Analysis, design and "in silico" evaluation of e-selectin antagonists

E-selectin, is member of a family of cell-adhesion proteins, which plays a crucial role in many physiological processes and diseases [1], and in particular, in the early phases of the inflammatory response. Its role is to promote the tethering and the rolling of leukocytes along the endothelial surface [2]. These steps are then followed by integrin-mediated firm adhesion and final transendothelial migration. Therefore, control of the leukocyte-endothelial cell adhesion process may be useful in cases, where excessive recruitment of leukocytes can contribute to acute or chronic diseases such as stroke, reperfusion injury, psoriasis or rheumatoid arthritis [3]. In this work, efforts to develop in silico-based protocols to study the interaction between E-selectin and its ligands, are presented. Hence, different protocols had to be developed and validated. In particular, a new procedure for the analysis of the conformational preferences of E-selectin antagonists was established and the results compared to those obtained with the MC(JBW)/SD approach, which had already demonstrated its validity in the past [161,168]. Thus, the comparison between the two protocols permitted to recognize a different conformational preference of the two methods for the orientation of the sialic acid moiety of sLex (3) (torsions Φ3 and Ψ3, Figure A), which reflects the contrasting opinions existing for the conformation adopted by sLex (3) in solution [150–168]. A more detailed analysis revealed that probably both approaches deliver only a partially correct view and that in reality, in solution, sLex (3) exists as a mixture of low energy conformers and not as supposed to date [150–154,161–163] as a population of a single conformer. In addition, a docking routine was established and the impact of different partialcharge methods and of explicit solvation on the binding mode studied. MD simulations enabled to gain an insight into the dynamical character of the protein-ligand interactions. In particular, the observations done in an atomic-force microscopy study [350], describing the interactions between the carboxylic group of sLex and Arg97, and between the 3– and 4–hydroxyls of fucose and the calcium ion, as the two main energy barriers for the dissociation process of the protein-ligand complex, found confirmation in our MD-investigations. Thus, these two contacts always lasted longer than any other in the MD simulation. QSAR-models with Quasar [270–272,351] and Raptor [315,316,335] were successfully derived and will permit a semi-quantitative in silico estimation of the binding affinity for the ligands that will be designed in the future. Finally, the developed protocols and models were applied for the development of new E-selectin antagonists. Unfortunately, to date, only few biological data is available to evaluate our design strategies. However, the impact of the ligand’s pre-organization on the binding affinity could be established at least for the Lexcore of sLex (3). Hence, the importance of the exo-anomeric effect, of the steric compression, and of the hydrophobic interaction between the methyl group of fucose and the β-face of galactose was clearly demonstrated

Acid Mine Drainage (AMD): causes, treatment and case studies

This paper describes Acid Mine Drainage (AMD) generation and its associated technical issues. As AMD is recognized as one of the more serious environmental problems in the mining industry, its causes, prediction and treatment have become the focus of a number of research initiatives commissioned by governments, the mining industry, universities and research establishments, with additional inputs from the general public and environmental groups. In industry, contamination from AMD is associated with construction, civil engineering mining and quarrying activities. Its environmental impact, however, can be minimized at three basic levels: through primary prevention of the acid-generating process; secondary control, which involves deployment of acid drainage migration prevention measures; and tertiary control, or the collection and treatment of effluent. (c) 2005 Elsevier Ltd. All rights reserved

Overview On Extraction and Separation of Rare Earth Elements from Red Mud: Focus on Scandium

The article provides an overview of the methods used for processing of red mud to extract rare earth elements (REEs). Red mud is a toxic and highly alkaline waste. Several methods have been adopted and been practiced all over the world for the processing of red mud. Complex processing of red mud is cost-effective since red mud contains elements such as iron, aluminum, titanium, calcium, and rare earth metals. It has been observed that the acid leaching of red mud can almost completely recover the rare earth elements in the solution with various individual techniques and also a combination of them. Therefore, the choice of extraction method depends on the form in which the element occurs in the solution. However, relatively low concentrations of rare earth in the solution and significant amounts of impurities increase the cost of getting the final commercial products. To ensure the cost-effectiveness of the process involving rare earth's extraction from red mud, it is necessary to increase their content by several times. This article presents the various studies that have been carried out in these aspects and the possibility of making this resource a sustainable one for REE extraction with a special focus on scandium replenishment

