzburg’s advanced pico-satellite bus, realizing a generic modular satellite architecture and standardized interfaces for all subsystems. The modular platform ensures reusability, scalability, and increased testability due to its flexible subsystem interface which allows efficient and compact integration of the entire satellite in a plug-and-play manner.
Beside systematic design for testability, a high degree of operational robustness is achieved by the consequent implementation of redundancy of crucial subsystems. This is combined with efficient fault detection, isolation and recovery mechanisms. Thus, the UWE-3 platform, and in particular the on-board data handling system and the electrical power system, offers one of the most efficient pico-satellite architectures launched in recent years and provides a solid basis for future extensions.
The in-orbit performance results of the pico-satellite UWE-3 are presented and summarize successful operations since its launch in 2013. Several software extensions and adaptations have been uploaded to UWE-3 increasing its capabilities. Thus, a very flexible platform for in-orbit software experiments and for evaluations of innovative concepts was provided and tested.
Ongoing changes in spaceflight – continuing miniaturization, declining costs of rocket launches and satellite components, and improved satellite computing and control capabilities – are advancing Satellite Formation Flying (SFF) as a research and application area. SFF enables new applications that cannot be realized (or cannot be realized at a reasonable cost) with conventional single-satellite missions. In particular, distributed Earth observation applications such as photogrammetry and tomography or distributed space telescopes require precisely placed and controlled satellites in orbit.
Several enabling technologies are required for SFF, such as inter-satellite communication, precise attitude control, and in-orbit maneuverability. However, one of the most important requirements is a reliable distributed Guidance, Navigation and Control (GNC) strategy. This work addresses the issue of distributed GNC for SFF in 3D with a focus on Continuous Low-Thrust (CLT) propulsion satellites (e.g., with electric thrusters) and concentrates on circular low Earth orbits. However, the focus of this work is not only on control theory, but control is considered as part of the system engineering process of typical small satellite missions. Thus, common sensor and actuator systems are analyzed to derive their characteristics and their impacts on formation control. This serves as the basis for the design, implementation, and evaluation of the following control approaches: First, a Model Predictive Control (MPC) method with specific adaptations to SFF and its requirements and constraints; second, a distributed robust controller that combines consensus methods for distributed system control and $H_{\infty}$ robust control; and finally, a controller that uses plant inversion for control and combines it with a reference governor to steer the controller to the target on an optimal trajectory considering several constraints. The developed controllers are validated and compared based on extensive software simulations. Realistic 3D formation flight scenarios were taken from the Networked Pico-Satellite Distributed System Control (NetSat) cubesat formation flight mission. The three compared methods show different advantages and disadvantages in the different application scenarios. The distributed robust consensus-based controller for example lacks the ability to limit the maximum thrust, so it is not suitable for satellites with CLT. But both the MPC-based approach and the plant inversionbased controller are suitable for CLT SFF applications, while showing again distinct advantages and disadvantages in different scenarios.
The scientific contribution of this work may be summarized as the creation of novel and specific control approaches for the class of CLT SFF applications, which is still lacking methods withstanding the application in real space missions, as well as the scientific evaluation and comparison of the developed methods.
Dementia is a complex neurodegenerative syndrome that by 2050 could affect about 135 Million people worldwide. People with dementia experience a progressive decline in their cognitive abilities and have serious problems coping with activities of daily living, including
orientation and wayfinding tasks. They even experience difficulties in finding their way in a familiar environment. Being lost or fear of getting lost may consequently develop into other psychological deficits such as anxiety, suspicions, illusions, and aggression. Frequent results are social isolation and a reduced quality of life. Moreover, the lives of relatives and
caregivers of people with dementia are also negatively affected.
Regarding navigation and orientation, most existing approaches focus on outdoor environment and people with mild dementia, who have the capability to use mobile devices. However, Rasquin (2007) observe that even a device with three buttons may be too complicated for
people with moderate to severe dementia. In addition, people who are living in care homes mainly perform indoor activities. Given this background, we decided to focus on designing a system for indoor environments for people with moderate to severe dementia, who are unable
or reluctant to use smartphone technology.
