OPEN FAU

Online publication system of Friedrich-Alexander-Universität Erlangen-Nürnberg

The online publication system OPEN FAU is the central publication platform for Open Access publishing for all members of Friedrich-Alexander-Universität. Qualified works from research and teaching may be published here free of charge, either as a primary or secondary publication. The full texts are permanently available worldwide and are findable and citable via catalogues and search engines.

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Recent Submissions

Doctoral thesis

Open Access

Luminescent supraparticles with adjustable ID functionality

(2024-06-28) Miller, Franziska

The traceability and authentication of products based on object identification are of great value in our fast-moving, interconnected, and digitized world. The authenticated originality of a product's subcomponents makes it possible to transparently trace value chains and ensure the sustainable manufacture and quality of a product. Thus, object identification used for anticounterfeiting measures can contribute to sustainability. At the same time, object identification enables the traceability of product cycles even after the product has reached the end of its life span. In the context of recycling processes, it is possible to separate materials by their type based on their identification (ID) markers. Apart from this, ID tags are also suitable for involvement in digital transformation. More precisely, machine-readable ID tags enable communication and interaction between machines, which is why they could make a decisive contribution to industrial automation and digitization. However, commercial ID systems such as barcodes, serial numbers, or radio-frequency identification (RFID) chips reach their limits when marking the smallest product components, have relatively low counterfeit resistance, and can only be applied superficially to products. Miniaturized, material-based markers as micron-sized additives, can be flexibly incorporated into a wide variety of materials and applied to even the smallest product components. These machine-readable markers are based on intrinsic, physical properties of the marker material and link physical objects with information stored in a database. As an alternative to conventional marking strategies, they, therefore, offer the opportunity to utilize the full potential of object identification. A variety of such markers are based on optical signals, such as luminescence or reflection. There are several ways in which luminescence-based coding can be implemented. Besides graphical and spatially resolved coding, spectral coding is appealing. In this self-referenced, ratiometric coding strategy, relative emission intensity ratios of spectrally distinguishable signals are detected independent of ID tag orientation or concentration and converted into numerical codes. In this work, it is shown that this ratiometric coding principle can also be realized using supraparticles (SPs) with a precisely adjustable ID signature based on luminescence signals. SPs are hierarchically structured, micron-scaled units composed of individual nanoparticles (NPs). These SPs were produced according to a modular principle using forced assembly via spray-drying. In this flexible process, a wide variety of NPs with different physicochemical properties can be combined to form self-contained units. The resulting SPs not only carry combined features of the NPs but also new functionalities that result from NPs interaction within the hierarchically structured entities. The functionalities of SPs can stem from the structure itself, known as emergence, from the colocation of diverse, functional building blocks, or the coupling of individual particles in close proximity. When luminescent NPs with spectrally distinguishable narrow emission bands are combined into SPs, micron-sized ID-carrying additives are created that can be flexibly integrated into objects for their authentication. In Chapter 3.1, SPs are described that carry such a ratiometric luminescent ID signature in detail. For this purpose, four different types of CaF2 NP were synthesized using a co-precipitation reaction, containing one type of Ln3+ ion each (Ln3+ = Tm3+, Tb3+, Dy3+, and Sm3+, respectively). Upon excitation with shortwave UV light, the synthesized CaF2:Ln3+ NPs exhibited characteristic narrow emission bands in the blue, green, yellow, and red spectral regions. A subsequent thermal treatment led to a significant increase in the NPs' emission intensity, thereby enhancing their luminescence properties. Forced assembly of different types of CaF2:Ln3+ NPs in precisely defined quantitative ratios by spray-drying resulted in SPs possessing spectral ID signatures based on relative emission intensity ratios. The ID-bearing additives carry the combined luminescence properties of their NP subunits as self-contained units due to the earlier-mentioned SP colocalization functionality. A thermal treatment step of the SPs after spray-drying activated characteristic optical properties of the Ln3+-containing NPs by crystallization and diffusion processes. By varying the quantity-weighted ratio of each NP type, the relative emission intensity ratios of the resulting SP and thus its ID signature were precisely adjusted. The flexible process of spray-drying makes it possible to equip these ID-bearing SPs with additional nano-sized building blocks, resulting in further ID functionalities of the SPs. In addition to the colocalization effects, coupling effects, i.e., interactions of the NPs near each other, also come into play here. Hence, SP-based ID labels