Photodynamic therapy has been established as one of the approaches for the treatment of various malignant tumors. While most of the reagents used for this purpose are porphyrin derivatives, there is a strong motivation for finding novel and better sensitizers. Perylenediimides are known for their photo- and chemical stability, but they do not have absorptions in the red end of the visible spectrum. However, recently reported green perylenediimides which have dialkylamino substituents on the perylene core, provide an alternative. To that end, we have designed and synthesized novel green perylenediimides with remarkable water solubility at neutral pH and absorption peaks beyond 650 nm. We demonstrated that on red-light excitation, singlet oxygen trap 1,3-diphenyl-iso-benzofuran is rapidly degraded. We also carried out cell culture experiments / an important parameter to be optimized for practical application as a novel photodynamic therapy agent was the excited dye toxicity to dark toxicity. Our results confirmed that these novel perylenediimides acted as sensitizers generating singlet oxygen and the initial in vitro biological experiments demonstrated their potential utility in photodynamic therapy.

The central issue in this thesis is configurationality, which has broadly been defined in terms of a division of the world's languages based on their core syntactic structure. Specifically, languages are traditionally divided into so-called configurational and non-configurational languages. Configurational languages are assumed to be languages with many restrictions on word order, and non-configurational languages are assumed to be languages with very few or no word order restrictions. Many linguists posit a strict division between the two different types of languages. In this thesis I propose a non-derivational approach to configurationality, and I discuss in detail three posited characteristics of non-configurational languages (in comparison to configurational languages): free word order, discontinuous expressions and subject-object asymmetries in binding. I propose a four-way classification of languages instead of a two-way one, based on constraints on annotations on phrase structure nodes, both for argument functions and for information structural roles (such as topic and focus). I propose that this four-way distinction is what underlies configurationality. I show that discontinuous expressions and potentially subject-object symmetries follow from the nature of languages that have traditionally been classified as non-configurational. For my analysis I employ Lexical Functional Grammar (LFG), a non-derivational framework which is particularly well-suited to account for languages in which grammatical functions are not tied to specific phrase structural positions, due to its parallel architecture. This characteristic of LFG enables me to provide a straightforward classification of languages, by the ability to separate the influence of grammatical functions and information structural roles on word order and phrase structural configuration.

No description available.

L’Accident de Décompression présente un risque majeur pour les plongeurs. Il est admis que la formation de bulles circulantes est à l’origine de l’ADD. Cependant, une forte variabilité inter individuelle existe entre plongeurs, avec une faible corrélation entre bulles et symptômes de l’ADD. Plusieurs mécanismes physiologiques ont été liés à l’ADD, mais aucun d’entre eux ne semble déterminant dans la mise en place de la pathologie. Dans ce contexte, des techniques issues de la médecine de précision pourraient apporter de nouveaux éléments de compréhension.Durant cette thèse, nous avons effectué des études protéomiques afin d’étudier les possibles changements du protéome plasmatique de rats et de plongeurs suite à une plongée avec ou sans ADD, dans le but de trouver de potentiels biomarqueurs de développement précoce de l’ADD. Nous avons de plus mis en évidence une potentielle implication de processus inflammatoires dans la mise en place des symptômes de l’ADD. Un protocole de sélection a ensuite été utilisé dans le but de créer une nouvelle souche de rats résistante à l’ADD. Une résistance à l’ADD est apparue en l’espace d’une génération chez les femelles, deux chez les mâles. Une caractérisation physiologique de la souche résistante a montré une potentielle implication d’une région spécifique du chromosome X, ainsi que des modifications du fonctionnement du muscle lisse vasculaire, de la résistance aux espèces réactives de l’oxygène, de la consommation d’oxygène mitochondriale, et du système immunitaire. Les suites de cette caractérisation se focaliseront sur des études transcriptomiques et génétiques, en particulier sur la région d’intérêt du chromosome X. / Decompression Sickness is one of the most serious hazards for divers. It is usually admitted that DCS origins from circulating bubbles. However, a strong inter-individual variability exists between divers, resulting in a poor correlation between bubble grade and DCS symptoms. Several physiological mechanisms have been linked with DCS, but none of them appeared to be determinant in the onset of the pathology. In this context, medicine precision techniques may offer new insights, with a broader approach.During this thesis, we used proteomics to investigate changes of the plasma proteome of rats and divers during diving, with and without DCS, and aimed at finding biomarkers of early DCS development. We found that acute inflammation may play a role in the onset on DCS, and that proteomics may be fitted to look for new biomarkers. We also used a selection protocol to create a new DCS resistant rat strain, which was significantly more resistant than classic Wistar rats. Moreover, DCS resistance was gained in a matter of only 2 reproductions cycles (only 1 for females), which gives evidence of heritable components of DCS resistance/susceptibility that might be carried out by the X chromosome. A characterization of this DCS resistant strain showed a number of physiological adaptations gained during the selection process. Indeed, DCS resistant rats showed a decreased mitochondrial oxygen global consumption, a decrease of vascular smooth muscle contraction and relaxation as well as a raise of neutrophils count among males.Further characterization of the DCS resistant strain will focus on transcriptomic and genetic studies, especially on the genomic region of interest located on the X chromosome.

