Les travaux ont pour objectif de trouver des catalyseurs capables de remplacer les organo-étains pour la réticulation de matériaux adhésifs. La stratégie employée au laboratoire exploite des outils de la chimie en parallèle afin d’en tester un grand nombre pour accéder plus rapidement à la découverte de systèmes catalytiques performants. / The aim of this work is to discover new catalytic systems to replace organotin compounds. The strategy used on our laboratory exploits tools of high throughput experiments to test a large number of catalysts in the same time in order to discover new catalytic systems more quickly.

>Magister Scientiae - MSc / The Rosaceae family contains major temperate crops such as the domesticated apple(Malus x domestica Borkh.), peach (Prunus persica L. Batsch) and European pear (Pyrus communis L.). However, despite its evident economic importance, it is generally poorly studied in genomic terms, relative to the other major crop groups. Microsatellite and Diversity Array Technology (DArT) genetic markers have been exploited in this work and are essential tools in genetic map construction and marker-assisted selection (MAS) of high quality apples and other rosaceous crops. Microsatellites are advantageous in that they are co-dominant, highly polymorphic, abundant, transferable and reliably reproducible; hence their use in this study. In order for budbreak to take place in a timely and homogenous fashion, apple trees need a period of exposure to low temperatures.Within orchards the application of chemicals that induce budbreak in unsuitable environments is required to produce apples from cultivars that require high chilling levels. However, this and other practices using chemicals in orchards tend to pollute the environment. One of the solutions to this problem is to breed low chill apples such as ‘Anna’ cultivar, which was used as one of the parents in this study.This work was aimed at understanding the underlying genetic factors that determine chilling requirements for the time of initial vegetative budbreak trait in the apple cross ‘Anna’ x ‘Austin’. This was achieved through linkage map construction using SSR and DArT molecular markers followed by QTL analysis. This thesis has therefore exploited the large number of Expressed Sequence Tags (ESTs) and genome sequence data for the apple, using Tandem Repeats Finder, to design a total of 98 new SSR primers pairs. The other 369 SSR markers used in this work were from published work. JoinMap! 4.1 software was used to create an integrated genetic map with 17 linkage groups, for the domesticated apple cultivar, ‘Austin’ x ‘Anna’ mapping population with 80 individuals.The result of this process was a genetic map 1 212cM in length, and a total of 429 markers (314 DArT and 115 SSR), at an average density of a marker every 4 cM. This map was used identify the Quantitative Trait Loci (QTLs) determining chilling requirements for time of vegetative budbreak (IVB). In this process, putative IVB QTLs were identified in the ‘Anna’ x ‘Austin’ mapping population using the rMQM analysis function of MapQTL! 6.0, for both adult and seedling data collected over 3 growing seasons from 1996 to 1998. These QTLs were detected on linkage groups 2, 9 and 14,and explained 0.3 to 12.8 % of the observed phenotypic variation for the adult population,and 5.3 - 21 % for the seedling population. Seedling (LG 14) and adult (LGs 5, 7, 10) specific QTLs were also detected for the ‘Anna’ x ‘Austin’ cross. These QTLs will provide the basis for marker validation on related mapping populations in the apple breeding programme, and for the future identification of candidate genes controlling the process of budbreak.

