102 research outputs found

    Data archive for exploring pedestrian dynamics and its application in dimensioning of facilities for multidirectional streams

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    In this paper an overview of an open data archive with data from experiments investigating pedestrian dynamics is presented. As an example of the use of this data the analysis of recently published data about the capacity of crossings is shown

    Die entzĂŒndungshemmenden und antiviralen Effekte der induzierbaren HĂ€moxygenase-1 in der Leber bei der Maus

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    Since the prevalence of immune-mediated liver injury like HBV infection plays an important role in infectious diseases wordwide and the induction of the cytoprotective protein HO-1 has been shown to be beneficial in terms of ischemia/reperfusion injury during liver transplantation [Amersi F. et al., 1999], this study systematically elucidates the influence of inducible HO-1 in experimental models of immune-mediated and HBV related liver damage. In the first part of this work, the role of HO-1 on apoptotic liver damage by intravenous administration of anti-CD95 Ab in mice was examined. CoPP induces HO-1 mRNA as well as protein in liver tissue (KCs and hepatocytes) in a time-dependend manner. HO-1 induction protects mice and prolongs survival in apoptotic liver damage by reduction of caspase-3 activity. HO-1 overexpression was also achieved by adenoviral gene transfer. The protective effect after adenoviral gene transfer was abolished by SnPP, which is an HO specific inhibitor. Further on, the experiments demonstrated the relevance of HO-1 induction in hepatocytes for protection in apoptotic liver damage, since depletion of KCs did not abolish the protective effect. CO, as a product of heme degradation by induced HO-1, but neither BV nor ferritin mediates protection from apoptotic liver damage. In a second part of this study, the effect of inducible HO-1 on an in vivo model of immune-mediated liver injury was further investigated. Mice were sensitized with the hepatocytespecific transcriptional inhibitor GalN in combination with the macrophage activator lipopolysaccharide (LPS). Induction of HO-1 protects mice from GalN/LPS induced liver damage, prolongs survival and reduces expression of cytokines in plasma and liver tissue which are known to be critical and seem to be key mediators for development of liver injury, i.e. TNF-α and IFN-γ. Further on, administration of SnPP as an inhibitor of HO activity, even increases liver damage und reduces survival showing HO-1 as a crucial factor for protection and survival in immune-mediated liver injury. Single treatment with the products of HO-1 activity BV or MC, protects from liver damage, reduces caspase-3 activity but does not affect on cytokine expression and prolongation of survival. In contrast, ferritin as the third product of HO-1 induction did not show protective effects. Since none of the HO products alone prolonged survival following GalN/LPS treatment, or reduced cytokine production, a combined treatment with MC plus BV was performed. Through synergism of CO and BV, prolongation of survival and reduction of cytokine expression could be additionally achieved. Finally, pretreatment with anti-TNF-α Ab and anti-IFN-γ Ab before GalN/LPS challenge showed that protection from liver damage and prolongation of survival through induction of HO-1 is depended on reduction of TNF-α and independent on decrease of IFN-γ. In the last section of experiments and examinations, the role of HO-1 in different models of chronic and acute HBV infection was elucidated. In a model of acute HBV infection, HO-1 induction by CoPP protects wt mice from Ad-HBV-induced liver damage and additionally reduces signs of viral activity, i.e. HBV core protein in liver tissue and HBeAg in serum. In HBV transgenic mice, an in vivo model for chronic HBV disease, induction of HO-1 by CoPP as well as adenoviral overexpression of HO-1 leads to similar results with respect to HBV core and HBeAg and in addition decreases intrahepatic rcDNA. However, levels of HBeAg in serum could be only reduced after CoPP-derived HO-1 induction. Moreover, these results could be mostly confirmed by in vitro experiments through incubation of the HBV transfected cell line HepG2.2.15 with CoPP: virus replication (HBeAg and rcDNA) and virus release in supernatants (HBV DNA) were significantly reduced. Taken together, the results of this study might provide new impact on therapeutical approaches and could contribute to new strategies for the long-term management of immune-mediated liver injury and chronic HBV infections.Die PrĂ€valenz der immunvermittelten Lebererkrankungen, wie beispielsweise die Infektion mit HBV, nimmt eine weltweit entscheidende Rolle ein. Es konnte bereits gezeigt werden, dass durch Induktion des cytoprotektiven Proteins HĂ€moxygenase-1 (HO-1) hepatoprotektive Effekte bei der Abstoßung von Lebertransplantaten zu erwarten sind. Im Rahmen dieser Arbeit wurde nun die Wirkung der HO-1 in experimentellen Modellen des apoptotischen, immunvermittelten und HBV induzierten Leberschadens systematisch erforscht. Der erste Teil der Arbeit behandelt den Einfluss der HO-1 auf den apoptotischen Leberschaden durch intravenöse Injektion des anti-CD95 Antikörpers bei MĂ€usen. Cobaltprotoporphyrin-IX (CoPP) kann HO-1 auf Ebene der mRNA und des Proteins im Lebergewebe von MĂ€usen (Kupfferzellen und Hepatozyten) in einem zeitabhĂ€ngigen VerhĂ€ltnis induzieren. Diese Induktion schĂŒtzt vor apoptotischen Leberschaden und verlĂ€ngert das Überleben bei MĂ€usen durch Reduktion der Caspase-3 AktivitĂ€t. Die Überexpression der HO-1 konnte ebenso durch den adenoviralen Gentransfer erreicht werden. Der protektive Effekt des adenoviralen Gentransfers konnte durch die Gabe von Zinnprotoporphyrin-IX (SnPP), einem spezifischen Inhibitor der HĂ€moxygenase-AktivitĂ€t, aufgehoben werden. Des Weiteren stellte sich heraus, dass die induzierte HO-1 in den Hepatozyten von entscheidender Bedeutung ist, da eine Depletion von Kupfferzellen nicht zur Aufhebung des Schutzes vor apoptischem Leberschaden fĂŒhrt. Durch CO, einem Produkt, das durch den von der HO-1 katalysierten HĂ€mabbaus ensteht, jedoch nicht durch die beiden anderen Produkte BV oder Ferritin, konnte der HO-1 vermittelte Schutz substituiert werden. In einem zweiten Abschnitt dieser Arbeit wurde nun der Einfluss der induzierbaren HO-1 auf ein in vivo Modell des immunvermittelten Leberschadens weiter untersucht. Dabei wurden MĂ€use mit dem hepatozytenspezifischen Transkriptionsinhibitor D-Galactosamin sensibilisiert und gleichzeitig mit makrophagenaktivierenden Lipopolysacchariden (LPS) behandelt. Bei der Maus gelang es, durch Induktion der HO-1 den immunvermittelten Leberschaden nach Behandlung mit GalN/LPS zu verhindern, das Überleben zu verlĂ€ngern und die Expression von Cytokinen im Plasma und Lebergewebe, welche eine entscheidende SchlĂŒsselrolle beim immunvermittelten Leberschaden durch GalN/LPS spielen, zu reduzieren (v.a. TNF-α und IFN-γ). Weiterhin konnte durch Behandlung mit SnPP, dem Inhibitor der HĂ€moxygenase AktiviĂ€t, der Leberschaden sogar verstĂ€rkt und das Überleben deutlich verringert werden, was die Bedeutung der HO-1 als kritischen Faktor fĂŒr den Schutz und das Überleben im Modell des immunvermittelten Leberschadens unterstreicht. Die Einzelbehandlung mit den Produkten der HO-1 AktivitĂ€t BV oder Dichlormethan fĂŒhrte zu einem Schutz vor Leberschaden und reduzierte die Caspase-3 AktivitĂ€t; sie hatte allerdings keinen Einfluss auf die VerlĂ€ngerung des Überlebens und die Zytokinproduktion. Im Gegensatz dazu waren mit Ferritin als drittem Produkt der HO-1 Induktion keinerlei protektive Effekte nachweisbar. Da kein HĂ€moxygenase-Produkt einzeln zur VerlĂ€ngerung des Überlebens oder zur Verringerung der Cytokinexpression gefĂŒhrt hat, wurde eine Kombinationsbehandlung bestehend aus Dichlormethan und BV durchgefĂŒhrt. Durch den nun herbeigefĂŒhrten synergistischen Effekt von CO und BV konnte eine zusĂ€tzliche VerlĂ€ngerung des Überlebens und die Reduktion der Cytokinexpression erreicht werden. Schließlich zeigte eine Vorbehandlung mit anti-TNF-α und anti-IFN-γ Antikörpern kurz vor Behandlung mit GalN/LPS, dass der Schutz und die VerlĂ€ngerung des Überlebens ausschließlich von der TNF-α-Neutralisation, nicht aber von der IFN-γ-Blockade abhĂ€ngig sind. Die AufklĂ€rung der Rolle der HO-1 in verschiedenen Modellen der chronischen und akuten Hepatitis B Infektion stand im letzten Abschnitt dieser Studien im Mittelpunkt. ZunĂ€chst wurde in einem Modell der akuten HBV Infektion durch Ad-HBV induzierte LeberschĂ€digung bei MĂ€usen der protektive Effekt durch HO-1-Induktion gezeigt; zusĂ€tzlich konnten die Marker der viralen AktivitĂ€t, HBV core Protein im Lebergewebe und HBeAg im Serum reduziert werden. In einem in vivo Modell der chronischen HBV Infektion konnten bei HBV-transgenen MĂ€usen durch CoPP-induzierte als auch durch adenoviral ĂŒberexprimierte HO-1 Ă€hnliche Effekte bezĂŒglich HBV core und HBeAg erzielt und zusĂ€tzlich die intrahepatische rcDNA vermindert werden. Jedoch waren die HBeAg-Spiegel im Serum der MĂ€use nur durch CoPP-induzierte HO-1 reduzierbar. Des Weiteren konnten die Ergebnisse grĂ¶ĂŸtenteils durch in vitro Untersuchungen an HepG2.2.15 Zellen, einer mit HBV stabil transfizierten Zelllinie, bestĂ€tigt werden. Nach Inkubation der Zellen mit CoPP war die Virusreplikation (HBeAg und rcDNA) sowie die Virusfreisetzung in den ZellĂŒberstand (HBV DNA) jeweils signifikant vermindert. Zusammenfassend könnten die Ergebnisse dieser Untersuchungen neue Bedeutung fĂŒr therapeutische AnsĂ€tze erlangen und weiterfĂŒhrend zu neuen Strategien des Langzeitmanagements bei immunvermittelter LeberschĂ€digung und der chronischen Infektion mit HBV beitragen