Verb classifications have attracted a great deal of interest in both linguistics and natural language processing (NLP). They have proved useful for important tasks and applications, including e.g. computational lexicography, parsing, word sense disambiguation, semantic role labelling, information extraction, question-answering, and machine translation (Swier and Stevenson, 2004; Dang, 2004; Shi and Mihalcea, 2005; Kipper et al., 2008; Zapirain et al., 2008; Rios et al., 2011). Particularly useful are classes which capture generalizations about a range of linguistic properties (e.g. lexical, (morpho-)syntactic, semantic), such as those proposed by Beth Levin (1993). However, full exploitation of such classes in real-world tasks has been limited because no comprehensive or domain-specific lexical classification is available. This thesis investigates how Levin-style lexical semantic classes could be learned automatically from corpus data. Automatic acquisition is cost-effective when it involves either no or minimal supervision and it can be applied to any domain of interest where adequate corpus data is available. We improve on earlier work on automatic verb clustering. We introduce new features and new clustering methods to improve the accuracy and coverage. We evaluate our methods and features on well-established cross-domain datasets in English, on a specific domain of English (the biomedical) and on another language (French), reporting promising results. Finally, our task-based evaluation demonstrates that the automatically acquired lexical classes enable new approaches to some NLP tasks (e.g. metaphor identification) and help to improve the accuracy of existing ones (e.g. argumentative zoning).

D’un point de vue phraséologique, les couleurs constituent un des domaines source les plus enclins à l’exercice réinterprétatif. Les chromatismes qui en résultent sont chargés d’une grande force évocatrice, car, outre leur éventuelle motivation chromatique, ils véhiculent, à des degrés différents, les conventions culturelles et idiosyncrasiques de la communauté langagière qui les a créés. En effet, les chromatismes sont à la fois le reflet d’une perception ontologique universelle et le résultat d’une conventionnalisation ethnolinguistique propre à chaque langue. À travers de cette étude contrastive entre le français et l’espagnol des unités phraséologiques, lato sensu, contenant une lexie chromatique, nous mettons en relief les convergences et divergences entre les chromatismes créés par deux communautés langagières très proches. / From a phraseological perspective, colours are one of the most source fields most likely to be reinterpreted. The chromatic phraseological units obtained from this process contain an important evocative force. Besides their potential chromatic motivation, they convey, to different degrees, the cultural and idiosyncratic conventions established by the speech community that created them. In fact, chromatisms are at the same time the reflection of a universal ontological perception and the result of an ethnolinguistic conventionalisation inherent to each language. Through this contrastive study between French and Spanish phraseological units, which contain a chromatic word, we highlight the convergences and divergences between the chromatisms created by those close speech communities.