In the European Union an environmental risk assessment is required for the registration of new chemicals, biocides, pesticides and pharmaceuticals. In order to avoid the release of potential hazardous substances, various ecotoxicity tests are performed, including acute and chronic fish tests. As a consequence of the new program of the European Union “Registration, Evaluation and Authorisation of Chemicals” (REACH) the number of animal experiments for environmental risk assessment is expected to increase remarkably within the next years. On the other hand there is a strong societal demand for reducing the number of animal tests by using alternative in vitro models. According to EU directives, investigations using non-human vertebrate embryos are considered pain free in vitro methods and are therefore accepted as alternatives to animal experiments. For the acute fish test, the Danio rerio embryo test (DarT) has been established as a replacement method and included in national regulations at least for waste water (German Waste Water Dues Law). However, no alternatives for chronic fish tests are currently available. The overall goal of this thesis was to work towards such a replacement by extending DarT zu Gene-DarT. Toxicants will initially interact at the molecular level with consequences for physiology, fitness and survival. The analysis of gene expression patterns may unravel elements of these molecular events before any phenotypic changes are visible. The hypothesis of this thesis therefore was that chemical-sensitive genes in embryos exposed in a conventional DarT may indicate toxic impact of substances at sub-acute concentrations and thus enhance the sensitivity of the embryo toxicity test. Furthermore, unlike the conventional DarT-endpoints, gene expression analysis will provide insights into mechanistic processes underlying toxicity. The 3,4-dichloroaniline (3,4-DCA), which is used as a reference compound in the DarT, was selected as model chemical in this thesis. In a first step, differentially expressed genes in embryos exposed to 3,4-DCA were identified by microarray technology and RT-PCR techniques. Six dose-dependent significant differentially expressed genes were identified. These genes were involved in biotransformation pathways (cyp1a, ahr2), stress response (nrf2, maft, ho-1) and cell cycle control (fzr1). Differential expression upon 3,4-DCA exposure was detected below the LOEC (lowest observed effect concentration = 6.2 µM) of survival or developmental disorders of the embryo test (0.78 µM and above). For the validation of stage specific sensitivity, genes were also analysed in post-hatched stages. Extension of exposure to post-hatched stages resulted in a differential expression at lower concentrations as for the embryonic stages, indicating an improved sensitivity due to stage-specific sensitivity or exposure time. To confirm the adaptive function of the 3,4-DCA-sensitive genes, embryonic mRNA abundance was experimentally manipulated by knock down and overexpression. By injection of sense (mRNA) or antisense (siRNA) RNA in one-cell-stages of embryos, the transcript levels of genes were transiently enhanced or repressed in embryos exposed to 3,4-DCA. mRNA injection of the genes cyp1a, ho-1 and nrf2 reduced the number of embryos with 3,4-DCA-induced malformations. In contrast, siRNA injections for the same genes led to an increase in the severity and frequency of developmental disorders. The results clearly indicate the adaptive functions of the investigated genes or their corresponding proteins. This study demonstrates that the analysis of chemical-sensitive gene expression shows the potential to increase the sensitivity of conventional toxicity tests. The analysis of gene expression also provides additional mechanistic information for toxic action, e.g. in the presented study, the involvement of Ah-receptor regulated pathways as an adaptive response. Furthermore, the presented data indicate that functional manipulations, using mRNA and siRNA-injection, are suitable to evaluate the role of differentially expressed genes for toxicity.