with multi-layered ID systems result, which are described in more detail in Chapter 3.2 By combining the Ln3+-containing CaF2 NPs with organic fluorophores, hybrid ID SPs with more variable optical properties and thus ID coding variety were formed. The divergent response of the organic and inorganic luminescent NPs to high temperatures plays a pivotal role in this context. As described in Section 3.2.1, SPs were established possessing an initially hidden luminescent ID signature, that could be specifically and deliberately revealed. For this purpose, the code-giving Ln3+-containing CaF2 NPs were assembled in defined quantity ratios in the presence of an intensely luminescent fluorophore utilizing spray-drying. The broad emission band of the fluorophore initially dominated the emission spectrum of the hybrid SPs. Deliberate application of heat resulted in the thermal decomposition of the fluorophore with simultaneous crystallization of the Ln3+-containing CaF2 NPs, which is why the characteristic spectral Ln3+-ID signature was revealed in a thermally induced manner. Moreover, by spatially arranging the ID SPs, which exhibit different luminescence hues due to varying luminescence ID signatures, spatially resolved structures were generated. By combining Ln3+-containing CaF2 NPs with polystyrene (PS) NPs containing fluorophore molecules emitting in the blue, green, and red wavelength regions, dual-encoded SPs could be generated. This work is described in detail in Section 3.2.2 Initially, the hybrid SPs exhibit an ID signature, which is derived from the relative emission intensities of the organic fluorophores. By heat treatment, upon thermal decomposition of the organic SP components, the ID signature resulting from the Ln3+ emission signals was activated and the organic ID signature was irreversibly deactivated. Thus, information can be encoded and selectively retrieved or invalidated at multiple levels. By varying the NP quantity ratios, both ID signatures were precisely varied independently of each other. A variety of interactions of the NPs within the SPs have a significant impact on the optical and morphological properties of the SPs. By varying the SP architecture and composition, interactions between NPs (coupling effects) were explored and specifically utilized to optimize the SP ID functionality. For example, the implementation of a core-shell SP structure and the addition of SiO2 NPs had a beneficial effect on the luminescence and morphological properties of the encoded additives. In Section 3.2.3, the high-temperature stable properties of a Ln3+ containing calcium phosphate (CaP) nanomaterial were exploited for the development of refractory post-mortem ID SPs. They were synthesized according to a Pechini sol-gel synthesis with a subsequent annealing step. Through the addition of magnetic core (iron oxide (IO)) - shell (SiO2) NPs and SiO2 NPs into the Eu3+ and Tb3+ ion containing Pechini sol, and subsequently spray-drying the mixture followed by heat treatment, it became feasible to confer magnetic properties upon ratiometrically encoded SPs. Due to the spatial confinement of the magnetic NPs by their SiO2 shell, their transformation to anti-ferromagnetic hematite is delayed when exposed to heat. Accordingly, these thermostabilized SPs retained their magnetic properties after a fire event. As a result, these hybrid SPs could be magnetically separated from fire residues and purified, thereby enabling luminescent signal detection and thus readout of encoded information. In this project, it was again possible to optimize the properties of the post-mortem ID markers concerning their application by adding SiO2 NPs. Uncontrolled sintering of the SPs among each other to form undefined macroscale bulk materials could be prevented by the addition of SiO2 NPs to the SP system. This phenomenon was also used in the work described in Section 3.2.4 to provide NPs with high-temperature properties without sintering. Usually, high-temperature treatment of crystalline NPs is accompanied by undesirable uncontrollable sintering to macroscopic bulk materials. By combining crystalline NPs with SiO2 NPs in excess to form SPs by spray-drying, it was possible to achieve spatial segregation of crystalline NPs from each other within the particle composite. If these hybrid SPs were subjected to thermal treatment, the crystalline NPs could not sinter together. Subsequent treatment of the SPs with caustic soda led to the dissolution of the SiO2 and recovery of a crystalline nano sol with high-temperature properties. Exemplarily, the emission intensity of Eu3+ containing CaF2 NPs as well as the photocatalytic activity of TiO2 NPs were successfully increased using the described method. The work shows that SPs produced by spray-drying carry combined luminescence properties of the assembled luminophores. However, these optical properties are significantly influenced by the interaction of the different NPs placed near each other. Therefore, the NP arrangement and thus the SP architecture, as well as the quantity ratios of individual nanocomponents, represent parameters that could be tuned to optimize the optical properties of the SPs for their ID functionality. In addition, it was possible to generate SP-based, multilayer ID systems in which encoded information can be specifically modified by the effect of temperature. Due to their sophisticated features, these ID systems are particularly suitable for improving anti-counterfeiting. In general, due to their high-temperature stable ID signal, the ID tags developed herein are also interesting for applications where thermal processes are involved.

