ABSTRACT
Sleep debt accumulates during wakefulness, leading to increased slow wave activity (SWA) during sleep, an encephalographic marker for sleep need. The use-dependent demands of prior wakefulness increase sleep SWA locally. However, the circuitry and molecular identity of this "local sleep" remain unclear. Using pharmacology and optogenetic perturbations together with transcriptomics, we find that cortical brain-derived neurotrophic factor (BDNF) regulates SWA via the activation of tyrosine kinase B (TrkB) receptor and cAMP-response element-binding protein (CREB). We map BDNF/TrkB-induced sleep SWA to layer 5 (L5) pyramidal neurons of the cortex, independent of neuronal firing per se. Using mathematical modeling, we here propose a model of how BDNF's effects on synaptic strength can increase SWA in ways not achieved through increased firing alone. Proteomic analysis further reveals that TrkB activation enriches ubiquitin and proteasome subunits. Together, our study reveals that local SWA control is mediated by BDNF-TrkB-CREB signaling in L5 excitatory cortical neurons.
Subject(s)
Brain-Derived Neurotrophic Factor , Cyclic AMP Response Element-Binding Protein , Receptor, trkB , Signal Transduction , Brain-Derived Neurotrophic Factor/metabolism , Animals , Receptor, trkB/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Mice , Sleep/physiology , Male , Mice, Inbred C57BL , Pyramidal Cells/metabolism , Sleep, Slow-Wave/physiologyABSTRACT
The PU (partition-of-unity) based FE-RPIM QUAD4 (4-node quadrilateral) element was proposed for statics problems. In this element, hybrid shape functions are constructed through multiplying QUAD4 shape function with radial point interpolation method (RPIM). In the present work, the FE-RPIM QUAD4 element is further applied for structural dynamics. Numerical examples regarding to free and forced vibration analyses are presented. The numerical results show that: (1) If CMM (consistent mass matrix) is employed, the FE-RPIM QUAD4 element has better performance than QUAD4 element under both regular and distorted meshes; (2) The DLMM (diagonally lumped mass matrix) can supersede the CMM in the context of the FE-RPIM QUAD4 element even for the scheme of implicit time integration.
ABSTRACT
To avoid disadvantages caused by rotational degrees of freedom in the original Discontinuous Deformation Analysis (DDA), a new block displacement mode is defined within a time step, where displacements of all the block vertices are taken as the degrees of freedom. An individual virtual element space V1(Ω) is defined for a block to illustrate displacement of the block using the Virtual Element Method (VEM). Based on VEM theory, the total potential energy of the block system in DDA is formulated and minimized to obtain the global equilibrium equations. At the end of a time step, the vertex coordinates are updated by adding their incremental displacement to their previous coordinates. In the new method, no explicit expression for the displacement u is required, and all numerical integrations can be easily computed. Four numerical examples originally designed by Shi are analyzed, verifying the effectiveness and precision of the proposed method.
ABSTRACT
We demonstrate flow rectification, valveless pumping, or alternating to direct current (AC-to-DC) conversion in macroscale fluidic networks with loops. Inspired by the unique anatomy of bird lungs and the phenomenon of directed airflow throughout the respiration cycle, we hypothesize, test, and validate that multiloop networks exhibit persistent circulation or DC flows when subject to oscillatory or AC forcing at high Reynolds numbers. Experiments reveal that disproportionately stronger circulation is generated for higher frequencies and amplitudes of the imposed oscillations, and this nonlinear response is corroborated by numerical simulations. Visualizations show that flow separation and vortex shedding at network junctions serve the valving function of directing current with appropriate timing in the oscillation cycle. These findings suggest strategies for controlling inertial flows through network topology and junction connectivity.