TY - THES A1 - Arend, Marius T1 - Comparing genome-scale models of protein-constrained metabolism in heterotrophic and photosynthetic microorganisms N2 - Genome-scale metabolic models are mathematical representations of all known reactions occurring in a cell. Combined with constraints based on physiological measurements, these models have been used to accurately predict metabolic fluxes and effects of perturbations (e.g. knock-outs) and to inform metabolic engineering strategies. Recently, protein-constrained models have been shown to increase predictive potential (especially in overflow metabolism), while alleviating the need for measurement of nutrient uptake rates. The resulting modelling frameworks quantify the upkeep cost of a certain metabolic flux as the minimum amount of enzyme required for catalysis. These improvements are based on the use of in vitro turnover numbers or in vivo apparent catalytic rates of enzymes for model parameterization. In this thesis several tools for the estimation and refinement of these parameters based on in vivo proteomics data of Escherichia coli, Saccharomyces cerevisiae, and Chlamydomonas reinhardtii have been developed and applied. The difference between in vitro and in vivo catalytic rate measures for the three microorganisms was systematically analyzed. The results for the facultatively heterotrophic microalga C. reinhardtii considerably expanded the apparent catalytic rate estimates for photosynthetic organisms. Our general finding pointed at a global reduction of enzyme efficiency in heterotrophy compared to other growth scenarios. Independent of the modelled organism, in vivo estimates were shown to improve accuracy of predictions of protein abundances compared to in vitro values for turnover numbers. To further improve the protein abundance predictions, machine learning models were trained that integrate features derived from protein-constrained modelling and codon usage. Combining the two types of features outperformed single feature models and yielded good prediction results without relying on experimental transcriptomic data. The presented work reports valuable advances in the prediction of enzyme allocation in unseen scenarios using protein constrained metabolic models. It marks the first successful application of this modelling framework in the biotechnological important taxon of green microalgae, substantially increasing our knowledge of the enzyme catalytic landscape of phototrophic microorganisms. N2 - Genomweite Stoffwechselmodelle sind mathematische Darstellungen aller bekannten Reaktionen, die in einer Zelle ablaufen. In Kombination mit Einschränkungen, die auf physiologischen Messungen beruhen, wurden diese Modelle zur genauen Vorhersage von Stoffwechselflüssen und Auswirkungen von Manipulationene (z. B. Knock-outs) sowie zum Entwerfen von Metabolic Engineering Strategien verwendet. In jüngster Zeit hat sich gezeigt, dass proteinlimitierte Modelle, welche die Menge an Proteinen in einer Zelle als Modelbeschränkungen integrieren, ein erweitertes Modellierungspotenzial besitzen (insbesondere beim Überflussstoffwechsel) und gleichzeitig die Messungen der Nährstoffaufnahmerate eines Organismus optional machen. Die resultierenden Modelle quantifizieren die Unterhaltskosten eines bestimmten Stoffwechselflusses als die für die Katalyse erforderliche Mindestmenge an Enzymen. Die beobachtete Verbesserungen in den Voraussagefähigkeiten solcher Modelle werden durch die Parameterisierung mit unterschiedlichen in vitro und in vivo Approximationen der maximalen katalytischen Effizienz (Wechselzahl) aller Enyzme eines Organismus ermöglicht. In dieser Arbeit wurden verschiedene Verfahren zur Schätzung und Verfeinerung dieser Parameter auf der Grundlage von in vivo Proteomikdaten der Organismen Escherichia coli, Saccharomyces cerevisiae und Chlamydomonas reinhardtii entwickelt und angewendet. Der Unterschied zwischen den in vitro und in vivo berechneten katalytischen Raten für die drei Mikroorganismen wurde systematisch analysiert. Die Ergebnisse für die fakultativ heterotrophe Mikroalge C. reinhardtii erweitern die Menge an verfügbaren enzymkatalytischen Parametern für photosynthetische Organismen erheblich. Weiterhin deuten unsere Ergbnisse für C. reinhardtii auf eine globale Verringerung der Enzymeffizienz bei Heterotrophie im Vergleich zu anderen Wachstumsszenarien hin. Unabhängig vom modellierten