Doctoral thesis

Open Access

Neutrophils and Neutrophil Extracellular Traps in Autoimmune, Occlusive and Infectious Diseases

(2024-06-21) Zlatar, Leticija

Neutrophils have traditionally been viewed as simple cells limited to pro-inflammatory functions, which are essentially involved in the innate immune response. Even though their main functions include fighting infectious agents and promoting inflammation, their diverse and specialized roles recently gained more attention. Among others, neutrophils produce neutrophil extracellular traps (NETs), specialized structures composed of decondensed chromatin decorated with cytoplasmic and granular proteins. Their primary function is pathogen immobilization, facilitation of phagocytosis and ultimately, pathogen elimination. However, excessive neutrophil infiltration and activation at the site of injury ultimately precipitates chronic inflammation. An imbalance between NET formation and degradation is at the root of various pathologies. To address this issue, various treatment strategies to combat excessive NET activity are currently under development. Yet, the list of neutrophil- and NET-driven pathologies is continuously expanding, and the mechanisms behind many remain elusive. This thesis discusses our recent work on the role of neutrophils and NETs in autoimmune (rheumatoid arthritis, RA), occlusive (dacryolithiasis) and infectious diseases (tuberculosis, TBC). First, we discuss how a diet rich in salt contributes to arthritis exacerbation, by modulating neutrophils and their effector functions. We investigated the effect of sodium on neutrophils, and detected (I) elevated ROS levels in vitro, (II) arthritis exacerbation in vivo, and (III) increased in vitro activity of bone-resorbing osteoclasts upon the addition of ROS. These data indicate that under high salt conditions, ROS produced by the infiltrating neutrophils promotes bone erosion in RA. Further, we propose the role of neutrophils and NETs within the existing model of gradual formation and growth of mucopeptide concretions in the lacrimal sac, in a process termed dacryolithiasis. Neutrophils contribute to the initial, and NETs to the later stages of this process, the latter presumably by maintaining the pro-inflammatory environment and preventing efficient clearance. Lastly, we report increased neutrophil activation and circulatory NET formation in patients with TBC. Importantly, excessive amounts of NET degradation products can be detected in TBC patients with extensive tissue damage, and in patients with relapse, making NETs parameters discriminatory biomarkers. Further, caseating granulomas in TBC and other granulomatous diseases contain tissue-resident NETs, together with Z-form DNA, resistant to degradation by nucleases. Pulmonary vessels in TBC are occluded with neutrophil aggregates. Taken together, these findings highlight the dual role of neutrophils and NETs in the pathology of various diseases.

