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BACKGROUND: Genomic profiling of tumors from cancer patients facilitates molecular-guided therapy. The turnaround time is one of important issues to deliver results timely for clinical decisions. The Ion Torrent™ Genexus™ Integrated Sequencer automates all next generation sequencing (NGS) workflows and delivers results within a day. METHODS: In this study, we conducted a feasibility study to evaluate the detection rate of genomic alterations from cell-free total nucleic acid (cfTNA, containing cfDNA and cfRNA) of 119 non-small cell lung cancer using Oncomine Precision Assay on Genexus™ Integrated Sequencer. Oncomine Precision Assay (OPA) covers actionable mutations, copy number variations and fusion genes and that are applicable for the selection of targeted therapy. cfTNA isolated from plasma (derived from 14 ml of blood) were subjected to the Genexus system for library construction, templating, sequencing, and data analyses. RESULTS: The sequencing resulted in median overall depth of 35,773× and median molecular coverage of 2,192× with cfTNA input ranged from 11 to 36 ng. Among the 119 samples evaluated, we detected at least one genomic alteration in plasma cfTNA of 79 cases (66%). When comparing to standard-of-care testing, the sensitivity and specificity of mutation detection in non-small cell lung cancer related genes using liquid biopsy with Genexus-OPA ranged between 49–67% and 93–100%, respectively. 59% of actionable mutations, which were present in tumor tissues, were detected by the Genexus- Oncomine Precision Assay using plasma cfTNA. Among the 5 mutations detected from liquid biopsy only, three mutations are of level 1 evidence according to OncoKB database, highlighting the clinical utilities of liquid biopsy in addressing tumor heterogeneity. Extrathoracic metastasis and levels of lactate dehydrogenase (LDH), C-reactive protein (CRP) and Carcinoembryonic Antigen (CEA) are found to be associated with increased circulating tumor DNA detection. CONCLUSIONS: The Genexus™ Integrated Sequencer system is an automated, accurate NGS system with short turnaround time (TAT) that could assist clinicians to make more timely decision.

Homeostasis is achieved by balancing cell survival and death. In cancer cells, especially those carrying driver mutations, the processes and signals that promote apoptosis are inhibited, facilitating the survival and proliferation of these dysregulated cells. Apoptosis induction is an important mechanism underlying the therapeutic efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) for EGFR-mutated non-small cell lung cancer (NSCLC). However, the mechanisms by which EGFR-TKIs induce apoptosis have not been fully elucidated. A deeper understanding of the apoptotic pathways induced by EGFR-TKIs is essential for the developing novel strategies to overcome resistance to EGFR-TKIs or to enhance the initial efficacy through therapeutic synergistic combinations. Recently, therapeutic strategies targeting apoptosis have been developed for cancer. Here, we review the state of knowledge on EGFR-TKI-induced apoptotic pathways and discuss the therapeutic strategies for enhancing EGFR-TKI efficiency. We highlight the great progress achieved with third-generation EGFR-TKIs. In particular, combination therapies of EGFR-TKIs with anti-vascular endothelial growth factor/receptor inhibitors or chemotherapy have emerged as promising therapeutic strategies for patients with EGFR-mutated NSCLC. Nevertheless, further breakthroughs are needed to yield an appropriate standard care for patients with EGFR-mutated NSCLC, which requires gaining a deeper understanding of cancer cell dynamics in response to EGFR-TKIs.

Background Several companion diagnostic (CDx) tests for epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) have been approved. In our institute, the CDx test for EGFR‐TKIs was changed from the Therascreen test (Therascreen) to the Cobas EGFR v2 test (Cobas) because only Cobas was approved for the use of osimertinib in patients with EGFR‐mutated non‐small cell lung cancer (NSCLC) with T790M mutations. The clinical influence of switching the CDx test has not yet been examined comprehensively. Methods All serial patients with lung cancer tested for EGFR mutations with CDx tests between February 2014 and February 2016 at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research (JFCR) were enrolled in this analysis. Results Therascreen was used as a CDx test for EGFR‐TKI therapy in 607 patients between February 2014 and January 2015, and Cobas was used in 621 patients between February 2015 and February 2016. EGFR mutations were detected in 218 patients (35.9%) and 244 patients (39.3%) tested with Therascreen and Cobas, respectively. At the initial diagnosis, 400 and 459 patients were tested with Therascreen and Cobas, respectively. EGFR mutation subtypes, including del19, L858R, and others, were detected in 13.0%, 17.0%, and 2.5% of patients using Therascreen and 17.4%, 14.4%, and 1.5% of patients using Cobas, respectively. Conclusions No significant impact of switching from Therascreen to Cobas as the CDx test for EGFR mutations in clinical practice was observed. However, the detection pattern of the EGFR mutation subtypes between the two CDx tests was slightly different. Key points Significant findings of the study We examined the influence of changing the EGFR test in 1228 patients in total. The detection rate of EGFR mutations was similar. However, the detection pattern for EGFR subtype mutations was slightly different between the two tests. What this study adds Switching CDx tests from target polymerase chain reaction (PCR)‐ to next‐generation sequencing (NGS)‐based methods may lead to obvious changes in clinical practice. When the CDx test is required to change, the investigation of this influence is warranted in future studies., We examined the influence of changing the EGFR test among target PCR methods in 1228 patients in total. The detection rate of EGFR mutations was similar while the detection pattern for EGFR subtype mutations was slightly different between the two tests. In the future, switching companion diagnostic (CDx) tests from target PCR methods to NGS‐based methods may lead to obvious changes in clinical practice.

