L’avènement des nanotechnologies engendre une exposition accrue de l’homme aux nanomatériaux, représentant un risque d’un genre nouveau. A cet égard un grand nombre de recherches porte sur l’étude de leur toxicité. Néanmoins, les questions de dégradation et transformation des nanoparticules dans l’organisme sont encore peu abordées. Des études effectuées au laboratoire ont montré qu’après injection de nanoparticules d’oxyde de fer in vivo, celles-ci sont confinées dans les lysosomes où elles sont dégradées. Une partie de mes travaux de thèse se sont concentrés sur une voie possible de métabolisation des produits de dégradation issus de nanoparticules d’oxydes de fer par l’intermédiaire d’une protéine intervenant dans le métabolisme du fer, la ferritine. Nous avons élaboré plusieurs stratégies afin de détecter et de suivre le transfert de métaux vers la ferritine. Ces travaux ont permis de mettre en évidence un processus de prise en charge des produits de dégradation des nanoparticules d’oxyde de fer à l’échelle moléculaire. Une seconde partie de mes travaux ont été consacré au suivi des produits issus de la dégradation des nanoparticules d’oxyde de fer à l’échelle de l’organisme. La haute concentration endogène en fer rendant impossible ce suivi, une stratégie consistant à marquer les nanoparticules de fer avec un isotope du fer, le 57Fe, a permis de suivre les dynamiques de circulation des produits de dégradation in vivo sur une période de six mois. Nous avons également effectué un double marquage des nanoparticules, du cœur inorganique ainsi que de leur enrobage afin de caractériser leur intégrité in vivo / With the advent of nanotechnology, the exposure of humans to nanomaterials increased, representing a risk of a new kind. Although the potential toxicity of such nanomaterials is extensively studied, their long term fate, biotransformation and degradation in the organism are still poorly understood. It was demonstrated earlier in the laboratory, that after intravenous injection, iron oxide nanoparticles undergo local intracellular degradation within lysosomes. In this context, we are interested in the fate of by products from iron oxide nanoparticles. Part of my thesis has focused on a possible pathway for metabolizing these degradation products through a protein involved in iron metabolism, the ferritin. We first studied, in solution, the degradation processes of iron oxide nanoparticles in the presence of these proteins as well as the iron transfer processes from nanoparticles to ferritin. The difficulty is the high concentration of endogenous iron which makes impossible to demonstrate these in vivo transfers. Thus, we have developed a strategy, using doped iron oxide nanoparticles with a scarce element in the organism, to track these phenomena in vivo. This work highlighted a possible mechanism of biological recycling, remediation and detoxification of nanoparticles mediated by endogenous proteins at the molecular scale. A second part of my work was devoted to develop a multi-scale method to study the life cycle of metal oxide nanoparticles and their by products in organism. The main challenge is to differentiate iron stemming from the nanoparticles from the endogenous iron. This specific tracking problem is routinely encountered in geochemical studies and solved by labelling the target material with minor stable isotopes. Therefore, iron oxide nanoparticles enriched in the minor stable isotope 57Fe were synthetized and injected intravenously in mice to follow dynamic circulations of iron oxide nanoparticles and their byproducts. We have also labelled the coating to track the nanoparticles integrity in mice over a period of six month

