A priori reduction method for solving the two-dimensional Burgers’ equations

The two-dimensional Burgers’ equations are solved here using the A Priori Reduction method. This method is based on an iterative procedure which consists in building a basis for the solution where at each iteration the basis is improved. The method is called a priori because it does not need any prior knowledge of the solution, which is not the case if the standard Karhunen-Loéve decomposition is used. The accuracy of the APR method is compared with the standard Newton-Raphson scheme and with results from the literature. The APR basis is also compared with the Karhunen-Loéve basis.     

X‐Ray Crystallography and Free Energy Calculations Reveal the Binding Mechanism of A2A Adenosine Receptor Antagonists

We present a robust protocol based on iterations of free energy perturbation (FEP) calculations, chemical synthesis, biophysical mapping and X‐ray crystallography to reveal the binding mode of an antagonist series to the A_2A adenosine receptor (AR). Eight A_2AAR binding site mutations from biophysical mapping experiments were initially analyzed with sidechain FEP simulations, performed on alternate binding modes. The results distinctively supported one binding mode, which was subsequently used to design new chromone derivatives. Their affinities for the A_2AAR were experimentally determined and investigated through a cycle of ligand‐FEP calculations, validating the binding orientation of the different chemical substituents proposed. Subsequent X‐ray crystallography of the A_2AAR with a low and a high affinity chromone derivative confirmed the predicted binding orientation. The new molecules and structures here reported were driven by free energy calculations, and provide new insights on antagonist binding to the A_2AAR, an emerging target in immuno‐oncology.     

Fate of Sulfonamides and Tetracyclines in Meat during Pan Cooking: Focus on the Thermodegradation of Sulfamethoxazole

Although antimicrobials are generally found in trace amounts in meat, the human health risk they bear cannot be ignored. With the ultimate aim of making a better assessment of consumer exposure, this study explored the effects of pan cooking on sulfonamides and tetracyclines in meat. Screening of these antimicrobials in cooked meat was first performed by the European Union Reference Laboratory on the basis of HPLC-MS/MS analyses. A proof of concept approach using radiolabeling was then carried out on the most cooking-sensitive antimicrobial—sulfamethoxazole—to assess if a thermal degradation could explain the observed cooking losses. Degradation products were detected thanks to separation by HPLC and monitoring by online radioactivity detection. HPLC-Orbitrap HRMS analyses completed by 1D and 2D NMR experiments allowed the structural characterization of these degradation compounds. This study revealed that cooking could induce significant antimicrobial losses of up to 45% for sulfamethoxazole. Six potential degradation products of ¹⁴C-sulfamethoxazole were detected in cooked meat, and a thermal degradation pattern was proposed. This study highlights the importance of considering the cooking step in chemical risk assessment procedures and its impact on the level of chemical contaminants in meat and on the formation of potentially toxic breakdown compounds.     

Multiresidue analytical method for the determination of eight penicillin antibiotics in muscle tissue by ion-pair reversed-phase HPLC after precolumn derivatization.

A high-performance liquid chromatographic multiresidue method was developed for the determination of 8 penicillin compounds (benzylpenicillin, phenoxymethylpenicillin, ampicillin, amoxicillin, nafcillin, oxacillin, cloxacillin, and dicloxacillin) at trace levels in muscle tissue. This method involves extraction of the penicillins with phosphate buffer pH 9 followed by cleanup and concentration on a C18 solid-phase extraction column and reaction with benzoic anhydride at 50 degrees C for 5 min and with 1,2,4-triazole and mercury(II) chloride solution pH 9 at 65 degrees C for 10 min. The derivatized compounds are eluted on a C8 column with a mobile phase containing acetonitrile and phosphate buffer (pH 6; 0.1 mol/L) loaded with sodium thiosulfate and ion-pairing tetrabutylammonium hydrogenosulphate. The method detection limit is approximately 3-11 micrograms/kg and the limit of determination was evaluated down to 25 micrograms/kg in line with the criteria of the EU decision No. 93/256/EEC.     

Development and validation of a confirmatory method for the determination of 12 non steroidal anti-inflammatory drugs in milk using liquid chromatography-tandem mass spectrometry

A rapid and reliable LC-MS/MS method for the simultaneous confirmation of twelve non steroidal anti-inflammatory drugs (NSAIDs) in bovine milk was developed and fully validated in accordance with the European Commission Decision 2002/657/EC. The validation scheme was built in accordance with the MRLs or target analytical levels (EU-CRL recommended concentrations and detection capabilities) of the analytes, except for diclofenac for which the lower level of validation achieved was 0.5 μg kg(-1) whereas its MRL is 0.1 μg kg(-1). The NSAIDs investigated were as follows: phenylbutazone (PBZ), oxyphenylbutazone (OPB), naproxen (NP), mefenamic acid (MF), vedaprofen (VDP), flunixin (FLU), 5-hydroxyflunixin (FLU-OH), tolfenamic acid (TLF), meloxicam (MLX), diclofenac (DC), carprofen (CPF) and ketoprofen (KTP). Several extraction procedures had been investigated during the development phase. Finally, the best results were obtained with a procedure using only methanol as the extraction solvent, with an evaporation step included and no further purification. Chromatographic separation was achieved on a C18 analytical column and the run was split in 2 segments. Matrix effects were also investigated. Data acquisition implemented for the confirmatory purpose was performed by monitoring 2 MRM transitions per analyte under the negative electrospray mode. Mean relative recoveries ranged from 94.7% to 110.0%, with their coefficients of variation lying between 2.9% and 14.7%. Analytical limits expressed in terms of decision limits (CCα) were evaluated between 0.69 μg kg(-1) (FLU) and 27.54 μg kg(-1) (VDP) for non-MRL compounds, and at 0.10 (DC), 15.37 (MLX), 45.08 (FLU-OH), and 62.96 μg kg(-1) (TLF) for MRL compounds. The validation results proved that the method is suitable for the screening and confirmatory steps as implemented for the French monitoring plan for NSAID residue control in bovine milk.