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A quinone-impregnation process using scCO2 yielded nearly twice the specific capacity and higher rate properties than that with liquid sonication.

Supplementary Figures S1-8. Figure S1: Flowchart for mutation call. Figure S2: Quantification of performance of ddPCR analysis for EGFR T790M mutation. Figure S3: Analytical sensitivity of 0.001% for the ddPCR assay. Figure S4: Determination of false-positive events from wild-type control DNA and normal human genomic DNA. Figure S5: Determination of false-positive events in genomic DNA from formalin-fixed paraffin-embedded (FFPE) A549 cells. Figure S6: Detection of EGFR T790M mutant alleles in patients with EGFR T790M-containing primary tumors. Figure S7: Comparison of T790M mutation detection in 6 samples by different operators. Figure S8: Reproducibility of ddPCR analysis from 16 T790M-positive samples.

Purpose: The resistance to the EGFR tyrosine kinase inhibitors (TKI) is a major concern in non–small cell lung cancer (NSCLC) treatment. T790M mutation in EGFR accounts for nearly 50% of the acquired resistance to EGFR-TKIs. Earlier studies suggested that T790M mutation was also detected in TKI-naïve NSCLCs in a small cohort. Here, we use an ultra-sensitive droplet digital PCR (ddPCR) technique to address the incidence and clinical significance of pretreatment T790M in a larger cohort.Experimental Design: ddPCR was established as follows: wild-type or T790M mutation-containing DNA fragments were cloned into plasmids. Candidate threshold was identified using wild-type plasmid, normal human genomic DNA, and human A549 cell line DNA, which expresses wild type. Surgically resected tumor tissues from 373 NSCLC patients with EGFR-activating mutations were then examined for the presence of T790M using ddPCR.Results: Our data revealed a linear performance for this ddPCR method (R2 = 0.998) with an analytical sensitivity of approximately 0.001%. The overall incidence of the pretreatment T790M mutation was 79.9% (298/373), and the frequency ranged from 0.009% to 26.9%. The T790M mutation was detected more frequently in patients with a larger tumor size (P = 0.019) and those with common EGFR-activating mutations (P = 0.022), as compared with the others.Conclusions: The ultra-sensitive ddPCR assay revealed that pretreatment T790M was found in the majority of NSCLC patients with EGFR-activating mutations. ddPCR should be utilized for detailed assessment of the impact of the low frequency pretreatment T790M mutation on treatment with EGFR-TKIs. Clin Cancer Res; 21(15); 3552–60. ©2015 AACR.

Supplementary Materials and Methods, Reference and Supplementary Figure Legends

Supplementary Tables S1-5. Table S1: Primers and probes used for droplet digital PCR (ddPCR). Table S2: Determination of the limit of blank (LOB) from wild-type control DNA, normal human genomic DNA, and EGFR wild-type A549 genomic DNA. Table S3: Determination of the limit of blank (LOB) using genomic DNA from adjacent normal tissue samples of EGFR-activating mutation positive adenocarcinoma and EGFR wild-type squamous cell carcinoma. Table S4: Concordance between ddPCR and deep sequencing of EGFR T790M mutation. Table S5: Distribution of amplifiable DNA concentrations in the 377 analyzed samples.

Herein, we report the colloidal stability of emulsifier-free (EF-) triolein-in-water (TO/W) emulsions prepared by mixing TO and water using a high-powered bath-type ultrasonicator (HPBath-US; 28 kHz, 300 W) in the absence of emulsifiers such as surfactants. In particular, the effect of the temperature (15-60℃) on the colloidal stability of EF-TO/W emulsions was examined because this is important for the practical application of EF-TO/W emulsions, for example, in foods, pharmaceuticals, and cosmetics. We found that the colloidal stability of the EF-TO/W emulsions decreased with increase in the temperature from 15 to 25°C, whereas it increased with increase in temperature from 25 to 40°C, and the high colloidal stability of the EF-TO/W emulsions was maintained above 40°C. The reduction in the colloidal stability of EF-TO/W emulsions between 15 and 25°C is likely a result of the TO droplets formed by thermal motion, as well as enhanced Ostwald ripening at higher temperatures. On the other hand, the increase in the colloidal stability of the EF-TO/W emulsions from 25 to 40°C and their high colloidal stability above 40℃ is attributed to the reduction in the interfacial tension between TO and water at higher temperatures. This decrease in the interfacial tension between TO and water with temperature increase is related to the transformation of short-range ordered domains (clusters) of TO molecules in the liquid state, which increases the colloidal stability of the EF-TO/W emulsions.

