Einfluss einer einjährigen primärpräventiven Maßnahme auf das Ernährungs- und Bewegungsverhalten bei Haupt- und Förderschülern des 10. - 13. Lebensjahres

Ziel: Prävention von Übergewicht bei Kindern mit Risikoprofil (schwacher Sozialerstatus, elterlicher Migrationshintergrund) durch Beeinflussung des Wissens & Verhaltens sowie der Entwicklung gesundheitsrelevanter Parameter. Methode: Fünftägige Impulswoche + zwölf konsekutiven Auffrischungskontakten. Datenerhebung (T1, T6 und T12) mittels Fragebogen + Messung gesundheitsrelevanter Parameter. Ergebnisse: 192 Kinder (IG: 101, KG: 91). Übergewichtsrate: nach deutschen BMI-Perzentilwerten IG: 34,1%, KG: 42,0%, länderspezifisch IG: 37,8% KG: 41,9%. Diese konnten nicht signifikant beeinflusst werden. Bei den Jungen der IG kam es zu einer temporär signifikanten Reduktion des Körperfettanteils (1,5 kg). Das Bewegungsverhalten wurde positiv beeinflusst. Folgerung: Das Präventionsprogramm stellt für die Wissensverbesserung einen guten Ansatz dar, für eine dauerhaft positive Beeinflussung des Verhaltens & der gesundheitsrelevanten Daten der Probanden scheint eine Intensivere Intervention nötig

Molecular Insight Into the IRE1α-Mediated Type I Interferon Response Induced by Proteasome Impairment in Myeloid Cells of the Brain

Proteostasis is critical for cells to maintain the balance between protein synthesis, quality control, and degradation. This is particularly important for myeloid cells of the central nervous system as their immunological function relies on proper intracellular protein turnover by the ubiquitin-proteasome system. Accordingly, disruption of proteasome activity due to, e.g., loss-of-function mutations within genes encoding proteasome subunits, results in systemic autoinflammation. On the molecular level, pharmacological inhibition of proteasome results in endoplasmic reticulum (ER) stress-activated unfolded protein response (UPR) as well as an induction of type I interferons (IFN). Nevertheless, our understanding as to whether and to which extent UPR signaling regulates type I IFN response is limited. To address this issue, we have tested the effects of proteasome dysfunction upon treatment with proteasome inhibitors in primary murine microglia and microglia-like cell line BV-2. Our data show that proteasome impairment by bortezomib is a stimulus that activates all three intracellular ER-stress transducers activation transcription factor 6, protein kinase R-like endoplasmic reticulum kinase and inositol-requiring protein 1 alpha (IRE1α), causing a full activation of the UPR. We further demonstrate that impaired proteasome activity in microglia cells triggers an induction of IFNβ1 in an IRE1-dependent manner. An inhibition of the IRE1 endoribonuclease activity significantly attenuates TANK-binding kinase 1-mediated activation of type I IFN. Moreover, interfering with TANK-binding kinase 1 activity also compromised the expression of C/EBP homologous protein 10, thereby emphasizing a multilayered interplay between UPR and type IFN response pathway. Interestingly, the induced protein kinase R-like endoplasmic reticulum kinase-activation transcription factor 4-C/EBP homologous protein 10 and IRE1-X-box-binding protein 1 axes caused a significant upregulation of proinflammatory cytokine interleukin 6 expression that exacerbates STAT1/STAT3 signaling in cells with dysfunctional proteasomes. Altogether, these findings indicate that proteasome impairment disrupts ER homeostasis and triggers a complex interchange between ER-stress sensors and type I IFN signaling, thus inducing in myeloid cells a state of chronic inflammation

Lehrentwicklung als organisationaler Veränderungsprozess

Ausgehend von aktuellen Empfehlungen und Förderprogrammen zur Weiterentwicklung der Lehre, die auf das Zusammenwirken individueller und institutioneller Initiativen abheben, widmet sich der Beitrag Veränderungsprozessen in der Organisation Hochschule. Lehrentwicklung wird dazu als inkrementeller Innovationsprozess gerahmt, der auf unterschiedlichen Ebenen der Organisation ansetzen kann und im Zusammenhang mit externen Steuerungsimpulsen zu betrachten ist. Die Untersuchung exemplarischer Entwicklungsvorhaben beleuchtet dies näher anhand der involvierten Akteur*innen und der verfolgten Handlungsansätze, um Implikationen für die zukünftige Erforschung und Förderung von Lehrentwicklung abzuleiten

Evaluation of the performance of self-healing concrete at small and large scale under laboratory conditions