    Universal flow-density relation of single-file bicycle, pedestrian and car motion

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    The relation between flow and density is an essential quantitative characteristic to describe the efficiency of traffic systems. We have performed experiments with single-file motion of bicycles and compare the results with previous studies for car and pedestrian motion in similar setups. In the space-time diagrams we observe three different states of motion (free flow state, jammed state and stop-and-go waves) in all these systems. Despite of their obvious differences they are described by a universal fundamental diagram after proper rescaling of space and time which takes into account the size and free velocity of the three kinds of agents. This indicates that the similarities between the systems go deeper than expected.Comment: 5 pages, 5 figure

    Metalloporphyrins inactivate caspase-3 and -8

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    Activation of caspases represents one of the earliest biochemical indicators for apoptotic cell death. Therefore, measurement of caspase activity is a widely used and generally accepted method to determine apoptosis in a wide range of in vivo and in vitro settings. Numerous publications characterize the role of the heme-catabolizing enzyme heme oxygenase-1 (HO-1) in regulating apoptotic processes. Different metalloporphyrins representing inducers and inhibitors of this enzyme are often used, followed by assessment of apoptotic cell death. In the present work, we found that caspase-3-like activity, as well as activity of caspase-8 measured in either Fas (CD95) ligand-treated Jurkat T-lymphocytes or by the use of recombinant caspase-3 or -8, was inhibited by different metalloporphyrins (cobalt(III) protoporphyrin IX, tin and zinc II) protoporphyrin-IX). Moreover, employing the mouse model of Fas-induced liver apoptosis these properties of porphyrins could also be demonstrated in vivo. The metalloporphyrins were shown to inhibit caspase-3-mediated PARP cleavage. Molecular modeling studies demonstrated that porphyrins can occupy the active site of caspase-3 in an energetically favorable manner and in a binding mode similar to that of known inhibitors. The data shown here introduce metalloporphyrins as direct inhibitors of caspase activity. This finding points to the need for careful employment of metalloporphyrins as modulators of HO-1

    Crowding and Queuing in Entrance Scenarios: Influence of Corridor Width in Front of Bottlenecks

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    In this paper, we present results of an entrance experiment investigating the effect of the corridor width in front of a bottleneck on the density. The idea is based on a previous study suggesting that a guiding system in front of an entrance can reduce pushing of the waiting people and thus the density at the entrance. In our study we aim to find out to what extend the corridor width has an impact on crowding or queuing behavior and with that on the density. The results of the presented experiment suggest that the transition takes place between a corridor width of 1.2 m and 2.3 m. The total duration of each experimental run is not significantly influenced by the corridor width but by the width of the entrance itself, the number of participants and partly by the motivation. In general, the density in front of the gate as well as the area of high density is increased by widening the corridor and by intensifying the motivation of the participants. However, the results also suggest that also the number of participants significantly influences the occurrence of pushing and the level of density

