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Item Heterogeneity of treatment effects in internet- and mobile-based interventions for depression : a systematic review and meta-analysis(Universität Ulm, 2024-07-18) Terhorst, Yannik; Kaiser, Tim; Brakemeier, Eva-Lotta; Moshe, Isaac; Philippi, Paula; Cuijpers, Pim; Baumeister, Harald; Sander Lasse BosseImportance While the effects of internet- and mobile-based interventions (IMIs) for depression have been extensively studied, no systematic evidence is available regarding the heterogeneity of treatment effects (HTEs), indicating to what extent patient-by-treatment interactions exist and personalized treatment models might be necessary. Objective To investigate the HTEs in IMIs for depression as well as their efficacy and effectiveness. Data Sources A systematic search in Embase, MEDLINE, Central, and PsycINFO for randomized clinical trials and supplementary reference searches was conducted on October 13, 2019, and updated March 25, 2022. The search string included various terms related to digital psychotherapy, depression, and randomized clinical trials. Study Selection Titles, abstracts, and full texts were reviewed by 2 independent researchers. Studies of all populations with at least 1 intervention group receiving an IMI for depression and at least 1 control group were eligible, if they assessed depression severity as a primary outcome and followed a randomized clinical trial (RCT) design. Data Extraction and Synthesis This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. Risk of bias was evaluated using the Cochrane Risk of Bias Tool. HTE was investigated using logarithmic variance ratios (lnVR) and effect sizes using Hedges g. Three-level bayesian meta-regressions were conducted. Main Outcomes and Measures Heterogeneity of treatment effects was the primary outcome of this study; magnitudes of treatment effect sizes were the secondary outcome. Depression severity was measured by different self-report and clinician-rated scales in the included RCTs. Results The systematic review of 102 trials included 19 758 participants (mean [SD] age, 39.9 [10.58] years) with moderate depression severity (mean [SD] in Patient Health Questionnaire–9 score, 12.81 [2.93]). No evidence for HTE in IMIs was found (lnVR = −0.02; 95% credible interval [CrI], −0.07 to 0.03). However, HTE was higher in more severe depression levels (β̂ = 0.04; 95% CrI, 0.01 to 0.07). The effect size of IMI was medium (g = −0.56; 95% CrI, −0.46 to −0.66). An interaction effect between guidance and baseline severity was found (β̂ = −0.24, 95% CrI, −0.03 to −0.46). Conclusions and Relevance In this systematic review and meta-analysis of RCTs, no evidence for increased patient-by-treatment interaction in IMIs among patients with subthreshold to mild depression was found. Guidance did not increase effect sizes in this subgroup. However, the association of baseline severity with HTE and its interaction with guidance indicates a more sensitive, guided, digital precision approach would benefit individuals with more severe symptoms. Future research in this population is needed to explore personalization strategies and fully exploit the potential of IMI.Item Robust parahydrogen-induced polarization at high concentrations(Universität Ulm, 2024-07-24) Dagys, Laurynas; Korzeczek, Martin C.; Parker, Anna J.; Eills, James; Blanchard, John; Bengs, Christian; Levitt, Malcolm; Knecht, Stephan; Schwartz, Ilai; Plenio, Martin B.Parahydrogen-induced polarization (PHIP) is a potent technique for generating target molecules with high nuclear spin polarization. The PHIP process involves a chemical reaction between parahydrogen and a target molecule, followed by the transformation of nuclear singlet spin order into magnetization of a designated target nucleus through magnetic field manipulations. Although the singlet-to- magnetization polarization transfer process works effectively at moderate concentrations, it is observed to become much less efficient at high molar polarization, defined as the product of polarization and concentration. This strong dependence on the molar polarization is attributed to interference due to the field produced by the sample magnetization during polarization transfer, which leads to complex dynamics and can severely affect the scalability of the technique. We address this challenge with a pulse sequence that suppresses the influence of the distant dipolar field, while simultaneously achieving singlet-to- magnetization polarization transfer to the desired target spins, free from restrictions on the molar polarization.Item Untersuchung und echtzeitfähige Modellierung von temperaturabhängigen Stromverteilungen in Lithium-Ionen-Batterien durch Segmentierung(Universität Ulm, 2025-04-17) Menner, Sebastian; Buchholz, Michael; Danzer, MichaelLithium-Ionen-Batterien in Elektroautos sind unterschiedlichsten Umwelteinflüssen ausgesetzt und sollen dennoch zuverlässig das Fahrzeug mit ausreichend Leistung versorgen. Zudem müssen Überbelastungen vermieden werden, um Sicherheit zu gewährleisten und eine lange Lebensdauer erzielen zu können. Verantwortlich für diesen Schutz ist das Batteriemanagementsystem (BMS), welches die Betriebsgrenzen an den aktuellen Zustand der Batterie