An investigation into major factors in shunt capacitor switchingperformances by vacuum circuit breakers with copper-chromium contacts

The performance of vacuum circuit breakers in switching shunt capacitors depends much more on in-rush current than on interrupting current. This is because when contacts that were fused together by pre-arcs during contact closing are forcibly separated, large protrusions are formed on the contact surface, making it easier for microparticles to be detached from the protrusions. Microparticles are also produced on the entire surface of contacts by mechanical impact or cold weld. Current interruption of a certain magnitude, however, has a conditioning effect because moderate arcs can eliminate such microparticles and lower the protrusions. To clarify the relationship between the behavior of microparticles and the dielectric breakdown, a laser scattering technique was employed. The authors found a microparticle-induced breakdown phenomena that could explain the mechanism of long delayed restrikes that is occasionally observed in vacuum circuit breakers     

Linoleic Acid Upregulates Microrna-494 to Induce Quiescence in Colorectal Cancer

Cancer dormancy is a state characterized by the quiescence of disseminated cancer cells, and tumor recurrence occurs when such cells re-proliferate after a long incubation period. These cancer cells tend to be treatment resistant and one of the barriers to successful therapeutic intervention. We have previously reported that long-term treatment of cancer cells with linoleic acid (LA) induces a dormancy-like phenotype. However, the mechanism underpinning this effect has not yet been clarified. Here, we investigate the mechanism of LA-induced quiescence in cancer cells. We first confirmed that long-term treatment of the mouse colorectal cancer cell line CT26 with LA induced quiescence. When these cells were inoculated subcutaneously into a syngeneic mouse and fed with an LA diet, the inoculated cancer cells maintained the quiescent state and exhibited markers of dormancy. LA-treated CT26 cells showed reduced oxidative phosphorylation, glycolysis, and energy production as well as reduced expression of the regulatory factors Pgc1α and MycC. MicroRNA expression profiling revealed that LA induced an upregulation in miR-494. The expression of Pgc1α and MycC were both induced by an miR-494 mimic, and the LA-induced decrease in gene expression was abrogated by an miR-494 inhibitor. The expression of miR-494 was enhanced by the mitochondrial oxidative stress produced by LA. In a syngeneic mouse subcutaneous tumor model, growth suppression by an LA diet and growth delay by LA pretreatment + LA diet were found to have similar effects as administration of an miR-494 mimic. In contrast, the effects of LA were abrogated by an miR-494 inhibitor. Analysis of human colorectal cancer tissue revealed that miR-494 was present at low levels in non-metastatic cases and cases with simultaneous liver metastases but was expressed at high levels in cases with delayed liver metastases, which also exhibited reduced expression of PGC1α and MYCC. These results suggest that miR-494 is involved in cancer dormancy induced by high levels of LA intake and that this microRNA may be valuable in targeting dormant cancer cells.     

SIG-1451, a Novel,Non-Steroidal Anti-Inflammatory Compound,Attenuates Light-Induced Photoreceptor Degeneration by Affecting the Inflammatory Process

Age-related macular degeneration is a progressive retinal disease that is associated with factors such as oxidative stress and inflammation. In this study, we evaluated the protective effects of SIG-1451, a non-steroidal anti-inflammatory compound developed for treating atopic dermatitis and known to inhibit Toll-like receptor 4, in light-induced photoreceptor degeneration. SIG-1451 was intraperitoneally injected into rats once per day before exposure to 1000 lx light for 24 h; one day later, optical coherence tomography showed a decrease in retinal thickness, and electroretinogram (ERG) amplitude was also found to have decreased 3 d after light exposure. Moreover, SIG-1451 partially protected against this decrease in retinal thickness and increase in ERG amplitude. One day after light exposure, upregulation of inflammatory response-related genes was observed, and SIG-1451 was found to inhibit this upregulation. Iba-1, a microglial marker, was suppressed in SIG-1451-injected rats. To investigate the molecular mechanism underlying these effects, we used lipopolysaccharide (LPS)-stimulated rat immortalised Müller cells. The upregulation of C-C motif chemokine 2 by LPS stimulation was significantly inhibited by SIG-1451 treatment, and Western blot analysis revealed a decrease in phosphorylated I-κB levels. These results indicate that SIG-1451 indirectly protects photoreceptor cells by attenuating light damage progression, by affecting the inflammatory responses.     

Delay characteristics of surface charging on a cylindricalinsulator in vacuum

This paper describes the temporal characteristics of surface charging on a cylindrical insulator made of polymethylmethacrylate (PMMA) resin or alumina ceramic. The insulator is subjected to a dc voltage step or to a trapezoidal voltage in vacuum. The charging is observed by using an electrostatic probe located at the surface of the cathode close to the triple junction where the insulator, cathode and vacuum meet. The probe signal shows a step increase associated with the charging. The interval between the voltage rise and the charging, which is defined as the delay time of charging in this paper, ranges from 10 ^-5 s to 10 s depending on the material and the applied voltage. It also depends on the condition of the insulator-cathode interface, the electrical prestress and the surface roughness of the insulator. Among these factors, the surface roughness has the largest effect on the delay time. Two-dimensional Monte Carlo simulation based on the secondary emission electron avalanche model has been performed to analyze the charging progress. During the delay period, positive charge accumulates on the surface of the insulator near the cathode, which further accelerates the charging     

