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The composite materials envisioned in this study were fiber-reinforced woven composites, which were composed of fibers as the reinforcement and resin as the matrix. Fiber-reinforced thermoplastic woven composites had high productivity, high toughness, and excellent recyclability because the thermoplastic resin was inexpensive and can be formed in a short period of time. When spread tow were used, it was desirable to reduce void generation and impregnation time during resin impregnation. It was very important to evaluate and understand the mechanical properties and damage mechanisms in advance to ensure the safety and reliability of the structure. However, the woven structure of fiber bundles was complex, and various damage forms such as resin cracks in the matrix, cracks in the fiber bundle, and fiber breakage occur, making damage evaluation difficult. In this study, to investigate the damage evolution behavior of thermoplastic woven CFRP with spread tows, an analysis with the mesh superposition method was proposed and the numerical results were compared with the conventional method. As a result, we believed that the mesh superposition method was useful because the effort required for model creation can be reduced in models with thinner layer thicknesses in the mesh superposition analysis compared to the conventional analysis. [ABSTRACT FROM AUTHOR]

One-electron reduction of the cycloheptatrienyl and cycloheptatriene [Pd.sub.3] sandwich complexes have produced dimers with novel bitriangle [Pd.sub.6] moieties, where the parallel sandwich frameworks are retained. The [Pd.sub.3] triangle geometry has changed within the sandwich framework due to the different electronic demands of cycloheptatrienyl and cycloheptatriene ligands for the [[[Pd.sub.3].sup.2+] core both in the monomer and the dimers.

Recent studies have indicated that the intracellular concentration of chloride ions (Cl−) regulates gene expression in several types of cells and that Cl− modulators positively or negatively regulate the PI3K/AKT/mammalian target of rapamycin (mTOR) and signal transducer and activator of transcription (STAT)3 signaling pathways. We previously reported that the Ca2+‐activated Cl− channel anoctamine (ANO)1 regulated human epidermal growth factor receptor 2 (HER2) transcription in breast cancer YMB‐1 cells. However, the mechanisms underlying ANO1‐regulated HER2 gene expression have not yet been elucidated. In the present study, we showed the involvement of intracellular organelle ClC‐3 Cl−/H+ transporter in HER2 transcription in breast cancer MDA‐MB‐453 cells. The siRNA‐mediated inhibition of ClC‐3, but not ANO1, markedly repressed HER2 transcription in MDA‐MB‐453 cells. Subsequently, treatments with the AKT inhibitor AZD 5363 and mTOR inhibitor everolimus significantly enhanced HER2 transcription in MDA‐MB‐453 cells, whereas that with the STAT3 inhibitor 5,15‐diphenylporphyrin (5,15‐DPP) inhibited it. AKT and mTOR inhibitors also significantly enhanced HER2 transcription in YMB‐1 cells. The siRNA‐mediated inhibition of ClC‐3 and ANO1 resulted in increased AKT phosphorylation and decreased STAT3 phosphorylation in MDA‐MB‐453 and YMB‐1 cells, respectively. The intracellular Cl− channel protein CLIC1 was expressed in both cells; however, its siRNA‐mediated inhibition did not elicit the transcriptional repression of HER2. Collectively, our results demonstrate that intracellular Cl− regulation by ANO1/ClC‐3 participates in HER2 transcription, mediating the PI3K/AKT/mTOR and/or STAT3 signaling pathway(s) in HER2‐positive breast cancer cells, and support the potential of ANO1/ClC‐3 blockers as therapeutic options for patients with resistance to anti‐HER2 therapies. [ABSTRACT FROM AUTHOR]

The large-conductance Ca2+-activated K+ channel KCa1.1 plays an important role in the promotion of breast cancer cell proliferation and metastasis. The androgen receptor (AR) is proposed as a therapeutic target for AR-positive advanced triple-negative breast cancer. We herein investigated the effects of a treatment with antiandrogens on the functional activity, activation kinetics, transcriptional expression, and protein degradation of KCa1.1 in human breast cancer MDA-MB-453 cells using real-time PCR, Western blotting, voltage-sensitive dye imaging, and whole-cell patch clamp recording. A treatment with the antiandrogen bicalutamide or enzalutamide for 48 h significantly suppressed (1) depolarization responses induced by paxilline (PAX), a specific KCa1.1 blocker and (2) PAX-sensitive outward currents induced by the depolarizing voltage step. The expression levels of KCa1.1 transcripts and proteins were significantly decreased in MDA-MB-453 cells, and the protein degradation of KCa1.1 mainly contributed to reductions in KCa1.1 activity. Among the eight regulatory β and γ subunits, LRRC26 alone was expressed at high levels in MDA-MB-453 cells and primary and metastatic breast cancer tissues, whereas no significant changes were observed in the expression levels of LRRC26 and activation kinetics of PAX-sensitive outward currents in MDA-MB-453 cells by the treatment with antiandrogens. The treatment with antiandrogens up-regulated the expression of the ubiquitin E3 ligases, FBW7, MDM2, and MDM4 in MDA-MB-453 cells, and the protein degradation of KCa1.1 was significantly inhibited by the respective siRNA-mediated blockade of FBW7 and MDM2. Based on these results, we concluded that KCa1.1 is an androgen-responsive gene in AR-positive breast cancer cells, and its down-regulation through enhancements in its protein degradation by FBW7 and/or MDM2 may contribute, at least in part, to the antiproliferative and antimetastatic effects of antiandrogens in breast cancer cells. [ABSTRACT FROM AUTHOR]

