370 research outputs found

    Langerin-Heparin Interaction: Two Binding Sites for Small and Large Ligands as revealed by a combination of NMR Spectroscopy and Cross-Linking Mapping Experiments

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    Langerin is a C-type lectin present on Langerhans cells that mediates capture of pathogens in a carbohydrate-dependent manner, leading to subsequent internalization and elimination in the cellular organelles called Birbeck granules. This mechanism mediated by langerin was shown to constitute a natural barrier for HIV-1 particle transmission. Besides interacting specifically with high mannose and fucosylated neutral carbohydrate structures, langerin has the ability to bind sulfated carbohydrate ligands as 6-sulfated galactosides in the Ca2+ dependent binding site. Very recently langerin was demonstrated to interact with sulfated glycosaminoglycans (GAGs), in a Ca2+ independent way, resulting in the proposal of a new binding site for GAGs. Based on those results, we have conducted a structural study of the interactions of small heparin (HEP) like oligosaccharides with langerin in solution. Heparin-bead cross-linking experiments, an approach specifically designed to identify HEP/HS binding sites in proteins were first carried out and experimentally validated the previously proposed model for the interaction of Lg ECD with 6 kDa HEP. High-resolution NMR studies of a set of 8 synthetic HEP-like trisaccharides harboring different sulfation patterns demonstrated that all of them bound to langerin in a Ca2+ dependent way. The binding epitopes were determined by STD NMR and the bound conformations by transferred NOESY experiments. These experimental data were combined with docking and molecular dynamics and resulted in the proposal of a binding mode characterized by the coordination of calcium by the two equatorial hydroxyl groups OH3 and OH4 at the non-reducing end. The binding also includes the carboxylate group at the adjacent iduronate residue. Such epitope is shared by all the 8 ligands, explaining the absence of any impact on binding from their differences in substitution pattern. Finally, in contrast to the small trisaccharides, we demonstrated that a longer HEP-like hexasaccharide, bearing an additional O-sulfate group at the non-reducing end, which precludes binding to the Ca2+ site, interacts with langerin in the previously identified Ca2+ independent binding site

    Usefulness of an Intrapartum Ultrasound Simulator (IUSimℱ) for Midwife Training: Results from an RCT

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    Introduction: We conducted a randomized study to determine whether a training session on a dedicated simulator (IUSimℱ) would facilitate the midwives in learning the technique of transperineal intrapartum ultrasound. Methods: Following a 30-min multimedia presentation including images and videos on how to obtain and measure the angle of progression (AoP) and the head-perineum distance (HPD), 6 midwives with no prior experience in intrapartum ultrasound were randomly split into 2 groups: 3 of them were assigned to the "training group"and 3 to the "control group."The midwives belonging to the former group were taught to measure the 2 sonographic parameters during a 3-h practical session conducted on IUSimℱ under the supervision of an expert obstetrician. In the following 3 months, all the 6 midwives were asked to independently perform transperineal ultrasound during their clinical practice and to measure on the acquired images either the AoP or the HPD. The sonographic images were examined in blind by the teaching obstetrician who assigned a 0-3 score to the image quality (IQS) and to the measurement quality (MQS). Results: A total of 48 ultrasound images (24 patients) from 5 midwives were acquired and included in the study analysis. A midwife of the "training group"declined participation after the practical session. Independently from the randomization group, the image quality score (IQS + MQS) was significantly higher for the HPD compared with the AoP (2.5 ± 0.66 vs. 1.79 ± 1.14; p = 0.01). In the training group, the MQS of either AoP (2.66 ± 0.5 vs.1.46 ± 1.45. p = 0.038) and the HPD (2.9 ± 0.33 vs. 1.87 ± 0.83 p = 0.002) was significantly higher in comparison with the control group, while the IQS of both measurements was comparable between the 2 groups (1.91 ± 1.24 vs. 2.25 ± 0.865; p = 0.28). Conclusion: The use of a dedicated simulator may facilitate the midwives in learning how to measure the AoP and the HPD on transperineal ultrasound images

    Open source challenges for hospital information system (HIS) in developing countries: a pilot project in Mali

