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The regulation of RHEB subcellular localisation in early zebrafish myofibres
No full textDer Signalweg „mechanistic target of rapamycin complex 1“ (mTORC1) ist eine treibende
Kraft des Skelettmuskulaturwachstums, dies wird durch die Förderung der Hypertrophie
der Muskelzellen, Muskelfasern genannt, erzielt. Verschiedene Signalwege
konvergieren, um im Zytosol den direkt vorgeschalteten Aktivator von mTORC1, die
kleine GTPase RHEB, zu aktivieren. RHEB ist durch seine C-terminale Farnesylierung
an Endomembranen verankert, insbesondere an der des Lysosoms. Darüber hinaus kann
RHEB auch im Zellkern vorhanden sein, zum Beispiel im Zellkern embryonaler
Muskelfasern von Zebrabärblingen. Dort fördert RHEB unabhängig von mTORC1 das
Muskelwachstum. In adulten Zebrabärblingen ist RHEB jedoch vorwiegend im Zytosol
vorhanden. Dies weist auf eine Regulierung der subzellulären Lokalisation von RHEB
während der Entwicklung hin. In dieser Arbeit habe ich zunächst die zeitliche
Koordinierung der Zellkernlokalisation von RHEB in den embryonalen Muskelfasern von
Zebrabärblingen untersucht. Ich konnte zeigen, dass RHEB vor dem Schlüpfen, in den
embryonalen Stadien, im Zellkern lokalisiert ist. Diese Präsenz im Zellkern nahm nach
dem Schlüpfen nach und nach ab. Da das Schlüpfen mit einem Anstieg der
Muskelaktivität verbunden ist, habe ich den Effekt von Muskelkontraktion auf die
Zellkernlokalisation von RHEB untersucht. Das Reduzieren der Muskelaktivität führte zu
einer verlängerten Zellkernlokalisation von RHEB, das Erhöhen zu einer beschleunigten
Reduktion. Vor dem Hintergrund der fördernden Wirkung von Muskelkontraktion auf die
Muskelfaserreifung wäre es möglich, dass die skizzierten Erkenntnisse auf einen
allgemeinen Prozess hinweisen, der in Verbindung mit Zellreifung zu einer Abnahme der
Zellkernlokalisation von RHEB führt. Letztlich führte die Hemmung der Farnesylierung in
den Muskelfasern geschlüpfter Zebrabärblingen zu einer Retention von nuklearem
RHEB. Aufgrund dieser Ergebnisse nehme ich an, dass RHEB in unreifen Zellen in zwei
Formen auftritt, einerseits farnesyliert und zytosolisch und andererseits unfarnesyliert und
nuklear. Vollständige Zellreifung würde demnach zu einer vollständigen Farnesylierung
von RHEB führen, welches vorwiegend im Zytosol vorhanden wäre. Dies deutet zudem
darauf hin, dass nukleares RHEB bei der Zelldifferenzierung und der Zellreifung eine
Rolle spielt
Response of element cycling and budgets to nutrient additions in a tropical montane forest of Ecuador
Get PDFThe tropical montane forests in southern Ecuador are subject to rising nitrogen (N), low phosphorus (P), and episodic calcium (Ca) deposition. To investigate the response of the vegetation, soil organic layer and mineral soil to 0.3 m depth to increased nutrient inputs, we initiated in 2008 an interdisciplinary Nutrient Manipulation Experiment (NUMEX) at 2000 m a.s.l. We have applied N as urea at 50 kg ha−1 year−1, P as NaH2PO4 at 10 kg ha−1 year−1, combined N and P at 50 + 10 kg ha−1 year−1, and Ca (as CaCl2), at 10 kg ha−1 year−1. From 2008 to 2012, we set up annual budgets by calculating net fluxes of N, P, Ca and Na for the canopy, the organic layer and the mineral soil and determined δ15N values in the foliage of the four most abundant tree species, litterfall and organic layer. The addition of P and N + P increased P leaching from the canopy, suggesting a reduced retention of deposited P by canopy organisms. All added nutrients were largely retained in the soil organic layer and tightly cycled between the organic layer and the vegetation via litterfall and throughfall. The small leaching losses of N, P, Ca and Na from the organic layer were retained in the upper mineral soil. The retention of the added nutrients in the ecosystem indicated a strong nutrient demand. Nevertheless, the 15N enrichment in the organic layer was an early indicator of beginning N losses from the ecosystem by leaching and volatilization, which could not yet be detected by our flux-based budgeting approach
Horizontal Earth: A Novel Perspective on the Shear-Bond between Timber and Earth in Bending-Stressed Components
Get PDFThe development of innovative and sustainable building materials is becoming crucial in the construction industry, which is increasingly focusing on environmentally friendly and circular solutions to reduce its ecological footprint. The use of locally available and renewable resources, along with the reinterpretation of traditional building systems, can contribute to further establish the use of ecological and circular materials in construction.
