102 research outputs found
Metastabil állapotok feltérképezése a fehérjék nyomás-hőmérséklet fázisdiagramján = Exploring metastable states on the pressure-temperature phase diagram of proteins
Munkánk fĹ‘ cĂ©lkitűzĂ©se a fehĂ©rjĂ©k nyomás-hĹ‘mĂ©rsĂ©klet fázisdiagramjának vizsgálata, a fázisdiagram metastabil rĂ©giĂłinak felderĂtĂ©se, valamint a metastabil tartományok kinetikai jellemzĂ©se volt. Az elsĹ‘ Ă©vben meghatároztuk a tojásfehĂ©rje-lizozim, a mioglobin, apomioglobin, tormaperoxidáz Ă©s az alfa krisztallin denaturáciĂłs nyomás- Ă©s hĹ‘mĂ©rsĂ©klet-adatait. A rĂ©szletes mĂ©rĂ©sekre a lizozimot szemeltĂĽk ki. A második Ă©vben megmĂ©rtĂĽk a lizozim nyomásdenaturáciĂłs pontjait kĂĽlönbözĹ‘ hĹ‘mĂ©rsĂ©kleteken. Kiszámoltuk a fázisátalakulás termodinamikai paramĂ©tereit. Ă–sszehasonlĂtáskĂ©nt tanulmányoztuk a tetramer hemoglobin denaturáciĂłját ill. disszociáciĂłját, valamint a kĂ©t domĂ©nbĹ‘l állĂł foszfoglicerát kináz ill. a három domĂ©nes humán szĂ©rumalbumin fehĂ©rje szĂ©ttekeredĂ©sĂ©t is, amelynĂ©l Ăşjdonságnak számĂt, hogy a fĂ©lretekeredett forma mĂ©g a natĂvnál is stabilabbnak tűnik. A harmadik Ă©vben a lizozim nyomásdenaturáciĂłja utáni visszatekeredĂ©s során mĂ©rtĂĽk a másodlagos szerkezet Ăşjraalakulásának Ă©s a közben formálĂłdĂł aggregátumok megjelenĂ©sĂ©nek kinetikáját. MegállapĂtottuk, hogy ezek a folyamatok nem ĂrhatĂłk le egyszerű kĂ©tállapotĂş rendszert feltĂ©telezve. Egy több kompartmentes modellt dolgoztunk ki, amelyik leĂrja az aggregáciĂł többlĂ©pcsĹ‘s jellegĂ©t. A kinetikai állandĂłk nyomás- Ă©s hĹ‘mĂ©rsĂ©kletfĂĽggĂ©sĂ©bĹ‘l megállapĂtottuk az aktiváciĂłs tĂ©rfogatot Ă©s az aktiváciĂłs energiát. EredmĂ©nyeinket eddig 6 cikkben publikáltuk Ezeken kĂvĂĽl mĂ©g kĂ©t cikk van elĹ‘kĂ©szĂĽletben a felsorolt kinetikai eredmĂ©nyekbĹ‘l. | The main aim of the work was the study of the pressure-temperature phase diagram of the proteins, in order to explore metastable regions on the diagram, and to characterize the kinetics of the structural changes in these metastable regions. In the first year the denaturation temperatures and pressures were detected for hen egg white lysozyme, myoglobin, apomyoglobin, horseradish peroxidase and alpha crystallin. Lysozyme was selected for further detailed study. In the second year the pressure denaturation of lysozyme was measured at different temperatures, in order to construct the phase diagram. The thermodynamic parameters of the phase transitions were determined. For comparison the pressure denaturation of the tetrameric hemoglobin, the two-domain phosphoglycerate-kinase and the three-domain human serum albumin were also measured. In the latter case an interesting feature has been found, namely that the misfolded form was more stable than the native one. In the third year we measured the kinetics of the refolding and aggregation after a pressure unfolding. These processes could not be described by a simple two-state model. A multi-compartment model was developed to describe the successive steps of the process. We calculated the activation volume and activation energy, using the pressure and temperature dependence of the kinetic constants. The results have been published in 6 articles in peer-reviewed journals. Two other papers are in preparation
Systematic Identification and Analysis of Hazards for Automated Systems
The introduction of automation into technical systems promises many benefits, including performance increase, improved resource economy, and fewer harmful accidents. In particular, in the automotive sector, automated driving is seen as one key element in Vision Zero by eliminating common accident causes such as driving under the influence, reckless behavior, or distracted drivers. However, this is contrasted by new failure modes and hazards from the latest technologies. In this article, we address the problems of finding common sources of criticality for specific application classes and identifying and quantitatively assessing new sources of harm within particular automated driving systems
Expressing best practices in (risk) analysis and testing of safety-critical systems using patterns
The continuing pervasion of our society with safety-critical cyber-physical systems not only demands for adequate (risk) analysis, testing and verification techniques, it also generates growing experience on their use, which can be considered as important as the tools themselves for their efficient use. This paper introduces workflow patterns to describe such best practices in a systematic way that efficiently represents this knowledge, and also provides a way to relate different patterns, making them easier to identify and use, and cover as wide a range of experiences as possible. The value of the approach is demonstrated using some pattern examples from a collection developed in the Artemis-project MBAT. Finally, the paper presents a wiki-based approach for developing and maintaining the pattern collection
B Cell Recognition of Candida albicans Hyphae via TLR 2 Promotes IgG1 and IL-6 Secretion for T H 17 Differentiation
Candida albicans is usually a benign member of the human gut microbiota, but can become pathogenic under certain circumstances, for example in an immunocompromised host. The innate immune system, in particular neutrophils and macrophages, constitutes a crucial first line of defense against fungal invasion, however adaptive immunity may provide long term protection and thus allow vaccination of at risk patients. While T H 1 and T H 17 cells are important for antifungal responses, the role of B cells and antibodies in protection from C. albicans infection is less well defined. In this study, we show that C. albicans hyphae but not yeast, as well as fungal cell wall components, directly activate B cells via MyD88 signaling triggered by Toll- like receptor 2, leading to increased IgG1 production. While Dectin-1 signals and specific recognition by the B cell receptor are dispensable for B cell activation in this system, TLR2/MyD88 signals cooperate with CD40 signals in promoting B cell activation. Importantly, recognition of C. albicans via MyD88 signaling is also essential for induction of IL-6 secretion by B cells, which promotes T H 17 polarization in T-B cell coculture experiments. B cells may thus be activated directly by C. albicans in its invasive form, leading to production of antibodies and T cell help for fungal clearance
Criticality Metrics for Automated Driving: A Review and Suitability Analysis of the State of the Art
The large-scale deployment of automated vehicles on public roads has the
potential to vastly change the transportation modalities of today's society.
