311 research outputs found

    The development of the professionalism of adult educators: a biographical and learning perspective

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    To investigate the development of the professionalism of adult educators, we compare individuals’ narratives of their professional work at different times in their biographies. Using data from a qualitative longitudinal study, the paper includes two case studies through which we show phases of learning in the development of professionalism. We reconstruct forms and meanings of learning in this process. The study allows insights into differences in professional learning during the life course and the influence of institutional and social context in the development of professionalism. (DIPF/orig.

    Risk regulation, trade and international law : debating the precautionary principle in and around the WTO

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    The precautionary principle is one of the most contested principles in international law. In the context of trade regulation in particular, it has been a source of concern to those who fear that it might help to justify existing non-tariff barriers to trade or create additional ones. Proponents of the principle, in turn, argue that it is needed to fend off unwarranted health and environmental risks in situations where scientific uncertainty prevails, even if this works against the liberalisation of trade. In these contests the question of where and when the precautionary principle should be applied is inextricably linked to the question of what it means in the first place. Starting from the observation that consensus on a precise definition is missing both in legal-political practice and in academic scholarship, the present paper is concerned precisely with those practical interpretative contests which result from the principle’s ambiguity. We focus on attempts to agree legally binding definitions in the context of international trade regulation. The core of the paper is an empirical analysis of debates on several specific aspects of the precautionary principle, which were at issue during the past decade in four different, international institutions: the WTO dispute settlement, some of the WTO’s political committees, the Codex Alimentarius Commission (in particular its Committee on General Principles), and the conference of states which negotiated the Cartagena Protocol on Biosafety. Differences and similarities among these institutions are then analysed in a comparative perspective, taking up various contested issues one by one. From our findings we derive a set of hypotheses regarding the conditions under which, and the legal or political pathways on which, the precautionary principle (and perhaps other abstract normative ideas of a similar type as well) can make a difference to the outcomes of international decision-making

    Hemmung der Phosphodiesterase 4 (PDE4) reduziert experimentelle Hautfibrose durch Modulierung der Interleukin-6-Freisetzung aus M2 Makrophagen

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    Fibrosis is the defining characteristic of systemic sclerosis (SSc) as well as a major cause for morbidity and mortality among patients. Fibrosis affects the skin and many internal organs, including the lungs, heart and gastrointestinal tract. On a molecular level, fibrosis results from the accumulation of excessive amounts of extracellular matrix proteins released by chronically activated fibroblasts. Particularly in early phases of SSc, leukocytic infiltrates with macrophages, T cells and B cells are a common feature in affected organs. These inflammatory infiltrates are important sources of pro-fibrotic cytokines: The release of interleukin-6 (IL-6), transforming growth factor-β (TGF-β) and other pro-fibrotic mediators initiates pro-fibrotic processes through pathological activation of fibroblasts. In a subset of patients, these inflammatory processes persist and drive the progression of fibrotic disease manifestations. In recent years, increasing evidence suggests a specific subset of macrophages, so called alternatively activated M2 macrophages, as inflammatory key mediators in the pathogenesis of systemic sclerosis. Cyclic adenosine monosphosphate (cAMP) is a ubiquitous second messenger molecule that orchestrates physiological responses, amongst others inflammation. Its homeostasis is controlled by phosphodiesterases (PDEs), a superfamily of enzymes that catalyze the breakdown of cyclic AMP to inactive metabolites. The cAMP-specific PDE isoenzyme PDE4 is almost exclusively expressed within inflammatory cells. Pharmacological inhibition of PDE4 has well-established disease modifying activity in specific inflammatory diseases, including psoriasis, psoriatic arthritis and Behcet’s disease. In the present study, we evaluated pharmacological PDE4 inhibition as a novel therapeutic approach in treating fibrosis in SSc. In three different murine models, we observed that PDE4 inhibition blocks and treats dermal fibrosis in vivo: The first model is a classical inflammation-driven dermal fibrosis model, the bleomycin mouse model. With this model, we demonstrated that PDE4 inhibition can prevent the development of skin fibrosis. Using a modified bleomycin-induced fibrosis model we further showed that PDE4 inhibition also ameliorates already established fibrosis. Finally, we demonstrated the effect of PDE4 inhibition on a systemic level, using the mouse model of sclerodermatous chronic graft- versus-host disease (cGvHD). Consistently in all three in vivo models, pharmacological PDE4 inhibition resulted in reduced skin thickening, a decrease in fibrotic tissue as well as a decline in myofibroblast counts in the skin sections. Strikingly, we could observe a significant reduction in infiltrating leukocyte counts in all in vivo models. We hence hypothesized that PDE4 inhibition might carry out its anti-fibrotic effects by interfering with the cellular immune system. In fact, we demonstrated that pharmacological PDE4 inhibition has no direct effect on fibroblasts, as we could not observe any changes neither in activation of fibroblasts nor in their phenotype. Additionally, we showed that the anti-fibrotic effects of PDE4 inhibition are mediated through interference with the release of pro-fibrotic mediators, in particular with interleukin-6 (IL-6) from M2 but not from M1 macrophages in vitro. Consistent with these in vitro findings, we observed a significant reduction in IL-6 release in vivo in all three fibrosis models. Moreover, we detected a reduction of F4/80/arginase double positive M2 macrophages upon PDE4 blockade. We therefore assume that PDE4 inhibition acts exclusively on the pro-fibrotic M2 but not on the M1 phenotype. In conclusion, we found that blockade of PDE4 by specific inhibitors prevents and reduces dermal fibrosis by interfering with the release of pro-fibrotic mediators, in particular IL-6 from alternatively activated M2 macrophages

