Dimethyl Fumarate Induces Apoptosis via Inhibition of NF-κB and Enhances the Effect of Paclitaxel and Adriamycin in Human TNBC Cells

Triple-negative breast cancer (TNBC) has the poorest prognosis of all breast cancer subtypes. Recently, the activation of NF-κB, which is involved in the growth and survival of malignant tumors, has been demonstrated in TNBC, suggesting that NF-κB may serve as a new therapeutic target. In the present study, we examined whether dimethyl fumarate (DMF), an NF-κB inhibitor, induces apoptosis in TNBC cells and enhances the apoptosis-inducing effect of paclitaxel and adriamycin. Cell survival was analyzed by the trypan blue assay and apoptosis assay. Protein detection was examined by immunoblotting. The activation of NF-κB p65 was correlated with poor prognosis in patients with TNBC. DMF induced apoptosis in MDA-MB-231 and BT-549 cells at concentrations that were non-cytotoxic to the normal mammary cell line MCF-10A. Furthermore, DMF inhibited NF-κB nuclear translocation and Survivin, XIAP, Bcl-xL, and Bcl-2 expression in MDA-MB-231 and BT-549 cells. Moreover, DMF enhanced the apoptosis-inducing effect of paclitaxel and adriamycin in MDA-MB-231 cells. These findings suggest that DMF may be an effective therapeutic agent for the treatment of TNBC, in which NF-κB is constitutively active. DMF may also be useful as an adjuvant therapy to conventional anticancer drugs.     

Deep Phenotyping of Superficial Epidermolytic Ichthyosis due to a Recurrent Mutation in KRT2

Superficial epidermolytic ichthyosis (SEI) is an autosomal dominant inherited ichthyosis. SEI is caused by mutations in KRT2 and frequently shows erythroderma and widespread blistering at birth. We report the clinical manifestations of two patients from a Japanese family with SEI caused by a hotspot mutation, p.Glu487Lys, in KRT2. In addition, we summarize previous reports on SEI patients with the identical mutation. One of the two patients had disease onset at the age of 7 months. The other patient’s age of onset is unknown, but it was in childhood. Neither of the two patients showed erythroderma. To perform deep phenotyping, we studied the age of onset and the frequency of erythroderma in 34 reported SEI cases with the p.Glu487Lys mutation, including the present cases. Among the cases with sufficient clinical information, 44.4% of the cases that were due to p.Glu487Lys in KRT2 occurred at birth. Erythroderma was observed in 11.1% of the cases with p.Glu487Lys in KRT2.     

Experimental and numerical study on hydrodynamics of riparian vegetation

Recently, many channelized rivers tend to be heavily vegetated due to regime shifts in hydrological, fluvial and ecological processes. Dense vegetation in a river frequently obstructs a flood flow and reduces conveyance capacity of channels. On the other hand, river vegetation provides various ecological services such as habitats for various species and life, natural cycle of organic and inorganic substances, etc.. It is of engineering importance to understand vegetation hydrodynamics in order to preserve vegetation nature and keep a certain level of flow conveyance capacity. In view that willows tend to be densely vegetated along the shoreline of floodplains or sandbars, a field measurement, a physical model experiment and a numerical analysis were carried out for investigating hydrodynamics in an open channel with riparian vegetation. Discussion was made focusing on flow and shear layer structures developed around the vegetation canopy.     

Development and Evaluation of a Robust Sandwich Immunoassay System Detecting Serum WFA-Reactive IgA1 for Diagnosis of IgA Nephropathy

Aberrant glycosylation of IgA1 is involved in the development of IgA nephropathy (IgAN). There are many reports of IgAN markers focusing on the glycoform of IgA1. None have been clinically applied as a routine test. In this study, we established an automated sandwich immunoassay system for detecting aberrant glycosylated IgA1, using Wisteria floribunda agglutinin (WFA) and anti-IgA1 monoclonal antibody. The diagnostic performance as an IgAN marker was evaluated. The usefulness of WFA for immunoassays was investigated by lectin microarray. A reliable standard for quantitative immunoassay measurements was designed by modifying a purified IgA1 substrate. A validation study using multiple serum specimens was performed using the established WFA-antibody sandwich automated immunoassay. Lectin microarray results showed that WFA specifically recognized N-glycans of agglutinated IgA1 in IgAN patients. The constructed IgA1 standard exhibited a wide dynamic range and high reactivity. In the validation study, serum WFA-reactive IgA1 (WFA+-IgA1) differed significantly between healthy control subjects and IgAN patients. The findings indicate that WFA is a suitable lectin that specifically targets abnormal agglutinated IgA1 in serum. We also describe an automated immunoassay system for detecting WFA+-IgA1, focusing on N-glycans.     

