@inbook{13652,
  abstract     = {{Modellbasierte Konzepte und Simulationstechniken in Kombination mit digitalen Werkzeugen erweisen sich als Schlüssel, um das volle Potenzial biopharmazeutischer Produktionsprozesse zu erschließen, die mehrere herausfordernde Entwicklungs- und Prozessschritte enthalten. Einer dieser Schritte ist der zeit- und kostenintensive Zellproliferationsprozess (auch als Seed Train bezeichnet), um die Zellzahl vom Auftauen der Zellen bis zum Produktionsmaßstab zu erhöhen. Herausforderungen wie komplexer Zellstoffwechsel, Chargen-zu-Chargen-Variationen, Variabilitäten im Zellverhalten und Einflüsse von Änderungen der Kultivierungsbedingungen erfordern adäquate digitale Lösungen, um Informationen über den aktuellen und zukünftigen Prozesszustand bereitzustellen und korrekte Prozessentscheidungen abzuleiten.

Zu diesem Zweck haben sich digitale Seed Train Zwillinge als effizient erwiesen, die das zeitabhängige Verhalten wichtiger Prozessvariablen basierend auf mathematischen Modellen, Strategien und Anpassungsverfahren digital darstellen.

Dieses Kapitel skizziert die Notwendigkeit der Digitalisierung von Seed Trains, den Aufbau eines digitalen Seed Train Zwillings, die Rolle der Parameterschätzung und verschiedene statistische Methoden in diesem Zusammenhang, die auf mehrere Probleme im Bereich der Bioprozessierung anwendbar sind. Die Ergebnisse einer Fallstudie werden vorgestellt, um einen Bayes’schen Ansatz zur Parameterschätzung und Vorhersage eines industriellen Zellkultur-Seed Trains für die Seed Train Digitalisierung zu veranschaulichen.}},
  author       = {{Hernández Rodriguez, Tanja and Frahm, Björn}},
  booktitle    = {{Digitale Zwillinge - Werkzeuge und Konzepte für intelligente Bioproduktion}},
  editor       = {{Herwig, Christoph and Pörtner, Ralf and Möller, Johannes}},
  isbn         = {{978-3-031-75697-9}},
  keywords     = {{Bayes, Digitaler Zwilling, Parameterabschätzung, Seed-Train, Unsicherheit}},
  pages        = {{107--145}},
  publisher    = {{Springer }},
  title        = {{{Digitale Seed Train Zwillinge und statistische Methoden}}},
  doi          = {{https://doi.org/10.1007/978-3-031-75698-6_5}},
  year         = {{2025}},
}

@misc{13020,
  abstract     = {{Developing AI systems for automatic train operation (ATO) requires developers to have a deep understanding of the human tasks they are trying to replace. This paper fills this gap and translates the regulatory requirements from the context of German railways for the AI developer community. As a result, tasks such as train’s path monitoring for collision prediction, signal detection, door operation, etc. are identified. Based on this analysis, a functionally justified sensor setup with detailed configuration requirements is presented. This setup was also evaluated by a survey within the railway industry. The evaluated sensors include RGB/IR cameras, LIDARs, radars and ultrasonic sensors. Calculations and estimates for the evaluated sensors are presented graphically and included in this paper. However, the ultimate sensor setup is still a subject of research. The results of this paper also address the lack of training and test datasets for railway AI systems. It is proposed to acquire research datasets that will allow the training of domain adaptation algorithms to transform other datasets, thus increasing the number of available datasets. The sensor setup is also recommended for such research datasets.}},
  author       = {{Tagiew, Rustam and Leinhos, Dirk and von der Haar, Henrik and Klotz, Christian and Sprute, Dennis and Ziehn, Jens and Schmelter, Andreas and Witte, Stefan and Klasek, Pavel}},
  booktitle    = {{Discover Artificial Intelligence}},
  issn         = {{2731-0809}},
  keywords     = {{Automatic train operation, ATO, GoA3, GoA4, Perception, AI}},
  number       = {{1}},
  publisher    = {{Springer International Publishing }},
  title        = {{{Sensor system for development of perception systems for ATO}}},
  doi          = {{10.1007/s44163-023-00066-4}},
  volume       = {{3}},
  year         = {{2023}},
}

