Discovery of novel non-cyclam polynitrogenated CXCR4 coreceptor inhibitors

HIV cell fusion and entry have been validated as targets for therapeutic intervention against infection. Bicyclams were the first low-molecular-weight compounds to show specific interaction with CXCR4. The most potent bicyclam was AMD3100, in which the two cyclam moieties are tethered by a 1,4-phenylenebis(methylene) bridge. It was withdrawn from clinical trials owing to its lack of oral bioavailability and cardiotoxicity. We have designed a combinatorial library of non-cyclam polynitrogenated compounds by preserving the main features of AMD3100. At least two nitrogen atoms on each side of the p-phenylene moiety, one in the benzylic position and the other(s) in the heterocyclic system were maintained, and the distances between them were similar to the nitrogen atom distances in cyclam. A selection of diverse compounds from this library were prepared, and their in vitro activity was tested in cell cultures against HIV strains. This led to the identification of novel potent CXCR4 coreceptor inhibitors without cytotoxicity at the tested concentrations.     

Anti-Trypanosoma cruzi Activity of Metabolism Modifier Compounds

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and affects over 6 million people worldwide. Development of new drugs to treat this disease remains a priority since those currently available have variable efficacy and frequent adverse effects, especially during the long regimens required for treating the chronic stage of the disease. T. cruzi modulates the host cell-metabolism to accommodate the cell cytosol into a favorable growth environment and acquire nutrients for its multiplication. In this study we evaluated the specific anti-T. cruzi activity of nine bio-energetic modulator compounds. Notably, we identified that 17-DMAG, which targets the ATP-binding site of heat shock protein 90 (Hsp90), has a very high (sub-micromolar range) selective inhibition of the parasite growth. This inhibitory effect was also highly potent (IC₅₀ = 0.27 μmol L⁻¹) against the amastigote intracellular replicative stage of the parasite. Moreover, molecular docking results suggest that 17-DMAG may bind T. cruzi Hsp90 homologue Hsp83 with good affinity. Evaluation in a mouse model of chronic T. cruzi infection did not show parasite growth inhibition, highlighting the difficulties encountered when going from in vitro assays onto preclinical drug developmental stages.     

Power consumption reduction through elastic data rate adaptation in survivable multi-layer optical networks

Network survivability requires the provisioning of backup resources in order to protect active traffic against any failure scenario. Backup resources, however, can remain unused most of the time while the network is not in failure condition, inducing high power consumption wastage, if fully powered on. In this paper, we highlight the power consumption wastage of the additional resources for survivability in IP/multi-protocol label switching (MPLS) over dense wavelength division multiplexing multi-layer optical networks. We assume MPLS protection switching as the failure recovery mechanism in the network, a solution interesting for current network operators to ensure fast recovery as well as fine-grained recovery treatment per label switched path. Next, we quantitatively show how elastic optical technologies can effectively reduce such a power consumption by dynamically adjusting the data rate of the transponders to the carried amount of traffic.     

Quality of industrial pectin extracted from peach pomace at different pH and temperatures

Two molecular characteristics of pectin related to good gelling properties of the polysaccharide are degree of esterification (DE) and length of molecular chain. Industrial pectin from peach pomace was extracted at different pH and temperatures. DE, acetyl content, intrinsic viscosity and molecular weight of the samples were analysed, and the effect of the extraction conditions on these parameters were studied. On the basis that high DE and intrinsic viscosity indicate good gelling pectin or good quality of pectin has chains with low acetyl content, all extracted samples were compared using a multicriteria method in order to find the best extraction conditions. © 1999 Society of Chemical Industry     

Ecological Compensation Estimation of Soil and Water Conservation Based on Cost-Benefit Analysis

Soil and water conservation ecological compensation can be simply defined as a monetary payment to offset the environmental loss. An illustration is given in this study describing the payment compensation to water resource conservation and soil losses in Erlongshan reservoir catchment, China. A semi-distributed hydrological SWAT model was applied to establish compensation standard considering six scenarios of land use changes by combined application of remote sensing and geographic information systems. Cost-benefit analysis (CBA) method is applied to evaluate the function of soil and water conservation, of which marginal opportunity cost and market value methods have been explored calculate the cost and benefit of water and soil conservation ecological function from provider and beneficiaries. Finally the ecological compensation of soil and water conservation for different land-use scenarios is calculated incorporating benefit apportion coefficient. The results provide an economically evaluated and market-oriented standard for the study of eco-compensation of environmental services and will be of great benefit to the implementation of soil and water conservation at a mesoscale catchment scale.     

Low-intensity optical bistability in an active Fabry-Perot mirror induced by input-phase-insensitive parametric downconversion

A Fabry-Perot resonator filled with second-order nonlinear optical material is investigated. Attention is devoted to making the resonator act as a nonlinear mirror for ultralow-intensity light signals that can be switched by a control beam at the second-harmonic frequency. The interaction process is an input-phase-independent parametric downconversion. The theoretical problem is solved through implementation of a dummy variable method optimized for a parametric process. Efficient amplification and bistability of low-intensity signals have been found.     

Forthcoming Contributions

Table of Contents

Forthcoming Contributions     

Reconstructing 3D light microscopic images using the EM algorithm

An iterative method to recover perfectly focused images from a set of light microscopic images is proposed. The method is based on the EM algorithm, and it assumes a prior knowledge about the Point Spread Function of the optical system, as well as about the optical parameter settings of the acquisition system. The method is applied to the visualization of integrated circuit samples through an optical microscope and to the recovery of their depth information.     

An analysis of the determinants in Economics and Business publications by Spanish universities between 1994 and 2004

The objective of this study consists, firstly, of quantifying differences between Spanish universities’ output (in terms of publications and citations), and secondly, analysing its determinants. The results obtained show that there are factors which have a positive influence on these indicators, such as having a third-cycle programme, with public financing obtained in competitive selection procedures, having a large number of full-time researchers or involvement in collaborations with international institutions. However, other factors which appear to have the opposite effect were also noted. These include a higher number of students per lecturer or a lower proportion of lecturers with recognised six-year periods.