The protein folding problem involves understanding how the tertiary structure of a protein is related to its primary structure. Hence, understanding the thermodynamics associated with the rate-limiting steps for the formation of the earliest events in folding is most crucial to understanding how proteins adopt native secondary and tertiary structures. In order to elucidate the mechanism and pattern of protein folding, an extensively studied protein, Cytochrome-c (Cc), was chosen as a folding system to obtain detailed time-resolved thermodynamic profiles for the earliest events in the protein folding process. Cytochrome-c is an ideal system for understanding the folding process for several reasons. One being that the system can unfold and refold reversibly without the loss of the covalently attached heme group. A number of studies have shown that under denaturing conditions, ferrous Cc (Fe2+Cc) heme group in the presence of carbon monoxide (CO) results in a disruption of the axial heme Methionine-80 (Met80) bond ultimately unfolding the protein. CO-photolysis of this ferrous species results in the formation of a transient unfolded protein that is poised in a non-equilibrium state with the equilibrium state being that of the native folded Fe2+Cc complex. This allows for the refolding reaction of the protein to be photo-initiated and monitor on ns - ms timescales. While CO cannot bind to the ferric form, nitrogen monoxide (NO) photo-release has been developed to photo-trigger ferric Cc (Fe3+Cc) unfolding under denaturing conditions. Photo-dissociation of NO leaves the Fe3+complex in a conformational state that favors unfolding thus allowing the early unfolding events of Fe3+Cc to be probed. Overall the results presented here involve the use of the ligands CO and NO along with photoacoustic calorimetry (PAC) to photo-trigger the folding/unfolding reaction of Cc (and modified Cc). Thus, obtaining enthalpy and molar volume changes directly associated with the initial folding/unfolding events occurring in the reaction pathways of both Fe2+ and Fe3+Cc systems that are most essential to understanding the driving forces involved in forming the tertiary native conformation. The PAC data shows that folding of proteins results from a hierarchy of events that potentially includes the formation of secondary structures, hydrophobic collapse, and/or reorganization of the tertiary complex occurring over ~ns – tens of µs time ranges. In addition, the PAC kinetic fits presented in this work is the first to report Cc folding exhibiting heterogeneous kinetics (in some cases) by utilizing a stretched exponential decay function.

Ce travail de thèse est consacré au développement de la technique de fluorescence induite par laser (LIF) à deux photons appliquée à la molécule CO pour des mesures en flammes à haute pression. Différents schémas d'excitation laser à deux photons et de fluorescence sont comparés afin de déterminer celui qui est le mieux adapté à la détection de CO en milieux de combustion. Le schéma de transitions électroniques B1 Σ+ - X1 Σ+ (230 nm) / B1 Σ+ - A1 Π(483 nm) est sélectionné. Un code de calcul des spectres LIF à deux photons de CO est développé pour prédire l'évolution du signal sur une large gamme de températures et de pressions. Des mesures dans une cellule à haute température et haute pression, et dans une flamme laminaire CH4/air à 1 bar sont réalisées de 300 à 1750 K, et de 1 à 13 bar. Les résultats indiquent une dépendance polynomiale d'ordre 2 du décalage spectral avec la pression ainsi que l'asymétrie du spectre qui croît avec la pression entre 300 et 860 K. La limite de détectivité de CO par LIF en ponctuel est estimée de 500 ppm en flamme à 1 bar. L'effet de la température sur les profils spectraux est bien reproduit par la simulation. La comparaison des profils mesurés en flamme à 1 bar avec les profils simulés donne une température de 1750 +-50 K, en accord avec celle prédite par le modèle de combustion. L'effet de la pression sur le profil spectral (décalage, élargissement et asymétrie) est correctement simulé en considérant un profil collisionnel de Lindholm de 1 à 5 bar à 300 K, et de 1 à 7 bar à 860 K. L'imagerie de fluorescence induite par laser de CO a été développée en flamme à 1 bar. La limite de détectivité est déterminée de 900 ppm pour nos conditions expérimentales. / This work is dedicated to the development of two-photon laser induced fluorescence (LIF) of COfor application in high-pressure flames. Different two-photon excitation and fluorescence schemes arecompared in order to determine which one is more suitable for the detection of CO in flames. TheB1Σ+ -X1Σ+ (230 nm)/B1Σ+ -A1Π (483 nm) electronic transitions scheme is chosen. A numericalcode of two-photon LIF spectra is developed to predict the evolution of fluorescence signals over awide range of temperatures and pressures. Measurements in a high temperature and high pressure celland in a laminar CH4/air flame at 1 bar are performed from 300 to 1750 K and from 1 to 13 bars.Results indicate a square dependence of the collisional shift upon pressure and a large asymmetry ofthe spectrum at high pressure between 300 and 860 K. The detection limit is estimated to be 500 ppmin flame at 1 bar. Influence of temperature on LIF spectra is well reproduced by the simulations. Comparisonbetween measured and simulated excitation spectra lead to a flame temperature of 1750+-50K, in accordance with combustion modelling. The Lindholm profile is used in order to reproduce thepressure-dependence of the spectrum in the range 1 to 5 bars at 300 K, and 1 to 7 bars at 860 K.Planar laser induced fluorescence imaging of CO is developed in flame at 1 bar. The detection limit is900 ppm in our experimental conditions.

