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Electromagnetic field analysis coupled with motion using the tableau approach has been applied to high-speed circuit breakers of eddy current repulsion mechanisms. This breaker has an opening time of 1 ms and break time less than 1 cycle (20 ms). The driving part of the breaker is composed of electromagnetic repulsion mechanisms and disk springs with nonlinear characteristics. The mechanisms are composed of two fixed coils and one repulsion plate. A numeric experiment has been applied to investigate the dynamic behavior of the electromagnetic repulsion mechanism using the equivalent circuit method. Calculation results were in good agreement with both measurement results and calculation results by FEM on an experimental model. In addition, repulsive forces depending on material conductivities have been researched. © 2005 Wiley Periodicals, Inc. Electr Eng Jpn, 152(4): 8–16, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20149 [ABSTRACT FROM AUTHOR]

Investigates the relationship between impulse breakdown voltage and electrode surface roughness in vacuum gaps of copper. Role of conductor surfaces in high voltage devices; Differences in the effect of surface roughness between uniform and non-uniform electric fields; Features of surface roughness.

Studies the density distribution of copper neutral atoms and the velocity of atoms emitted from a cathode spot, using a two-dimensional (2-D) laser-induced fluorescence (LIF). Experimental details; Results and discussion of the density distribution of copper neutral atoms of vacuum arcs; Conclusion.

Background: Conquering acquired resistance to osimertinib remains a major challenge in treating patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Thus, we aimed to determine the safety and efficacy of combination treatment with osimertinib and afatinib for patients with acquired resistance to osimertinib. Methods: This open-label phase I study was a feasibility study of the combination of afatinib and osimertinib for patients with advanced EGFR-positive NSCLC who had progressive disease after receiving osimertinib. The primary endpoint was to determine the maximum tolerated dose (MTD). We enrolled patients who received afatinib at three different dose levels (level 1, 20 mg; level 2, 30 mg; level 3, 40 mg) combined with osimertinib at a standard dose of 80 mg once per day. Results: Thirteen patients were enrolled in this study. The MTD was defined as 30 mg afatinib when combined with daily oral administration of osimertinib (80 mg). The most frequent adverse events were diarrhea (76.9%), anemia (76.9%), and rash (69.2%). Considering the toxicity profiles during all treatment periods, the recommended oral dose of afatinib was determined as 20 mg daily, with an osimertinib dose of 80 mg. For all evaluable patients (n = 12), the response rate was 7.7% and the disease-control rate was 46.2%. Conclusion: Combination therapy with osimertinib and afatinib was tolerable; however, the synergistic effect of afatinib with osimertinib may be limited in osimertinib-resistant patients. Trial registration: Japan Registry of Clinical Trials ID: jRCTs051180008, registered date: 08/11/2018. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with Anaplastic lymphoma kinase (ALK)-positive lung cancer after progression of ALK-tyrosine kinase inhibitor have limited treatment options. This study shows clinical efficacy of the combination of alectinib and bevacizumab with acceptable toxicity in patients with ALK-positive lung cancer after ALK-TKI failure. Anaplastic lymphoma kinase (ALK)-positive lung cancer is a rare cancer that occurs in approximately 5% of non-small-cell lung cancer (NSCLCs) patients. Despite the excellent efficacy of ALK-tyrosine kinase inhibitor in ALK-positive NSCLCs, most patients experience resistance. We conducted a phase II study to investigate the combination of alectinib with bevacizumab in ALK-positive NSCLC patients after failure of alectinib. In this study, ALK-positive nonsquamous NSCLC patients previously treated with alectinib received bevacizumab 15 mg/kg on day 1 every 3 weeks and alectinib 600 mg/day until disease progression. The primary endpoints were progression-free survival (PFS) and the safety of alectinib and bevacizumab. The secondary endpoints included overall survival (OS) and correlation of circulating tumor DNA and plasma proteins with PFS. Of the 12 patients treated, the median PFS was 3.1 months (95% CI 1.2–16.1), and the median OS was 24.1 months (95% CI 8.3-not estimable). The EML4-ALK fusion gene in circulating tumor DNA was significantly correlated with shorter PFS (1.2 months vs. 11.4 months, HR 5.2, p = 0.0153). Two patients experienced grade 3 adverse events; however, none of the patients required dose reduction. Although the primary endpoint was not met, alectinib combined with bevacizumab showed clinical efficacy in ALK-positive patients. [ABSTRACT FROM AUTHOR]

Progress in the development of carbon nanotubes (CNTs) has stimulated great interest among industries providing new applications. Meanwhile, toxicological evaluations on nanomaterials are advancing leading to a predictive exposure limit for CNTs, which implies the possibility of designing safer CNTs. To pursue safety by design, the redox potential in reactions with CNTs has been contemplated recently. However, the chemical reactivity of CNTs has not been explored kinetically, so that there is no scheme to express a redox reaction with CNTs, though it has been investigated and reported. In addition, the reactivity of CNTs is discussed with regard to impurities that consist of transition metals in CNTs, which obfuscates the contribution of CNTs to the reaction. The present work aimed at modeling CNT scavenging in aqueous solution using a kinetic approach and a simple first-order reaction scheme. The results show that CNTs follow the redox reaction assumption in a simple chemical system. As a result, the reaction with multiwalled CNTs is semiquantitatively denoted as redox potential, which suggests that their biological reactions may also be evaluated using a redox potential scheme. [ABSTRACT FROM AUTHOR]

