Les nitrones sont de composés diamagnétiques qui additionnent les radicaux libres pour former des adduits nitroxyde détectables par résonance paramagnétique électronique (RPE). Récemment les nitrones linéaires telles que l’α-phényl-N-tert-butylnitrone (PBN) et ses dérivés ont été proposées comme nouvelles thérapeutiques dans des pathologies à stress oxydant. Dans ce contexte nous avons synthétisé une vingtaine de PPNs originales, dérivés β-phosphorylés de la PBN, dont le groupe phényle a été substitué par des groupes ayant des effets électroniques sur la fonction nitrone ou a été conçu de manière à former un fragment phénolique présent dans certains antioxydants naturels. Il s’agissait de combiner le bon outil de détection des radicaux que sont les PPNs aux éventuels effets antioxydants et donneurs de NO● de ces nitrones. Nous avons réalisé une évaluation des propriétés antioxydantes des nouvelles PPNs au moyen de différents tests biochimiques ainsi qu'une étude par RPE permettant de déterminer leur réactivité in vitro sur plusieurs types de radicaux libres d'intérêt biologique. Nous avons sélectionné les PPNs ayant les meilleures propriétés afin d'examiner leur impact pharmacologique dans un modèle d'endothélium aortique de rat soumis à un stress oxydant. Dans une deuxième partie, nous avons greffé sur certaines des PPNs synthétisées des chaînes alkyles de différentes longueurs dont la terminaison triphénylphosphonium confère à ces nitrones une affinité particulière pour la mitochondrie, principale source cellulaire de production radicalaire. Nous avons ensuite évalué par RPE la capacité de ces 5 nouvelles mito-PPNs à piéger les radicaux libres alkyle et alcoxy in vitro. / Nitrones are diamagnetic compounds commonly used as probes to monitor biological free radical formation by the spin trapping (ST)/electron paramagnetic resonance coupling (EPR). In addition the growing interest in the therapeutic potential of α-phenyl-N-tert-butylnitrone (PBN) derivatives led researchers to develop analogs having improved protective properties and bioavailability. Among these, PPNs are β-phosphorylated analogues of PBN which form more persistent spin adducts than PBN toward oxygen-centered radicals. In this context we have synthesized twenty new hybrid PPNs having their aromatic ring substituted either by groups which can bring electronic and steric effects to the nitrone function or mimic natural antioxidant moieties. We evaluated the antioxidant properties of the new PPNs with a series of specific assays and we used ESR to study PPNs properties in ST toward a wide array of biologically-relevant free radicals, and their intrinsic nitric oxide releasing properties. The most promising compounds were than tested as vasorelaxant and antioxidant free radicals detectors in rat aortic rings. Protection by PPNs was assessed by measuring vascular response preservation and biochemical indices in aortic tissue. The second purpose dealt with the synthesis of new mitochondrial targeted PPNs with the aim to reach the primary biological source of endogenous production of free radicals. Using EPR we have assessed their ability to scavenge alkyl and alkoxy free radicals in vitro which allowed us to envisage a potential use of this probe against lipid peroxidation at mitochondrial level.