Le système de l’hème oxygenase-1 (HO-1) constitue un système essentiel pour la vie grâce à ses activités anti-inflammatoire et anti-oxydante lui conférant une capacité de protection importante face à une multitude de pathologies. Les produits de dégradation de l’hème par l’hème oxygénase, essentiellement le CO, participent activement dans la protection procurée par le système de l’HO-1. Par conséquence, l’exploitation pharmacologique de ce système s’est montrée d’un intérêt particulier pour une application clinique potentielle. Dans ce contexte, le but de ce travail était la caractérisation de nouvelles molécules qui activent ce système de protection.Tout d’abord, CORM-401, une nouvelle molécule ayant le Mn comme métal et qui libère 3CO/mole de la molécule, a été caractérisée dans un contexte cardiovasculaire. CORM-401 a induit une relaxation significative et immédiate des anneaux aortiques pré-contractés avec de l’épinéphrine. En parallèle, CORM-401 s’est montré sensible au stress oxydant et la libération du CO par CORM-401 s’est accélérée significativement en présence des oxydants comme H2O2, ce qui s’est traduit par une relaxation plus poussée des anneaux aortiques. En plus, CORM-401 a induit la migration des cellules endothéliales EA.hy926, l’augmentation d’expression de différents facteurs angiogéniques ainsi que la phosphorylation de p38 MAPK et Akt. P38 MAPK et HO-1 se sont montrés impliqués dans la signalisation de l’angiogenèse induite par CORM-401.En parallèle, une nouvelle classe de molécule nommée HYCOs a été récemment synthétisée par notre groupe. Ces molécules sont formées par la liaison d’un inducteur de Nrf2/HO-1 à un CO-RM dans le but d’induire une réponse immédiate à la libération du CO et une réponse plus tardive à l’induction de Nrf2/HO-1. Les deux premières molécules de cette classe, HYCO-1 et HYCO-2, ont libéré du CO en solution d’une manière concentration-dépendante et HYCO-1 s’est montré plus efficace que HYCO-2 en termes d’induction de Nrf2 dans différentes lignées cellulaires. HYCO-1 a réduit significativement la production de nitrite par les cellules microgliales BV2 et les macrophages RAW 264.7 stimulées avec du LPS. Par conséquence, ces deux molécules ont prouvé la réussite du concept des HYCOs. / The heme oxygenase-1 (HO-1) pathway has emerged as a vital multifaceted system with important capacities of protection during pathological conditions characterized by oxidative stress and inflammation. The byproducts of this pathway, CO, BV and BR, were shown to contribute actively in mediating these protective effects. Thus the exploitation of the HO-1 pathway by different pharmacological tools seems to have interesting potential in clinical application. In this context, we aimed to characterize the biochemical and pharmacological activities of molecules targeting this pathway.First, a new Mn-based CO-RM named CORM-401 that releases 3CO/mole of compound with a slow kinetic was characterized in a cardiovascular context. CORM-401 induced immediate and significant relaxation in pre-contracted isolated aortic rings. Interestingly, CORM-401 has also shown to be susceptible to an oxidative environment since H2O2 potently enhanced the CO release by this compound and enhanced its vasodilatory effect. In addition, CORM-401 promoted the migration of EA.hy926 endothelial cells and induced the expression of different angiogenic factors along with the phosphorylation of P38 MAPK and Akt. HO-1 and p38 MAPK both participated in mediating the angiogenic effect of CORM-401.In parallel, a new class of hybrid molecules, named HYCOs, was recently synthesized by our group. These molecules were designed to possess an Nrf2 inducer moiety coordinated to a CO-RM in the purpose of inducing a prompt effect by the CO release and a delayed induction of Nrf2/HO-1 by the Nrf2 inducer moiety. HYCO-1 and HYCO-2, the first two compounds of this class, both released CO in solution in a concentration-dependent manner and HYCO-1 was more potent than HYCO-2 in inducing Nrf2 in different cell lines. HYCO-1 also significantly reduced nitrite production in BV2 microglia and RAW 264.7 macrophages stimulated with LPS. With these two molecules, the concept of designing HYCOs has proven its feasibility and its success.