Improving therapeutic strategies for extensive-stage small cell lung cancer (ES-SCLC) remains a challenge. To date, no reports have directly compared the efficacy and safety of immune checkpoint inhibitors plus platinum–etoposide (ICIs+EP) with platinum–irinotecan (IP) or directly compared different ICIs+EP for previously untreated ES-SCLC. This study used a Bayesian approach for network meta-analysis to compare efficacy and safety between ICIs+EP and IP and between each pair of three ICIs+EP. The six treatment arms were: pembrolizumab plus platinum–etoposide (Pem+EP), durvalumab plus platinum–etoposide (Dur+EP), atezolizumab plus platinum–etoposide (Atz+EP), platinum–amrubicin (AP), IP, and platinum–etoposide (EP). No significant differences in overall survival were observed between ICIs+EP and IP and between each pair of three ICIs+EP. The incidence of ≥grade 3 adverse events (G3-AEs) was significantly higher in ICIs+EP than IP, whereas no significant difference was found in G3-AEs between each pair of three ICIs+EP. The incidence of ≥grade 3 neutropenia and thrombocytopenia was significantly higher in ICIs+EP than IP, whereas the incidence of ≥grade 3 diarrhea was significantly lower in ICIs+EP than IP. These findings will help clinicians better select treatment strategies for ES-SCLC.

Background The usefulness of the Oncomine Dx Target test (Oncomine Dx), a next‐generation sequencing (NGS) test, has already been proven in clinical trials. However, NGS requires high‐quality tumor samples and takes a long time to generate results. The feasibility of NGS for use in advanced non‐small cell lung cancer (NSCLC) patients in clinical practice has not yet been determined. Methods Patients serially diagnosed with advanced NSCLC were evaluated in our hospital. The Oncomine Dx, Cobas EGFR mutation test (Cobas EGFR), and ALK‐IHC were performed. The patients were divided into four sets: the full analysis set (FAS) that referred to patients diagnosed with NSCLC, the intent to perform companion diagnostics (CDx) set (IPS) that referred to patients in which CDx had been ordered regardless of sample quality, the per‐performed CDx set (PPS) that referred to patients who could undergo CDx regardless of the results, and the per‐completed CDx set (CCS) that referred to patients in which informative results were received from the CDx. Results The total number of patients analyzed in the study was 167. The IPS/FAS of Oncomine Dx (80.2%) was lower than that of the ALK‐IHC (85.0%) and Cobas EGFR (92.8%). The CCS/FAS of Oncomine Dx (65.9%) was lower than that of the ALK‐IHC (82.0%) and Cobas EGFR (92.2%). PPS/IPS and CCS/PPS of the Oncomine Dx with nonsurgical biopsy ranged between 78.6% and 90.9%, which was lower than those patients who underwent surgical resection (95.0% and 100%). Conclusions The feasibility of Oncomine Dx in clinical practice was lower than the other CDx. The feasibility of Oncomine Dx will increase by improving the biopsy procedure. Key points Significant study findings The usefulness of a next‐generation sequencing (NGS) test has been proven in clinical trials.The feasibility of NGS is lower than other diagnostics in clinical practice especially with regard to nonsurgical biopsy. What this study adds It is necessary to improve the feasibility of NGS in clinical practice.To improve NGS feasibility, turnaround time must be shortened, and larger samples must be obtained during surgical procedures., The feasibility of Oncomine Dx in clinical practice is relatively low compared with that of the ALK‐IHC and Cobas EGFR.

This is the first direct observation that surface proton hopping occurs on SrZrO3 perovskite even under a H2 (i.e. dry) atmosphere. Understanding proton conduction mechanisms on ceramic surfaces under a H2 atmosphere is necessary to investigate the role of proton hopping on the surface of heterogeneous catalysts in an electric field. In this work, surface protonics was investigated using electrochemical impedance spectroscopy (EIS). To extract the surface proton conduction, two pellets of different relative densities were prepared: a porous sample (R.D. = 60%) and a dense sample (R.D. = 90%). Comparison of conductivities with and without H2 revealed that only the porous sample showed a decrease in the apparent activation energy of conductivity by supplying H2. H/D isotope exchange tests revealed that the surface proton is the dominant conductive species over the porous sample with H2 supply. Such identification of a dominant conductive carrier facilitates consideration of the role of surface protonics in chemical reactions.