Adopting user-centered design approach, context and requirements of people with dementia were gathered as a first step to understand needs and difficulties (especially in spatial disorientation and wayfinding problems) experienced in dementia care facilities. Then, an "Implicit Interactive Intelligent (III) Environment" for people with dementia was proposed emphasizing implicit interaction and natural interface. The backbone of this III Environment is based on supporting orientation and navigation tasks with three systems: a Monitoring system, an intelligent system, and a guiding system. The monitoring system and intelligent system automatically detect and interpret the locations and activities performed by the users i.e. people with dementia. This approach (implicit input) reduces cognitive workload as well as physical workload on the user to provide input. The intelligent system is also aware of context, predicts next situations (location, activity), and decides when to provide an appropriate service to the users. The guiding system with intuitive and dynamic environmental cues (lighting with color) has the responsibility for guiding the users to the places they need to be.
Overall, three types of a monitoring system with Ultra-Wideband and iBeacon technologies, different techniques and algorithms were implemented for different contexts of use.
They showed a high user acceptance with a reasonable price as well as decent accuracy and precision. In the intelligent system, models were built to recognize the users’ current activity, detect the erroneous activity, predict the next location and activity, and analyze the
history data, detect issues, notify them and suggest solutions to caregivers via visualized web interfaces. About the guiding systems, five studies were conducted to test and evaluate the effect of lighting with color on people with dementia. The results were promising. Although
several components of III Environment in general and three systems, in particular, are in place (implemented and tested separately), integrating them all together and employing this in the dementia context as a fully properly evaluation with formal stakeholders (people with
dementia and caregivers) are needed for the future step.
With the miniaturization of satellites a fundamental change took place in the space industry. Instead of single big monolithic satellites nowadays more and more systems are envisaged consisting of a number of small satellites to form cooperating systems in space. The lower costs for development and launch as well as the spatial distribution of these systems enable the implementation of new scientific missions and commercial services.
With this paradigm shift new challenges constantly emerge for satellite developers, particularly in the area of wireless communication systems and network protocols.
Satellites in low Earth orbits and ground stations form dynamic space-terrestrial networks. The characteristics of these networks differ fundamentally from those of other networks.
The resulting challenges with regard to communication system design, system analysis, packet forwarding, routing and medium access control as well as challenges concerning the reliability and efficiency of wireless communication links are addressed in this thesis.
The physical modeling of space-terrestrial networks is addressed by analyzing existing satellite systems and communication devices, by evaluating measurements and by implementing a simulator for space-terrestrial networks.
The resulting system and channel models were used as a basis for the prediction of the dynamic network topologies, link properties and channel interference. These predictions allowed for the implementation of efficient routing and medium access control schemes for space-terrestrial networks. Further, the implementation and utilization of software-defined ground stations is addressed, and a data upload scheme for the operation of small satellite formations is presented.
A complete simulation system is proposed that can be used as an educational tool by physicians in training basic skills of Minimally Invasive Vascular Interventions. In the first part, a surface model is developed to assemble arteries having a planar segmentation. It is based on Sweep Surfaces and can be extended to T- and Y-like bifurcations. A continuous force vector field is described, representing the interaction between the catheter and the surface. The computation time of the force field is almost unaffected when the resolution of the artery is increased.
The mechanical properties of arteries play an essential role in the study of the circulatory system dynamics, which has been becoming increasingly important in the treatment of cardiovascular diseases. In Virtual Reality Simulators, it is crucial to have a tissue model that responds in real time. In this work, the arteries are discretized by a two dimensional mesh and the nodes are connected by three kinds of linear springs. Three tissue layers (Intima, Media, Adventitia) are considered and, starting from the stretch-energy density, some of the elasticity tensor components are calculated. The physical model linearizes and homogenizes the material response, but it still contemplates the geometric nonlinearity. In general, if the arterial stretch varies by 1% or less, then the agreement between the linear and nonlinear models is trustworthy.
In the last part, the physical model of the wire proposed by Konings is improved. As a result, a simpler and more stable method is obtained to calculate the equilibrium configuration of the wire. In addition, a geometrical method is developed to perform relaxations. It is particularly useful when the wire is hindered in the physical method because of the boundary conditions. The physical and the geometrical methods are merged, resulting in efficient relaxations. Tests show that the shape of the virtual wire agrees with the experiment. The proposed algorithm allows real-time executions and the hardware to assemble the simulator has a low cost.