@misc{13021,
  abstract     = {{Natural ventilation in a building is an effective way to achieve acceptable indoor air quality. Ventilation dilutes contaminants such as bioeffluents generated by occupants, substances emitted from building materials, and the water vapor generated by occupants’ activities. In a building that requires heating and cooling, adequate ventilation is crucial to minimize energy consumption while maintaining healthy indoor air quality. However, measuring the actual magnitude of the natural ventilation rate, including infiltration through the building envelope and airflow through the building openings, is not always feasible. Although international and national standards suggested the required ventilation rates to maintain acceptable indoor air quality in buildings, they did not offer action plans to achieve or evaluate those design ventilation rates in buildings in use. In this study, the occupant-generated carbon dioxide (CO2) tracer gas decay method was applied to estimate the ventilation rates in an office room in Seoul, South Korea, from summer to winter. Using the method, real-time ventilation rates can be calculated by monitoring indoor and outdoor CO2 concentrations without injecting a tracer gas. For natural ventilation in the test room, 145 mm-diameter circular openings on the fixed glass were used. As a result, first, the indoor CO2 concentrations were used as an indicator to evaluate how much the indoor air quality deteriorated when all the windows were closed in an occupied office room compared to the international standards for indoor air quality. Moreover, we found out that the estimated ventilation rates varied depending on various environmental conditions, even with the same openings for natural ventilation. Considering the indoor and outdoor temperature differences and outdoor wind speeds as the main factors influencing the ventilation rates, we analyzed how they affected the ventilation rates in the different seasons of South Korea. When the wind speeds were calm, less than 2 m/s, the temperature difference played as a factor that influenced the estimated ventilation rates. On the other hand, when the temperature differences were low, less than 3 °C, the wind speed was the primary factor. This study raises awareness about the risk of poor indoor air quality in office rooms that could lead to health problems or unpleasant working environments. This study presents an example of estimating the ventilation rates in an existing building. By using the presented method, the ventilation rate in an existing building can be simply estimated while using the building as usual, and appropriate ventilation strategies for the building can be determined to maintain the desired indoor air quality.}},
  author       = {{Seol, Hyeonji and Arztmann, Daniel and Kim, Naree and Balderrama, Alvaro}},
  booktitle    = {{Sustainability}},
  issn         = {{2071-1050}},
  keywords     = {{Management, Monitoring, Policy and Law, Renewable Energy, Sustainability and the Environment, Geography, Planning and Development, Building and Construction}},
  number       = {{13}},
  publisher    = {{MDPI}},
  title        = {{{Estimation of Natural Ventilation Rates in an Office Room with 145 mm-Diameter Circular Openings Using the Occupant-Generated Tracer-Gas Method}}},
  doi          = {{10.3390/su15139892}},
  volume       = {{15}},
  year         = {{2023}},
}

@misc{11377,
  abstract     = {{<jats:p>consuming and often performed rather empirically. Efficient optimization of multiple objectives such as process time, viable cell density, number of operating steps &amp; cultivation scales, required medium, amount of product as well as product quality depicts a promising approach. This contribution presents a workflow which couples uncertainty-based upstream simulation and Bayes optimization using Gaussian processes. Its application is demonstrated in a simulation case study for a relevant industrial task in process development, the design of a robust cell culture expansion process (seed train), meaning that despite uncertainties and variabilities concerning cell growth, low variations of viable cell density during the seed train are obtained. Compared to a non-optimized reference seed train, the optimized process showed much lower deviation rates regarding viable cell densities (&lt;10% instead of 41.7%) using five or four shake flask scales and seed train duration could be reduced by 56 h from 576 h to 520 h. Overall, it is shown that applying Bayes optimization allows for optimization of a multi-objective optimization function with several optimizable input variables and under a considerable amount of constraints with a low computational effort. This approach provides the potential to be used in the form of a decision tool, e.g., for the choice of an optimal and robust seed train design or for further optimization tasks within process development.}},
  author       = {{Hernández Rodriguez, Tanja and Sekulic, Anton and Lange-Hegermann, Markus and Frahm, Björn}},
  booktitle    = {{Processes}},
  issn         = {{2227-9717}},
  keywords     = {{Gaussian processes, Bayes optimization, Pareto optimization, multi-objective, cell culture, seed train}},
  number       = {{5}},
  publisher    = {{MDPI AG}},
  title        = {{{Designing Robust Biotechnological Processes Regarding Variabilities Using Multi-Objective Optimization Applied to a Biopharmaceutical Seed Train Design}}},
  doi          = {{10.3390/pr10050883}},
  volume       = {{10}},
  year         = {{2022}},
}