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    <p>Abstract</p> <p>Background</p> <p>We are currently witnessing a significant increase in use of Open Source tools in the field of health. Our study aims to research the potential of these software packages for developing countries. Our experiment was conducted at the Centre Hospitalier Mere Enfant in Mali.</p> <p>Methods</p> <p>After reviewing several Open Source tools in the field of hospital information systems, Mediboard software was chosen for our study. To ensure the completeness of Mediboard in relation to the functionality required for a hospital information system, its features were compared to those of a well-defined comprehensive record management tool set up at the University Hospital "La Timone" of Marseilles in France. It was then installed on two Linux servers: a first server for testing and validation of different modules, and a second one for the deployed full implementation. After several months of use, we have evaluated the usability aspects of the system including feedback from end-users through a questionnaire.</p> <p>Results</p> <p>Initial results showed the potential of Open Source in the field of health IT for developing countries like Mali.</p> <p>Five main modules have been fully implemented: patient administrative and medical records management of hospital activities, tracking of practitioners' activities, infrastructure management and the billing system. This last component of the system has been fully developed by the local Mali team.</p> <p>The evaluation showed that the system is broadly accepted by all the users who participated in the study. 77% of the participants found the system useful; 85% found it easy; 100% of them believe the system increases the reliability of data. The same proportion encourages the continuation of the experiment and its expansion throughout the hospital.</p> <p>Conclusions</p> <p>In light of the results, we can conclude that the objective of our study was reached. However, it is important to take into account the recommendations and the challenges discussed here to avoid several potential pitfalls specific to the context of Africa.</p> <p>Our future work will target the full integration of the billing module in Mediboard and an expanded implementation throughout the hospital.</p

    The E00-110 experiment in Jefferson Lab's Hall A: Deeply Virtual Compton Scattering off the Proton at 6 GeV

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    We present final results on the photon electroproduction (e⃗p→epγ\vec{e}p\rightarrow ep\gamma) cross section in the deeply virtual Compton scattering (DVCS) regime and the valence quark region from Jefferson Lab experiment E00-110. Results from an analysis of a subset of these data were published before, but the analysis has been improved which is described here at length, together with details on the experimental setup. Furthermore, additional data have been analyzed resulting in photon electroproduction cross sections at new kinematic settings, for a total of 588 experimental bins. Results of the Q2Q^2- and xBx_B-dependences of both the helicity-dependent and helicity-independent cross sections are discussed. The Q2Q^2-dependence illustrates the dominance of the twist-2 handbag amplitude in the kinematics of the experiment, as previously noted. Thanks to the excellent accuracy of this high luminosity experiment, it becomes clear that the unpolarized cross section shows a significant deviation from the Bethe-Heitler process in our kinematics, compatible with a large contribution from the leading twist-2 DVCS2^2 term to the photon electroproduction cross section. The necessity to include higher-twist corrections in order to fully reproduce the shape of the data is also discussed. The DVCS cross sections in this paper represent the final set of experimental results from E00-110, superseding the previous publication.Comment: 48 pages, 32 figure

    The roles of transparency and trust in the relationship between corruption and citizen satisfaction

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    Reducing corruption and improving citizen satisfaction are important aims of government, yet the link between these two policy aims has rarely been explored. This article reports a study into the roles played by transparency and trust in the relationship between governmental corruption and citizen satisfaction with public services. The study was based on data gathered in South Korea to evaluate a specific initiative that had sought to reduce corruption and increase citizen satisfaction with public works programmes. The data indicated that the relationship between corruption and satisfaction was moderated by transparency and partially mediated by trust. Points for practitioners: The study sheds light on the roles of transparency and trust in the relationship between corruption and citizen satisfaction with public services, and thus provides insights for developing policy aimed at curtailing corruption and improving satisfaction

    Scaling Tests of the Cross Section for Deeply Virtual Compton Scattering

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    We present the first measurements of the \vec{e}p->epg cross section in the deeply virtual Compton scattering (DVCS) regime and the valence quark region. The Q^2 dependence (from 1.5 to 2.3 GeV^2) of the helicity-dependent cross section indicates the twist-2 dominance of DVCS, proving that generalized parton distributions (GPDs) are accessible to experiment at moderate Q^2. The helicity-independent cross section is also measured at Q^2=2.3 GeV^2. We present the first model-independent measurement of linear combinations of GPDs and GPD integrals up to the twist-3 approximation.Comment: 5 pages, 4 figures, 2 tables. Text shortened for publication. References added. One figure remove

    Deeply Virtual Compton Scattering off the neutron

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    The present experiment exploits the interference between the Deeply Virtual Compton Scattering (DVCS) and the Bethe-Heitler processes to extract the imaginary part of DVCS amplitudes on the neutron and on the deuteron from the helicity-dependent D(e⃗,eâ€ČÎł)X({\vec e},e'\gamma)X cross section measured at Q2Q^2=1.9 GeV2^2 and xBx_B=0.36. We extract a linear combination of generalized parton distributions (GPDs) particularly sensitive to EqE_q, the least constrained GPD. A model dependent constraint on the contribution of the up and down quarks to the nucleon spin is deduced.Comment: Published in Phys. Rev. Let

    Exclusive Neutral Pion Electroproduction in the Deeply Virtual Regime

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    We present measurements of the ep->ep pi^0 cross section extracted at two values of four-momentum transfer Q^2=1.9 GeV^2 and Q^2=2.3 GeV^2 at Jefferson Lab Hall A. The kinematic range allows to study the evolution of the extracted hadronic tensor as a function of Q^2 and W. Results will be confronted with Regge inspired calculations and GPD predictions. An intepretation of our data within the framework of semi-inclusive deep inelastic scattering has also been attempted
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