KMT2A-AFF1 (MLL-AF4), formed by chromosomal translocation t(4;11), is observed specifically in infant pro-B acute lymphoblastic leukemia, and the main driver of leukemogenesis. In this study, a human ...induced pluripotent stem cell (hiPSC) line harboring KMT2A-AFF1 (IMSUTi002-A-2), which has the ability to simultaneously induce the doxycycline-inducible expression of KMT2A-AFF1 and EGFP, was established. This hiPSC can be a powerful model for understanding infant leukemia and risk assessment of leukemogenesis.
Linear dichroism (LD) is a differential polarized light absorption spectroscopy used for studying filamentous molecules such as DNA and protein filaments. In this study, we review the applications of ...LD for the analysis of DNA-protein interactions. LD signals can be measured in a solution by aligning the sample using flow-induced shear force or a strong electric field. The signal generated is related to the local orientation of chromophores, such as DNA bases, relative to the filament axis. LD can thus assess the tilt and roll of DNA bases and distinguish intercalating from groove-binding ligands. The intensity of the LD signal depends upon the degree of macroscopic orientation. Therefore, DNA shortening and bending can be detected by a decrease in LD signal intensity. As examples of LD applications, we present a kinetic study of DNA digestion by restriction enzymes and structural analyses of homologous recombination intermediates, i.e., RecA and Rad51 recombinase complexes with single-stranded DNA. LD shows that the DNA bases in these complexes are preferentially oriented perpendicular to the filament axis only in the presence of activators, suggesting the importance of organized base orientation for the reaction. LD measurements detect DNA bending by the CRP transcription activator protein, as well as by the UvrB DNA repair protein. LD can thus provide information about the structures of protein-DNA complexes under various conditions and in real time.
We demonstrate that the use of asymptotic expansion as prior knowledge in the “deep BSDE solver”, which is a deep learning method for high dimensional BSDEs proposed by Weinan et al. (Deep ...learning-based numerical methods for high-dimensional parabolic partial differential equations and backward stochastic differential equations,
2017b
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arXiv:1706.04702
), drastically reduces the loss function and accelerates the speed of convergence. We illustrate the technique and its implications by using Bergman’s model with different lending and borrowing rates as a typical model for FVA as well as a class of solvable BSDEs with quadratic growth drivers. We also present an extension of the deep BSDE solver for reflected BSDEs representing American option prices.
In this paper, we propose a topology optimization method based on the covariance matrix adaptation evolution strategy (CMA-ES) as a method for solving multimodal structural optimization problems. ...CMA-ES optimizes level set functions as design variables to minimize the fitness value that is regularized to avoid the ill-posedness of topology optimization using a perimeter constraint. Explicit boundaries between the material and void are obtained using the iso-surface of linearly interpolated level set functions. To show the effectiveness of the proposed method for multimodal structural optimization problems, topology optimization for optical and carpet cloaks is numerically demonstrated. The proposed computational strategy is robust to the settings of the initial configurations, even if the topology optimization problems have multimodal distributions of solutions that include many local minima with insufficient performance, and stably improves the regularized fitness value. The obtained optimal configurations have good performance, and we can obtain them without the trial and error of seeking appropriate initial configurations and adapting strategy parameters.
•This paper proposed CMA-ES-based topology optimization using a level set expression.•A box constraint handling technique that adapts the penalty function was proposed.•The minimized fitness was regularized by the perimeter constraint imposed explicitly.•As numerical examples, optical and carpet cloaks were designed for both polarized and unpolarized light.•The fitness is robustly improved without seeking an appropriate initial configuration and adjusting strategy parameters.
A plasma pattern is reproduced by coupling simulations between a particle-in- cell with Monte Carlo collisions model and a finite-difference time-domain simulation for an electromagnetic wave ...propagation when an external magnetic field is applied to the breakdown volume inside a microwave-rocket nozzle. The propagation speed and energy-absorption rate of the plasma are estimated based on the breakdown simulation, and these are utilized to reproduce shock wave propagation, which provides impulsive thrust for the microwave rocket. The shock wave propagation is numerically reproduced by solving the compressible Euler equation with an energy source of the microwave heating. The shock wave is asymmetrically generated inside the nozzle when the electron cyclotron resonance region has a lateral offset, which generates lateral and angular impulses for postural control of the vehicle. It is possible to develop an integrated device to maintain beaming ight of the microwave rocket, achieving both axial thrust improvement and postural control, by controlling the spatial distribution of the external magnetic field.
Peripheral tissue injury/inflammation can alter the properties of somatic sensory pathways, resulting in behavioral hypersensitivity and pathological and/or chronic pain, including increased ...responses to pain caused by both noxious stimuli (hyperalgesia) and normally innocuous stimuli (allodynia). Although there are increasing reports that glia in the spinal cord contribute to the maintenance of pathological pain, recent evidence suggests that activation of satellite glia in sensory ganglia may also play an important role in the development of hyperalgesia and allodynia. There is evidence that non-synaptically released chemical mediators derived from both neurons and satellite glia may trigger chronic pain via autocrine and/or paracrine mechanisms and that augmented excitability of primary afferent neurons results in changes in central pain-signaling neurons (central sensitization). The focus of the present review is on the contribution of the activation of satellite glia in sensory ganglia to pathological pain. In addition, we discuss potential therapeutic targets in satellite glia–neuronal interactions for the prevention of pathological pain.
Abstract
A two-dimensional (2D) axisymmetric fluid modeling for plasma dynamics was coupled with an electromagnetic wave propagation to capture the electromagnetic wave and plasma structures on the ...microwave-driven in-tube accelerator (MITA) concept. The electromagnetic wave injected into a waveguide was focused on at the vehicle’s rear side through reflection processes by the front mirror and the waveguide. An overcritical plasma was created at the high-intensity electric field region because of enhancement of an electron-impact ionization. The incident microwave was reflected by the plasma with overcritical density and a standing wave was induced in front of the dense plasma because the reflected wave overlapped with the incident microwave. In addition to wave enhancement by standing process, the strong electric field region was obtained at edges of the overcritical plasma because of wave diffraction, which can affect a shock wave strength and thrust performance of the MITA.
The characteristics of air entrainment in hydraulic jumps below a sluice gate were systematically investigated. The air entrainment region is divided into the advective diffusion region and the ...breaking region. For the advective diffusion region, it was found that the air concentration for a fully developed inflow is larger than that for an undeveloped inflow under a given inflow Froude number. For a partially developed inflow, the air concentration in the advective diffusion region depends on the boundary layer development of the supercritical inflow. The air concentration in the breaking region is nearly independent of the inflow conditions of the boundary layer development. Regarding the effect of the inflow Froude number, the air concentration in both the advective diffusion and breaking regions increases with the inflow Froude number under a given boundary layer development. The air entrainment mechanism in jumps is explained for both the advective diffusion and breaking regions.
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