Assessment of the Activity of Decoquinate and Its Quinoline-O-Carbamate Derivatives against Toxoplasma gondii In Vitro and in Pregnant Mice Infected with T. gondii Oocysts

The quinolone decoquinate (DCQ) is widely used in veterinary practice for the treatment of bacterial and parasitic infections, most notably, coccidiosis in poultry and in ruminants. We have investigated the effects of treatment of Toxoplasma gondii in infected human foreskin fibroblasts (HFF) with DCQ. This induced distinct alterations in the parasite mitochondrion within 24 h, which persisted even after long-term (500 nM, 52 days) treatment, although there was no parasiticidal effect. Based on the low half-maximal effective concentration (IC₅₀) of 1.1 nM and the high selectivity index of >5000, the efficacy of oral treatment of pregnant mice experimentally infected with T. gondii oocysts with DCQ at 10 mg/kg/day for 5 days was assessed. However, the treatment had detrimental effects, induced higher neonatal mortality than T. gondii infection alone, and did not prevent vertical transmission. Thus, three quinoline-O-carbamate derivatives of DCQ, anticipated to have better physicochemical properties than DCQ, were assessed in vitro. One such compound, RMB060, displayed an exceedingly low IC₅₀ of 0.07 nM, when applied concomitantly with the infection of host cells and had no impact on HFF viability at 10 µM. As was the case for DCQ, RMB060 treatment resulted in the alteration of the mitochondrial matrix and loss of cristae, but the changes became apparent at just 6 h after the commencement of treatment. After 48 h, RMB060 induced the expression of the bradyzoite antigen BAG1, but TEM did not reveal any other features reminiscent of bradyzoites. The exposure of infected cultures to 300 nM RMB060 for 52 days did not result in the complete killing of all tachyzoites, although mitochondria remained ultrastructurally damaged and there was a slower proliferation rate. The treatment of mice infected with T. gondii oocysts with RMB060 did reduce parasite burden in non-pregnant mice and dams, but vertical transmission to pups could not be prevented.     

To what extent does the dual Banach spaceE′ determine the polynomials overE?

We show that under conditions of regularity, ifE′ is isomorphic toF′, then the spaces of homogeneous polynomials overE andF are isomorphic. Some subspaces of polynomials more closely related to the structure of dual spaces (weakly continuous, integral, extendible) are shown to be isomorphic in full generality.     

Weighted bankruptcy rules and the museum pass problem

In this paper we introduce and characterize some allocation rules for weighted bankruptcy problems. We illustrate the relevancy of weighted bankruptcy by applying it to analyse the museum pass problem, introduced by Ginsburgh and Zang (2003). This application is completed with the analysis of real data for the “Card Musei” of the Municipality of Genova.     

A generalization of the half-normal distribution

In this paper we introduce an extension of the half-normal distribution in order to model a great variety of non-negative data. Its hazard rate function can be decreasing or increasing, depending on its parameters. Some properties of this new distribution are presented. For example, we give a general expression for the moments and a stochastic representation. Also, the cumulative distribution function, the hazard rate function, the survival function and the quantile function can be easily evaluated. Maximum likelihood estimators can be computed by using numerical procedures. Finally, a real-life dataset has been presented to illustrate its applicability.     

Lie algebras with quadratic dimension equal to 2

The quadratic dimension of a Lie algebra is defined as the dimension of the linear space spanned by all its invariant non-degenerate symmetric bilinear forms. We prove that a quadratic Lie algebra with quadratic dimension equal to 2 is a local Lie algebra, this is to say, it admits a unique maximal ideal. We describe local quadratic Lie algebras using the notion of double extension and characterize those with quadratic dimension equal to 2 by the study of the centroid of such Lie algebras. We also give some necessary or sufficient conditions for a Lie algebra to have quadratic dimension equal to 2. Examples of local Lie algebras with quadratic dimension larger than 2 are given.     

Measures on the Product of Compact Spaces

 If K is an uncountable metrizable compact space, we prove a “factorization” result for a wide variety of vector valued Borel measures μ defined on K ⁿ . This result essentially says that for every such measure μ there exists a measure μ′ defined on K such that the measure μ of a product A ₁ × ⋯ × A _n of Borel sets of K equals the measure μ′ of the intersection A ₁′∩⋯∩A _n ′, where the A _i ′’s are certain transforms of the A _i ’s. Partially supported by DGICYT grant PB97-0240. Received August 23, 2001; in revised form March 21, 2002     

Full prediction of the broadband optical modulation performance of a twisted nematic liquid crystal cell

We present a procedure to obtain the physical parameters responsible of twisted nematic liquid crystal (LC) cells optical modulation. The novelty of our approach is based on the use of spectroscopic measurements of the light transmitted by the system polarizer-LC cell-analyzer, combined with a previously proposed simple physical model of the LC twist and tilt distribution along cell. The procedure involves two steps: the first one yields off-state parameters like the LC director orientation, the twist angle, and the optical path difference (cell gap); the second step yields the effective retardances of the central and edge LC layers. The use of a spectroscopic method provides a full characterization of the LC cell as a function of both the voltage and the wavelength. The complete procedure leads to a very accurate prediction of the transmitted light broadband spectrum, as well as the complex (amplitude and phase) modulation for any wavelength within the calibration range.     

Polarization vortices generation by diffraction from a four quadrant polarization mask

In this work we analyze the generation of an array of polarization singularities (polarization vortices) in the diffracted field produced by a simple four quadrant polarization mask, which transmits two orthogonal linear states in different quadrants. We use the Jones matrix method to analyze the polarization and diffraction characteristics of the diffracted field. We show that the same four quadrant mask can be used to generate either azimuth or ellipticity singularities simply by changing the input polarization. We experimentally verify the theory by generating the four quadrant polarization mask using a twisted nematic liquid crystal display. We show experimental results that confirm the theoretical predictions.     

Globally optimized packings of non-uniform size spheres in $$\mathbb {R}^{d}$$: a computational study

In this work we discuss the following general packing problem: given a finite collection of d-dimensional spheres with (in principle) arbitrarily chosen radii, find the smallest sphere in \(\mathbb {R}^{d}\) that contains the given d-spheres in a non-overlapping arrangement. Analytical (closed-form) solutions cannot be expected for this very general problem-type: therefore we propose a suitable combination of constrained nonlinear optimization methodology with specifically designed heuristic search strategies, in order to find high-quality numerical solutions in an efficient manner. We present optimized sphere configurations with up to \(n = 50\) spheres in dimensions \(d = 2, 3, 4, 5\). Our numerical results are on average within 1% of the entire set of best known results for a well-studied model-instance in \(\mathbb {R}^{2}\), with new (conjectured) packings for previously unexplored generalizations of the same model-class in \(\mathbb {R}^{d}\) with \(d= 3, 4, 5.\) Our results also enable the estimation of the optimized container sphere radii and of the packing fraction as functions of the model instance parameters n and 1 / n, respectively. These findings provide a general framework to define challenging packing problem-classes with conjectured numerical solution estimates.