La position a priori anti-ottomane, élaborée par des philosophes comme Volney et Montesquieu, en Syrie a été largement partagée par les voyageurs du XIXe siècle et même complétée par l'ensemble des travaux réalisés tout au long du XIXe siècle. Ainsi, voyageurs scientifiques, philosophes, consuls, journalistes ou même poètes, se sont presque tous impliqués dans l'élaboration et la circulation des clichés et des idées reçues sur la Syrie et sur le système turc en Syrie perçu comme une tyrannie globale. Les voyageurs participent ainsi avec leurs écrits, directement ou indirectement, à pérenniser la vision du « despotisme oriental» élaborée par leurs prédécesseurs et relayée dans un premier temps par Volney. Celui-ci, à peine arrivé en Syrie en 1783, dénonçait la misère dont il rendait aussitôt responsables les Turcs. Les autres voyageurs ont presque tous fait le concept de despotisme oriental et ont approuvé dans leurs récits l'auteur du Voyage en Égypte et en Syrie. D'une manière générale, on comprend que l'espace syrien évoque aux voyageurs des souvenirs ancestraux et leur rappelle un passé aussi bien religieux qu'historique parfois très proche. Par là-même, la Syrie, exotique, mythique ou pittoresque, a représenté un intérêt tout particulier pour les voyageurs-écrivains, les touristes et les scientifiques en quête d'exotisme et d'un retour aux sources. / The a priori anti-Ottoman position, developed by philosophers such as Volney and Montesquieu, in Syria, was largely shared by travelers in the 19th century. This preconceived philosophy was reinforced and "completed" by the entire collection of works written throughout the 19th century. Traveling scientists, philosophers, consuls, journalists, and even poets were almost all involved in developing and circulating ideas and clichés regarding Syria and the idea that Turkish rule in Syria was tyrannous. Travelers, as well as their writings, directly or indirectly perpetuated the vision of "Oriental tyranny." This vision, developed by predecessors, was first communicated in writing by Volney. In 1783, he had barely just arrived in Syria, when he began denouncing the misery he encountered, forwhich he held Turkish officials immediately responsible. Other travelers almost all supported the idea of "Oriental Tyranny" and agreed with the author of Voyage en Egypte et en Syrie in their writings.Generally speaking, Syria makes travelers think of their forefathers and reminds them of the past (in both a historic and religious context) that is in reality not that distant from the present. Moreover, those in search of getting back to the basics and the exotic; traveling writers, tourists, and scientists, took a particular interest in the exotic, mythic or picturesque Syria.

Les hétérocycles azotés occupent une place importante en chimie organique et médicinale et, à ce titre, constituent des cibles de choix pour le développement de réactions toujours plus efficaces et faciles d’emploi. Les travaux antérieurs, réalisés au laboratoire URCOM sur l’accès aux γ-lactames, ont servi de base pour développer une méthodologie impliquant des conditions douces qui ont mis en évidence les propriétés spécifiques des N-alkoxy amides pour accéder aux γ- et δ-lactames hautement fonctionnalisés de manière hautement diastéréosélective selon un processus domino. Cette méthodologie a aussi pu être étendue aux hydantoïnes, 2-imino-thiazolidin-4-ones et thiazinan-4-ones qui constituent également des molécules étudiées en chimie médicinale. En parallèle, une comparaison de réactivité entre N-alkoxy amides et N-alkyl amides a montré la meilleure réactivité des composés N-alkoxylés pour l’obtention de ces différents hétérocycles azotés. Cette différence de réactivité a été attribuée à la possible chélation du contre anion alcalins des bases minérales utilisées dans notre approche par les N-alkoxy amides. Les conditions douces ont permis d’envisager des versions organocatalysées énantiosélectives ou multicomposantes des réactions précédentes conduisant à des résultats préliminaires intéressants. / Nitrogen-containing heterocycles are key compounds in organic and medicinal chemistry and continue to attract synthetic effort for the development of more efficient and convenient reaction. Previous work carried out at the URCOM laboratory for the access to γ-lactams has provided the basis for developing a highly diastereoselective methodology under mild conditions that has demonstrated the specific properties of N-alkoxy amides, allowing the access to γ- and δ-lactams following a domino process. This methodology also allowed the access to hydantoïns, 2-imino thiazolidin-4-ones and thiazinan-4-ones which are compounds of importance in medicinal chemistry. In parallel, a comparison of reactivity between N-alkoxy and N-alkyl amides was carried out in order to demonstrate the better reactivity of the N-alkoxy amide compounds. This better reactivity was attributed to a possible chelation of the alkali metal counter anion of the mineral bases used in our conditions by the N-alkoxy amides. These mild conditions allowed organocatalyzed enantioselective or multicomponents approaches providing interesting preliminary results.