Optical properties of photoluminescent polycrystalline CuLa0.98Eu0.02O2 thin film prepared by pulsed laser deposition at room temperature

Smooth CuLa_0.98Eu_0.02O₂ thin film has successfully been prepared by pulsed laser deposition method at room temperature. Crystal structure of the obtained film was almost same as that of CuLa_0.98Eu_0.02O₂ polycrystalline ceramic. Orange luminescence with high intensity due to ⁵D₀ – ⁷F_0,1 transitions of Eu³⁺, which was an evidence of Eu³⁺ substitution for La³⁺ site in LaO₆ octahedra with the inversion symmetry, was also observed in the obtained film. The optical band gap of CuLa_0.98Eu_0.02O₂ was measured to be 2.85 eV from absorption spectroscopy.     

Punch-through protection of SSDs in beam accidents

We have tested the effectiveness of punch-through protection (PTP) structures on n-on-p AC-coupled Silicon strip detectors using pulses from an 1064 nm IR laser, which simulate beam accidents. The voltages on the strips are measured as a function of the bias voltage and compared with the results of DC I-V measurements, which are commonly used to characterize the PTP structures. We find that the PTP structures are only effective at very large currents (several mA), and clamp the strips to much larger voltages than assumed from the DC measurements. We also find that the finite resistance of the strip implant compromises the effectiveness of the PTP structures.     

Surface Waves on Superfluid <Superscript>4</Superscript>He Under Reduced Gravity

Superfluid ⁴He was produced on a small jet plane for the first time using a small GM-refrigerator to condense the liquid and a scroll pump to get the superfluid by evaporation. The surface wave on superfluid under 0.5g _E, 0.1g _E and 0.05g _E, together with 2g _E and 1g _E, was successfully examined by an optical method utilizing parabolic flight. Here, g _E is the gravitational constant on the ground. Assuming that only the fundamental mode was excited as determined by the sample cell width, the resonance peak in the frequency domain was well reproduced by the gravity wave with corresponding gravity constant.     

A study of reactor neutrino monitoring at the experimental fast reactor JOYO

We carried out a study of neutrino detection at the experimental fast reactor JOYO using a 0.76 tons gadolinium loaded liquid scintillator detector. The detector was set up on the ground level at 24.3 m from the JOYO reactor core of 140 MW thermal power. The measured neutrino event rate from reactor on-off comparison was 1.11±1.24(stat.)±0.46(syst.) events/day. Although the statistical significance of the measurement was not enough, backgrounds in such a compact detector at the ground level were studied in detail and MC simulations were found to describe the data well. A study for improvement of the detector for future such experiments is also shown.     

Measurement of tongue–artificial nipple contact pressure during infant sucking

To clarify the motor function of the infant tongue during sucking, we developed an artificial nipple that contained multiple small built‐in force sensors integrated with a PC‐based system which is capable of measuring tongue–artificial nipple contact pressures in real time. The force sensor is a cantilever structure with a small, thin stainless steel beam where an all‐purpose foil strain gauge is attached to the surface of the beam. An artificial nipple made of an elastomer containing these sensors is connected through an amplifier and an A/D converter to a PC via a USB port. Using this system, measurements were taken in three infants whose oral feeding was well established and in one infant of low birth weight. The results from each force sensor showed a pressure waveform of a nearly simple harmonic motion that indicated a peristalsis‐like movement of the tongue; the sucking frequency was found to be about two times per second. In addition, in the low‐birth‐weight infant, the pressure changed as the infant grew. © 2012 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.     

Connection‐Strength Estimation of Neuronal Networks by Fitting for Izhikevich Model

Recently, there has been abundant research using multineuron recording, but there are many problems with extracting the features from the obtained spike time series, which are huge in volume and complex. Here we introduce a new method of estimating synaptic connection strengths between neurons by fitting to the Izhikevich model by maximum likelihood estimation. We demonstrate that our method can estimate connection strengths from spike time series given by a simulated neural ensemble and can estimate nonconnectivity between two independent cultured neuronal networks. These results suggest that our method is applicable to network and plasticity analysis of neuronal networks.