A Gaia-X-based Ecosystem for Manufacturing: Lessons Learned from the Project Gaia-X4ICM

Digitalization is the most important driver of innovation and a strategic goal throughout the manufacturing industry. In the context of Industry 4.0, many ideas, concepts, and visions have been developed to make production technology more efficient, flexible, precise, and sustainable through digital added value. Various research activities, such as innovative value streams, product tracing, and carbon footprinting, require an increased level of data exchange and digital service usage. Ecosystems like Gaia-X are seen as key enablers to address these challenges and foster value co-creation between participants. Although great progress has already been made, the current status of Gaia-X falls short of the potential of ecosystems due to a lack of actual implementations and related experiences. The aim of the project Gaia-X4ICM was to establish the idea of digital ecosystems for manufacturing, to enable the coupling with production systems, and thus to create the basis for a strong scaling innovation platform for the ICM and beyond for research and industry. Research groups and institutes from the University of Stuttgart (ISW, IFSW, HLRS) and the Karlsruhe Institute of Technology (wbk, AIFB, SCC) have formed an interdisciplinary cooperation to achieve these goals. This manuscript summarizes key lessons learned and research findings of applying the principles of Gaia-X-based ecosystems to manufacturing industries

Validation of the OECD reproduction test guideline with the New Zealand mudsnail Potamopyrgus antipodarum using trenbolone and prochloraz

The Organisation for Economic Cooperation and Development (OECD) provides several standard test methods for the environmental hazard assessment of chemicals, mainly based on primary producers, arthropods, and fish. In April 2016, two new test guidelines with two mollusc species representing different reproductive strategies were approved by OECD member countries. One test guideline describes a 28-day reproduction test with the parthenogenetic New Zealand mudsnail Potamopyrgus antipodarum. The main endpoint of the test is reproduction, reflected by the embryo number in the brood pouch per female. The development of a new OECD test guideline involves several phases including inter-laboratory validation studies to demonstrate the robustness of the proposed test design and the reproducibility of the test results. Therefore, a ring test of the reproduction test with P. antipodarum was conducted including eight laboratories with the test substances trenbolone and prochloraz and results are presented here. Most laboratories could meet test validity criteria, thus demonstrating the robustness of the proposed test protocol. Trenbolone did not have an effect on the reproduction of the snails at the tested concentration range (nominal: 10-1000 ng/L). For prochloraz, laboratories produced similar EC10 and NOEC values, showing the inter-laboratory reproducibility of results. The average EC10 and NOEC values for reproduction (with coefficient of variation) were 26.2 µg/L (61.7%) and 29.7 µg/L (32.9%), respectively. This ring test shows that the mudsnail reproduction test is a well-suited tool for use in the chronic aquatic hazard and risk assessment of chemicals

Wirkmuster hormonaktiver Substanzen im Zebrabärbling (Danio rerio) : neue methodische Bewertungsansätze unter Berücksichtigung unterschiedlicher Belastungsszenarien

