Purely (Non-)Strongly Real Beauville Groups

We discuss Beauville groups whose corresponding Beauville surfaces are either always strongly real or never strongly real producing several infinite families of examples

Identification of the amino-acetonitrile derivative monepantel (AAD 1566) as a new anthelmintic drug development candidate

Anthelmintic resistance has become a global phenomenon in gastro-intestinal nematodes of farm animals, including multi-drug resistance against the three major classes of anthelmintics. There is an urgent need for an anthelmintic with a new mode of action. The recently discovered amino-acetonitrile derivatives (AADs) offer a new class of synthetic chemicals with anthelmintic activity. The evaluation of AADs was pursued applying in vitro assays and efficacy and tolerability studies in rodents, sheep, and cattle. Amongst various suitable compounds, AAD 1566 eliminated many tested pathogenic nematode species, both at larval and adult stages, at a dose of 2.5 mg/kg bodyweight in sheep and 5.0 mg/kg bodyweight in cattle. The same doses were sufficient to cure animals infected with resistant or multi-drug-resistant nematode isolates. These findings, complemented by the good tolerability and low toxicity to mammals, suggest that AAD 1566, monepantel, would be a suitable anthelmintic drug development candidate

Haemonchus contortus Acetylcholine Receptors of the DEG-3 Subfamily and Their Role in Sensitivity to Monepantel

Gastro-intestinal nematodes in ruminants, especially Haemonchus contortus, are a global threat to sheep and cattle farming. The emergence of drug resistance, and even multi-drug resistance to the currently available classes of broad spectrum anthelmintics, further stresses the need for new drugs active against gastro-intestinal nematodes. A novel chemical class of synthetic anthelmintics, the Amino-Acetonitrile Derivatives (AADs), was recently discovered and the drug candidate AAD-1566 (monepantel) was chosen for further development. Studies with Caenorhabditis elegans suggested that the AADs act via nicotinic acetylcholine receptors (nAChR) of the nematode-specific DEG-3 subfamily. Here we identify nAChR genes of the DEG-3 subfamily from H. contortus and investigate their role in AAD sensitivity. Using a novel in vitro selection procedure, mutant H. contortus populations of reduced sensitivity to AAD-1566 were obtained. Sequencing of full-length nAChR coding sequences from AAD-susceptible H. contortus and their AAD-1566-mutant progeny revealed 2 genes to be affected. In the gene monepantel-1 (Hco-mptl-1, formerly named Hc-acr-23H), a panel of mutations was observed exclusively in the AAD-mutant nematodes, including deletions at intron-exon boundaries that result in mis-spliced transcripts and premature stop codons. In the gene Hco-des-2H, the same 135 bp insertion in the 5′ UTR created additional, out of frame start codons in 2 independent H. contortus AAD-mutants. Furthermore, the AAD mutants exhibited altered expression levels of the DEG-3 subfamily nAChR genes Hco-mptl-1, Hco-des-2H and Hco-deg-3H as quantified by real-time PCR. These results indicate that Hco-MPTL-1 and other nAChR subunits of the DEG-3 subfamily constitute a target for AAD action against H. contortus and that loss-of-function mutations in the corresponding genes may reduce the sensitivity to AADs

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Orientably-regular maps on twisted linear fractional groups

We present an enumeration of orientably-regular maps with automorphism group isomorphic to the twisted linear fractional group $M(q^2)$ for any odd prime power $q$