80 research outputs found

    Copyright law

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    Contents Editorial Research Articles Formats as Media of Cooperation / Axel Volmar Thematic Focus: Copyright Law Editorial: The Reference as Part of the Art Form. A Turning Point in Copyright Law? / Dagmar Hoffmann, Nadine Klass The Concept of “Pastiche” in Directive 2001/29/EC in the Light of the German Case Metall auf Metall / FrĂ©dĂ©ric Döhl Transformative Works and German Copyright Law as Matters of Boundary Work / Kamila Kempfert, Wolfgang Reißmann Negotiating Legal Knowledge, Community Values, and Entrepreneurship in Fan Cultural Production / Sophie G. EinwĂ€chter Referencing in Academia: Video Essay, Mashup, Copyright / Eckart Voigts, Katerina Marshfield Re-Use under US Copyright Law: Fair Use as a Best Practice or Just a Myth of Balance in Copyright? / Sibel Kocatepe Reports Grounded Design in a Value Sensitive Context / Volker Wulf in conversation with Batya Friedma

    The extrafollicular response is sufficient to drive initiation of autoimmunity and early disease hallmarks of lupus

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    IntroductionMany autoimmune diseases are characterized by germinal center (GC)-derived, affinity-matured, class-switched autoantibodies, and strategies to block GC formation and progression are currently being explored clinically. However, extrafollicular responses can also play a role. The aim of this study was to investigate the contribution of the extrafollicular pathway to autoimmune disease development.MethodsWe blocked the GC pathway by knocking out the transcription factor Bcl-6 in GC B cells, leaving the extrafollicular pathway intact. We tested the impact of this intervention in two murine models of systemic lupus erythematosus (SLE): a pharmacological model based on chronic epicutaneous application of the Toll-like receptor (TLR)-7 agonist Resiquimod (R848), and 564Igi autoreactive B cell receptor knock-in mice. The B cell intrinsic effects were further investigated in vitro and in autoreactive mixed bone marrow chimeras.ResultsGC block failed to curb autoimmune progression in the R848 model based on anti-dsDNA and plasma cell output, superoligomeric DNA complexes, and immune complex deposition in glomeruli. The 564Igi model confirmed this based on anti-dsDNA and plasma cell output. In vitro, loss of Bcl-6 prevented GC B cell expansion and accelerated plasma cell differentiation. In a competitive scenario in vivo, B cells harboring the genetic GC block contributed disproportionately to the plasma cell output.DiscussionWe identified the extrafollicular pathway as a key contributor to autoimmune progression. We propose that therapeutic targeting of low quality and poorly controlled extrafollicular responses could be a desirable strategy to curb autoreactivity, as it would leave intact the more stringently controlled and high-quality GC responses providing durable protection against infection

    Supporting agri-food projects to implement climate change adaptation through the interactive online tool ‘CRISP’

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    Introduction International agri-food system programmes are increasingly seeking to mainstream climate action across their portfolios. A range of methods and tools exists, but there is no “ready-to-use” tool that allows a cost- and time-effective climate risk assessment for specific agri-food systems and the development of adaptation hypotheses. The Deutsche Gesellschaft fĂŒr Internationale Zusammenarbeit (GIZ), with Eurac Research and the Alliance of Bioversity International and the International Centre for Tropical Agriculture (CIAT), set out to provide an easy-to-use tool that considers the specific characteristics of agri-food systems under a changing climate. Objectives The Climate Risk Planning & Managing Tool for development programmes in agri-food systems (CRISP) is a web-based tool for projects planners and implementers in the agri-food sector. It allows them to identify starting points for climate risk management and develop adaptation hypotheses to backstop their intervention’s design – in a quick and easy way. Methodology Using the impact chain methodology as a framework, we undertook a literature search to identify relevant climate risks in the context of selected agro-ecological systems across five regions. We organised the findings into an extensive knowledge database. We then co-designed a tool with potential users that would allow the database to be queried in different ways depending on the user needs. Findings Potential users of the tool see promise in using it to improve their programming in the agri-food sector. They suggest expanding the knowledge database to include more agro-ecological systems, value chain concepts and national policy-related data. Significance of the work for policy and practice The CRISP tool will help users to identify starting points for climate risk management. The tool provides science-based evidence and linkages to complementary tools and approaches to implement climate actions. It will assist practitioners in the agri-food sector to develop adaptation hypotheses to help guide the project from the planning phase onward

    A Major Role for the Plasmodium falciparum ApiAP2 Protein PfSIP2 in Chromosome End Biology