Dipeptidyl aminopeptidase IV (DAP IV or DPP IV) from Pseudoxanthomonas mexicana WO24 (PmDAP IV) preferentially cleaves substrate peptides with Pro or Ala at the P1 position [NH2-P2-P1(Pro/Ala)-P1′-P2′...]. For crystallographic studies, the periplasmic form of PmDAP IV was overproduced in Escherichia coli, purified and crystallized in complex with the tripeptide Lys-Pro-Tyr using the hanging-drop vapour-diffusion method. Kinetic parameters of the purified enzyme against a synthetic substrate were also determined. X-ray diffraction data to 1.90 Å resolution were collected from a triclinic crystal form belonging to space group P1, with unit-cell parameters a = 88.66, b = 104.49, c = 112.84 Å, α = 67.42, β = 68.83, γ = 65.46°. Initial phases were determined by the molecular-replacement method using Stenotrophomonas maltophilia DPP IV (PDB entry ) as a template and refinement of the structure is in progress. [ABSTRACT FROM AUTHOR]

The intermediate-conductance Ca2+-activated K+ channel KCa3.1 is involved in the promotion of tumor growth and metastasis, and is a potential therapeutic target and biomarker for cancer. Histone deacetylase inhibitors ( HDACis) have considerable potential for cancer therapy, however, the effects of HDACis on ion channel expression have not yet been investigated in detail. The results of this study showed a significant decrease in KCa3.1 transcription by HDAC inhibition in the human breast cancer cell line YMB-1, which functionally expresses KCa3.1. A treatment with the clinically available, class I, II, and IV HDAC inhibitor, vorinostat significantly downregulated KCa3.1 transcription in a concentration-dependent manner, and the plasmalemmal expression of the KCa3.1 protein and its functional activity were correspondingly decreased. Pharmacological and si RNA-based HDAC inhibition both revealed the involvement of HDAC2 and HDAC3 in KCa3.1 transcription through the same mechanism. The downregulation of KCa3.1 in YMB-1 was not due to the upregulation of the repressor element-1 silencing transcription factor, REST and the insulin-like growth factor-binding protein 5, IGFBP5. The significant decrease in KCa3.1 transcription by HDAC inhibition was also observed in the KCa3.1-expressing human prostate cancer cell line, PC-3. These results suggest that vorinostat and the selective HDACis for HDAC2 and/or HDAC3 are effective drug candidates for KCa3.1-overexpressing cancers. [ABSTRACT FROM AUTHOR]

Dipeptidyl peptidase 11 from Porphyromonas gingivalis (PgDPP11) preferentially cleaves substrate peptides with Asp and Glu at the P1 position [NH2-P2-P1(Asp/Glu)-P1′-P2′...]. For crystallographic studies, PgDPP11 was overproduced in Escherichia coli, purified and crystallized using the hanging-drop vapour-diffusion method. X-ray diffraction data to 1.82 Å resolution were collected from an orthorhombic crystal form belonging to space group C2221, with unit-cell parameters a = 99.33, b = 103.60, c = 177.33 Å. Structural analysis by the multi-wavelength anomalous diffraction method is in progress. [ABSTRACT FROM AUTHOR]

