Mycobacterium tuberculosis, the causative agent of pulmonary tuberculosis, infects one-third of the world’s human population. Despite the multiplicity of antimicrobial mechanisms mounted by its host, M. tuberculosis shows a remarkable ability to survive either by evoking survival strategies or by interference with critical macrophage functions that are required to successfully respond to the infection. It has been postulated that the outcome of exposure to M. tuberculosis (in terms of disease symptoms) largely depends upon the selective gene expression of tuberculosis bacilli along with activation of specific signaling pathways in the infected host cells during different phases of infection. In this perspective, determination of the complete genome sequence of Mycobacterium tuberculosis has provided crucial information with respect to the physiology of this bacterium and the pathogenesis of tuberculosis. However, putative functional annotation to all hypothetical proteins coded by M. tuberculosis genome remains complex. One important outcome of the genome-sequencing project was the discovery of two new multigene families designated PE and PPE. About 10% of the M. tuberculosis coding capacity is devoted to the PE and PPE genes, named for the Pro-Glu (PE) and Pro-Pro-Glu (PPE) motifs near the N terminus of their gene products. In addition to these motifs, proteins of PE family share N-terminal domains of approximately 100 amino acids, whereas the PPE proteins possess an N-terminal domain of about 180 amino acids. Many PE and PPE proteins are composed only of these N-terminal homologous domains. However, other members possess an additional C-terminal segment of variable length, often composed of multiple copies of polymorphic GC rich sequences (PGRS). The uniqueness of the PE genes is further illustrated by the fact that these genes are restricted to mycobacteria. However, despite their abundance in mycobacteria, very little is known regarding the expression or the functions of PE family genes. Although the PE and PPE families of mycobacterial proteins are the focus of intense research, no precise function has so far been unraveled for any member of these families. In perspective of above-mentioned observations, we have chosen Rv0754 as a representative PE family gene. Rv0754 was shown to be upregulated in tubercle bacilli upon infection of bone marrow derived macrophages as well as in M. tuberculosis isolated from alveolar macrophages of infected mice. In the current investigation, we demonstrate that Rv0754 is hypoxia responsive gene based on promoter or transcript expression analysis. Further, extensive bioinformatics analysis predicated that Rv0754 posses possible Phosphoglycerate Mutase domain, an enzyme known for its significant role not only in the glycolytic pathway of the carbohydrate metabolism, but also for the crucial cell fate decision during conditions like oxidative stress as well as infection. Experimental data clearly suggests that hypoxic environment dependent expression of Rv0754 imparts resistance to macrophages from oxidative stress. These findings could be attributed to the presence of catalytically active Phosphoglycerate Mutase domain of Rv0754. More often, sophisticated regulation/modulation of key signaling events regulate the critical cell fate decisions during oxidative stress. In this context, TLR2 dependent triggering of PI3K-ERK1/2- NF-κB signaling axis by Rv0754 may be operative in imparting resistance to oxidative stress. Further, Rv0754 triggers COX-2 expression by activating PI3K-ERK1/2-NF-κB cascade in mouse macrophages. These observations are of relevance as Rv0754 is associated with cell wall and is exposed outside the surface of the bacterium suggesting the possible access to intracellular compartments of the infected macrophages. Additionally, Rv0754 elicited humoral antibody reactivities in a panel of human sera or in cerebrospinal fluid samples obtained from different clinical categories of tuberculosis patients. DNA immunizations experiments in mice clearly suggested that Rv0754 is an immunodominant antigen demonstrating significant T cell and humoral reactivity. These observations clearly advocate that Rv0754 protein is expressed in vivo during active infection with M. tuberculosis and that the Rv0754 is immunogenic. Taken together, our findings suggest that Rv0754 is a novel PE_PGRS protein with unique features which could generate conditions that favor survival of the mycobacteria.