Les lichens, organismes symbiotiques associant un champignon et un partenaire photosynthétique (algue verte et/ou cyanobactérie), sont caractérisés par la biosynthèse de métabolites secondaires uniques dotés de bioactivités variées. Pour valoriser au mieux cette ressource privilégiée, des méthodes innovantes de spectrométrie de masse ont été développées dans le but de minimiser la préparation de l’échantillon et la durée des analyses. Deux techniques de spectrométrie de masse ont été évaluées en ce sens : le DART-MS et le LDI-MS. L’apport de chacune de ces deux méthodes a pu être établi sur un large panel de lichens, représentant une part importante de l’espace chimique couvert par ces organismes. Il a été démontré que des profils chimiques complets pouvaient être obtenus respectivement à partir de thalles lichéniques et d’extraits acétoniques totaux. Compte tenu de la très large utilisation de la CCM pour l’analyse chimique de lichens, les possibilités offertes par le couplage de la CCM à l’ionisation electrospray ont également été explorées. Une seconde partie de ces travaux avait pour but de cartographier la distribution des métabolites secondaires au sein du thalle lichénique. À ces fins, des analyses d’imagerie LDI ont été réalisées sur une coupe transversale d’un lichen crustacé modèle : Ophioparma ventosa. Ce lichen a été étudié en phytochimie pour identifier six napthopyranones à partir des apothécies dont quatre nouvelles structures. Les principaux métabolites de ce lichen ont pu être imagés par LDI-MSI avec une résolution spatiale de 50 μm environ. Une corrélation entre la distribution des molécules et leur rôle écologique présumé permet d’avancer des hypothèses d’écologie chimique. Des approches conjointes reliant histolocalisation et étude génétique des partenaires de la symbiose ont été entreprises. La recherche des gènes de la biosynthèse de la mycosporine sérinol chez les symbiontes isolés de Lichina pygmaea par microdissection capture laser a été initiée en ce sens. D’autres approches innovantes comme l’analyse cristallographique par diffraction de poudre par les rayons X sont également abordées dans ce document articulé autour de six publications issues de ce travail et de deux articles en cours de soumission. / Lichens are self-sustaining symbiotic partnerships comprising a fungus associated with a green alga and/or a cyanobacteria. This consortium produces unique secondary metabolites that are endowed with various biological activities. To harness this privileged chemodiversity, innovative mass spectrometry techniques were developed in the course of this study to accelerate the dereplicative holdup through both a minimal sample preparation and a decrease of the time of analysis. Two approaches were considered during this work: DART-MS and LDI-MS and their adequacy for lichen dereplication was assessed on a vast array of samples encompassing a wide range of metabolites. Both of them facilitated complete chemical profiles, respectively from unprocessed lichen material and crude acetone extracts. Since TLC still enjoys a wide-spread popularity among lichenologists, the advantages offered by TLC-ESI-MS hyphenation were evaluated as well. A second part of this manuscript focused on the histolocalization of lichen metabolites. For this purpose, LDI mass spectrometry imaging studies were undertaken on the crustose lichen Ophioparma ventosa. The phytochemical investigation of this species afforded the isolation of six naphthopyranones from its apothecia, four of them being new molecules. LDI-MSI revealed the distribution patterns of all the main metabolites of this lichen, reaching a spatial resolution of 50 μm. Most interestingly, the distribution pattern of imaged metabolites within the thallus is highly organized and is related to their ecological relevance. Joint strategies combining histolocalization and genetic investigation of lichen symbionts separated using laser capture microdissection were also considered. As such, an investigation of the biosynthesis of mycosporine serinol within Lichina pygmaea dissociated symbionts was initiated. Further analytical strategies such as X-ray powder diffraction are introduced in this thesis that contains six publications and two drafts to be submitted.

In the European Union an environmental risk assessment is required for the registration of new chemicals, biocides, pesticides and pharmaceuticals. In order to avoid the release of potential hazardous substances, various ecotoxicity tests are performed, including acute and chronic fish tests. As a consequence of the new program of the European Union “Registration, Evaluation and Authorisation of Chemicals” (REACH) the number of animal experiments for environmental risk assessment is expected to increase remarkably within the next years. On the other hand there is a strong societal demand for reducing the number of animal tests by using alternative in vitro models. According to EU directives, investigations using non-human vertebrate embryos are considered pain free in vitro methods and are therefore accepted as alternatives to animal experiments. For the acute fish test, the Danio rerio embryo test (DarT) has been established as a replacement method and included in national regulations at least for waste water (German Waste Water Dues Law). However, no alternatives for chronic fish tests are currently available. The overall goal of this thesis was to work towards such a replacement by extending DarT zu Gene-DarT. Toxicants will initially