A Fault Injection Method for Generating Error-correction Exercises in Algorithm Learning

In this paper we propose a method for generating errorcorrection exercises for undergraduate students in computer science who learn algorithms. Our main goal is to inject faults automatically into a correct source code that implements an algorithm to be studied. The proposed method utilizes design paradigm of the algorithm to determine effective fault types and positions in a source code. We have developed a prototype system and evaluated the appropriateness of the generated exercises to algorithm study. We carried out error-correction exercises in an algorithm class, and most students evaluated that the exercises are effective for algorithm study

Maoto, a Traditional Japanese Herbal Medicine, Inhibits Uncoating of Influenza Virus

We previously reported in randomized controlled trials that maoto, a traditional herbal medicine, showed clinical and virological efficacy for seasonal influenza. In this study, a culturing system for influenza was used to test the effect of maoto. A549 cells in the culture were infected with influenza virus A (PR8) and followed after treatment with maoto; the virus titers in the culture supernatant, intracellular viral proteins, and viral RNA were determined. When infected cells were cultured with maoto for 24 hr, the virus titer and protein were significantly reduced compared with medium only. Other subtypes, A/H3N2, H1N1pdm, and B, were also inhibited by maoto. Proliferation of viral RNA in a 6 hr culture was inhibited by maoto in the early phase, especially in the first 30 min. Focusing on the entry step of the influenza virus, we found that endosomal pH, regulated by vacuolar-type H+ ATPase (V-ATPase) located in the membrane, was increased when treated with maoto. We also found that uncoating of influenza viruses was also inhibited by maoto, resulting in the increase of the number of virus particles in endosomes. These results strongly suggest that the inhibition of endosomal acidification by maoto results in blocking influenza virus entry to cytoplasm, probably through the inhibition of V-ATPase. The present study provides evidence that supports the clinical use of maoto for the treatment of influenza

1,3a,6a-Triazapentalene derivatives as photo-induced cytotoxic small fluorescent dyes

1,3a,6a-Triazapentalene (TAP) is a compact fluorescent chromophore whose fluorescence properties vary greatly depending on the substituents on the TAP ring. This study investigated the photo-induced cytotoxicities of various TAP derivatives. Among the derivatives, 2-p-nitrophenyl-TAP showed significant cytotoxicity to HeLa cells under UV irradiation but no cytotoxicity without UV. In addition, the photo-induced cytotoxicity of 2-p-nitirophenyl-TAP was found to be cancer cell selective and effective against HeLa cells and HCT 116 cells. Under UV irradiation, 2-p-nitrophenyl-TAP generated reactive oxygen species (ROS) that induced an apoptosis and ferroptosis in cancer cells. Therefore, it was revealed that 2-p-nitrophenyl-TAP is the most compact dye that can generate ROS by photoirradiation

Author Correction:C151 in KEAP1 is the main cysteine sensor for the cyanoenone class of NRF2 activators, irrespective of molecular size or shape

Correction to: Scientific Reportshttps://doi.org/10.1038/s41598-018-26269-9, published online 23 May 2018 This Article contains an error in Figure 3.As a result of an error during the preparation of the figures for this Article, the western blots shown in Figure 3A and 3B contained an additional lane for the protein Tubulin. This is because an additional sample was loaded in the last lane of the gel to prevent potential stretching of the gel in this lane during electrophoresis if left empty. It was subsequently left uncropped from the tubulin blot shown in the published figure. The corrected Figure 3 and its accompanying legend appear below. C151 in KEAP1 is the primary sensor for MCE-23 and MCE-1 in MEF cells. Western blot analyses of total cell lysates of KEAP1-knockout MEF cells rescued with either wild-type (WT), single cysteine mutant C151S, double cysteine mutant C273W/C288E or triple cysteine mutant C151S/C273W/C288E of mouse N-terminally tagged HA-KEAP1. Cells (3 × 105 per well), growing in 6-well plates, were exposed to vehicle (0.1% DMSO) (A,B), MCE-23 (A) or MCE-1 (B) for 3 h, after which the cells were lysed. Immunoblotting was performed on cell lysates using antibodies raised against NRF2, HA and α-tubulin.</p

Silverrush. Xii. Intensity Mapping for Ly Α Emission Extending over 100-1000 Comoving Kpc Around Z ∼2-7 Laes with Subaru Hsc-Ssp and Chorus Data