Organismus konnte gezeigt werden, dass geschätzte in vivo Wechselzahlen die Genauigkeit der Vorhersagen von Proteinmengen im Vergleich zu in vitro Werten verbessern. Um die Vorhersagen von Proteinmengen weiter zu verbessern, wurden Modelle aus dem Bereich des maschinellen Lernens trainiert, die Prediktoren basierend auf der proteinlimitierten Modellierung und der Proteinsequenz integrieren. Die Kombination der beiden Arten von Prediktoren übertraf die Leistung von Modellen mit nur einer Art von Prediktoren und lieferte gute Vorhersageergebnisse, ohne auf experimentelle Transkriptionsdaten angewiesen zu sein. Die vorgestellte Arbeit stellt einen wertvollen Fortschritt bei der Vorhersage der Enzymallokation in unbekannten Szenarien unter Verwendung von proteinlimitierten Stoffwechselmodellen dar. Sie markiert die erste erfolgreiche Anwendung dieses Modellierungsverfahren in dem biotechnologisch wichtigen Taxon der grünen Mikroalgen und erweitert unser Wissen über die enzymkatalytische Landschaft phototropher Mikroorganismen entscheidend. T2 - Vergleich und Analyse genomweiter Modelle des protein-limitierten Metabolismus in heterotrophen und photosynthetischen Microorganismen KW - Metabolic Modeling KW - Systems Biology KW - Computational Biology KW - Proteomics KW - computergestützte Biologie KW - metabolische Modellierung KW - Proteomics KW - Systembiologie Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-651470 ER - TY - JOUR A1 - Luna, Lisa A1 - Korup, Oliver T1 - Seasonal landslide activity lags annual precipitation pattern in the Pacific Northwest JF - Geophysical research letters N2 - Seasonal variations in landslide activity remain understudied compared to recent advances in landslide early warning at hourly to daily timescales. Here, we learn the seasonal pattern of monthly landslide activity in the Pacific Northwest from five heterogeneous landslide inventories with differing spatial and temporal coverage and reporting protocols combined in a Bayesian multi-level model. We find that landslide activity is distinctly seasonal, with credible increases in landslide intensity, inter-annual variability, and probability marking the onset of the landslide season in November. Peaks in landslide probability in January and intensity in February lag the annual peak in mean monthly precipitation and landslide activity is more variable in winter than in summer, when landslides are rare. For a given monthly rainfall, landslide intensity at the season peak in February is up to 10 times higher than at the onset in November, underlining the importance of antecedent seasonal hillslope conditions. KW - landslide KW - seasonality KW - Pacific Northwest KW - Bayesian multi-level models KW - logistic regression KW - negative binomial regression Y1 - 2022 U6 - https://doi.org/10.1029/2022GL098506 SN - 0094-8276 SN - 1944-8007 VL - 49 IS - 18 PB - Wiley CY - Hoboken, NJ ER - TY - JOUR A1 - Lachmair, Martin A1 - Fischer, Martin H. A1 - Gerjets, Peter T1 - Action-control mappings of interfaces in virtual reality: a study of embodied interaction JF - Frontiers in virtual reality N2 - The development of interface technologies is driven by the goal of making interaction more positive through natural action-control mappings. In Virtual Reality (VR), the entire body is potentially involved for interaction, using such mappings with a maximum of degrees of freedom. The downside is the increase in interaction complexity, which can dramatically influence interface design. A cognitive perspective on detailed aspects of interaction patterns is lacking in common interface design guidelines, although it can be helpful to make this complexity controllable and, thus, make interaction behavior predictable. In the present study, the distinction between grounding, embodiment, and situatedness (the GES framework) is applied to organize aspects of interactions and to compare them with each other. In two experiments, zooming into or out of emotional pictures through changes of arm span was examined in VR. There are qualitatively different aspects during such an interaction: i) perceptual aspects caused by zooming are fundamental for human behavior (Grounding: closer objects appear bigger) and ii) aspects of gestures correspond to the physical characteristics of the agents (Embodiment: little distance of hands signals little or, in contrast, "creating more detail"). The GES-framework sets