Sunitinib and Pterostilbene Combination Treatment Exerts Antitumor Effects in Gastric Cancer via Suppression of PDZD8

The use of molecular-targeted drugs in the treatment of gastric cancer is increasing. However, the variety of molecular-targeted drugs in gastric cancer is still limited, and the development of new molecular-targeted therapies is required. The effect of combining sunitinib (SUN) with pterostilbene (PTE) on the human gastric cancer cell lines TMK1 and MKN74 was examined in in vitro and in vivo. Compared with SUN or PTE treatment alone, cotreatment induced pronounced suppression of cell proliferation, with a marked increase in oxidative stress. SUN was associated with a significant retention of mitochondrial Fe²⁺. SUN-treated cells decreased expression of PDZ domain-containing protein 8 (PDZD8). Knockdown of PDZD8 in both cells induced Fe²⁺ retention, and siPDZD8+PTE markedly suppressed cell proliferation with suppressed oxidative phosphorylation, as did the combination of SUN+PTE. In a nude mouse tumor model, a pronounced antitumor effect was observed with SUN+PTE treatment compared to SUN alone. PDZD8 may be a newly discovered off-target for SUN, and that the combined use of PTE with SUN significantly promotes antitumor activity in gastric cancer cell lines. The combined use of SUN and PTE might be a new molecular-targeted therapy for gastric cancer.     

Developmental Formation of the GABAergic and Glycinergic Networks in the Mouse Spinal Cord

Gamma-aminobutyric acid (GABA) and glycine act as inhibitory neurotransmitters. Three types of inhibitory neurons and terminals, GABAergic, GABA/glycine coreleasing, and glycinergic, are orchestrated in the spinal cord neural circuits and play critical roles in regulating pain, locomotive movement, and respiratory rhythms. In this study, we first describe GABAergic and glycinergic transmission and inhibitory networks, consisting of three types of terminals in the mature mouse spinal cord. Second, we describe the developmental formation of GABAergic and glycinergic networks, with a specific focus on the differentiation of neurons, formation of synapses, maturation of removal systems, and changes in their action. GABAergic and glycinergic neurons are derived from the same domains of the ventricular zone. Initially, GABAergic neurons are differentiated, and their axons form synapses. Some of these neurons remain GABAergic in lamina I and II. Many GABAergic neurons convert to a coreleasing state. The coreleasing neurons and terminals remain in the dorsal horn, whereas many ultimately become glycinergic in the ventral horn. During the development of terminals and the transformation from radial glia to astrocytes, GABA and glycine receptor subunit compositions markedly change, removal systems mature, and GABAergic and glycinergic action shifts from excitatory to inhibitory.     

Omeprazole Suppresses Oxaliplatin-Induced Peripheral Neuropathy in a Rodent Model and Clinical Database

(1) Background: Oxaliplatin is used as first-line chemotherapy not only for colorectal cancer but also for gastric and pancreatic cancers. However, it induces peripheral neuropathy with high frequency as an adverse event, and there is no effective preventive or therapeutic method. (2) Methods: The effects of omeprazole, a proton pump inhibitor (PPI), on oxaliplatin-induced peripheral neuropathy (OIPN) was investigated using an in vivo model and a real-world database. (3) Results: In a rat model, oxaliplatin (4 mg/kg, i.p., twice a week for 4 weeks) caused mechanical hypersensitivity accompanied by sciatic nerve axonal degeneration and myelin sheath disorder. Repeated injection of omeprazole (5–20 mg/kg, i.p., five times per week for 4 weeks) ameliorated these behavioral and pathological abnormalities. Moreover, omeprazole did not affect the tumor growth inhibition of oxaliplatin in tumor bearing mice. Furthermore, clinical database analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) suggests that the group using omeprazole has a lower reporting rate of peripheral neuropathy of oxaliplatin-treated patients than the group not using (3.06% vs. 6.48%, p < 0.001, reporting odds ratio 0.44, 95% confidence interval 0.32–0.61). (4) Conclusions: These results show the preventing effect of omeprazole on OIPN.     

Structural Analysis of Crystalline R(+)-α-Lipoic Acid-α-cyclodextrin Complex Based on Microscopic and Spectroscopic Studies

R(+)-α-lipoic acid (RALA) is a naturally-occurring substance, and its protein-bound form plays significant role in the energy metabolism in the mitochondria. RALA is vulnerable to a variety of physical stimuli, including heat and UV light, which prompted us to study the stability of its complexes with cyclodextrins (CDs). In this study, we have prepared and purified a crystalline RALA-αCD complex and evaluated its properties in the solid state. The results of ¹H NMR and PXRD analyses indicated that the crystalline RALA-αCD complex is a channel type complex with a molar ratio of 2:3 (RALA:α-CD). Attenuated total reflection/Fourier transform infrared analysis of the complex showed the shift of the C=O stretching vibration of RALA due to the formation of the RALA-αCD complex. Raman spectroscopic analysis revealed the significant weakness of the S–S and C–S stretching vibrations of RALA in the RALA-αCD complex implying that the dithiolane ring of RALA is almost enclosed in glucose ring of α-CD. Extent of this effect was dependent on the direction of the excitation laser to the hexagonal morphology of the crystal. Solid-state NMR analysis allowed for the chemical shift of the C=O peak to be precisely determined. These results suggested that RALA was positioned in the α-CD cavity with its 1,2-dithiolane ring orientated perpendicular to the plane of the α-CD ring.