Epilobium hirsutum L. (Onagraceae) is a flowering, tall and perennial plant and native to Eurasia. It shows analgesic, anti-microbial and anti-proliferative activity, and it is used in our country as an alternative medicine. The pharmacological effect of Epilobium hirsutum L. could be explained by the presence of polyphenolics including steroids, tannins and flavonoids in the aerial parts. Viscum album L. (Loranthaceae) is a shrub that grows as an epiphyte on the branches of deciduous trees. It involves in the enhancement of macrophage phagocytic and cytotoxic mediated abilities as well as the strengthening the immune system. CYP24A1 and CYP27B1 are members of cytochrome P450 superfamily and the most important enzymes involved in the metabolism of vitamin D3. CYP27B1 and CYP24A1 are mitochondrial enzymes and also known as 25-hydroxyvitamin D3 1alpha-hydroxylase and 24-hydroxylase, respectively. CYP24A1 involves in 24-hydroxylation of 25-OH-D3 and 1,25-(OH)2D3 which is required for the catabolism of vitamin D3 compounds while CYP27B1 involves in 1&alpha / -hydroxylation of 25-OH-D3 into 1,25-(OH)2D3. In this study, in vivo effects of Epilobium hirsutum and Viscum album (subspecies growing on pine-trees-subsp. austriacum (Wiesb.) Vollmann) on rat liver CYP24A1 and CYP27B1 mRNA and protein expressions were investigated. To achieve this goal, 37.5 mg water extract of Epilobium hirsutum L./kg body weight/day was intraperitoneally injected to male rats for 9 days. To study the effect of Viscum album L., 10 mg water extract of Viscum album L./kg body weight/day was injected with the same conditions. After decapitation, livers were removed and S1.5 fractions were prepared. Effects of Epilobium hirsutum L. and Viscum album L. on rat liver mRNA and protein expressions were analyzed by qRT-PCR and western blotting, respectively. Epilobium hirsutum L. extract caused 31% and 18% decrease in rat liver CYP24A1 (p&lt / 0.0001) and CYP27B1 (p&lt / 0.05) protein expressions, respectively. The effect of Epilobium hirsutum L. on mRNA expression of CYP24A1 could not be observed, because CYP24A1 mRNA was almost undetectable in liver. Injection of Epilobium hirsutum L. to rats caused 2.7 fold increase in mRNA expression of CYP27B1 with respect to controls and normalized with GAPDH (Glyceraldehyde 3-phosphate dehydrogenase) expression as an internal reference (p&lt / 0.005). Viscum album L. caused 17% decrease in CYP24A1 protein expression (p&lt / 0.05). When rats injected with plant extract of Viscum album L., 18% decrease in CYP27B1 protein expression was observed (p&lt / 0.05). The effect of Viscum album L. on mRNA expression of CYP24A1 could not be observed since CYP24A1 mRNA was almost undetectable in liver. Injection of Viscum album L. to rats caused 3.8 fold increase in mRNA expression of CYP27B1 with respect to controls and normalized with GAPDH (Glyceraldehyde 3-phosphate dehydrogenase) expression as an internal reference (p&lt / 0.005). In conclusion, vitamin D3 metabolism may be affected by medicinal plants Epilobium hirsutum L. and Viscum album L. due to the changes in mRNA and protein expressions of CYP24A1 and CYP27B1 enzymes.

The effects of diabetes on cytochrome P450 dependent drug metabolizing enzymes have not to be clarified yet. The most widely used animals in these studies have been rats, and information regarding the effects of diabetes on cytochrome P450 dependent procarcinogen/carcinogen metabolism in rabbits is limited. In the present study, we investigated, for the first time, the influence of benzene on liver, kidney and lung microsomal cytochrome P450 dependent drug metabolizing enzyme activities, protein and mRNA levels in diabetic and non-diabetic rabbits. Male New Zealand rabbits were made diabetic by a single dose of alloxan treatment in this study. AST, ALT and LDH enzyme activities in the blood serum and lipid peroxidation in liver microsomes were found to increase in diabetic, benzene treated and benzene treated diabetic rabbits. Besides these, CYP2E1 dependent NDMA N-demethylase and p-nitrophenol hydroxylase activities and CYP2E1 protein level were found to increase in liver and kidney of diabetic and benzene-treated rabbits. The combined effects of benzene and diabetes on these activities and protein level were found to be additive. Although diabetes caused induction of pulmonary CYP2E1 protein level and associated enzyme activities, benzene treatment of rabbits resulted in no change in enzyme activities and protein level in lung. The level of mRNA was investigated by Real-Time PCR. Accordingly, hepatic CYP2E1 mRNA level was increased 6.71-, 10.53- and 12.93-fold in diabetic, benzene treated and benzene treated diabetic rabbits with respect to the control animals. Similarly, renal CYP2E1 mRNA level was found in increase in these rabbits. In addition to CYP2E1, CYP3A6 associated enzyme activity, erythromycin N-demethylase, CYP3A6 protein and mRNA level were found to increase in diabetic rabbit liver and lung. Unlike diabetes, benzene treatment caused suppression of CYP3A6 protein and inhibition of associated enzyme activity in liver. There was no significant change in the erythromycin N-demethylase activity and CYP3A6 level of liver and lung as a result of benzene treatment of diabetic rabbits. Moreover, diabetes induced CYP1A2 protein and mRNA level and CYP1A associated enzyme activities in the rabbit liver. On the other hand, benzene caused statistically insignificant decreases in CYP1A dependent enzyme activities and CYP1A2 protein level in liver. CYP1A associated enzyme activities, CYP1A2 protein and mRNA levels were not changed in the liver of benzene treated diabetics. The results of the present work indicate that both diabetes and benzene stimulate metabolic activation toxic chemicals metabolized by CYP2E1 such as NDMA and benzene by inducing CYP2E1 which results in the formation of increased amounts of reactive metabolites. Application of benzene to diabetic rabbits further elevates expression and activities of the CYP2E1. As a result of additive induction of the CYP2E1 in benzene treated diabetics, further increase the risk of hepatotoxicity produced by toxins may be observed when compared to the separate treatments. This may in turn further potentiate the risk of organ toxicity and mutagenesis in liver and kidney of these subjects. As in the case of CYP2E1, the risk of carcinogenesis due to induction of CYP1A may be increased in diabetic subjects. Moreover, in diabetic and benzene exposed subjects, alteration of drug clearance and clinical drug toxicity may be observed due to induction or suppression of CYP3A.