Experiments were carried out to determine if pretreatment of cells with N-Methyl-N'-Nitro-N-Nitrosoguanidine (a potent alkylating agent known to induce DNA repair) would affect Herpes Simplex Virus Replication. The data demonstrated a 1.5 fold increase in virus yield, a 2 fold increase in HSV specific TK activity and no change in HSV specific DNA polymerase activity in MNNG treated cultures. The effects of MNNG treatment on virus replication and enzyme expression are discussed. / Thesis / Master of Science (MSc)

1,2-Diazetidine is a four-membered ring heterocyclic compound which has two adjacent nitrogen atoms. However, the syntheses of C-unsubstituted 1,2-diazetidines are rarely reported in the literature. C-unsubstituted 1,2-diazetidines were synthesized through an operationally simple intermolecular vicinal disubstitution reaction between 1,2-dibromoethane and hydrazine with N-arylsulfonyl as the protecting group. Several different types of C-unsubstituted 1,2-diazetidines derivatives were synthesized with either two of the same or two different N-arylsulfonyl groups. The electronic and steric properties were analyzed using Raman spectroscopy and computational calculations. Then, several synthetic applications were demonstrated with 1,2-ditosyl-1,2-diazetidine (DTD). As a synthetic application, a nucleophilic ring-opening reaction of the diazetidine was identified through various thiol selective cleavage of the N‒N bond, resulting in the stereoselective formation of a new class of N-sulfenylimine. Furthermore, DTD underwent FeBr2-catalyzed retro [2+2] ring-opening and sustained release of formaldimine (FI) in situ in a reaction medium which is the simplest imine used amidomethylative reagent. Therefore, the effective available concentration can be controlled at low levels in the reaction medium. Moreover, the sustained release of FI was able to interrupt the amidomethylative process with α- methylstyrene and FeBr2 as the catalyst and resulted in 4-phenyl-1,2,3,6-tetrahydropyrimidine (PTPH) as a product. The PTPH is a neurotoxic compound used to induce Parkinson’s disease in animal models. In addition, sustained release of FI allowed to switch the selectivity from alkene, imine, and imine arrangement into alkene, imine, and alkene arrangement in [2+2+2] cycloaddition reaction and led to form piperidines as a product which is the most observed heterocycle in marketed drug molecules. Chromane derivatives are observed in pharmaceuticals and natural products. Chirally pure chromane derivatives were synthesized through ruthenium-catalyzed chiral transient directing-mediated enantioselective C–H activation. Interestingly, a phosphate was involved in the deprotonation step, the rate-determining step with a 5.3 KIE value.