interact at the molecular level with consequences for physiology, fitness and survival. The analysis of gene expression patterns may unravel elements of these molecular events before any phenotypic changes are visible. The hypothesis of this thesis therefore was that chemical-sensitive genes in embryos exposed in a conventional DarT may indicate toxic impact of substances at sub-acute concentrations and thus enhance the sensitivity of the embryo toxicity test. Furthermore, unlike the conventional DarT-endpoints, gene expression analysis will provide insights into mechanistic processes underlying toxicity. The 3,4-dichloroaniline (3,4-DCA), which is used as a reference compound in the DarT, was selected as model chemical in this thesis. In a first step, differentially expressed genes in embryos exposed to 3,4-DCA were identified by microarray technology and RT-PCR techniques. Six dose-dependent significant differentially expressed genes were identified. These genes were involved in biotransformation pathways (cyp1a, ahr2), stress response (nrf2, maft, ho-1) and cell cycle control (fzr1). Differential expression upon 3,4-DCA exposure was detected below the LOEC (lowest observed effect concentration = 6.2 µM) of survival or developmental disorders of the embryo test (0.78 µM and above). For the validation of stage specific sensitivity, genes were also analysed in post-hatched stages. Extension of exposure to post-hatched stages resulted in a differential expression at lower concentrations as for the embryonic stages, indicating an improved sensitivity due to stage-specific sensitivity or exposure time. To confirm the adaptive function of the 3,4-DCA-sensitive genes, embryonic mRNA abundance was experimentally manipulated by knock down and overexpression. By injection of sense (mRNA) or antisense (siRNA) RNA in one-cell-stages of embryos, the transcript levels of genes were transiently enhanced or repressed in embryos exposed to 3,4-DCA. mRNA injection of the genes cyp1a, ho-1 and nrf2 reduced the number of embryos with 3,4-DCA-induced malformations. In contrast, siRNA injections for the same genes led to an increase in the severity and frequency of developmental disorders. The results clearly indicate the adaptive functions of the investigated genes or their corresponding proteins. This study demonstrates that the analysis of chemical-sensitive gene expression shows the potential to increase the sensitivity of conventional toxicity tests. The analysis of gene expression also provides additional mechanistic information for toxic action, e.g. in the presented study, the involvement of Ah-receptor regulated pathways as an adaptive response. Furthermore, the presented data indicate that functional manipulations, using mRNA and siRNA-injection, are suitable to evaluate the role of differentially expressed genes for toxicity.

L'utilisation du LiDAR en télédétection permet une description précise de l'architecture du couvert végétal. L'objet de cette thèse est le développement des approches d'inversion de mesures LiDAR à l'aide d'une modélisation physique et statistique du signal dans le but d'estimer des propriétés biophysiques de cultures dominantes (blé, maïs) du Sud-Ouest de la France et d'un couvert forestier en Chine. Le travail a tout d'abord porté sur l'estimation du LAI et la hauteur des cultures par inversion de formes d'onde LiDAR à faible empreinte. Une base de données de simulations de formes d'onde réalistes des cultures est réalisée à l'aide du modèle de transfert radiatif (MTR) DART. L'inversion consiste à utiliser la technique de table de correspondance qui consiste à chercher la simulation la plus proche de l'observation réelle. Le travail a ensuite porté sur l'estimation du profil de LAI des arbres de la forêt. Une approche variationnelle d'estimation du profil de LAI par inversion de formes d'ondes est proposée. Elle repose sur un MTR simplifié et une technique de lissage du profil de LAI s'appuyant sur les chaines de Markov. La formulation bayésienne du problème, nous amène à une fonction de coût non-linéaire. Elle est minimisée à l'aide d'une nouvelle technique de gradient multi-échelle. Les approches développées montrent bien leurs performances en les appliquant sur des données réelles de cultures (maïs et blé) et de milieu forestier. / The use of LiDAR in remote sensing allows a precise description of the vegetation cover architecture. The aim of this thesis is the development of LiDAR data inversion approaches using physical and statistical signal modeling in order to estimate the biophysical properties of dominant crops (wheat, maize) of the South-West of France and a forest cover in China. The work firstly focused on estimating LAI and crop height by small footprint LiDAR waveforms inversion. A realistic crop waveform simulations database is performed using the Radiative Transfer Model (MTR) DART. The inversion consists in using the Look up Table technique which consists of looking for the closest simulation to the actual observation. The second inversion approach focused on LAI profile estimation of the forest trees. A variational approach to estimate LAI by waveform inversion is proposed. It relies on a simplified MTR and LAI profile smoothing technique based on Markov chains. The Bayesian formulation of the problem leads us to a non-linear cost function. It is minimized using a new multi-scale gradient technique. The developed approaches show clearly their performance by applying them to real crop data (corn and wheat) and forest.

