Post-blast explosive residue : a review of formation and dispersion theories and experimental research

The presence of undetonated explosive residues following high order detonations is not uncommon, however the mechanism of their formation, or survival, is unknown. The existence of these residues impacts on various scenarios, for example their detection at a bomb scene allows for the identification of the explosive charge used, whilst their persistence during industrial explosions can affect the safety and environmental remediation efforts at these sites. This review article outlines the theoretical constructs regarding the formation of explosive residues during detonation and their subsequent dispersal and deposition in the surrounding media. This includes the chemical and physical aspects of detonation and how they could allow for undetonated particles to remain. The experimental and computational research conducted to date is discussed and compared to the theory in order to provide a holistic review of the phenomeno

Street canyon concentration estimation coupling the RANS model MISKAM and the micromixing Lagrangian model LAGFLUM

The stationary three-dimensional Lagrangian stochastic model LAGFLUM has been coupled with MISKAM to simulate numerically the higher statistical moments of concentration for a passive scalar in the 3D turbulent flow corresponding to MUST wind tunnel experiment. LAGFLUM is based on the coupling of a macromixing scheme founded on the well-mixed condition, while the micromixing scheme utilizes the IECM. The LAGFLUM input data have been obtained by using the output of the MISKAM model applied to the MUST experiment. The results show a reasonable agreement between simulated and measured statistical moments of concentration

An essential type I nitroreductase from Leishmania major can be used to activate leishmanicidal prodrugs.

Nitroaromatic prodrugs are used to treat a range of microbial infections with selectivity achieved by specific activation reactions. For trypanosomatid parasites this is mediated by type I nitroreductases (NTRs). Here, we demonstrate that the causative agent of leishmaniasis, Leishmania major, expresses a FMN-containing NTR (LmNTR) that metabolises a wide range of substrates and based on electron donor and acceptor preferences may function as a NADH:quinone oxidoreductase. Using gene deletion approaches, we demonstrate that this activity is essential to L. major promastigotes, the parasite forms found in the insect vector. Intriguingly, although LmNTR+/- heterozygote promastigote parasites could differentiate into infectious form metacyclic cells, these were unable to establish infections in cultured mammalian cells and cause delayed pathology in mice. Further, we exploit the LmNTR activity evaluating a library of nitrobenzylphosphoramide mustards using biochemical and phenotypic screens. We identify a subset of compounds that display significant growth inhibitory properties against the intracellular parasite form found in the mammalian host. The leishmanicidal activity was shown to be LmNTR specific as the LmNTR+/- heterozygote promastigotes displayed resistance to the most potent mustards. We conclude that LmNTR can be targeted for drug development by exploiting its prodrug activating property or by designing specific inhibitors to block its endogenous function

An essential type I nitroreductase from Leishmania major can be used to activate leishmanicidal prodrugs.

Nitroaromatic prodrugs are used to treat a range of microbial infections with selectivity achieved by specific activation reactions. For trypanosomatid parasites, this is mediated by type I nitroreductases. Here, we demonstrate that the causative agent of leishmaniasis, Leishmania major, expresses an FMN-containing nitroreductase (LmNTR) that metabolizes a wide range of substrates, and based on electron donor and acceptor preferences, it may function as an NADH:quinone oxidoreductase. Using gene deletion approaches, we demonstrate that this activity is essential to L. major promastigotes, the parasite forms found in the insect vector. Intriguingly, LmNTR(+/-) heterozygote promastigote parasites could readily differentiate into infectious metacyclic cells but these were unable to establish infections in cultured mammalian cells and caused delayed pathology in mice. Furthermore, we exploit the LmNTR activity evaluating a library of nitrobenzylphosphoramide mustards using biochemical and phenotypic screens. We identify a subset of compounds that display significant growth inhibitory properties against the intracellular parasite form found in the mammalian hosts. The leishmanicidal activity was shown to be LmNTR-specific as the LmNTR(+/-) heterozygote promastigotes displayed resistance to the most potent mustards. We conclude that LmNTR can be targeted for drug development by exploiting its prodrug activating property or by designing specific inhibitors to block its endogenous function