No description available.

Depuis plus de cinquante ans, les puissances occidentales ont créé toutes sortes de réseaux militaires internationaux, afin de renforcer leurs liens et harmoniser leurs techniques, leurs équipements et leurs façons de faire. Jusqu’à ce jour, ces regroupements sont demeurés largement ignorés de la discipline des relations internationales. Or, la mondialisation des échanges et l’essor des technologies de l’information ont ouvert les processus politiques à de nouveaux acteurs, y compris en matière de sécurité, jetant un éclairage nouveau sur le rôle, la mission et les responsabilités que les États délèguent à ces réseaux. En menant une analyse approfondie d’un réseau militaire, le Multinational Interoperability Council, cette recherche a pour objectifs de définir les réseaux militaires internationaux en tant que catégorie d’analyse des relations internationales, de documenter empiriquement leur fonctionnement et de mieux comprendre leur rôle dans le champ de la sécurité internationale. Pour ce faire, la démarche propose de recourir à l’appareil conceptuel de l’institutionnalisme relationnel, de la théorie des champs et du tournant pratiques en relations internationales. Cette combinaison permet d’aborder les dimensions institutionnelle, cognitive et pratique de l’action collective au sein du réseau étudié. L’analyse nous apprend que, malgré une influence limitée, le MIC produit une identité, des capacités, des préférences et des effets qui lui sont propres. Les acteurs du MIC ont eux-mêmes généré certaines conditions de son institutionnalisation, et sont parvenus à faire du réseau, d’abord conçu comme une structure d’échanges d’informations, un acteur intentionnel du champ de la sécurité internationale. Le MIC ne peut agir de façon autonome, sans contrôle des États. Cependant, les relations établies entre les militaires qui y participent leur offrent des capacités – le capital social, politique et d’expertise – dont ils ne disposeraient pas autrement, et qu’ils peuvent mobiliser dans leurs interactions avec les autres acteurs du champ. / For more than fifty years, Western powers have created many different forms of international military networks, in order to strengthen their ties and harmonize their technics, equipment and ways of doing things. To date, these groups have remained largely ignored by the academic discipline of International Relations. And yet, globalization and the rise of information technologies have provided many new actors with an access to political processes, including in the field of security. This evolution sheds new light on the role, mission and responsibilities that states assign to these networks. This research conducts an in-depth analysis of one military network, the Multinational Interoperability Council. The aim of this analysis is threefold: to define international military networks as a category of analysis for International Relations, to document empirically their functioning, and to understand their role in the field of internal security. To do so, the analytical framework combines the conceptual apparatus of relational institutionalism, the theory of social fields, and the methodological tools of the practice turn in International Relations. This combination allows for addressing the institutional, cognitive and practical dimensions of collective action within the network. The analysis reveals that, despite a limited influence, the MIC produces its own identity, capabilities, preferences and effects. The MIC’s actors have been able to create the conditions of its institutionalization, and they have succeeded in turning the network into an intentional actor of the international security field, while it was originally created as a mere structure of exchange of information. The MIC is not able to act autonomously, without states’ control. However, the relations established by the military who belong to it have provided them with capabilities – social, political and expertise capitals – that they would not otherwise possess, and which they can mobilize in their interactions with other actors of the field.