    Supporting the Transformation to Climate Neutral Production with Shop Floor Management

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    The European Green Deal proposes the transformation to climate neutrality by 2050. Especially for manufacturing companies and their production sites, this transformation is a big challenge. Every aspect of the value stream needs to be re-evaluated and adjusted to reach the new target state of climate neutral production. In the last decades, many companies used lean management methods to improve production in the dimensions of time, quality, and cost. However, a growing number of studies show that lean methods can also be used to drive sustainability goals (with the target state being climate neutral production). This paper analyses the suitability of shop floor management, a popular lean method, in the context of climate neutral production. To this end, a literature research has been conducted to summarize the goals of shop floor management and the success factors for the transformation to climate neutral production. Then the results are contrasted and overlaps are analysed to identify possible shop floor management tools to accelerate the transformation to climate neutral production. Finally, the findings are briefly discussed and summarized in a matrix. The paper closes with specific recommendations for further research in this area

    Konzeptionelle Betrachtungen zu divergierenden Konstruktionen des Studienerfolgs

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    Das Konstrukt „Studienerfolg“ wird von verschiedenen Akteuren/-innen der Hochschullandschaft unterschiedlich verstanden. Insbesondere zwischen UniversitĂ€ten und Fachhochschulen sowie dualen Hochschulen bestehen divergierende Auffassungen. Der Beitrag zeigt exemplarisch die MultidimensionalitĂ€t des Konstrukts Studienerfolg mit seinen verschiedenen Ursachen auf und benennt Implikationen, die diese MultidimensionalitĂ€t fĂŒr Erfolgsmessung und -bewertung in der Innen- und Außenwirkung hat. Der Fokus liegt auf Unterschieden zwischen den Hochschularten hinsichtlich des Studienverlaufs und der BerufsfĂ€higkeit

    Process for Climate Strategy Development in Industrial Companies

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    Climate neutrality has been gaining more and more attention as a long-term goal for companies among different industries. Since this goal can hardly be achieved in the short term and requires a complex interaction of different measures, it calls for a strategic approach. This article presents a strategy process for manufacturing companies striving for climate neutrality. The strategy process consists of three macro phases: preparation phase, strategy development phase and operational implementation phase, which are iteratively carried out. The macro phases are each divided into different meso phases, which include guiding questions that must be answered by different internal stakeholders and process participants. Moreover, necessary results are described which must be available after each phase to enter the next one. The procedure is based on existing models for the description of strategy processes and approaches from the field of energy and environmental management. It combines them into a strategic approach for deriving climate strategies of industrial companies. The developed strategy process is applied to and evaluated at the ETA factory at the Technical University of Darmstadt

    Identifying pre-bariatric subtypes based on temperament traits, emotion dysregulation, and disinhibited eating: A latent profile analysis

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    Objective: The efficacy of bariatric surgery has been proven; however, a subset of patients fails to achieve expected long-term weight loss postoperatively. As differences in surgery outcome may be influenced by heterogeneous psychological profiles in pre-bariatric patients, previous subtyping models differentiated patients based on temperament traits. The objective of the present study was to expand these models by additionally considering emotion dysregulation and disinhibited eating behaviors for subtyping, as these factors were associated with maladaptive eating behaviors and poor post-bariatric weight loss outcome. Methods: Within a prospective multicenter registry, N = 370 pre-bariatric patients were examined using interview and self-report questionnaires. A latent profile analysis was performed to identify subtypes based on temperament traits, emotion dysregulation, and disinhibited eating behaviors. Results: Five pre-bariatric subtypes were identified with specific profiles regarding self control, emotion dysregulation, and disinhibited eating behaviors. Subtypes were associated with different levels of eating disorder psychopathology, depression, and quality of life. The expanded model increased variance explanation compared to temperament-based models. Conclusion: By adding emotion dysregulation and disinhibited eating behaviors to previous subtyping models, specific pre-bariatric subtypes emerged with distinct psychological deficit patterns. Future investigations should test the predictive value of these subtypes for post bariatric weight loss and health-related outcomes
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