Cooperation of Mtmr8 with PI3K Regulates Actin Filament Modeling and Muscle Development in Zebrafish

Background: It has been shown that mutations in at least four myotubularin family genes (MTM1, MTMR1, 2 and 13) are causative for human neuromuscular disorders. However, the pathway and regulative mechanism remain unknown. Methodology/Principal Findings: Here, we reported a new role for Mtmr8 in neuromuscular development of zebrafish. Firstly, we cloned and characterized zebrafish Mtmr8, and revealed the expression pattern predominantly in the eye field and somites during early somitogenesis. Using morpholino knockdown, then, we observed that loss-of-function of Mtmr8 led to defects in somitogenesis. Subsequently, the possible underlying mechanism and signal pathway were examined. We first checked the Akt phosphorylation, and observed an increase of Akt phosphorylation in the morphant embryos. Furthermore, we studied the PH/G domain function within Mtmr8. Although the PH/G domain deletion by itself did not result in embryonic defect, addition of PI3K inhibitor LY294002 did give a defective phenotype in the PH/G deletion morphants, indicating that the PH/G domain was essential for Mtmr8's function. Moreover, we investigated the cooperation of Mtmr8 with PI3K in actin filament modeling and muscle development, and found that both Mtmr8-MO1 and Mtmr8-MO2+LY294002 led to the disorganization of the actin cytoskeleton. In addition, we revealed a possible participation of Mtmr8 in the Hedgehog pathway, and cell transplantation experiments showed that Mtmr8 worked in a non-cell autonomous manner in actin modeling. Conclusion/Significance: The above data indicate that a conserved functional cooperation of Mtmr8 with PI3K regulates actin filament modeling and muscle development in zebrafish, and reveal a possible participation of Mtmr8 in the Hedgehog pathway. Therefore, this work provides a new clue to study the physiological function of MTM family members.

Modeling sub-threshold current-voltage characteristics in thin film transistors

In this paper, we present a physically-based compact model for the sub-threshold behavior in a TFT with an amorphous semiconductor channel. Both drift and diffusion current components are considered and combined using an harmonic average. Here, the diffusion component describes the exponential current behavior due to interfacial deep states, while the drift component is associated with presence of localized deep states formed by dangling bonds broken from weak bonds in the bulk and follows a power law. The proposed model yields good agreement with measured results. © 2013 IEEE.

Corrugated all-composite sandwich structures. Part 1: Modeling

An analytical model for the compressive and shear response of monolithic and hierarchical corrugated composite cores has been developed. The stiffness model considers the contribution in stiffness from the bending- and the shear deformations of the core members in addition to the stretching deformation. The strength model is based on the normal stress and shear stress distribution over each core member when subjected to a shear or compressive load condition. The strength model also accounts for initial imperfections. In part 1 of this series, the analytical model is described and the results are compared to finite element predictions. In part 2, the analytical model is compared to experimental results and the behaviour of the corrugated structures is investigated more thoroughly using failure mechanism maps. © 2008 Elsevier Ltd. All rights reserved.

Modeling the carbon nanofiber addressed liquid crystal microlens array from experimentally observed optical phenomena

This paper presents a novel method of using experimentally observed optical phenomena to reverse-engineer a model of the carbon nanofiber-addressed liquid crystal microlens array (C-MLA) using Zemax. It presents the first images of the optical profile for the C-MLA along the optic axis. The first working optical models of the C-MLA have been developed by matching the simulation results to the experimental results. This approach bypasses the need to know the exact carbon nanofiber-liquid crystal interaction and can be easily adapted to other systems where the nature of an optical device is unknown. Results show that the C-MLA behaves like a simple lensing system at 0.060-0.276 V/μm. In this lensing mode the C-MLA is successfully modeled as a reflective convex lens array intersecting with a flat reflective plane. The C-MLA at these field strengths exhibits characteristics of mostly spherical or low order aspheric arrays, with some aspects of high power aspherics. It also exhibits properties associated with varying lens apertures and strengths, which concur with previously theorized models based on E-field patterns. This work uniquely provides evidence demonstrating an apparent "rippling" of the liquid crystal texture at low field strengths, which were successfully reproduced using rippled Gaussian-like lens profiles. © 2014 Published by Elsevier B.V.

Design and modeling of an integrated device for acoustic resonance spectroscopy

This paper investigates the design and modelling of an integrated device for acoustic resonance spectroscopy (ARS). Miniaturisation of such platforms can be achieved using MEMS technology thereby enabling scaling of device dimensions to investigate smaller specimens while simultaneously operating at higher frequencies. We propose an integrated device where the transducers are mounted in close proximity with the specimen to be analysed (e.g. by integrating ultrasound transducers within a microfluidic channel). A finite element (FE) model and a simplified analytical model have been constructed to predict the acoustic response of a sample embedded in such a device configuration. A FE simulation is performed in COMSOL by embedding the piezoelectric transducers in representative fluid media. Resonant frequencies associated with the measurement can be extracted from this data. The response of various media modelled through FEA matches with analytical predictions for a range of biological media. A variety of biological media may be identified by using the measured resonant frequencies as a signature of relevant physical characteristics. The paper establishes the modelling basis of an integrated acoustic resonant spectrometer that is then applied to examine the impact of geometrical scaling on system resolution. © 2013 IEEE.

Advanced modeling of periodic structures in SEA

The SEA properties of a periodic structure are computed from the FE analysis of a single periodic cell. The periodic theory is used in conjunction with FE so that any geometry can be considered. Some efficient algorithms have been implemented to get the subsystems intrinsic properties (modal density, damping, and equivalent mass), as well as the coupling properties of the subsystem with acoustic subsystems (radiation and transmission). Comparisons with analytical results validate the method. © (2006) by the Katholieke Universiteit Leuven Department of Mechanical Engineering All rights reserved.