anpasst. Für eine optimale Regelung muss dieser Zustand möglichst gut bekannt sein. Ein Problem dabei ist, dass sich die Batteriezellen aufgrund von Inhomogenitäten und Asymmetrien, sowohl in der Zelle selbst als auch außerhalb, nicht gleichmäßig erwärmen. Dies führt zu ungleichen Verteilungen der Stromdichte innerhalb der Zellen, die vom BMS nicht gemessen werden können. Je genauer die lokalen Stromdichten jedoch bekannt sind, desto präziser kann die Begrenzung des Gesamtstroms der Batterie angepasst werden. Das Ziel dieser Arbeit besteht daher in der messtechnischen Untersuchung solcher temperaturbedingter, inhomogener Stromverteilungen. Hierzu wird ein segmentierter Ansatz verfolgt, bei dem eine großformatige Pouchzelle durch eine Parallelschaltung aus kleineren Segmentzellen nachgebildet wird. Ein geeignetes Messkonzept wurde erarbeitet, umgesetzt und erfolgreich validiert. Durch gezieltes Aufbringen von Temperaturgradienten werden inhomogene Stromverteilungen provoziert und in der Parallelschaltung gemessen. Anhand dieser Ergebnisse lassen sich Gesetzmäßigkeiten ableiten, die einen näherungsweise linearen Zusammenhang zwischen Stromverteilung, Temperaturgradient und Gesamtstromstärke während kurzen Strompulsen herstellen. Zudem besteht eine quadratische Abhängigkeit des Stromgradienten zur absoluten Temperatur. Der Ladezustand spielt hierbei nur eine untergeordnete Rolle. Die Resultate für kurze Strompulse können außerdem mit Einschränkungen auf dynamische Stromprofile, wie sie in realen Fahrzeugen auftreten, übertragen werden. Auf Basis der gewonnenen Erkenntnisse wird abschließend ein neuartiger Modellansatz vorgestellt, der bei Kenntnis der aktuellen Temperaturverteilung und dem Gesamtstrom die lokale Stromverteilung echtzeitfähig auf dem BMS bestimmen kann. Hierbei wurde auf ein speicher- und recheneffizientes Design, einfache Parametrierbarkeit sowie hohe Robustheit Wert gelegt. Das Modell wird gegen einen klassischen Modellansatz auf Grundlage von Ersatzschaltbildmodellen verglichen und erfüllt die gesetzten Ansprüche.Item Power electronic converters for avionic application(Universität Ulm, 2025-04-17) Bhattacharya, Sumantra; Kallo, Josef; Neuburger, MartinAviation is one of the leading sources of carbon dioxide (CO2) emissions in the world. Therefore, full-electric aircraft are garnering a lot of attention from researchers, as they are seen as the inevitable future of the aviation industry if we are to move forward to an emission-free world. Today, hybrid-electric aircraft often employ a hybrid drive train using green energy sources such as batteries and fuel cells. Efficient and robust power electronic converters are vital to the success of the electrification of aircraft. This thesis presents three DC–DC converter concepts that are suitable for avionic applications. The first converter described in this thesis is a 3.0 kW LLC converter that was designed for high-voltage to low-voltage conversion with a very high current output. An experimental prototype was built to verify the operating principle. The second converter looked at ways to make LLC converters fault tolerant. In aerospace applications, a fault-tolerant topology is highly desirable to reduce the need for redundant components and weight by removing backup systems. To solve this issue, a new LLC-based converter with a reconfigurable fault-tolerant architecture was developed. With the help of a specially designed secondary side, the proposed converter can reconfigure itself so that even if one of the semiconductor switches permanently fails, the converter can still maintain power at nominal voltage levels, ensuring that the vital functionality of the aircraft is preserved. Finally, a 2.0 kW experimental prototype is built to verify and demonstrate the operation of the proposed reconfigurable LLC converter. In the final part of the thesis, a multi-input, multiport DC-DC converter was proposed. Integrating different voltage sources (such as fuel cells and batteries) to supply power to different loads at different voltage levels and controlling the flow of power is an arduous task. Currently, this is achieved by using a combination of complex passive circuitry and DC-DC converters. As a solution, a new galvanically isolated DC-DC converter topology is proposed that integrates a battery and fuel cells as input sources and is capable of supplying power to a high-voltage (HV) load and a low-voltage (LV) load simultaneously. This converter offers flexibility in terms of the direction of power from sources to the load, between sources, and in the reverse direction from the load to the sources (recuperation). The functioning of the converter is verified using a real-time hardware-in-the-loop (HiL) test. This new concept is easily scalable and can be adopted in any drive train of all-electric aircraft of different sizes that use fuel cells and batteries.Item Improving pancreatic lineage commitment of human pluripotent stem cells in terms of pancreas development and disease modelling(Universität Ulm, 2025-04-17) Merz, Sarah; Kleger, Alexander; Geiger, Hartmut; Liebau, StefanPancreatic lineage differentiation has predominantly focused on driving the generation of functional β-cells, given their significance in diabetes research and