92 research outputs found

    The Common Market: Between International and Municipal Law

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    SoK: Delegation and Revocation, the Missing Links in the Web's Chain of Trust

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    The ability to quickly revoke a compromised key is critical to the security of any public-key infrastructure. Regrettably, most traditional certificate revocation schemes suffer from latency, availability, or privacy problems. These problems are exacerbated by the lack of a native delegation mechanism in TLS, which increasingly leads domain owners to engage in dangerous practices such as sharing their private keys with third parties. We analyze solutions that address the long-standing delegation and revocation shortcomings of the web PKI, with a focus on approaches that directly affect the chain of trust (i.e., the X.509 certification path). For this purpose, we propose a 19-criteria framework for characterizing revocation and delegation schemes. We also show that combining short-lived delegated credentials or proxy certificates with an appropriate revocation system would solve several pressing problems.Comment: IEEE European Symposium on Security and Privacy (EuroS&P) 202

    Genome sequencing of evolved aspergilli populations reveals robust genomes, transversions in A. flavus, and sexual aberrancy in non-homologous end-joining mutants

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    BACKGROUND: Aspergillus spp. comprises a very diverse group of lower eukaryotes with a high relevance for industrial applications and clinical implications. These multinucleate species are often cultured for many generations in the laboratory, which can unknowingly propagate hidden genetic mutations. To assess the likelihood of such events, we studied the genome stability of aspergilli by using a combination of mutation accumulation (MA) lines and whole genome sequencing. RESULTS: We sequenced the whole genomes of 30 asexual and 10 sexual MA lines of three Aspergillus species (A. flavus, A. fumigatus and A. nidulans) and estimated that each MA line accumulated mutations for over 4000 mitoses during asexual cycles. We estimated mutation rates of 4.2 × 10-11 (A. flavus), 1.1 × 10-11 (A. fumigatus) and 4.1 × 10-11 (A. nidulans) per site per mitosis, suggesting that the genomes are very robust. Unexpectedly, we found a very high rate of GC → TA transversions only in A. flavus. In parallel, 30 asexual lines of the non-homologous end-joining (NHEJ) mutants of the three species were also allowed to accumulate mutations for the same number of mitoses. Sequencing of these NHEJ MA lines gave an estimated mutation rate of 5.1 × 10-11 (A. flavus), 2.2 × 10-11 (A. fumigatus) and 4.5 × 10-11 (A. nidulans) per base per mitosis, which is slightly higher than in the wild-type strains and some ~ 5-6 times lower than in the yeasts. Additionally, in A. nidulans, we found a NHEJ-dependent interference of the sexual cycle that is independent of the accumulation of mutations. CONCLUSIONS: We present for the first time direct counts of the mutation rate of filamentous fungal species and find that Aspergillus genomes are very robust. Deletion of the NHEJ machinery results in a slight increase in the mutation rate, but at a rate we suggest is still safe to use for biotechnology purposes. Unexpectedly, we found GC→TA transversions predominated only in the species A. flavus, which could be generated by the hepatocarcinogen secondary metabolite aflatoxin. Lastly, a strong effect of the NHEJ mutation in self-crossing was observed and an increase in the mutations of the asexual lines was quantifiedEspaña, MINECO grant number BIO2015-6714

    RNAseq analysis of Aspergillus fumigatus in blood reveals a just wait and see resting stage behavior

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    Background: Invasive aspergillosis is started after germination of Aspergillus fumigatus conidia that are inhaled by susceptible individuals. Fungal hyphae can grow in the lung through the epithelial tissue and disseminate hematogenously to invade into other organs. Low fungaemia indicates that fungal elements do not reside in the bloodstream for long. Results: We analyzed whether blood represents a hostile environment to which the physiology of A. fumigatus has to adapt. An in vitro model of A. fumigatus infection was established by incubating mycelium in blood. Our model allowed to discern the changes of the gene expression profile of A. fumigatus at various stages of the infection. The majority of described virulence factors that are connected to pulmonary infections appeared not to be activated during the blood phase. Three active processes were identified that presumably help the fungus to survive the blood environment in an advanced phase of the infection: iron homeostasis, secondary metabolism, and the formation of detoxifying enzymes. Conclusions: We propose that A. fumigatus is hardly able to propagate in blood. After an early stage of sensing the environment, virtually all uptake mechanisms and energy-consuming metabolic pathways are shut-down. The fungus appears to adapt by trans-differentiation into a resting mycelial stage. This might reflect the harsh conditions in blood where A. fumigatus cannot take up sufficient nutrients to establish self-defense mechanisms combined with significant growth

    The Transcription Factor Ndt80 Does Not Contribute to Mrr1-, Tac1-, and Upc2-Mediated Fluconazole Resistance in Candida albicans

