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Effect of Methoxylated Sites in Sn-Beta Zeolite on Glucose TransformationsTran, Caterina 14 August 2015 (has links)
Cellulose, a major constituent of biomass, is a promising source of sustainable energy. A key step in the conversion of cellulose to a platform chemical is glucose isomerization to fructose. Sn-Beta zeolite catalyzes this reaction with high yield. The effect of methanol as a reaction medium on glucose transformations catalyzed by Sn-Beta has not been quantified. Here, density functional calculations are employed to elaborate on the effect of methanol medium, specifically to determine how reaction pathways and energy barriers are affected by methoxylation of Sn or Si groups at the active sites in Sn-Beta. Calculations suggest that the presence of the neighboring silanol group is necessary for glucose isomerization. If the silanol group is altered by methoxylation glucose epimerization is promoted and will likely occur. These results provide additional understanding of the active site of Sn-Beta for glucose transformations and are insightful for novel catalyst design and development.
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Efficient carbohydrate synthesis by controlled inversion strategiesDong, Hai January 2006 (has links)
<p>The Lattrell-Dax method of nitrite-mediated substitution of carbohydrate triflates is an efficient method to generate structures of inverse configuration. In this study it has been demonstrated that a neighboring equatorial ester group plays a highly important role in this carbohydrate epimerization reaction, inducing the formation of inversion compounds in good yields. Based on this effect, efficient synthetic routes to a range of carbohydrate structures, notably β-D-mannosides and β-D-talosides, were designed. By use of the ester activation effect for neighboring groups, a double parallel as well as a double serial inversion strategy was developed.</p>
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Efficient carbohydrate synthesis by controlled inversion strategiesDong, Hai January 2006 (has links)
The Lattrell-Dax method of nitrite-mediated substitution of carbohydrate triflates is an efficient method to generate structures of inverse configuration. In this study it has been demonstrated that a neighboring equatorial ester group plays a highly important role in this carbohydrate epimerization reaction, inducing the formation of inversion compounds in good yields. Based on this effect, efficient synthetic routes to a range of carbohydrate structures, notably β-D-mannosides and β-D-talosides, were designed. By use of the ester activation effect for neighboring groups, a double parallel as well as a double serial inversion strategy was developed. / QC 20101111
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Progesterone metabolites : learning, tolerance, antagonism & metabolismÖfverman, Charlotte January 2009 (has links)
Progesterone metabolites as allopregnanolone, isoallopregnanolone and tetrahydrodeoxy-corticosterone (THDOC) are increased in the luteal phase of the menstrual cycle, throughout pregnancy and during stress. Allopregnanolone and THDOC are neurosteroids with 3α-hydroxy, 5α-configurations and positive modulating effect on the GABAA receptor. They have similar properties and effect, and share the same binding sites on the GABAA receptor. Isoallopregnanolone has a 3β-hydroxy, 5α-configuration and a diverse effect as a proposed antagonist to both allopregnanolone and THDOC. Neurosteroids are thought to exert their effect predominantly at extrasynaptic GABAA receptors, containing for example α4- or α5-subunits. Such receptors are involved in the tonic response. Different subunits have diverse distribution pattern in the brain and are involved in different functions. The α5-subunit, mainly expressed in the hippocampus, is involved in learning, while α4 is more widespread and involved in e.g. anxiety and anaesthesia. The aim of the present thesis was to contribute to the knowledge about selected progesterone metabolites and their effects on learning and tolerance development, as well as their metabolism. Also basic characteristics between different α-subunits of the GABAA receptor were evaluated. The thesis shows that the effect of bicuculline and pentobarbital is not dependent on the α-subunit isoform of the GABAA receptor expressed in oocytes. Acute tolerance developed after allopregnanolone-induced anaesthesia with a decrease at both mRNA and protein levels of the GABAA receptor α4-subunit in the thalamus VPM nucleus. A negative correlation between the α4 mRNA and the increased dose of allopregnanolone needed to maintain the anaesthesia level was also shown. In addition, allopregnanolone induces a learning impairment in the Morris water maze test, when high concentrations of allopregnanolone are present in the brain. This impairment is not possible to reverse by isoallopregnanolone. In α5β3γ2L-transfected HEK-293 cells THDOC induces a baseline shift of its own and also potentiate the GABA-current. Neither of those THDOC effects can be inhibited by isoallopregnanolone. Instead isoallopregnanolone shows an agonistic effect on the THDOC-potentiation of the GABA-response. The main allopregnanolone metabolites identified, 5α-DHP and isoallopregnanolone, as well as allopregnanolone itself are mainly localized to the brain after an i.v. injection. After an isoallopregnanolone injection there is a more even distribution of the given steroid and the metabolites between plasma and brain. There is an epimerisation between isoallopregnanolone and allopregnanolone and vice versa. In conclusion, the present thesis shows that the α4-subunit in the thalamus VPM nucleus is likely to be involved in the acute tolerance development against allopregnanolone and that allopregnanolone-induced learning impairment is likely to be hippocampus dependent. The lack of antagonistic effect of isoallopregnanolone on the THDOC-induced α5β3γ2L-GABAA response, together with epimerisation of isoallopregnanolone to allopregnanolone, could explain why isoallopregnanolone does not work as an antagonist to the allopregnanolone-induced learning impairment in a hippocampus dependent learning task.