The examination and identification of hormone active substances has great economical and also political relevance. Chemicals, plant protection products and biocides identified as so-called endocrinedisruptors (ED) are produced in great amounts and released to the environment. Following EU authorization processes they are handled under hazard based assessment. Moreover, pharmaceutical hormones for human or veterinary use can interact directly with the hormone system at very low concentrations. By wastewater and surface run-off the ED substances can enter the aquatic environment and thus can be a threat for fish populations. The aim of this work was to examine different biological parameters characterizing an endocrine active impact on the sexual endocrine system of zebrafish following an exposure to ED substances. The first part of this thesis aimed to analyse the sensitivity of indicative parameters, i.e. biomarkers, with focus on receptor mediated and enzyme modulated mechanisms. Effect concentrations of both indicative and population relevant endpoints derived from short term and long term studies, respectively, were compared. The data obtained was used to close data gaps for less studied endocrine modes of action. In a next step, the use of these results within a tiered testing approach to identify hormone active substances in fish was discussed. The results were considered within a proposal for a new testing guideline within the OECD framework to analyse the endocrine impacts in an extended one generation reproduction test using zebrafish(Danio rerio) as test species. The proposed test design considers an existing test protocol with Japanese medaka (Oryzias latipes) and is intended to be placed in the OECD guideline developing program. The aim of the second part of this thesis was to assess the effect of a pulsed exposure to an EDsubstance. An important aspect of endocrine modes of action can be the distance between exposure to an ED substance and the final manifestation of an effect. Two fish life cycle tests were performed. A first study under continuous exposure aimed to get information on the intrinsic toxicity while in a second study a static approach was performed to deliver information on effects after a very short (pulsed) exposure. By comparison of continuous and pulsed application, exposure related effect thresholds and sensitive windows of exposure were identified. Based on the studies described in this thesis, but furthermore using historical data from Fraunhofer IME and literature data, the most relevant and sensitive windows of exposure and effect manifestation were identified and ranked according to their population relevance. The effect concentrations obtained for the lipoprotein vitellogenin and the sex steroide 11-ketotestosterone in blood plasma were in good compliance with effect levels derived for population relevant parameters. Within a tiered testing approach to identify an impact of endocrine active compounds in fish, the significance and value of biomarker responses could be confirmed. Apical endpoints were identified considering their relevance for fish populations. These are life stage specific survival rates, generation time, reproduction capacity and finally sex ratio. Considering the time until an effect becomes evident after a pulsed exposure to an ED compound, the parameters could moreover be ranked. Life stage specific mortalities can occur already shortly after a single exposure pulse. Sub-lethal effects can become evident in a delay of growth. If this delay is lasting it will finally prolong the time until maturation and can delay the total generation time. More sustainable are impacts on reproduction capacity as survival of population essentially depends on it. If the exposure results in an alteration and significant shift of sex ratio in a fish group, the final impact is irreversible and means most and sustainable adverse consequences for the affected fish population. To find an appropriate test strategy for identification of an ED substance affective to fish populations, it has to be considered that depending on the mode of action there can be a gap between the sensitive time period where exposure occurs and the time point an effect becomes evident. For most of the modes of action assessed, an exposure of the sexual development induced effects with relevance for fish population. This refers to Estrogen receptor (ER) –agonists and –antagonists, to Androgen receptor (AR) –agonists and finally to Aromatase inhibitors. For AR –antagonists and inhibitors of the basic steroid synthesis, not enough data was available to identify the sensitive exposure window. Effects with population relevance were found in terms of a reduction of reproduction capability (ER -agonists and –antagonists, AR-antagonists, Inhibitors of basic steroid synthesis), or became evidentby a shift in sex ratio (ER –antagonists, AR –agonists and aromatase inhibitors). A delay in development in terms of reduced growth and a delay of the time to first spawning were observed for ER –agonists. The indicative parameters vitellogenin and 11-keto testosterone showed corresponding sensitivity compared to the affected sensitive population relevant endpoints for most of the mode of actions assessed. However, for AR –agonists the vitellogenin response was less sensitive by several concentration steps, i.e. one order of magnitude, compared to the most sensitive apical endpoint. For the AR -Antagonist, the steroide 11-keto testosterone was more sensitive than vitellogenin. To find an appropriate definite test to identify an ED substance with impact on fish populations, the sensitivity of the different parameters has to be considered. Fish life cycle tests (FLCT) are able to record all population relevant and indicative parameters. However, these studies are cost and time consuming. If the available data pool already allows to derive information on endpoint sensitivity for a test substance, the test strategy can be adapted. If it can be expected that e.g. sex ratio will be affected, a more focussed test can be sufficient, e.g. a fish sexual development test (FSDT).For the future assessment of hazard or risk of ED substances to the environment it will be necessary to derive mechanistic data to find explanation for the effect observed. Beside the well known and described ED modes of action (i.e. enzyme and receptor interactions), the challenge will be to interpret the recorded effects for new substance classes as there are often related to different steps of steroid synthestis. Tailored test methods have to be developed and has to be integrated in the current assessment strategies for EDs

Electrocortical responses in anticipation of avoidable and inevitable high and low intensity stimulation

Similiar to the studies by Rösler & Gamer (2019) and Merscher et al. (2022), participants will observe naturalistic images on a PC screen while electrocortical activity, heart rate, skin conductance, and eye movements are recorded. In addition, we want to assess breathing depth and frequency to test for possible effects on the findings of heart rate deceleration. The naturalistic stimuli consist of 160 different images selected to be affectively neutral, depict naturalistic scenes, contain no particularly salient features, and be relatively uniform and symmetrical. The color and form of the cue preceding each trial will be indicative of the trial type: participants will be instructed to expect either an avoidable or inevitable stimulation after the disappearance of the naturalistic picture. The color of the cue will inform participants about the intensity of the electrical stimulation with the high-intensity stimulation being painful but tolerable and the low-intensity stimulation being much less painful or even non-painful. The shape of the symbol will be indicative of whether the trial is active or passive: in the avoidable shock trials, the stimulus can be evaded by quickly hitting the space bar upon stimulus offset