@misc{7578,
  abstract     = {{In recent years considerable research efforts have been made to provide evidence for a nexus be-tween game design elements in non-game contexts. Our research presents a new approach to bridge game design elements and educational theory: defining a set of motivational “patterns” used for peda-gogical purposes in university teaching scenarios. To this end, we will build upon preliminary empirical results from a research project called EMPAMOS®. It derived a set of motivational elements frequently used in social game designs. Our hypothesis is that these elements resemble on a structural level and are directly transferable to motivational factors in online education contexts. 
Focused on cooperative teaching and learning, we develop a curriculum to enable educators to im-plement motivational molecules from game design in their learning settings. The paper presents basic premises and a preliminary structure of the curriculum. By examining educational settings in terms of a “broken game”, we provide a new perspective on the prerequisites for learning at the university level.}},
  author       = {{Bröker, Thomas and Schmulius, Nina and Schmohl, Tobias and Dulisch, Fabian and Marquardt, Sabrina and Höllen, Max and Voit, Thomas and Zinger, Benjamin}},
  booktitle    = {{New Perspectives in Science Education}},
  keywords     = {{cooperative learning, gamification, motivation, train-the-trainer, curriculum}},
  location     = {{Florenz}},
  pages        = {{22--26}},
  publisher    = {{Libreriauniversitaria.it}},
  title        = {{{What Can Educators Learn from Social Game Design in University Online Teaching?}}},
  volume       = {{11}},
  year         = {{2022}},
}

@inbook{10193,
  abstract     = {{Development and optimization of biopharmaceutical production processes with cell cultures is cost- and time-consuming and often performed rather empirically. Efficient optimization of multiple objectives such as process time, viable cell density, number of operating steps & cultivation scales, required medium, amount of product as well as product quality depicts a promising approach. This contribution presents a workflow which couples uncertainty-based upstream simulation and Bayes optimization using Gaussian processes. Its application is demonstrated in a simulation case study for a relevant industrial task in process development, the design of a robust cell culture expansion process (seed train), meaning that despite uncertainties and variabilities concerning cell growth, low variations of viable cell density during the seed train are obtained. Compared to a non-optimized reference seed train, the optimized process showed much lower deviation rates regarding viable cell densities (<10% instead of 41.7%) using five or four shake flask scales and seed train duration could be reduced by 56 h from 576 h to 520 h. Overall, it is shown that applying Bayes optimization allows for optimization of a multi-objective optimization function with several optimizable input variables and under a considerable amount of constraints with a low computational effort. This approach provides the potential to be used in the form of a decision tool, e.g., for the choice of an optimal and robust seed train design or for further optimization tasks within process development.}},
  author       = {{Hernández Rodriguez, Tanja and Sekulic, Anton and Lange-Hegermann, Markus and Frahm, Björn}},
  booktitle    = {{Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing}},
  editor       = {{Pörtner, Ralf and Möller, Johannes}},
  isbn         = {{978-3-0365-5210-1}},
  issn         = {{2227-9717}},
  keywords     = {{Gaussian processes, Bayes optimization, Pareto optimization, multi-objective, cell culture, seed train}},
  pages        = {{21--48}},
  publisher    = {{MDPI}},
  title        = {{{Designing robust biotechnological processes regarding variabilities using multi-objective optimization applied to a biopharmaceutical seed train design}}},
  doi          = {{https://doi.org/10.3390/pr10050883}},
  volume       = {{special issue}},
  year         = {{2022}},
}