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Chimie prébiotique : rôle et importance des intermédiaires 5(4H)-oxazolones dans l’activation et l’élongation C-terminale des peptides, et dans l’émergence de l’homochiralité / Prebiotic chemistry : role and importance of 5(4H)-oxazolone intermediates in the C-terminus activation and elongation of peptides, and in the emergence of homochiralityBeaufils, Damien 06 November 2015 (has links)
L'élongation de peptides ou d'acides aminés N-acylés via une activation C-terminale (par exemple par un carbodiimide) est délaissée en synthèse peptidique à cause de l'épimérisation rapide des intermédiaires 5(4H)- oxazolones issus de cette activation. Au contraire, cela représente une voie prometteuse en chimie prébiotique où les substrats sont a priori racémiques, et où une étape d'épimérisation peut favoriser un scénario protométabolique / autocatalytique d'émergence de l'homochiralité. Partant de travaux récents qui montraient clairement que l'activation C-terminale de peptides en milieu aqueux procède surtout via une 5(4H)-oxazolone, nous avons étudié la stéréosélectivité des couplages peptidiques qui en résultent dans des conditions prébiotiques plausibles (milieu aqueux dilué à pH faiblement acide). Notre étude sur des peptides modèles (préparés par des méthodes classiques de synthèse peptidique et comportant un résidu tyrosine qui facilite l'analyse par HPLC) visait à évaluer l'effet de la configuration des résidus voisins ou des nucléophiles ; elle a montré la formation d'excès diastéréomériques significatifs en faveur de dérivés homochiraux, sous l'influence prépondérante de la chiralité du nucléophile.Nous avons ensuite étudié la réactivité de dipeptides libres dans les mêmes conditions, pour évaluer la formation compétitive de dicétopipérazine (DCP), qui est susceptible de bloquer l'élongation au-delà du dipeptide. La formation de DCP est prépondérante à partir de dipeptides faiblement activés, mais n'a pas lieu en présence d'agents d'activation de potentiel élevé (e.g. l'EDC) qui favorisent la formation plus rapide d'oxazolone et permet l'élongation peptidique ; ces derniers résultats soulignent l'importance prébiotique de potentiels d'activation élevés. / The elongation of peptides or N-acylamino acids through C-terminus activation is usually avoided in peptide synthesis, because of the fast epimerisation of 5(4H)-oxazolones intermediates resulting form such activation. Conversely, it represents a promising perspective in prebiotic chemistry where substrates are assumed to be racemic, and where an epimerisation step may favour a protometabolic / autocatalytic scenario of emergence of homochirality.Based on recent works which clearly showed that the C-terminus activation of peptides in aqueous media mostly proceed through a 5(4H)-oxazolone, we investigated the stereoselectivity of peptide couplings resulting therefrom under plausible prebiotic conditions (dilute aqueous medium at weakly acidic pH). Our study on model peptides (prepared by classical peptide synthesis methods, and bearing a tyrosine residue which facilitates HPLC analysis), aimed at assessing the influence of the configuration of the vicinal peptide residue or of the nucleophile; we observed significant diastereomeric excesses in favour of homochiral sequences, under the preponderant influence of the chirality of the nucleophile.Then we investigated the reactivity of free dipeptides under the same conditions, to assess the extent of diketopiperazine (DKP) formation, which may prevent further elongation beyond dipeptides. While DCP formation is preponderant from weakly activated peptides, id does not occur in the presence of high potential activation agents (e.g. EDC), which favour the faster formation of oxazolone and allow subsequent peptide eleongation; these last results undeline the prebiotic importance of high activation potentials.