The COVID-19 pandemic affected international exchange programs due to travel restrictions. There are few reports of online international exchange programs in medical area and no report of interactive activities among students together for several months. To the best of our knowledge, we needed to seek the effective approach to conduct online exchange program. We experienced online collaboration works to promote internationalization in occupational therapy (OT) undergraduate education. The aim of this study is to examine the usability and effectiveness of an interactive online international exchange program, and discuss its usefulness and challenges. The three-month program was newly developed, and aimed at cultivating an international perspective, understanding OT, and learning basic research skills. Students’ interests and the development of their motivation were considered in the program consisting of synchronous and asynchronous lectures, a collaboration research project, group work, and report assignments. Through the program, students were satisfied with the program contents and had the precious experience to develop international relationships. The online exchange program provided students with the opportunity to experience and learn OT education internationally at an economical cost, and to achieve program goal during the regular semester. In this program, students not only acquired knowledge in their professional field, but also cultivated their international communication skills in English from small group activities and social activities. Considering various communication methods was an important aspect in the virtual environment leading to a successful program. In medical education, an online program can be an effective and practical measure for international exchange.

Study design Cross-sectional study. Objective To develop a binary classification model for cervical myelopathy (CM) screening based on a machine learning algorithm using Leap Motion (Leap Motion, San Francisco, CA, USA), a novel non-contact sensor device. Summary of background data Progress of CM symptoms are gradual and cannot be easily identified by the patients themselves. Therefore, screening methods should be developed for patients of CM before deterioration of myelopathy. Although some studies have been conducted to objectively evaluate hand movements specific to myelopathy using cameras or wearable sensors, their methods are unsuitable for simple screening outside hospitals because of the difficulty in obtaining and installing their equipment and the long examination time. Methods In total, 50 and 28 participants in the CM and control groups were recruited, respectively. The diagnosis of CM was made by spine surgeons. We developed a desktop system using Leap Motion that recorded 35 parameters of fingertip movements while participants gripped and released their fingers as rapidly as possible. A support vector machine was used to develop the binary classification model, and a multiple linear regression analysis was performed to create regression models to estimate the total Japanese Orthopaedic Association (JOA) score and the JOA score of the motor function of the upper extremity (MU-JOA score). Results The binary classification model indexes were as follows: sensitivity, 84.0%; specificity, 60.7%; accuracy, 75.6%; area under the curve, 0.85. The Spearman's rank correlation coefficient between the estimated score and the total JOA score was 0.44 and that between the estimated score and the MU-JOA score was 0.51. Conclusion Our binary classification model using a machine learning algorithm and Leap Motion could classify CM with high sensitivity and would be useful for CM screening in daily life before consulting doctors and telemedicine.Level of Evidence: 3.

Background Many previous studies have demonstrated that minor-frequency pretreatment T790M mutation (preT790M) could be detected by ultrasensitive methods in a considerable number of treatment-naïve, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC) cases. However, the impact of preT790M in resected cases on prognosis remains unclear. Methods We previously reported that preT790M could be detected in 298 (79.9%) of 373 surgically resected, EGFR-mutated NSCLC patients. Therefore, we investigated the impact of preT790M on recurrence-free survival (RFS) and overall survival (OS) in this cohort by multivariate analysis. All patients were enrolled from July 2012 to December 2013, with follow-up until November 30, 2017. Results The median follow-up time was 48.6 months. Using a cutoff value of the median preT790M allele frequency, the high-preT790M group (n = 151) had significantly shorter RFS (hazard ratio [HR] = 1.51, 95% confidence interval [CI]: 1.01–2.25, P = 0.045) and a tendency for a shorter OS (HR = 1.87, 95% CI: 0.99–3.55, P = 0.055) than the low-preT790M group (n = 222). On multivariate analysis, higher preT790M was independently associated with shorter RFS (high vs low, HR = 1.56, 95% CI: 1.03–2.36, P = 0.035), irrespective of advanced stage, older age, and male sex, and was also associated with shorter OS (high vs low, HR = 2.16, 95% CI: 1.11–4.20, P = 0.024) irrespective of advanced stage, older age, EGFR mutation subtype, and history of adjuvant chemotherapy. Conclusions Minor-frequency, especially high-abundance of, preT790M was an independent factor associated with a poor prognosis in patients with surgically resected, EGFR-mutated NSCLC.

Glycine was applied as the leachant for the hydrothermal leaching of lithium-ion battery (LIB) cathode materials, LiCoO2 and LiNiO2, at 90–180 °C for 5–90 min. LiCoO2 was completely leached at 180 ...