<p>Compounds labelled with ¹¹C (<i>β</i>⁺, t_1/2 = 20.4 min) are used in positron emission tomography (PET), which is a quantitative non-invasive molecular imaging technique. It utilizes computerized reconstruction methods to produce time-resolved images of the radioactivity distribution in living subjects. </p><p>The feasibility of preparing [¹¹C]methyl iodide from [¹¹C]methane and iodine via a single pass through a non-thermal plasma reactor was explored. [¹¹C]Methyl iodide with a specific radioactivity of 412 ± 32 GBq/µmol was obtained in 13 ± 3% decay-corrected radiochemical yield within 6 min via catalytic hydrogenation of [¹¹C]carbon dioxide (24 GBq) and subsequent iodination, induced by electron impact. </p><p>Labelled ethyl-, propyl- and butyl iodide was synthesized, within 15 min, via palladium-mediated carbonylation using [¹¹C]carbon monoxide. The carbonylation products, labelled carboxylic acids, esters and aldehydes, were reduced to their corresponding alcohols and converted to alkyl iodides. [1-¹¹C]Ethyl iodide was obtained via palladium-mediated carbonylation of methyl iodide with a decay-corrected radiochemical yield of 55 ± 5%. [1-¹¹C]Propyl iodide and [1-¹¹C]butyl iodide were synthesized via the hydroformylation of ethene and propene with decay-corrected radiochemical yields of 58 ± 4% and 34 ± 2%, respectively. [1-¹¹C]Ethyl iodide was obtained with a specific radioactivity of 84 GBq/mmol from 10 GBq of [¹¹C]carbon monoxide. [1-¹¹C]Propyl iodide was synthesized with a specific radioactivity of 270 GBq/mmol from 12 GBq and [1-¹¹C]butyl iodide with 146 GBq/mmol from 8 GBq. </p><p>Palladium-mediated hydroxycarbonylation of acetylene was used in the synthesis of [1-¹¹C]acrylic acid. The labelled carboxylic acid was converted to its acid chloride and subsequently treated with amine to yield <i>N-</i>[<i>carbonyl</i>-¹¹C]benzylacrylamide. In an alternative method, [<i>carbonyl</i>-¹¹C]acrylamides were synthesized in decay-corrected radiochemical yields up to 81% via palladium-mediated carbonylative cross-coupling of vinyl halides and amines. Starting from 10 ± 0.5 GBq of [¹¹C]carbon monoxide, <i>N-</i>[<i>carbonyl</i>-¹¹C]benzylacrylamide was obtained in 4 min with a specific radioactivity of 330 ± 4 GBq/µmol. </p>

Compounds labelled with 11C (β+, t1/2 = 20.4 min) are used in positron emission tomography (PET), which is a quantitative non-invasive molecular imaging technique. It utilizes computerized reconstruction methods to produce time-resolved images of the radioactivity distribution in living subjects. The feasibility of preparing [11C]methyl iodide from [11C]methane and iodine via a single pass through a non-thermal plasma reactor was explored. [11C]Methyl iodide with a specific radioactivity of 412 ± 32 GBq/µmol was obtained in 13 ± 3% decay-corrected radiochemical yield within 6 min via catalytic hydrogenation of [11C]carbon dioxide (24 GBq) and subsequent iodination, induced by electron impact. Labelled ethyl-, propyl- and butyl iodide was synthesized, within 15 min, via palladium-mediated carbonylation using [11C]carbon monoxide. The carbonylation products, labelled carboxylic acids, esters and aldehydes, were reduced to their corresponding alcohols and converted to alkyl iodides. [1-11C]Ethyl iodide was obtained via palladium-mediated carbonylation of methyl iodide with a decay-corrected radiochemical yield of 55 ± 5%. [1-11C]Propyl iodide and [1-11C]butyl iodide were synthesized via the hydroformylation of ethene and propene with decay-corrected radiochemical yields of 58 ± 4% and 34 ± 2%, respectively. [1-11C]Ethyl iodide was obtained with a specific radioactivity of 84 GBq/mmol from 10 GBq of [11C]carbon monoxide. [1-11C]Propyl iodide was synthesized with a specific radioactivity of 270 GBq/mmol from 12 GBq and [1-11C]butyl iodide with 146 GBq/mmol from 8 GBq. Palladium-mediated hydroxycarbonylation of acetylene was used in the synthesis of [1-11C]acrylic acid. The labelled carboxylic acid was converted to its acid chloride and subsequently treated with amine to yield N-[carbonyl-11C]benzylacrylamide. In an alternative method, [carbonyl-11C]acrylamides were synthesized in decay-corrected radiochemical yields up to 81% via palladium-mediated carbonylative cross-coupling of vinyl halides and amines. Starting from 10 ± 0.5 GBq of [11C]carbon monoxide, N-[carbonyl-11C]benzylacrylamide was obtained in 4 min with a specific radioactivity of 330 ± 4 GBq/µmol.

Στο πεδίο κρατήρων του Κόλπου του Ελαιώνα, παρατηρήθηκε διαφυγή γλυκού νερού (Christodoulou et al., 2002). Προκειμένου να διαπιστωθεί αν ο παράκτιος υδροφόρος εκφορτίζεται στη θάλασσα, έγινε δειγματοληψία νερού σε πηγές και γεωτρήσεις στη χέρσο και πραγματοποιήθηκαν υδροχημικές και ισοτοπικές αναλύσεις. / Groundwater seepage was observed in the pockmark field in Eleonas Bay (Christodoulou et al., 2002). In order to find out if the coastal aquifer seeps through the seafloor, water samples were taken from springs and boreholes and hydrochemical and isotopic analyses took place.