Despite accounting for only a small proportion of all skin cancers, malignant melanoma
displays a serious health risk with increasing incidence and high mortality rate. Fortunately,
advances in the treatment of malignant melanoma now prolong survival and enhance response
and treatment efficacy. Established biomarkers help evaluate disease progression and
facilitate choosing appropriate and individual treatment options. However, the need for easily
accessible and reliable biomarkers is rising to predict patient-specific clinical outcome.
Eosinophil infiltration into the tumor and high peripheral eosinophil counts prior and during
treatment have been associated with better response in patients for various cancer entities,
including melanoma. An analysis of a heterogeneous study cohort reported high serum ECP
levels in non-responders. Hence, eosinophil frequency and serum ECP as a soluble
eosinophil-secreted mediator were suggested as prognostic biomarkers in melanoma. We
examined whether melanoma patients treated with first-line targeted therapy could also benefit
from the effects of eosinophils. In total, 243 blood and serum samples from patients with
advanced melanoma were prospectively and retrospectively collected before and after drug
initiation. To link eosinophil function to improved clinical outcome, soluble serum markers and
peripheral blood counts were used for correlative studies using a homogeneous study cohort.
In addition, functional and phenotypical characterizations provided insights into the expression
profile and activity of freshly isolated eosinophils, including comparisons between patients and
healthy donors.
Our data showed a significant correlation between high pre-treatment blood eosinophil counts
and improved response to targeted therapy and by trend to combinatorial immunotherapy in
patients with metastatic melanoma. In accordance with previous studies our results links
eosinophil blood counts to better response in melanoma patients. High pre-treatment ECP
serum concentration correlated with response to immunotherapy but not to targeted therapy.
Eosinophils from healthy donors and patients showed functional and phenotypical similarities.
Functional assays revealed a strong cytotoxic potential of blood eosinophils towards
melanoma cells in vitro, inducing apoptosis and necrosis. In addition, in vitro cytotoxicity was
an active process of peripheral eosinophils and melanoma cells with bidirectional features and
required close cell-cell interaction. The extent of cytotoxicity was dose-dependent and showed
susceptibility to changes in physical factors like adherence. Importantly, we provide evidence
of an additive tumoricidal function of eosinophils and combinatorial targeted therapy in vitro. In
summary, we give valuable insights into the complex and treatment-dependent role of
eosinophils in melanoma. As a result, our data support the suggestion of eosinophils and their
secreted mediators as potential prognostic biomarkers. It will take additional studies to
examine the molecular mechanisms that underlie our findings.
Dielektrische Elastomersensoren sind aus Elastomermaterialien aufgebaute Sensoren mit einem kapazitiven Messprinzip. In ihrer einfachsten Form bestehen sie aus einer dehnbaren Elastomerfolie als Dielektrikum, die beidseitig mit leitfähigen und ebenfalls dehnbaren Schichten als Elektroden bedeckt ist.
Damit entsteht ein mechanisch verformbarer elektrischer Kondensator, dessen Kapazität mit der Dehnung der Elastomerfolie stetig ansteigt. Neben solchen Dehnungssensoren lassen sich mit einem geeigneten geometrischen Aufbau auch dielektrische Elastomersensoren realisieren, bei denen eine elektrische Kapazität mit einem angelegten Druck bzw. einer Kraft auf die Oberfläche, mit einer Scherkraft oder mit der Annäherung eines elektrisch leitfähigen oder polarisierbaren Körpers wie z. B. der menschlichen Hand messbar ansteigt.
Durch ihre vielfältige Funktion, intrinsische Verformbarkeit und flächige Ausgestaltung weisen Dielektrische Elastomersensoren erhebliches Potential in der Schaffung smarter, sensitiver Oberflächen auf. Dabei sind weitgehende und individuelle Adaptionen auf den jeweiligen Anwendungszweck durch Abstimmung geometrischer, mechanischer und elektrischer Eigenschaften möglich. Die bisherige Forschung beschränkt sich jedoch auf die Analyse und Optimierung einzelner Aspekte ohne das Potential einer übergreifenden systemischen Perspektive zu nutzen.
