Taeyoung Ha

Phosphorylation of amyloid precursor protein (APP) at Thr668 regulates the nuclear translocation of the APP intracellular domain and induces neurodegeneration.

ABSTRACT Amyloid precursor protein (APP) has eight potential phosphorylation sites in its cytoplasmic domain. Recently, it has demonstrated that the constitutive phosphorylation of APP at T668 (APP695 isoform numbering) was observed specifically in the brain. Neuron-specific phosphorylation of APP at T668 is thought to be important for neuronal functions of APP, although its exact physiological significance remains to be clarified. In this study, we show that the phosphorylation of the APP intracellular domain (AICD) at T668 is essential for its binding to Fe65 and its nuclear translocation and affects the resultant neurotoxicity, possibly mediated through the induction of glycogen synthase kinase 3β and tau phosphorylation by enhancing the formation of a ternary complex with Fe65 and CP2 transcription factor. Taken together, these results suggest that the phosphorylation of AICD at T668 contributes to the neuronal degeneration in Alzheimers disease (AD) by regulating its translocation into the nucleus and then affects neurodegeneration; therefore, the specific inhibitor of T668 phosphorylation might be the target of AD therapy.

Waveform inversion using a back-propagation algorithm and a Huber function norm

Waveforminversionfacesdifficultieswhenappliedtoreal seismic data, including the existence of many kinds of noise. The 1 -norm is more robust to noise with outliers than the least-squares method. Nevertheless, the least-squares method is preferred as an objective function in many algorithms because the gradient of the 1 -norm has a singularity when the residual becomes zero. We propose a complex-valued Huber function for frequency-domain waveform inversion that combines the 2 -norm for small residuals with the 1 -norm for large residuals. We also derive a discretized formula for the gradient of the Huber function. Through numericaltestsonsimplesyntheticmodelsandMarmousidata, we find the Huber function is more robust to outliers and coherent noise.We apply our waveform-inversion algorithm to field data taken from the continental shelf under the East Sea in Korea. In this setting, we obtain a velocity model whose syntheticshotprofilesaresimilartotherealseismicdata.

S100a9 Knockdown Decreases the Memory Impairment and the Neuropathology in Tg2576 Mice, AD Animal Model

Inflammation, insoluble protein deposition and neuronal cell loss are important features in the Alzheimers disease (AD) brain. To investigate the regulatory genes responsible for the neuropathology in AD, we performed microarray analysis with APPV717I-CT100 transgenic mice, an animal model of AD, and isolated the S100a9 gene, which encodes an inflammation-associated calcium binding protein. In another AD animal model, Tg2576 mouse brain, and in human AD brain, induction of S100a9 was confirmed. The endogenous expression of S100a9 was induced by treatment with Aβ or CT peptides in a microglia cell line, BV2 cells. In these cells, silencing study of S100a9 showed that the induction of S100a9 increased the intracellular calcium level and up-regulated the inflammatory cytokines (IL-1β and TNFα) and iNOS. S100a9 lentiviral short hairpin RNA (sh-S100a9) was injected into the hippocampus region of the brains of 13-month-old Tg2576 mice. At two months after injection, we found that knockdown of S100a9 expression had improved the cognition decline of Tg2576 mice in the water maze task, and had reduced amyloid plaque burden. These results suggest that S100a9 induced by Aβ or CT contributes to cause inflammation, which then affects the neuropathology including amyloid plaques burden and impairs cognitive function. Thus, the inhibition of S100a9 is a possible target for AD therapy.

Emergent Behavior of a Cucker-Smale Type Particle Model With Nonlinear Velocity Couplings

In this note, we present a Cucker-Smale type flocking model with nonlinear velocity couplings, and derive sufficient conditions for the formation of flocking in terms of communication weight and initial spatial, velocity standard deviations.

Traveltime and amplitude calculations using the damped wave solution

Because of its computational efficiency, prestack Kirchhoff depth migration remains the method of choice for all but the most complicated geological depth structures. Further improvement in computational speed and amplitude estimation will allow us to use such technology more routinely and generate better images. To this end, we developed a new, accurate, and economical algorithm to calculate first-arrival traveltimes and amplitudes for an arbitrarily complex earth model. Our method is based on numerical solutions of the wave equation obtained by using well-established finite-difference or finite-element modeling algorithms in the Laplace domain, where a damping term is naturally incorporated in the wave equation. We show that solving the strongly damped wave equation is equivalent to solving the eikonal and transport equations simultaneously at a fixed reference frequency, which properly accounts for caustics and other problems encountered in ray theory. Using our algorithm, we can easily calculate first-arrival traveltimes for given models. We present numerical examples for 2-D acoustic models having irregular topography and complex geological structure using a finite-element modeling code.

