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Aging is associated with bone loss, which can lead to osteoporosis and high fracture risk. This coincides with the enhanced formation of bone marrow adipose tissue (BMAT), suggesting a negative effect of bone marrow adipocytes on skeletal health. Increased BMAT formation is also observed in pathologies such as obesity, type 2 diabetes and osteoporosis. However, a subset of bone marrow adipocytes forming the constitutive BMAT (cBMAT), arise early in life in the distal skeleton, contain high levels of unsaturated fatty acids and are thought to provide a physiological function. Regulated BMAT (rBMAT) forms during aging and obesity in proximal regions of the bone and contain a large proportion of saturated fatty acids. Paradoxically, BMAT accumulation is also enhanced during caloric restriction (CR), a life-span extending dietary intervention. This indicates, that different types of BMAT can form in response to opposing nutritional stimuli with potentially different functions.
To this end, two types of nutritional interventions, CR and high fat diet (HFD), that are both described to induce BMAT accumulation were carried out. CR markedly increased BMAT formation in the proximal tibia and led to a higher proportion of unsaturated fatty acids, making it similar to the physiological cBMAT. Additionally, proximal and diaphyseal tibia regions displayed higher adiponectin expression. In aged mice, CR was associated with an improved trabecular bone structure. Taken together, these findings demonstrate, that the type of BMAT that forms during CR might provide beneficial effects for local bone stem/progenitor cells and metabolic health. The HFD intervention performed in this thesis showed no effect on BMAT accumulation and bone microstructure. RNA Seq analysis revealed alterations in the composition of the collagen-containing extracellular matrix (ECM).
In order to investigate the effects of glucose homeostasis on osteogenesis, differentiation capacity of immortalized multipotent mesenchymal stromal cells (MSCs) and osteochondrogenic progenitor cells (OPCs) was analyzed. Insulin improved differentiation in both cell types, however, combination of with a high glucose concentration led to an impaired mineralization of the ECM. In the MSCs, this was accompanied by the formation of adipocytes, indicating negative effects of the adipocytes formed during hyperglycemic conditions on mineralization processes. However, the altered mineralization pattern and structure of the ECM was also observed in OPCs, which did not form any adipocytes, suggesting further negative effects of a hyperglycemic environment on osteogenic differentiation.
In summary, the work provided in this thesis demonstrated that differentiation commitment of bone-resident stem cells can be altered through nutrient availability, specifically glucose. Surprisingly, both high nutrient supply, e.g. the hyperglycemic cell culture conditions, and low nutrient supply, e.g. CR, can induce adipogenic differentiation. However, while CR-induced adipocyte formation was associated with improved trabecular bone structure, adipocyte formation in a hyperglycemic cell-culture environment hampered mineralization. This thesis provides further evidence for the existence of different types of BMAT with specific functions.
Während zur Geschichte des Strafrechts in der alten Bundesrepublik bislang lediglich überblicksartige Gesamtdarstellungen und Monographien zu einzelnen Deliktsbereichen existierten, nimmt dieser Band einige prägnante Facetten des Besonderen Teils detailreich in den Blick und setzt damit das Projekt fort, das die Herausgeber 2020 mit dem bereits erschienenen Band zum Allgemeinen Teil begonnen haben. Auch hier interessieren die einzelnen Teilbereiche weniger dogmengeschichtlich als in ihrer Interaktion mit der Strafrechtswissenschaft, -praxis, -politik und gesellschaftlichen Veränderungen. Die individuellen Zugänge, die die Autorinnen und Autoren hierzu gesucht haben, sollen in ihrer methodischen Vielfalt durchaus als Experiment verstanden werden.
With the surging reliance on videoconferencing tools, users may find themselves staring at their reflections for hours a day. We refer to this phenomenon as self-referential information (SRI) consumption and examine its consequences and the mechanism behind them. Building on self-awareness research and the strength model of self-control, we argue that SRI consumption heightens the state of self-awareness and thereby depletes participants’ mental resources, eventually undermining virtual meeting (VM) outcomes. Our findings from a European employee sample revealed contrary effects of SRI consumption across speaker vs listener roles. Engagement with self-view is positively associated with self-awareness, which, in turn, is negatively related to satisfaction with VM process, perceived productivity, and enjoyment. Looking at the self while listening to others exhibits adverse direct and indirect (via self-awareness) effects on VM outcomes. However, looking at the self when speaking exhibits positive direct effects on satisfaction with VM process and enjoyment.
Die Beschaffung von Leistungen zur medizinischen Rehabilitation wurde durch den neuen § 15 SGB VI zum 1. Juli 2023 grundlegend reformiert. Seither gilt ein mehrstufiges System aus Zulassung der Rehabilitationskliniken, Belegungsvertrag, Belegungsentscheidung und Vergütung. Sämtliche Beschaffungsstufen werden von der DRV Bund durch verbindliche Entscheidungen gesteuert.
