14 research outputs found
Debugging of Web Applications with Web-TLR
Web-TLR is a Web verification engine that is based on the well-established
Rewriting Logic--Maude/LTLR tandem for Web system specification and
model-checking. In Web-TLR, Web applications are expressed as rewrite theories
that can be formally verified by using the Maude built-in LTLR model-checker.
Whenever a property is refuted, a counterexample trace is delivered that
reveals an undesired, erroneous navigation sequence. Unfortunately, the
analysis (or even the simple inspection) of such counterexamples may be
unfeasible because of the size and complexity of the traces under examination.
In this paper, we endow Web-TLR with a new Web debugging facility that supports
the efficient manipulation of counterexample traces. This facility is based on
a backward trace-slicing technique for rewriting logic theories that allows the
pieces of information that we are interested to be traced back through inverse
rewrite sequences. The slicing process drastically simplifies the computation
trace by dropping useless data that do not influence the final result. By using
this facility, the Web engineer can focus on the relevant fragments of the
failing application, which greatly reduces the manual debugging effort and also
decreases the number of iterative verifications.Comment: In Proceedings WWV 2011, arXiv:1108.208
Interactions of the periplasmic binding protein CeuE with Fe(III) n-LICAM(4-) siderophore analogues of varied linker length
Bacteria use siderophores to mediate the transport of essential Fe(III) into the cell. In Campylobacter jejuni the periplasmic binding protein CeuE, an integral part of the Fe(III) transport system, has adapted to bind tetradentate siderophores using a His and a Tyr side chain to complete the Fe(III) coordination. A series of tetradentate siderophore mimics was synthesized in which the length of the linker between the two iron-binding catecholamide units was increased from four carbon atoms (4-LICAM(4-)) to five, six and eight (5-, 6-, 8-LICAM(4-), respectively). Co-crystal structures with CeuE showed that the inter-planar angles between the iron-binding catecholamide units in the 5-, 6- and 8-LICAM(4-) structures are very similar (111°, 110° and 110°) and allow for an optimum fit into the binding pocket of CeuE, the inter-planar angle in the structure of 4-LICAM(4-) is significantly smaller (97°) due to restrictions imposed by the shorter linker. Accordingly, the protein-binding affinity was found to be slightly higher for 5- compared to 4-LICAM(4-) but decreases for 6- and 8-LICAM(4-). The optimum linker length of five matches that present in natural siderophores such as enterobactin and azotochelin. Site-directed mutagenesis was used to investigate the relative importance of the Fe(III)-coordinating residues H227 and Y288
Dissociations in the effects of beta2-adrenergic receptor agonists on cAMP formation and superoxide production in human neutrophils: Support for the concept of functional selectivity
In neutrophils, activation of the beta2-adrenergic receptor (beta2AR), a Gs-coupled receptor,
inhibits inflammatory responses, which could be therapeutically exploited. The aim of this study was to
evaluate the effects of various beta2AR ligands on adenosine-3',5'-cyclic monophosphate (cAMP)
accumulation and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-induced superoxide anion
(O2*-) production in human neutrophils and to probe the concept of ligand-specific receptor
conformations (also referred to as functional selectivity or biased signaling) in a native cell system.
cAMP concentration was determined by HPLC/tandem mass spectrometry, and O2*- formation was
assessed by superoxide dismutase-inhibitable reduction of ferricytochrome c. beta2AR agonists were
generally more potent in inhibiting fMLP-induced O2*- production than in stimulating cAMP
accumulation. (-)-Ephedrine and dichloroisoproterenol were devoid of any agonistic activity in the
cAMP assay, but partially inhibited fMLP-induced O2*- production. Moreover, (-)-adrenaline was equiefficacious
in both assays whereas the efficacy of salbutamol was more than two-fold higher in the O2*-
assay. In contrast to the agonists, the effects of beta2AR antagonists were comparable between the two
parameters on neutrophils. Differences between the data from neutrophils and recombinant test
systems were observed for the beta2AR agonists as well as for the beta2AR antagonists. Lastly, we
obtained no evidence for an involvement of protein kinase A in the inhibition of fMLP-induced O2*-
production after beta2AR-stimulation, although, in principle, cAMP-increasing substances can inhibit
O2*- production. Taken together, our data corroborate the concept of ligand-specific receptor
conformations with unique signaling capabilities and suggest that the beta2AR inhibits O2*-
production in a cAMP-independent manner