HEALCON is an EU-FP7 project which aims to develop self-healing concrete to create durable and sustainable concrete structures. While during the first years of the project the self-healing materials (including the healing agents and suitable encapsulation methodologies) and monitoring techniques were designed and tested at lab-scale, large scale elements have been tested near the end of the project to verify the feasibility and efficiency of the self-healing concrete under conditions closer to reality. For this paper, two types of healing agents were investigated for use in mortar and concrete. The first type of healing agent studied was a coated superabsorbent polymer (C-SAP). It is known that the autogenous healing capacity is increased by incorporation of superabsorbent polymers (SAPs) in mortar/concrete. The agents present in the crack can absorb intruding water, swell and block the crack, leading to immediate sealing, but can also exude moisture to the surrounding concrete environment stimulating healing of the concrete by hydration of unreacted cement particles or by CaCO3 precipitation. The disadvantage of these SAPs in the fresh mortar/concrete mix is however that they absorb large quantities of mixing water, leading to unwanted effects (e.g. loss of workability and macro-pore formation). By coating of the SAPs, we want to eliminate this disadvantage. The fluid bed spraying of the different layers was applied by VTT. A second healing agent studied, is a biogenic healing agent, namely a Mixed Ureolytic Culture (MUC). This type of healing agent was developed by Avecom in order to reduce the cost associated with the production of pure bacterial strains. This mixed ureolytic culture is moreover self-protecting and does not need any further encapsulation. At first, the performance of the healing agents itself was evaluated. For the coated SAPs, the swelling performance and swelling rate were determined, showing that the coating can limit the uptake of water during the first 10-15 minutes. For the MUC, the ureolytic and CaCO3 precipitating capacity was determined, immediately after production of the MUC and after 3 months of storage. The results show the potential of these mixed cultures to be used as self-healing agent in mortar/concrete, but also show a decrease of their effectiveness with time. Subsequently, the healing agents were incorporated in mortar mixes at UGent. A dosage of 1 wt% relative to the cement content caused a large reduction of the mechanical properties of the mortar (up to ~ 50%), except for the coated SAP. The sealing efficiency was evaluated with the water flow test, as designed by one of the project partners in HEALCON. The performance of reference mixes was compared to that of self-healing mixes with SAP, coated SAP or MUC (+ urea). Results showed that for cracks with a width less than 0.150 mm, all mortars were sealed (almost) completely after storage for 28 days in wet-dry environment (12 h wet – 12 h dry) after crack creation. For cracks with a larger width, differences were noticed between the different specimens. Moreover, also the immediate sealing effect induced by the presence of SAPs could be noticed. It has to be noted however that the crack width plays an important role but is varying along the crack length (within a specimen) and between specimens, making the analysis more difficult. In order to extend the application to concrete, self-healing and reference reinforced concrete beams (2500 x 400 x 200 mm) were produced at the Danish Technological Institute. The self-healing concretes contained coated SAPs or MUC. Moreover, the beams were equipped with corrosion sensors that are connected to a wireless monitoring system, developed by the Technology-Transfer- Initiative at the University of Stuttgart. The multi reference electrodes (MuRE) were installed alongside the reinforcements and measure the corrosion potential at certain positions. Data is collected in sufficiently dense intervals by battery powered nodes that transmit the data wirelessly to a base station and further on to a database where it can be accessed through a web based application for data analysis over the internet. At the age of 28 days, three-point bending cracks up to 0.6 mm were created in the beams. Subsequently, the beams were regularly sprayed with water (four times one hour per day) for 6 weeks and afterwards, the beams were, once a week, exposed to 3 wt% NaCl solution for 24 h. Evaluation of the self-healing performance by microscopic analysis (crack microscopy and analysis of thin sections) showed that for the reference beam and beam with MUC no significant healing could be noticed (probably because of insufficient supply of nutrients for the bacteria). For the beams with coated SAPs, the smaller cracks (0.1 and 0.2 mm) were partly closed. Continuous corrosion monitoring showed corrosion in the reference and MUC beams already after the first exposure to NaCl solution. Onset of corrosion was delayed in the case the beams contained coated SAPs

Exposure to Melan-A/MART-126-35 tumor epitope specific CD8+T cells reveals immune escape by affecting the ubiquitin-proteasome system (UPS)