Structure I and II gas hydrates were observed in the same sediment cores of a mud volcano in the Kukuy Canyon, Lake Baikal. The sII gas hydrate contained about 13-15% of ethane, whereas the sI gas hydrate contained about 1-5% of ethane and placed beneath the sII gas hydrate. We measured isotopic composition of dissociation gas from both type gas hydrates and dissolved gas in pore water. We found that ethane δD of sI gas hydrate (from -196 to -211 ‰) was larger than that of sII (from -215 to -220 ‰), whereas methane δ13C, methane δD and ethane δD in both hydrate structures were almost the same. δ13C of methane and ethane in gas hydrate seemed several permil smaller than those in pore water. These results support the following idea that the current gas in pore water is not the source of these gas hydrates of both structures. Isotopic data also provide useful information how the “double structure” gas hydrates formed.

In quantitative proteomics, many of the LC-MS based approaches employ stable isotopic labelling to provide relative quantitation of the proteome in different cell states. In a typical approach, peptides are first detected and identified by tandem MS scans prior to quantifying proteins. This provides the researcher with a large amount of data that are not useful for quantitation. It is desirable to improve the throughput of current approaches to make proteomics a more routine experiment with an enhanced capacity to detect differentially expressed proteins. This thesis reports the developments towards this goal, including an assessment of the viability of stable dimethyl labelling for comparative proteomic measurements and the evaluation of a dynamic algorithm called Parallel Isotopic Tag Screening (PITS) for the detection of isotopically labelled peptides for quantitative proteomics without the use of tandem MS scans.

Coral reefs are highly complex and also highly threatened ecosystems. Population growth and the unsustainable use of coral reefs have resulted in 55% of the world’s reefs being considered degraded. Fishing, the primary ‘local’ threat on most reefs, has altered the composition of most reef communities. As a result, very few pristine coral reefs remain. Typically, coral reef research is done via underwater visual censuses, providing abundance estimates but no indication of trophic interactions, therefore we know relatively little about the structure of intact reef food webs. Understanding how human activities affect trophic structure and feeding interactions among resident reef species may be important for coral reef conservation. Here, I apply stable isotope analysis to coral reef piscivorous fishes from Kiritimati (Republic of Kiribati), the world’s largest atoll. I examine dietary niche metrics of five focal species (Cephalopholis argus, Cephalopholis urodeta, Aphareus furca, Lutjanus bohar, and Lutjanus fulvus) and of the piscivore functional group as a whole, across an anthropogenic disturbance gradient that results from the atoll’s heavily skewed geographic population distribution. Using bootstrapped stable carbon (δ13C) and nitrogen (δ15N) isotope values, controlled for body size effects and analysed with Bayesian methods using the SIAR (Stable Isotope Analysis in R) program, I provide evidence of isotopic niche differentiation in C. argus and L. fulvus relative to other sampled species in terms of niche width metrics and mean δ13C and δ15N values. I also analyse the effect of fishing pressure at an individual level (controlling for body size effects on stable isotope signatures for each species), population level (accounting for observed differences in body size distributions across the fishing pressure gradient for each species), and the ‘community’ level (accounting for body size and relative abundance differences of the five piscivores across the fishing pressure gradient). These metrics reveal species-specific changes in niche metrics of three of the focal species at the individual level: C. urodeta, showed regionally distinct niche width metrics but no apparent correlation with fishing pressure, while A. furca and L. bohar, both had broader niche width metrics in heavily fished areas. No significant effect of fishing pressure was found at population or community levels. This study provides the first evidence using stable isotopes that fishing can alter the diets of coral reef fishes. The mechanism by which it can do so, while not entirely clear, would most likely be by expanding a given species’ dietary diversity by either forcing it to switch to non-preferred prey items or changing the diet and/or body size of its prey items, both of which would reflect significant ecological changes within a community. This thesis provides evidence of the utility of stable isotope analyses in answering important ecological questions in coral reef food webs, and reveals that fishing can affect reef communities at the most fundamental level of trophic interactions. / Graduate / 0329 / burrilladrian@gmail.com