therapy. However, for comprehensive disease modeling and a better understanding of the entire pancreas, including its interactions and functions, it is likewise crucial to generate cells of the exocrine compartment. The objective of the first part of this doctoral thesis was to optimize the differentiation of hESCs toward the pancreatic lineage. This included a detailed characterization of pancreatic progenitors to understand their marker profiles and cellular heterogeneity, and to direct their further specification into endocrine and exocrine lineages. Additionally, this work aimed to implement an ex vivo culture system to achieve robust, long-term maturation of pancreatic cells. The second part of the thesis aimed to utilize the optimized differentiation system for modelling monogenic neonatal diabetes (Figure 2). In this specific case, a child diagnosed with severe neonatal diabetes, and his family history of T2D, served as basis for this study. This part of the doctoral thesis involved integrating gene engineering with pancreatic differentiation, various sequencing approaches and functionality assays to decipher the underlying disease mechanisms. A key focus was to elucidate the regulatory role of a non-coding region on ONECUT1 expression and its impact on islet development.Item Heterogeneity and incompressibility in the evolution of elastic wires(Universität Ulm, 2025-04-17) Langer, Leonie; Dall'Acqua, Anna; Schnürer, OliverElastic wires are mathematical curves composed of matter. They have no thickness but exhibit bending stiffness. Although elastic wires do not exist in the real world, they are widely used in modeling. Examples include the modeling of plant stems, polymers such as DNA, marine cables, and hair movement in digital simulations. The elastic energy of a sufficiently smooth regular curve describing an elastic wire is defined as the integral of the squared curvature. In the last decades, several authors have studied the L2-gradient flow of the elastic energy in different variants. In this monograph, we briefly present the underlying theory and background, summarize their results, and then focus on two new variants. First, we consider elastic wires with a heterogeneity described by a density function. We define a generalization of the elastic energy, which depends on material parameters, captures the interplay between curvature and density effects and resembles the Canham-Helfrich functional. Describing the closed planar curve by its inclination angle, the L2-gradient flow of this energy is a nonlocal coupled parabolic system of second order. We discuss local well-posedness, global existence and convergence. Then, we show that the (non)preservation of quantities such as convexity as well as the asymptotic behavior of the system depend delicately on the choice of material parameters. Second, we study the evolution of elastic wires under the assumption of incompressiblity and derive a gradient flow of the elastic energy which preserves the enclosed area of the evolving planar curves. Contrary to an earlier approach based on a fourth order equation featuring nonlocal Lagrange multipliers, we give priority to the locality of the evolution and propose a sixth order gradient flow equation with no nonlocal terms. For this flow, we establish a global existence result. When including an additional term penalizing length, we prove convergence to an area constrained critical point of the elastic energy.Item Uptake, distribution and elimination of intranasally-delivered immunoglobulin G in vivo and suggestions for intranasal drug formulations tailored for the olfactory mucosa(Universität Ulm, 2025-04-16) Gänger, Stella; Zimmermann, Katharina; Barth, HolgerNeurological diseases such as Multiple Sclerosis, Alzheimer's, Parkinson's, and psychiatric disorders impact the central nervous system (CNS), necessitating effective therapies to enhance patient health. Therefore, the development of pharmacologically active drugs that modulate the pathophysiological processes of these diseases is crucial. However, targeting CNS disorders poses significant challenges. The blood-brain barrier (BBB) is a formidable protective system that prevents up to 95% of molecules from reaching the CNS, complicating the delivery of therapeutically effective drug concentrations via oral or intravenous routes. Intrathecal administration on the other hand carries infection risks and can deter patient compliance. To address these challenges, a new approach for effective CNS disorder treatment is needed. Nose-to-brain (N2B) drug delivery offers a promising solution. Unlike traditional methods, the nose-to-brain pathway bypasses the BBB, facilitating drug uptake directly into the CNS. This method not only enhances patient compliance but also supports long-term therapy administration. To develop pharmacologically active drugs for nose-to-brain transport, a thorough understanding of drug delivery pathways is essential. Prior to this thesis, the nose-to-brain transport mechanism of immunoglobulin G (IgG) was not well elucidated. Therefore, a primary objective of this study was to investigate the uptake, distribution and the elimination of IgG antibodies from the olfactory mucosa to the CNS. This work has made a significant contribution