Doctoral thesis

Open Access

Usability-Aspekte und klinisch-translationaler Nutzen sensorbasierter Gangparameter aus dem Homemonitoring

(2024) Reichhardt, Theresa Marie

Background and objective The digitalization of medicine and the abundant availability of wearable inertial sensors enables recording of body-related health data such as activity and movement in the home environment, usually referred to as homemonitoring. Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Due to chronic progression of motor symptoms “wearables” (portable end devices with integrated inertial sensors) may be particularly appropriate for objectively assessing impairment in movement patterns like gait along the disease course. This thesis aimed to evaluate adherence and usability of a sensor-based gait analysis system in homemonitoring in PD patients and to define clinical-translational target parameters. Methods The gait analysis system consists of two inertial sensors (accelerometers and gyroscopes) attached to the patients' shoes. The physical raw data from the shoe sensors were converted into metric gait parameters (mean + coefficient of variation (CV) of stride length, maximum toe clearance and gait velocity) using established algorithms. Gait parameters were used for statistical analysis. 20 PD patients were included in this retrospective cohort analysis. These underwent a two-week homemonitoring phase flanked by two clinical visits, including sensor-based gait analysis (@lab measurement) and comprehensive clinical and questionnaire-based assessment (LED, H&Y, UPDRS-III, PIGD, TUG, 2-minute-walk test, SUS). During homemonitoring the patients were required to wear the gait analysis system throughout the day (at least eight hours per day) and to perform standardized gait tests three times a day (@home measurement). In @lab and @home measurements a 4x10m test was performed as a standardized gait test in three speeds (preferred, fast, slow). The preferred speed was the basis for the statistical analysis of this thesis. Results After excluding two patients (individual problems, data loss) complete data sets were available from N=18 patients. A total of 601 gait tests in preferred speed have been recorded in homemonitoring. At 16,7 ± 2,8 days in homemonitoring gait tests were performed on 12,8 ± 1,3 days resulting in a daily adherence of 78,3 ± 13,1%. Test adherence, i.e. the proportion of gait tests actually performed in relation to expected tests, was 87,7 ± 13,5%. The System Usability Scale (SUS) achieved a score of 70.56 ± 14.83. The comparison of @lab and @home measurements revealed significant differences in all gait parameters that were analyzed. The correlations of clinical assessment to @lab and @home parameters showed significant correlations with comparable or stronger correlations found for @home parameters. For severity of illness (H&Y) and severity of motor symptoms (UPDRS-III) @home parameters showed significantly stronger correlations with CV of stride length than @lab parameters. Moreover, in @home measurements H&Y and UPDRS-III correlated significantly to CV of gait speed, while in @lab measurements no significant correlations were found. The PIGD subscore of UPDRS-III as a clinical measure of postural instability and gait difficulty correlated significantly to the following @home parameters: mean stride length, CV of stride length and CV of gait velocity. In @lab parameters only a correlation of PIGD to CV of stride length could be found. Conclusion Home-based adherence of the sensor system is comparable to current studies. There is good acceptance of the system as measured by SUS. Gait parameters @home compared to @lab reveal a slower, more small-stepped and shuffling gait pattern in the unsupervised @home setting with stronger correlations to clinically assessed motor impairment (H&Y, PIGD, UPDRS-III). The reason for this could be environment-, examiner- or cognition-dependent. Nevertheless, the fact that variability of gait parameters measured in homemonitoring correlate more strongly with certain motor impairments and the disease stage speaks for an additional benefit of homemonitoring compared to isolated measurement within the clinic.