L'objectif général de cette thèse est de mieux comprendre l'influence d'anciens sites miniers sur la contamination en métaux (Cd, Hg, Tl, Pb, Zn) et métalloïdes (As, Sb) de l'hydrosystème aval. Une attention particulière a été portée à l'antimoine (Sb), dont le comportement dans les cours d'eau contaminés par les drainages miniers reste mal connu et dont la signature isotopique pourrait permettre de tracer différentes sources et processus. Le site d'étude est le bassin des Gardons dans le Gard ; ce cours d'eau Cévenol draine de nombreux sites miniers abandonnés (Pb, Zn, Sb, charbon). L'enrichissement en métaux et métalloïdes a été étudié dans les sédiments actuels et anciens du bassin des Gardons. Un historique de la contamination métallique a été reconstitué à l'aide d'une archive sédimentaire. Les sources prépondérantes de métaux et métalloïdes dans les sédiments ont été déterminées ainsi que la mobilité potentielle de ces éléments vers la phase aqueuse. En complément, les variations de concentrations en métaux et métalloïdes dans les phases dissoute et particulaire ont été étudiées lors d'un épisode de crue grâce à un échantillonnage à haute résolution temporelle. Dans leur ensemble, les résultats montrent que les anciennes mines du bassin des Gardons contribuent à l'enrichissement en métaux et métalloïdes du cours d'eau aval, particulièrement en période de crue. Plus spécifiquement, le comportement de l'antimoine a été étudié dans un affluent du Gardon impacté par du drainage minier acide en aval de l'ancienne mine de Carnoulès et la composition isotopique de l'antimoine a été déterminée dans des eaux prélevées sur le bassin des Gardons et de l'Orb amont, après mise au point d'un protocole de purification/pré-concentration de Sb. Les résultats mettent en évidence le potentiel des isotopes de l'antimoine pour tracer l'origine de cet élément et les processus qu'il subit au cours de son transfert dans les cours d'eau impactés par du drainage de mine. / The overall objective of this thesis was to improve understanding of the influence of former mining sites on metal (Cd, Hg, Tl, Pb, Zn) and metalloid (As, Sb) contamination of the downstream hydrosystem. A special care was given to antimony (Sb), its behavior in mining-impacted streams remains poorly known and its isotopic signature could be usefull to track sources and processes. The study site is the Gardon River watershed in the south-east of France which drains many abandoned mining sites (Pb, Zn, Sb, coal). Metal and metalloid enrichment was studied in current and historical sediments of the Gardon River watershed. A sedimentary archive was used to investigate past metal contamination history. The prevailing metal and metalloid sources in sediments were determined together with the potential mobility of these elements toward the aqueous phase. In addition, dissolved and particulate metal and metalloid concentration variations were studied during a flood event using a high temporal resolution sampling. Altogether, the results suggest that former mining sites of the Gardon River watershed contribute to metal and metalloid enrichment of the downstream hydrosystem, especially during floods. More specifically, antimony behavior was investigated in a tributary of the Gardon River which is impacted by acid mine drainage originating from the disused Carnoulès mine and antimony isotopic composition was determined in waters collected in the Gardon River watershed and in the Upper Orb River after developing a protocol for preconcentrating and purifying Sb. The results highlight the potential of antimony isotopes to track the origin of this element and the processes that it undergoes during its transfer in streams impacted by mine drainage.