You don’t see what I see: The effect of gaze camouflage and social anxiety on social attention in naturalistic situations

Research question: To what extent does trait social anxiety and the use of shaded versus clear eye-tracking glasses influence gaze behavior and physiological responses in natural situations? Methodological Approach: To cover a wide spectrum of trait social anxiety, potential study participants previously complete a screening questionnaire that assesses the presence and severity of DSM-5 criteria for social anxiety disorder. In the study, participants are instructed to take an approximately 30-minute walk. No specific route is given. During the walk, gaze behavior, physiological responses (heart rate and electrodermal activity), and the chosen route are recorded. Participants will receive a mobile eye tracker with shaded or clear lenses with the members of the two groups matched for gender and social anxiety. By doing so we aim to investigate the influence of social desirability on natural gaze behavior. After the walk, participants are asked to wait briefly in the study room with a confederate allegedly being another participant filling out questionnaires. The presence of another person allows the measurement of attentional processes during a natural interaction with a stranger. After a brief waiting period, the confederate initiates a short, scripted interaction with the participant. Afterward, the participants are again asked to complete the screening questionnaire as well as some further questionnaires on social anxiety, autism spectrum traits, and social competence (SPAI, SIAS, AQ-K, ISK-K). To ensure that the participants' behavior occurs spontaneously and intuitively, rather than being controlled top-down, they are told that the eye tracker is used to record pupillary responses and the sports watch is used to measure pulse. In addition, participants are not informed in advance that the waiting situation is also a situation of interest for the current study. Subsequently, all participants will be fully informed about the manipulation, the relevant dependent variables, and the necessity of the experimental procedure. They can then again object to anonymized use and analysis of the data and request their immediate and complete deletion

The effect of gaze camouflage and social anxiety on social attention in naturalistic situations

This study investigated how trait social anxiety and gaze camouflage influence gaze behavior, place preference, and autonomic responses (heart rate and skin conductance) using a naturalistic field-like experimental design

The influence of social anxiety and visual exploration on threat responding and generalization

Fear generalization has been identified as an important mechanism that might contribute to the etiology and maintenance of anxiety disorders. It is, however, yet unclear to what degree attentional processes contribute to overgeneralization of fear in clinical samples. To address this issue, we utilized a set of facial photographs that was meticulously created such that pairs of faces could either be distinguished by looking into the eyes or the region around mouth and nose, respectively. These pairs were then employed as CS+ and CS− in a differential fear conditioning paradigm followed by a generalization test with morphs in steps of 20%, creating a continuum between CS+ and CS−. In a sample with diverse levels of social anxiety (N = 87), we demonstrated that the amount of fear generalization depends on attentional orienting towards diagnostic facial features. While social anxiety did not affect the shape of generalization gradients, we observed elevated threat ratings, altered visual exploration patterns, and a distinct multi-phasic heart rate modulation in participants with higher social anxiety. In summary, fear generalization depends on attentional deployment. Future work should build on these findings to further explore these processes in clinical populations

How and when social anxiety manifests: A meta-analysis investigating the effects of social anxiety on subjective distress, autonomic and endocrine measures, and visual attention in different experimental settings

This meta-analysis explored whether the effects of social anxiety on subjective, autonomic and endocrine responses as well as visual attention differ according to the characteristics of the experimental setting. We specifically focused on the degree of social interaction, the aversiveness of the stressor, the naturalism of the situation, and the experimental phase (i.e., anticipation, reactivity, and recovery)

How and when social anxiety manifests: A meta-analysis investigating the effects of social anxiety on subjective distress, autonomic and endocrine measures, and visual attention in different experimental settings

This meta-analysis explored whether the effects of social anxiety on subjective, autonomic and endocrine responses as well as visual attention differ according to the characteristics of the experimental setting. We specifically focused on the degree of social interaction, the aversiveness of the stressor, the naturalism of the situation, and the experimental phase (i.e., anticipation, reactivity, and recovery)