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This study evaluated the effect of enarodustat on cardiac repolarization in healthy subjects. Enarodustat (20 and 150 mg [supratherapeutic dose]), placebo, and moxifloxacin (positive control, 400 mg) were administered orally to males and females (N = 54) in a crossover fashion. Continuous 12‐lead Holter electrocardiogram (ECG) data were obtained before and after dosing, and blood samples were obtained for pharmacokinetic assessments of enarodustat, its circulating metabolite (R)‐M2, and moxifloxacin. Central tendency analysis was performed for relevant ECG parameters, the relationship between individual‐corrected interval from beginning of the QRS complex to end of the T wave in the frontal plane (QTcI, the primary end point) and plasma concentrations of enarodustat and (R)‐M2 were assessed, and ECG waveforms were evaluated for morphological changes. The supratherapeutic dose resulted in 7‐ and 9‐fold higher geometric mean maximum concentrations for enarodustat and (R)‐M2, respectively, than the 20 mg dose. Based on time point analysis, the upper bound of the 2‐sided 90% confidence interval (CI) for QTcI did not exceed 10 milliseconds at any of the time points for either dose. Based on QTcI‐concentration analysis, the slopes for enarodustat and (R)‐M2 were not statistically different than 0, and the upper bounds of the 2‐sided 90% CI for QTcI at the geometric mean maximum concentrations for the supratherapeutic dose were 1.97 and 1.68 milliseconds for enarodustat and (R)‐M2, respectively. The lower bound of the 2‐sided 90% CI for moxifloxacin was ≥5 milliseconds, demonstrating assay sensitivity. The study demonstrated no clinically relevant effect of enarodustat and (R)‐M2 on cardiac repolarization. There was no evidence of any clinically significant effect on the PR interval and QRS duration, and ECG waveforms showed no new clinically relevant morphological changes. [ABSTRACT FROM AUTHOR]

Abstract: Memristive devices acting as high‐performance in‐memory computing fabrics have attracted much attention for nonvolatile parallel architectures to break the von Neumann bottleneck. Here, for the first time, a nonvolatile digital logic system with three‐terminal Pt/SiO2/Pt/Ag/GeTe/Ta one‐memristor‐one‐resistor (1M1R) structure is presented. Programmable nonvolatile Boolean logic gates and clocked sequential logic blocks including D latch and D flip‐flop are experimentally implemented, based on which a 4‐bit linear‐feedback shift register with timing design is functionally verified in simulation. With information generation, processing, transmission, and storage performing within the same 1M1R‐based logic blocks, these results consolidate the feasibility of building memristive digital computing system for future non‐von Neumann computing. [ABSTRACT FROM AUTHOR]

BACKGROUND Some oleaginous fungi can produce large amounts of polyunsaturated fatty acids ( PUFAs) which serve many physiological functions. Numerous desaturases are critical for the synthesis of PUFAs. This study aimed to investigate the regulation of lipid production and desaturase gene expression in Mortierella sp. AGED in response to different environmental factors, and the relationships between lipid production and desaturase gene expression. RESULTS The fatty acid composition and mRNA levels of desaturase genes were significantly changed under low temperatures. With the exception of Δ5-desaturase, the transcript levels of all desaturase genes increased at a temperature of 20 °C. Changes in content of lipid and PUFAs responding to low temperature were consistent with desaturase gene expression. Time course studies on gene expression showed that mRNA levels of four desaturase genes increased rapidly after transferring the cells to low temperature. Ethanol (1.5% v/v) increased the transcript levels of Δ9-, Δ6- and Δ5-desaturase genes significantly and of Δ12-desaturase gene slightly. Different metal ions such as Ca2+, Zn2+ and Fe3+ could stimulate PUFA synthesis and up-regulate desaturase gene transcription, while Cu2+ inhibited desaturase gene expression and lipid accumulation. CONCLUSION This study should enable us to understand the regulatory mechanism of desaturase gene expression and lipid synthesis. It is helpful to improve PUFA productivity in Mortierella sp. AGED. © 2016 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

A sulfone-functionalized metal-organic framework (MOF), USTC-253, has been synthesized that exhibits a much higher CO2 uptake capacity (168-182 %) than the corresponding unfurnished MOFs. The introduction of trifluoroacetic acid (TFA) during the synthesis of USTC-253 affords defect-containing USTC-253-TFA with exposed metal centers, which has an increased CO2 uptake (167 %) compared to pristine USTC-253. USTC-253-TFA exhibits a very high ideal adsorption solution theory selectivity ( S=75) to CO2 over N2 at 298 K. In addition, USTC-253-TFA demonstrates good catalytic activity and recyclability in the cycloaddition of CO2 and epoxide at room temperature under 1 bar CO2 pressure as a result of the presence of Lewis and Brønsted acid sites, which were evaluated by diffuse reflectance infrared Fourier transform spectroscopy with a CO probe molecule. We propose that the CO2 adsorption capability has a positive correlation with the catalytic performance toward CO2 conversion. [ABSTRACT FROM AUTHOR]

The development of in‐memory computing has opened up possibilities to build next‐generation non‐von‐Neumann computing architecture. Implementation of logic functions within the memristors can significantly improve the energy efficiency and alleviate the bandwidth congestion issue. In this work, the demonstration of arithmetic logic unit functions is presented in a memristive crossbar with implemented non‐volatile Boolean logic and arithmetic computing. For logic implementation, a standard operating voltage mode is proposed for executing reconfigurable stateful IMP, destructive OR, NOR, and non‐destructive OR logic on both the word and bit lines. No additional voltages are needed beyond "VP" and its negative component. With these basic logic functions, other Boolean functions are constructed within five devices in at most five steps. For arithmetic computing, the fundamental functions including an n‐bit full adder with high parallelism as well as efficient increment, decrement, and shift operations are demonstrated. Other arithmetic blocks, such as subtraction, multiplication, and division are further designed. This work provides solid evidence that memristors can be used as the building block for in‐memory computing, targeting various low‐power edge computing applications. [ABSTRACT FROM AUTHOR]