aspects of Grounding against aspects of Embodiment, thus allowing to predict human behavior regarding these qualitatively different aspects. For the zooming procedure, the study shows that Grounding can overrule Embodiment in interaction design. Thus, we propose GES as a cognitive framework that can help to inform interaction guidelines for user interface design in VR. KW - embodied interaction KW - grounded cognition KW - virtual reality KW - action-control mapping KW - zooming KW - valence KW - user interface KW - embodiment Y1 - 2022 U6 - https://doi.org/10.3389/frvir.2022.976849 SN - 2673-4192 VL - 3 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Ruszkiewicz, Joanna A1 - Papatheodorou, Ylea A1 - Jäck, Nathalie A1 - Melzig, Jasmin A1 - Eble, Franziska A1 - Pirker, Annika A1 - Thomann, Marius A1 - Haberer, Andreas A1 - Rothmiller, Simone A1 - Bürkle, Alexander A1 - Mangerich, Aswin T1 - NAD+ Acts as a protective factor in cellular stress response to DNA alkylating agents JF - Cells : open access journal N2 - Sulfur mustard (SM) and its derivatives are potent genotoxic agents, which have been shown to trigger the activation of poly (ADP-ribose) polymerases (PARPs) and the depletion of their substrate, nicotinamide adenine dinucleotide (NAD+). NAD+ is an essential molecule involved in numerous cellular pathways, including genome integrity and DNA repair, and thus, NAD+ supplementation might be beneficial for mitigating mustard-induced (geno)toxicity. In this study, the role of NAD+ depletion and elevation in the genotoxic stress response to SM derivatives, i.e., the monofunctional agent 2-chloroethyl-ethyl sulfide (CEES) and the crosslinking agent mechlorethamine (HN2), was investigated with the use of NAD+ booster nicotinamide riboside (NR) and NAD+ synthesis inhibitor FK866. The effects were analyzed in immortalized human keratinocytes (HaCaT) or monocyte-like cell line THP-1. In HaCaT cells, NR supplementation, increased NAD+ levels, and elevated PAR response, however, did not affect ATP levels or DNA damage repair, nor did it attenuate long- and short-term cytotoxicities. On the other hand, the depletion of cellular NAD+ via FK866 sensitized HaCaT cells to genotoxic stress, particularly CEES exposure, whereas NR supplementation, by increasing cellular NAD+ levels, rescued the sensitizing FK866 effect. Intriguingly, in THP-1 cells, the NR-induced elevation of cellular NAD+ levels did attenuate toxicity of the mustard compounds, especially upon CEES exposure. Together, our results reveal that NAD+ is an important molecule in the pathomechanism of SM derivatives, exhibiting compound-specificity. Moreover, the cell line-dependent protective effects of NR are indicative of system-specificity of the application of this NAD+ booster. KW - nicotinamide adenine dinucleotide KW - NAD booster; KW - mustard agents KW - nicotinamide riboside KW - DNA damage KW - sulfur mustard KW - poly(ADP-ribosylation) KW - PARP Y1 - 2023 U6 - https://doi.org/10.3390/cells12192396 SN - 2073-4409 VL - 12 IS - 19 PB - MDPI CY - Basel ER - TY - JOUR A1 - Sagu Tchewonpi, Sorel A1 - Rawel, Harshadrai M. A1 - Rohn, Sascha T1 - Targeted bottom-up mass spectrometry approach for the relative quantification of post-translational modification of bovine κ-casein during milk fermentation JF - Molecules N2 - kappa-casein (kappa-CN) is one of the key components in bovine milk, playing a unique role in the structuration of casein micelles. It contains in its chemical structure up to sixteen amino acid residues (mainly serine and threonine) susceptible to modifications, including glycosylation and phosphorylation, which may further be formed during milk processing. In this study, changes in post-translational modification (PTM) of kappa-CN during bovine milk fermentation were investigated. One-to-five-day fermented milk samples were produced. A traditional bottom-up proteomics approach was used to establish a multiple-reaction monitoring (MRM) method for relative quantification of kappa-CN PTM. Endoproteinase Glu-C was found to efficiently digest the kappa-CN molecule. The developed LC-MS method was validated by performing assessments of linearity, precision, repeatability, reproducibility, limit of detection (LOD), and limit of quantification (LOQ). Among the yielded peptides, four of them containing serine and threonine residues were identified and the unmodified as well as the