Doctoral thesis

Open Access

Fostering Pre-Service Teacher Reflection through AI-Based Feedback: From Understanding AI Acceptance to Developing Effective AI-Driven Feedback

(2024) Zhang, Chengming

Learning from experiences is crucial for pre-service teacher to become professional teacher. As a bridge between theory and practice, reflection contributes to their professional development. However, reflection often requires exploring much tacit knowledge, which needs guidance from professionals. Indeed, many pre-service teachers do not receive adequate support due to lack of time for teacher educators and large student populations. Recently, advancements in artificial intelligence (AI) have led to the development of automated feedback systems. These systems provide prompt and relevant feedback to pre-service teachers, enhancing opportunities for professional development. In the context of digital reform, this dissertation aims to explore the role of AI in fostering pre-service teacher reflection. It seeks to investigate the acceptance of AI within teacher education, enhance deep understanding of reflective writing, and develop suitable AI-driven feedback mechanisms. More specifically, the research objectives are threefold: (i) to investigate pre-service teachers’ AI acceptance and to determine whether gender plays a moderating role; (ii) to assess the quality of reflective writing and explore its vital predictive indicators; (iii) to develop an AI feedback system specifically designed to enhance the quality of pre-service teachers’ reflection. Through these objectives, the research seeks to provide innovative technological support for the professional development of pre-service teachers. Employing a diverse array of research methods and incorporating multiple data types, this thesis systematically synthesizes and presents the findings from three publications. The results are structured to highlight the contributions of each study, providing a overview of the research outcomes. In the discussion section, I delve into the factors influencing AI acceptance and examine how gender moderates this process. Additionally, I also discuss the transparency and explainability of AI feedback algorithms. Based on these discussions, this thesis proposes a series of recommendations for improving future educational research.

Doctoral thesis

Open Access

High-fat diet promotes a systemic Il-17 immune response and exacerbates psoriasis-like murine dermatitis

(2024-05-26) Eriksson, Daniel

Obesity has been found to be increasing significantly during the last decades all over the world. Although obesity is known to be associated with several debilitating conditions such as diabetes and heart disease, the role of obesity in autoimmune disease remains to be fully characterized. Furthermore, although closely related with obesity, the role of diet and the intestinal microbiome in autoimmune diseases is of rising interest. This work aimed at elucidating the relationship between obesity, diet and the intestinal microbiome in the autoimmune disease psoriasis. In order to do this, the diet induced obesity model was used and mice were fed a high-fat diet over several weeks. Psoriasis like murine dermatitis was then induced in these mice by topical treatment with imiquimod on the ear for 3 days. Furthermore, the impact of the intestinal microbiome was investigated by depleting the microbiome with vancomycin in mice fed either a high-fat or a normal diet followed by treating them with imiquimod. It was found that high-fat diet feeding resulted in an increase in body weight and the high-fat diet fed mice were found to have an increased ear and skin thickness following imiquimod treatment. Increased levels of T-cells and granulocytes as well as increased mRNA levels of Il17 were also found in the ears of imiquimod treated mice fed a high-fat diet. This effect was found to be associated with dietary fat, but not carbohydrate or protein. Furthermore, high-fat diet feeding was found to promote the development of psoriasis like murine dermatitis through an intestinal microbiome mediated mechanism. Mechanistically, dietary fat induced a systemic inflammation characterized by increased levels of systemic IL-17. The most significant source of this systemic inflammation was attributed to IL-17 production by splenic pools of IL-17 producing lymphocytes, specifically γδ T-cells, as well as αβ T- cells in the mesenteric lymph node. It was found that high-fat diet feeding alone, without topical treatment with imiquimod, was sufficient to induce the production of IL-17 by the γδ T-cells in the spleen as well as mild signs of dermatitis. Also, it was found that treatment with vancomycin, an antibiotic which has very low oral bioavailability, rescues the high-fat diet induced psoriasis like murine dermatitis, however stool transfer from high-fat diet to regular diet fed mice was insufficient in order to aggravate the dermatitis. Furthermore, 6observations were made that high-fat diet induces a deficiency in the intestinal glycocalyx matrix but not intestinal permeability or intestinal inflammatory cytokine production. Lastly it was found that supplementation with Akkermansia muciniphila was able to ameliorate the high- fat diet induced psoriasis like murine dermatitis. In conclusion significant amounts of dietary fat results in systemic inflammation and this effect is attributed to defects in the intestinal barrier.