Cancer is the leading cause of death in Canada. Many cancer treatments are using chemotherapy, surgery and radiotherapy. In radiotherapy, photons are the most used ionizing radiation, however alpha particles have higher radiobiological impact which increases the efficiency of patient treatment delivery. Alpha Tau Medical Ltd. (Tel Aviv, Israël) has developed a new brachytherapy method using radioactive seeds. The seeds called DaRT, for Diffusing alpha emitters Radiation Therapy, are composed of 224-Ra atoms which come from 228-Th generator. Currently, these seeds are characterized by an alpha-spectrometer and Geiger-Muller counter or well chamber for quality control. This project offers a new characterization of DaRT seeds using liquid scintillation. Liquid scintillation allows alpha and beta particles detection with the help of liquid cocktail and employing a scintillation counter. The characterization with liquid scintillation allows establishing and quantifying 228-Th trace contamination on the DaRT seeds. Also, it provides a method for seed quality control before they are used on patients by estimating their activity from spectrums established with the liquid scintillation counter. The spectrums obtained also give the possibility of dose estimation using either mass or mass stopping power in water. The results of the dose are compared to expected values from the literature and to simulations. / Le cancer est la première cause de mortalité au Canada. De nombreuses techniques de traitement du cancer existent utilisant la chimiothérapie, la chirurgie et la radiothérapie. En radiothérapie, les photons sont les rayonnements ionisants les plus fréquemment utilisés, cependant les particules alpha présentent des propriétés radiobiologiques intéressantes augmentant l'efficacité des résultats du traitement prodigué au patient. Une nouvelle technique de curiethérapie ayant recourt à des grains a été développée par Alpha Tau Medical Ltd.(Tel Aviv, Israël). Pour ce faire les grains appelés DaRT, pour Radiothérapie par émetteurs-alpha diffusant, sont constitués d'atomes 224-Ra issu d'un processus de fabrication à l'aide d'un générateur de 228-Th. Ces grains sont actuellement caractérisés par spectromètre-alpha et compteur Geiger-Muller ou chambre à puit dans le cas du contrôle de qualité. Ce projet vise à proposer une nouvelle caractérisation des grains DaRT en recourant à la scintillation liquide. La scintillation liquide permet la détection des particules alpha et beta à l'aide de liquide scintillant et d'un compteur de scintillation. La caractérisation des grains avec la scintillation liquide permet d'établir et de quantifier la présence de trace de contamination de 228-Th. Cette technique de mesure de la radioactivité donne aussi la possibilité de réaliser le contrôle de qualité des grains avant son utilisation sur les patients en évaluant l'activité de ces derniers à partir des spectres obtenus par le compteur de scintillation liquide. Les spectres obtenus offrent la réalisation d'une estimation de la dose soit par la masse soit par le pouvoir d'arrêt massique des alpha dans l'eau. Les résultats de la dose sont comparés à des valeurs attendues de la littérature et de simulation.