by analyzing the Fc receptor-mediated nose-to-brain pathway for IgG in vivo and providing insights into the uptake and degradation of intranasally administered IgG. Key findings from the study include the transport of IgG along the olfactory sensory neurons (OSNs) through bulk-flow processes. It is hypothesized that IgG navigates through the spaces between neuronal bundles and the surrounding olfactory ensheathing cells (OECs) to enter the CNS from the lamina propria without requiring active transport. Once in the olfactory bulb, IgG are distributed throughout the CNS via passive flow in the cerebrospinal fluid until they reach their target sites. The study also investigated IgG uptake in the olfactory mucosa, with a focus on receptor-mediated uptake. It was confirmed that the Fc receptor FcRn is significantly involved in the uptake of both wild-type and deglycosylated IgG. The FcRn receptor is thought to trigger endosomal uptake, enabling transcytotic transport. While imaging methods have not conclusively demonstrated this, it is proposed that FcRn has a stronger affinity for deglycosylated IgG. This may account for the increased presence of deglycosylated IgG observed in the CNS. The expected role of FcγR could not be validated in this study, as no substantial co-localization of FcγR and IgG was detected. However, this is not necessarily a drawback, as FcγRs are linked to immune system activation, which should ideally be minimized during drug delivery. Consequently, further exploration of FcγR’s involvement in IgG transport is still needed. The study also found that IgGs are degraded within lysosomal compartments in the CNS and eliminated via cerebrospinal fluid drainage. A greater amount of deglycosylated IgG was detected in lysosomes compared to wild-type IgG. This may be due to the reduced stability of deglycosylated IgG, leading to faster degradation, or it could suggest that more deglycosylated IgG is taken up by the CNS, resulting in its higher concentration in lysosomes. From a medical perspective, this implies that higher or more frequent dosing of deglycosylated IgG may be needed to compensate for its accelerated degradation. Additionally, this thesis successfully applied a systematic approach, including data mining and expression analysis of tissue samples, to thoroughly examine the olfactory mucosa. It was predicted that the olfactory environment consists of a watery mucosal barrier with low salt concentration and neutral pH, which was confirmed by a small study using postmortem porcine tissue. This information is crucial for optimizing drug formulations. As a result, recommendations for suitable drug formulations were made, and the challenges of effective nose-to-brain drug delivery were addressed. Predictions regarding the ideal hydrogel patch formulation were meanwhile validated in a preclinical study with mini pigs, which confirmed the accuracy of the predictions. The patch exhibited good long-term stability and no toxic effects. Future research can now focus on establishing the dose-response curve for intranasally administered IgG.Item Methods for the systematic consideration of driver’s cognitive workload during the development of in-vehicle information systems(Universität Ulm, 2025-04-16) von Janczewski, Nikolai; Baumann, Martin; Krems, JosefWhile operating in-vehicle information systems (IVIS), drivers can be exposed to various forms of distraction that influence driving safety. Besides visual distraction, one kind of distraction is caused by cognitive load, which describes in particular the amount of information processing required. There is a need for methods to measure cognitive load in order to ensure that the concepts and designs of IVIS do not require too much cognitive load while driving. These methods have to fulfill specific requirements to be implemented into the development process of IVIS. This cumulative thesis therefore focuses on providing methods for IVIS designers in the development process to consider the construct of cognitive load (in addition to other factors such as visual distraction and usability). Since the methods are to be used by practitioners, an easy access and a certain level of efficiency to carry out the methods are postulated as requirements. To describe the information processing in IVIS operation, the in-vehicle information processing analysis tool (IVIPAT) is presented in study I. The study consists of two phases, in each of which N=15 IVIS practitioners and university researchers use this method to analyze a video-recorded IVIS operation sequence. By this analytic method developers can reflect the interaction based on information processing steps (e.g. search, identify, interpret). The steps are estimated in terms of the expected intensity. According to the results of study I IVIPAT helps to identify differences between concept variants, to uncover critical points in the process and to generate hypotheses for empirical tests. For empirical measurement of cognitive load when using IVIS, a subjective one-item measure based on the NASA-TLX mental dimension is presented in study II. In three different experiments, N=107 subjects are confronted with different levels of demand, which they then evaluate using the one-item measure. As