531 research outputs found
Viewpoint consistency in Z and LOTOS: A case study
Specification by viewpoints is advocated as a suitable method of specifying complex systems. Each viewpoint describes the envisaged system from a particular perspective, using concepts and specification languages best suited for that perspective. Inherent in any viewpoint approach is the need to check or manage the consistency of viewpoints and to show that the different viewpoints do not impose contradictory requirements. In previous work we have described a range of techniques for consistency checking, refinement, and translation between viewpoint specifications, in particular for the languages LOTOS and Z. These two languages are advocated in a particular viewpoint model, viz. that of the Open Distributed Processing (ODP) reference model. In this paper we present a case study which demonstrates how all these techniques can be combined in order to show consistency between a viewpoint specified in LOTOS and one specified in Z. Keywords: Viewpoints; Consistency; Z; LOTOS; ODP
Relaxation Dynamics of Pseudomonas aeruginosa Re^I(C)O_3(α-diimine)(HisX)^+ (X=83, 107, 109, 124, 126)Cu-^(II) Azurins
Photoinduced relaxation processes of five structurally characterized Pseudomonas aeruginosa Re^I(CO)_3(α-diimine)(HisX) (X = 83, 107, 109, 124, 126)Cu^(II) azurins have been investigated by time-resolved (psâns) IR spectroscopy and emission spectroscopy. Crystal structures reveal the presence of Re-azurin dimers and trimers that in two cases (X = 107, 124) involve van der Waals interactions between interdigitated diimine aromatic rings. Time-dependent emission anisotropy measurements confirm that the proteins aggregate in mM solutions (D2O, KPi buffer, pD = 7.1). Excited-state DFT calculations show that extensive charge redistribution in the ReI(CO)_3 â diimine ^3MLCT state occurs: excitation of this ^3MLCT state triggers several relaxation processes in Re-azurins whose kinetics strongly depend on the location of the metallolabel on the protein surface. Relaxation is manifested by dynamic blue shifts of excited-state Îœ(CO) IR bands that occur with triexponential kinetics: intramolecular vibrational redistribution together with vibrational and solvent relaxation give rise to subps, 2, and 8â20 ps components, while the ~10^2 ps kinetics are attributed to displacement (reorientation) of the Re^I(CO)_3(phen)(im) unit relative to the peptide chain, which optimizes Coulombic interactions of the Re^I excited-state electron density with solvated peptide groups. Evidence also suggests that additional segmental movements of Re-bearing ÎČ-strands occur without perturbing the reaction field or interactions with the peptide. Our work demonstrates that time-resolved IR spectroscopy and emission anisotropy of Re^I carbonylâdiimine complexes are powerful probes of molecular dynamics at or around the surfaces of proteins and proteinâprotein interfacial regions
Structure of Blood Coagulation Factor VIII in Complex with Anti-C2 Domain Inhibitory Antibody
Factor VIII (fVIII) is a procoagulant protein that binds to activated factor IX (fIXa) on platelet surfaces to form the intrinsic tenase complex. Due to the high immunogenicity of fVIII, generation of antibody inhibitors is a common occurrence in patients during hemophilia A treatment and spontaneously occurs in acquired hemophilia A patients. Non-classical antibody inhibitors, which block fVIII activation by thrombin and formation of the tenase complex, are the most common anti-C2 domain pathogenic inhibitors in hemophilia A murine models and have been identified in patient plasmas. In this study, we report on the X-ray crystal structure of a B domain-deleted bioengineered fVIII bound to the non classical antibody inhibitor, G99. While binding to G99 does not disrupt the overall domain architecture of fVIII, the C2 domain undergoes an ~8 Ă
translocation that is concomitant with breaking multiple domain-domain interactions. Analysis of normalized B-factor values revealed several solvent-exposed loops in the C1 and C2 domains which experience a decrease in thermal motion in the presence of inhibitory antibodies. Our results enhance our understanding on the structural nature of binding non-classical inhibitors and provide a structural dynamics-based rationale for cooperativity between anti-C domain inhibitors
Structure of Blood Coagulation Factor VIII in Complex With an Anti-C2 Domain Non-Classical, Pathogenic Antibody Inhibitor
Factor VIII (fVIII) is a procoagulant protein that binds to activated factor IX (fIXa) on platelet surfaces to form the intrinsic tenase complex. Due to the high immunogenicity of fVIII, generation of antibody inhibitors is a common occurrence in patients during hemophilia A treatment and spontaneously occurs in acquired hemophilia A patients. Non-classical antibody inhibitors, which block fVIII activation by thrombin and formation of the tenase complex, are the most common anti-C2 domain pathogenic inhibitors in hemophilia A murine models and have been identified in patient plasmas. In this study, we report on the X-ray crystal structure of a B domain-deleted bioengineered fVIII bound to the non-classical antibody inhibitor, G99. While binding to G99 does not disrupt the overall domain architecture of fVIII, the C2 domain undergoes an ~8 Ă
