Recent Submissions
Design for reliability in advanced technologies using machine learning
(2024) Klemme, Florian; Amrouch, Hussam (Prof. Dr.-Ing.)
This thesis focuses on the standard cell library, which is one of the core entities in the digital circuit design flow, to demonstrate the challenges and opportunities of advanced technology nodes. The standard cell library serves as a technology interface between the foundry and the circuit designer, enabling automatic mapping of high-level circuit descriptions to the technology of the foundry through the process of logic synthesis. In the past decade, the standard cell library has been continuously adapted to keep up with the demands of shrinking process nodes. This includes, e.g., the integration of more accurate timing models, process variation, or signal integrity for cross-talk and noise in the circuit. This thesis takes this development to the next level and presents approaches to bring machine learning and transistor self-heating into the standard cell library.
Spatiotemporal stop-and-go dynamics of the mitochondrial TOM core complex correlates with channel activity
(2022) Wang, Shuo; Findeisen, Lukas; Leptihn, Sebastian; Wallace, Mark I.; Hörning, Marcel; Nussberger, Stephan
Single-molecule studies can reveal phenomena that remain hidden in ensemble measurements. Here we show the correlation between lateral protein diffusion and channel activity of the general protein import pore of mitochondria (TOM-CC) in membranes resting on ultrathin hydrogel films. Using electrode-free optical recordings of ion flux, we find that TOM-CC switches reversibly between three states of ion permeability associated with protein diffusion. While freely diffusing TOM-CC molecules are predominantly in a high permeability state, non-mobile molecules are mostly in an intermediate or low permeability state. We explain this behavior by the mechanical binding of the two protruding Tom22 subunits to the hydrogel and a concomitant combinatorial opening and closing of the two β-barrel pores of TOM-CC. TOM-CC could thus represent a β-barrel membrane protein complex to exhibit membrane state-dependent mechanosensitive properties, mediated by its two Tom22 subunits.
ER stress-induced cell death proceeds independently of the TRAIL-R2 signaling axis in pancreatic β cells
(2022) Hagenlocher, Cathrin; Siebert, Robin; Taschke, Bruno; Wieske, Senait; Hausser, Angelika; Rehm, Markus
Prolonged ER stress and the associated unfolded protein response (UPR) can trigger programmed cell death. Studies in cancer cell lines demonstrated that the intracellular accumulation of TRAIL receptor-2 (TRAIL-R2) and the subsequent activation of caspase-8 contribute significantly to apoptosis induction upon ER stress. While this might motivate therapeutic strategies that promote cancer cell death through ER stress-induced caspase-8 activation, it could also support the unwanted demise of non-cancer cells. Here, we therefore investigated if TRAIL-R2 dependent signaling towards apoptosis can be induced in pancreatic β cells, whose loss by prolonged ER stress is associated with the onset of diabetes. Interestingly, we found that elevated ER stress in these cells does not result in TRAIL-R2 transcriptional induction or elevated protein levels, and that the barely detectable expression of TRAIL-R2 is insufficient to allow TRAIL-induced apoptosis to proceed. Overall, this indicates that apoptotic cell death upon ER stress most likely proceeds independent of TRAIL-R2 in pancreatic β cells. Our findings therefore point to differences in ER stress response and death decision-making between cancer cells and pancreatic β cells and also have implications for future targeted treatment strategies that need to differentiate between ER stress susceptibility of cancer cells and pancreatic β cells.