Although this pursuit has been initiated decades ago, there still exist open
challenges in reliably ensuring that such vehicles operate safely in open
contexts. While functional safety is a well-established concept, the question
of measuring the behavioral safety of a vehicle remains subject to research.
One way to both objectively and computationally analyze traffic conflicts is
the development and utilization of so-called criticality metrics. Contemporary
approaches have leveraged the potential of criticality metrics in various
applications related to automated driving, e.g. for computationally assessing
the dynamic risk or filtering large data sets to build scenario catalogs. As a
prerequisite to systematically choose adequate criticality metrics for such
applications, we extensively review the state of the art of criticality
metrics, their properties, and their applications in the context of automated
driving. Based on this review, we propose a suitability analysis as a
methodical tool to be used by practitioners. Both the proposed method and the
state of the art review can then be harnessed to select well-suited measurement
tools that cover an application's requirements, as demonstrated by an exemplary
execution of the analysis. Ultimately, efficient, valid, and reliable
measurements of an automated vehicle's safety performance are a key requirement
for demonstrating its trustworthiness
Uniformly curated signaling pathways reveal tissue-specific cross-talks and support drug target discovery
Motivation: Signaling pathways control a large variety of cellular processes.
However, currently, even within the same database signaling pathways are often
curated at different levels of detail. This makes comparative and cross-talk
analyses difficult. Results: We present SignaLink, a database containing 8
major signaling pathways from Caenorhabditis elegans, Drosophila melanogaster,
and humans. Based on 170 review and approx. 800 research articles, we have
compiled pathways with semi-automatic searches and uniform, well-documented
curation rules. We found that in humans any two of the 8 pathways can
cross-talk. We quantified the possible tissue- and cancer-specific activity of
cross-talks and found pathway-specific expression profiles. In addition, we
identified 327 proteins relevant for drug target discovery. Conclusions: We
provide a novel resource for comparative and cross-talk analyses of signaling
pathways. The identified multi-pathway and tissue-specific cross-talks
contribute to the understanding of the signaling complexity in health and
disease and underscore its importance in network-based drug target selection.
Availability: http://SignaLink.orgComment: 9 pages, 4 figures, 2 tables and a supplementary info with 5 Figures
and 13 Table
Quantitative Timed Analysis of Interactive Markov Chains
Abstract This paper presents new algorithms and accompanying tool support for analyzing interactive Markov chains (IMCs), a stochastic timed 1 1 2-player game in which delays are exponentially distributed. IMCs are compositional and act as semantic model for engineering for-malisms such as AADL and dynamic fault trees. We provide algorithms for determining the extremal expected time of reaching a set of states, and the long-run average of time spent in a set of states. The prototypical tool Imca supports these algorithms as well as the synthesis of ε-optimal piecewise constant timed policies for timed reachability objectives. Two case studies show the feasibility and scalability of the algorithms.
Simulation of Abstract Scenarios: Towards Automated Tooling in Criticality Analysis
While the introduction of automated vehicles to public roads promises various ecological, economical and societal benefits, reliable verification & validation processes that guarantee safe operation of automated vehicles are subject to ongoing research. As automated vehicles are safety-critical complex systems, operating in an open context, the uncountable infinite set of potentially critical situations renders traditional, distance-based approaches to verification & validation infeasible. Leveraging the power of abstraction, current scenario-based approaches aim at reducing this complexity by elic-itation of representative scenario classes while simultaneously shifting significant analysis and testing efforts to virtual environments. In this work we bridge the gap between high-level, abstract scenario specifications and state-of-the-art detailed vehicle and traffic simulators. While the first allow for coverage argumentation with the definition of finite and well manageable sets of scenario classes the latter is necessary for a in-depth assessment of the vehicle implementation and its interaction with the physical environment. We present a method and prototypical implementation based on constraint solving techniques to generate (sets of) concrete simulation tasks defined in the well established OpenDRIVE/OpenSCENARIO formats from abstract scenarios specified as Traffic Sequence Charts. The feasibility is demonstrated using a highway parallel overtaking scenario as a running example
Workshop “PPP – Eignung und Vorgehensweise bei Hochschulprojekten“
Am 4. Oktober 2007 fand im Rahmen des Forschungsprojektes „Lebenszyklusorientiertes Management öffentlicher Liegenschaften am Beispiel von Hochschulen und Wissenschaftseinrichtungen“ in Weimar der Workshop „PPP-Eignung und Vorgehensweise bei Hochschulprojekten“ mit über 60 Vertretern von Hochschulen, Studentenwerken, Ministerien, PPP Task Forces und Liegenschaftsbetrieben der Länder statt. Im Beitrag erfolgt die Zusammenstellung der Präsentationen der Referenten
- …