Nonconforming finite element methods for the simulation of waves in viscoelastic solids

The propagation of waves in two- and three-dimensional bounded viscoelastic media is described in the space–frequency domain, leading to a Helmholtz-type boundary value problem, which is noncoercive, non-Hermitian, and complex valued. First-order absorbing boundary conditions are derived and used to minimize spurious reflections from the artificial boundaries. The paper consists of two parts. In Part I we describe the global procedures for the approximate solution of the problem. Simplicial and rectangular nonconforming finite element methods are employed for the spatial discretization. Optimal error estimate in a broken energy and L2(Ω) norms are derived using a bootstrapping argument of Schatz. Also a hybridization of these procedures is analyzed. In Part II we define and analyze nonoverlapping domain decomposition iterative methods. Convergence results are derived and numerical experiments showing the potential applicability in seismology are presented.

Refraction traveltime tomography using damped monochromatic wavefield

For complicated earth models, wave-equation–based refraction-traveltime tomography is more accurate than ray-based tomography but requires more computational effort. Most of the computational effort in traveltime tomography comes from computing traveltimes and their Fr ´ echet derivatives, which for ray-based methods can be computed directly. However, in most wave-equation traveltime-tomography algorithms, the steepest descent direction of the objective function is computed by the backprojection algorithm, without computing a Fr ´ echet derivative directly. We propose a new wave-based refraction-traveltime– tomography procedure that computes Fr ´ echet derivatives directly and efficiently. Our method involves solving a damped-wave equation using a frequency-domain, finite-element modeling algorithm at a single frequency and invoking the reciprocity theorem. A damping factor, which is commonly used to suppress wraparound effects in frequency-domain modeling, plays the role of suppressing multievent wavefields. By limiting the wavefield to a single first arrival, we are able to extract the first-arrival traveltime from the phase term without applying a time window. Computing the partial derivative of the damped wave-equation solution using the reciprocity theorem enables us to compute the Fr ´ echet derivative of amplitude, as well as that of traveltime, with respect to subsurface parameters. Using the Marmousi-2 model, we demonstrate numerically that refraction traveltime tomography with large-offset data can be used to provide the smooth initial velocity model necessary for prestack depth migration.

Asymptotic dynamics for the Cucker–Smale-type model with the Rayleigh friction

We study the asymptotic flocking dynamics for the Cucker?Smale-type second-order continuous-time dynamical system with the Rayleigh friction. For mean-field communications with a positive lower bound, we show that an asymptotic flocking occurs for any compactly supported initial configuration in a large coupling regime. In contrast, in a small coupling regime, an asymptotic flocking is possible for a restricted class of initial configurations near complete flocking states. We also present several numerical simulations and compare them with our analytical results.

Nonlinear instability of the one-dimensional Vlasov-Yukawa system

We discuss the nonlinear instability of some class of stationary solutions to the one-dimensional Vlasov–Yukawa system with a mass parameter m. The Vlasov–Yukawa system corresponds to the short-range correction of the repulsive Vlasov–Poisson system arising from plasma physics. We show that the stationary solutions satisfying the Penrose condition are nonlinearly unstable in small mass regime. In a large mass regime, the massiveness of force carrier particles acts as stabilizer in a finite time interval. We present several numerical results to confirm our analytical results.

Magnetotelluric inversion via reverse time migration algorithm of seismic data

We propose a new algorithm for two-dimensional magnetotelluric (MT) inversion. Our algorithm is an MT inversion based on the steepest descent method, borrowed from the backpropagation technique of seismic inversion or reverse time migration, introduced in the middle 1980s by Lailly and Tarantola. The steepest descent direction can be calculated efficiently by using the symmetry of numerical Greens function derived from a mixed finite element method proposed by Nedelec for Maxwells equation, without calculating the Jacobian matrix explicitly. We construct three different objective functions by taking the logarithm of the complex apparent resistivity as introduced in the recent waveform inversion algorithm by Shin and Min. These objective functions can be naturally separated into amplitude inversion, phase inversion and simultaneous inversion. We demonstrate our algorithm by showing three inversion results for synthetic data.