Owing to their key role in mucosal functioning as surface barriers with biospecific interaction potentials, the mucins are interesting candidates for use as surface modifiers in biomaterials applications. In this work, “mild” fractionation procedures were used to prepare mucins of bovine (BSM), porcine (PGM), and human (MG1) origin. Biophysicochemical analysis showed the prepared mucins to differ in size, charge, conformation, and composition. In turn, these factors were shown to govern mucin adsorption on hydrophilic and hydrophobic model surfaces. To enable for detailed coating analysis, methods for the qualitative and quantitative analysis of mucin-based coatings were developed. Of particular interest, a method for the determination of the fraction of surface-exposed, presumed bioactive proteins in a complex mucin coating was described. It was shown, using microscopy and activation assays, that mucin precoating effectively suppresses the neutrophil response towards a polymeric model biomaterial. Under optimal coating conditions, all mucins performed equally well, thus indicating them to be functionally similar. Coating analysis suggested that efficient mucin surface-shielding is critical for good mucin coating performance. Following a study on the complexation of albumin with preadsorbed mucin, we investigated the effect of mucin precoating on the conformation and neutrophil-activating properties of adsorbed host proteins. We found that mucin precoating greatly reduces the strong immune-response normally caused by adsorbed proinflammatory proteins (IgG and sIgA). Detailed coating analysis revealed that the fraction of surface-exposed protein in the mucin-protein composite influences the neutrophil response. Unexpectedly low neutrophil activation for composites containing near-monolayer concentrations of exposed IgG, suggested IgG to act synergistically with mucin on the surface. Conformational analysis supported this by showing that a preadsorbed mucin layer could stabilize adsorbed IgG through complexation. Our findings link well to the complex in vivo situation and suggest that functional mucosal mimics can be created in situ for improved biomaterials performance.

This report has investigated the ethical issues associated with mining or processing of materials that make them considered as controversial. For each material, the main areas of use and the top producing countries are analysed, followed by social and/or environmental issues as well as potential problems in the future. In total, 13 materials are discussed, of which most are minerals. The overall issues, that are recurring throughout the report and are important to be aware of are: child labor, low safety standards, mining activity resulting in deforestation or harming biodiversity, mining processes that affect communities (e.g. because of large water consumption) and the risks associated with widespread illegal mining. The report also provides research about organisations and initiatives that aim to affect the problems, and gives a brief view over tools that can be used to increase awareness of these issues.

Le complexe mafique–ultramafique lité Yacouba est intrusif au sein des granulites gneissiques du domaine archéen de Man (3,6-2,78 Ga) dans la région de Biankouma-Sipilou (ouest de la Côte d'Ivoire). Dans le secteur de Samapleu, il est composé de trois entités ; dépôt principal de Samapleu (SM), l’Extension 1 de Samapleu (E1) et l’occurrence de Yorodougou (Yo). Il comprend des horizons de webstérites, péridotites, chromitites, norites, gabbro-norites. Ces horizons (épaisseur cumulée de 80 à 200 m) sont inclinés de 70 à 80° vers le SE ; présentent une zonation concentrique, qui sont autant de caractéristiques d’un dyke ; un enracinement à plus de 600 m à partir de la surface avec une jonction des intrusions (SM, E1) plus en profondeur. Les contacts avec l’encaissant gneissique (localement site E1) sont marqués par une zone hybride (condition P = 7,5±1Kbar et T = 850°C ± 100°C) interprétées comme le résultat d'un métamorphisme de contact lors de la mise en place de l’intrusion en base de croûte à environ 22 km de profondeur. Les gneiss et granulites du socle, tout comme les faciès de la zone hybride, préservent des âges archéens (~2,78 Ga, U-Pb sur zircon). Des cristaux de rutile observés dans la zone hybride révèlent un âge U-Pb de 2,09 Ga interprété comme l'âge du métamorphisme de contact et donc de la mise en place de l'intrusion.La minéralisation en Ni-Cu (essentiellement disséminée avec des veines sulfurées subverticales semi-massives à massives) est composée de pentlandite, chalcopyrite, pyrrhotite, rarement pyrite. La texture des sulfures varie de matricielle, en filets, en gouttelettes, ou brèchique. Les réserves estimées des dépôts de Samapleu (SM et E1) font