part of the study, the scale is validated in the IVIS research environment and the capabilities are emphasized. In conclusion, since it is a one-item measure, the survey is time-saving and allows a large number of repetitions, e.g. when comparing numerous concept variants within one experiment. As a calibration method for cognitive load when using IVIS the n-back task is presented in study III. The meta-analysis with N=20 studies and more than 800 subjects aims to confirms the validity of the n-back task and identifies moderator variables that need to be considered when designing empirical measurements with the help of the n-back task. Finally, the thesis provides a proposal for using IVIPAT, subjective measurement of cognitive load and the n-back task in combination within the development process. This should ultimately help to develop IVIS with adequate cognitive workload during user operation.Item Cryo-EM observation of the amyloid key structure of polymorphic TDP-43 amyloid fibrils(Universität Ulm, 2024-01-12) Sharma, Kartikay; Stockert, Fabian; Shenoy, Jayakrishna; Berbon, Mélanie; Abdul-Shukkoor, Muhammed Bilal; Habenstein, Birgit; Loquet, Antoine; Schmidt, Matthias; Fändrich, MarcusThe transactive response DNA-binding protein-43 (TDP-43) is a multi-facet protein involved in phase separation, RNA-binding, and alternative splicing. In the context of neurodegenerative diseases, abnormal aggregation of TDP-43 has been linked to amyotrophic lateral sclerosis and frontotemporal lobar degeneration through the aggregation of its C-terminal domain. Here, we report a cryo-electron microscopy (cryo-EM)-based structural characterization of TDP-43 fibrils obtained from the full-length protein. We find that the fibrils are polymorphic and contain three different amyloid structures. The structures differ in the number and relative orientation of the protofilaments, although they share a similar fold containing an amyloid key motif. The observed fibril structures differ from previously described conformations of TDP-43 fibrils and help to better understand the structural landscape of the amyloid fibril structures derived from this protein.Item Coherent networks of uncoupled digital radars(Universität Ulm, 2025-04-16) Werbunat, David; Waldschmidt, Christian; Vossiek, MartinIn a radar network, multiple radars operate cooperatively, enabling simultaneous sensing from multiple perspectives. This collaboration is particularly valuable when the radars are coherent—enabling bistatic signal processing, where one radar evaluates the signal from one or multiple others, without being affected by synchronization errors. The greatest flexibility is provided by uncoupled coherent radar networks, which do not rely on reference signals distributed via cables. Nonetheless, these networks are also the most challenging to synchronize. Digital radars, however, offer promising opportunities for new synchronization and multiplexing techniques: By exploiting their highly flexible digital baseband signal generation and processing capabilities, signal processing limitations of conventional analog radars can be overcome. This thesis presents a comprehensive investigation into the potential of digital radars to overcome the key challenges of uncoupled coherent radar networks. Specifically, these are synchronization and multiplexing. To this end, three different radar network concepts are proposed, verified, and evaluated, leveraging different characteristics of the respective signal modulation. These include the use of single-carrier signals, as employed by phase-modulated continuous wave (PMCW) radars and multi-carrier signals as used by orthogonal frequency-division multiplexing (OFDM) radars.Item Evaluation of batteries for all-electric aircraft: a combined experimental and simulative study(Universität Ulm, 2025-04-16) Hoenicke, Pia; Kallo, Josef; Leibfried, ThomasTo meet the current trend of aircraft electrification, batteries as energy carriers are promising. Before implementing batteries in an aircraft, they have to be tested for the special conditions. NCA (Ni, Co, Al), NMC (Ni, Mn, Co) and LFP (Fe, P) lithium-ion batteries are favorable either with regards to specific energy or safety. Therefore, three commercial lithium-ion battery cells of these types were measured and characterized. The NCA and LFP types were cylindrical cells and the NMC type was a pouch cell. The measurements included current, temperature, humidity and pressure variations. Strong temperature dependency on the cell performance (up to 55 % specific energy loss from +60 to -30 °C) as well as strong current dependency (up to 63 % specific energy loss between 0.2C and maximum current) was found for all three cell types. None of the cells showed any humidity dependency. During the low-pressure tests, the NMC cell showed a slight pressure influence in their impedance spectra. An ohmic resistance increase of around 0.1 mΩ per 25 kPa and an impedance increase for low state of charge levels at 25 kPa was observed. The cylindrical cells (LFP and NCA) did not show pressure dependency. The hard cylindrical containers probably prevent the cell inside to be exposed to lower pressure. However, none of the cells showed strong pressure dependency. Assessing aircraft