Meeting sustainable development goals via robotics and autonomous systems
(2022) Guenat, Solène; Purnell, Phil; Davies, Zoe G.; Nawrath, Maximilian; Stringer, Lindsay C.; Babu, Giridhara Rathnaiah; Balasubramanian, Muniyandi; Ballantyne, Erica E. F.; Bylappa, Bhuvana Kolar; Chen, Bei; De Jager, Peta; Del Prete, Andrea; Di Nuovo, Alessandro; Ehi-Eromosele, Cyril O.; Eskandari Torbaghan, Mehran; Evans, Karl L.; Fraundorfer, Markus; Haouas, Wissem; Izunobi, Josephat U.; Jauregui-Correa, Juan Carlos; Kaddouh, Bilal Y.; Lewycka, Sonia; MacIntosh, Ana C.; Mady, Christine; Maple, Carsten; Mhiret, Worku N.; Mohammed-Amin, Rozhen Kamal; Olawole, Olukunle Charles; Oluseyi, Temilola; Orfila, Caroline; Ossola, Alessandro; Pfeifer, Marion; Pridmore, Tony; Rijal, Moti L.; Rega-Brodsky, Christine C.; Robertson, Ian D.; Rogers, Christopher D. F.; Rougé, Charles; Rumaney, Maryam B.; Seeletso, Mmabaledi K.; Shaqura, Mohammed Z.; Suresh, L. M.; Sweeting, Martin N.; Taylor Buck, Nick; Ukwuru, M. U.; Verbeek, Thomas; Voss, Hinrich; Wadud, Zia; Wang, Xinjun; Winn, Neil; Dallimer, Martin
Robotics and autonomous systems are reshaping the world, changing healthcare, food production and biodiversity management. While they will play a fundamental role in delivering the UN Sustainable Development Goals, associated opportunities and threats are yet to be considered systematically. We report on a horizon scan evaluating robotics and autonomous systems impact on all Sustainable Development Goals, involving 102 experts from around the world. Robotics and autonomous systems are likely to transform how the Sustainable Development Goals are achieved, through replacing and supporting human activities, fostering innovation, enhancing remote access and improving monitoring. Emerging threats relate to reinforcing inequalities, exacerbating environmental change, diverting resources from tried-and-tested solutions and reducing freedom and privacy through inadequate governance. Although predicting future impacts of robotics and autonomous systems on the Sustainable Development Goals is difficult, thoroughly examining technological developments early is essential to prevent unintended detrimental consequences. Additionally, robotics and autonomous systems should be considered explicitly when developing future iterations of the Sustainable Development Goals to avoid reversing progress or exacerbating inequalities.
Methylation of recombinant mononucleosomes by DNMT3A demonstrates efficient linker DNA methylation and a role of H3K36me3
(2022) Bröhm, Alexander; Schoch, Tabea; Dukatz, Michael; Graf, Nora; Dorscht, Franziska; Mantai, Evelin; Adam, Sabrina; Bashtrykov, Pavel; Jeltsch, Albert
Recently, the structure of the DNMT3A2/3B3 heterotetramer complex bound to a mononucleosome was reported. Here, we investigate DNA methylation of recombinant unmodified, H3KC4me3 and H3KC36me3 containing mononucleosomes by DNMT3A2, DNMT3A catalytic domain (DNMT3AC) and the DNMT3AC/3B3C complex. We show strong protection of the nucleosomal bound DNA against methylation, but efficient linker-DNA methylation next to the nucleosome core. High and low methylation levels of two specific CpG sites next to the nucleosome core agree well with details of the DNMT3A2/3B3-nucleosome structure. Linker DNA methylation next to the nucleosome is increased in the absence of H3K4me3, likely caused by binding of the H3-tail to the ADD domain leading to relief of autoinhibition. Our data demonstrate a strong stimulatory effect of H3K36me3 on linker DNA methylation, which is independent of the DNMT3A-PWWP domain. This observation reveals a direct functional role of H3K36me3 on the stimulation of DNA methylation, which could be explained by hindering the interaction of the H3-tail and the linker DNA. We propose an evolutionary model in which the direct stimulatory effect of H3K36me3 on DNA methylation preceded its signaling function, which could explain the evolutionary origin of the widely distributed “active gene body-H3K36me3-DNA methylation” connection.
Navigating complexities towards sustainable food crops production : local practices for climate change adaptation in rural Ghana
(2022) Dambeebo, Daniel; Dakyaga, Francis; Derbile, Emmanuel K.