Horizontally spanning structures offer significant opportunities for resource conservation, as they typically require large amounts of material for their realisation. Earth, a widely available yet often overlooked building material, possesses acceptable compressive properties and is traditionally used for walls, such as wattle and daub. Combining earth with timber, which resists tensile forces effectively, broadens its applications to include elements subject to bending stress as slabs. This strategic material pairing also lowers the need for wood - a crucial aspect given its limited availability.
The application of the hybrid material system in bending-stressed components poses several technical challenges, the most significant being the need for efficient shear force transfer between timber and earth to guarantee a reliable material bond. To analyse the shear transfer capacity of the timber-earth-composite, several push-out tests were conducted - a proven method for timber-concrete-composites. Various types of fasteners, such as screws and wooden shear connectors, were implemented to ensure efficient force transfer between the materials. The resulting bond characteristics were evaluated for scalability in two full-scale components.
Various modelling approaches, including the γ-method and the truss model method, have been investigated, with particular emphasis on the truss model to capture the non-linear behaviour of earth materials and the bond conditions identified through component testing. The objective is to establish a viable calculation method that facilitates the scaling up of timber-earth slab spans, allowing for the identification of optimal configurations of material arrangement and thickness, and thereby enhancing their potential for real-world applications.
Timber-earth-components represent a sustainable composite material that not only meets structural requirements but also offers advantages in sound and fire protection, as well as thermal mass, therefore providing a promising alternative for the construction industry
BARZAKH – Earth construction and participatory Design with Mixed – Media
Get PDFThis article explores earthen materials in particular mudbricks (adobe), a traditional material in Egypt and the Middle East, as a contemporary building material by integrating local craftsmanship, engineering, and advanced digital technology. Although often perceived as a low-tech option in under-resourced communities, the project BARZAKH برزخ – aims to reposition earth bricks within a contemporary architectural, structural and social context. By incorporating mixed-media-tools such as Virtual and Augmented Reality the project fosters collaborative design and building experiences, enhancing shared awareness of sustainable practices. The project’s methodology reconnects people with the handmade craft of mudbrick construction through immersive digital tools.
In New Gourna (Luxor) – alongside Hassan Fathy’s pioneering sustainable architecture – students and locals co-designed and collaboratively built BARZAKH – a curvelinear mudbrick wall constructed using a digitally guided assembly strategy. The project’s digital workflow seamlessly linked the immersive architectural design process (VR) conducted in the design studio with structural design and on-site construction of this public seating element. Following Hassan Fathy’s Principle “Construire avec le people” (1) BARZAKH fosters a participatory methodology embedding collaborative engagement throughout all project phases. By reimagining mudbrick as a viable and per se resilient alternative to CO-intensive materials, the project advocates for its relevance in contemporary architecture
Mitigation strategies for confidentiality violations in software architecture using ranked feature importance
Get PDFA quality attribute like confidentiality is critical to trustworthy software but unfortunately, very challenging to
ensure. This is because modern software systems are complex and interconnected. Architecture-based confiden-
tiality analysis enables the early detection of violations, helping to mitigate risks before deployment. However,
uncertainty in software systems and their environments complicates precise and comprehensive architectural
analysis. Additionally, the complexity of software models and the exponential growth of uncertainty scenarios
pose significant challenges for automated mitigation, often leaving software architects to resolve confidentiality
violations manually, a process that is both time-intensive and error-prone.
In this paper, we extend our machine-learning-based approach to mitigate confidentiality violations. Specif-
ically, we introduce a novel mitigation strategy inspired by TCP Congestion Control, as well as a strategy that
capitalizes on clustering techniques to dynamically adjust batch sizes. Our evaluation on three real-world soft-
ware architectures demonstrates that our extended approach can mitigate confidentiality violations while out-
performing the state-of-the-art. Whereas previously the upper limit was 60 times runtime reduction, now we
achieve 2298 times reduction, with the median being an elevenfold reduction. Our statistical analysis confirms
that the added TCP-inspired strategy is significantly cheaper than the state-of-the-art baseline (Friedman test
= .025 and Nemenyi post hoc test = .039), while also having a strong practical impact (Kendall’s W = 0.721).