    Single strontium Rydberg ion confined in a Paul trap

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    Trapped Rydberg ions are a promising new system for quantum information processing. They have the potential to join the precise quantum operations of trapped ions and the strong, long-range interactions between Rydberg atoms. Combining the two systems is not at all straightforward. Rydberg atoms are severely affected by electric fields which may cause Stark shifts and field ionization, while electric fields are used to trap ions. Thus, a thorough understanding of the physical properties of Rydberg ions due to the trapping electric fields is essential for future applications. Here we report the observation of two fundamental trap effects. First, we investigate the interaction of the Rydberg electron with the trapping electric quadrupole fields which leads to Floquet sidebands in the excitation spectra. Second, we report on the modified trapping potential in the Rydberg state compared to the ground state which results from the strong polarizability of the Rydberg ion. By controlling both effects we observe resonance lines close to their natural linewidth demonstrating an unprecedented level of control of this novel quantum platform

    Motivations for Adolescent COVID-19 Vaccination: A Comparative Study of Adolescent and Caregiver Perspectives in Germany

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    Given the crucial role of vaccination in halting the COVID-19 pandemic, it is imperative to understand the factors that motivate adolescents to get vaccinated. We surveyed adolescents and their accompanying guardians scheduled to receive a COVID-19 vaccination (Comirnaty) in an urban region in Germany in mid-2021 regarding their motivation for getting vaccinated and collected data on their sociodemographic characteristics, medical history, vaccination status, and any history of COVID-19 infection in the family. We also queried information strategies related to the SARS-CoV-2 pandemic. Motivations for getting vaccinated were similar among adolescents and their parents. The primary reasons for vaccination were protection against SARS-CoV-2-related illness and gaining access to leisure facilities. This was not influenced by gender, health status, migration background, or the presence of chronic or acute diseases. The percentage of parents who had received SARS-CoV-2 immunization and the proportion of parents with a high level of education were higher among study participants than in the general population. Adolescents were especially willing to be vaccinated if they came from a better educational environment and had a high vaccination rate in the family. Emphasizing the importance of vaccination among all segments of the population and removing barriers to vaccines may lead to an ameliorated acceptance of COVID-19 vaccines