suitability with a battery model instead of building and integrating a real battery stack is more efficient and economical since resources and time can be saved. A battery model based on RC circuits was built and parameterized using real measurements like pulse tests, electrochemical impedance spectroscopy and open circuit voltage measurements of all three battery types. RC-parameters obtained from pulse tests showed better accuracy than parameters from electrochemical impedance spectroscopy and were therefore implemented into the battery cell simulation. This battery cell model was extended to a battery system model and connected to an inverter-motor-model to build a battery-only aircraft. The simulation showed that the NMC battery is the most suitable to build a battery-only aircraft since the NMC cells have the highest specific energy as pouch cells which leads to a larger flight range at the same weight. However, the examined battery-only aircraft cannot fulfill the flight reserve for the used specific flight profile and even small distance extensions lead to large weight increase. Hybrid aircraft using batteries and fuel cells are more suited for longer distances due to the high specific energy of hydrogen. Therefore, a fuel cell battery hybrid-electric aircraft model was built by adding a fuel cell model and a self-developed power distribution system to connect battery, fuel cell and inverter-motor system in a direct hybrid. For the hybrid aircraft, the NCA battery was most suitable for the specific flight profile since the combined powering of fuel cell and battery via the power distribution system was balanced best and therefore led to lowest weight. The simulation further showed this hybrid aircraft using a fuel cell and an NCA battery system even has SOC flight reserves and still works at lower temperatures like 0 °C where the battery capacity is decreased.Item Identification of IER3 as a novel modulator of the osteogenic differentiation of mesenchymal stem cells(Universität Ulm, 2025-04-15) Küppers, Oliver; Ignatius, Anita; Scharffetter-Kochanek, Karin; Herrmann, MariettaMesenchymal stem cells (MSCs) have gained tremendous interest due to their overall potent pro-regenerative and immunomodulatory properties. In recent years, various in vitro and preclinical studies have investigated different priming (“licensing”) approaches to enhance MSC functions for specific therapeutic purposes. In this study, we primed bone marrow-derived human MSCs (hMSCs) with an inflammation cocktail designed to mimic the elevated levels of inflammatory mediators found in serum of patients with severe injuries, such as bone fractures. We observed a significantly enhanced osteogenic differentiation potential of primed hMSCs compared to untreated controls. By RNA-sequencing analysis, we identified the immediate early response 3 (IER3) gene as one of the top-regulated genes upon inflammatory priming. Small interfering RNA knock-down experiments established IER3 as a novel positive regulator of osteogenic differentiation. Mechanistic analysis further revealed that IER3 deletion significantly downregulated bone marrow stromal cell antigen 2 (BST2) expression and extracellular signal-related kinase 1/2 (ERK1/2) phosphorylation in hMSCs, suggesting that IER3 regulates osteogenic differentiation through BST2 and ERK1/2 signaling pathway activation. On the basis of these findings, we propose IER3 as a novel therapeutic target to promote hMSC osteoblastogenesis, which might be of high clinical relevance, for example, in patients with osteoporosis or compromised fracture healing.Item A Generic Taxonomy for Steganography Methods(Universität Ulm, 2025-04-09) Wendzel, Steffen; Caviglione, Luca; Mazurczyk, Wojciech; Mileva, Aleksandra; Dittmann, Jana; Krätzer, Christian; Lamshöft, Kevin; Vielhauer, Claus; Hartmann, Laura; Keller, Jörg; Neubert, Tom; Zillien, SebastianA unified understanding of terms is essential for every scientific discipline: steganography is no exception. Being divided into several domains (e.g., network and text steganography), it is crucial to provide a unified terminology as well as a taxonomy that is not limited to few applications or areas. A prime attempt towards a unified understanding of terms was conducted in 2015 with the introduction of a pattern-based taxonomy for network steganography. In 2021, the first work towards a pattern-based taxonomy for all domains of steganography was proposed. However, this initial attempt still faced several shortcomings, e.g., remaining inconsistencies and a lack of patterns for several steganography domains. As the consortium who published the previous studies on steganography patterns, we present the first comprehensive pattern-based taxonomy tailored to fit all known domains of steganography, including smaller and emerging areas, such as filesystem, IoT/CPS, and AI/ML steganography. To make our contribution more effective and promote the use of the taxonomy to advance research, we also provide a unified description method joint with a thorough tutorial on its utilization.Item Immunogenetic-pathogen networks shrink in Tome’s spiny rat, a generalist rodent inhabiting disturbed landscapes(Universität Ulm, 2024-02-10) Fleischer, Ramona; Eibner, Georg