Recent studies have indicated that the intracellular concentration of chloride ions (Cl - ) regulates gene expression in several types of cells and that Cl - modulators positively or negatively regulate the PI3K/AKT/mammalian target of rapamycin (mTOR) and signal transducer and activator of transcription (STAT)3 signaling pathways. We previously reported that the Ca 2+ -activated Cl - channel anoctamine (ANO)1 regulated human epidermal growth factor receptor 2 (HER2) transcription in breast cancer YMB-1 cells. However, the mechanisms underlying ANO1-regulated HER2 gene expression have not yet been elucidated. In the present study, we showed the involvement of intracellular organelle ClC-3 Cl - /H + transporter in HER2 transcription in breast cancer MDA-MB-453 cells. The siRNA-mediated inhibition of ClC-3, but not ANO1, markedly repressed HER2 transcription in MDA-MB-453 cells. Subsequently, treatments with the AKT inhibitor AZD 5363 and mTOR inhibitor everolimus significantly enhanced HER2 transcription in MDA-MB-453 cells, whereas that with the STAT3 inhibitor 5,15-diphenylporphyrin (5,15-DPP) inhibited it. AKT and mTOR inhibitors also significantly enhanced HER2 transcription in YMB-1 cells. The siRNA-mediated inhibition of ClC-3 and ANO1 resulted in increased AKT phosphorylation and decreased STAT3 phosphorylation in MDA-MB-453 and YMB-1 cells, respectively. The intracellular Cl - channel protein CLIC1 was expressed in both cells; however, its siRNA-mediated inhibition did not elicit the transcriptional repression of HER2. Collectively, our results demonstrate that intracellular Cl - regulation by ANO1/ClC-3 participates in HER2 transcription, mediating the PI3K/AKT/mTOR and/or STAT3 signaling pathway(s) in HER2-positive breast cancer cells, and support the potential of ANO1/ClC-3 blockers as therapeutic options for patients with resistance to anti-HER2 therapies., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

The large-conductance Ca 2+ -activated K + channel K Ca 1.1 plays an important role in the promotion of breast cancer cell proliferation and metastasis. The androgen receptor (AR) is proposed as a therapeutic target for AR-positive advanced triple-negative breast cancer. We herein investigated the effects of a treatment with antiandrogens on the functional activity, activation kinetics, transcriptional expression, and protein degradation of K Ca 1.1 in human breast cancer MDA-MB-453 cells using real-time PCR, Western blotting, voltage-sensitive dye imaging, and whole-cell patch clamp recording. A treatment with the antiandrogen bicalutamide or enzalutamide for 48 h significantly suppressed (1) depolarization responses induced by paxilline (PAX), a specific K Ca 1.1 blocker and (2) PAX-sensitive outward currents induced by the depolarizing voltage step. The expression levels of K Ca 1.1 transcripts and proteins were significantly decreased in MDA-MB-453 cells, and the protein degradation of K Ca 1.1 mainly contributed to reductions in K Ca 1.1 activity. Among the eight regulatory β and γ subunits, LRRC26 alone was expressed at high levels in MDA-MB-453 cells and primary and metastatic breast cancer tissues, whereas no significant changes were observed in the expression levels of LRRC26 and activation kinetics of PAX-sensitive outward currents in MDA-MB-453 cells by the treatment with antiandrogens. The treatment with antiandrogens up-regulated the expression of the ubiquitin E3 ligases, FBW7, MDM2, and MDM4 in MDA-MB-453 cells, and the protein degradation of K Ca 1.1 was significantly inhibited by the respective siRNA-mediated blockade of FBW7 and MDM2. Based on these results, we concluded that K Ca 1.1 is an androgen-responsive gene in AR-positive breast cancer cells, and its down-regulation through enhancements in its protein degradation by FBW7 and/or MDM2 may contribute, at least in part, to the antiproliferative and antimetastatic effects of antiandrogens in breast cancer cells.

Vitamin D (VD) reduces the risk of breast cancer and improves disease prognoses. Potential VD analogs are being developed as therapeutic agents for breast cancer treatments. The large-conductance Ca 2+ -activated K⁺ channel K Ca 1.1 regulates intracellular Ca 2+ signaling pathways and is associated with high grade tumors and poor prognoses. In the present study, we examined the effects of treatments with VD receptor (VDR) agonists on the expression and activity of K Ca 1.1 in human breast cancer MDA-MB-453 cells using real-time PCR, Western blotting, flow cytometry, and voltage-sensitive dye imaging. Treatments with VDR agonists for 72 h markedly decreased the expression levels of K Ca 1.1 transcripts and proteins in MDA-MB-453 cells, resulting in the significant inhibition of depolarization responses induced by paxilline, a specific K Ca 1.1 blocker. The specific proteasome inhibitor MG132 suppressed VDR agonist-induced decreases in K Ca 1.1 protein expression. These results suggest that K Ca 1.1 is a new downstream target of VDR signaling and the down-regulation of K Ca 1.1 through the transcriptional repression of K Ca 1.1 and enhancement of K Ca 1.1 protein degradation contribute, at least partly, to the antiproliferative effects of VDR agonists in breast cancer cells., Competing Interests: The authors declare no conflict of interest.