667 research outputs found

    Two-in-One: Activation and Inactivation at the Intracellular Gate of a Kv Channel

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    Nonlinear lattice model of viscoelastic Mode III fracture

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    We study the effect of general nonlinear force laws in viscoelastic lattice models of fracture, focusing on the existence and stability of steady-state Mode III cracks. We show that the hysteretic behavior at small driving is very sensitive to the smoothness of the force law. At large driving, we find a Hopf bifurcation to a straight crack whose velocity is periodic in time. The frequency of the unstable bifurcating mode depends on the smoothness of the potential, but is very close to an exact period-doubling instability. Slightly above the onset of the instability, the system settles into a exactly period-doubled state, presumably connected to the aforementioned bifurcation structure. We explicitly solve for this new state and map out its velocity-driving relation

    Arrested Cracks in Nonlinear Lattice Models of Brittle Fracture

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    We generalize lattice models of brittle fracture to arbitrary nonlinear force laws and study the existence of arrested semi-infinite cracks. Unlike what is seen in the discontinuous case studied to date, the range in driving displacement for which these arrested cracks exist is very small. Also, our results indicate that small changes in the vicinity of the crack tip can have an extremely large effect on arrested cracks. Finally, we briefly discuss the possible relevance of our findings to recent experiments.Comment: submitted to PRE, Rapid Communication

    Adjunctive quetiapine for serotonin reuptake inhibitor-resistant obsessive-compulsive disorder: A meta-analysis of randomised controlled treatment trials

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    Small studies have shown positive effects from adding a variety of antipsychotic agents in patients with obsessive–compulsive disorder who are unresponsive to treatment with serotonin reuptake inhibitors. The evidence, however, is contradictory. This paper reports a meta-analysis of existing double-blind randomized placebo-controlled studies looking at the addition of the second-generation antipsychotic quetiapine in such cases. Three studies fulfilled the inclusion criteria. Altogether 102 individuals were subjected to analysis using Review Manager (4.2.7). The results showed evidence of efficacy for adjunctive quetiapine (< 400 mg/day) on the primary efficacy criterion, measured as changes from baseline in total Yale–Brown Obsessive Compulsive Scale scores (P = 0.008), the clinical significance of which was limited by between-study heterogeneity. The mechanism underlying the effect may involve serotonin and/or dopamine neurotransmission

    Selective serotonin reuptake inhibitors (SSRIs) may improve behavioral inhibition in patients with obsessive compulsive disorder: a feasibility study

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    © 2023 Published by Elsevier B.V. This is an open access conference article under the Creative Commons Attribution-NonCommercial-NoDerivatives CC BY-NC-ND licence, https://creativecommons.org/licenses/by-nc-nd/4.0/Peer reviewe

    Closed-state inactivation involving an internal gate in Kv4.1 channels modulates pore blockade by intracellular quaternary ammonium ions.

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    Voltage-gated K(+) (Kv) channel activation depends on interactions between voltage sensors and an intracellular activation gate that controls access to a central pore cavity. Here, we hypothesize that this gate is additionally responsible for closed-state inactivation (CSI) in Kv4.x channels. These Kv channels undergo CSI by a mechanism that is still poorly understood. To test the hypothesis, we deduced the state of the Kv4.1 channel intracellular gate by exploiting the trap-door paradigm of pore blockade by internally applied quaternary ammonium (QA) ions exhibiting slow blocking kinetics and high-affinity for a blocking site. We found that inactivation gating seemingly traps benzyl-tributylammonium (bTBuA) when it enters the central pore cavity in the open state. However, bTBuA fails to block inactivated Kv4.1 channels, suggesting gated access involving an internal gate. In contrast, bTBuA blockade of a Shaker Kv channel that undergoes open-state P/C-type inactivation exhibits fast onset and recovery inconsistent with bTBuA trapping. Furthermore, the inactivated Shaker Kv channel is readily blocked by bTBuA. We conclude that Kv4.1 closed-state inactivation modulates pore blockade by QA ions in a manner that depends on the state of the internal activation gate

    Phase-Field Model of Mode III Dynamic Fracture

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    We introduce a phenomenological continuum model for mode III dynamic fracture that is based on the phase-field methodology used extensively to model interfacial pattern formation. We couple a scalar field, which distinguishes between ``broken'' and ``unbroken'' states of the system, to the displacement field in a way that consistently includes both macroscopic elasticity and a simple rotationally invariant short scale description of breaking. We report two-dimensional simulations that yield steady-state crack motion in a strip geometry above the Griffith threshold.Comment: submitted to PR

    Crack Front Waves and the dynamics of a rapidly moving crack

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    Crack front waves are localized waves that propagate along the leading edge of a crack. They are generated by the interaction of a crack with a localized material inhomogeneity. We show that front waves are nonlinear entities that transport energy, generate surface structure and lead to localized velocity fluctuations. Their existence locally imparts inertia, which is not incorporated in current theories of fracture, to initially "massless" cracks. This, coupled to crack instabilities, yields both inhomogeneity and scaling behavior within fracture surface structure.Comment: Embedded Latex file including 4 figure

    Dynamical stability of the crack front line

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    Dynamical stability of the crack front line that propagates between two plates is studied numerically using the simple two-dimensional mass-spring model. It is demonstrated that the straight front line is unstable for low speed while it becomes stable for high speed. For the uniform model, the roughness exponent in the slower speed region is fairly constant around 0.4 and there seems to be a rough-smooth transition at a certain speed. For the inhomogeneous case with quenched randomness, the transition is gradual.Comment: 14 pages, 7 figure
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