213 research outputs found

    Coordination of Dynamic Software Components with JavaBIP

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    JavaBIP allows the coordination of software components by clearly separating the functional and coordination aspects of the system behavior. JavaBIP implements the principles of the BIP component framework rooted in rigorous operational semantics. Recent work both on BIP and JavaBIP allows the coordination of static components defined prior to system deployment, i.e., the architecture of the coordinated system is fixed in terms of its component instances. Nevertheless, modern systems, often make use of components that can register and deregister dynamically during system execution. In this paper, we present an extension of JavaBIP that can handle this type of dynamicity. We use first-order interaction logic to define synchronization constraints based on component types. Additionally, we use directed graphs with edge coloring to model dependencies among components that determine the validity of an online system. We present the software architecture of our implementation, provide and discuss performance evaluation results.Comment: Technical report that accompanies the paper accepted at the 14th International Conference on Formal Aspects of Component Softwar

    Costs and benefits of provocation in bacterial warfare

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    Bacteria live in dense environments where competition for space and resources is fierce. For this reason, they often use diffusible toxins to eliminate closely related strains. Some toxins trigger systematic retaliation, raising the question of the role of provocation in bacterial warfare. We combine mathematical modeling and experiments to study the costs and benefits of provocation. In one-to-one encounters, provocation is costly as it leads to strong counterattacks. However, with three or more strains present, provocation can provide benefits via a “divide-and-conquer” effect, whereby a strain forces its opponents to wipe each other out. This effect could be harnessed as a targeted antibacterial approach; adding low levels of certain antibiotics to communities can promote warfare and cross-elimination between strains

    Characterization of Complex Proteoform Mixtures by Online Nanoflow Ion-Exchange Chromatography-Native Mass Spectrometry

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    The characterization of proteins and complexes in biological systems is essential to establish their critical properties and to understand their unique functions in a plethora of bioprocesses. However, it is highly difficult to analyze low levels of intact proteins in their native states (especially those exceeding 30 kDa) with liquid chromatography (LC)-mass spectrometry (MS). Herein, we describe for the first time the use of nanoflow ion-exchange chromatography directly coupled with native MS to resolve mixtures of intact proteins. Reference proteins and protein complexes with molecular weights between 10 and 150 kDa and a model cell lysate were separated using a salt-mediated pH gradient method with volatile additives. The method allowed for low detection limits (0.22 pmol of monoclonal antibodies), while proteins presented nondenatured MS (low number of charges and limited charge state distributions), and the oligomeric state of the complexes analyzed was mostly kept. Excellent chromatographic separations including the resolution of different proteoforms of large proteins (>140 kDa) and a peak capacity of 82 in a 30 min gradient were obtained. The proposed setup and workflows show great potential for analyzing diverse proteoforms in native top-down proteomics, opening unprecedented opportunities for clinical studies and other sample-limited applications

    Bayesian probabilities for occurrence of large earthquakes in the seismogenic sources of Japan and Phillipine during the period 1998-2017

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    Στην μελέτη αυτή γίνεται χρήση της στατιστικής Bayes με σκοπό την εκτίμηση των πιθανοτήτων γένεσης μελλοντικών μεγάλων σεισμών, υιοθετώντας την υπόθεση ότι οι σεισμοί ακολουθούν κατανομή Poisson. Η μέθοδος που χρησιμοποιείται εκτιμά την πιθανότητα υπέρβασης σεισμών με καθορισμένο κατώφλι μεγέθους σε χρονικό διάστημα 20 ετών, δηλ. 1998-2017. Αυτό το κατώφλι επιλέγει να είναι το μέγεθος μεγαλύτερο ή ίσο του Μ=7.0. Οι πιθανότητες που εκτιμήθηκαν με τον τρόπο αυτό μπορεί να θεωρηθούν ότι παρουσιάζουν την σεισμικότητα. Στην συνέχεια με τα αποτελέσματα αυτά χαράσσονται γραμμές (καμπύλες) που παρουσιάζουν την διακύμανση της σεισμικότητας μεταξύ των σεισμογενών πηγών των περιοχών της Ιαπωνίας και των Φιλιππίνων. Οι γραφικές αυτές παραστάσεις, όπου εμφανίζεται η μεταβαλλόμενη σεισμικότητα είναι πολλαπλά χρήσιμες τόσο για θεωρητικούς όσο και για πρακτικούς σκοπούς.The Bayesian statistics is adopted in 11 seismic sources of Japan and 14 of Philippine in order to estimate the probabilities of occurrence of large future earthquakes, assuming that earthquakes occurrence follows the Poisson distribution. The Bayesian approach applied represents the probability that a certain cut-off magnitude (or larger) will exceed in a given time interval of 20 years, that is 1998-2017. This cut-off magnitude is chosen the one with M=7.0 or greater. In this case we can consider these obtained probabilities as a seismic hazard presentation. More over curves are produced which present the fluctuation of the seismic hazard between these seismic sources. These graphs of varying probability are useful either for engineering or other practical purpose

    c-Type cytochrome biogenesis can occur via a natural Ccm system lacking CcmH, CcmG, and the heme-binding histidine of CcmE

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    The Ccm cytochrome c maturation System I catalyzes covalent attachment of heme to apocytochromes c in many bacterial species and some mitochondria. A covalent, but transient, bond between heme and a conserved histidine in CcmE along with an interaction between CcmH and the apocytochrome have been previously indicated as core aspects of the Ccm system. Here, we show that in the Ccm system from Desulfovibrio desulfuricans, no CcmH is required, and the holo-CcmE covalent bond occurs via a cysteine residue. These observations call for reconsideration of the accepted models of System I-mediated c-type cytochrome biogenesis

    Breaking antimicrobial resistance by disrupting extracytoplasmic protein folding

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    Antimicrobial resistance in Gram-negative bacteria is one of the greatest threats to global health. New antibacterial strategies are urgently needed, and the development of antibiotic adjuvants that either neutralize resistance proteins or compromise the integrity of the cell envelope is of ever-growing interest. Most available adjuvants are only effective against specific resistance proteins. Here we demonstrate that disruption of cell envelope protein homeostasis simultaneously compromises several classes of resistance determinants. In particular, we find that impairing DsbA-mediated disulfide bond formation incapacitates diverse β-lactamases and destabilizes mobile colistin resistance enzymes. Furthermore, we show that chemical inhibition of DsbA sensitizes multidrug-resistant clinical isolates to existing antibiotics and that the absence of DsbA, in combination with antibiotic treatment, substantially increases the survival of Galleria mellonella larvae infected with multidrug-resistant Pseudomonas aeruginosa. This work lays the foundation for the development of novel antibiotic adjuvants that function as broad-acting resistance breakers.British Society for Antimicrobial Chemotherapy BSAC-2018-0095NC3Rs NC/V001582/1Biological Sciences Research Council BB/V007823/1Academy of Medical Sciences SBF006\104
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