translocation that is concomitant with breaking multiple domain-domain interactions. Analysis of normalized B-factor values revealed several solvent-exposed loops in the C1 and C2 domains which experience a decrease in thermal motion in the presence of inhibitory antibodies. These results enhance our understanding on the structural nature of binding non-classical inhibitors and provide a structural dynamics-based rationale for cooperativity between anti-C1 and anti-C2 domain inhibitors
Observation of resonances consistent with pentaquark states in decays
Observations of exotic structures in the channel, that we refer to
as pentaquark-charmonium states, in decays are
presented. The data sample corresponds to an integrated luminosity of 3/fb
acquired with the LHCb detector from 7 and 8 TeV pp collisions. An amplitude
analysis is performed on the three-body final-state that reproduces the
two-body mass and angular distributions. To obtain a satisfactory fit of the
structures seen in the mass spectrum, it is necessary to include two
Breit-Wigner amplitudes that each describe a resonant state. The significance
of each of these resonances is more than 9 standard deviations. One has a mass
of MeV and a width of MeV, while the second
is narrower, with a mass of MeV and a width of MeV. The preferred assignments are of opposite parity, with one
state having spin 3/2 and the other 5/2.Comment: 48 pages, 18 figures including the supplementary material, v2 after
referee's comments, now 19 figure
Search for hidden-sector bosons in decays
A search is presented for hidden-sector bosons, , produced in the decay
, with and
. The search is performed using -collision data
corresponding to 3.0 fb collected with the LHCb detector. No significant
signal is observed in the accessible mass range
MeV, and upper limits are placed on the branching fraction product
as
a function of the mass and lifetime of the boson. These limits are of
the order of for lifetimes less than 100 ps over most of the
range, and place the most stringent constraints to date on many
theories that predict the existence of additional low-mass bosons.Comment: All figures and tables, along with supplementary material, are
available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-036.htm
Measurement of the lifetime
Using a data set corresponding to an integrated luminosity of ,
collected by the LHCb experiment in collisions at centre-of-mass energies
of 7 and 8 TeV, the effective lifetime in the
decay mode, , is measured to be ps. Assuming
conservation, corresponds to the lifetime of the light
mass eigenstate. This is the first measurement of the effective
lifetime in this decay mode.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-017.htm
Measurement of the branching fraction ratio
Using collision data collected by LHCb at center-of-mass energies
= 7 TeV and 8 TeV, corresponding to an integrated luminosity of 3
fb, the ratio of the branching fraction of the decay relative to that of the
decay is measured to be 0.268 0.032 (stat) 0.007 (syst) 0.006
(BF). The first uncertainty is statistical, the second is systematic, and the
third is due to the uncertainties on the branching fractions of the and decays. This
measurement is consistent with the previous LHCb result, and the statistical
uncertainty is halved.Comment: 17 pages including author list, 2 figure
Measurement of the mass and lifetime of the baryon
A proton-proton collision data sample, corresponding to an integrated
luminosity of 3 fb collected by LHCb at and 8 TeV, is used
to reconstruct , decays. Using the , decay mode for calibration, the lifetime ratio and absolute
lifetime of the baryon are measured to be \begin{align*}
\frac{\tau_{\Omega_b^-}}{\tau_{\Xi_b^-}} &= 1.11\pm0.16\pm0.03, \\
\tau_{\Omega_b^-} &= 1.78\pm0.26\pm0.05\pm0.06~{\rm ps}, \end{align*} where the
uncertainties are statistical, systematic and from the calibration mode (for
only). A measurement is also made of the mass difference,
, and the corresponding mass, which
yields \begin{align*} m_{\Omega_b^-}-m_{\Xi_b^-} &= 247.4\pm3.2\pm0.5~{\rm
MeV}/c^2, \\ m_{\Omega_b^-} &= 6045.1\pm3.2\pm 0.5\pm0.6~{\rm MeV}/c^2.
\end{align*} These results are consistent with previous measurements.Comment: 11 pages, 5 figures, All figures and tables, along with any
supplementary material and additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-008.htm
Constraints on the unitarity triangle angle from Dalitz plot analysis of decays
The first study is presented of CP violation with an amplitude analysis of
the Dalitz plot of decays, with , and . The analysis is based on a data sample corresponding to
of collisions collected with the LHCb detector. No
significant CP violation effect is seen, and constraints are placed on the
angle of the unitarity triangle formed from elements of the
Cabibbo-Kobayashi-Maskawa quark mixing matrix. Hadronic parameters associated
with the decay are determined for the first time. These
measurements can be used to improve the sensitivity to of existing and
future studies of the decay.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-059.html;
updated to correct figure 9 (numerical results unchanged
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