modified variants of each of them were relatively quantified. These peptides were (1) IPTINTIASGEPTSTTE ([140, 158]), (2) STVATLE ([162, 168]), (3) DSPE ([169, 172]), and (4) INTVQVTSTAV ([180, 190]). Distribution analysis between unmodified and modified peptides revealed that over 50% of kappa-CN was found in one of its modified forms in milk. The fermentation process further significantly altered the composition between unmodified/modified kappa-CN, with glycoslaytion being predominant compared to phosphorylation (p < 0.01). Further method development towards alpha and beta-CN fractions and their PTM behavior would be an asset to better understand the changes undergone by milk proteins and the micellar structure during fermentation. KW - bovine milk KW - fermentation KW - kappa-casein KW - post-translational modifications KW - glycosylation KW - phosphorylation KW - mass spectrometry Y1 - 2022 U6 - https://doi.org/10.3390/molecules27185834 SN - 1420-3049 VL - 27 IS - 18 PB - MDPI CY - Basel ER - TY - JOUR A1 - Horvat, Anja Kranjc A1 - Wiener, Jeff A1 - Schmeling, Sascha Marc A1 - Borowski, Andreas T1 - What does the curriculum say? Review of the particle physics content in 27 high-school physics curricula JF - Physics N2 - This international curricular review provides a structured overview of the particle physics content in 27 state, national, and international high-school physics curricula. The review was based on a coding manual that included 60 concepts that were identified as relevant for high-school particle physics education. Two types of curricula were reviewed, namely curricula with a dedicated particle physics chapter and curricula without a dedicated particle physics chapter. The results of the curricular review show that particle physics concepts are explicitly or implicitly present in all reviewed curricula. However, the number of particle physics concepts that are featured in a curriculum varies greatly across the reviewed curricula. We identified core particle physics concepts that can be found in most curricula. Here, elementary particles, fundamental interactions, and charges were identified as explicit particle physics concepts that are featured in more than half of the reviewed curricula either as content or context. Indeed, theoretical particle physics concepts are more prominent in high-school physics curricula than experimental particle physics concepts. Overall, this international curricular review provides the basis for future curricular development with respect to particle physics and suggests an increased inclusion of experimental particle physics concepts in high-school physics curricula. KW - curricular review KW - particle physics KW - high-school education Y1 - 2022 U6 - https://doi.org/10.3390/physics4040082 SN - 2624-8174 VL - 4 IS - 4 SP - 1278 EP - 1298 PB - MDPI CY - Basel ER - TY - CHAP A1 - Grum, Marcus ED - Shishkov, Boris T1 - Managing multi-site artificial neural networks’ activation rates and activation cycles T2 - Business modeling and software design : 14th International Symposium, BMSD 2024, Luxembourg City, Luxembourg, July 1–3, 2024, proceedings N2 - Traditionally, business models and software designs used to model the usage of artificial intelligence (AI) at a very specific point in the process or rather fix implemented application. Since applications can be based on AI, such as networked artificial neural networks (ANN) on top of which applications are installed, these on-top applications can be instructed directly from their underlying ANN compartments [1]. However, with the integration of several AI-based systems, their coordination is a highly relevant target factor for the operation and improvement of networked processes, such as they can be found in cross-organizational production contexts spanning multiple distributed locations. This work aims to extend prior research on managing artificial knowledge transfers among interlinked AIs as coordination instrument by examining effects of different activation types (respective activation rates and cycles) on by ANN-instructed production machines. In a design-science-oriented way, this paper conceptualizes rhythmic state descriptions for dynamic systems and associated 14 experiment designs. Two experiments have been realized, analyzed and evaluated thereafter in regard with their activities and processes induced. Findings show that the simulator [2] used