Hard carbon (HC) is the most promising candidate for sodium-ion battery anode materials. Several material properties such as intensity ratio of the Raman spectrum, lateral size of HC crystallite (La ), and interlayer distance (d002 ) have been discussed as factors affecting anode performance. However, these factors do not reflect the bulk property of the Na+ intercalation reaction directly, since Raman analysis has high surface sensitivity and La and d002 provide only one-dimensional crystalline information. Herein, it was proposed that the crystallite interlayer area (Ai ) defined using La , d002 , and stacking height (Lc ) governs Na+ intercalation behavior of various HCs. It was revealed that various wood-derived HCs exhibited the similar total capacity of approximately 250 mAh g-1 , whereas the Na+ intercalation capacity (Ci ) was proportional to Ai with the correlation coefficient of R2 =0.94. The evaluation factor of Ai was also adaptable to previous reports and strongly correlated with their Ci , indicating that Ai is more widely adaptable than the conventional evaluation methods.

Background/aim Molecular targeted agents have been successfully developed against solid tumors and their use is also being investigated for the treatment of malignant pleural mesothelioma (MPM). We have previously reported von Hippel Lindau (VHL) mutations detected by massive parallel sequencing technology in samples of patients with MPM. Here, we conducted an in vitro study to investigate the therapeutic approaches in VHL-mutant MPM. Materials and methods Three MPM cell lines with or without a VHL mutation were used and the effects of molecular-targeted agents on growth inhibition were evaluated. Based on the characteristics of the molecular targeted agents that exhibited growth inhibitory effect, the effects of knockdown by siRNA were also evaluated. Results NCI-H28 MPM cells harboring the VHL L89H mutation were sensitive to YC-1, known as an inhibitor of hypoxia inducible factor (HIF)-1α, and YC-1treatment induced massive apoptosis in a dose-and-time-dependent manner. Knockdown of HIF-1α by siRNA partially inhibited the growth of NCI-H28 cells, suggesting that an additional blockade may be required to completely inhibit growth signaling. Conclusion The VHL mutation may predict tumor responses to YC-1, a HIF-1α inhibitor.

Mechanical stimulation is well known to be important for maintaining tissue and organ homeostasis. Here, we found that hydrostatic pressure induced nuclear translocation of a forkhead box O (FOXO) transcription factor DAF-16, in C. elegans within minutes, whereas the removal of this pressure resulted in immediate export of DAF-16 to the cytoplasm. We also monitored DAF-16-dependent transcriptional changes by exposure to 1 MPa pressure for 5 min, and found significant changes in collagen and other genes in a DAF-16 dependent manner. Lifespan was markedly prolonged with exposure to cyclic pressure treatment (1 MPa once a day for 5 min from L1 larvae until death). Furthermore, age-dependent decline in locomotor activity was suppressed by the treatment. In contrast, the nuclear translocation of the yes-associated protein YAP-1 was not induced under the same pressure conditions. Thus, moderate hydrostatic pressure improves ageing progression through activation of DAF-16/FOXO in C. elegans.

The first run of continuous hydrothermal leaching of lithium-ion battery cathode materials, LiCoO2, was performed using citric acid as the leachant at 200 °C. The flow system was specially designed and customized. Prior to the hydrothermal leaching experiments, a three-layer model was used to predict the flow state in this flow system, and a cold flow test using two kinds of flow lines was performed to determine the conditions in the preliminary experiments. Finally, the pulp density of the slurry and the flow rate were set to 10 g L−1 and 30 ml min−1, respectively, for the continuous hydrothermal leaching experiments. At 60 min after the start of slurry feeding, the leaching efficiency of Li and Co reached 81.3% and 92.7%, respectively, and can continue to increase with the extension of time. The successful run indicated that the process of hydrothermal leaching is feasible and promising to be applied in practice. Meanwhile, a problem of acid corrosion caused by the use of citric acid during this process was revealed and is expected to be resolved using inner coating materials with high acid corrosion resistance or organic acids with low or no acid corrosion as the leachant.

Inexpensive, high-performing, and environmentally friendly energy storage devices are required for smart grids that efficiently utilize renewable energy. Energy storage devices consisting of organic active materials are promising because organic materials, especially quinones, are ubiquitous and usually do not require harsh conditions for synthesis, releasing less CO2 during mass production. Although fundamental research-scale aqueous quinone-based organic supercapacitors have shown excellent energy storage performance, no practical research has been conducted. We aimed to develop a practical-scale aqueous-quinone-based organic supercapacitor. By connecting 12 cells of size 10 cm × 10 cm × 0.5 cm each in series, we fabricated a high-voltage (> 6 V) aqueous organic supercapacitor that can charge a smartphone at a 1 C rate. This is the first step in commercializing aqueous organic supercapacitors that could solve environmental problems, such as high CO2 emissions, air pollution by toxic metals, and limited electricity generation by renewable resources.