Diese Arbeit widmet sich daher der Betrachtung der Sensorik als Gesamtsystem, sowohl horizontal - von abstrakten Modellen bis zur Fertigung und prototypischen Anwendung - als auch vertikal über die Komponenten Material, Struktur und Elektronik.
Hierbei wurden in mehreren Teilgebieten eigenständige neue Erkenntnisse und Verbesserungen erzielt, die anschließend in die übergreifende Betrachtung des Gesamtsystems integriert wurden. So wurden in den theoretischen Vorarbeiten neue Konzepte zur ortsaufgelösten Erfassung mehrerer physikalischer Größen und zur elektrischen und mechanischen Modellierung entwickelt. Die abgeleiteten Materialanforderungen wurden in eine tiefgehende Charakterisierung der verwendeten Elastomer-Kompositwerkstoffe überführt, in der neuartige analytische Methoden in Form von dynamischer elektromechanischer Testung und nanoskaliger Computertomographie zur Aufklärung der inneren Wechselwirkungen zum Einsatz kamen.
Im Bereich der automatisierten Prozessierung wurde ein für die komplexen mehrschichtigen Elektrodenstrukturen geeigneter neuer lasergestützer substraktiver Fertigungprozess etabliert, der zudem die Brücke zu elastischer Elektronik schlägt.
In der abschließenden Anwendungsevaluierung wurden mehrere ortsaufgelöste und multimodale Gesamtsysteme aufgebaut und geeignete Messelektronik und Software entwickelt. Abschließend wurden die Systeme mit einem eigens entwickelten robotischen Testsystem charakterisiert und zudem das Potential der Auswertung mittels maschinellem Lernen aufgezeigt.
Die Rolle transposabler Elemente in der Genese des malignen Melanom im Fischmodell Xiphophorus
(2023)
Der Name der transposablen Elemente beruht auf ihrer Fähigkeit, ihre genomische Position verändern zu können. Durch Chromosomenaberrationen, Insertionen oder Deletionen können ihre genomischen Transpositionen genetische Instabilität verursachen. Inwieweit sie darüber hinaus regulatorischen Einfluss auf Zellfunktionen besitzen, ist Gegenstand aktueller Forschung ebenso wie die daraus resultierende Frage nach der Gesamtheit ihrer biologischen Signifikanz. Die Weiterführung experimenteller Forschung ist unabdingbar, um weiterhin offenen Fragen nachzugehen. Das Xiphophorus-Melanom-Modell stellt hierbei eines der ältesten Tiermodelle zur Erforschung des malignen Melanoms dar. Durch den klar definierten genetischen Hintergrund eignet es sich hervorragend zur Erforschung des bösartigen schwarzen Hautkrebses, welcher nach wie vor die tödlichste aller bekannten Hautkrebsformen darstellt. Die hier vorliegende Arbeit beschäftigt sich mit der Rolle transposabler Elemente in der malignen Melanomgenese von Xiphophorus.
Die Einführung von zielgerichteter Therapie und Immuntherapie hat die Behandlungsmöglichkeiten des Melanoms revolutioniert. Jedoch profitieren viele Patienten nicht langfristig von diesen Therapien. Derzeit werden klinische Studien durchgeführt, die zielgerichtete Therapie und Immuntherapie miteinander kombinieren.
In dieser Arbeit wurden in vitro Untersuchungen an den drei BRAF-V600E-mutieren Melanomzelllinien UACC 257, Malme 3M und Sk-Mel 5 unter kombinierter MAPK-Inhibitortherapie durchgeführt. Es wurden die aus der klinischen Routine bekannten Kombinationen aus BRAF- und MEK-Inhibitor – Vemurafenib und Cobimetinib, Dabrafenib und Trametinib sowie Encorafenib und Binimetinib – verwendet. Es wurde untersucht, ob obige zielgerichtete Therapeutika einen Effekt auf immunologische Marker im Melanom haben und ob sich eine der Kombinationen in ihrer Wirkung signifikant von den übrigen unterscheidet.
