336 research outputs found

    Forcing and Velocity Correlations in a Vibrated Granular Monolayer

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    The role of forcing on the dynamics of a vertically shaken granular monolayer is investigated. Using a flat plate, surprising negative velocity correlations are measured. A mechanism for this anti-correlation is proposed with support from both experimental results and molecular dynamics simulations. Using a rough plate, velocity correlations are positive, and the velocity distribution evolves from a gaussian at very low densities to a broader distribution at high densities. These results are interpreted as a balance between stochastic forcing, interparticle collisions, and friction with the plate.Comment: 4 pages, 5 figure

    Identifying Outages In User-Facing Products Based On Search Statistics

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    A method is disclosed for identifying outages in user-facing products based on search statistics. The method includes collecting search queries related to a user-facing product from a search engine. The method further includes generating statistics based on the collected search queries. The statistics may indicate spikes based on the product and failure-related terms associated therewith. Based on the statistics, the spikes for searches related to outage of the product are identified. Further, on identifying the spikes, alerts may be issued to an appropriate technical team related to the outage

    Non-equilibrium two-phase coexistence in a confined granular layer

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    We report the observation of the homogenous nucleation of crystals in a dense layer of steel spheres confined between two horizontal plates vibrated vertically. Above a critical vibration amplitude, two-layer crystals with square symmetry were found to coexist in steady state with a surrounding granular liquid. By analogy to equilibrium hard sphere systems, the phase behavior can be explained through entropy maximization. However, dramatic non-equilibrium effects are present, including a significant difference in the granular temperatures of the two phases.Comment: 4 pages, 3 figures, RevTex4 forma

    Sequence-Specific, Nanomolar Peptide Binding via Cucurbit[8]uril-Induced Folding and Inclusion of Neighboring Side Chains

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    This paper describes the molecular recognition of the tripeptide Tyr-Leu-Ala by the synthetic receptor cucurbit[8]uril (Q8) in aqueous buffer with nanomolar affinity and exceptional specificity. This combination of characteristics, which also applies to antibodies, is desirable for applications in biochemistry and biotechnology but has eluded supramolecular chemists for decades. Building on prior knowledge that Q8 binds to peptides with N-terminal aromatic residues, a library screen of 105 peptides was designed to test the effects of residues adjacent to N-terminal Trp, Phe, or Tyr. The screen used tetramethylbenzobis(imidazolium) (MBBI) as a fluorescent indicator and resulted in the unexpected discovery that MBBI can serve not only as a turn-off sensor via the simultaneous inclusion of a Trp residue but also as a turn-on sensor via the competitive displacement of MBBI upon binding of Phe- or Tyr-terminated peptides. The unusual fluorescence response of the Tyr series prompted further investigation by 1H NMR spectroscopy, electrospray ionization mass spectrometry, and isothermal titration calorimetry. From these studies, a novel binding motif was discovered in which only 1 equiv of peptide binds to Q8, and the side chains of both the N-terminal Tyr residue and its immediate neighbor bind within the Q8 cavity. For the peptide Tyr-Leu-Ala, the equilibrium dissociation constant value is 7.2 nM, whereas that of its sequence isomer Tyr-Ala-Leu is 34 ÎĽM. The high stability, recyclability, and low cost of Q8 combined with the straightforward incorporation of Tyr-Leu-Ala into recombinant proteins should make this system attractive for the development of biological applications

    FRAP to Characterize Molecular Diffusion and Interaction in Various Membrane Environments

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    Fluorescence recovery after photobleaching (FRAP) is a standard method used to study the dynamics of lipids and proteins in artificial and cellular membrane systems. The advent of confocal microscopy two decades ago has made quantitative FRAP easily available to most laboratories. Usually, a single bleaching pattern/area is used and the corresponding recovery time is assumed to directly provide a diffusion coefficient, although this is only true in the case of unrestricted Brownian motion. Here, we propose some general guidelines to perform FRAP experiments under a confocal microscope with different bleaching patterns and area, allowing the experimentalist to establish whether the molecules undergo Brownian motion (free diffusion) or whether they have restricted or directed movements. Using in silico simulations of FRAP measurements, we further indicate the data acquisition criteria that have to be verified in order to obtain accurate values for the diffusion coefficient and to be able to distinguish between different diffusive species. Using this approach, we compare the behavior of lipids in three different membrane platforms (supported lipid bilayers, giant liposomes and sponge phases), and we demonstrate that FRAP measurements are consistent with results obtained using other techniques such as Fluorescence Correlation Spectroscopy (FCS) or Single Particle Tracking (SPT). Finally, we apply this method to show that the presence of the synaptic protein Munc18-1 inhibits the interaction between the synaptic vesicle SNARE protein, VAMP2, and its partner from the plasma membrane, Syn1A

    Scaling test for Wilson twisted mass QCD

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    We present a first scaling test of twisted mass QCD with pure Wilson quarks for a twisting angle of pi/2. We have computed the vector meson mass and the pseudoscalar decay constant for different values of beta at fixed value of r_0 m_PS. The results obtained in the quenched approximation are compared with data for pure Wilson and non-perturbatively O(a) improved Wilson computations. We show that our results from Wilson twisted mass QCD show clearly reduced lattice spacing errors, consistent with O(a) improvement and without the need of any improvement terms added. These results thus provide numerical evidence of the prediction in ref. [1].Comment: 15 pages, 4 figures; v2: two typos corrected, accepted for publication in Phys. Lett.

    Bias estimation in study design: a meta-epidemiological analysis of transcatheter versus surgical aortic valve replacement

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    Background: Paucity of RCTs of non-drug technologies lead to widespread dependence on non-randomized studies. Relationship between nonrandomized study design attributes and biased estimates of treatment effects are poorly understood. Our purpose was to estimate the bias associated with specific nonrandomized study attributes among studies comparing transcatheter aortic valve implantation with surgical aortic valve replacement for the treatment of severe aortic stenosis. Results: We included 6 RCTs and 87 nonrandomized studies. Surgical risk scores were similar for comparison groups in RCTs, but were higher for patients having transcatheter aortic valve implantation in nonrandomized studies. Nonrandomized studies underestimated the benefit of transcatheter aortic valve implantation compared with RCTs. For example, nonrandomized studies without adjustment estimated a higher risk of postoperative mortality for transcatheter aortic valve implantation compared with surgical aortic valve replacement (OR 1.43 [95% CI 1.26 to 1.62]) than high quality RCTs (OR 0.78 [95% CI 0.54 to 1.11). Nonrandomized studies using propensity score matching (OR 1.13 [95% CI 0.85 to 1.52]) and regression modelling (OR 0.68 [95% CI 0.57 to 0.81]) to adjust results estimated treatment effects closer to high quality RCTs. Nonrandomized studies describing losses to follow-up estimated treatment effects that were significantly closer to high quality RCT than nonrandomized studies that did not. Conclusion: Studies with different attributes produce different estimates of treatment effects. Study design attributes related to the completeness of follow-up may explain biased treatment estimates in nonrandomized studies, as in the case of aortic valve replacement where high-risk patients were preferentially selected for the newer (transcatheter) procedure
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