| 1. |
- Getir, Sinem, et al.
(författare)
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Co-evolution of software architecture and fault tree models: An explorative case study on a pick and place factory automation system.
- 2013
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Ingår i: Proc. of the 5th International Workshop on Non-functional Properties in Modeling, September 29, Miami, USA, 2013. ; :1074
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Konferensbidrag (refereegranskat)abstract
- Safety-critical systems are subject to rigorous safety analyses, e.g., hazard analyses. Fault trees are a deductive technique to derive the combination of faults which cause a hazard. There is a tight relationship between fault trees and system architecture as the components contain the faults and the component structure influences the fault combinations. In this paper, we describe an explorative case study on multiple evolution scenarios of a factory automation system. We report on the evolution steps on the system architecture models and fault trees and how the evolution steps in the different models relate to each other.
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| 2. |
- Haider, Susanne, et al.
(författare)
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Raman microspectroscopy reveals long-term extracellular activity of Chlamydiae
- 2010
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Ingår i: Molecular Microbiology. - : Blackwell Publishing. - 0950-382X .- 1365-2958. ; 77:3, s. 687-700
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Tidskriftsartikel (refereegranskat)abstract
- The phylum Chlamydiae consists exclusively of obligate intracellular bacteria. Some of them are formidable pathogens of humans, while others occur as symbionts of amoebae. These genetically intractable bacteria possess a developmental cycle consisting of replicative reticulate bodies and infectious elementary bodies, which are believed to be physiologically inactive. Confocal Raman microspectroscopy was applied to differentiate between reticulate bodies and elementary bodies of Protochlamydia amoebophila and to demonstrate in situ the labelling of this amoeba symbiont after addition of isotope-labelled phenylalanine. Unexpectedly, uptake of this amino acid was also observed for both developmental stages for up to 3 weeks, if incubated extracellularly with labelled phenylalanine, and P. amoebophila remained infective during this period. Furthermore, P. amoebophila energizes its membrane and performs protein synthesis outside of its host. Importantly, amino acid uptake and protein synthesis after extended extracellular incubation could also be demonstrated for the human pathogen Chlamydia trachomatis, which synthesizes stress-related proteins under these conditions as shown by 2-D gel electrophoresis and MALDI-TOF/TOF mass spectrometry. These findings change our perception of chlamydial biology and reveal that host-free analyses possess a previously not recognized potential for direct experimental access to these elusive microorganisms.
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| 3. |
- Horn, T., et al.
(författare)
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The TTC 2014 movie database case
- 2014
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Ingår i: 7th Transformation Tool Contest, TTC 2014, Part of the Software Technologies: Applications and Foundations, STAF 2014; York; United Kingdom; 25 July 2014. - 1613-0073. ; 1305, s. 93-97
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Konferensbidrag (refereegranskat)abstract
- Social networks and other web 2.0 platforms use huge amounts of data to offer new services to customers. Often this data can be expressed as huge graphs and thus could be seen as a potential new application field for model transformations. However, this application area requires that model transformation tools scale to models with millions of objects. This transformation case targets this application area by using the IMDb movie database as a model. The transformation deals with identifying all actor couples which perform together in a set of at least three movies.
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| 4. |
- Omsland, Anders, et al.
(författare)
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Chlamydial metabolism revisited : interspecies metabolic variability and developmental stage-specific physiologic activities
- 2014
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Ingår i: FEMS Microbiology Reviews. - : Oxford University Press (OUP). - 0168-6445 .- 1574-6976. ; 38:4, s. 779-801
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Tidskriftsartikel (refereegranskat)abstract
- Chlamydiae are a group of obligate intracellular bacteria comprising important human and animal pathogens as well as symbionts of ubiquitous protists. They are characterized by a developmental cycle including two main morphologically and physiologically distinct stages, the replicating reticulate body and the infectious nondividing elementary body. In this review, we reconstruct the history of studies that have led to our current perception of chlamydial physiology, focusing on their energy and central carbon metabolism. We then compare the metabolic capabilities of pathogenic and environmental chlamydiae highlighting interspecies variability among the metabolically more flexible environmental strains. We discuss recent findings suggesting that chlamydiae may not live as energy parasites throughout the developmental cycle and that elementary bodies are not metabolically inert but exhibit metabolic activity under appropriate axenic conditions. The observed host-free metabolic activity of elementary bodies may reflect adequate recapitulation of the intracellular environment, but there is evidence that this activity is biologically relevant and required for extracellular survival and maintenance of infectivity. The recent discoveries call for a reconsideration of chlamydial metabolism and future in-depth analyses to better understand how species- and stage-specific differences in chlamydial physiology may affect virulence, tissue tropism, and host adaptation.
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| 5. |
- Sixt, Barbara Susanne, et al.
(författare)
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Developmental cycle and host interaction of Rhabdochlamydia porcellionis, an intracellular parasite of terrestrial isopods
- 2013
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Ingår i: Environmental Microbiology. - : John Wiley & Sons. - 1462-2912 .- 1462-2920. ; 15:11, s. 2980-2993
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Tidskriftsartikel (refereegranskat)abstract
- Environmental chlamydiae are a diverse group of obligate intracellular bacteria related to well-known pathogens of humans. To date, only very little is known about chlamydial species infecting arthropods. In this study, we used cocultivation with insect cells for recovery and maintenance of Rhabdochlamydia porcellionis, a parasite of the crustacean host Porcellio scaber. In vitro, the infection cycle of R. porcellionis was completed within 7 days, resulting in the release of infectious particles by host cell lysis. Lack of apoptosis induction during the entire course of infection, combined with a reduced sensitivity of infected cultures to experimentally induced programmed cell death, indicates that R. porcellionis like its human pathogenic relatives counteracts this host defence mechanism. Interestingly, the rod-shaped variant of R. porcellionis, proposed to represent their mature infective stage, was not detected in cell culture, suggesting that its development may require prolonged maturation or may be triggered by specific conditions encountered only in the animal host. This first cell culture-based system for the cultivation and investigation of an arthropod-associated chlamydial species will help to better understand the biology of a so far neglected group of chlamydiae and its recently suggested potential to cause disease in humans.