L’émergence des souches bactériennes résistantes aux antibiotiques est un phénomène inquiétant, qui se répand à travers le monde. Staphylococcus aureus et Pseudomonas aeruginosa sont des bactéries pathogènes opportunistes multi résistantes qui peuvent causer plusieurs maladies. Cependant, ces bactéries deviennent difficiles à traiter avec des antibiotiques sans occasionner de toxicité. Alors pour trouver des solutions, c’est nécessaire de développer de nouvelles molécules afin de combattre les agents pathogènes résistants. Grâce à leur action pharmacologique, les fluorures exercent un certain effet antibactérien au niveau de l'émail des dents; donc, leur association aux antibiotiques pourrait bien a méliorer l’activité antimicrobienne. De ce fait, nous nous sommes proposés d’étudier les activités in vitro de la vancomycine (VAN), l’oxacilline (OXA), la ceftazidime (CFT) et la méropenème (MER) libre ou associée au fluorure de sodium (NaF) et fluorure de lithium (LiF) qui ont été évaluées sur des souches S.aureus et P.aeruginosa sensibles et résistantes, par la méthode de la microdilution en bouillon, déterminant leur concentration minimale inhibitrice (CMI), leur concentration minimale bactéricide (CMB), leur courbe cinétique (Time-Kill). Leur cytotoxicité sur les globules rouges humains, et leur stabilité à la température de 4°C et 22°C ont été étudiées. Les associations des antimicrobiens aux dérivés des fluorures ont montré une amélioration de l’effet des antibiotiques par la réduction des leurs concentrations et toxicité pour traiter correctement ces pathogènes résistants. Par conséquent, des antibiotiques associés aux dérivés de fluorure pourraient devenir une option de traitement contre des souches résistantes afin de diminuer la toxicité causée par de fortes doses des antibiotiques conventionnels. / The emergence of bacterial strains resistant to antibiotics is a worrying phenomenon, which has spread worldwide. Staphylococcus aureus and Pseudomonas aeruginosa are multi-resistant opportunistic pathogenic bacteria that can cause many diseases. However, they have become difficult to treat with antibiotics without causing toxicity to humans. It is therefore necessary to develop new molecules against resistant pathogens to combat this problem. Due to their pharmacological action, fluorides have an antibacterial effect on tooth enamel which suggests that their combination with antibiotics could improve antimicrobial activity. Thus, we proposed to study in vitro activities of vancomycin (VAN), oxacillin (OXA), ceftazidime (CFT) and meropenem (MER) alone or combined with sodium fluoride (NaF) and lithium fluoride (LiF ) that were evaluated against resistant and susceptible strains of S. aureus and P. aeruginosa by antimicrobial susceptibility testing , in determining their minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and kinetics (Time-Kill). The evaluation of cytotoxicity on human red blood cells, and determination of stability at two different temperatures (4°C, 22°C) were also performed. Associations of antibiotics with fluoride derivatives showed an improvement by increasing the effect of antibiotics with minimal levels necessary to achieve the same result by reducing their toxicity and to properly kill these resistant pathogens. Therefore, antibiotics associated with fluoride derivatives could become a treatment option against resistant strains and at the same time reduce the toxicity caused by high doses of conventional antibiotics.

This work was aimed at developing novel tools that utilize HINT, an empirical forcefield capable of quantitating both hydrophobic and hydrophilic (hydropathic) interactions, for implementation in theoretical biology and drug discovery/design. The role of hydrophobicity in determination of macromolecular structure and formation of complexes in biological molecules is undeniable and has been the subject of research across several decades. Hydrophobicity is introduced, with a review of its history and contemporary theories. This is followed by a description of various methods that quantify this all-pervading phenomenon and their use in protein folding and contemporary drug design projects – including a detailed overview of the HINT forcefield. The specific aim of this dissertation is to introduce our attempts at developing new methods for use in the study of antibacterial drug resistance and antiviral drug discovery. Multidrug efflux is commonly regarded as a fast growing problem in the field of medicine. Several species of microbes are known to have developed resistance against almost all classes of antibiotics by various modes-of-action, which include multidrug transporters (a.k.a. efflux pumps). These proteins are present in both