plus de 40 millions de tonnes à une teneur moyenne de 0,25% Ni et 0,22% Cu dans la partie supérieure des intrusions (Sama Nickel-CI, Août 2013). Des MGP riches en palladium (Pd) sont associés aux sulfures et plusieurs bandelettes de chromite sont également présentes. Ces observations suggèrent un liquide sulfuré immiscible formé à partir du liquide silicaté initial consécutivement à la saturation en soufre du système. Ces sulfures d’origine essentiellement mantellique ont été probablement formés par injection de plusieurs magmas. Cependant une partie de ces sulfures aurait pu se former par l’assimilation des roches granulitiques encaissantes.La composition du liquide parent révèle une composition de basalte à forte teneur en MgO et faible teneur en Ti et suggère que les intrusions de Samapleu se sont formées par fusion du manteau supérieur sous l’influence d'un panache mantellique. Ainsi, lors de leurs remontées, le magma a assimilé les roches granulites encaissantes environnantes. / The Yacouba layered complex intrudes the archean (3.6-2.78 Ga) Man field in the Biankouma-Sipilou area, western Ivory Coast. In Samapleu area, the complex is composed of three entities; Samapleu Main (SM); Samapleu Extension 1 (E1) and Yorodougou (Yo). It includes websterites, peridotites, chromitites, norites, gabbro-norites horizons. These horizons (total thickness of 80 to 200 m) inclined at 70-80° to the SE; arranged symmetrically with mafic layers at the center and ultramafic layers at both margins, are features of a dyke ; show a root more than 600 m from the surface with a junction intrusion (SM, E1) in more depth.At the E1 site, contacts of intrusions with the country rock gneiss are characterized by a hybrid zone (condition P = 7.5±1Kbar and T = 850°C ± 100°C) attributed to contact metamorphism during intrusion of the complex in the lower crust at a depth of about 22 km. Zircons in country rock gneisses and granulites, as well as in the hybrid facies, yield archean ages of ~ 2.78 Ga. Rutiles in the hybrid zone give a U-Pb age of 2.09 Ga, which is interpreted as the age of contact metamorphism and emplacement of the intrusion.The Ni-Cu mineralization (disseminated mainly with subvertical and semi-massive to massive sulfide veins) is composed of pentlandite, chalcopyrite, pyrrhotite and rare pyrite. The SM and E1 sites contain Ni and Cu sulfide deposit with reserves estimated as more than 40 million tons grading 0.25% Ni and 0.22% Cu in the upper portion (Sama Nickel-CI, August 2013). The sulfide textures range from matrix ore, net-textured, droplets or breccia textures. Zones enriched in PGM, particularly Pd, are associated with the sulfides and several chromite bands are also present. These observations suggest that an immiscible sulfide liquid formed from a parental silicate liquid and percolated through the crystal pile. These sulfides mainly mantle origin were probably formed by injecting several magmas. However few of these sulfides may have formed by the assimilation of country rocks.The parental melt composition has a basalt rich MgO and low Ti and suggest Samapleu intrusions were formed by melting of the upper mantle under the influence of a mantle plume. Thus, during its ascent, magma has assimilated the granulites country rocks.

Approved for public release, distribution is unlimited / Commander, Logistics Group, Western Pacific (COMLOGWESTPAC) is concerned with the delivery of high priority material, ordnance, and passengers to U.S. Navy ships due to a very large operations area and limited Combat Logistics Force (CLF) assets. High-speed vessels (HSVs) may have the potential to improve the delivery of these materials when used to complement existing logistics shuttle ships. This thesis quantifies current levels of traditional naval logistics support and provides comparison to HSV-based alternatives in various scenarios. The CLF Scenario Analysis Tool (CLFSAT), a newly developed discrete event simulation model of naval logistics support, performs the analysis. Given a scenario depicting combatant movements and operations, CLFSAT provides insight into the comparative performance of different supporting naval logistics force structures. This analysis determines that HSVs can be effective logistics platforms in specific scenarios when distributing high priority material, ordnance, and stores. HSVs are very effective in small theaters with short transit distances, but for larger theaters, their effectiveness is inversely proportional to distance from the Forward Logistics Site. Regardless of theater size, HSVs show significant improvements in theater distribution of "low density, high priority" cargo, such as precision guided munitions (PGMs) or critical repair parts when customers are outside COD range. / Lieutenant Commander, United States Navy