@misc{10590,
  abstract     = {{Das Kriechende Netzblatt, Goodyera repens, das von den Vorständen der Arbeitskreise Heimische Orchideen Deutschlands (AHOs) zur Orchidee des Jahres 2021 gewählt wurde, wird vorgestellt. Namensgebung, morphologische Merkmale und Lebenszyklus sowie Ökologie und Lebensräume werden charakterisiert. Das Areal der Art wird beschrieben und die Verbreitung für Deutschland kartographisch dargestellt. Gefährdungsursachen werden erörtert und Schutzmaßnahmen aufgezeigt. Abschließend werden signifikante Konsequenzen des Klimawandels für die Art diskutiert und in Beispielen dargelegt.}},
  author       = {{Klüber, Marco and Lohr, Mathias}},
  booktitle    = {{Journal europäischer Orchideen : Mitteilungsblatt des AHO Baden-Württemberg }},
  issn         = {{0945-7909}},
  keywords     = {{Orchidaceae, Goodyera repens, Orchid of the Year 2021, characteristics, distribution, life history, monitoring, threats, conservation status, protection, Germany.}},
  number       = {{1-2}},
  pages        = {{3--27}},
  publisher    = {{AHO}},
  title        = {{{Das Kriechende Netzblatt Goodyera repens (L.) R.Br. – Orchidee  des Jahres 2021 }}},
  volume       = {{54}},
  year         = {{2022}},
}

@misc{11376,
  abstract     = {{<jats:p>concentration is an important objective. The phenotype of the cells in a reactor plays an important role. Are clonal cell populations showing high cell-specific growth rates more favorable than cell lines with higher cell-specific productivities or vice versa? Five clonal Chinese hamster ovary cell populations were analyzed based on the data of a 3-month-stability study. We adapted a mechanistic cell culture model to the experimental data of one such clonally derived cell population. Uncertainties and prior knowledge concerning model parameters were considered using Bayesian parameter estimations. This model was used then to define an inoculum train protocol. Based on this, we subsequently simulated the impacts of differences in growth rates (±10%) and production rates (±10% and ±50%) on the overall cultivation time, including making the inoculum train cultures; the final production phase, the volumetric titer in that bioreactor and the ratio of both, defined as overall process productivity. We showed thus unequivocally that growth rates have a higher impact (up to three times) on overall process productivity and for product output per year, whereas cells with higher productivity can potentially generate higher product concentrations in the production vessel.}},
  author       = {{Hernández Rodriguez, Tanja and Morerod, Sophie and Pörtner, Ralf and Wurm, Florian M. and Frahm, Björn}},
  booktitle    = {{Processes}},
  issn         = {{2227-9717}},
  keywords     = {{clonal cell population, phenotypic diversity, inoculum train, uncertainty-based, cell culture model, biopharmaceutical manufacturing}},
  number       = {{6}},
  publisher    = {{MDPI AG}},
  title        = {{{Considerations of the Impacts of Cell-Specific Growth and Production Rate on Clone Selection—A Simulation Study}}},
  doi          = {{10.3390/pr9060964}},
  volume       = {{9}},
  year         = {{2021}},
}

@misc{7518,
  abstract     = {{The sharing economy provides short-term access to products without the risks associated with ownership. While extant research primarily examined it in the context of affluent consumer segments, the sharing economy may offer opportunities for consumers at the base of the economic pyramid, where ownership risks prevent access to products that could create societal benefits. Drawing from risk perception theory, we examine how access-based services, as an alternative to ownership, can mitigate perceived risk dimensions. An experimental study reveals that, in contrast to consumers with higher income, low-income consumers perceive access-based services to entail less financial risk, resulting in a greater inclination to access a good than to own it. In a second study, we explore these differences by comparing access with a risk mitigation strategy. We find that at the base of the pyramid, access is perceived to entail less financial risk than both ownership and ownership with a warranty. The results indicate the importance of the sharing economy for addressing the limited availability of resources for alleviating poverty. Based on our findings, we derive implications for consumers and service providers at the base of the pyramid, and discuss how the COVID-19 pandemic may be detrimental to the identified opportunities.}},
  author       = {{Schäfers, Tobias and Narayanamurthy, Gopalakrishnan and Moser, Roger and Leban, Marina}},
  booktitle    = {{Psychology & Marketing}},
  issn         = {{1520-6793}},
  keywords     = {{access-based services, base of the pyramid, risk perception theory, sharing economy}},
  number       = {{11}},
  pages        = {{2073--2088}},
  publisher    = {{Wiley}},
  title        = {{{The sharing economy at the base of the economic pyramid: How access‐based services can help overcome ownership risks}}},
  doi          = {{10.1002/mar.21541}},
  volume       = {{38}},
  year         = {{2021}},
}

