4 research outputs found

    Chemo-enzymatic synthesis of NPN cofactor taking advantage of ADP-ribosyl cyclase and LarC cyclometallase promiscuous activities

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    The nickel-pincer nucleotide cofactor (NPN) is a widespread organometallic cofactor required for lactate racemase (LarA) and for α-hydroxy acid racemases and epimerases of the LarA superfamily. Its biosynthesis, which starts with nicotinic acid adenine dinucleotide (NaAD), requires three enzymes: LarB, LarC, and LarE, and can be performed in vitro with purified enzymes. Nevertheless, as LarE and LarC are single turnover enzymes, the in vitro NPN biosynthesis requires huge amounts of enzymes (particularly 2 equivalents of LarE), which hampers the study of NPN and of NPN-dependent enzymes. By using adenosine diphosphate (ADP)-ribosyl cyclase (ARC), we exchanged the nicotinamide moiety in NAD+ with synthetic pyridine-3,5-bisthiocarboxylic acid in order to synthesize the novel intermediate pyridinium-3,5-bisthiocarboxylic acid adenine dinucleotide (P2TAD). The latter could be produced at a multimilligram scale allowing its characterization by Nuclear Magnetic Resonance (NMR) and mass spectrometry. Interestingly, P2TAD could directly be used by LarC in order to generate the NPN cofactor, bypassing both LarB and LarE. Globally, a new chemoenzymatic route towards NPN was developed via the intermediate P2TAD, which should facilitate the biochemical and biotechnological investigations on NPN binding enzymes

    A Framework to Evaluate Aircraft Trajectory Generation Methods

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    Aircraft trajectory generation is a widely addressed problem with applications including emergency trajectory generation, collision risk models, air traffic flow and capacity management or airspace design. State of the art methods to generate individual trajectories and optimise some performance or emergency criterion may lack of realism with respect to common situations implemented by air traffic controllers. On the other hand, statistical data-driven methods to generate aircraft trajectories excel at imitating operational practice but may be difficult to implement even in simulations due to aircraft performance limitations. This contribution proposes a common baseline to compare literature and bleeding-edge methods to generate air traffic trajectories. Keeping in mind that the most appropriate criterion should always depend on the targeted application, we present here an extensive set of metrics to evaluate the quality of generated trajectories, before assessing two generation methods in light of these indicators.Control & Simulatio

    Provision of instructions to drink ad libitum or according to thirst sensation: impact during 120 km of cycling in the heat in men

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    The terms drinking to thirst and ad libitum drinking are used interchangeably, but should they? We investigated the differences in how athletes consume fluids during exercise when instructed to drink according to thirst or ad libitum. Using a randomized, crossover and counterbalanced design, 10 males (27 4 y) cycled 120 km (48 4% of peak power, 33C, 40% relative humidity) on two occasions, while drinking water according to thirst or ad libitum. Participants covered the cycling trials in 222 11 min (p = 0.29). Although the body mass loss at the end of exercise and total volume of water consumed were similar between trials, thirst perception before each sip and the volume consumed per sip were significantly higher with thirst than ad libitum drinking, whereas the total number of sips was significantly lower with thirst than ad libitum drinking. Perceived exertion, rectal temperature and heart rate were all significantly higher with thirst than ad libitum drinking, but the difference was trivial. In conclusion, thirst and ad libitum drinking are associated with different drinking patterns, but equally maintain fluid balance during prolonged exercise. The terms drinking to thirst and ad libitum drinking can be used interchangeably for guiding fluid intake during prolonged exercise. NOVELTY • Both strategies are associated with different patterns of fluid ingestion during prolonged exercise, but are equally effective in maintaining fluid balance; • Perceived exertion, rectal temperature and heart rate are regulated dissimilarly by thirst and ad libitum drinking, but the difference is trivial.The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author
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