The National Institute for Occupational Safety and Health (NIOSH) has shown that carbon monoxide (CO) exposure levels which can induce carboxyhemoglobin (COHb) formation in excess of 5 percent can result in serious health consequences. In Dade County, Florida county vehicle inspectors are routinely exposed to CO on the job. To evaluate CO exposure levels, a Ecolyzer direct reading CO meter was placed in inspection lanes in 10 Dade County vehicle inspection stations. The results of this study indicate that in 3 stations, an 8-hour time-weighted exposure to carbon monoxide will induce inspector COHb levels in excess of 5 percent, and all stations have work sites where inspectors encounter ceiling exposure levels which may alter their predicted level of COHb formation. Although CO exposure in Dade County vehicle inspection stations was found to be influenced by several factors, the extent and severity of exposure can be reduced by engineering and administrative controls.

This Master´s thesis deals with the verification calculation of boiler which burns brown coal for the application of the selective catalytic reduction method. The thesis is divided into several parts. In the first of all is performed the calculation of the furnace chamber which involves stoichiometrics calculations and enthalpy calculations of air and flue gas. In the second part the heat balance of the boiler, the boiler losses and the thermal efficiency are determined. After all the heating surfaces are calculed for the verify the dimensions. In the conclusion of the thesis we looked for the temperature range which is used for the SCR application. Then the improvements for the appropriate temperature range are designed.

The thesis is focused on the possibility of intoxication by selected chemicals at home or in public places. Especially the danger of carbon monoxide poisoning. We’re assessing the current state of the level of awareness and prevention in the Czech Republic. The thesis prepared an overview of the current state of intoxication busy the carbon monoxide in the Czech Republic and the level of medical procedures. There are evaluated measures, which are aimed to reduce the frequency of poisoning. The outcome of the thesis is to design a set of measures, which are designed to eliminate health risks to the population and raise public awareness. The thesis was carried out their own research facilities, household detectors, carbon monoxide at a pre-selected location.

<p>Degradacija kvaliteta vazduh kao najosetljivijeg dela životne<br />sredine, predstavlja jedan od glavnih problema sa kojim se<br />suočava savremeno društvo. Saobraćaj, naročito kada je reč o<br />velikim urabanim sredinama, je identifikovan kao glavni izvor<br />hazardnog ugljen-monoksida. Formiranje modela predstavlja<br />neophodan preduslov u procesu prognoze koncentracije ugljen-<br />monoksida u ambijentalnom vazdhu, a samim tim i osnovu za<br />provođenja mera i aktivnosti u procesu poboljšanja stanja i<br />kvaliteta vazduha u velikim urbanim sredinama.</p> / <p>Degradation of quality of air, as the most fragile part of<br />environment, is one of the main problems that humanity faces<br />today. Traffic, particularly when it comes to large urban areas, has<br />been identified as a main source of hazardous carbon monoxide.<br />This model development is identified as a necessary postulate in a<br />process of foreseeing the amount of carbon monoxide in<br />surrounding air, and with that, this is also a basis for conducting<br />measures and activities that aim to improve overall air quality in<br />large urban areas.</p>

Zr-based materials have found their main application in the nuclear field having high corrosion resistance and low neutron absorption cross-section. The oxide layer that is formed on the surface of these alloys is meant to be the barrier between the metal and the corrosive environment. The deterioration of this protective layer limits the lifetime of these alloys. A better understanding of the transport phenomena, which take place in the oxide layer during oxidation, could be beneficial for the development of more resistant alloys. In the present study, oxygen and hydrogen transport through the zirconia layer during oxidation of Zr-based materials at temperatures around 400C have been investigated using the isotope-monitoring techniques Gas Phase Analysis and Secondary Ion Mass Spectrometry. The processes, which take place at oxide/gas and oxide/metal interface, in the bulk oxide and metal, have to be considered in the investigation of the mechanism of hydration and oxidation. Inward transport of oxygen and hydrogen species can be influenced by modification of the surface properties. We found that CO molecules adsorbed on Zr surface can block the surface reaction centers for H2 dissociation, and as a result, hydrogen uptake in Zr is reduced. On the other hand, coating the Zr surface with Pt, resulted in increased oxygen dissociation rate at the oxide/gas interface. This generated enhanced oxygen transport towards the oxide/metal interface and formation of thicker oxides. Our results show that at temperatures relevant for the nuclear industry, oxygen dissociation efficiency decreases in the order: Pt &gt; Zr2Fe &gt; Zr2Ni &gt; ZrCr2 ≥ Zircaloy-2. Porosity development in the oxide scales generates easy diffusion pathways for molecules across the oxide layer during oxidation. A novel method for evaluation of the gas diffusion, gas concentration and effective pore size of oxide scales is presented in this study. Effective pore sizes in the nanometer range were found for pretransition oxides on Zircaloy-2. A mechanism for densification of oxide scales by obtaining a better balance between inward oxygen and outward metal transport is suggested. Outward Zr transport can be influenced by the presence of hydrogen in the oxide/metal substrate. Inward oxygen transport can be promoted by oxygen dissociating elements such as Fe-containing second phase particles. The results suggest furthermore that a proper choice of the second-phase particle composition and size distribution can lead to the formation of dense oxides, which are characterized by low oxygen and hydrogen uptake rates during oxidation.