@inbook{7983,
  abstract     = {{For the manufacturing of complex biopharmaceuticals using bioreactors with cultivated mammalian cells, high product concentration is an important objective. The phenotype of the cells in a reactor plays an important role. Are clonal cell populations showing high cell-specific growth rates more favorable than cell lines with higher cell-specific productivities or vice versa? Five clonal Chinese hamster ovary cell populations were analyzed based on the data of a 3-month-stability study. We adapted a mechanistic cell culture model to the experimental data of one such clonally derived cell population. Uncertainties and prior knowledge concerning model parameters were considered using Bayesian parameter estimations. This model was used then to define an inoculum train protocol. Based on this, we subsequently simulated the impacts of differences in growth rates (±10%) and production rates (±10% and ±50%) on the overall cultivation time, including making the inoculum train cultures; the final production phase, the volumetric titer in that bioreactor and the ratio of both, defined as overall process productivity. We showed thus unequivocally that growth rates have a higher impact (up to three times) on overall process productivity and for product output per year, whereas cells with higher productivity can potentially generate higher product concentrations in the production vessel.}},
  author       = {{Hernández Rodriguez, Tanja and Morerod, Sophie and Pörtner, Ralf and Wurm, Florian M. and Frahm, Björn}},
  booktitle    = {{Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing}},
  isbn         = {{978-3-0365-5210-1}},
  issn         = {{2227-9717 }},
  keywords     = {{clonal cell population, phenotypic diversity, inoculum train, uncertainty-based, cell culture model, biopharmaceutical manufacturing}},
  pages        = {{49--74}},
  publisher    = {{MDPI}},
  title        = {{{Considerations of the impacts of cell-specific growth and production rate on clone selection – a simulation study}}},
  doi          = {{10.3390/pr9060964}},
  volume       = {{special issue}},
  year         = {{2021}},
}

@inbook{3349,
  abstract     = {{Model-based concepts and simulation techniques in combination with digital tools emerge as a key to explore the full potential of biopharmaceutical production processes, which contain several challenging development and process steps. One of these steps is the time- and cost-intensive cell proliferation process (also called seed train) to increase cell number from cell thawing up to production scale. Challenges like complex cell metabolism, batch-to-batch variation, variabilities in cell behavior, and influences of changes in cultivation conditions necessitate adequate digital solutions to provide information about the current and near future process state to derive correct process decisions.
For this purpose digital seed train twins have proved to be efficient, which digitally display the time-dependent behavior of important process variables based on mathematical models, strategies, and adaption procedures.
This chapter will outline the needs for digitalization of seed trains, the construction of a digital seed train twin, the role of parameter estimation, and different statistical methods within this context, which are applicable to several problems in the field of bioprocessing. The results of a case study are presented to illustrate a Bayesian approach for parameter estimation and prediction of an industrial cell culture seed train for seed train digitalization.}},
  author       = {{Hernández Rodriguez, Tanja and Frahm, Björn}},
  booktitle    = {{Digital Twins Tools and Concepts for Smart Biomanufacturing}},
  editor       = {{Herwig, Christoph  and Pörtner, Ralf  and Möller, Johannes }},
  isbn         = {{978-3-030-71659-2}},
  issn         = {{1616-8542}},
  keywords     = {{Bayes, Digital twin, Parameter estimation, Seed train, Uncertainty}},
  pages        = {{97–131}},
  publisher    = {{Springer}},
  title        = {{{Digital Seed Train Twins and Statistical Methods}}},
  doi          = {{https://doi.org/10.1007/10_2020_137}},
  volume       = {{176}},
  year         = {{2021}},
}

