Cyclophilin Inhibition Protects Against Experimental Acute Kidney Injury and Renal Interstitial Fibrosis

Cyclophilins have important homeostatic roles, but following tissue injury, cyclophilin A (CypA) can promote leukocyte recruitment and inflammation, while CypD can facilitate mitochondrial-dependent cell death. This study investigated the therapeutic potential of a selective cyclophilin inhibitor (GS-642362), which does not block calcineurin function, in mouse models of tubular cell necrosis and renal fibrosis. Mice underwent bilateral renal ischemia/reperfusion injury (IRI) and were killed 24 h later: treatment with 10 or 30 mg/kg/BID GS-642362 (or vehicle) began 1 h before surgery. In the second model, mice underwent unilateral ureteric obstruction (UUO) surgery and were killed 7 days later; treatment with 10 or 30 mg/kg/BID GS-642362 (or vehicle) began 1 h before surgery. GS-642362 treatment gave a profound and dose-dependent protection from acute renal failure in the IRI model. This protection was associated with reduced tubular cell death, including a dramatic reduction in neutrophil infiltration. In the UUO model, GS-642362 treatment significantly reduced tubular cell death, macrophage infiltration, and renal fibrosis. This protective effect was independent of the upregulation of IL-2 and activation of the stress-activated protein kinases (p38 and JNK). In conclusion, GS-642362 was effective in suppressing both acute kidney injury and renal fibrosis. These findings support further investigation of cyclophilin blockade in other types of acute and chronic kidney disease.     

Trends and driving forces of low-carbon energy technology innovation in China’s industrial sectors from 1998 to 2017: from a regional perspective

Low-carbon energy technology (LC) innovation contributes to both environmental protection and economic development. Using the panel data of 30 provinces/autonomous regions/municipalities in China from 1998 to 2017, this paper constructs a two-layer logarithmic mean Divisia index (LMDI) model to uncover the factors influencing the variation of the innovation of LC in China’s industrial sectors, including the alternative energy production technology (AEPT) and the energy conversation technology (ECT). The results show that China’s industrial LC patent applications rapidly increased after 2005 and AEPT patent applications outweighed ECT patent applications all the time with a gradually narrowing gap. Low-carbon degree played the dominant role in promoting the increase in China’s industrial LC patent applications, followed by the economic scale, R&D (research and development) efficiency, and R&D share. Economic structure contributed to the increases in LC patent applications in the central and the western regions, while led to the decreases in the eastern region, the north-eastern region, and Chinese mainland Xizang(Tibet) Autonoomous Region is not considered due to lack of data. This note applies to the entire article.. Low-carbon degree and economic scale were two main contributors to the growths of both industrial AEPT patent applications and ECT patent applications in Chinese mainland and the four regions. Several policy recommendations are made to further promote industrial innovation in China.     

A side-sensitive synthetic coefficient of variation chart

Control charts for monitoring the coefficient of variation (γ) are useful for processes with an inconsistent mean (μ) and a standard deviation (σ) which changes with μ, by monitoring the consistency in the ratio σ over μ. The synthetic-γ chart is one of the charts proposed to monitor γ, and its attractiveness lie in waiting until a second point to fall outside the control limits before a decision is made. However, existing synthetic-γ charts do not differentiate between the points falling outside the upper control limit (UCL) and lower control limit (LCL). Hence, this paper proposes a side-sensitive synthetic-γ chart, where successive nonconforming samples must either fall above the UCL or below the LCL. Formulae to compute the average run length (ARL), the standard deviation of the run length (SDRL) and expected average run length (EARL) are derived using the Markov chain approach, and the algorithms to obtain the optimal charting parameters are proposed. Subsequently, the optimal charting parameters, ARL, SDRL and EARL values for various numerical examples are shown. Comparisons show that the side-sensitive synthetic-γ chart consistently outperforms the existing synthetic-γ chart, especially for small shifts. The proposed chart also consistently outperforms the Shewhart-γ chart, while showing comparable or better performance than the Exponentially Weighted Moving Average (EWMA) chart for most shift sizes, except for very small shifts. Finally, this paper shows the implementation of the proposed chart on an industrial example.     