[EN] Human milk contains a large number of oligosaccharides, either free or bound to proteins and lipids, and their physiological role is mostly unknown. These oligosaccharides are resistant to host gastrointestinal digestion and therefore, a significant proportion reaches the infant colon, where they can be substrates for the resident microbiota. Lacto-N-biose (LNB) and galacto-N-biose (GNB) are the core type-1 sugar structures in HMO and mucin glycoproteins, respectively. They are fermented by species of the genus Bifidobacterium, but, there is no data about their utilization by the genus Lactobacillus. There is also no information for this genus about the metabolism of N-acetyllactosamine (LacNAc), which constitutes the type-2 sugar core in HMO, and lacto-N-triose, which forms part of the structure of lacto-N-tetraose, one of the most abundant HMOs. Lactobacillus casei is a lactic acid bacteria isolated from several environmental niches such as milk, meat, and reproductive and gastrointestinal tracts of animals and humans. In addition, some strains are used as starter cultures in the dairy industry and also as probiotics. The capability of L. casei species to survive in the gastrointestinal tract would depend in part of its ability to metabolize the available carbohydrates. In this Thesis we have shown that this strain is able to grow using LNB, GBN, LacNAc, and lacto-N-triose as carbon sources, and we have characterized the corresponding metabolic pathways. L. casei contains a gene cluster, gnbREFGBCDA, involved in the metabolism of GNB, LNB and also N-acetylgalactosamine. Transcriptional analysis showed that the gnb operon is regulated by substrate-specific induction mediated by the transcriptional repressor GnbR. Upstream of the gnb operon, there are two genes, bnaG and manA, encoding a b-N-acetylglucosaminidase precursor and a mannose-6P isomerase. It has been shown that BnaG is an extracellular wall-attached enzyme and that it is involved on lacto-N-triose metabolism. ManA enzyme is involved in the utilization of the mannose moiety of 3'-N-acetylglucosaminyl-mannose, which is a carbon source for L. casei BL23. Finally, in this strain, LacNAc is transported and phosphorylated by the lactose PTS and it is intracellularly hydrolyzed by the phospho-b-galactosidase LacG into galactose-6P and GlcNAc. Transcriptional analysis showed that the lac operon, in addition to lactose, is also induced by LacNAc. In an effort to better understand the metabolism and bioactive potential of HMO, sufficient quantities are required. In order to have enough amounts of LNB and GNB to test their biological activities, both disaccharides have been synthesized in vitro using the transglycosylation activity of the GnbG glycosyl hydrolase isolated from L. casei. Transglycosylation reactions were scaled and the resulting products were purified, and the yields obtained were 10.7 ± 0.2 g/L of LNB and 10.8 ± 0.3 g/l of GNB. Both disaccharides were used in vitro to determine their potential prebiotic properties using 33 Lactobacillus strains corresponding to 13 different species. It was determined that 21 strains, corresponding to the species L. casei, Lactobacillus rhamnosus, Lactobacillus zeae, Lactobacillus gasseri and Lactobacillus johnsonii were able to metabolize both GNB as LNB. Recently, some scientific evidences suggest an immunomodulatory function for HMO. In vitro analyses to assay this function have been performed for LNB and GNB, and for two fucosyloligosaccharides (Fuc-a-1,3-GlcNAc and Fuc-a-1,6-GlcNAc) previously synthesized in our laboratory. The four disaccharides were able to significantly increase IFN-g production in Peripheral Blood Mononuclear Cells (PBMC). Fuc-a-1,6-GlcNAc was also able to significantly reduce the production of IL13. These results suggest a stimulatory effect on the immune system, and in the particular case of Fuc-a-1,6-GlcNAc, a polarizing effect of immune response Th1 / Th2 towards Th1 populations. / [ES] La leche humana contiene una gran cantidad de