gram-positive and gram-negative bacteria and extrude molecules of various classes. They protect the efflux pump-expressing bacterium from harmful effects of exogenous agents by simply evacuating the latter. Perhaps the best characterized mechanism amongst these is that of the AcrA-AcrB-TolC efflux pump. Data is available in literature and perhaps also in proprietary databases available with pharmaceutical companies, characterizing this pump in terms of the minimum inhibitory concentration ratios (MIC ratios) for various antibiotics. We procured a curated dataset of 32 β-lactam and 12 antibiotics of other classes from this literature. Initial attempts at studying the MIC ratios of β-lactam antibiotics as a function of their three dimensional topology via 3D-quantitative structure activity relationship (3D-QSAR) technology yielded seemingly good models. However, this methodology is essentially designed to address single receptor-ligand interactions. Molecules being transported by the efflux pump must undoubtedly be involved in multiple interactions with the same. Notably, such methods require a pharmacophoric overlap of ligands prior to the generation of models, thereby limiting their applicability to a set of structurally-related compounds. Thus, we designed a novel method that takes various interactions between antibiotic agents and the AcrA-AcrB-TolC pump into account in conjunction with certain properties of the drugs. This method yielded mathematical models that are capable of predicting high/low efflux with significant efficiency (>93% correct). The development of this method, along with the results from its validation, is presented herein. A parallel aim being pursued by us is to discover inhibitors for hemagglutinin-neuraminidase (HN) of human parainfluenza virus type 3 (HPIV3) by in silico screening. The basis for targeting HN is explored, along with commentary on the methodology adopted during this effort. This project yielded a moderate success rate of 34%, perhaps due to problems in the computational methodology utilized. We highlight one particular problem – that of emulating target flexibility – and explore new avenues for overcoming this obstacle in the long run. As a starting point towards enhancing the tools available to us for virtual screening in general (and for discovering antiviral compounds in specific), we explored the compatibility between sidechain rotamer libraries and the HINT scoring function. A new algorithm was designed to optimize amino acid residue sidechains, if provided with the backbone coordinates, by generating sidechain positions using the Dunbrack and Cohen backbone-dependent rotamer library and scoring them with the HINT scoring function. This rotamer library was previously used by its developers previously to design a very successful sidechain optimization algorithm called SCWRL. Output structures from our algorithm were compared with those from SCWRL and showed extraordinary similarities as well as significant differences, which are discussed herein. This successful implementation of HINT in our sidechain optimization algorithm establishes the compatibility between this forcefield and sidechain rotamer libraries. Future aims in this project include enhancement of our current algorithm and the design of a new algorithm to explore partial induced-fit in targets aimed at improving current docking methodology. This work shows significant progress towards the implementation of our hydropathic force field in theoretical modeling of biological systems in order to enhance our ability to understand atomistic details of inter- and intramolecular interactions which must form the basis for a wide variety of biological phenomena. Such efforts are key to not only to understanding the said phenomena, but also towards a solid basis for efficient drug design in the future.

Água purificada para uso em ambientes de saúde e preparação industrial de produtos médico-odonto-hospitalar deve ter uma carga reduzida de contaminação microbiológica e pirogênio. As amostras analisadas foram coletadas em 13 (treze) diferentes estágios de um sistema de purificação de água, sendo isoladas 78 colônias. Para a identificação dos microrganismos foram utilizados: (i) identification system for non-enteric gram-negative rods (api 20 NE, bio Mérieux) e (ii) identification system for enteric and nonfermenter (BBL crystal, Becton Dickinson). De acordo com os resultados pode-se observar uma maior prevalência para Pseudomonas aeruginosa 32,05% (25 colônias dentre as 78 isoladas); Pseudomonas picketti 23,08% (18); Pseudomonas vesiculares 12,82% (10); Pseudomonas diminuta 11,54% (09); Flavobacterium aureum 6,42% (05); Pseudomonas fluorescences 5,13% (04); Acinetobacter Iwoffi 2,56% (02); Pseudomonas