Equilibria,kinetics and mechanism for the degradation of the cytotoxic compound L-NG-nitroarginine

L-N^G-nitroarginine (LNNA), an analog of L-arginine, is a competitive inhibitor of nitric oxide synthase which causes the selective reduction of blood flow to tumor cells. Despite the potential of LNNA to function as an adjuvant in cancer therapies, its poor solubility and stability have hindered the development of an injectable formulation of LNNA that is suitable for human administration. This work, for the first time, details a systematic study on the determination of equilibrium K_a constants and the rate law of LNNA degradation. The four K_a values of LNNA were determined to be 1.03, 1.10?×?10^?2, 2.51?×?10^?10, and 1.33?×?10^?13 M. From the kinetic and equilibrium studies, we have shown that the deprotonated form of LNNA is the main form of LNNA that undergoes degradation in aqueous media at room temperature. The rate law of LNNA degradation was found to be first order with respect to OH^? concentration and first order with respect to LNNA^? concentration. The rate constant at 25?°C and 1?atm was determined to be 0.04453 M^?1min^?1. A base catalyzed mechanism of LNNA degradation was proposed based on the kinetic study. The mechanism was found to be very useful in explaining the discrepancies and changes of the rate law at different pH values. It is thus recommended that LNNA should be formulated as a concentrated solution in acidic conditions for maximum chemical stability during storage and be diluted with a basic solution to near physiological pH just before administration.     

Incorporation of sugarcane bagasse in the development of high dietary fibre noodles

Sugarcane bagasse (SB) is one of the most abundant food wastes. In this research, SB was incorporated into the development of noodles at three different ratios, i.e. 5%, 10% and 15%. Total dietary fibre of noodles significantly increased from 3.39% (control noodles; – without SB) to 13.85% with 15% SB incorporation. All SB incorporated noodles (SBNs) were qualified to be labelled as ‘High in dietary fibre’. The 15% SBN had the highest fibre content and lowest dialyzable glucose, but the organoleptic properties were the lowest. Due to that, 5% SBN was deemed to be the most suitable ratio for noodles incorporation, as it had the closest value towards the commercial noodles in terms of colour, texture, fibre content and dialyzable glucose concentration of noodles samples. In terms of sensory evaluation, the 5% SBN had the highest overall acceptability, and the ratio was suitable for noodles development.     

A semantic-aware log generation method for network activities

International Journal of Information Security - Context-aware network logging is becoming more prevalent for enterprise networks, data centers, and forensics. Monitoring agents are strategically...     

Dielectric strength of Al2O3/silicone composites after high‐temperature aging

Silicones are widely used for electrical insulation owing to their high dielectric strength and thermal stability. However, recent studies revealed insufficient stability of silicone for high‐temperature applications. To study the effect of Al₂O₃ fiber on silicone stability, we measured the dielectric strength of unfilled silicone and Al₂O₃/silicone composites as a function of aging time at 250°C in air and analyzed data by Weibull probability distribution to determine characteristic dielectric strength (E₀) and shape parameter (β). Prior to aging, unfilled silicone and composites had similar behavior, with E₀ at about 20 kV/mm and β > 15. During aging, unfilled silicone developed both micro‐ and macrocracks, with β dropped below five in 240 h and E₀ decreased significantly. Composites developed microcracks, with β dropped below 5 in longer time and E₀ remained almost constant. Addition of Al₂O₃ slowed down crack growth in silicone matrix, resulting in longer lasting high‐temperature dielectric materials. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41170.     

Phase equilibria and dielectric properties of Bi3+(5/2)xMg2−xNb3–(3/2)xO14−x cubic pyrochlores

Subsolidus pyrochlores with the proposed formula, Bi_3+(5/2)xMg_2−xNb_3−(3/2)xO_14−x (0.14≤x≤0.22) were successfully synthesised at the firing temperature of 1025 °C using conventional solid-state reaction. The excess Bi³⁺ charge was offset by removal of relative proportion of Mg²⁺ and Nb⁵⁺ together with creation of oxygen non-stoichiometry in order to preserve electroneutrality of the system. These samples were crystallised in cubic structure with space group of Fd3m, No. 227 and their refined lattice parameters were in the range of 10.5706 (3)–10.5797 (7) Å. The surface morphologies of the samples as confirmed by scanning electron microscopy analysis were of irregular shaped grains while their crystallite sizes of ~30–85 nm were calculated using the Scherrer equation and the Williamson–Hall method. No thermal event was discernable indicating these pyrochlores were thermally stable within a studied temperature range of ~30–1000 °C. The recorded dielectric constants of Bi_3+(5/2)xMg_2−xNb_3−(3/2)xO_14−x (0.14≤x≤0.22) subsolidus pyrochlores were generally above ~160 and their dielectric losses were in the order of 10⁻⁴–10⁻³ at the frequency of 1 MHz and temperature of ~30 °C. Meanwhile, these ceramic samples also exhibited negative temperature coefficient of relative permittivity between −528 and −742 ppm/°C in the temperature range of ~30–300 °C.