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    The pathogenic yeast Candida albicans can develop resistance to the widely used antifungal agent fluconazole, which inhibits ergosterol biosynthesis, by the overexpression of genes encoding multidrug efflux pumps or ergosterol biosynthesis enzymes. Zinc cluster transcription factors play a central role in the transcriptional regulation of drug resistance. Mrr1 regulates the expression of the major facilitator MDR1, Tac1 controls the expression of the ABC transporters CDR1 and CDR2, and Upc2 regulates ergosterol biosynthesis (ERG) genes. Gain-of-function mutations in these transcription factors result in constitutive overexpression of their target genes and are responsible for fluconazole resistance in many clinical C. albicans isolates. The transcription factor Ndt80 contributes to the drug-induced upregulation of CDR1 and ERG genes and also binds to the MDR1 and CDR2 promoters, suggesting that it is an important component of all major transcriptional mechanisms of fluconazole resistance. However, we found that Ndt80 is not required for the induction of MDR1 and CDR2 expression by inducing chemicals. CDR2 was even partially derepressed in ndt80Δ mutants, indicating that Ndt80 is a repressor of CDR2 expression. Hyperactive forms of Mrr1, Tac1, and Upc2 promoted overexpression of MDR1, CDR1/CDR2, and ERG11, respectively, with the same efficiency in the presence and absence of Ndt80. Mrr1- and Tac1-mediated fluconazole resistance was even slightly enhanced in ndt80Δ mutants compared to wild-type cells. These results demonstrate that Ndt80 is dispensable for the constitutive overexpression of Mrr1, Tac1, and Upc2 target genes and the increased fluconazole resistance of strains that have acquired activating mutations in these transcription factors

    A multinational survey on the infrastructural quality of paediatric intensive care units

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    Background: The aim of the present study was to assess whether paediatric intensive care units (PICUs) in three central European countries comply with guidelines concerning infrastructure provided by the European Society of Intensive Care Medicine (ESICM). Between July 2016 and May 2017, a survey was conducted based on the ESICM guidelines. The questionnaire was structured into four categories: structural quality, diagnostic/therapeutic equipment, personnel and organization. All PICUs treating paediatric patients in the D-A-CH region [Germany (D), Austria (A) and Switzerland (CH)] were researched through the national societies. A total of 126 PICUs were contacted (D: 106;A: 12;and CH: 8).Results: Eighty-five of 126 PICUs responded (D: 67%;A: 61%;and CH: 100%). A median of 500 patients was treated annually (D: 500;A: 350;and CH: 600) with a median of 12 beds (D: 12;A: 8;and CH: 12). Recommendations regarding infrastructure were met as follows: structural quality 62% in D, 71% in A and 75% in CH;diagnostic/therapeutic equipment: 87% in D, 91% in A and 89% in CH;personnel: 65% in D, 87% in A and 85% in CH;and organization: 75% in D, 73% in A and 88% in CH.Conclusion: sThis survey reveals deficits concerning structural quality in all countries. Furthermore, shortcomings regarding personnel were found in Germany and for organization in Germany and Austria. These issues need to be addressed urgently to further improve treatment quality and patient safety in the future

    Giovanni Boccaccio. Italienisch-deutscher Kulturtransfer von der Frühen Neuzeit bis zur Gegenwart

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    Italien und Deutschland – kaum zwei andere Kulturen in Europa sind so stark miteinander verbunden wie diese beiden, sei es geschichtlich oder kulturell. Am wirkmächtigsten war sicherlich die Übernahme des Gedankenguts der italienischen Renaissance, in deren Folge Wissen aus gesellschaftlichen, wissenschaftlichen und kulturellen Bereichen den Weg nach Deutschland fand, darunter auch die Kenntnis von Giovanni Boccaccios Werken, die sich auf deutschsprachige Kontexte auswirkten. Der vorliegende Tagungsband versammelt die Beiträge zur gleichnamigen Tagung „Giovanni Boccaccio. Italienisch-deutscher Kulturtransfer von der Frühen Neuzeit bis zur Gegenwart“ (Bamberg, 21. bis 23. November 2013), die sich mit vielfältigen Aspekten der Boccaccio-Rezeption auseinandersetzen

    Bats in the anthropogenic matrix: Challenges and opportunities for the conservation of chiroptera and their ecosystem services in agricultural landscapes

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    Intensification in land-use and farming practices has had largely negative effects on bats, leading to population declines and concomitant losses of ecosystem services. Current trends in land-use change suggest that agricultural areas will further expand, while production systems may either experience further intensification (particularly in developing nations) or become more environmentally friendly (especially in Europe). In this chapter, we review the existing literature on how agricultural management affects the bat assemblages and the behavior of individual bat species, as well as the literature on provision of ecosystem services by bats (pest insect suppression and pollination) in agricultural systems. Bats show highly variable responses to habitat conversion, with no significant change in species richness or measures of activity or abundance. In contrast, intensification within agricultural systems (i.e., increased agrochemical inputs, reduction of natural structuring elements such as hedges, woods, and marshes) had more consistently negative effects on abundance and species richness. Agroforestry systems appear to mitigate negative consequences of habitat conversion and intensification, often having higher abundances and activity levels than natural areas. Across biomes, bats play key roles in limiting populations of arthropods by consuming various agricultural pests. In tropical areas, bats are key pollinators of several commercial fruit species. However, these substantial benefits may go unrecognized by farmers, who sometimes associate bats with ecosystem disservices such as crop raiding. Given the importance of bats for global food production, future agricultural management should focus on “wildlife-friendly” farming practices that allow more bats to exploit and persist in the anthropogenic matrix so as to enhance provision of ecosystem services. Pressing research topics include (1) a better understanding of how local-level versus landscape-level management practices interact to structure bat assemblages, (2) the effects of new pesticide classes and GM crops on bat populations, and (3) how increased documentation and valuation of the ecosystem services provided by bats could improve attitudes of producers toward their conservation
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