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| 6. |
- Sixt, Barbara Susanne, et al.
(författare)
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Lack of effective anti-apoptotic activities restricts growth of Parachlamydiaceae in insect cells
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- The fundamental role of programmed cell death in host defense is highlighted by the multitude of anti-apoptotic strategies evolved by various microbes, including the well-known obligate intracellular bacterial pathogens Chlamydia trachomatis and Chlamydia (Chlamydophila) pneumoniae. As inhibition of apoptosis is assumed to be essential for a successful infection of humans by these chlamydiae, we analyzed the anti-apoptotic capacity of close relatives that occur as symbionts of amoebae and might represent emerging pathogens. While Simkania negevensis was able to efficiently replicate within insect cells, which served as model for metazoan-derived host cells, the Parachlamydiaceae (Parachlamydia acanthamoebae and Protochlamydia amoebophila) displayed limited intracellular growth, yet these bacteria induced typical features of apoptotic cell death, including formation of apoptotic bodies, nuclear condensation, internucleosomal DNA fragmentation, and effector caspase activity. Induction of apoptosis was dependent on bacterial activity, but not bacterial de novo protein synthesis, and was detectable already at very early stages of infection. Experimental inhibition of host cell death greatly enhanced parachlamydial replication, suggesting that lack of potent anti-apoptotic activities in Parachlamydiaceae may represent an important factor compromising their ability to successfully infect non-protozoan hosts. These findings highlight the importance of the evolution of anti-apoptotic traits for the success of chlamydiae as pathogens of humans and animals.
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| 7. |
- Sixt, Barbara Susanne, et al.
(författare)
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Metabolic features of Protochlamydia amoebophila elementary bodies--a link between activity and infectivity in Chlamydiae
- 2013
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- The Chlamydiae are a highly successful group of obligate intracellular bacteria, whose members are remarkably diverse, ranging from major pathogens of humans and animals to symbionts of ubiquitous protozoa. While their infective developmental stage, the elementary body (EB), has long been accepted to be completely metabolically inert, it has recently been shown to sustain some activities, including uptake of amino acids and protein biosynthesis. In the current study, we performed an in-depth characterization of the metabolic capabilities of EBs of the amoeba symbiont Protochlamydia amoebophila. A combined metabolomics approach, including fluorescence microscopy-based assays, isotope-ratio mass spectrometry (IRMS), ion cyclotron resonance Fourier transform mass spectrometry (ICR/FT-MS), and ultra-performance liquid chromatography mass spectrometry (UPLC-MS) was conducted, with a particular focus on the central carbon metabolism. In addition, the effect of nutrient deprivation on chlamydial infectivity was analyzed. Our investigations revealed that host-free P. amoebophila EBs maintain respiratory activity and metabolize D-glucose, including substrate uptake as well as host-free synthesis of labeled metabolites and release of labeled CO2 from (13)C-labeled D-glucose. The pentose phosphate pathway was identified as major route of D-glucose catabolism and host-independent activity of the tricarboxylic acid (TCA) cycle was observed. Our data strongly suggest anabolic reactions in P. amoebophila EBs and demonstrate that under the applied conditions D-glucose availability is essential to sustain metabolic activity. Replacement of this substrate by L-glucose, a non-metabolizable sugar, led to a rapid decline in the number of infectious particles. Likewise, infectivity of Chlamydia trachomatis, a major human pathogen, also declined more rapidly in the absence of nutrients. Collectively, these findings demonstrate that D-glucose is utilized by P. amoebophila EBs and provide evidence that metabolic activity in the extracellular stage of chlamydiae is of major biological relevance as it is a critical factor affecting maintenance of infectivity.
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| 8. |
- Sixt, Barbara Susanne, et al.
(författare)
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Proteomic analysis reveals a virtually complete set of proteins for translation and energy generation in elementary bodies of the amoeba symbiont Protochlamydia amoebophila
- 2011
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Ingår i: Proteomics. - : Wiley-VCH Verlagsgesellschaft. - 1615-9853 .- 1615-9861. ; 11:10, s. 1868-1892
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Tidskriftsartikel (refereegranskat)abstract
- Chlamydiae belong to the most successful intracellular bacterial pathogens. They display a complex developmental cycle and an extremely broad host spectrum ranging from vertebrates to protozoa. The family Chlamydiaceae comprises exclusively well-known pathogens of humans and animals, whereas the members of its sister group, the Parachlamydiaceae, naturally occur as symbionts of free-living amoebae. Comparative analysis of these two groups provides valuable insights into chlamydial evolution and mechanisms for microbe-host interaction. Based on the complete genome sequence of the Acanthamoeba spp. symbiont Protochlamydia amoebophila UWE25, we performed the first detailed proteome analysis of the infectious stage of a symbiotic chlamydia. A 2-D reference proteome map was established and the analysis was extensively complemented by shotgun proteomics. In total, 472 proteins were identified, which represent 23.2% of all encoded proteins. These cover a wide range of functional categories, including typical house-keeping proteins, but also putative virulence-associated proteins. A number of proteins that are not encoded in genomes of Chlamydiaceae were observed and the expression of 162 proteins classified as hypothetical or unknown proteins could be demonstrated. Our findings indicate that P. amoebophila exploits its additional genetic repertoire (compared with the Chlamydiaceae), and that its elementary bodies are remarkably well equipped with proteins involved in transcription, translation, and energy generation.
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