oligosacáridos, libres o unidos a lípidos y proteínas, y su función fisiológica es mayoritariamente desconocida. Estos oligosacáridos son resistentes a la digestión y una gran proporción llega al intestino del lactante, donde pueden ser substratos para la microbiota. La lacto-N-biosa (LNB) y la galacto-N-biosa (GNB) son las estructuras tipo-1 que forman el núcleo de los oligosacáridos de la leche humana (OLH) y de las glicoproteínas de la mucina, respectivamente. Los dos azúcares son fermentados por especies del género Bifidobacterium, pero no hay datos acerca de su utilización por el género Lactobacillus. Tampoco hay información para este género acerca del metabolismo de la N-acetil-lactosamina (LacNAc), que constituye la cadena de azúcar tipo-2 en los OLH, y de la lacto-N-triosa, que forma parte de la estructura de la lacto-N-tetraosa, uno de los OLH más abundantes. La capacidad de Lactobacillus casei, de prevalecer en el sistema gastrointestinal dependerá en parte de su versatilidad metabólica para utilizar los carbohidratos disponibles. En la presente Tesis Doctoral se ha demostrado que la cepa L. casei BL23 se puede cultivar en presencia de LNB, GBN, LacNAc, y lacto-N-triosa como fuentes de carbono. En el metabolismo de la LNB, GNB y también N-acetilgalactosamina (GalNAc) está implicado el operon gnbREFGBCDA. Análisis transcripcionales demostraron que el operon gnb está regulado por inducción del substrato mediada por el represor transcripcional GnbR. Por encima del operon gnb, hay dos genes bnaG y manA, que codifican para el precursor de una b-N-acetilglucosaminidasa y una manosa-6P isomerasa. Se ha demostrado que BnaG es un enzima extracelular unido a la pared celular y que está implicado en el metabolismo de la lacto-N-triosa. El enzima ManA está implicada en el metabolismo de la manosa presente en el disacárido 3'-N-acetilglucosaminil-manosa, el cual es también una fuente de carbono para L. casei BL23. Por último, en esta cepa se ha demostrado que la LacNAc es transportada y fosforilada por el PTS de la lactosa e hidrolizada intracelularmente por la fosfo-b-galactosidasa LacG en galactosa-6P y GlcNAc. Análisis transcripcionales demostraron que el operon lac, además de por lactosa, está también inducido por LacNAc. Para intentar comprender mejor el metabolismo y potencial bioactivo de los OLH se necesitan cantidades adecuadas de éstos. Con el objeto de disponer de LNB y GNB en cantidad suficiente para ensayar su actividad biológica, se han sintetizado in vitro ambos disacáridos utilizando para ello la capacidad de transglicosidación de la glicosil hidrolasa GnbG aislada de L. casei. Las reacciones de transglicosidación se escalaron, los productos resultantes se purificaron, y se obtuvieron rendimientos de 10.7 ± 0.2 g/l de LNB y 10.8 ± 0.3 g/l de GNB. Ambos disacáridos fueron utilizados in vitro para determinar sus propiedades prebióticas potenciales con 33 cepas de Lactobacillus correspondientes a 13 especies diferentes. Se determinó que 21 de las cepas, correspondientes a las especies L. casei, Lactobacillus rhamnosus, Lactobacillus zeae, Lactobacillus gasseri y Lactobacillus johnsonii fueron capaces de metabolizar tanto GNB como LNB. Existen evidencias científicas recientes que les atribuyen a los OLH propiedades inmunomoduladoras, así que se han determinado éstas in vitro para LNB y GNB, y para dos fucosiloligosacáridos (Fuc-a-1,3-GlcNAc y Fuc-a-1,6-GlcNAc) sintetizados anteriormente en nuestro laboratorio. Se ha demostrado que los cuatro disacáridos son capaces de incrementar significativamente la producción de IFN-g en Células Mononucleares de Sangre Periférica. El Fuc-a-1,6-GlcNAc además fue capaz de reducir significativamente la producción de IL13. Estos resultados sugieren un efecto estimulante del sistema inmune y en el caso particular del Fuc-a-1,6-GlcNAc un efecto polarizador de la respuesta inmune Th1/Th2 / [CA] La llet humana conté una gran quantitat d'oligosacàrids, lliures o conjugats amb lípids o proteïnes i la seua funció fisiològica és majoritàriament