Attractive interactions between functional groups in crowded molecules: The solid state structures of diethyl 2-cyano(2 '-nitrophenyl)methyltartronate and diethyl (2 '-,6 '-dinitrophenyl)methyltartronate

The molecular structures of two substituted diethyl tartronates show a variety of interactions between functional groups. Oxygen atoms interact with the electron deficient carbon and nitrogen atoms of nitrile and nitro groups which in response show small distortions from their normal geometries. Short O . . . H contacts between benzyl hydrogen atoms and ortho nitro groups indicate some weak hydrogen bonding effects. Crystal data: C15H16N2O7, Mr = 336.3, a = 7.668(2), b = 7.961(3), c = 15.244(3) Angstrom, alpha = 86.78(1), beta = 81.56(1), gamma = 61.92(1)degrees, triclinic, P (1) over bar, Z = 2; C14H16N2O9, MY = 356.3, a = 7.786(2), b = 10.324(2), c = 11.155(4) Angstrom, alpha = 71.43(2), beta = 77.21(2), gamma = 76.40(3)degrees, triclinic, P (1) over bar and Z = 2

In vitro and in vivo pharmacodynamics of three novel antileishmanial lead series

Objectives: Three new chemical series (bicyclic nitroimidazoles, aminopyrazoles and oxaboroles) were selected by Drugs for Neglected Diseases initiative as potential new drug leads for leishmaniasis. Pharmacodynamics studies included both in vitro and in vivo efficacy, cross-resistance profiling against the current antileishmanial reference drugs and evaluation of their cidal activity potential. Methods: Efficacy against the reference laboratory strains of Leishmania infantum (MHOM/MA(BE)/67/ITMAP263) and L. donovani (MHOM/ET/67/L82) was evaluated in vitro on intracellular amastigotes and in vivo in the early curative hamster model. Cidal activity was assessed over a period of 15 days in an in vitro ‘time-to-kill’ assay. Cross-resistance was assessed in vitro on a panel of L. infantum strains with different degrees of resistance to either antimony, miltefosine or paromomycin. Results: All lead compounds showed potent and selective in vitro activity against the Leishmania strains tested and no cross-resistance could be demonstrated against any of the current antileishmanial drugs. Cidal activity was obtained in vitro for all series within 15 days of exposure with some differences noted between L. donovani and L. infantum. When evaluated in vivo, all lead compounds showed high efficacy and no adverse effects were observed. Conclusions: The new lead series were shown to have cidal pharmacodynamic activity. The absence of cross-resistance with any of the current antileishmanial drugs opens possibilities for combination treatment to reduce the likelihood of treatment failures and drug resistance. Keywords: Leishmania, Efficacy, Pharmacodynamics, Oxaboroles, Aminopyrazoles, Nitroimidazole

Optimal control of Atlantic population Canada geese

Management of Canada geese (Branta canadensis) can be a balance between providing sustained harvest opportunity while not allowing populations to become overabundant and cause damage. In this paper, we focus on the Atlantic population of Canada geese and use stochastic dynamic programming to determine the optimal harvest strategy over a range of plausible models for population dynamics. There is evidence to suggest that the population exhibits significant age structure, and it is possible to reconstruct age structure from surveys. Consequently the harvest strategy is a function of the age composition, as well as the abundance, of the population. The objective is to maximize harvest while maintaining the number of breeding adults in the population between specified upper and lower limits. In addition, the total harvest capacity is limited and there is uncertainty about the strength of density-dependence. We find that under a density-independent model, harvest is maximized by maintaining the breeding population at the highest acceptable abundance. However if harvest capacity is limited, then the optimal long-term breeding population size is lower than the highest acceptable level, to reduce the risk of the population growing to an unacceptably large size. Under the proposed density-dependent model, harvest is maximized by maintaining the breeding population at an intermediate level between the bounds on acceptable population size; limits to harvest capacity have little effect on the optimal long-term population size. It is clear that the strength of density-dependence and constraints on harvest significantly affect the optimal harvest strategy for this population. Model discrimination might be achieved in the long term, while continuing to meet management goals, by adopting an adaptive management strategy