Globally, food crops production has been challenged by the impacts of climate change. Climate change scholars have argued that rural dwellers, particularly smallholder farmers who engage in food crops production, suffer the most due to their low capacity to adapt. A growing body of knowledge also suggests that local practices serve as safeguards, that enable smallholder farmers to lessen their vulnerability in food crops production. However, limited scholarly insight has been advanced about sustainable food production via the use of local practices. Through the mixed research approach, the study contributes to local practices and climate adaptation debates by examining the various local practices of smallholder farmers, the challenges they encounter with the use of such practices and the possibility for sustainable food crops production in the future in Ghana. The findings suggest that smallholders encounter multiple drawbacks in attempt to utilize local practices to adapt food crops production to climate change including the advent of modern farming inputs/practices. Even when multiple local practices (the planting of multiple crops’ varieties, switching between crops and livestock rearing, reducing cultivatable land size) are utilized, only the increment in farm size, the use of income/remittances of rural–urban migrants to support food crops production, and early cultivation offered some possibilities of sustaining improvement in food crops production for the future. Therefore, the study concluded that local practices are not necessarily panaceas for sustaining food crops production under climate change. The study recommended that further studies pay attention to the sustainability of local practices under climate change.
‘Falling heads’ : investigating reflexive responses to head-neck perturbations
(2022) Wochner, Isabell; Nölle, Lennart V.; Martynenko, Oleksandr V.; Schmitt, Syn
Background: Reflexive responses to head-neck perturbations affect the injury risk in many different situations ranging from sports-related impact to car accident scenarios. Although several experiments have been conducted to investigate these head-neck responses to various perturbations, it is still unclear why and how individuals react differently and what the implications of these different responses across subjects on the potential injuries might be. Therefore, we see a need for both experimental data and biophysically valid computational Human Body Models with bio-inspired muscle control strategies to understand individual reflex responses better.
Methods: To address this issue, we conducted perturbation experiments of the head-neck complex and used this data to examine control strategies in a simulation model. In the experiments, which we call ’falling heads’ experiments, volunteers were placed in a supine and a prone position on a table with an additional trapdoor supporting the head. This trapdoor was suddenly released, leading to a free-fall movement of the head until reflexive responses of muscles stopped the downwards movement.
Results: We analysed the kinematic, neuronal and dynamic responses for all individuals and show their differences for separate age and sex groups. We show that these results can be used to validate two simple reflex controllers which are able to predict human biophysical movement and modulate the response necessary to represent a large variability of participants.
Conclusions: We present characteristic parameters such as joint stiffness, peak accelerations and latency times. Based on this data, we show that there is a large difference in the individual reflexive responses between participants. Furthermore, we show that the perturbation direction (supine vs. prone) significantly influences the measured kinematic quantities. Finally, ’falling heads’ experiments data are provided open-source to be used as a benchmark test to compare different muscle control strategies and to validate existing active Human Body Models directly.
Methods: To address this issue, we conducted perturbation experiments of the head-neck complex and used this data to examine control strategies in a simulation model. In the experiments, which we call ’falling heads’ experiments, volunteers were placed in a supine and a prone position on a table with an additional trapdoor supporting the head. This trapdoor was suddenly released, leading to a free-fall movement of the head until reflexive responses of muscles stopped the downwards movement.
Results: We analysed the kinematic, neuronal and dynamic responses for all individuals and show their differences for separate age and sex groups. We show that these results can be used to validate two simple reflex controllers which are able to predict human biophysical movement and modulate the response necessary to represent a large variability of participants.
Conclusions: We present characteristic parameters such as joint stiffness, peak accelerations and latency times. Based on this data, we show that there is a large difference in the individual reflexive responses between participants. Furthermore, we show that the perturbation direction (supine vs. prone) significantly influences the measured kinematic quantities. Finally, ’falling heads’ experiments data are provided open-source to be used as a benchmark test to compare different muscle control strategies and to validate existing active Human Body Models directly.