putida 2,56% (02); Pseudomonas alcaligenes 1,28% (01); Pseudomonas paucimobilis 1,28% (01), Flavobacterium multivorum 1,28% (01). A eficácia dos agentes sanitizantes utilizados para higienização dos diferentes pontos foi determinada pela concentração inibitória mínima (CIM) e tempo de redução decimal (valor D). Como o hipoclorito de sódio é largamente utilizado na higienização do tanque de água de alimentação, tanque de estocagem da água purificada e nas linhas de distribuição aos pontos de uso, este foi testado frente a todos os microrganismos sendo observado menor resistência para Escherichia coli ATCC 25922 (0.06%=600mg/L), quando comparada a P. aeruginosa isolada e identificada (O,25%=2500mg/L). O tempo de redução decimal (Valor D) da Escherichia coli ATCC 25922 foi de 4 minutos e o valor D da P. aeruginosa isolada e identificada e isolada in house foi de 9 minutos. / The samples of water, which were taken directly from the public distribution water tank and at twelve different stages of a typical purification system, were analyzed for the identification of isolated bacteria. The efficacy of the chemical sanitizers used in the stages of the system, over the isolated and identified bacteria in the sampling water, was valuated by the minimum inhibitory concentration (MIC and decimal reduction time (D-values). According to the miniature kits used in the identification, there was a prevalence of isolation by P. aeruginosa 32,05 % , P. picketti (Ralstonia picketti) 23,08%, P. vesiculares 12,82%, P. diminuta 11.54%, F.aureum 6,42%, P.fluorescens 5,13%, A.lowffi 2,56%, P.putida 2,56%, P. alcaligenes 1,28%, P.paucimobilis 1,28%, and F. multivorum 1,28%. The efficacy of the agents varied with the concentration and time of contact to reduce a decimal logarithmic (loglO) population (n cycles): (i) 0.5% citric acid (0= 4 min) for 30 min reduced n=7 cycles; (ii) 0.5% chloridric acid (0= 6 min) for 30 min reduced n= 4 cycles; (iii) 70% alcohol (0= 9 min) for 1.0 min (n=0.2 cycles); (iv) 0.5% sodium bisulphite (0= 6 min) for 90 min (n=14 cycles); (v) 0.4% sodium hydroxide (0= 8 min) for 30 min (n=3.0 cycles); (vi) 0.5% sodium hypochlorite (0=9 min) for 180 min (n = 19 cycles); (vii) mixture of hydrogen peroxide (2,2%) plus peracetic acid (0.45%), 0= 6 min, contact time of 180 min, reduced n = 32 cycles of the population. The sterility assurance level (SAL) of 10-6 was attained for the 0.5% sodium hypochlorite solution applied in the water purified storage tank and distribution loop; and for the mixture of H2O2 plus peracetic acid, used in the reverse osmose and in the deionizator systems.

Água purificada para uso em ambientes de saúde e preparação industrial de produtos médico-odonto-hospitalar deve ter uma carga reduzida de contaminação microbiológica e pirogênio. As amostras analisadas foram coletadas em 13 (treze) diferentes estágios de um sistema de purificação de água, sendo isoladas 78 colônias. Para a identificação dos microrganismos foram utilizados: (i) identification system for non-enteric gram-negative rods (api 20 NE, bio Mérieux) e (ii) identification system for enteric and nonfermenter (BBL crystal, Becton Dickinson). De acordo com os resultados pode-se observar uma maior prevalência para Pseudomonas aeruginosa 32,05% (25 colônias dentre as 78 isoladas); Pseudomonas picketti 23,08% (18); Pseudomonas vesiculares 12,82% (10); Pseudomonas diminuta 11,54% (09); Flavobacterium aureum 6,42% (05); Pseudomonas fluorescences 5,13% (04); Acinetobacter Iwoffi 2,56% (02); Pseudomonas putida 2,56% (02); Pseudomonas alcaligenes 1,28% (01); Pseudomonas paucimobilis 1,28% (01), Flavobacterium multivorum 1,28% (01). A eficácia dos agentes sanitizantes utilizados para higienização dos diferentes pontos foi determinada pela concentração inibitória mínima (CIM) e tempo de redução decimal (valor D). Como o hipoclorito de sódio é largamente utilizado na higienização do tanque de água de alimentação, tanque de estocagem da água purificada e nas linhas de distribuição aos pontos de uso, este foi testado frente a todos os microrganismos sendo observado menor resistência para Escherichia coli ATCC 25922 (0.06%=600mg/L), quando comparada a P. aeruginosa isolada e identificada (O,25%=2500mg/L). O tempo de redução decimal (Valor D) da Escherichia coli ATCC 25922 foi de 4 minutos e o valor D da P. aeruginosa isolada e identificada e isolada in house foi de 9 minutos. / The samples of water, which were taken directly from the public distribution water tank and at twelve different stages of a typical purification system, were analyzed for the identification of isolated bacteria. The efficacy of the chemical sanitizers used in the stages of the system, over the isolated and identified bacteria in the