Rh ion-exchanged MFI-type aluminosilicate zeolites with different Al distributions were prepared for controlling the location, state, and size of Rh species. The MFI-type aluminosilicate zeolite with the framework Al atoms predominantly located inside the channel intersections leads to the formation of relatively large Rh species, which were confirmed by ultraviolet-visible (UV-vis) and infrared (IR) spectroscopies. Moreover, this catalyst showed a high catalytic activity for the oxidative reforming reaction of methane.

Simple Summary Improving treatment strategies for refractory or relapsed advanced non-small-cell lung cancer (NSCLC) remains a challenge. Efficacy and safety of the immune checkpoint inhibitors (ICIs), nivolumab (Niv) plus atezolizumab (Atz), were compared with those of ramucirumab (Ram) plus docetaxel (Doc), and the efficacy and safety of these two ICIs were compared with each other, using patient groups without programmed cell death ligand-1 (PD-L1) constraint. Additionally, efficacy and safety of, Niv, Atz, and pembrolizumab (Pem) were compared using a PD-L1 positive (≥1%) subgroup with refractory or relapsed advanced NSCLC. Niv or Atz was found to be more effective and safer than Ram plus Doc in groups without PD-L1 constraint. In the PD-L1 positive subgroup, Pem (10 mg/kg) showed the highest efficacy for ensuring overall survival, followed by Niv, Pem (2 mg/kg), Atz, and Doc. These results may help clinicians select and evaluate treatment options for relapsed or refractory advanced NSCLC. Abstract The efficacy and safety of immune checkpoint inhibitors (ICIs) in refractory or relapsed advanced non-small-cell lung cancer (NSCLC) have not yet been compared with those of ramucirumab (Ram) plus docetaxel (Doc). Furthermore, comprehensive comparisons between ICIs have not been conducted to date. In the current study, a Bayesian network meta-analysis of related phase III clinical trials was performed to compare the efficacy and safety of Ram+Doc, Niv, Atz, and Doc treatments in patient groups lacking the PD-L1 constraint. Surface under the cumulative ranking area (SUCRA) revealed that the overall survival (OS) of patients treated with Niv was the highest, followed by Atz, Ram+Doc, and Doc. Regarding grades 3–5 treatment-related adverse events (G3–5AEs), the use of Niv was ranked the safest, followed by Atz, Doc, and Ram+Doc. Significant differences in OS were observed between Niv and Ram+Doc, while significant differences in G3–5AEs were observed between Ram+Doc and Niv or Atz. In the PD-L1 positive (≥1%) patient subgroup, Pem (10 mg/kg) ranked the highest in efficacy for OS, followed by Niv, Pem (2 mg/kg), Atz, and Doc. These findings may expectedly provide oncologists with useful insights into therapeutic selection for refractory or relapsed advanced NSCLC.

Simple Summary The treatment of anaplastic lymphoma kinase (ALK) rearrangement-positive (ALK-p) advanced non-small cell lung cancer (NSCLC) remains a challenge. We compared the safety and efficacy of lorlatinib and alectinib in patients with ALK-p ALK-inhibitor‒naïve advanced NSCLC (in overall participants and in the Asian and non-Asian subgroups). The results showed that in the overall participant group, the efficacy of lorlatinib and alectinib was not significantly different in terms of progression-free survival (PFS) and overall survival (OS). Although in the Asian subgroup, PFS was not significantly different upon treatment with lorlatinib or alectinib, in the non-Asian subgroup, PFS was significantly better in response to lorlatinib than with alectinib. Grade 3 or higher adverse events in the overall participant group were significantly more frequent with lorlatinib than with alectinib. These results will provide valuable information that would enable the improvement of treatment strategies for ALK-p ALK-inhibitor‒naïve advanced NSCLC. Abstract To date, there have been no head-to-head randomized controlled trials (RCTs) comparing the safety and efficacy of lorlatinib and alectinib in anaplastic lymphoma kinase (ALK) rearrangement-positive (ALK-p) ALK-inhibitor‒naïve advanced non-small cell lung cancer (NSCLC). We performed a network meta-analysis comparing six treatment arms (lorlatinib, brigatinib, alectinib, ceritinib, crizotinib, and platinum-based chemotherapy) in overall participants and in Asian and non-Asian subgroups. Primary endpoints were progression-free survival (PFS), overall survival (OS), and grade 3 or higher adverse events (G3-AEs). There were no significant differences between lorlatinib and alectinib in overall participants for both PFS (hazard ratio [HR], 0.742; 95% credible interval [CrI], 0.466–1.180) and OS (HR, 1.180; 95% CrI, 0.590–2.354). In the Asian subgroup, there were no significant differences in PFS between lorlatinib and alectinib (HR, 1.423; 95% CrI, 0.748–2.708); however, in the non-Asian subgroup, PFS was significantly better with lorlatinib than with alectinib (HR, 0.388; 95% CrI, 0.195–0.769). The incidence of G3-AEs in overall participants was significantly higher with lorlatinib than with alectinib (risk ratio, 1.918; 95% CrI, 1.486–2.475). These results provide valuable information regarding the safety and efficacy of lorlatinib in ALK-p ALK-inhibitor‒naïve advanced NSCLC. Larger head-to-head RCTs are needed to validate the study results.