and experiments designed and realized, here, (I) enable research on ANN activation types, (II) illustrate ANN-based production networks disrupted by activation types and clarify the need for harmonizing them. Further, (III) management interventions are derived for harmonizing interlinked ANNs. This study establishes the importance of site-specific coordination mechanisms and novel forms of management interventions as drivers of efficient artificial knowledge transfer. Y1 - 2024 SN - 978-3-031-64072-8 SN - 978-3-031-64073-5 U6 - https://doi.org/10.1007/978-3-031-64073-5_17 SP - 258 EP - 269 PB - Springer CY - Cham ER - TY - JOUR A1 - Shlapunov, Alexander A. A1 - Tarchanov, Nikolaj Nikolaevič T1 - Inverse image of precompact sets and regular solutions to the Navier-Stokes equations JF - Vestnik Udmurtskogo Universiteta. Matematika, mechanika, kompʹjuternye nauki N2 - We consider the initial value problem for the Navier-Stokes equations over R-3 x [0, T] with time T > 0 in the spatially periodic setting. We prove that it induces open injective mappings A(s): B-1(s) -> B-2(s-1) where B-1(s), B-2(s-1) are elements from scales of specially constructed function spaces of Bochner-Sobolev typeparametrized with the smoothness index s is an element of N. Finally, we prove that a map Asis surjective if and only if the inverse image A(s)(- 1) (K) of any pre compact set K from the range of the map Asis bounded in the Bochner space L-s([0, T], L-r(T-3))with the Ladyzhenskaya-Prodi-Serrin numbers s, r. KW - Navier-Stokes equations KW - regular solutions Y1 - 2022 U6 - https://doi.org/10.35634/vm220208 SN - 1994-9197 SN - 2076-5959 VL - 32 IS - 2 SP - 278 EP - 297 PB - Udmurtskij gosudarstvennyj universitet CY - Iževsk ER - TY - CHAP A1 - Grum, Marcus ED - Shishkov, Boris T1 - Researching multi-site artificial neural networks’ activation rates and activation cycles T2 - Business modeling and software design : 14th International Symposium, BMSD 2024, Luxembourg City, Luxembourg, July 1–3, 2024, proceedings N2 - With the further development of more and more production machines into cyber-physical systems, and their greater integration with artificial intelligence (AI) techniques, the coordination of intelligent systems is a highly relevant target factor for the operation and improvement of networked processes, such as they can be found in cross-organizational production contexts spanning multiple distributed locations. This work aims to extend prior research on managing their artificial knowledge transfers as coordination instrument by examining effects of different activation types (respective activation rates and cycles) on by Artificial Neural Network (ANN)-instructed production machines. For this, it provides a new integration type of ANN-based cyber-physical production system as a tool to research artificial knowledge transfers: In a design-science-oriented way, a prototype of a simulation system is constructed as Open Source information system which will be used in on-building research to (I) enable research on ANN activation types in production networks, (II) illustrate ANN-based production networks disrupted by activation types and clarify the need for harmonizing them, and (III) demonstrate conceptual management interventions. This simulator shall establish the importance of site-specific coordination mechanisms and novel forms of management interventions as drivers of efficient artificial knowledge transfer. Y1 - 2024 SN - 978-3-031-64072-8 SN - 978-3-031-64073-5 U6 - https://doi.org/10.1007/978-3-031-64073-5_12 SP - 186 EP - 206 PB - Springer CY - Cham ER - TY - JOUR A1 - Steinrötter, Björn A1 - Schauer, Lina Marie T1 - Lauterkeitsrechtliche Behandlung von Dark Patterns JF - Wettbewerb in Recht und Praxis N2 - Online-Nutzer begegnen regelmäßig unterschwelligen manipulativen Designstrategien von Anbietern digitaler Produkte, welche sie zu rechtsgeschäftlich relevanten Entscheidungen bewegen sollen, die sie womöglich nicht - oder zumindest nicht so - beabsichtigt haben. Man spricht in diesem Zusammenhang von (vielgestaltig denkbaren) „Dark Patterns“ (dt. „dunkle Muster“). Der Beitrag geht der Frage nach, inwiefern diese insbesondere lauterkeitsrechtlich zulässig sind. Y1 - 2024 UR - https://www.juris.de/r3/document/jzs-WRP-2024-08-002-873 SN - 0172-049X SN - 1435-3059 VL - 38 IS - 8 SP - 873 EP - 882 PB - Deutscher Fachverlag CY - Frankfurt am Main ER -