京都大学 / 新制・課程博士 / 博士(人間・環境学) / 甲第23265号 / 人博第980号 / 新制||人||232(附属図書館) / 2020||人博||980(吉田南総合図書館) / 京都大学大学院人間・環境学研究科相関環境学専攻 / (主査)教授 吉田 寿雄, 教授 田部 勢津久, 教授 中村 敏浩 / 学位規則第4条第1項該当 / Doctor of Human and Environmental Studies / Kyoto University / DFAM

An energy transition can be defined as the adoption of a new primary energy system. As such, it is a structural change that implies a broad shift in technologies and behaviors in order to replace one source of energy with another. Energy transitions motivated by economic, climate, and/or health goals are taking place everywhere in the world. Air pollution, a consequence of fossil fuel-based and solid fuel-based energy use among other sources, is the largest environmental health risk accounting for 6.4 million premature deaths annually. Given the health implications of our energy systems and the social drivers of energy use, access, and burden, energy transitions have the potential to impact health outcomes and associated disparities in a context-dependent manner. The research presented in this dissertation has two objectives: 1) to evaluate the distribution of benefits from energy transitions in the United States (US) and in Ghana; 2) to identify and characterize health outcomes that are relevant to these transitions but are currently understudied. Chapters 2 and 3 are anchored in the US energy policy context. Chapter 2 focuses on the transition away from coal as the primary source of energy in the US and its implications for particulate matter pollution and preterm births. Leveraging a novel dispersion model, I assessed the association between coal PM2.5 and preterm birth rates along with effect modification by race/ethnicity. We observed a positive non-linear relationship between coal PM2.5 and preterm birth rate, which plateaued at higher levels of pollution. The findings of this study suggest that the transition away from coal may have reduced preterm birth rates in the US, but that the association was stronger among non-Hispanic White women compared to non-Hispanic Black women. In Chapter 3, I use a mixed-methods framework to evaluate the first pilot of gas-to-electric stove transition in low-income housing in the US. Through a collaboration with a community-based environmental justice group in New York City, we monitored indoor air quality in participants homes pre- and post-intervention, conducted controlled cooking tests, and carried out focus groups to characterize their experience. Post-intervention, daily NO2 concentrations were 46.3% (95% CI: -67.8%, -10.3%) lower in the intervention arm compared to the control arm. Participants were unanimously pleased with the transition, which had simultaneously improved their cooking experience and partially addressed energy insecurity concerns that plagued their building. Chapters 4 and 5 contribute to the characterization of the health implications associated with Ghana’s commitment to increase access to liquified petroleum gas (LPG) nationally. In Chapter 4, we aimed to describe the country-level incidence of severe cooking-related burns by fuel type in use and to identify effect modifiers. We conducted a nationally representative (n = 7,389) household energy use survey in all 16 regions of Ghana. The incidence rate (95% CI) of cooking-related burns per 1000 person-years among working age females was 8.3 (7.2; 12.0) per 1000 person-years, which was 8 times higher than that of working age males. Among adults, the odds of experiencing a cooking-related burn were doubled among solid fuel users compared to primary LPG users. In Chapter 5, we aimed to understand the effect of an LPG intervention on personal exposure to household air pollution in a peri-urban setting of Ghana and to characterize the distribution of benefits between male and female household members quantitatively and qualitatively. The difference-in-differences results suggested a reduction in exposure to carbon monoxide due to the intervention (-14.2%, 95% CI: -44.1%, 31.6%), which might have benefited male and female participants to the same extent. Importantly, focus group discussions suggested that the ability that LPG affords to cook “on demand” could negatively impact intra-household dynamics and expectations in a way that has not been previously documented. Taken together, our findings from two distinct socioeconomic contexts, highlight the non-uniform distribution of benefits from energy transitions, especially when benefits that are not mediated by air pollution are considered. These results contribute to the understanding that social drivers of inequities should be integrated in the design of energy policies and interventions aimed at generating equitable outcomes. Future directions include a detailed characterization of the context-dependent relative contributions of indoor and outdoor air pollution sources as well as a more systematic integration of quantitative and qualitative methods in policy evaluation.