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Humanas, Departamento de Geografia, Programa de Pós-graduação, 2018. / A expansão tecnológica nas últimas décadas vem promovendo transformações significativas na sociedade e também na aviação civil, pois é um dos setores que mais se desenvolve no cenário mundial. Para permitir a continuidade do crescimento e os benefícios dele decorrentes, a Organização de Aviação Civil Internacional (ICAO) desenvolveu o conceito CNS/ATM, ainda no início dos anos 80, de forma a estruturar as bases da aviação do futuro. Dentro do conceito, a Navegação Baseada em Performance (PBN) é ferramenta fundamental e tida como prioridade da Organização de Aviação Civil Internacional (ICAO). A PBN utiliza avanços tecnológicos, voos mais curtos, rápidos, seguros, econômicos, menos poluentes e proporciona a maximização do espaço aéreo. Nesse sentido, este estudo tem como objetivos apresentar o processo PBN no Brasil demonstrando a relação com os sistemas de navegação global por satélite e seus sistemas de acréscimo de sinal; as especificações de navegação que são usadas no espaço aéreo nacional; e comparar rotas PBN com rotas convencionais em relação a distâncias, ao consumo de combustível e emissão de dióxido de carbono (CO2) utilizando para isso a metodologia da ICAO de Cálculo de Emissão de Dióxido de Carbono e tendo base a análise multitemporal do tráfego aéreo nacional nos últimos doze anos. Os resultados apontam vantagens expressivas da PBN frente à navegação aérea convencional nos aspectos estudados. Na rota Brasília – Manaus, ao longo de um ano, é possível economizar 438 mil litros de combustível com 821 toneladas de CO2 podendo deixar de serem emitidas à atmosfera. Em um panorama temporal de doze anos, economizar-se-ia aproximadamente 50 milhões de litros de combustível e se evitaria a emissão de 107 bilhões de toneladas de CO2 na rota São Paulo/Congonhas – Rio de Janeiro/Santos Dumont, voando-se exclusivamente em rotas PBN com trajetória direta. Embora as rotas PBN impõem o cumprimento de vários requisitos para sua implementação, elas permitem o incremento de tráfego, a acessibilidade ao espaço aéreo, diminuição de distâncias percorridas, economia de combustível e redução da emissão de dióxido de carbono na atmosfera. / The technological expansion in the last decades has been promoting significant transformations in society and also in civil aviation, since it is one of the sectors that develops most in the world scenario. To enable continuity of growth and the resulting benefits, the International Civil Aviation Organization (ICAO) developed the CNS / ATM concept in the early 1980s in order to structure the aviation bases of the future. Within the concept, Performance Based Navigation (PBN) is a fundamental tool and considered a priority of the International Civil Aviation Organization (ICAO). PBN uses technological advancements, shorter, faster, safer, cheaper, less polluting flights and maximizes airspace. In this sense, this study aims to present the PBN process in Brazil demonstrating the relationship with global satellite navigation systems and their augmentations systems; navigation specifications that are used in national airspace; and compare PBN routes with conventional routes in terms of distances, fuel consumption and carbon dioxide (CO2) emissions using the ICAO Carbon Dioxide Emission Calculation methodology and based on multi-temporal traffic analysis over the last twelve years. The results point to the PBN advantages over conventional air navigation in the studied aspects. On the Brasilia - Manaus route, over a year, it is possible to save 438 thousand liters of fuel with 821 tons of CO2, whose emission can be avoided into the atmosphere. In a twelve-year timeframe, approximately 50 million liters of fuel would be saved and the emission of 107 billion tons of CO2 would be avoided on the São Paulo / Congonhas - Rio de Janeiro / Santos Dumont route, flying exclusively on PBN routes with direct trajectory. Although PBN routes require compliance with so many requirements for their implementation, they allow for increased traffic, accessibility to airspace, reduction of distances traveled, fuel economy and reduction of the emission of carbon dioxide in the atmosphere.

Heteroaryl nitrone spin traps have been suggested to act as free radical scavengers. The geometry optimizations and the single-point energies of the spin trapping reactions of the heteroaryl nitrones, 5,5-dimethylpyrroline-N-oxide (DMPO) and α-phenyl-N-t-butylnitrone (PBN) have been computationally studied using ab initio (Hartree-Fock (HF) and second-order Møller-Plesset (MP2)) methods and Density Functional Theory (DFT) methods. The effects of new heteroaryl substituents on a parent nitrone spin trap have been examined at the HF and MP2 levels with the 6-31G*, and cc-pVnZ (n=D, T, Q) basis sets. The thermodynamics of the spin trapping at the C-site and O-site with •H, •CH3 and •OH radicals were studied at the HF/6-31G* and DFT/m06/6-31G* levels. The addition reactions favor at the C-sites and the double adducts are thermodynamically more stable than the mono adducts. The spin trapping of DMPO, PBN and α(Z)-(3-methylfuroxan-4-yl)-N-tert-butylnitrone (FxBN) with •OH have also been studied.

This master’s thesis deals with technologies intended for flight control during approach and landing. The main focus is on perspective approach systems, including differential technology systems. The thesis is to serve as a study aid for pilots and students of Air Traffic study programme. The main aim of this thesis is to create a qualified whole of perspective and used approach systems. Individual systems include basic characteristics and assessment of their future use. The thesis also includes an analysis of the possibility of implementing the DGNSS system at the airport with multiple runways. Prague-Ruzyně airport was chosen for this purpose. The implementation of this system is compared to other precision approach systems.

The cyclic nitrone 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), and the lesser known linear phenyl-N-tert-butylnitrone (PBN) and its phosphorylated analogues have been used as spin traps for the investigation of free radicals in biological systems. Theoretical work on these molecules suggests that there are important differences in their properties between biological systems and isolated molecules in the gas phase, most likely resulting from intra and intermolecular hydrogen bonding. Most dielectric solvation models such as the polarized continuum model and COSMO are incapable of direct determination of solvent-spin trap chemical interactions. To examine this, hybrid models incorporating COSMO for long range effects and discrete solvent molecules for short range effects, at the DFT/B3LYP/6-31G* level of theory, have been used to study the stabilization and alteration of the spin trap molecules properties in protic and aprotic polar solvents. The hybrid models have been successfully implemented to support the prominent role played by hydrogen bonding interactions in the stabilization of spin traps.