Efficient processing of target antigens by the ubiquitin-proteasome-system (UPS) is essential for treatment of cancers by T cell therapies. However, immune escape due to altered expression of IFN-γ-inducible components of the antigen presentation machinery and consequent inefficient processing of HLA- dependent tumor epitopes can be one important reason for failure of such therapies. Here, we show that short-term co-culture of Melan-A/MART-1 tumor antigen-expressing melanoma cells with Melan-A/MART-126-35-specific cytotoxic T lymphocytes (CTL) led to resistance against CTL-induced lysis because of impaired Melan-A/MART-126-35 epitope processing. Interestingly, deregulation of p97/VCP expression, which is an IFN-γ-independent component of the UPS and part of the ER-dependent protein degradation pathway (ERAD), was found to be essentially involved in the observed immune escape. In support, our data demonstrate that re-expression of p97/VCP in Melan-A/MART-126-35 CTL-resistant melanoma cells completely restored immune recognition by Melan-A/MART-126-35 CTL. In conclusion, our experiments show that impaired expression of IFN-γ-independent components of the UPS can exert rapid immune evasion of tumor cells and suggest that tumor antigens processed by distinct UPS degradation pathways should be simultaneously targeted in T cell therapies to restrict the likelihood of immune evasion due to impaired antigen processing

Thermodiffusion in liquid alloys measured by X-ray radiography

Thermodiffusion (or Soret effect) describes the formation of a concentration gradient induced by a temperature gradient in binary or multicomponent mixtures. This cross-coupling effect of heat and mass transfer influences the homogeneity of doped semiconductors and grown crystals as well as the microstructure formation in alloys. The calculation of thermodiffusion by molecular dynamic simulation can be very sensitive to the specific potential. Recently improved theories were proposed but the database to validate models for thermodiffusion in liquid alloys is scarce. For several organic mixtures the Soret coefficients have been measured with high accuracy. However, for liquid alloys only very few Soret coefficients are known due to experimental challenges at the required high temperatures. We use X-radiography in combination with a high temperature furnace for space- and time-resolved measurements of the concentration distribution in the sample. This offers increased process control and makes the simultaneous measurement of interdiffusion possible. We present measurements of the Soret coefficient in aluminium-rich Al-Ag alloys at different concentrations. This alloy was chosen because of the high contrast between the two components in the X-ray spectrum used and because interdiffusion coefficients are known from independent measurements. The obtained interdiffusion coefficient are compared to literature values on the same system which corroborates the measured Soret coefficients. Silver is observed to migrate to the cold side

Measurement of the Soret coefficient in liquid Al-Ag alloys using X-ray radiography

Thermodiffusion, also called Soret effect, is the separation of the components of a mixture toward the hot/cold regions in a nonuniform temperature distribution. The effect is observed to influence a wide range of systems, from ocean water over magma and crystal growth to stellar plasma. For several organic mixtures the Soret coefficients have been measured with high accuracy. However, for liquid alloys only very few Soret coefficients are known, the reasons being the experimental challenges at the required high temperatures, such as convection, and difficulties of direct analysis. We present our work on determining the Soret coefficient of liquid aluminium-silver in a concentration range of 20 to 55 at.% Ag, using X-ray radiography (XRR). Silver is observed to migrate to the cold side. Thanks to the in-situ measurements with XRR, the transient concentration separation can also be analysed, which makes determination of the inter-diffusion coefficient possible. This inter-diffusion coefficient is then compared to literature values on the same system, corroborating the measured Soret coefficient

Immunogenic cell death triggered by impaired deubiquitination in multiple myeloma relies on dysregulated type I interferon signaling

Introduction Proteasome inhibition is first line therapy in multiple myeloma (MM). The immunological potential of cell death triggered by defects of the ubiquitin-proteasome system (UPS) and subsequent perturbations of protein homeostasis is, however, less well defined. Methods In this paper, we applied the protein homeostasis disruptors bortezomib (BTZ), ONX0914, RA190 and PR619 to various MM cell lines and primary patient samples to investigate their ability to induce immunogenic cell death (ICD). Results Our data show that while BTZ treatment triggers sterile type I interferon (IFN) responses, exposure of the cells to ONX0914 or RA190 was mostly immunologically silent. Interestingly, inhibition of protein de-ubiquitination by PR619 was associated with the acquisition of a strong type I IFN gene signature which relied on key components of the unfolded protein and integrated stress responses including inositol-requiring enzyme 1 (IRE1), protein kinase R (PKR) and general control nonderepressible 2 (GCN2). The immunological relevance of blocking de-ubiquitination in MM was further reflected by the ability of PR619-induced apoptotic cells to facilitate dendritic cell (DC) maturation via type I IFN-dependent mechanisms. Conclusion Altogether, our findings identify de-ubiquitination inhibition as a promising strategy for inducing ICD of MM to expand current available treatments