Dispersive instability appears in time-domain solutions of classical cochlear models. In this letter, a derivation of optimal initial data is presented to minimize the effect of instability. A second-order accurate implicit boundary integral method is introduced. Numerical solutions of two-dimensional models show that the optimal initial conditions work successfully in time-domain steady-state computations for both the zero Neumann and zero Dirichlet fluid pressure boundary conditions at the helicotrema.

DNA microarray analysis has emerged as a leading technology to enhance our understanding of gene regulation and function in cellular mechanism controls on a genomic scale. This technology has advanced to unravel the genetic machinery of biological rhythms by collecting massive gene-expression data in a time course. Here, we present a statistical model for clustering periodic patterns of gene expression in terms of different transcriptional profiles. The model incorporates biologically meaningful Fourier series approximations of gene periodic expression into a mixture-model-based likelihood function, thus producing results that are likely to be closer to biological relevance, as compared to those from existing models. Also because the structures of the time-dependent means and covariance matrix are modeled, the new approach displays increased statistical power and precision of parameter estimation. The

We study a class of nonlinear nonlocal cochlear models of the transmission line type, describing the motion of basilar membrane (BM) in the cochlea. They are damped dispersive partial differential equations (PDEs) driven by time dependent boundary forcing due to the input sounds. The global well-posedness in time follows from energy estimates. Uniform bounds of solutions hold in the case of bounded nonlinear damping. When the input sounds are multi-frequency tones, and the nonlinearity in the PDEs is cubic, we construct smooth quasi-periodic solutions (multi-tone solutions) in the weakly nonlinear regime, where new frequencies are generated due to nonlinear interaction. When the input consists of two tones at frequencies f 1, f 2 (f 1< f 2), and high enough intensities, numerical results illustrate the formation of combination tones at 2f 1 f 2 and 2f 2 f 1, in agreement with hearing experiments. We visualize

Macrophage activation and persistent inflammation contribute to the pathological process of spinal cord injury (SCI). It was reported that M2 macrophages were induced at 37 days after SCI but M2 markers were reduced or eliminated after 1 week. By contrast, M1 macrophage response is rapidly induced and then maintained at injured spinal cord. However, factors that modulate macrophage phenotype and function are poorly understood. We developed a model to distinguish bonemarrow derived macrophages (BMDMs) from residential microglia and explored how BMDMs change their phenotype and functions in response to the lesionrelated factors in injured spinal cord. Infiltrating BMDMs expressing higher Mac2 and lower CX3CR1 migrate to the epicenter of injury, while microglia expressing lower Mac2 but higher CX3CR1 distribute to the edges of lesion. Myelin debris at the lesion site switches BMDMs

Macrophages play an important role in the inflammatory responses involved with spinal cord injury (SCI). We have previously demonstrated that infiltrated bone marrow-derived macrophages (BMDMs) engulf myelin debris, forming myelin-laden macrophages (mye-M). These mye-M promote disease progression through their pro-inflammatory phenotype, enhanced neurotoxicity, and impaired phagocytic capacity for apoptotic cells. We thus hypothesize that the excessive accumulation of mye-M is the root of secondary injury, and that targeting mye-M represents an efficient strategy to improve the local inflammatory microenvironment in injured spinal cords and to further motor neuron function recovery. In this study, we administer murine embryonic stem cell conditioned media (ESC-M) as a cell-free stem cell based therapy to treat a mouse model of SCI. We showed that BMDMs, but not microglial cells, engulf myelin debris generated at the injury site. Phagocytosis of myelin debris leads to the formation of mye-M in the injured spinal cord, which are surrounded by activated microglia cells. These mye-M are pro-inflammatory and lose the normal macrophage phagocytic capacity for apoptotic cells. We therefore focus on how to trigger lipid efflux from mye-M and thus restore their function. Using ESC-M as an immune modulating treatment for inflammatory damage after SCI, we rescued mye-M function and improved functional locomotor recovery. ESC-M treatment on mye-M resulted in improved exocytosis of internalized lipids and a normal capacity for apoptotic cell phagocytosis. Furthermore, when ESC-M was administered