169 research outputs found

    Early evaluation of security functionality in software projects - some experience on using the common criteria in a quality management process

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    This paper documents the experiences of assurance evaluation during the early stage of a large software development project. This project researches, contracts and integrates privacy-respecting software to business environments. While assurance evaluation with ISO 15408 Common Criteria (CC) within the certification schemes is done after a system has been completed, our approach executes evaluation during the early phases of the software life cycle. The promise is to increase quality and to reduce testing and fault removal costs for later phases of the development process. First results from the still-ongoing project suggests that the Common Criteria can define a framework for assurance evaluation in ongoing development projects.Dieses Papier dokumentiert den Versuch, mittels der Common Criteria nach ISO 15408 bereits wĂ€hrend der Erstellung eines Softwaresystems dessen Sicherheitseigenschaften zu ĂŒberprĂŒfen. Dies geschieht im Gegensatz zur ĂŒblichen Post-Entwicklungs-Evaluation

    Evaluation der multicolor Fluoreszenz-in-situ-Hybridisierung zur Diagnostik von Harnblasentumoren

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    Die Fluoreszenz-in-situ-Hybridisierung (mFISH) ermöglicht die Diagnostik von Urothelkarzinomen mit einer höheren SensitivitĂ€t als die Urinzytologie bei einer vergleichbaren SpezifitĂ€t. Unsicherheiten bestehen jedoch aufgrund einer erheblichen Schwankungsbreite der publizierten Ergebnisse und der geringen SensitivitĂ€t in der Diagnostik von nicht muskelinvasiven gut differenzierten Tumoren. Anhand der Urinuntersuchungen (144) konnte fĂŒr die mFISH eine SensitivitĂ€t von 49,5 % bei einer SpezifitĂ€t von 81,5 % festgestellt werden. FĂŒr pTa-, pT1- und fĂŒr muskelinvasive Tumoren (≄ pT2a) ließ sich eine SensitivitĂ€t von 35,9, 62,5 und 100 %, fĂŒr die G1-, G2- und G3-Tumoren 35,6, 60,7 und 91,7 % ermitteln. Die zum Vergleich parallel angefertigte Urinzytologie konnte eine SensitivitĂ€t von 41,5 % (pTa: 35,6, pT1: 45,8, pT2a: 87,5, G1: 30,3, G2 und G3: 60 %) bei einer SpezifitĂ€t von 79,3 % erreichen. Durch die Kombination beider Methoden (Zytologie und mFISH) ließ sich die SensitivitĂ€t auf 57,5 % (pTa: 46,2, pT1: 75, Âł pT2a: 100, G1: 41,4, G2: 80,7 und G3: 91,7 %) erhöhen. Die SpezifitĂ€t betrug hierbei 74,2 %. Eine höhere SensitivitĂ€t von 74 % ergab sich fĂŒr die parallel durchgefĂŒhrten mFISH des Tumormateriales (73 FĂ€lle) (pTa: 70,6, pT1: 76,9, pT2a: 85,7, pT3a: 100, pT3b: 100, G1: 68,8, G2: 75 und G3: 100 %). Es konnte gezeigt werden, dass die mFISH im Vergleich zur Urinzytologie eine höhere SensitivitĂ€t bei vergleichbarer SpezifitĂ€t aufweist. Bei schlecht differenzierten Tumoren und muskelinvasiven Befunden ist eine sichere Aussage möglich. Durch die Kombination der Urinzytologie mit der mFISH kann eine weitere Verbesserung der SensitivitĂ€t erreicht werden. Anhand des Vergleiches mit den Tumorgewebeproben ließen sich Ansatzpunkte fĂŒr eine Verbesserung des Tests erkennen. So besteht die Möglichkeit durch weitere Sonden, welche frĂŒhe genetische VerĂ€nderungen der Urothelkarzinome erfassen, die SensitivitĂ€t dieses Tests zu erhöhen

    Social Networks im Zeitalter des demographischen Wandels: Senioren als „Digital Immigrants“ in virtuellen Umgebungen