Joachim; Schwensow, Nina Isabell; Pirzer, Fabian; Paraskevopoulou, Sofia; Mayer, Gerd; Corman, Victor Max; Drosten, Christian; Wilhelm, Kerstin; Heni, Alexander Christoph; Sommer, Simone; Schmid, Dominik WernerAnthropogenic disturbance may increase the emergence of zoonoses. Especially generalists that cope with disturbance and live in close contact with humans and livestock may become reservoirs of zoonotic pathogens. Yet, whether anthropogenic disturbance modifies host-pathogen co-evolutionary relationships in generalists is unknown. We assessed pathogen diversity, neutral genome-wide diversity (SNPs) and adaptive MHC class II diversity in a rodent generalist inhabiting three lowland rainforest landscapes with varying anthropogenic disturbance, and determined which MHC alleles co-occurred more frequently with 13 gastrointestinal nematodes, blood trypanosomes, and four viruses. Pathogen-specific selection pressures varied between landscapes. Genome-wide diversity declined with the degree of disturbance, while MHC diversity was only reduced in the most disturbed landscape. Furthermore, pristine forest landscapes had more functional important MHC–pathogen associations when compared to disturbed forests. We show co-evolutionary links between host and pathogens impoverished in human-disturbed landscapes. This underscores that parasite-mediated selection might change even in generalist species following human disturbance which in turn may facilitate host switching and the emergence of zoonoses.Item Investigating the interplay between gaming disorder and functional impairments in professional esports gaming(Universität Ulm, 2024-03-19) Pontes, Halley M.; Rumpf, Hans-Jürgen; Selak, Špela; Montag, ChristianAbstract The relationship between Gaming Disorder (GD) and the experience of functional impairments has received considerable theoretical attention in the recent past and current diagnostic approaches underscore the centrality of functional impairments as a requirement for GD diagnosis. However, there is limited empirical evidence illuminating the interplay between GD and functional impairments, particularly among specific vulnerable groups. The present study seeks to bridge this gap by investigating an English-speaking sample ( N = 5198) comprising an age- and gender-matched group of Professional Gamers (PG, n = 2599) and Non-Professional Gamers (NPG, n = 2599) sub-sampled from a larger sample of 192,260 individuals. The results revealed that PG were at a greater risk for GD compared to NPG as the prevalence rate of GD among PG (3.31%) was significantly higher and almost doubled that of NPG (1.73%), with PG further exhibiting higher overall GD symptom-load and weekly time spent gaming compared to NPG. Furthermore, PG reported experiencing significantly higher frequency of gaming-related functional impairments compared to NPG, with the in particular affected areas for both PG and NPG being ‘ school and/or work ’, ‘ physical health ’, and ‘ family ’, with other key differences emerging in relation to other outcomes. Overall, the present findings show that not only GD symptom-load but also some functional impairment is higher in PG compared to NPG which highlights the need to develop and support prevention and intervention strategies for this at-risk population.Item Insights into psychological characteristics of persons (not) agreeing to use an e-coach-application to reduce elevated Internet Use Disorder tendencies(Universität Ulm, 2024-09-26) Montag, Christian; Elhai, Jon D.; Kannen, Christopher; Bischof, Anja; Brandt, Dominique; Schmidt, Hannah; Rozgonjuk, Dimitri; Rumpf, Hans-JürgenThe present work aims to shed light on the question of whether certain psychological characteristics go along with choosing an e-coach offer to support healthy Internet use when reporting elevated Internet Use Disorder (IUD) tendencies. Data were from a large-scale stepped care approach study to treat persons with varying degrees of IUD tendencies. Recruitment for advertising the download of a smartphone app included social media, videos by influencers, paid ads, TV, radio, newspapers, workshops, and vocational schools. We contrasted a final sample of 184 declining, 907 agreeing, and 216 agreeing but not providing follow-up details needed to use such an e-coach, as well as 995 who did not explicitly decline or agree to participate (but refrained from using the e-coach). Participants were compared on several study variables, including sociodemographics, mental health, fear of missing out, personality, perceived stress, and IUD tendencies. Interestingly, we observed only two significant findings when contrasting the aforementioned groups using ANOVA. First, the group not agreeing to use the e-coach was associated with the lowest IUD tendencies and highest conscientiousness scores. Second, agreeing to use the e-coach was associated with older age. Further significant differences could be observed, but in general the accompanying effect sizes were very mild. In sum, the present study findings support the idea that greater subjective burden of IUD might result in more willingness to seek e-help, but also the personality trait of conscientiousness and a person’s age might play a role here.Item The concerted action of SEPT9 and EPLIN