desconeguda. Aquests oligosacàrids són resistents a la digestió i una gran proporció arriba a l'intestí dels lactants, on poden ser substrat per a la microbiota. La lacto-N-biosa (LNB) i la galacto-N-biosa (GNB) són les estructures tipus-1 que conformen el nucli dels oligosacàrids de la llet humana (OLH) i de les glicoproteïnes de la mucina, respectivament. Els dos sucres són fermentats per espècies del gènere Bifidobacterium, però no existeixen dades sobre l'ús pel gènere Lactobacillus. Tampoc no hi ha informació per a aquest gènere sobre el metabolisme de la N-acetil-lactosamina (LacNAc), que cosntitueix la cadena de sucre tipus-2 als OLH i de la lacto-N-triosa, que forma part de l'estructura de als OLH tipus-1 i 2. La capacitat de L. casei, una bactèria làctica aïllada de múltiples nínxols ambientals, de prevaler al sistema gastrointestinal dependrà en part de la seua versatilitat metabòlica per a utilitzar els carbohidrats disponibles. A la present tesi doctoral s'ha demostrat que la soca L. casei BL23 es pot cultivar en presència de LNB, GBN, LacNAc i lacto-N-triosa com a fonts de carboni. Al metabolisme de la LNB, GNB i també de la N-acetilgalactosamina (GalNAc) està implicat l'operó gnbREFGBCDA. Anàlisi transcripcionals demostraren que l'operó gnb està regulat per inducció del substrat mitjançant el repressor transcripcional GnbR. A sobre de l'operó gnb, hi ha dos gens bnaG i manA, que codifiquen per al precursor d'una b-N-acetilglucosaminidasa i una manosa-6P isomerasa. S'ha demostrat que BnaG és un enzim extracel·lular unit a la paret cel·lular i que està implicat en el metabolisme de la lacto-N-triosa. Aquesta és hidrolitzada per BnaG en lactosa i N-acetilglucosamina (GlcNAc). L'enzim ManA està implicada en el metabolisme de la manosa present al disacàrid 3-N-acetilglucosaminil-manosa, el qual també representa una font de carboni per a L. casei BL23. Per concloure, en aquesta soca s'ha demostrat que la LacNAc és transportada i fosforilada pel PTS de la lactosa i hidrolitzada intracel·lularment per la fosfo-b-galactosidasa LacG en galactosa-6P i GlcNAc. Anàlisi transcripcionals demostraren que l'operó lac, a més de per lactosa està induït per LacNAc. Per intentar comprendre millor el metabolisme i potencial bioactiu dels OLH es necessiten quantitats adequades d'aquests. A fi de disposar de LNB i GNB en quantitats suficients per a assajar la seua activitat biològica, s'han sintetitzat in vitro ambdós disacàrids utilitzant per a tal la capacitat de trasglicosidació de la glicosil hidrolasa GnbG aïllada de L. casei. Les reaccions de transglicosidació s'escalaren, els productes resultants es purificaren i s'obtingueren rendiments de 10.7 ± 0.2 g/l de LNB y 10.8 ± 0.3 g/l de GNB. Ambdós disacàrids foren utilitzats in vitro per a determinar les seues propietats prebiòtiques potencials amb 33 soques de Lactobacillus corresponents a 13 espècies diferents. Es determinà que 21 de les soques, corresponents a les espècies L. casei, Lactobacillus rhamnosus, Lactobacillus zeae, Lactobacillus gasseri i Lactobacillus johnsonii foren capaces de metabolitzar tant GNB com LNB. Existeixen evidències científiques recents que atribueixen als OLH propietats immunomoduladores, així que s'han determinat aquestes in vitro per a LNB i GNB i per als dos fucosiloligosacàrids (Fuc-a-1,3-GlcNAc y Fuc-a-1,6-GlcNAc) sintetitzats anteriorment al nostre laboratori. S'ha demostrat que els quatre disacàrids són capaços d'incrementar significativament la producció de IFN-g en Cèllules Mononuclears de Sang Perifèrica. El Fuc-a-1,6-GlcNAc a més, fou capaç de reduir significativament la producció de IL13. Aquests resultats suggereixen un efecte estimulant del sistema immune i en el cas particular del Fuc-a-1,6-GlcNAc un efecte pol / Bidart Costoya, G. (2016). Metabolismo y síntesis de oligosacáridos de la leche humana mediante la utilización de enzimas glicosil hidrolasas de Lactobacillus casei [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/70898