Dieses neue Beschaffungssystem verstößt gegen das Wettbewerbsrecht der Europäischen Union und ist deshalb unwirksam. Das Unionsrecht (Art. 106 Abs. 1 AEUV), aber auch das nationale Kartellrecht (§ 19 Abs. 2 Nr. 1 GWB) und das Verfassungsrecht (Art. 12 Abs. 1 GG) verlangen eine Trennung von hoheitlichen Befugnissen und unternehmerischen Funktionen der Rentenversicherungsträger. Anderenfalls ist die gebotene Gleichbehandlung (Nichtdiskriminierung) der Rehabilitationskliniken freigemeinnütziger und privater Träger mit den Rehabilitationskliniken der Rentenversicherungsträger bei der Erbringung von Leistungen zur medizinischen Rehabilitation nicht gewährleistet.
Dieses Trennungsprinzip ist verletzt. Denn die Rentenversicherungsträger nehmen hoheitliche Zulassungs-, Belegungs- und Vergütungsaufgaben wahr und sind gleichzeitig unternehmerisch mit eigenen Rehabilitationseinrichtungen auf dem Markt der Erbringung von Leistungen zur medizinischen Rehabilitation tätig. Freigemeinnützige und private Rehabilitationskliniken werden auf allen Stufen der Beschaffung gegenüber den Kliniken der Rentenversicherungsträger diskriminiert. Das gilt insbesondere für die Belegungsentscheidungen der Rentenversicherungsträger, weil hierdurch systematisch eigene Kliniken gegenüber freigemeinnützigen und privaten Kliniken begünstigt werden.
Volatile supply and sales markets, coupled with increasing product individualization and complex production processes, present significant challenges for manufacturing companies. These must navigate and adapt to ever-shifting external and internal factors while ensuring robustness against process variabilities and unforeseen events. This has a pronounced impact on production control, which serves as the operational intersection between production planning and the shop- floor resources, and necessitates the capability to manage intricate process interdependencies effectively. Considering the increasing dynamics and product diversification, alongside the need to maintain constant production performances, the implementation of innovative control strategies becomes crucial.
In recent years, the integration of Industry 4.0 technologies and machine learning methods has gained prominence in addressing emerging challenges in production applications. Within this context, this cumulative thesis analyzes deep learning based production systems based on five publications. Particular attention is paid to the applications of deep reinforcement learning, aiming to explore its potential in dynamic control contexts. Analysis reveal that deep reinforcement learning excels in various applications, especially in dynamic production control tasks. Its efficacy can be attributed to its interactive learning and real-time operational model. However, despite its evident utility, there are notable structural, organizational, and algorithmic gaps in the prevailing research. A predominant portion of deep reinforcement learning based approaches is limited to specific job shop scenarios and often overlooks the potential synergies in combined resources. Furthermore, it highlights the rare implementation of multi-agent systems and semi-heterarchical systems in practical settings. A notable gap remains in the integration of deep reinforcement learning into a hyper-heuristic.
To bridge these research gaps, this thesis introduces a deep reinforcement learning based hyper- heuristic for the control of modular production systems, developed in accordance with the design science research methodology. Implemented within a semi-heterarchical multi-agent framework, this approach achieves a threefold reduction in control and optimisation complexity while ensuring high scalability, adaptability, and robustness of the system. In comparative benchmarks, this control methodology outperforms rule-based heuristics, reducing throughput times and tardiness, and effectively incorporates customer and order-centric metrics. The control artifact facilitates a rapid scenario generation, motivating for further research efforts and bridging the gap to real-world applications. The overarching goal is to foster a synergy between theoretical insights and practical solutions, thereby enriching scientific discourse and addressing current industrial challenges.
The contribution explores how an understanding of neoliberal subjectification in socio-economic education can serve to counteract the trend marketisation of democracy. Drawing on Foucault’s lectures on biopolitics and Brown’s current analysis of neoliberalism, it lays out a sociological explanation that treats the idea of homo economicus as a structuring element of our society and outlines the threat this poses to the liberal democratic order. The second part of the contribution outlines – through immanent critique – an ideology-critical analytical competence that uses key problems to illuminate socially critical perspectives on social reality. The objective is to challenge some of the foundations of social order (Salomon, D. Kritische politische Bildung. Ein Versuch. In B. Widmaier & Overwien, B. (Hrsg.), Was heißt heute kritische politische Bildung? (S. 232–239). Wochenschau, 2013) in pursuit of the ultimate objective of an educated and assertive citizenry.