Aim Frailty and sarcopenia affect the prognosis and quality of life of patients with chronic obstructive pulmonary disease (COPD). However, it remains uncertain which model is the most suitable for evaluating vulnerability in patients with COPD. We evaluated the validity of three frailty models - the Kihon Checklist (KCL), the Japanese version of the Cardiovascular Health Study and the Study of Osteoporotic Fractures - and one sarcopenia model for older patients with COPD. Methods This cross-sectional study included 201 older (aged ≥65 years) outpatients with COPD. We used three frailty models and one sarcopenia model to identify their correlation with various indices that can evaluate the status of COPD and determine the most ideal model for evaluating vulnerability in patients with COPD. Results The highest prevalence of frailty (38%) and lowest prevalence of robustness (26%) were observed using the KCL. Although all models reflected the characteristics of COPD, the KCL yielded the strongest correlations with clinically important physical, psychological and prognostic indices. The KCL yielded statistically significant differences in almost all indices among the three intergroup comparisons (robust, pre-frailty and frailty). The KCL was superior in extracting mood disorders to the other models. Conclusion Although all investigated models were useful, the KCL was the most suitable for evaluating the frailty status and might enable interventions in patients with COPD. Geriatr Gerontol Int 2019; 19: 896-901.

Background Most patients treated with anaplastic lymphoma kinase (ALK)‐tyrosine kinase inhibitors for ALK‐positive non‐small cell lung cancer (NSCLC) develop resistance, leading to metastasis, with progression to the central nervous system (CNS) being a primary concern. Although alectinib has better CNS penetration than crizotinib, patients treated with alectinib also develop CNS progression. CNS metastases more likely occurs during crizotinib treatment due to less blood‐brain barrier (BBB) penetration capability than alectinib. CNS progression pattern may be different during crizotinib and alecitinib treatment. Understanding the characteristics of CNS progression is important for developing treatment strategies. Aims We compared the clinical‐radiographic characteristics of CNS metastases among patients undergoing crizotinib and alectinib treatment for ALK‐positive NSCLCs. Methods and results We retrospectively analyzed the radiographic and clinical characteristics of CNS progression in ALK‐positive NSCLC patients treated with crizotinib or alectinib at our hospital between July 2011 and May 2020. CNS and systemic tumor progression were evaluated using computed tomography or magnetic resonance imaging. Fifty‐three and 65 patients were treated with crizotinib and alectinib, respectively. Baseline CNS metastasis was observed in 18 and 27 patients in the crizotinib and alectinib groups, respectively. Among the patients in the crizotinib and alectinib groups who developed disease progression, 15/49 (30.6%) and 9/44 (20.5%) had CNS progression, respectively (P = .344). Intra‐CNS progression‐free survival was significantly longer in the alectinib group than in the crizotinib group (median: 14.0 vs 5.6 months, P = .042). The number of CNS metastases sized ≥3 cm, rate of peritumoral brain edema, and the second progression pattern after treatment continuation was not significantly different between the groups. Conclusion We observed no significant difference in the clinical‐radiographic characteristics of CNS progression between patients undergoing crizotinib and alectinib treatments. Local therapy, including stereotactic radiosurgery, for CNS progression may be suitable and important following alectinib and crizotinib treatment.

The process of combining heterogeneous catalysts and direct current (DC) electric fields can achieve high catalytic activities, even under mild conditions (

Background/aim The Renin-Angiotensin system (RAS) induces immunosuppression in the tumor microenvironment, and RAS inhibitors (RASi) improve the tumor immune microenvironment. We evaluated the impact of RASi on the efficacy anti-programmed cell death-1/Ligand-1 (anti-PD-1/PD-L1) antibodies. Patients and methods This retrospective study analyzed non-small cell lung cancer (NSCLC) patients who received anti-PD-1/PD-L1 antibodies monotherapy as second- or later-line treatment. We classified patients into those with or without use of RASi. Results A total of 256 NSCLC patients were included and 37 patients used RASi. The median PFS of patients treated with RASi was significantly longer than that of patients treated without (HR=0.59, 95%CI=0.40-0.88). The median OS of patients treated with RASi tended to be longer than that of patients treated without (HR=0.71, 95%CI=0.45-1.11). Conclusion The use of RASi was associated with a significantly longer PFS in NSCLC patients treated with anti-PD-1/PD-L1 antibodies. RASi use may enhance the efficacy of anti-PD-1/PD-L1 antibodies.

