413 research outputs found

    Fracture Strength and Failure Modes of Endodontically Treated Premolars Restored with Compact and Hollow Composite Posts Subjected to Cyclic Fatigue

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    Physical and mechanical properties of continuous carbon or glass fiber reinforced endodontic posts are relevant to increase the retention and resistance of the tooth‐restoration system. Hollow posts have been recently designed for delivering the luting cement through the post hole, thus enhancing the post‐dentin interface by reducing the risk of air bubbles formation. Methods: Three type of endodontic posts, a carbon fiber hollow post, a glass fiber hollow post and a compact glass fiber post were investigated. Mechanical properties of these posts were assessed through bending tests. Teeth were subjected to fatigue cycling and the strength of restored teeth was detected through static tests. Failure modes were investigated through optical and scanning electron microscopy. Results show that composite posts increase the mechanical stability by more than 100% compared to premolars restored with particulate composite. Carbon fiber posts retain the highest strength (1467 N ± 304 N) among the investigated post and core restoration, but an unfavorable type of fracture has been observed, preventing the tooth re‐treatment. Instead, more compliant posts (i.e., glass fiber reinforced composite, providing a strength of 1336 N ± 221 N), show a favorable mode of fracture that allows the re‐treatment of teeth in the case that failure occurs. Glass fiber hollow posts show a good trade‐off between strength and a favorable type of fracture

    Chemical modulation of the 1-(Piperidin-4-yl)-1,3-dihydro-2h-benzo[d]imidazole-2-one scaffold as a novel NLRP3 inhibitor

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    In the search for new chemical scaffolds able to afford NLRP3 inflammasome inhibitors, we used a pharmacophore-hybridization strategy by combining the structure of the acrylic acid derivative INF39 with the 1-(piperidin-4-yl)1,3-dihydro-2H-benzo[d]imidazole-2-one substructure present in HS203873, a recently identified NLRP3 binder. A series of differently modulated benzo[d]imidazole-2-one derivatives were designed and synthesised. The obtained compounds were screened in vitro to test their ability to inhibit NLRP3-dependent pyroptosis and IL-1ÎČ release in PMA-differentiated THP-1 cells stimulated with LPS/ATP. The selected compounds were evaluated for their ability to reduce the ATPase activity of human recombinant NLRP3 using a newly developed assay. From this screening, compounds 9, 13 and 18, able to concentration-dependently inhibit IL-1ÎČ release in LPS/ATP-stimulated human macrophages, emerged as the most promising NLRP3 inhibitors of the series. Computational simulations were applied for building the first complete model of the NLRP3 inactive state and for identifying possible binding sites available to the tested compounds. The analyses led us to suggest a mechanism of protein–ligand binding that might explain the activity of the compounds

    Measuring the Invisible Higgs Width at the 7 and 8 TeV LHC

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    The LHC is well on track toward the discovery or exclusion of a light Standard Model (SM)-like Higgs boson. Such a Higgs has a very small SM width and can easily have large branching fractions to physics beyond the SM, making Higgs decays an excellent opportunity to observe new physics. Decays into collider-invisible particles are particularly interesting as they are theoretically well motivated and relatively clean experimentally. In this work we estimate the potential of the 7 and 8 TeV LHC to observe an invisible Higgs branching fraction. We analyze three channels that can be used to directly study the invisible Higgs branching ratio at the 7 TeV LHC: an invisible Higgs produced in association with (i) a hard jet; (ii) a leptonic Z; and (iii) forward tagging jets. We find that the last channel, where the Higgs is produced via weak boson fusion, is the most sensitive, allowing branching fractions as small as 40% to be probed at 20 inverse fb for masses in the range between 120 and 170 GeV, including in particular the interesting region around 125 GeV. We provide an estimate of the 8 TeV LHC sensitivity to an invisibly-decaying Higgs produced via weak boson fusion and find that the reach is comparable to but not better than the reach at the 7 TeV LHC. We further estimate the discovery potential at the 8 TeV LHC for cases where the Higgs has substantial branching fractions to both visible and invisible final states.Comment: 23 pages, 7 figures. v2: version published in JHEP. 8 TeV analysis adde

    Structure of Fat Jets at the Tevatron and Beyond

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    Boosted resonances is a highly probable and enthusiastic scenario in any process probing the electroweak scale. Such objects when decaying into jets can easily blend with the cornucopia of jets from hard relative light QCD states. We review jet observables and algorithms that can contribute to the identification of highly boosted heavy jets and the possible searches that can make use of such substructure information. We also review previous studies by CDF on boosted jets and its measurements on specific jet shapes.Comment: invited review for a special "Top and flavour physics in the LHC era" issue of The European Physical Journal C, we invite comments regarding contents of the review; v2 added references and institutional preprint number

    Nonminimal Couplings in the Early Universe: Multifield Models of Inflation and the Latest Observations

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    Models of cosmic inflation suggest that our universe underwent an early phase of accelerated expansion, driven by the dynamics of one or more scalar fields. Inflationary models make specific, quantitative predictions for several observable quantities, including particular patterns of temperature anistropies in the cosmic microwave background radiation. Realistic models of high-energy physics include many scalar fields at high energies. Moreover, we may expect these fields to have nonminimal couplings to the spacetime curvature. Such couplings are quite generic, arising as renormalization counterterms when quantizing scalar fields in curved spacetime. In this chapter I review recent research on a general class of multifield inflationary models with nonminimal couplings. Models in this class exhibit a strong attractor behavior: across a wide range of couplings and initial conditions, the fields evolve along a single-field trajectory for most of inflation. Across large regions of phase space and parameter space, therefore, models in this general class yield robust predictions for observable quantities that fall squarely within the "sweet spot" of recent observations.Comment: 17pp, 2 figs. References added to match the published version. Published in {\it At the Frontier of Spacetime: Scalar-Tensor Theory, Bell's Inequality, Mach's Principle, Exotic Smoothness}, ed. T. Asselmeyer-Maluga (Springer, 2016), pp. 41-57, in honor of Carl Brans's 80th birthda

    Distinguishing Binders from False Positives by Free Energy Calculations: Fragment Screening Against the Flap Site of HIV Protease

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    Molecular docking is a powerful tool used in drug discovery and structural biology for predicting the structures of ligand–receptor complexes. However, the accuracy of docking calculations can be limited by factors such as the neglect of protein reorganization in the scoring function; as a result, ligand screening can produce a high rate of false positive hits. Although absolute binding free energy methods still have difficulty in accurately rank-ordering binders, we believe that they can be fruitfully employed to distinguish binders from nonbinders and reduce the false positive rate. Here we study a set of ligands that dock favorably to a newly discovered, potentially allosteric site on the flap of HIV-1 protease. Fragment binding to this site stabilizes a closed form of protease, which could be exploited for the design of allosteric inhibitors. Twenty-three top-ranked protein–ligand complexes from AutoDock were subject to the free energy screening using two methods, the recently developed binding energy analysis method (BEDAM) and the standard double decoupling method (DDM). Free energy calculations correctly identified most of the false positives (≄83%) and recovered all the confirmed binders. The results show a gap averaging ≄3.7 kcal/mol, separating the binders and the false positives. We present a formula that decomposes the binding free energy into contributions from the receptor conformational macrostates, which provides insights into the roles of different binding modes. Our binding free energy component analysis further suggests that improving the treatment for the desolvation penalty associated with the unfulfilled polar groups could reduce the rate of false positive hits in docking. The current study demonstrates that the combination of docking with free energy methods can be very useful for more accurate ligand screening against valuable drug targets
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