We conduct intensity mapping to probe for extended diffuse Lyα emission around Lyα emitters (LAEs) at z ∼2-7, exploiting very deep (∼26 mag at 5σ) and large-area (∼4.5 deg2) Subaru/Hyper Suprime-Cam narrowband (NB) images and large LAE catalogs consisting of a total of 1540 LAEs at z = 2.2, 3.3, 5.7, and 6.6 obtained by the HSC-SSP and CHORUS projects. We calculate the spatial correlations of these LAEs with ∼1-2-billion-pixel flux values of the NB images, deriving the average Lyα surface brightness (SBLyα ) radial profiles around the LAEs. By carefully estimating systematics such as fluctuations of sky background and point-spread functions, we detect Lyα emission at 100-1000 comoving kpc around z = 3.3 and 5.7 LAEs at the 3.2σ and 3.7σ levels, respectively, and tentatively (=2.0σ) at z = 6.6. The emission is as diffuse as ∼10-20-10-19 erg s-1 cm-2 arcsec-2 and extended beyond the virial radius of a dark matter halo with a mass of 1011 M. While the observed SBLyα profiles have similar amplitudes at z = 2.2-6.6 within the uncertainties, the intrinsic SBLyα profiles (corrected for the cosmological dimming effect) increase toward high redshifts. This trend may be explained by increasing hydrogen gas density due to the evolution of the cosmic volume. Comparisons with theoretical models suggest that extended Lyα emission around an LAE is powered by resonantly scattered Lyα photons in the CGM and IGM that originate from the inner part of the LAE and/or neighboring galaxies around the LAE

Anti-Tumor Effect against Human Cancer Xenografts by a Fully Human Monoclonal Antibody to a Variant 8-Epitope of CD44R1 Expressed on Cancer Stem Cells

BACKGROUND: CD44 is a major cellular receptor for hyaluronic acids. The stem structure of CD44 encoded by ten normal exons can be enlarged by ten variant exons (v1-v10) by alternative splicing. We have succeeded in preparing MV5 fully human IgM and its class-switched GV5 IgG monoclonal antibody (mAb) recognizing the extracellular domain of a CD44R1 isoform that contains the inserted region coded by variant (v8, v9 and v10) exons and is expressed on the surface of various human epithelial cancer cells. METHODS AND PRINCIPAL FINDINGS: We demonstrated the growth inhibition of human cancer xenografts by a GV5 IgG mAb reshaped from an MV5 IgM. The epitope recognized by MV5 and GV5 was identified to a v8-coding region by the analysis of mAb binding to various recombinant CD44 proteins by enzyme-linked immunosorbent assay. GV5 showed preferential reactivity against various malignant human cells versus normal human cells assessed by flow cytometry and immunohistological analysis. When ME180 human uterine cervix carcinoma cells were subcutaneously inoculated to athymic mice with GV5, significant inhibition of tumor formation was observed. Furthermore, intraperitoneal injections of GV5markedly inhibited the growth of visible established tumors from HSC-3 human larynx carcinoma cells that had been subcutaneously transplanted one week before the first treatment with GV5. From in vitro experiments, antibody-dependent cellular cytotoxicity and internalization of CD44R1 seemed to be possible mechanisms for in vivo anti-tumor activity by GV5. CONCLUSIONS: CD44R1 is an excellent molecular target for mAb therapy of cancer, possibly superior to molecules targeted by existing therapeutic mAb, such as Trastuzumab and Cetuximab recognizing human epidermal growth factor receptor family

Stimulatory actions of lysophosphatidic acid on mouse ATDC5 chondroprogenitor cells.

Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are bioactive lysophospholipids that affect various cellular processes through G protein-coupled receptors. In our current study, we found by in situ hybridization that E11.5 mouse embryos strongly expressed the LPA receptor subtype LPA(1) in cartilaginous bone primordia and the surrounding mesenchymal cells. However, despite their wide-ranging actions, the roles of lysophospholipids in chondrogenesis remain poorly understood. The mouse clonal cell line ATDC5 undergoes a sequential differentiation of chondroprogenitor cells in vitro. Undifferentiated and differentiated ATDC5 cells express LPA(1) and other lysophospholipid receptors including S1P receptor S1P(1) and S1P(2). Taking advantage of this cell model, we studied the effects of LPA on the activities of chondroprogenitor cells. LPA markedly stimulates both DNA synthesis and the migration of ATDC5 chondroprogenitor cells in culture, whereas S1P suppresses the migration of these cells. Treatment with Ki16425, an LPA(1)- and LPA(3)-specific receptor antagonist, suppressed the fetal bovine serum-stimulated migration of ATDC5 cells by almost 80%. These results indicate that LPA plays an important role in the activation of chondroprogenitor cells