The development of simple catalysts with high performance in the selective oxidation of methane to syngas at low temperature has attracted much attention. Here we report a nickel-based solid catalyst for the oxidation of methane, synthesised by a facile impregnation method. Highly dispersed ultra-small NiO particles of 1.6 nm in size are successfully formed on the MOR-type zeolite. The zeolite–supported nickel catalyst gives continuously 97–98% methane conversion, 91–92% of CO yield with a H2/CO ratio of 2.0, and high durability without serious carbon deposition onto the catalyst at 973 K. DFT calculations demonstrate the effect of NiO particle size on the C-H dissociation process of CH4. A decrease in the NiO particle size enhances the production of oxygen originating from the NiO nanoparticles, which contributes to the oxidation of methane under a reductive environment, effectively producing syngas. Catalytic oxidation of methane to syngas is an important process, but efficient and stable catalyts remain in demand. Here dispersion of nickel on zeolites yields nickel oxide nanoparticles as small as 1.6 nm which act as selective and efficient catalysts for conversion of methane to syngas.

Chronic obstructive pulmonary disease (COPD) is a respiratory illness characterized by airflow limitation and chronic respiratory symptoms with a global prevalence estimated to be more than 10% in 2010 and still on the rise. Furthermore, hypercapnic subject COPD leads to an increased risk of mortality, morbidity, and poor QoL (quality of life) than normocapnic subjects. Series of studies showed the usefulness of the forced oscillation technique (FOT) to measure small airway closure. Traditional findings suggested that hypercapnia may not be the main treating targets, but recent findings suggested that blood stream CO2 may lead to a worse outcome. This study aimed to seek the relationship between CO2 and small airway closure by using FOT. Subjects with COPD (n = 124, hypercapnia 22 and normocapnia 102) were analyzed for all pulmonary function values, FOT values, and arterial blood gas analysis. Student&rsquo, s t-test, Spearman rank correlation, and multi linear regression analysis were used to analyze the data. COPD subjects with hypercapnia showed a significant increase in R5, R20, Fres, and ALX values, and a greater decrease in X5 value than normocapnic patients. Also, multiple linear regression analysis showed R5 was associated with hypercapnia. Hypercapnia may account for airway closure among subjects with COPD and this result suggests treating hypercapnia may lead to better outcomes for such a subject group.

To date, no head-to-head trials have compared the efficacy of brigatinib and alectinib against anaplastic lymphoma kinase (ALK) rearrangement-positive (ALK-p), ALK-inhibitor-naïve, advanced non-small cell lung cancer (NSCLC) with central nervous system (CNS) metastasis. We conducted an indirect treatment comparison (ITC) between brigatinib and alectinib, with crizotinib as a common comparator, using a Bayesian model with non-informative prior distribution and assessed the between-study heterogeneity of the studies. The primary efficacy endpoint was progression-free survival (PFS), and efficacy was ranked using the surface under the cumulative ranking (SUCRA) curve values. ITC analysis showed that there were no significant differences in PFS between the brigatinib and alectinib arms. However, the SUCRA values revealed that alectinib ranked the highest by efficacy in the overall patient population, whereas brigatinib ranked the highest by efficacy in the CNS metastasis sub-group. Although there were no significant differences in the incidence of G3–5 adverse events between the brigatinib and alectinib arms in the overall patient population, the data were deemed insufficient for the CNS metastasis sub-group analysis. This study provides critical information to clinicians regarding the efficacy of brigatinib for ALK-p, ALK-inhibitor-naïve, advanced NSCLC patients, with and without CNS metastasis. Larger randomized, controlled trials are warranted to confirm our results.

This is the first direct observation that surface proton hopping occurs on SrZrO

The catalytic steam reforming of dimethyl ether (DME) in an electric field was carried out and the effects of proton hopping induced by the electric field on a Pd-supported CeO2 catalyst surface were investigated. The hydrolysis of DME was promoted even on Pd/CeO2 catalyst by the application of the electric field at low temperatures (in the range of 423–623 K), while the direct decomposition of DME was suppressed. The apparent activation energy in this temperature range was much lower with (17.2 kJ mol−1) than without (79.0 kJ mol−1) the electric field. Kinetic analyses demonstrated that the effect of the reactant partial pressures was also markedly different with and without the electric field. The effect of the partial pressure of water and electrochemical impedance spectra strongly suggest that surface proton hopping promotes the steam reforming of DME in an electric field at low temperatures.

