78 research outputs found

    Validity-Guided Synthesis of Reactive Systems from Assume-Guarantee Contracts

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    Automated synthesis of reactive systems from specifications has been a topic of research for decades. Recently, a variety of approaches have been proposed to extend synthesis of reactive systems from proposi- tional specifications towards specifications over rich theories. We propose a novel, completely automated approach to program synthesis which reduces the problem to deciding the validity of a set of forall-exists formulas. In spirit of IC3 / PDR, our problem space is recursively refined by blocking out regions of unsafe states, aiming to discover a fixpoint that describes safe reactions. If such a fixpoint is found, we construct a witness that is directly translated into an implementation. We implemented the algorithm on top of the JKind model checker, and exercised it against contracts written using the Lustre specification language. Experimental results show how the new algorithm outperforms JKinds already existing synthesis procedure based on k-induction and addresses soundness issues in the k-inductive approach with respect to unrealizable results.Comment: 18 pages, 5 figures, 2 table

    Cryopreservation and cryotherapy of grapevine (Vitis vinifera L.)

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    This study aimed at testing the efficiency of a droplet-vitrification cryopreservation protocol in eliminating selected grapevine viruses. The cryopreservation protocol led to approximately 50 % recovery with cultivar 'Portan' and five international cultivars tested, but very low recovery was noted with Croatian cultivars. GFLV and GLRaV-3, two (economically important grapevine) viruses were eliminated in a high percentage (up to 100 %) of plants regenerated from cryopreserved shoot tips. Virus sanitation was observed as well in samples before liquid nitrogen exposure. Genetic stability of plants regenerated after cryopreservation was studied using AFLP markers. Polymorphic fragments were observed in non-cryopreserved and cryopreserved samples treated with PVS2 solution, the number of which increased with increasing durations of exposure to PVS2 solution

    NCO-sP(EO-stat-PO) Coatings on Gold Sensors—a QCM Study of Hemocompatibility

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    The reliability of implantable blood sensors is often hampered by unspecific adsorption of plasma proteins and blood cells. This not only leads to a loss of sensor signal over time, but can also result in undesired host vs. graft reactions. Within this study we evaluated the hemocompatibility of isocyanate conjugated star shaped polytheylene oxide—polypropylene oxide co-polymers NCO-sP(EO-stat-PO) when applied to gold surfaces as an auspicious coating material for gold sputtered blood contacting sensors. Quartz crystal microbalance (QCM) sensors were coated with ultrathin NCO-sP(EO-stat-PO) films and compared with uncoated gold sensors. Protein resistance was assessed by QCM measurements with fibrinogen solution and platelet poor plasma (PPP), followed by quantification of fibrinogen adsorption. Hemocompatibility was tested by incubation with human platelet rich plasma (PRP). Thrombin antithrombin-III complex (TAT), β-thromboglobulin (β-TG) and platelet factor 4 (PF4) were used as coagulation activation markers. Furthermore, scanning electron microscopy (SEM) was used to visualize platelet adhesion to the sensor surfaces. Compared to uncoated gold sensors, NCO-sP(EO-stat-PO) coated sensors revealed significant better resistance against protein adsorption, lower TAT generation and a lower amount of adherent platelets. Moreover, coating with ultrathin NCO-sP(EO-stat-PO) films creates a cell resistant hemocompatible surface on gold that increases the chance of prolonged sensor functionality and can easily be modified with specific receptor molecules

    The European Vitis Database (www.eu-vitis.de) – a technical innovation through an online uploading and interactive modification system

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    The objective of the European Vitis Database is to safeguard and enhance germplasm by monitoring its preservation. Two issues are strongly related to that purpose: (1) participation of collections covering almost all grape biodiversity and (2) assessment of accessions trueness to type. In the scope of the European project GrapeGen06 efforts have been made towards both objectives. The 35 participating grape germplasm repositories are found between the Iberian Peninsula and Transcaucasia, thus covering a broad range of grape diversity. Altogether they maintain 32,410 accessions. However with respect to biodiversity, gaps are still evident and further collections need to be included and trueness to type assessment absolutely needs to be pursued to organize duplication of endangered genotypes. Within the GrapeGen06 project focus was laid on the establishment of a database conferring the collection holders a high degree of responsibility and independence. Hence for the first time in a European Central Crop Database an on-line uploading application and an interactive modification system for data administration was implemented. These innovations disburden the database manager and offer the curators of collections more flexibility. Prerequisites for data import, descriptors applied, access levels, database contents, uploading, export and search functions are described

    Agnostic B cell selection approach identifies antibodies against K. pneumoniae that synergistically drive complement activation

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    Antibody-dependent complement activation plays a key role in the natural human immune response to infections. Currently, the understanding of which antibody-antigen combinations drive a potent complement response on bacteria is limited. Here, we develop an antigen-agnostic approach to stain and single-cell sort human IgG memory B cells recognizing intact bacterial cells, keeping surface antigens in their natural context. With this method we successfully identified 29 antibodies against K. pneumoniae, a dominant cause of hospital-acquired infections with increasing antibiotic resistance. Combining genetic tools and functional analyses, we reveal that the capacity of antibodies to activate complement on K. pneumoniae critically depends on their antigenic target. Furthermore, we find that antibody combinations can synergistically activate complement on K. pneumoniae by strengthening each other's binding in an Fc-independent manner. Understanding the molecular basis of effective complement activation by antibody combinations to mimic a polyclonal response could accelerate the development of antibody-based therapies against problematic infections

    C1q binding to surface-bound IgG is stabilized by C1r(2)s(2) proteases

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    Complement is an important effector mechanism for antibodymediated clearance of infections and tumor cells. Upon binding to target cells, the antibody's constant (Fc) domain recruits complement component C1 to initiate a proteolytic cascade that generates lytic pores and stimulates phagocytosis. The C1 complex (C1qr2s2) consists of the large recognition protein C1q and a heterotetramer of proteases C1r and C1s (C1r2s2). While interactions between C1 and IgG-Fc are believed to be mediated by the globular heads of C1q, we here find that C1r2s2 proteases affect the capacity of C1q to form an avid complex with surface-bound IgG molecules (on various 2,4-dinitrophenol [DNP]-coated surfaces and pathogenic Staphylococcus aureus). The extent to which C1r2s2 contributes to C1q-IgG stability strongly differs between human IgG subclasses. Using antibody engineering of monoclonal IgG, we reveal that hexamer-enhancing mutations improve C1q-IgG stability, both in the absence and presence of C1r2s2. In addition, hexamer-enhanced IgGs targeting S. aureus mediate improved complement-dependent phagocytosis by human neutrophils. Altogether, these molecular insights into complement binding to surface-bound IgGs could be important for optimal design of antibody therapies.Transplantation and autoimmunit
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