sampling water, was valuated by the minimum inhibitory concentration (MIC and decimal reduction time (D-values). According to the miniature kits used in the identification, there was a prevalence of isolation by P. aeruginosa 32,05 % , P. picketti (Ralstonia picketti) 23,08%, P. vesiculares 12,82%, P. diminuta 11.54%, F.aureum 6,42%, P.fluorescens 5,13%, A.lowffi 2,56%, P.putida 2,56%, P. alcaligenes 1,28%, P.paucimobilis 1,28%, and F. multivorum 1,28%. The efficacy of the agents varied with the concentration and time of contact to reduce a decimal logarithmic (loglO) population (n cycles): (i) 0.5% citric acid (0= 4 min) for 30 min reduced n=7 cycles; (ii) 0.5% chloridric acid (0= 6 min) for 30 min reduced n= 4 cycles; (iii) 70% alcohol (0= 9 min) for 1.0 min (n=0.2 cycles); (iv) 0.5% sodium bisulphite (0= 6 min) for 90 min (n=14 cycles); (v) 0.4% sodium hydroxide (0= 8 min) for 30 min (n=3.0 cycles); (vi) 0.5% sodium hypochlorite (0=9 min) for 180 min (n = 19 cycles); (vii) mixture of hydrogen peroxide (2,2%) plus peracetic acid (0.45%), 0= 6 min, contact time of 180 min, reduced n = 32 cycles of the population. The sterility assurance level (SAL) of 10-6 was attained for the 0.5% sodium hypochlorite solution applied in the water purified storage tank and distribution loop; and for the mixture of H2O2 plus peracetic acid, used in the reverse osmose and in the deionizator systems.

<p>This thesis presents methods for air sampling and determination of isocyanates, amines, aminoisocyanates and anhydrides. These organic compounds are generated during thermal degradation of polymers such as polyurethane (PUR) or epoxy.</p><p>Isocyanates, amines and anhydrides are airway irritants known to cause occupational asthma. Some of the compounds are listed as human carcinogens. Many workers are exposed.</p><p>Isocyanates and anhydrides are reactive and needs to be immediately derivatized during sampling. Methods have been developed for determination of airborne isocyanates, aminoisocyanates and anhydrides using di-n-butylamine (DBA) as reagent to form stabile urea derivatives or amide derivatives. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) enabled detection limits as low as 10 attomoles. A nitrogen-selective LC-detector enabled quantification of DBA-derivatives in reference solutions. </p><p>A novel sampler is presented. The sampler consists of a denuder in series with a three-stage cascade impactor and an end filter. The sampler made it possible to reveal the distribution of isocyanates between gas and different particle size fractions. During thermal degradation of PUR, isocyanates were associated to particle size fractions (<1 µm) that may penetrate to the lower airways. The distribution during 8 minutes changes noticeably. Aromatic isocyanates become associated to small particles (<1 µm). As a reference method, air-sampling was performed using an impinger filled with di-n-butylamine (DBA) in toluene, connected in series with a glass fiber filter. There was a good agreement between the denuder-impactor sampler and the reference method.</p>

This thesis presents methods for air sampling and determination of isocyanates, amines, aminoisocyanates and anhydrides. These organic compounds are generated during thermal degradation of polymers such as polyurethane (PUR) or epoxy. Isocyanates, amines and anhydrides are airway irritants known to cause occupational asthma. Some of the compounds are listed as human carcinogens. Many workers are exposed. Isocyanates and anhydrides are reactive and needs to be immediately derivatized during sampling. Methods have been developed for determination of airborne isocyanates, aminoisocyanates and anhydrides using di-n-butylamine (DBA) as reagent to form stabile urea derivatives or amide derivatives. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) enabled detection limits as low as 10 attomoles. A nitrogen-selective LC-detector enabled quantification of DBA-derivatives in reference solutions. A novel sampler is presented. The sampler consists of a denuder in series with a three-stage cascade impactor and an end filter. The sampler made it possible to reveal the distribution of isocyanates between gas and different particle size fractions. During thermal degradation of PUR, isocyanates were associated to particle size fractions (&lt;1 µm) that may penetrate to the lower airways. The distribution during 8 minutes changes noticeably. Aromatic isocyanates become associated to small particles (&lt;1 µm). As a reference method, air-sampling was performed using an impinger filled with di-n-butylamine (DBA) in toluene, connected in series with a glass fiber filter. There was a good agreement between the denuder-impactor sampler and the reference method.