Abstract: MHC class I-restricted peptide-based vaccination therapies have been conducted to treat cancer patients, because CD8+ CTL can efficiently induce apoptosis of tumor cells in an MHC class I-restricted epitope-specific manner. Interestingly, clinical responders are known to demonstrate reactivity to epitopes other than those used for vaccination; however, the mechanism underlying how antitumor T cells with diverse specificity are induced is unclear. In this study, we demonstrated that dendritic cells (DCs) that engulfed apoptotic tumor cells in the presence of non-tumor MHC class II-restricted epitope peptides, OVA323–339, efficiently presented tumor-associated antigens upon effector-dominant CD4+ T cell balance against regulatory T cells (Treg) for the OVA323–339 epitope. Th1 and Th17 induced tumor-associated antigens presentation of DC, while Th2 ameliorated tumor-antigen presentation for CD8+ T cells. Blocking experiments with anti-IL-23p19 antibody and anti-IL-23 receptor indicated that an autocrine mechanism of IL-23 likely mediated the diverted tumor-associated antigens presentation of DC. Tumor-associated antigens presentation of DC induced by OVA323–339 epitope-specific CD4+ T cells resulted in facilitated antitumor immunity in both priming and effector phase in vivo. Notably, this immunotherapy did not require pretreatment to reduce Treg induced by tumor. This strategy may have clinical implications for designing effective antitumor immunotherapies. [Copyright &y& Elsevier]

This paper presents a design and testing of a new high-speed electromagnetic driving mechanism for a high-voltage vacuum circuit breaker (VCB). This mechanism is based on a high-speed electromagnetic repulsion and a permanent magnet spring (PMS). This PMS is introduced instead of the conventional disk spring due to its low spring energy and more suitable force characteristics for VCB application. The PMS has been optimally designed by the 3D nonlinear finite-elements magnetic field analysis and investigated its internal friction and eddy-current effect. Furthermore, we calculated the dynamic of this mechanism coupling with the electromagnetic field and circuit analysis, in order to satisfy the operating characteristics—contact velocity, response time, and so on, required for the high-speed VCB. A prototype VCB, which was built based on the above analysis, shows sufficient operating performance. Finally, the short circuit interruption tests were carried out with this prototype breaker, and we have been able to verify its satisfying performance. © 2008 Wiley Periodicals, Inc. Electr Eng Jpn, 163(1): 34–40, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20398 [ABSTRACT FROM AUTHOR]

Background: Although the clinical efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) in EGFR‐mutant non‐small cell lung cancer (NSCLC) patients has been demonstrated, their efficacy in EGFR‐mutant NSCLCs with central nervous system (CNS) metastases and the role of radiotherapy remain unclear. This study aimed to determine if it is preferable to add upfront cranial radiotherapy to EGFR‐TKIs in patients with EGFR‐mutant NSCLC with newly diagnosed brain metastases. Methods: We retrospectively analyzed the data of EGFR‐mutant NSCLC patients with CNS metastases who received EGFR‐TKIs as a first‐line therapy. Results: A total of 104 patients were enrolled and 39 patients received upfront brain radiotherapy, while 65 patients received first and second generation EGFR‐TKIs first. The median time to treatment failure (TTF) was 7.8 months (95% confidence interval [CI]: 6.3–9.4). The median survival time (MST) was 24.0 months (95% CI: 20.1–30.1). The overall response rate of the CNS was 37%. The median CNS progression‐free survival (PFS) was 13.2 months (95% CI: 10.0–16.2). Brain radiotherapy prior to EGFR‐TKI prolonged TTF (11.2 vs. 6.8 months, P = 0.038) and tended to prolong CNS‐PFS (15.6 vs. 11.1 months, P = 0.096) but was not significantly associated with overall survival (MST 26.1 vs. 24.0 months, P = 0.525). Univariate and multivariate analyses indicated that poor performance status and the presence of extracranial metastases were poor prognostic factors related to overall survival. Conclusion: EGFR‐TKI showed a favorable effect for EGFR‐mutant NSCLC patients with CNS metastases. Prolonged TTF and CNS‐PFS were observed with upfront brain radiotherapy. [ABSTRACT FROM AUTHOR]

CBP-93872 suppresses maintenance of DNA double-stranded break-induced G2 checkpoint, by inhibiting the pathway between ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) activation. To examine the potential use of CBP-93872 for clinical applications, we analyzed the synergistic effects of platinum-containing drugs, oxaliplatin and cisplatin, pyrimidine antimetabolites, gemcitabine and 5-fluorouracil (5-FU), in combination with CBP-93872, on cell lethality in colorectal and pancreatic cancer cell lines. Treatment with CBP-93872 significantly increased cancer cell sensitivities to various chemotherapeutic agents tested through suppression of checkpoint activation. Our results thus reveal that combination treatment of CBP-93872 with known chemotherapeutic agents inhibits phosphorylation of ATR and Chk1, and induces cell death. [ABSTRACT FROM AUTHOR]

SUMMARY A new mechanical CBM (condition-based maintenance) system for an electromagnetically actuated vacuum circuit breaker (VCB) has been developed. This CBM function has a new monitoring method using analysis of the coil current profile of the actuator operation. The VCB has three sets of vacuum interrupters, insulating rods, contact pressure springs, and electromagnetic actuators. The electromagnetic actuators control each phase independently. We have clarified the variation in the actuator's current profile by the developed analytical method when the valve of friction, contact erosion, and driving capacitance change. We have established a diagnostic method for the mechanical condition using this current profile analysis. With this method, a new remote monitoring system of the mechanical condition using current monitors on the actuator's controller has been developed and mounted on VCB for cubicle-type gas insulated switchgears rating from 7.2 kV to 84 kV. The maintenance for mechanical parts of VCB changes to the CBM system from the conventional TBM (time-based maintenance) system using this monitoring system. The developed mechanical CBM system significantly reduces the life cycle cost including the labor cost of maintenance. [ABSTRACT FROM AUTHOR]