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    Diese Dissertation thematisiert den Umgang von Senioren mit virtuellen Umgebungen. Insbesondere liegt der Betrachtungsfokus auf Social Network Sites (SNSs), allerdings werden andere virtuelle Umgebungen nicht ausgeschlossen. Diese Betrachtung geschieht unter der BerĂŒcksichtigung zweier aktueller Trends. Das so entstehende Spannungsfeld zwischen der steigenden Interaktion in diesen virtuellen Netzwerken generell und einem demographischen Wandel hin zur gesellschaftlichen Alterung umfasst die HaupteinflĂŒsse fĂŒr die Themenstellung. Gegenstand der Analyse dieser Arbeit ist, wie Senioren den Umgang mit den virtuellen Umgebungen erlernen können. Dies setzt am eingangs beschriebenen Unterschied zwischen „Digital Natives“ und „Digital Immigrants“ (zu denen auch die Senioren gehören) an, den sogenannten „Digital Divide“. Um die Kluft in der FĂ€higkeit des Umgangs mit diesen Umgebungen zu ĂŒberwinden, hilft ein VerstĂ€ndnis ĂŒber die LernansĂ€tze der Senioren bei einem effizienteren Design der virtuellen Umgebungen (wie z.B. SNS). Zur Analyse der LernansĂ€tze wird exemplarisch die Lerntheorie des Lerndreiecks von Knud Illeris als ErklĂ€rungshilfe herangezogen

    Thermorheology of living cells: impact of temperature variations on cell mechanics

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    Upon temperature changes, we observe a systematic shift of creep compliance curves J (t) for single living breast epithelial cells. We use a dual-beam laser trap (optical stretcher) to induce temperature jumps within milliseconds, while simultaneously measuring the mechanical response of whole cells to optical force. The cellular mechanical response was found to differ between sudden temperature changes compared to slow, long-term changes implying adaptation of cytoskeletal structure. Interpreting optically induced cell deformation as a thermorheological experiment allows us to consistently explain data on the basis of time–temperature superposition, well known from classical polymer physics. Measured time shift factors give access to the activation energy of the viscous flow of MCF-10A breast cells, which was determined to be 80 kJ mol−1. The presented measurements highlight the fundamental role that temperature plays for the deformability of cellular matter. We propose thermorheology as a powerful concept to assess the inherent material properties of living cells and to investigate cell regulatory responses upon environmental changes

    LC-MS/MS-based proteome profiling in Daphnia pulex and Daphnia longicephala: the Daphnia pulex genome database as a key for high throughput proteomics in Daphnia

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    <p>Abstract</p> <p>Background</p> <p>Daphniids, commonly known as waterfleas, serve as important model systems for ecology, evolution and the environmental sciences. The sequencing and annotation of the <it>Daphnia pulex </it>genome both open future avenues of research on this model organism. As proteomics is not only essential to our understanding of cell function, and is also a powerful validation tool for predicted genes in genome annotation projects, a first proteomic dataset is presented in this article.</p> <p>Results</p> <p>A comprehensive set of 701,274 peptide tandem-mass-spectra, derived from <it>Daphnia pulex</it>, was generated, which lead to the identification of 531 proteins. To measure the impact of the <it>Daphnia pulex </it>filtered models database for mass spectrometry based <it>Daphnia </it>protein identification, this result was compared with results obtained with the Swiss-Prot and the <it>Drosophila melanogaster </it>database. To further validate the utility of the <it>Daphnia pulex </it>database for research on other <it>Daphnia </it>species, additional 407,778 peptide tandem-mass-spectra, obtained from <it>Daphnia longicephala</it>, were generated and evaluated, leading to the identification of 317 proteins.</p> <p>Conclusion</p> <p>Peptides identified in our approach provide the first experimental evidence for the translation of a broad variety of predicted coding regions within the <it>Daphnia </it>genome. Furthermore it could be demonstrated that identification of <it>Daphnia longicephala </it>proteins using the <it>Daphnia pulex </it>protein database is feasible but shows a slightly reduced identification rate. Data provided in this article clearly demonstrates that the <it>Daphnia </it>genome database is the key for mass spectrometry based high throughput proteomics in <it>Daphnia</it>.</p

    The MarR-Type Repressor MhqR Confers Quinone and Antimicrobial Resistance in Staphylococcus aureus

