Effect of Air Gap on Electrical Tree in Epoxy Resin Under High Frequency Bipolar Square-Wave Voltage

Insulation fails quickly under high-frequency AC high voltage, especially bipolar square-wave voltage with a high dV/dt. It is of great significance to study the failure mechanism of epoxy casting insulation under such kind of voltage. In this paper, pin-plane epoxy casting insulation samples with air gaps were prepared, and the relation between the electrical trees under the high frequency bipolar square-wave voltage and the air gap conditions and voltage frequencies (1~20 kHz) were studied. Results indicated that, with the presence of air gaps, the electrical trees were bush-type and had a relatively slow growth rate, which was different from the fast-growing branch-type trees in the samples without air gap. The electrical tree characteristics related with the size of air gap and voltage frequency were also studied. The electrical tree grew faster under higher voltage frequency or with a smaller air gap. Results proved that discharge introduced a lot of defects for the surface layer of the epoxy resin samples and hence induced the possibility of multi-directional expansion of electrical trees. In addition, the resulting heat accumulation and unique charge transport synergistically affected the electrical tree characteristics under the high frequency bipolar square-wave voltage.     

MDA5 complements TLR3 in suppression of neuroblastoma

Toll-like receptor3 (TLR3) has been confirmed to be differentially expressed in neuroblastoma (NB), and predicts a favorable prognosis with a high expression in tumor tissues. Treatment with TLR3 agonist - polyinosinic-polycytidylic acid [poly(I:C)] could induce significant but limited apoptosis in TLR3-expressing NB cells, suggesting that other viral RNA sensors, including melanoma differentiation-associated gene 5 (MDA5) and retinoic acid-inducible gene-I (RIG-I) in the cytosolic compartment might also be implicated in poly(I:C)-induced NB cell death. MDA5 and RIG-I were induced by poly(I:C) to express in two of six NB cell lines, SK-N-AS (AS) and SK-N-FI, which were associated with up-regulation of caspase9 and active caspase3. While knockdown of either MDA5 or RIG-I alone is ineffective to decrease caspase9 and active caspase3, simultaneously targeting MDA5 and TLR3 showed the best effect to rescue poly(I:C) induced up-regulation of mitochondrial antiviral signaling protein (MAVS), caspase9, active caspase3, and apoptosis in AS cells. Over-expression of MDA5 in FaDu cells resulted in significantly less colony formation and more poly(I:C)-induced cell death. Further studies in human NB tissue samples revealed that MDA5 expression in NB tissues predicted a favorable prognosis synergistically with TLR3. Our findings indicate that MDA5 may serve as a complementary role in the TLR3 activated suppression of NB.     

Berberine regulates the Notch1/PTEN/PI3K/AKT/mTOR pathway and acts synergistically with 17-AAG and SAHA in SW480 colon cancer cells

ContextBerberine (BBR) is used to treat diarrhoea and gastroenteritis in the clinic. It was found to have anticolon cancer effects.ObjectiveTo study the anticolon cancer mechanism of BBR by connectivity map (CMAP) analysis.Materials and methodsCMAP based mechanistic prediction was conducted by comparing gene expression profiles of 10 μM BBR treated MCF-7 cells with that of clinical drugs such as helveticoside, ianatoside C, pyrvinium, gossypol and trifluoperazine. The treatment time was 12 h and two biological replications were performed. The DMSO-treated cells were selected as a control. The interaction between 100 μM BBR and target protein was measured by cellular thermal shift assay. The protein expression of 1–9 μM BBR treated SW480 cells were measured by WB assay. Apoptosis, cell cycle arrest, mitochondrial membrane potential (MMP) of 1–9 μM BBR treated SW480 cells were measured by flow cytometry and Hoechst 33342 staining methods.ResultsCMAP analysis found 14 Hsp90, HDAC, PI3K or mTOR protein inhibitors have similar functions with BBR. The experiments showed that BBR inhibited SW480 cells proliferation with IC₅₀ of 3.436 μM, induced apoptosis, autophage, MMP depolarization and arrested G1 phase of cell cycle at 1.0 μM. BBR dose-dependently up-regulated PTEN, while inhibited Notch1, PI3K, Akt and mTOR proteins at 1.0–9.0 μM (p < 0.05). BBR also acted synergistically with Hsp90 and HDAC inhibitor (0.01 μM) in SW480 cells at 0.5 and 1.0 μM.Discussion and conclusionsThe integrative gene expression-based chemical genomic method using CMAP analysis may be applicable for mechanistic studies of other multi-targets drugs.