För att hitta en svensk motsvarighet till infant observation, eller naturalistic infant observation, har jag genomgående i denna studie använt begreppet spädbarnsobservationer. Begreppet refererar till Tavistockklinikens spädbarnsobservationer av barn, nyfödda upp till två och ett halvt års ålder. Syftet med studien har varit att utforska, undersöka och beskriva en spädbarnsobservation enligt Tavistockmodellen i ljuset av Sterns teori. Det är ofrånkomligt och har förefallit ytterst viktigt att beskriva och benämna mina egna upplevelser, erfarenheter och inställning till spädbarnsobservation. Samt att tolka och analysera dess eventuella betydelse för min kunskaps- och professionsutveckling i psykoterapeutiskt arbete som psykoterapeut. Studien är en kvalitativ studie, baserad på observation av ett nyfött barn upp till 1 ó års ålder samt dess relation till sin mor, far och syskon. Observationsmaterialet skrevs ned efter vart och ett av observations- tillfällena. Materialet analyserades genom Burnard´s (1991) stegvisa process De identifierade huvudrubrikerna är 1) Barnets utvecklingslinje 2) Förälderns utvecklingslinje 3) Samspelsutvecklingen 4) Min observatörsroll. Empirin belyses genom D. N. Sterns självutveckling. Spädbarnsobservationen var en enormt lärorik process. Klinisk kunskap om ett barns normal-utveckling är av stor betydelse. Vidare har min egen neutralitet och omedveten kommunikation betytt mycket för vidare psykoterapeutiskt arbete. Önskemål finns att genomföra fler spädbarnsobservationer för att bekräfta eller dementera erfarenheterna från nu gjord observation.

This thesis is concerned with various problems associated with the factorisation and feedback stabilisation of multidimensional linear discrete systems, which may be represented by rational matrices in several variables. Some factorisation techniques for polynomial and rational matrices in several variables have been explored and applied to the study of feedback stabilisation of multidimensional linear systems. The work presented here may be divided into two parts. The first part (Chapters 2 and 3) is concerned with two-dimensional systems, while the second part (Chapters 4 and 5) deals with three- and higher-dimensional systems. The emphasis of the first part is placed on the development of constructive algorithms for several kinds of factorisation of polynomial and rational matrices in two variables. In Chapter 2, an algorithm for obtaining primitive factorisation of polynomial matrices in two variables is developed, which is then followed by an algorithm for the decomposition of a rational matrix in two variables into factor coprime matrix fraction descriptions. Chapter 3 presents a procedure for the analysis and compensator design of two-dimensional feedback systems. A constructive algorithm for solving a Diophantine-type equation in two variables is derived. A necessary and sufficient condition for the feedback stabilisability of two-dimensional systems is obtained. The complete set of stabilising compensators for a given two-dimensional plant is then characterised. The role played by the matrix fraction description approach in the study of three- and higher dimensional systems, particularly with respect to the feedback stabilisation of these systems, is then investigated in detail in the second part. Chapter 4 deals with various kinds of factorisations for polynomial and rational matrices in three or more variables. For example, a criterion for the existence of primitive factorisation of a class of polynomial matrices in three or more variables is derived. By introducing a new concept: <i>generating polynomials</i>, it is shown that a direct generalisation of several existing results in two-dimensional systems theory to their higher-dimensional counterparts is not possible. In chapter 5, applying the generating polynomials, we obtain a stability test and a necessary and sufficient condition for feedback stabilisability of three- and higher-dimensional systems.

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No description available.

No description available.