Cancer is the second leading cause of death after cardiovascular diseases in the world. Many of the chemical carcinogens need metabolic activation that catalyzed by cytochrome P450 and Phase II enzymes in order to exert their genotoxic and carcinogenic effects. Hence one possible mechanism is that phenolic compounds may alter anticarcinogenic effects is through an interaction with these enzymes either by the inhibition or activation of certain forms, leading to a reduced production of the ultimate carcinogen. Therefore anti-carcinogen activity of tannic acid, a hydrolyzable plant polyphenol, has a crucial importance to prevent conversion of pro-carcinogens to their carcinogenic form. Tannic acid is produced from secondary metabolism of plants and is found in edible vegetables, fruits and nuts, especially tea, cocoa, coffee and wine. In the present work, modulation of rabbit liver and kidney microsomal P450 dependent aniline 4-hydroxylase, N-nitrosodimethylamine N-demethylase and p-nitrophenol hydroxylase activities and cytosolic phase II enzymes / glutathione S-transferase (GST), NAD(P)H:quinone oxidoreductase:1 (NQO1) were studied in the presence of tannic acid at concentrations ranging from 0.5 &micro / M to 150 &micro / M in the reaction medium. The results obtained in this study were shown that tannic acid significantly inhibited the activities of p-nitrophenol hydroxylase, aniline 4-hydroxylase, NDMA N-demethylase, glutathione S-transferase, NAD(P)H:quinine oxidoreductase 1. Tannic acid was found to be the most potent inhibitor of cytosolic glutathione S-transferase with IC50 of 0.33 &micro / M and the least potent inhibitor of microsomal aniline 4-hydroxylase.with IC50 of 60.26 &micro / M. Effect of tannic acid on enzyme activities was further studied for both mode and type of inhibition. For this purpose various concentrations of the substrate were examined at various tannic acid concentrations. Lineweaver-Burk and Dixon plots were then generated from the resulting data sets. The Km value and inhibition constants (KI) were determined from double reciprocal and Dixon plot of the enzyme activity versus substrate and inhibitor concentration, respectively. Tannic acid was shown to be a noncompetitive inhibitor for liver cytosolic GST, NQO1 and microsomal aniline 4- hydroxylase enzymes with KI of 0.3 &micro / M, 41 &micro / M and 54.7 &micro / M, respectively. On the other hand, in kidney tissues, tannic acid was an uncompetitive inhibitor of cytosolic GST, while it was noncompetitive inhibitor for cytosolic NQO1 with a KI of 12.6 &micro / M. These results indicate that tannic acid may modulate cytochrome P450 dependent and Phase II enzymes and influence the metabolic activation of xenobiotics mediated by these enzymes.

Grass family is most important family in plant kingdom due to intensive usage of crops in agriculture. To date, molecular biology researches on grass family have had limitations because of inappropriate characteristics of barley and wheat to conduct experiments on them. Brachypodium distachyon that belongs to grass family has recently emerged as a model organism for crops. It shares common characteristics for a model plant due to its small genome, small physical plant size, a short lifecycle, and less demanding growth requirements / as other model organisms / Arabidopsis thaliana, Oryza sativa, and Zea mays (Draper et al. 2001). Especially after appreciating, the genetic distance of O. sativa to grasses (Garvin et al. 2008), it become a key organism to understand complicated genomic organization of agriculturally valuable grasses. Virus-induced gene silencing (VIGS) is one of the revolutionary methods allowing a rapid and effective loss of a gene function through RNA interference (Holzberg et al. 2002 / Liu et al. 2008). Barley stripe mosaic virus (BSMV) is still the most effective vector used in monocot gene silencing. It has a tripartite RNA genome having a wide range of infection ability for monocots including barley, oat, wheat, and maize as host (Holzberg et al. 2002 / Scofield 2005). In this thesis, Phytoene desaturase (PDS) gene of Brachypodium distachyon was silenced via BSMV mediated VIGS. Additionally, with Green fluorescence protein (GFP) bearing BSMV transcripts, GFP expression was observed under fluorescent microscope. To our knowledge, this is the first report demonstrating a VIGS via BSMV in Brachypodium distachyon. The success of virus induced gene silencing method in Brachypodium distachyon, will be a new convenient tool for evaluating functions of crop genes in this model organism.