Modeling phytoplankton dynamics in the River Darling (Australia) using the radial basis function neural network

A radial basis function neural network was employed to model the abundance of cyanobacteria. The trained network could predict the populations of two bloom forming algal taxa with high accuracy, Nostocales spp. and Anabaena spp., in the River Darling, Australia. To elucidate the population dynamics for both Nostocales spp. and Anabaena spp., sensitivity analysis was performed with the following results. Total Kjeldahl nitrogen had a very strong influence on the abundance of the two algal taxa, electrical conductivity had a very strong negative relationship with the population of the two algal species, and flow was identified as one dominant factor influencing algal blooms after a scatter plot revealed that high flow could significantly reduce the algal biomass for both Nostocales spp. and Anabaena spp. Other variables such as turbidity, color, and pH were less important in determining the abundance and succession of the algal blooms.

Modeling current-voltage behaviour in oxide TFTs combining trap-limited conduction with percolation

Current-voltage behaviour of oxide TFTs is modeled based on trap-limited conduction and percolation theories. The mobility has a power-law dependence, in which percolation controls the exponent while trap states determine constant term in the power law. The proposed model, which is fully physically-based, provides a good agreement with measured transistor characteristics as well as transient operations of fabricated pixel test circuits for oxide-based OLED displays. © 2013 Society for Information Display.

De novo RNA synthesis and homology modeling of the classical swine fever virus RNA polymerase

Classical swine fever virus (CSFV) non-structural protein 5B (NS5B) encodes an RNA-dependent RNA polymerase (RdRp), a key enzyme which initiates RNA replication by a de novo mechanism without a primer and is a potential target for anti-virus therapy. We expressed the NS5B protein in Escherichia coli. The rGTP can stimulate de novo initiation of RNA synthesis and mutation of the GDD motif to Gly-Asp-Asp (GAA) abolishes the RNA synthesis. To better understand the mechanism of viral RNA synthesis in CSFV, a three-dimensional model was built by homology modeling based on the alignment with several virus RdRps. The model contains 605 residues folded in the characteristic fingers, palm and thumb domains. The fingers domain contains an N-terminal region that plays an important role in conformational change. We propose that the experimentally observed promotion of polymerase efficiency by rGTP is probably due to the conformational changes of the polymerase caused by binding the rGTP. Mutation of the GDD to GAA interferes with the interaction between the residues at the polymerase active site and metal ions, and thus renders the polymerase inactive. (c) 2005 Elsevier B.V. All rights reserved.

Modeling of cyanobacterial blooms in hypereutrophic Lake Dianchi, China

Compared with other approaches for modeling and predicting, artificial neural networks are more effective in describing complex and non-linear systems. The occurrence of cyanobacterial blooms has been a continuous and serious problem over the past decades in hypereutrophic Lake Dianchi. Yet, the main factor(s) initiating these blooms remain(s) unclear. During 2001-2002 at 40 sampling sites in Lake Dianchi, physicochemical parameters possibly relating to the blooms were measured. Parameters directly or indirectly relating to the cyanobacterial blooms were used as driving factors in a back-propagation network to model the concentration of chlorophyll a. According to sensitivity analysis, chemical oxygen demand was identified as a very significant environmental factor for algal growth in Lake Dianchi.

AMPS modeling of light J-V characteristics of a-Si based solar cells

AMPS (Analysis of microelectronic and photonic structures) mode,which was developed by Pennsylvania State University, has been used to module the light J-V characteristics of a-Si solar cells with a structure of TCO/p-a-SiC:H/i-a-Si:H/n-a-Si:H/ metal. The effects of valence band offset and contact barriers at p/i and TOC/p, n/metal interfaces on the light J-V characteristics have been examined. The modeling has qualitatively categorized and explained the non-ideal J-V behaviors (rollover, crossover, Voc shift,and rollunder) observed in a-Si based solar cells.

A highly efficient beam propagation method for modeling step-index waveguides with tilt interface

Based on a new finite-difference scheme and Runge-Kutta method together with transparent boundary conditions (TBCs), a novel beam propagation method to model step-index waveguides with tilt interfaces is presented. The modified scheme provides an precies description of the tilt interface of the nonrectangular waveguide structure, showing a much better efficiency and accuracy comparing with the previously presented formulas.

Optical constants of cubic GaN/GaAs(001): Experiment and modeling

The optical constants epsilon(E)=epsilon(1)(E)+iepsilon(2)(E) of unintentionally doped cubic GaN grown on GaAs(001) have been measured at 300 K using spectral ellipsometry in the range of 1.5-5.0 eV. The epsilon(E) spectra display a structure, associated with the critical point at E-0 (direct gap) and some contribution mainly coming from the E-1 critical point. The experimental data over the entire measured spectral range (after oxide removal) has been fit using the Holden-Munoz model dielectric function [M. Munoz et al., J. Appl. Phys. 92, 5878 (2002)]. This model is based on the electronic energy-band structure near critical points plus excitonic and band-to-band Coulomb-enhancement effects at E-0, E-0 + Delta(0) and the E-1, E-1 + Delta(1), doublet. In addition to evaluating the energy of the E-0 critical point, the binding energy (R-1) of the two-dimensional exciton related to the E-1 critical point was estimated using the effective mass/k.p theory. The line, shape of the imaginary part of the cubic-GaN dielectric function shows excitonic effects at room temperature not withstanding that the exciton was not resolved. (C) 2003 American Institute of Physics.