Three Small Molecule Entities (MPK18, MPK334 and YAK308) with Activity against Haemonchus contortus In Vitro

Due to widespread multi-drug resistance in parasitic nematodes of livestock animals, there is an urgent need to discover new anthelmintics with distinct mechanisms of action. Extending previous work, here we screened a panel of 245 chemically-diverse small molecules for anti-parasitic activity against Haemonchus contortus—an economically important parasitic nematode of livestock. This panel was screened in vitro against exsheathed third-stage larvae (xL3) of H. contortus using an established phenotypic assay, and the potency of select compounds to inhibit larval motility and development assessed in dose-response assays. Of the 245 compounds screened, three—designated MPK18, MPK334 and YAK308—induced non-wildtype larval phenotypes and repeatedly inhibited xL3-motility, with IC₅₀ values of 45.2 µM, 17.1 µM and 52.7 µM, respectively; two also inhibited larval development, with IC₅₀ values of 12.3 µM (MPK334) and 6.5 µM (YAK308), and none of the three was toxic to human liver cells (HepG2). These findings suggest that these compounds deserve further evaluation as nematocidal candidates. Future work should focus on structure–activity relationship (SAR) studies of these chemical scaffolds, and assess the in vitro and in vivo efficacies and safety of optimised compounds against adults of H. contortus.     

High-speed all-optical switching in ion-implanted silicon-on-insulator microring resonators

We demonstrate high-speed all-optical switching via vertical excitation of an electron-hole plasma in an oxygen-ion implanted silicon-on-insulator microring resonator. Based on the plasma dispersion effect the spectral response of the device is rapidly modulated by photoinjection and subsequent recombination of charge carriers at artificially introduced fast recombination centers. At an implantation dose of 1 x 10(12) cm(-2) the carrier lifetime is reduced to 55 ps, which facilitates optical switching of signal light in the 1.55 mum wavelength range at modulation speeds larger than 5 Gbits/s.     

Isolation and Structural Elucidation of Armeniaspirols A–C: Potent Antibiotics against Gram‐Positive Pathogens

In an antibiotic lead discovery program, the known strain Streptomyces armeniacus DSM19369 has been found to produce three new natural products when cultivated on a malt‐containing medium. The challenging structural elucidation of the isolated compounds was achieved by using three independent methods, that is, chemical degradation followed by NMR spectroscopy, a computer‐assisted structure prediction algorithm, and X‐ray crystallography. The compounds, named armeniaspirol A–C ( 2 – 4 ), exhibit a compact, hitherto unprecedented chlorinated spiro[4.4]non‐8‐ene scaffold. Labeling experiments with [1‐¹³C] acetate, [1,2‐¹³C2] acetate, and [U‐¹³C] proline suggest a biosynthesis through a rare two‐chain mechanism. Armeniaspirols displayed moderate to high in vitro activities against Gram‐positive pathogens such as methicillin‐resistant S. aureus (MRSA) or vancomycin resistant E. faecium (VRE). As analogue 2 was active in vivo in an MRSA sepsis model, and showed no development of resistance in a serial passaging experiment, it represents a new antibiotic lead structure.     

The golden number and Fibonacci sequences in the design of voting structures

Some distinguished types of voters, as vetoes, passers or nulls, as well as some others, play a significant role in voting systems because they are either the most powerful or the least powerful voters in the game independently of the measure used to evaluate power. In this paper we are concerned with the design of voting systems with at least one type of these extreme voters and with few types of equivalent voters. With this purpose in mind we enumerate these special classes of games and find out that its number always follows a Fibonacci sequence with smooth polynomial variations. As a consequence we find several families of games with the same asymptotic exponential behavior except for a multiplicative factor which is the golden number or its square. From a more general point of view, our studies are related with the design of voting structures with a predetermined importance ranking.     