There is an urgent need to develop renewable sources of energy and use existing resources in an efficient manner. In this study, in order to improve the utilization of unused biomass and develop green processes and sustainable technologies for energy production and storage, unused Douglas fir sawdust (SD) was transformed into catalysts for the oxygen reduction reaction. Fe and N were doped into SD during hydrothermal carbonization, and the N- and Fe-doped wood-derived carbon (Fe/N/SD) was carbonized in a nitrogen atmosphere. After the catalyst had been calcined at 800°C, its showed the highest current density (−5.86 mAcm −2 at 0.5 V versus reversible hydrogen electrode or RHE) and E onset value (0.913 V versus RHE). Furthermore, its current density was higher than that of Pt/C (20 wt% Pt) (−5.66 mA cm −2 @0.5 V versus RHE). Finally, after 50 000 s, the current density of sample Fe/N/SD (2 : 10 : 10) remained at 79.3% of the initial value. Thus, the synthesized catalysts, which can be produced readily at a low cost, are suitable for use in various types of energy generation and storage devices, such as fuel cells and air batteries. This article is part of the theme issue ‘Bio-derived and bioinspired sustainable advanced materials for emerging technologies (part 2)’.

Nitrogen-containing compounds, especially primary amines, are vital building blocks in nature and industry. Herein, a protocol is developed that shows in situ formed N-formyl quasi-catalytic species afford highly selective synthesis of formamides or amines with controllable levels from a variety of aldehyde- and ketone-derived platform chemical substrates under solvent-free conditions. Up to 99% yields of mono-substituted formamides are obtained in 3 min. The C-N bond formation and N-formyl species are prevalent in the cascade reaction sequence. Kinetic and isotope labeling experiments explicitly demonstrate that the C-N bond is activated for subsequent hydrogenation, in which formic acid acts as acid catalyst, hydrogen donor and as N-formyl species source that stabilize amine intermediates elucidated with density functional theory. The protocol provides access to imides from aldehydes, ketones, carboxylic acids, and mixed-substrates, requires no special catalysts, solvents or techniques and provides new avenues for amination chemistry., Processes for efficient production of primary, secondary or ternary aminated compounds are constant challenges for chemical and pharmaceutical industries. Here, the authors develop selective and sustainable amination chemistry widely applicable to chemical substrates via formic acid.

Rubratoxin A, a potent inhibitor of PP2A, is known to suppress smooth muscle contraction. The inhibitory role of PP2A in smooth muscle contraction is still unclear. In order to clarify the regulatory mechanisms of PP2A on vascular smooth muscle contractility, we examined the effects of rubratoxin A on the Ca2+-induced contraction of β-escin skinned carotid artery preparations from guinea pigs. Rubratoxin A at 1 µM and 10 µM significantly inhibited skinned carotid artery contraction at any Ca2+ concentration. The data fitting to the Hill equation in [Ca2+]-contraction relationship indicated that rubratoxin A decreased Fmax-Ca2+ and increased [Ca2+]50, indices of Ca2+ sensitivity for the force and myosin-actin interaction, respectively. These results suggest that PP2A inhibition causes downregulation of the myosin light chain phosphorylation and direct interference with myosin-actin interaction.

In this study, we conducted an initial screening of ZrO2 and M/ZrO2 (M = Al, Ca, Ce, Pr, and Y) catalysts employing a batch apparatus first and then applied the selected catalyst (Ce0.1Zr0.9O2) into a natural convection circulation system with dehydrating agents, for the direct synthesis of dimethyl carbonate (DMC) from methanol (MeOH) and CO2. During the initial screening, Ce0.1Zr0.9O2 showed the highest DMC yield at ∼ 0.64% with 100% selectivity at 170 °C. The catalytic reactivities of ZrO2 and M/ZrO2 solid solutions followed the order: Ce/ZrO2 > Y/ZrO2 > Pr/ZrO2 ≈ ZrO2 > Al/ZrO2 > Ca/ZrO2. The relationship between physical properties and the activity of the catalysts was evaluated. As a result, the specific surface area and the acidity/basicity were considered to be irrelevant to the catalytic activity. However, a clear relationship between the temperature-programmed desorption (TPD) profile of MeOH and the reactivity was revealed: the increase of the weak affinity sites leads to the increase of reactivity. During the direct DMC synthesis over Ce0.1Zr0.9O2 catalyst employing the natural convection circulation system with molecular sieves 3A, the DMC yield reached up to 14.3% with 100% selectivity, which was the highest yield so far using M/ZrO2 catalysts. Prior to the experiment with the natural convection circulation system, the initial conditions were determined based on the experimental results employing the batch apparatus, previous literature, and estimation results. Moreover, some factors affecting the DMC yield using the circulation system were studied, including the reaction rate, the circulation rate of the flow in the circulation system, and the dehydration rate in the dehydration part.