To elucidate the reaction mechanism of catalytic steam reforming of methane in an electric field, operando–diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) has been used to investigate methane dissociative adsorption at low temperatures using CH4, H2O, and their isotopes. Operando-analyses demonstrated that methane was adsorbed and converted into CO and CO2 more when CD4 and/or D2O was used instead of CH4 and/or H2O. This observed “inverse” kinetic isotope effect is based on the difference of C H H vibrational energy level at the transition state. Furthermore, CO2-methanation, which is the reverse reaction of steam reforming of methane, was irreversible with H2O in an electric field. These results demonstrate that the proton collision promoted methane activation irreversibly, even at low temperatures in an electric field.

Ammonia is an important chemical feedstock and is produced by Ru or Fe catalyst so far. We investigated Co catalyst for low temperature ammonia synthesis in an electric field. Well-reduced Co/Ce0.5Zr0.5O2 catalyst showed high activity for ammonia synthesis even at 473 K in the electric field. Various characterizations including kinetic tests, operando DRIFTS measurements, TEM observations, and XAFS measurements, revealed that the active site is the interface between supported Co and Ce0.5Zr0.5O2 oxide support, thanks to the surface protonics derived from an electric field.

We have found that an electric field brings high yield on low temperature catalytic ammonia synthesis over Cs/Ru/SrZrO3 catalyst. The role of the electric field is investigated based on kinetics and isotope effects.Results show that the electric field promotes proton hopping on the catalyst surface, and it brings a change in the reaction mechanism from the conventional one to the N2H+ intermediate mechanism. In the electric field, N2H+ intermediate plays an important role, enabling low-temperature ammonia synthesis.

Surface protonic transport on cerium oxide (CeO 2 ) was investigated using electrochemical impedance spectroscopy (EIS). CeO 2 pellets showing low relative density: approximately 60%, was prepared for the purpose. The structure and morphology of the prepared CeO 2 pellets were confirmed from XRD and SEM measurements. Results show that the pellets had a pure cubic phase, with open pores on which water can be adsorbed. Electrochemical impedance spectroscopy measurements were taken to evaluate the surface protonic transport on CeO 2 as a function of temperature and as a function of partial pressure of water ( P H2O ) at 400 °C. Investigations of the temperature dependence of the conductivity revealed that only the conductivities of surface grain bulk ( σ intra ) and surface grain boundary ( σ inter ) increased with decreasing temperatures under wet conditions ( P H2O = 0.026 atm). The P H2O dependence of surface conductivities ( σ intra and σ inter ) revealed that σ intra increases strongly with P H2O at 400 °C. These findings provide evidence that water adsorbates play an important role in surface protonic transport on CeO 2 at low temperatures. Surface protonic transport at low temperatures can contribute to the expansion of applications for electrical and catalytic processes.

We accomplished efficient electrocatalytic low-temperature ammonia synthesis with the highest yield reported to date., Highly efficient ammonia synthesis at a low temperature is desirable for future energy and material sources. We accomplished efficient electrocatalytic low-temperature ammonia synthesis with the highest yield ever reported. The maximum ammonia synthesis rate was 30 099 μmol gcat –1 h–1 over a 9.9 wt% Cs/5.0 wt% Ru/SrZrO3 catalyst, which is a very high rate. Proton hopping on the surface of the heterogeneous catalyst played an important role in the reaction, revealed by in situ IR measurements. Hopping protons activate N2 even at low temperatures, and they moderate the harsh reaction condition requirements. Application of an electric field to the catalyst resulted in a drastic decrease in the apparent activation energy from 121 kJ mol–1 to 37 kJ mol–1. N2 dissociative adsorption is markedly promoted by the application of the electric field, as evidenced by DFT calculations. The process described herein opens the door for small-scale, on-demand ammonia synthesis.

Background Thus far, studies on Klebsiella pneumoniae carbapenemase (KPC)-producing organisms have only been reported in those with a history of foreign travel, and a specific Japanese KPC-producing isolate has not yet been reported. Case presentation We describe a Japanese patient, with no history of travel to foreign countries, admitted due to aspiration pneumonia, and a KPC-producing isolate detected in his sputum. Fortunately, his pneumonia resolved. His close contacts did not have a history of foreign travel, and the isolate was not detected in other patients. Conclusions The potential for KPC-producing organisms to become endemic in Japan is currently of great concern.

The lens-less technique of microwave holography is expected to provide information of three-dimensional structures of plasma with a wide field of view. From the complex amplitudes of waves, which are observed on a single planar array of antennas, we will be able to obtain an imaging of the three-dimensional object. With a geometry of back-scattering observation, the feasibility is examined with a numerical tool of electromagnetic analysis on dielectric objects. With respect to the variety of the dielectric constant and shape of object, it is shown that useful information can be acquired in regarding the complex amplitude distribution at planar detector.