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    The heterochromatic environment and physical clustering of chromosome ends at the nuclear periphery provide a functional and structural framework for antigenic variation and evolution of subtelomeric virulence gene families in the malaria parasite Plasmodium falciparum. While recent studies assigned important roles for reversible histone modifications, silent information regulator 2 and heterochromatin protein 1 (PfHP1) in epigenetic control of variegated expression, factors involved in the recruitment and organization of subtelomeric heterochromatin remain unknown. Here, we describe the purification and characterization of PfSIP2, a member of the ApiAP2 family of putative transcription factors, as the unknown nuclear factor interacting specifically with cis-acting SPE2 motif arrays in subtelomeric domains. Interestingly, SPE2 is not bound by the full-length protein but rather by a 60kDa N-terminal domain, PfSIP2-N, which is released during schizogony. Our experimental re-definition of the SPE2/PfSIP2-N interaction highlights the strict requirement of both adjacent AP2 domains and a conserved bipartite SPE2 consensus motif for high-affinity binding. Genome-wide in silico mapping identified 777 putative binding sites, 94% of which cluster in heterochromatic domains upstream of subtelomeric var genes and in telomere-associated repeat elements. Immunofluorescence and chromatin immunoprecipitation (ChIP) assays revealed co-localization of PfSIP2-N with PfHP1 at chromosome ends. Genome-wide ChIP demonstrated the exclusive binding of PfSIP2-N to subtelomeric SPE2 landmarks in vivo but not to single chromosome-internal sites. Consistent with this specialized distribution pattern, PfSIP2-N over-expression has no effect on global gene transcription. Hence, contrary to the previously proposed role for this factor in gene activation, our results provide strong evidence for the first time for the involvement of an ApiAP2 factor in heterochromatin formation and genome integrity. These findings are highly relevant for our understanding of chromosome end biology and variegated expression in P. falciparum and other eukaryotes, and for the future analysis of the role of ApiAP2-DNA interactions in parasite biology

    The Phrenic Component of Acute Schizophrenia – A Name and Its Physiological Reality

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    Decreased heart rate variability (HRV) was shown for unmedicated patients with schizophrenia and their first-degree relatives, implying genetic associations. This is known to be an important risk factor for increased cardiac mortality in other diseases. The interaction of cardio-respiratory function and respiratory physiology has never been investigated in the disease although it might be closely related to the pattern of autonomic dysfunction. We hypothesized that increased breathing rates and reduced cardio-respiratory coupling in patients with acute schizophrenia would be associated with low vagal function. We assessed variability of breathing rates and depth, HRV and cardio-respiratory coupling in patients, their first-degree relatives and controls at rest. Control subjects were investigated a second time by means of a stress task to identify stress-related changes of cardio-respiratory function. A total of 73 subjects were investigated, consisting of 23 unmedicated patients, 20 healthy, first-degree relatives and 30 control subjects matched for age, gender, smoking and physical fitness. The LifeShirt¼, a multi-function ambulatory device, was used for data recording (30 minutes). Patients breathe significantly faster (p<.001) and shallower (p<.001) than controls most pronouncedly during exhalation. Patients' breathing is characterized by a significantly increased amount of middle- (p<.001), high- (p<.001), and very high frequency fluctuations (p<.001). These measures correlated positively with positive symptoms as assessed by the PANSS scale (e.g., middle frequency: r = 521; p<.01). Cardio-respiratory coupling was reduced in patients only, while HRV was decreased in patients and healthy relatives in comparison to controls. Respiratory alterations might reflect arousal in acutely ill patients, which is supported by comparable physiological changes in healthy subjects during stress. Future research needs to further investigate these findings with respect to their physiological consequences for patients. These results are invaluable for researchers studying changes of biological signals prone to the influence of breathing rate and rhythm (e.g., functional imaging)

    Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

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    A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

    Effects of a cognitive training on spatial learning and associated functional brain activations

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    BACKGROUND: Both cognitive and physical exercise have been discussed as promising interventions for healthy cognitive aging. The present study assessed the effects of cognitive training (spatial vs. perceptual training) and physical training (endurance training vs. non-endurance training) on spatial learning and associated brain activation in 33 adults (40–55 years). Spatial learning was assessed with a virtual maze task, and at the same time neural correlates were measured with functional magnetic resonance imaging (fMRI). RESULTS: Only the spatial training improved performance in the maze task. These behavioral gains were accompanied by a decrease in frontal and temporal lobe activity. At posttest, participants of the spatial training group showed lower activity than participants of the perceptual training group in a network of brain regions associated with spatial learning, including the hippocampus and parahippocampal gyrus. No significant differences were observed between the two physical intervention groups. CONCLUSIONS: Functional changes in neural systems associated with spatial navigation can be induced by cognitive interventions and seem to be stronger than effects of physical exercise in middle-aged adults
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