No description available.

L’émergence des souches bactériennes résistantes aux antibiotiques est un phénomène inquiétant, qui se répand à travers le monde. Staphylococcus aureus et Pseudomonas aeruginosa sont des bactéries pathogènes opportunistes multi résistantes qui peuvent causer plusieurs maladies. Cependant, ces bactéries deviennent difficiles à traiter avec des antibiotiques sans occasionner de toxicité. Alors pour trouver des solutions, c’est nécessaire de développer de nouvelles molécules afin de combattre les agents pathogènes résistants. Grâce à leur action pharmacologique, les fluorures exercent un certain effet antibactérien au niveau de l'émail des dents; donc, leur association aux antibiotiques pourrait bien a méliorer l’activité antimicrobienne. De ce fait, nous nous sommes proposés d’étudier les activités in vitro de la vancomycine (VAN), l’oxacilline (OXA), la ceftazidime (CFT) et la méropenème (MER) libre ou associée au fluorure de sodium (NaF) et fluorure de lithium (LiF) qui ont été évaluées sur des souches S.aureus et P.aeruginosa sensibles et résistantes, par la méthode de la microdilution en bouillon, déterminant leur concentration minimale inhibitrice (CMI), leur concentration minimale bactéricide (CMB), leur courbe cinétique (Time-Kill). Leur cytotoxicité sur les globules rouges humains, et leur stabilité à la température de 4°C et 22°C ont été étudiées. Les associations des antimicrobiens aux dérivés des fluorures ont montré une amélioration de l’effet des antibiotiques par la réduction des leurs concentrations et toxicité pour traiter correctement ces pathogènes résistants. Par conséquent, des antibiotiques associés aux dérivés de fluorure pourraient devenir une option de traitement contre des souches résistantes afin de diminuer la toxicité causée par de fortes doses des antibiotiques conventionnels. / The emergence of bacterial strains resistant to antibiotics is a worrying phenomenon, which has spread worldwide. Staphylococcus aureus and Pseudomonas aeruginosa are multi-resistant opportunistic pathogenic bacteria that can cause many diseases. However, they have become difficult to treat with antibiotics without causing toxicity to humans. It is therefore necessary to develop new molecules against resistant pathogens to combat this problem. Due to their pharmacological action, fluorides have an antibacterial effect on tooth enamel which suggests that their combination with antibiotics could improve antimicrobial activity. Thus, we proposed to study in vitro activities of vancomycin (VAN), oxacillin (OXA), ceftazidime (CFT) and meropenem (MER) alone or combined with sodium fluoride (NaF) and lithium fluoride (LiF ) that were evaluated against resistant and susceptible strains of S. aureus and P. aeruginosa by antimicrobial susceptibility testing , in determining their minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and kinetics (Time-Kill). The evaluation of cytotoxicity on human red blood cells, and determination of stability at two different temperatures (4°C, 22°C) were also performed. Associations of antibiotics with fluoride derivatives showed an improvement by increasing the effect of antibiotics with minimal levels necessary to achieve the same result by reducing their toxicity and to properly kill these resistant pathogens. Therefore, antibiotics associated with fluoride derivatives could become a treatment option against resistant strains and at the same time reduce the toxicity caused by high doses of conventional antibiotics.