Mittels MTS-Assay und Zellzyklusanalysen konnte eine konzentrationsabhängige Wirkung der Inhibitoren gezeigt und in ihrer Wirkung vergleichbare Inhibitorkonzentrationen eingestellt werden. Unter kombinierter MAPK-Inhibitortherapie zeigte sich ein begrenzter Effekt auf die theoretische Immunogenität des Melanoms. So konnte eine erhöhte MHC-I-Expression (+14 %) und eine verminderte PD-L1-Expression (-24 %) gezeigt werden. Die gewählten Dosen an Inhibitoren induzierten keinen ER-Stress. Ebenso konnte keine Ekto-Calreticulin-Expression auf lebenden Zellen nachgewiesen werden. Zwischen den drei Inhibitorkombinationen zeigten sich keine signifikanten Unterschiede.
Die in dieser Arbeit gezeigten begrenzten immunologischen Effekte unter kombinierter MAPK-Inhibitortherapie legen nahe, dass eine Kombination mit Immuntherapie in Teilen synergistisch wirken könnte. Hier sind die Ergebnisse weiterer Studien abzuwarten, die zielgerichtete und Immuntherapie miteinander kombinieren, um ein tiefgreifenderes Verständnis bzgl. etwaiger Synergien zu generieren. Da zwischen den Inhibitorkombinationen keine signifikanten Unterschiede hinsichtlich ihrer Wirkung auf die Immunogenität des Melanoms gefunden wurden, ist anzunehmen, dass sie sich grundsätzlich alle gleichermaßen für eine Kombination mit einer Immuntherapie eignen. Die gezeigte MHC-I-Erhöhung trat bereits bei geringen Inhibitorkonzentrationen auf. Möglicherweise genügt bei einer Kombination mit Immuntherapie bereits eine niedrige Dosis der zielgerichteten Therapie, um die Immuntherapie zu boostern. Um die Frage nach einer möglichen Kombinationstherapie fortwährend zu analysieren, sollten zusätzliche Aspekte der Immunogenität unter kombinierter MAPK-Inhibitortherapie untersucht und die Inhibitortitration zum Vergleich der zielgerichteten Therapeutika weiter präzisiert werden.
ICIs sind inzwischen integrales Therapiemittel vieler Tumoren, selbst in nicht metastasierten Stadien. Das Management von dabei eventuell entstehenden Nebenwirkungen bleibt wichtiger Bestandteil der Therapie vor allem im fortgeschrittenen Alter. Retrospektive Untersuchungen wie unsere tragen dazu bei, das in vielen klinischen Studien unterrepräsentierte Patientenkollektiv älterer Patienten in den klinischen Alltag sowie in Therapieentscheidungen und -planungen zu integrieren.
Der primäre Studienendpunkt unserer Arbeit unterstützt wichtige Erkenntnisse anderer Studien, dass irAEs insgesamt unter älteren Patienten nicht häufiger auftreten. Zwischen allen drei Altersklassen von ~55, ~70 und ~80 Jahren zeigten sich keine signifikanten Unterschiede im Auftreten von irAEs aller Grade, wobei irAEs Grad III/IV etwas häufiger bei ~80-Jährigen auftraten. In unserem Fall stellten wir fest, dass auftretende irAEs im Alter häufiger behandelt wurden, und dass die Immuntherapie häufiger pausiert oder abgebrochen wurde. Zudem war der Anteil an Therapieabbrüchen unter den älteren Patienten wegen bestimmter Ereignisse wie TRAEs und dem Einsatz von Glukokortikoiden höher als bei jüngeren Patienten.
Die Ergebnisse unserer Studie deuten außerdem darauf hin, dass selbst unter Polypharmazie und Multimorbidität irAEs nicht häufiger bei Älteren auftraten. Ebenso können wir die interessante Beobachtung verzeichnen, dass Patienten mit >5 Medikamenten und gleichzeitig >5 Erkrankungen signifikant mehr irAEs Grad III/IV aufwiesen oder mehr Patienten Glukokortikoide verabreicht bekommen haben. Auch der Anteil an Interventionsbedarf oder Therapieabbruch war hier in allen Altersklassen höher. Es stellt sich die Frage, inwiefern hohes Alter, Komorbidität und Polypharmazie Risikofaktoren für Interventionsbedarf oder Therapieabbruch in der Immuntherapie sind, und ob ihnen eher besondere Gewichtung als Risikofaktor zukommt als dem Alter selbst.