This extended work deepens our understanding of the nature of uncertainty and also of the techniques optimally
suited to mitigating the violations caused by uncertainties. It takes us one step closer to designing trustworthier
systems
Electron spin resonance measurements of radiation-induced radicals under conventional and ultra-high dose rate electron irradiation
No full textUltra-high dose rate (UHDR) radiotherapy has been shown in preclinical studies to reduce normal tissue toxicity without compromising tumour control, a phenomenon referred to as the Flash effect. The radiochemical and biological mechanisms responsible for this effect remain unclear. This study investigates radical formation and oxygen depletion under UHDR and conventional dose rate (CDR) conditions to gain mechanistic insight. Radical formation was investigated using electron spin resonance (ESR) spectroscopy with both spin trapping and spin probe techniques. Oxygen consumption was monitored continuously during irradiation to complement radical yield measurements. E3 medium containing either spin traps (DMPO, DEPMPO, BMPO) or spin probes (CMH, TMTH, CAT1H) was prepared under hypoxic, physioxic, and normoxic conditions. Irradiations were performed at the Electron Linac for beams with high Brilliance and low Emittance at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) with 30 MeV electrons across a broad range of dose rates (0.1 Gy s–10 Gy s). Spin probe measurements enabled consistent comparisons between CDR and UHDR, revealing a significant dependence of spin concentration on both oxygenation and dose rate. In contrast, spin trapping showed reduced radical yields with decreasing oxygen levels, but no significant dose-rate dependence. Direct comparisons between UHDR and CDR were limited by differences in the decay kinetics of the spin adducts. Oxygen measurements confirmed a reduced oxygen consumption at UHDR, with the extent of depletion strongly dependent on initial oxygen concentration. The results support the hypothesis that UHDR conditions promote radical–radical recombination, shifting the reaction equilibrium and reducing the pool of radicals available to react in the homogeneous chemical phase, particularly with oxygen. The combined application of ESR spin trapping, spin probes, and real-time oxygen measurements offers complementary insight into dose-rate-dependent radical processes
Ca-ion storage enhancement of Ca-pillared vanadium oxide using a malonic-assisted solution combustion process and a novel aqueous AC//Ca(NO₃)₂//CaVO/C hybrid cell
No full textThe Influence of Electrolyte Formulation on Gas Evolution in Sodium‐Ion Batteries with NaMnO₂ Cathode
Get PDFSodium-ion batteries (SIBs) are considered a promising alternative to lithium-ion batteries due to the high availability of sodium resources. Among the various candidates for the positive electrode, layered (O3-type) NaMnO2 has attracted considerable attention. However, understanding of its interfacial stability remains limited. Differential electrochemical mass spectrometry (DEMS) is a powerful tool for monitoring gas evolution and therefore provides valuable insights into side reactions occurring at the interface between anode/cathode and electrolyte. In this work, the gassing behavior of SIB half-cells with NaMnO2 cathode and six representative electrolyte formulations is investigated using DEMS. The results show that electrolytes with fluoroethylene carbonate effectively suppress parasitic reactions and promote the formation of passivating interphases, resulting in improved performance and limited gas release. PC-based electrolytes appear to be more stable than EC-based electrolytes, especially in combination with NaClO4. The use of NaPF6 is associated with increased H2 evolution and possible manganese dissolution, thereby impairing interfacial stability and releasing more lattice oxygen. An increase in the upper cutoff potential enhances gas release, indicating more severe (electro)chemical oxidation of the electrolyte. Overall, this study paves the way for new strategies for tailoring electrolytes to improve the cyclability and safety of SIBs
Bayesian experimental design in production engineering: a comprehensive performance and robustness study
Get PDFIn production engineering, the identification of optimal process parameters is essential to advance product quality and overall equipment effectiveness. Optimizing and adapting process parameters through experimental design is relevant for different phases of the life cycle of a production process: (i) design and development of new processes, (ii) failure analysis and optimization, and (iii) adaptation and calibration in series production. Existing experimental design approaches tend to be inefficient because they comprise static, non-adaptive methodologies that separate experiment design from execution and analysis. Instead, Bayesian Optimization (BO) offers an adaptive and data-efficient methodology for experimental design termed Bayesian experimental design (BED). In BED, the selection of an experiment is re-evaluated in each iteration based on previous experiment results according to an acquisition function that aims to maximize the informational content of each experiment. However, the configuration of BO algorithms for specific optimization problems requires extensive knowledge of both BO and process characteristics. The mean and covariance functions of the surrogate model, the acquisition function, and initial data sampling must be individually configured and significantly influence overall optimization performance, preventing widespread adoption in production engineering practice. To guide the configuration of BO algorithms for optimizing production processes, in this paper, we perform an extensive benchmark study with a total of 15,360 experiments. We evaluate the performance of a variety of BO algorithm configurations (including kernels, acquisition functions, and initial sampling sizes) on a total of eight optimization problems with a noiseless and a noisy variant each. The performance and robustness analysis reveals significant performance differences between individual BO algorithm configurations. The results of our benchmarking serve as empirical references based on which we derive actionable guidelines for the application of BED in production engineering