Phytochromes are red light (R) and far-red light (FR) receptors that play important roles in many aspects of plant growth and development. Phytochromes mainly function in the nucleus and regulate sets of genes by inhibiting negatively acting basic helix-loop-helix transcription factors named PHYTOCHROME INTERACTING FACTORs (PIFs) in Arabidopsis thaliana. Although R/FR photoreversible responses and phytochrome genes are well documented in diverse lineages of plants, the extent to which phytochrome signaling is mediated by gene regulation beyond angiosperms remains largely unclear. Here, we show that the liverwort Marchantia polymorpha, an emerging model basal land plant, has only one phytochrome gene, Mp-PHY, and only one PIF gene, Mp-PIF. These genes mediate typical low fluence responses, which are reversibly elicited by R and FR, and regulate gene expression. Mp-phy is light-stable and translocates into the nucleus upon irradiation with either R or FR, demonstrating that the single phytochrome Mp-phy exhibits combined biochemical and cell-biological characteristics of type I and type II phytochromes. Mp-phy photoreversibly regulates gemma germination and downstream gene expression by interacting with Mp-PIF and targeting it for degradation in an R-dependent manner. Our findings suggest that the molecular mechanisms for light-dependent transcriptional regulation mediated by PIF transcription factors were established early in land plant evolution.

Catalytic water gas shift for hydrogen production in the temperature range of 423–873 K, was examined imposing an electric field to the catalyst bed. Reaction trends were investigated based on thermodynamic equilibrium and chemical kinetic law. Pt/La–ZrO2 was chosen as an active catalyst through our screening tests, and the effect of the electric field on the catalytic activity was investigated by changing reaction temperatures and applied electric currents. Although the reaction was ruled by thermodynamic equilibrium at high temperatures, drastic promotion of the reaction by applying the electric field was observed at low temperatures in a kinetic region. Drastic decrease of apparent activation energy for WGS was observed by imposing the electric field to the catalyst bed. Various isotopic transient tests revealed that the reaction mechanism changed by the application of electric field, and redox mechanism using surface lattice oxygen played an important role in case of the catalytic WGS in the electric field.

Background: Chronic obstructive pulmonary disease (COPD) and asthma have similar clinical features and are both exacerbated by airway infection. Objective: To determine whether garenoxacin mesylate hydrate (GRNX) added to the standard care for bacterial infection-induced acute exacerbation of asthma or COPD in adults has clinical benefits. Method: This single-arm clinical trial was conducted from January 2015 to March 2016. Adults with a history of asthma or COPD for more than 12 months were recruited within 48 h of presentation with fever and acute deterioration of asthma or COPD requiring additional intervention. Participants were administered 400 mg GRNX daily for 7 days without additional systemic corticosteroids or other antibiotics. The primary outcome was efficacy of GRNX based on clinical symptoms and blood test results after 7 days of treatment. Secondary outcomes were: (1) comparison of the blood test results, radiograph findings, and bacterial culture surveillance before and after treatment; (2) effectiveness of GRNX after 3 days of administration; (3) analyzation of patient symptoms based on patient diary; and (4) continued effectiveness of GRNX on 14th day after the treatment (visit 3). Results: The study included 44 febrile patients (34 asthma and 10 COPD). Frequently isolated bacteria included Moraxella catarrhalis (n = 6) and Klebsiella pneumoniae (n = 4). On visit 2, 40 patients responded, and no severe adverse events were observed. All secondary outcomes showed favorable results. Conclusion: GRNX effectively treated asthma and COPD patients with acute bacterial infection without severe adverse events. Further research with a larger study population is needed.

Background: Omalizumab, an anti-immunoglobulin E (IgE) monoclonal antibody, inhibits the binding of circulating IgE to mast cells and basophils, resulting in fewer episodes of airway inflammation, asthma symptoms and exacerbations in patients with severe allergic asthma. Treatment of patients with asthma using omalizumab increases serum total IgE (tIgE) levels. However, little is known about the influence of omalizumab on allergen-specific IgE (sIgE). Methods: tIgE and sIgE in 47 adult patients with severe asthma were measured with a fluorescent enzyme immunoassay (ImmunoCAP-FEIA) before and after omalizumab treatment. Results: Treatment with omalizumab increased tIgE and sIgE levels. The increases in sIgE by class category after omalizumab treatment were positively correlated with baseline sIgE positivity before treatment. The mean changes in sIgE levels after omalizumab treatment were also correlated with baseline sIgE levels before treatment. The mean changes in tIgE levels were positively correlated with the mean changes in IgE levels against Dermatophagoides pteronyssinus, crude house dust, Japanese cedar and moth. Omalizumab markedly influenced the negative-to-positive seroconversion rate for IgE against Japanese cedar (30.8%), Candida (29.0%) and moth (28.0%). Finally, all patients with negative-to-positive seroconversion for Japanese cedar-specific IgE had cedar pollinosis before beginning omalizumab treatment. Conclusions: The changes in sIgE levels after omalizumab treatment may be dependent on the baseline sIgE levels. Our data may indicate the presence of undetectable but functional sIgE.