Documenting research software in engineering science
(2022) Hermann, Sibylle; Fehr, Jörg
The reuse of research software needs good documentation, however, the documentation in particular is often criticized. Especially in non-IT specific disciplines, the lack of documentation is attributed to the lack of training, the lack of time or missing rewards. This article addresses the hypothesis that scientists do document but do not know exactly what they need to document, why, and for whom. In order to evaluate the actual documentation practice of research software, we examined existing recommendations, and we evaluated their implementation in everyday practice using a concrete example from the engineering sciences and compared the findings with best practice examples. To get a broad overview of what documentation of research software entailed, we defined categories and used them to conduct the research. Our results show that the big picture of what documentation of research software means is missing. Recommendations do not consider the important role of researchers, who write research software, whose documentation takes mainly place in their research articles. Moreover, we show that research software always has a history that influences the documentation.
Investigation of chip jamming and drill breakage in deep-hole drilling using Smoothed Particle Hydrodynamics
(2024) Baumann, Andreas; Eberhard, Peter
Single-lip deep hole drilling is characterized by a high-quality hole and a high level of productivity achieved. It is performed using high feed rates in a single pass, and, therefore, chips must be removed by the cooling liquid. However, chip jamming is a significant problem when chips wrap around the tool, leading to marks on the borehole wall and an increased drilling torque, potentially causing sudden tool failure. The Smoothed Particle Hydrodynamics method is applied to simulate the challenging fluid flow and elastic bodies. A first approach is developed to model the effects of chip jamming and the possible consequence of drill breakage for a deeper understanding of the process behavior.
Gestión de la Recarga del Acuífero: una contribución a la solución del problema del agua en Lima, Perú : Informe final del proyecto NEWA-LIMA
(Stuttgart : Universität Stuttgart, 2025) Fesch, Katharina; Hügler, Michael; León, Christian D.; Perez, Hiraida; Stauder, Stefan; Xanke, Julian; Manrique, Elizabeth (Übersetzerin)
El proyecto NEWA-LIMA “Nuevos recursos hídricos y tratamiento innovador de aguas residuales para regiones metropolitanas áridas, tomando como ejemplo Lima, Perú”, financiado por el Ministerio del Ambiente de Alemania (BMUV) durante el período 2022 a 2024 tuvo como objetivo demostrar que la Recarga Gestionada de Acuíferos es un método natural y de bajo costo para el uso a largo plazo de los recursos hídricos subterráneos, contribuyendo de este modo a la solución de los problemas de agua en Lima.
Lima es una de las regiones metropolitanas más áridas del mundo, por lo que el abastecimiento de agua para sus 10 millones de habitantes, así como para la industria y el comercio, representa un gran desafío que requerirá de inversiones significativas en los próximos años. Los ríos locales llevan agua solamente durante la época de avenida en los Andes y los recursos de agua subterránea son limitados. Este informe presenta las soluciones desarrolladas y los resultados obtenidos en este proyecto. Tras exhaustivas investigaciones preliminares, se construyó una planta piloto MAR en el terreno de una planta de tratamiento de aguas residuales (PTAR) en el valle del río Lurín. Constó de tres pozas de tierra para la infiltración de las aguas residuales tratadas, así como varios piezómetros. Fue operada en colaboración con la Empresa de Servicio de Agua Potable y Alcantarillado de Lima (SEDAPAL) durante un periodo de 17 meses. El rendimiento de depuración del paso por el suelo fue registrado mediante exhaustivos análisis microbiológicos y químicos del agua, incluidas sustancias antropogénicas y el innovador “análisis relacionado con el impacto” (WBA). Las investigaciones complementarias a pequeña escala con adsorción de carbón activado y ósmosis inversa evaluaron el uso de estas tecnologías avanzadas de tratamiento de agua. Se revisó el marco legal vigente y las implicaciones sociales de los proyectos MAR en Perú. La elaboración de un modelo local de aguas subterráneas y de un concepto para el uso de filtros percoladores en el tratamiento de aguas residuales sirvieron para definir recomendaciones respecto a una aplicación MAR a gran escala en el valle de Lurín.