Optimal control of the freezing time in the Hegselmann–Krause dynamics

We study the optimal control problem of minimizing the freezing time in the discrete Hegselmann–Krause (HK) model of opinion dynamics. The underlying model is extended with a set of strategic agents that can freely place their opinion at every time step. Indeed, if suitably coordinated, the strategic agents can significantly lower the freezing time of an instance of the HK model. We give several lower and upper worst-case bounds for the freezing time of a HK system with a given number of strategic agents, while still leaving some gaps for future research.     

Structure of neutron-rich nuclei around the N = 126 closed shell; the yrast structure of 205Au126 up to spin-parity I^{\pi} = (19/2+)

Heavy neutron-rich nuclei have been populated through the relativistic fragmentation of a $\ensuremath ^{208}_{\ 82}{\rm Pb}$ beam at $\ensuremath E/A = 1$ GeV on a $\ensuremath 2.5 {\rm g/cm^2}$ thick Be target. The synthesised nuclei were selected and identified in-flight using the fragment separator at GSI. Approximately 300 ns after production, the selected nuclei were implanted in an $\ensuremath \sim 8$ mm thick perspex stopper, positioned at the centre of the RISING $\ensuremath \gamma$ -ray detector spectrometer array. A previously unreported isomer with a half-life $\ensuremath T_{1/2} = 163(5)$ ns has been observed in the N = 126 closed-shell nucleus $\ensuremath ^{205}_{\ 79}{\rm Au}$ . Through $ \gamma$ -ray singles and $ \gamma$ - $ \gamma$ coincidence analysis a level scheme was established. The comparison with a shell model calculation tentatively identifies the spin-parity of the excited states, including the isomer itself, which is found to be $\ensuremath I^{\pi} = (19/2^+)$ .     

Particle tracking velocimetry of the flow field around a collapsing cavitation bubble

The velocity field in the vicinity of a laser-generated cavitation bubble in water is investigated by means of particle tracking velocimetry (PTV). Two situations are explored: a bubble collapsing spherically and a bubble collapsing aspherically near a rigid wall. In the first case, the accuracy of the PTV method is assessed by comparing the experimental data with the flow field around the bubble as obtained from numerical simulations of the radial bubble dynamics. The numerical results are matched to the experimental radius–time curve extracted from high-speed photographs by tuning the model parameters. Trajectories of tracer particles are calculated and used to model the experimental process of the PTV measurement. For the second case of a bubble collapsing near a rigid wall, both the bubble shape and the velocity distribution in the fluid around the bubble are measured for different standoff parameters γ at several instants in time. The results for γ > 1 are compared with the corresponding results of a boundary-integral simulation. For both cases, good agreement between simulation and experiment is found.     

Relationship between structure and retention of polychlorinated diphenyl ethers (PCDE) in HRGC in comparison with other groups of halogenated aromatic compounds

The GC-retention of 106 polychlorinated diphenyl ethers (PCDE) has been examined on five different stationary phases representing a broad range of polarities: CP Sil8/10%C18 (Sil8-type with 10% of octadecyl groups), SE 54 (methyl-/5% phenyl-polysiloxane), OV 1701 (7% phenyl-/7% cyanopropyl-polysiloxane), DB Dioxin (a polysiloxane phase, which incorporates 44% methyl, 28% phenyl, 20% cyanopropyl and 8% polyethylene groups) and SP 2331 (90% biscyanopropyl-/10% phenylcyanopropyl (1:1)-polysiloxane). Standard narrow-bore columns (0.2–0.3 mm i.d.) were used.Structural principles for the retention of the PCDEs in gas chromatography were compared with the retention behaviour of the closely related polychlorinated biphenyls (PCB) and the tetrachloro-methyl-diphenylmethanes (tetrachlorobenzyltoluenes, TCBT). The structure-retention behaviour of the PCDEs is partly similar to the TCBTs in spite of the differences in polarity. The differences between the structure-retention behaviour of the PCDEs and the PCBs can best be explained with the increasing possibility of a coplanar arrangement of PCBs with a decreasing number of chlorine substituents in the ortho positions of the phenyl-phenyl bond.