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.     

Natural motion animation through constraining and deconstraining at will

This paper presents a computational technique for creating whole-body motions of human and animal characters without reference motion. Our work enables animators to generate a natural motion by dragging a link to an arbitrary position with any number of links pinned in the global frame, as well as other constraints such as desired joint angles and joint motion ranges. The method leads to an intuitive pin-and-drag interface where the user can generate whole-body motions by simply switching on or off or strengthening or weakening the constraints. This work is based on a new interactive inverse kinematics technique that allows more flexible attachment of pins and various types of constraints. Editing or retargeting captured motion requires only a small modification to the original method, although it can also create natural motions from scratch. We demonstrate the usefulness and advantage of our method with a number of example motion clips.     

Assistant force compensation for hand movement of patients by using exogenous signals and/or neurophysiological signals

Because functional diseases of the brain can cause disabilities related to human movement control, a compensation method was developed for improving the performance of hand movements. The compensation for human hand movements can be carried out by adding an assistant force that is generated from artificial equipment attached to a human arm. From the experiment on visual target tracking, it was found that the tracking trajectory was adequately represented by a dynamic model of the motion of an articulated industrial robot arm, and the different abilities for movement control among healthy people and patients were classified by different model parameters as position loop gain, velocity loop gain, and response delay. Dynamic force compensation was approached by considering the different control features of the patients. The effectiveness of the proposed compensation method was verified in a simulation study on an actual industrial robot arm. A human-machine interface, e.g., a brain-computer interface (BCI), for realizing the control of artificial equipment to compensate for human hand movements is also presented and discussed.     

Effect of annealing conditions on the uniformity of undoped Semi-Insulating InP

Recently, it was found that undoped semi-insulating InP can be obtained by highpressure annealing of high purity materials. The reproducibility and the uniformity was, however, not satisfactory. In the present work, we found that not only Fe concentrations but also Cr and Ni concentrations in annealed wafers were slightly increased during annealing. Since it seems that the origin of the contamination was due to the vapor source of red phosphorus, conductive InP with a trace amount of Fe was annealed under low phosphorus vapor pressure in order to reduce the contamination. By preventing the contamination of Cr and Ni, preparation of semi-insulating InP became highly reproducible. The minimum Fe concentration for realizing semi-insulating InP was found to be 1 x 10¹⁵cm⁻³. It was also found that the better resistivity uniformity can be obtained at higher annealing temperatures.     

Properties of Starch Films and their Improvement

The tensile strengths and elongations of starch films prepared from various unmodified and modified starches were measured. These properties were improved by addition of urea and polyvinyl alcohol to the starch paste. The results obtained were as follows.

• 1 The heating temperature greatly affected the tensile strength and elongation of various unmodified starches. Potato starch gave the best film.
• 2 Introduction of hydroxyethyl groups into corn starch had unexpectedly little affect on the properties of the films.
• 3 A combination of hydroxyethylation and acid-modification slightly improved the properties of the films.
• 4 No film could be obtained after combinations of hydroxyethylation and hypochlorite-oxidation, pyrodextrinization or α-amylase-dextrinization. However, addition of urea to these modified starches resulted in good films.
• 5 On addition of urea the elongation of starch films increased and the pastes adhered uniformly to water repellent surfaces.
• 6 A film with the best properties was prepared from a mixture of 67% acid-modified hydroxyethyl starch, 13% urea and 20% polyvinyl alcohol.

     

Studies on the Structure of Leguminosae Starches. 1. Solubility in Dimethyl Sulfoxide and by Enzymatic Action

In order to elucidate the granular structure of the leguminous starches the speed of solubilization of several starches was determined by digestion with dimethyl sulfoxide and with α-amylase. By microscopic investigations with normal and polarized light different forms of erosion were observed in the different starches, all of them less intense than those observed in cereal starches. It was concluded that the starch granules of mucunã seeds are the most homogeneous and have the least porous structure, followed by chick pea, jack, lablab and guanda beans. It is supposed that maturation, climate and soil influence the cristallinity of the granules, resulting in different digestibility.     

Uterine Deletion of Bmal1 Impairs Placental Vascularization and Induces Intrauterine Fetal Death in Mice

Recently, it was demonstrated that the expression of BMAL1 was decreased in the endometrium of women suffering from recurrent spontaneous abortion. To investigate the pathological roles of uterine clock genes during pregnancy, we produced conditional deletion of uterine Bmal1 (cKO) mice and found that cKO mice could receive embryo implantation but not sustain pregnancy. Gene ontology analysis of microarray suggested that uterine NK (uNK) cell function was suppressed in cKO mice. Histological examination revealed the poor formation of maternal vascular spaces in the placenta. In contrast to WT mice, uNK cells in the spongiotrophoblast layer, where maternal uNK cells are directly in contact with fetal trophoblast, hardly expressed an immunosuppressive NK marker, CD161, in cKO mice. By progesterone supplementation, pregnancy could be sustained until the end of pregnancy in some cKO mice. Although this treatment did not improve the structural abnormalities of the placenta, it recruited CD161-positive NK cells into the spongiotrophoblast layer in cKO mice. These findings indicate that the uterine clock system may be critical for pregnancy maintenance after embryo implantation.     

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.