Traumatic brain injury (TBI) is a major cause of mortality and disability. As common sequelae in survivors of TBI are disabling functional, emotional and cognitive disturbances, improved treatment of TBI patients is urgently needed. At present, no neuroprotective pharmacological treatment exists. The formation of oxygen-centered free radicals, reactive oxygen species (ROS), is considered an important event in the pathophysiology of TBI. In the present thesis, the fluid percussion (FPI) and controlled cortical contusion injury models of TBI in rats were used. Two nitrone radical scavengers, α-Phenyl-N-tert -butyl nitrone (PBN) and the sulfonated analogue of PBN, 2-sulfophenyl-N-tert-butyl nitrone (S-PBN), were used as tools to study the role of ROS in TBI. Pre-treatment with PBN (30 mg/kg) improved morphological and cognitive outcome after severe controlled cortical contusion injury. Treatment with equimolar doses of PBN and S-PBN administered 30 min after FPI followed by a 24 h intravenous infusion improved morphological outcome. Only S-PBN improved cognitive outcome as assessed in the Morris Water Maze. Surprisingly, pre-treatment with PBN increased the number of apoptotic neurons at 24 hours after injury despite a reduced lesion volume. FPI resulted in an early increase in glucose uptake and a reduction in regional cerebral blood flow (rCBF) assessed by fluoro-2-deoxyglucose (FDG) and hexamethylpropylene amine oxime (HMPAO) autoradiography. At 12 h, a marked reduction in glucose uptake and rCBF ensued. These TBI-induced changes were attenuated by PBN and S-PBN pre-treatment. A method for ROS detection using 4-hydroxybenzoate in conjunction with microdialysis was evaluated. The results showed a marked increase in ROS formation as assessed by an increase in the single adduct 3,4-DHBA, lasting 90 min after injury. In a separate study, PBN and S-PBN equally reduced 3,4-DHBA formation despite no detectable brain concentrations of S-PBN at 30 or 60 min post-injury. In conclusion, ROS play an important role in the injury process after TBI. We report a method for ROS detection with potential clinical utility. Nitrones increased ROS elimination and improved functional and morphological outcome. Nitrone treatment may have a clinical potential as a neuroprotective concept in TBI.

The thesis focuses on issues of the procedures in the terminal manoeuvring area (TMA) at regional airports. The goal is to provide a complex study of possible implementation of instrumental arrivals, departures and approaches on the basis of the requirements of the Performance Based Navigation (PBN) at a particular regional airport in the Czech Republic (Kunovice airport). The simulative evaluation of the operational impacts caused by the suggested changes in TMA Brno and CTR Kunovice is also a part of the thesis. The last section is focused on providing a generic methodology describing the process of design and evaluation of PBN procedures.

No description available.

It is a major clinical problem that survival rates after out-of-hospital cardiac arrest have not markedly improved during the last decades, despite extensive research and the introduction of new interventions. However, recent studies have demonstrated promising treatments such as targeted temperature management (TTM) and methylene blue (MB). In our first study, we investigated the effect of MB administered during experi-mental cardiopulmonary resuscitation (CPR) in the setting of postponed hypother-mia in piglets. We set out to study if MB could compensate for a delay to establish targeted TTM. The study demonstrated that MB more than compensated for 30 min delay in induction of TTM. The effect of MB added to that of TTM. The second study examined the effects of TTM and S-PBN on the endothelin system and nitric oxide synthases (NOS) after prolonged CA in a porcine CPR mod-el. The study was designed to understand the cardioprotective mechanism of S-PBN and TTM by their influence on the endothelin system and NOS regulation. We veri-fied for the first time, that these two cardioprotective postresuscitative interventions activate endothelin-1 and its receptors concomitantly with eNOS and nNOS in the myocardium. We concluded that nitric oxide and endothelin pathways are implicated in the postresuscitative cardioprotective effects of TTM. The third study compared survival and hemodynamic effects of low-dose amio-darone and vasopressin to vasopressin in a porcine hypovolemic CA model. The study was designed to evaluate whether resuscitation with amiodarone and vasopressin compared to vasopressin alone would have an impact on resuscitation success, survival, and hemodynamic parameters after hemorrhagic CA. We found that combined resuscitation with amiodarone and vasopressin after hemorrhagic circulatory arrest resulted in greater 3-hour survival, better preserved hemodynamic parameters and smaller myocardial injury compared to resuscitation with vasopressin only. In our fourth study we planned to compare hemodynamic parameters between the treatment group (milrinone, esmolol and vasopressin; MEV) and control group (vasopressin only) during resuscitation from prolonged cardiac arrest in piglets. The study was designed to demonstrate if MEV treatment improved hemodynamics or cardiac damage compared to controls. We demonstrated that MEV treatment reduced cardiac injury compared with vasopressin alone.