@misc{13372,
  abstract     = {{This bachelor thesis explores the adaptive reuse of the former Telekom high-rise at Kesselbrink in Bielefeld, a vacant modernist office tower awaiting new purpose. The project proposes a mixed-use transformation that reinterprets the building as a “city within the city,” inspired by Le Corbusier’s Unité d’Habitation in Marseille. The existing structure is strategically reduced to its essential load-bearing concrete frame and floor slabs, preserving the structural skeleton while enabling radical spatial reconfiguration.
Prefabricated timber modules are inserted and cantilevered between the reinforced-concrete columns, extending the usable floor area and introducing a warm, contemporary material contrast to the original façade. This intervention not only increases density and flexibility but also redefines the tower’s appearance, giving it a cosmopolitan and forward-looking architectural identity. The ground floor is conceived as an open and publicly accessible urban platform, activating the surrounding plaza and strengthening social interaction. Upper floors are redesigned as affordable and attractive living spaces for young residents, encouraging a diverse and vibrant community within the building.
A newly designed park-like rooftop landscape provides recreational space and panoramic views over the city, enhancing environmental quality and urban connectivity. By combining structural preservation, modular timber construction, public programming, and residential reuse, the proposal demonstrates how high-rise retrofitting can generate social, ecological, and economic value simultaneously. The project positions adaptive reuse as a viable strategy for sustainable urban regeneration and architectural longevity.}},
  author       = {{Konschake, Leon}},
  keywords     = {{Adaptive Reuse, Mixed-Use Development, High-Rise Transformation, City within the City, Modular Timber Construction, Prefabrication, Structural Preservation, Concrete Skeleton, Cantilevered Modules, Urban Regeneration, Public Ground Floor, Youth Housing, Rooftop Landscape, Sustainability, Social Impact, Ecological Design, Economic Viability, Cosmopolitan Architecture}},
  publisher    = {{Technische Hochschule Ostwestfalen-Lippe}},
  title        = {{{TreeTower}}},
  year         = {{2020}},
}

@inbook{2394,
  abstract     = {{For the production of biopharmaceuticals a seed train is required to generate an adequate number of cells for inoculation of the production bioreactor. This seed train is time- and cost-intensive but offers potential for optimization. A method and a protocol are described for the seed train mapping, directed modeling without major effort, and its optimization regarding selected optimization criteria such as optimal points in time for cell passaging. Furthermore, the method can also be applied for the set-up of a new seed train, for example for a new cell line. Although the chapter is directed towards suspension cell lines, the method is also generally applicable, e.g. for adherent cell lines.}},
  author       = {{Frahm, Björn}},
  booktitle    = {{Animal Cell Biotechnology}},
  isbn         = {{9781627037327}},
  issn         = {{1064-3745}},
  keywords     = {{Seed train Optimization Modeling Prediction Space-Time-Yield (STY) Systems approach Bioinformatics Computational biotechnology Suspension Production}},
  pages        = {{355--367}},
  publisher    = {{Humana Press}},
  title        = {{{Seed Train Optimization for Cell Culture}}},
  doi          = {{10.1007/978-1-62703-733-4_22}},
  volume       = {{1104}},
  year         = {{2013}},
}

@inbook{10214,
  abstract     = {{For the production of biopharmaceuticals a seed train is required to generate an adequate number of cells for inoculation of the production bioreactor. This seed train is time- and cost-intensive but offers potential for optimization. A method and a protocol are described for the seed train mapping, directed modeling without major effort, and its optimization regarding selected optimization criteria such as optimal points in time for cell passaging. Furthermore, the method can also be applied for the set-up of a new seed train, for example for a new cell line. Although the chapter is directed towards suspension cell lines, the method is also generally applicable, e.g. for adherent cell lines.}},
  author       = {{Frahm, Björn}},
  booktitle    = {{Animal Cell Biotechnology - Methods and Protocols}},
  editor       = {{Pörtner, Ralf}},
  isbn         = {{978-1-62703-732-7}},
  issn         = {{1940-6029}},
  keywords     = {{Seed train, Optimization, Modeling, Prediction, Space-Time-Yield (STY), Systems approach, Bioinformatics, Computational biotechnology, Suspension, Production}},
  pages        = {{355–367}},
  publisher    = {{Humana Press}},
  title        = {{{Seed Train Optimization for Cell Culture}}},
  doi          = {{10.1007/978-1-62703-733-4_22}},
  volume       = {{1104}},
  year         = {{2013}},
}