Conditional recurrent neural networks for broad applications in nonlinear optics.

We present a novel implementation of conditional long short-term memory recurrent neural networks that successfully predict the spectral evolution of a pulse in nonlinear periodically-poled waveguides. The developed networks offer large flexibility by allowing the propagation of optical pulses with ranges of energies and temporal widths in waveguides with different poling periods. The results show very high agreement with the traditional numerical models. Moreover, we are able to use a single network to calculate both the real and imaginary parts of the pulse complex envelope, allowing for successfully retrieving the pulse temporal and spectral evolution using the same network.

Design, synthesis, molecular modelling and in vitro cytotoxicity analysis of novel carbamate derivatives as inhibitors of Monoacylglycerol lipase.

Monoacylglycerol lipase (MAGL) has an essential role in the catabolic pathway of the endocannabinoid 2-arachidonoylglycerol, which makes it a potential target for highly specific inhibitors for the treatment of a number of diseases. We designed and synthesized a series of carbamate analogues of URB602. We evaluated their inhibitory activity toward human MAGL in vitro both in cell culture and lysates. The target compounds exhibited moderate to excellent inhibitory activity against MAGL. The most promising compound 2b showed good inhibitory activity with IC50 value of 4.5 ±â€¯0.70 µM reducing MAGL activity to 82% of controls at 10 µM compared to 66% for the parent compound URB602. Interestingly, compounds 2b and 2c induce cell death through the inhibition of MAGL. Molecular modelling approaches and docking studies, used to investigate inhibitory profiles, indicated that trifluoromethyl substitutions of the aryl group and the benzene ring present at the oxygen side of the carbamate molecule had a significant impact on the activity.

Synthesis and characterization of a new fluorogenic substrate for monoacylglycerol lipase and application to inhibition studies.

Human monoacylglycerol lipase (MAGL), a soluble serine hydrolase that belongs to the α/ß hydrolase fold superfamily, regulates 2-arachidonoyl glycerol level in the endocannabinoid system, which is implicated in a number of severe diseases, and therefore, inhibition of MAGL activity is crucial in the treatment of these diseases. We have synthesized a red fluorogenic substrate, 7-hydroxyresorufinyl-arachidonate (7-HRA), for a new MAGL assay. This assay is simple, sensitive, and reliable and useful for identifying compounds that modulate MAGL activity. In addition, the assay emits red fluorescence, which can significantly reduce interference due to compound fluorescence and dust or lint, all of which fluoresce in the blue wavelength. MAGL catalyzes the hydrolysis of 7-HRA to generate arachidonic acid and a highly red fluorescent resorufin, excitation at 571 nm and emission at 588 nm, with a Km of 0.87 µM and Vmax of 26 nmol min(-1) mg protein(-1). The known MAGL inhibitors URB602, methyl arachidonyl fluorophosphonate, and JZL184 were used to validate the test assay. The assay was highly reproducible with an overall average Z' value of 0.80. This new red fluorogenic substrate and the resulting enzyme assay could be used in high-throughput screening to identify and develop new potential MAGL inhibitors.