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    Aims: Quinone compounds are electron carriers and have antimicrobial and toxic properties due to their mode of actions as electrophiles and oxidants. However, the regulatory mechanism of quinone resistance is less well understood in the pathogen Staphylococcus aureus. Results: Methylhydroquinone (MHQ) caused a thiol-specific oxidative and electrophile stress response in the S. aureus transcriptome as revealed by the induction of the PerR, QsrR, CstR, CtsR, and HrcA regulons. The SACOL2531-29 operon was most strongly upregulated by MHQ and was renamed as mhqRED operon based on its homology to the Bacillus subtilis locus. Here, we characterized the MarR-type regulator MhqR (SACOL2531) as quinone-sensing repressor of the mhqRED operon, which confers quinone and antimicrobial resistance in S. aureus. The mhqRED operon responds specifically to MHQ and less pronounced to pyocyanin and ciprofloxacin, but not to reactive oxygen species (ROS), hypochlorous acid, or aldehydes. The MhqR repressor binds specifically to a 9–9 bp inverted repeat (MhqR operator) upstream of the mhqRED operon and is inactivated by MHQ in vitro, which does not involve a thiol-based mechanism. In phenotypic assays, the mhqR deletion mutant was resistant to MHQ and quinone-like antimicrobial compounds, including pyocyanin, ciprofloxacin, norfloxacin, and rifampicin. In addition, the mhqR mutant was sensitive to sublethal ROS and 24 h post-macrophage infections but acquired an improved survival under lethal ROS stress and after long-term infections. Innovation: Our results provide a link between quinone and antimicrobial resistance via the MhqR regulon of S. aureus. Conclusion: The MhqR regulon was identified as a novel resistance mechanism towards quinone-like antimicrobials and contributes to virulence of S. aureus under long-term infections

    Complex thermorheology of living cells

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    Temperature has a reliable and nearly instantaneous influence onmechanical responses of cells.As recently published, MCF-10Anormal epithelial breast cells follow the time–temperature superposition (TTS) principle. Here,wemeasured thermorheological behaviour of eightcommoncell types within physiologically relevant temperatures and appliedTTS to creep compliance curves.Our results showed that superposition is not universal and was seen in four of the eight investigated cell types. For the other cell types, transitions of thermorheological responses were observed at 36 °C.Activation energies (EA)were calculated for all cell types and ranged between 50 and 150 kJmol−1.The scaling factors of the superposition of creep curves were used to group the cell lines into three categories. They were dependent on relaxation processes aswell as structural composition of the cells in response tomechanical load and temperature increase.This study supports the view that temperature is a vital parameter for comparing cell rheological data and should be precisely controlledwhen designing experiments

    Thermal instability of cell nuclei

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    DNA is known to be a mechanically and thermally stable structure. In its double stranded form it is densely packed within the cell nucleus and is thermo-resistant up to 70 °C. In contrast, we found a sudden loss of cell nuclei integrity at relatively moderate temperatures ranging from 45 to 55 °C. In our study, suspended cells held in an optical double beam trap were heated under controlled conditions while monitoring the nuclear shape. At specific critical temperatures, an irreversible sudden shape transition of the nuclei was observed. These temperature induced transitions differ in abundance and intensity for various normal and cancerous epithelial breast cells, which clearly characterizes different cell types. Our results show that temperatures slightly higher than physiological conditions are able to induce instabilities of nuclear structures, eventually leading to cell death. This is a surprising finding since recent thermorheological cell studies have shown that cells have a lower viscosity and are thus more deformable upon temperature increase. Since the nucleus is tightly coupled to the outer cell shape via the cytoskeleton, the force propagation of nuclear reshaping to the cell membrane was investigated in combination with the application of cytoskeletal drugs

    Testing the differential adhesion hypothesis across the epithelial− mesenchymal transition

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    Weanalyze the mechanical properties of three epithelial/mesenchymal cell lines (MCF-10A, MDAMB- 231, MDA-MB-436) that exhibit a shift in E-, N- and P-cadherin levels characteristic of an epithelial−mesenchymal transition associated with processes such as metastasis, to quantify the role of cell cohesion in cell sorting and compartmentalization. Wedevelop a unique set of methods to measure cell–cell adhesiveness, cell stiffness and cell shapes, and compare the results to predictions from cell sorting in mixtures of cell populations.Wefind that the final sorted state is extremely robust among all three cell lines independent of epithelial or mesenchymal state, suggesting that cell sorting may play an important role in organization and boundary formation in tumours.Wefind that surface densities of adhesive molecules do not correlate with measured cell–cell adhesion, but do correlate with cell shapes, cell stiffness and the rate at which cells sort, in accordance with an extended version of the differential adhesion hypothesis (DAH). Surprisingly, theDAHdoes not correctly predict the final sorted state. This suggests that these tissues are not behaving as immiscible fluids, and that dynamical effects such as directional motility, friction and jamming may play an important role in tissue compartmentalization across the epithelial−mesenchymal transition
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