    PU.1 controls fibroblast polarization and tissue fibrosis

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    Fibroblasts are polymorphic cells with pleiotropic roles in organ morphogenesis, tissue homeostasis and immune responses. In fibrotic diseases, fibroblasts synthesize abundant amounts of extracellular matrix, which induces scarring and organ failure. By contrast, a hallmark feature of fibroblasts in arthritis is degradation of the extracellular matrix because of the release of metalloproteinases and degrading enzymes, and subsequent tissue destruction. The mechanisms that drive these functionally opposing pro-fibrotic and pro-inflammatory phenotypes of fibroblasts remain unknown. Here we identify the transcription factor PU.1 as an essential regulator of the pro-fibrotic gene expression program. The interplay between transcriptional and post-transcriptional mechanisms that normally control the expression of PU.1 expression is perturbed in various fibrotic diseases, resulting in the upregulation of PU.1, induction of fibrosis-associated gene sets and a phenotypic switch in extracellular matrix-producing pro-fibrotic fibroblasts. By contrast, pharmacological and genetic inactivation of PU.1 disrupts the fibrotic network and enables reprogramming of fibrotic fibroblasts into resting fibroblasts, leading to regression of fibrosis in several organs

    Epigenomic profiling of prostate cancer identifies differentially methylated genes in TMPRSS2:ERG fusion-positive versus fusion-negative tumors

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    Background: About half of all prostate cancers harbor the TMPRSS2:ERG (T2E) gene fusion. While T2E-positive and T2E-negative tumors represent specific molecular subtypes of prostate cancer (PCa), previous studies have not yet comprehensively investigated how these tumor subtypes differ at the epigenetic level. We therefore investigated epigenome-wide DNA methylation profiles of PCa stratified by T2E status. Results: The study included 496 patients with clinically localized PCa who had a radical prostatectomy as primary treatment for PCa. Fluorescence in situ hybridization (FISH) "break-apart" assays were used to determine tumor T2E- fusion status, which showed that 266 patients (53.6 %) had T2E-positive PCa. The study showed global DNA methylation differences between tumor subtypes. A large number of differentially methylated CpG sites were identified (false-discovery rate [FDR] Q-value Conclusions: This study identified substantial differences in DNA methylation profiles of T2E-positive and T2E-negative tumors, thereby providing further evidence that different underlying oncogenic pathways characterize these molecular subtypes

    Single strontium Rydberg ion confined in a Paul trap

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    Trapped Rydberg ions are a promising new system for quantum information processing. They have the potential to join the precise quantum operations of trapped ions and the strong, long-range interactions between Rydberg atoms. Combining the two systems is not at all straightforward. Rydberg atoms are severely affected by electric fields which may cause Stark shifts and field ionization, while electric fields are used to trap ions. Thus, a thorough understanding of the physical properties of Rydberg ions due to the trapping electric fields is essential for future applications. Here we report the observation of two fundamental trap effects. First, we investigate the interaction of the Rydberg electron with the trapping electric quadrupole fields which leads to Floquet sidebands in the excitation spectra. Second, we report on the modified trapping potential in the Rydberg state compared to the ground state which results from the strong polarizability of the Rydberg ion. By controlling both effects we observe resonance lines close to their natural linewidth demonstrating an unprecedented level of control of this novel quantum platform

    Prostate Cancer Risk Is not Altered by TP53AIP1 Germline Mutations in a German Case-Control Series

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    Prostate cancer susceptibility has previously been associated with truncating germline variants in the gene TP53AIP1 (tumor protein p53 regulated apoptosis inducing protein 1). For two apparently recurrent mutations (p.Q22fs and p.S32X) a remarkable OR of 5.1 was reported for prostate cancer risk. Since these findings have not been validated so far, we genotyped p.Q22fs and p.S32X in two German series with a total of 1,207 prostate cancer cases and 1,495 controls. The truncating variants were not significantly associated with prostate cancer in none of the two cohorts, nor in the combined analysis [odds ratio (OR) = 1.16; 95% confidence interval (CI 95%) = 0.62–2.15; p = 0.66]. Carriers showed no significant differences in family history of prostate cancer, age at diagnosis, Gleason score or PSA at diagnosis when compared to non-carrier prostate cancer cases. The large sample size of the combined cohort rejects a high-risk effect greater than 2.2 and indicates a limited role of TP53AIP1 in prostate cancer predisposition
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