Catalytic reverse water gas shift reaction was conducted in an electric field (denoted as E-RWGS) over various catalysts at low temperature as 423 K. A platinum catalyst supported on lanthanum doped zirconia (Pt/La-ZrO 2 ) showed the highest yield (ca. 40%) for the E-RWGS reaction even at such low temperature condition. In contrast to a bare oxide catalyst, metal loading catalysts showed higher activities and efficiencies for the reaction. Roles of the impregnated platinum and doped lanthanum on the catalytic activity were investigated, and we found that loaded platinum worked as an active site for the E-RWGS reaction, and La doping stabilized the structure of ZrO 2 . The effect of the electric field was discussed based on thermodynamic evaluation and experimental results.

Catalytic steam reforming of methane for hydrogen production proceeds even at 473 K over 1 wt% Pd/CeO2 catalyst in an electric field, thanks to the surface protonics. Kinetic analyses demonstrated the synergetic effect between catalytic reaction and electric field, revealing strengthened water pressure dependence of the reaction rate when applying an electric field, with one-third the apparent activation energy at the lower reaction temperature range. Operando–IR measurements revealed that proton conduction via adsorbed water on the catalyst surface occurred during electric field application. Methane was activated by proton collision at the Pd–CeO2 interface, based on the inverse kinetic isotope effect. Proton conduction on the catalyst surface plays an important role in methane activation at low temperature. This report is the first describing promotion of the catalytic reaction by surface protonics.

Summary Flow pattern, pressure drop, and water holdup were measured for oil/water flow in horizontal, hilly terrain (±0.5 and ±3°), and vertical pipelines at a temperature of approximately 35 (±5) °C and a pressure of approximately 245 kPa using the large-scale multiphase-flow test facility of Japan Oil, Gas and Metals Natl. Corp. (JOGMEC). Test lines of 4.19-in. (106.4-mm) inner diameter (ID) and 120-m total length were used, which included a 40-m horizontal or hilly terrain (near-horizontal) and a 10-m vertical test section sequentially connected. The flow pattern was determined by visual observation with video recordings, and a flow-pattern map was made for each condition. New flow patterns were identified for horizontal and hilly terrain flow such as oil flow in a snake-like shape at top of pipe at high rate of water flow and water flow at bottom of pipe at high rate of oil flow. New holdup and pressure-drop data are presented for each flow condition. Flow rate and inclination angle influence holdup and pressure-drop behaviors. In vertical flow, when the oil superficial velocity exceeds a certain value, the pressure drop decreases exponentially as the superficial oil velocity, vSO, increases. Slippage between the phases was analyzed using the measured water holdup plotted against the input water cut with inlet-oil flow rate as a parameter and slip velocity vs. measured water holdup. It was found that the slippage changed significantly with slight changes in inclination angle. This paper provides new experimental data of flow pattern, water holdup, and pressure drop measured particularly at horizontal, hilly terrain, and vertical conditions, with large-diameter pipes. This is indispensable information for developing reliable prediction models for oil/water two-phase and gas/oil/water three-phase flow in pipelines.

Experimental and model studies were performed on two-phase flow behavior at high-pressure conditions. The experiments were conducted using nitrogen and water in a test loop of 106.4 mm diameter pipe with inclination angles of 0°, 1°, and 3° at 2060 kPa. The liquid holdup data of 81 runs for each inclination angle were analyzed to identify the flow pattern. The mechanistic model developed for low pressures was modified for high-pressure conditions. The model first detects the flow pattern, and then calculates liquid holdup and pressure drop based on the flow pattern. For dispersed-bubble flow, the critical bubble size mechanisms were also applicable at high pressures to predict a flow region in the flow pattern map, and the slip model of liquid holdup showed better matches with the experimental data than the non-slip model. For stratified flow, the flow region in the flow pattern map extended to higher liquid flow rates than at low pressures. Sequential application of the Taitel-Dukler and BendiksenEspedal criteria could correctly identify the stratified and non-stratified flow transition, and the Lockhart-Martinelli correlation based on the shear stresses could evaluate the liquid holdup much better than the common correlation based on the material balance. Elongated-bubble flow changed directly into dispersed-bubble flow as the liquid flow rate increases. Excellent performance of the model was demonstrated by error analyses of liquid holdup and pressure drop calculations.