The field I’m working in is “design through construction”. Construction as a field in fashion design when creating has expanded and there are many views upon how one can work whit-in this field. I’m working with a cut and then bending or displacing it through placing it on the body so it creates volume which starts from its vertex. One could say that it works like an inverted dart. This way to work has a potential to create volume that stands out from the body without using standard ways e.g. like adding a new pattern piece or build a crinoline. It might answer to the question: How can one create shape or arrange shape without adding anchor points? Therefor I explore the relation between body and shape through inverted dart. I’ve been executing experiments through a trial and error method diverged in three steps when in the physi- cal part examine my aim in tests based on the body pressing a cut apart which gives an effect in the vertex of the cut. Through my research I’ve have come to a conclusion that the body in itself can transform garment trough an inverted dart by stepping into it. The relation between the body and material through the inverted dart has qualities were body can arrange dress and define it trough folding fabric and body can through the inverted dart make room for itself. This idea and development is relating to the basics when make dress, body and material and how we can work whit these opponents. Instead of thinking about new variables like new technical tools, e.g. the laser cutter when pushing boundaries one can also take new turns with basics. In this work the body defines dress through the inverted dart (an interaction between body and dress) and create new ways of handling fabric and shape. This perspective on design and art can also been used when working in other fields when distort basic prin- ciples to create new expression. As an example there might be possibilities to develop basics in architecture by studying society and therefore understand fundamental values in this field and, how you by change these variables can develop design.

Electrical methods of geophysical survey are known to produce results that are hard to predict at different times of the year, and under differing weather conditions. This is a problem which can lead to misinterpretation of archaeological features under investigation. The dynamic relationship between a ‘natural’ soil matrix and an archaeological feature is a complex one, which greatly affects the success of the feature’s detection when using active electrical methods of geophysical survey. This study has monitored the gradual variation of measured resistivity over a selection of study areas. By targeting difficult to find, and often ‘missing’ electrical anomalies of known archaeological features, this study has increased the understanding of both the detection and interpretation capabilities of such geophysical surveys. A 16 month time-lapse study over 4 archaeological features has taken place to investigate the aforementioned detection problem across different soils and environments. In addition to the commonly used Twin-Probe earth resistance survey, electrical resistivity imaging (ERI) and quadrature electro-magnetic induction (EMI) were also utilised to explore the problem. Statistical analyses have provided a novel interpretation, which has yielded new insights into how the detection of archaeological features is influenced by the relationship between the target feature and the surrounding ‘natural’ soils. The study has highlighted both the complexity and previous misconceptions around the predictability of the electrical methods. The analysis has confirmed that each site provides an individual and nuanced situation, the variation clearly relating to the composition of the soils (particularly pore size) and the local weather history. The wide range of reasons behind survey success at each specific study site has been revealed. The outcomes have shown that a simplistic model of seasonality is not universally applicable to the electrical detection of archaeological features. This has led to the development of a method for quantifying survey success, enabling a deeper understanding of the unique way in which each site is affected by the interaction of local environmental and geological conditions.

The increasing usage of social networking sites, such as Facebook has changed the way that corporations and customer interact with each other. New ways of customer-corporation interactions evolve constantly, enabling customers to participate and co-create value with the corporations. An organisation that has taken this a step further is Skånetrafiken, which uses Facebook as a channel for its customer service. This thesis focuses in the interactions that occur between Skånetrafiken and its customers, which in this case takes place on Facebook.   The purpose of this thesis is to explore the what, how and why customer and corporation interaction occur on Skånetrafiken's Facebook page. In order to approach the phenomenon of co-creation, we conducted a case study as a research design and strategy. Data collection methods we used were observations on Skånetrafiken’s Facebook page, an interview and a focus group discussion.     The findings indicate that there must be an engagement for the co-creation process to begin and that the co-creation process is continuous rather than a fixed model. It further turned out that different types of interactions occur, not only customer-to-corporation, but also customer-to-customer and customer-to-employee interactions. The limitations of the study imply that the findings cannot be generalised on all organisations since only one organisation have been examined. This thesis further gives a practical implication by presenting an applicable framework for co-creation on Facebook. Additionally, few if any have previously studied phenomenon of co-creation on Facebook, which contributes to the original value of the thesis.