La spectroscopie d'absorption moléculaire est un outil incontournable non seulement pour la physique fondamentale et la métrolgie mais aussi pour des domaines aussi divers que les sciences environnementales, la planétologie ou l'astrophysique. Ces dernières années, des techniques spectroscopiques qui exploitent l'amplification résonnante d'interaction entre lumière laser et molécules dans une cavité optique ont fourni des détectivités exceptionnelles sur l'axe d'absorption, tandis que l'axe de fréquence des spectromètres n'atteignait généralement pas le même niveau de précision.Dans cette thèse, nous avons répondu à ce défi en développant la spectroscopie en cavité par temps de déclin stabilisée en fréquence par rétroaction optique (OFFS-CRDS en anglais). Cette nouvelle technique présente une combinaison unique de stabilité et résolution fréquentielles sub-kHz, d'un niveau d'intensité lumineuse intra-cavité de l'ordre du kW/cm^2, d'une detectivite de 2 x 10^(−13) cm^(−1)Hz^(-1/2) limitée par le bruit de photons, et d'une limite de détection de 8.4 x 10^(−14) cm^(−1) sur une plage spectrale étroite. Ces performances inédites sont dues à l'asservissement de la cavité spectroscopique à un laser balayé en fréquence par modulation à bande latérale unique et stabilisé par rétroaction optique avec une cavité en V de réference ultrastable. Pour transférer la cohérence de ce laser sub-kHz à des lasers plus bruiteux dans d'autres gammes spectrales à travers un peigne de fréquence optique, nous avons exploré une nouvelle méthode de clonage de phase par une correction anticipative à large bande passante et démontré une erreur résiduelle de phase de 113 mrad. En appliquant l'OFFS-CRDS à la spectroscopie du CO2 à 1.6 μm, nous avons obtenu un spectre large bande avec une dynamique de 8 x 10^5, et nous avons déterminé douze fréquences de transition absolues avec une exactitude de l'ordre du kHz en mesurant des Lamb dips sub-Doppler en absorption saturée avec un dispositif équipé d'un peigne de fréquence. Par ailleurs, nous avons procédé à une analyse détaillée des sources d'erreurs systematiques en CRDS et nous avons déduit une formule analytique pour le déclin de cavité non-exponentiel dans un régime faiblement saturé qui est susceptible de contribuer à de futures mesures de moments de transition dipolaire indépendantes de la concentration. Nos résultats ouvrent des perspectives prometteuses pour des applications métrologiques de l'OFFS-CRDS, comme par exemple l'étude de profils de raie poussés, la mesures de rapports isotopiques et la spectroscopie d'absorption saturée extensive dans le proche infrarouge. / High-precision molecular absorption spectroscopy is a powerful tool for fundamental physics and metrology, as well as for a broad range of applications in fields such as environmental sciences, planetology and astrophysics. In recent years, spectroscopic techniques based on the enhanced interaction of laser light with molecular samples in high-finesse optical cavities have provided outstanding detection sensitivities on the absorption axis, while the spectrometer frequency axis rarely met as high precision standards.In this thesis, we addressed this challenge by the development of Optical Feedback Frequency-Stabilized Cavity Ring-Down Spectroscopy (OFFS-CRDS). This novel technique features a unique combination of sub-kHz frequency resolution and stability, kW/cm^2-level intracavity light intensity, a shot-noise limited absorption detectivity down to 2 x 10^(−13) cm^(−1)Hz^(-1/2), as well as a detection limit of 8.4 x 10^(−14) cm^(−1) on a narrow spectral interval. This unprecedented performance is based on the tight Pound-Drever-Hall lock of the ring-down cavity to a single-sideband-tuned distributed-feedback diode laser which is optical-feedback-stabilized to a highly stable V-shaped reference cavity. To transfer the coherence of this sub-kHz laser source to noisier lasers in other spectral regions through an optical frequency comb, we have explored a novel high-bandwidth feed-forward phase cloning scheme and demonstrated a residual phase error as low as 113 mrad. Applying OFFS-CRDS to the spectroscopy of CO_2 near 1.6 μm, we obtained a broadband spectrum with a dynamic range of 8 x 10^5 and retrieved twelve absolute transition frequencies with kHz-accuracy by measuring sub-Doppler saturated absorption Lamb dips with a comb-assisted setup. Furthermore, we have performed a comprehensive analysis of systematic error sources in CRDS and derived an analytic formula for the non-exponential ring-down signal in a weakly saturated regime, which may contribute towards future concentration-independent transition dipole moment measurements. Our results open up promising perspectives for metrological applications of OFFS-CRDS, such as advanced absorption lineshape studies, isotopic ratio measurements and extensive saturated absorption spectroscopy in the near infrared.

In this work we generalize existing theory of low-energy collisions of atomic hydrogen with its anion. We extend the non-local resonance model for this system by adding new discrete state and two continua that are coupled with it. We calculate numerically cross sections for associative electron detachment process that is important for models of early universe. We add cross section for collision detachment and show spectra of outgoing electrons. We show how the isotopic effect is involved in studied collision. We also calculate charge transfer, elastic scattering cross sections, and reaction rates for hydrogen collisions with deuterium anion. We compare our results with recent experiments and we discuss their reliability. Powered by TCPDF (www.tcpdf.org)