modulates the adhesion and migration of human fibroblasts(Universität Ulm, 2024-05-07) Hecht, Matthias; Alber, Nane; Marhoffer, Pia; Johnsson, Nils; Gronemeyer, ThomasSeptins are cytoskeletal proteins that participate in cell adhesion, migration, and polarity establishment. The septin subunit SEPT9 directly interacts with the single LIM domain of epithelial protein lost in neoplasm (EPLIN), an actin-bundling protein. Using a human SEPT9 KO fibroblast cell line, we show that cell adhesion and migration are regulated by the interplay between both proteins. The low motility of SEPT9-depleted cells could be partly rescued by increased levels of EPLIN. The normal organization of actin-related filopodia and stress fibers was directly dependent on the expression level of SEPT9 and EPLIN. Increased levels of SEPT9 and EPLIN enhanced the size of focal adhesions in cell protrusions, correlating with stabilization of actin bundles. Conversely, decreased levels had the opposite effect. Our work thus establishes the interaction between SEPT9 and EPLIN as an important link between the septin and the actin cytoskeleton, influencing cell adhesion, motility, and migration.Item Predicting life engagement and happiness from gaming motives and primary emotional traits before and during the COVID pandemic: a machine learning approach(Universität Ulm, 2024-06-24) Dagum, Nolan; Pontes, Halley M.; Montag, ChristianAbstract The present study investigated whether life engagement and happiness can be predicted from gaming motives and primary emotional traits. Two machine learning algorithms (random forest model and one-dimensional convolutional neural network) were applied using a dataset from before the COVID-19 pandemic as the training dataset. The algorithms derived were then applied to test if they would be useful in predicting life engagement and happiness from gaming motives and primary emotional systems on a dataset collected during the pandemic. The best prediction values were observed for happiness with ρ = 0.758 with explained variance of R 2 = 0.575 when applying the best performing algorithm derived from the pre-COVID dataset to the COVID dataset. Hence, this shows that the derived algorithm based on the pre-pandemic data set, successfully predicted happiness (and life engagement) from the same set of variables during the pandemic. Overall, this study shows the feasibility of applying machine learning algorithms to predict life engagement and happiness from gaming motives and primary emotional systems. © In Copyright http://rightsstatements.org/vocab/InC/1.0/Item Depressive inclinations mediate the association between personality (neuroticism/conscientiousness) and TikTok Use Disorder tendencies(Universität Ulm, 2024-02-17) Montag, Christian; Markett, SebastianAbstract Background We introduce a novel measure for assessing TikTok overuse, called the TikTok Use Disorder-Questionnaire (TTUD-Q). As part of ongoing investigations into the suitability of the World Health Organization’s (WHO) framework for diagnosing Gaming Disorder in the context of social media overuse, we developed this questionnaire by adapting the WHO framework, replacing the term “gaming” with “TikTok use”. Methods In order to address this question, we investigated the psychometric properties of the newly designed TTUD-Q and assessed its associations with the BFI-10 (assessing the Big Five of Personality) and the PHQ-8 (assessing depressive tendencies). Results In this study, involving a final sample of 378 participants, we observed that higher levels of neuroticism were linked to greater tendencies toward TikTok Use Disorder (TTUD). Furthermore, we identified that this association was mediated by depressive tendencies. Similar trends emerged when investigating the relationship between lower levels of conscientiousness and higher TTUD tendencies, with depressive tendencies once again serving as a mediator. Discussion Our research sets the foundation for future studies that should delve deeper into examining individual differences in TTUD using the WHO framework originally designed for Gaming Disorder.Item A Unified Self-Assessment Framework for Autonomous Driving Stacks Using Subjective Logic(Universität Ulm, 2025-03) Wodtko, Thomas; Griebel, Thomas; Buchholz, Michael; Dietmayer, KlausSelf-assessment plays a critical and important role toward safe and robust autonomous driving. Current self-assessment approaches in this area focus on individual modules at specific positions within the autonomous driving stack. The literature lacks a unifying framework to combine various self-assessment information. Hence, this work provides a comprehensive self-assessment framework for autonomous driving stacks, combining and unifying existing self-assessment methods. For this framework, we propose using subjective logic as an interface to standardize the output of self-assessment modules. This allows the combination of different modules and their use in subsequent processing modules. Our approach can be deployed to existing autonomous vehicle software stacks without imposing any requirements on their functional parts, enabling easy integration. With this framework, we are aiming to contribute to the improvement of safety and reliability in autonomous driving.