Processing of Low-Quality Gibbsite-Kaolinite Bauxites

The results of studies on the processing of gibbsite-kaolinite bauxite are presented. The developed technology includes preliminary chemical activation and thermal transformation during enrichment to obtain a concentrate suitable for processing by the Bayer method. As a result of the chemical activation of gibbsite-kaolinite bauxite in a solution of sodium bicarbonate, a change in the phase composition occurs, which made it possible to improve the results of gravity enrichment with the production of a coarse-grained gibbsite fraction. The transformation of bauxite in the temperature range of 900–1000 °C is explained by the decomposition reactions of siderite, gibbsite, kaolinite, calcite, dolomite and sodium ferro-sulfide oxide, as well as the formation of sodium aluminosilicate, hematite, quartz and the chemically stable phase of corundum. The optimum firing temperature of bauxite is 950 °C, after which, as a result of alkaline treatment during chemical enrichment, the extraction of SiO2 into solution was 74.9%. A silicon modulus of enriched bauxite 10.9 units was obtained. As a result of the autoclave leaching of gibbsite-kaolinite bauxite after a two-stage enrichment, the maximum extraction of alumina into solution was 87.4%. The yield of red mud during the processing of bauxite enriched and calcined at 950 °C was 37.62%. During the autoclave leaching of bauxite without enrichment, the yield of red mud was 71%

A Review on Chemical versus Microbial Leaching of Electronic Wastes with Emphasis on Base Metals Dissolution

There is a growing interest in electronic wastes (e-wastes) recycling for metal recovery because the fast depletion of worldwide reserves for primary resources is gradually becoming a matter of concern. E-wastes contain metals with a concentration higher than that present in the primary ores, which renders them as an apt resource for metal recovery. Owing to such aspects, research is progressing well to address several issues related to e-waste recycling for metal recovery through both chemical and biological routes. Base metals, for example, Cu, Ni, Zn, Al, etc., can be easily leached out through the typical chemical (with higher kinetics) and microbial (with eco-friendly benefits) routes under ambient temperature conditions in contrast to other metals. This feature makes them the most suitable candidates to be targeted primarily for metal leaching from these waste streams. Hence, the current piece of review aims at providing updated information pertinent to e-waste recycling through chemical and microbial treatment methods. Individual process routes are compared and reviewed with focus on non-ferrous metal leaching (with particular emphasis on base metals dissolution) from some selected e-waste streams. Future outlooks are discussed on the suitability of these two important extractive metallurgical routes for e-waste recycling at a scale-up level along with concluding remarks

Recent advances on hydrometallurgical recovery of critical and precious elements from end of life electronic wastes - a review

International audienceWaste electrical and electronic equipment (WEEE) contains economically significant levels of precious, critical metals and rare earth elements, apart from base metals and other toxic compounds. Recycling and recovery of critical elements from WEEEs using a cost-effective technology are now one of the top priorities in metallurgy due to the rapid depletion of their natural resources. More than 150 publications on WEEE management, leaching and recovery of metals from WEEE were reviewed in this work, with special emphasize on the recent research (2015-2018). This paper summarizes the recent progress regarding various hydrometallurgical processes for the leaching of critical elements from WEEEs. Various methodologies and techniques for critical elements selective recovery (using ionic liquids, solvent extraction, electrowinning, adsorption, and precipitation) from the WEEEs leachates are discussed. Future prospects regarding the use of WEEEs as secondary resources for critical raw materials and its techno-economical and commercial beneficiaries are discussed