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Untersuchungen zur Epimerisierung und Transformation von ErgotalkaloidenMerkel, Stefan 02 July 2013 (has links)
Ergotalkaloide sind sekundäre Stoffwechselprodukte des parasitären Schlauchpilzes Claviceps purpurea der auf Getreide Mutterkörner (Sklerotien) bildet. In Sklerotien sind toxische Ergotalkaloide enthalten. Durch C. purpurea werden vorrangig sechs verschiedene Ergotalkaloid-Epimerenpaare gebildet, die toxischen C8-(R)-Epimere und die biologisch nicht relevanten C8-(S)-Epimere, die ineinander umgewandelt werden können. Das Ziel der Arbeit war es, die Epimerisierung der Ergotalkaloide während der Probenvorbereitung im Vergleich zu bisher bekannten Probenaufarbeitungsverfahren zu minimieren. Dieses gelang durch den Verzicht des Zusatzes starker Säuren oder Basen. Die aufgereinigten Extrakte können bei Raumtemperatur über 96 Stunden epimerisierungsfrei in einer tensidischen Acetonitril-Wasser-Lösung gelagert werden. Die Probenaufarbeitung mit anschließender Auftrennung über die Hochleistungsflüssigchromatographie und fluorimetrischer Detektion (HPLC-FLD) wurde für Roggenmehl und Speiseöl validiert und auf diese Martices angewendet. So konnten erstmals die Ergotalkaloidgehalte auch in Weizenkeimöl quantifiziert werden. Im zweiten Teil der Arbeit wurde das Epimerisierungsverhalten von Ergotalkaloiden bei Backversuchen und in vitro Verdauexperimenten untersucht. Das Backen resultierte in eine Verschiebung des Epimerengleichgewichtes auf die Seite der (S)-Epimere. Das angewendete in vitro Verdaumodell führte für die Ergotalkaloidepimerenpaare Ergotamin und Ergosin zu einer Verschiebung des Epimerengleichgewichtes auf die Seite der toxischen (R)-Epimere. Dagegen zeigten die Ergotalkaloide der Ergotoxingruppe eine Verschiebung des Epimerengleichgewichtes auf die Seite der (S)-Epimere. Der dritte Teil der Arbeit beschäftigt sich mit Ergotalkaloid-Konjugaten, die unter dem Einfluss von UV-Licht entstehen. Es wurden sechs Ergotalkaloid-Fettsäure-Konjugate synthetisiert und in Sklerotien über die HPLC in Verbindung mit massenspektrometrischer Detektion nachgewiesen. / Ergot alkaloids are secondary metabolites of the parasitic fungus Claviceps purpurea that forms sclerotia on cereals. These sclerotia contain toxic ergot alkaloids. C. purpurea forms six epimeric pairs of ergot alkaloids predominantly the toxic C8-(R)-epimers and the biologically inactive C8-(S)-epimers. In view of the fact that both epimeric forms can be transformed into one another, the objective of this work was to develop a novel sample preparation method that minimizes the epimerization rate compared to previously published methods. The presented sample preparation procedure minimizes epimerization of ergot alkaloids, as it operates without the addition of strong acidic or alkaline modifiers for matrix removal. After sample preparation, an ergot alkaloid containing extract in a sodium hexanesulfonate solution is obtained in which no epimerization after 96 hours was observed. Thus, the sample preparation allows extract storage at ambient temperature for prolonged HPLC analysis. This novel sample preparation followed by HPLC-flourescence analysis was validated for the matrices rye flour and wheat germ oil and was applied for food samples. This is the first time that the ergot alkaloid content in wheat germ oil was quantified. The second part of this work was the study of the epimerization behaviour of ergot alkaloids during baking and in vitro digestion. Baking of cookies resulted in a shift of the epimeric ratio towards the (S)-epimers. The in vitro digestion showed an ergot alkaloid specific shift of the epimeric ratio. The initial percentage of the (R)-epimer increased for ergotamine und ergosine. In contrast, ergot alkaloids of the ergotoxine type showed an epimeric shift towards their (S)-epimers. The third part of this work was the study of ergot alkaloid derivatives that are formed in combination with UV-light. Six different ergot alkaloid fatty acid derivates were synthesized and detected in sclerotia using a HPLC-MS/MS method.
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Modification des propriétés du polypropylène par mise en oeuvre réactive/Modification of polypropylene properties by reactive processingHenry, Gaëtan 26 April 2006 (has links)
Ce travail s'inscrit dans le cadre d'un projet soutenu par la Région wallonne et a été réalisé en collaboration entre les unités de Chimie Organique et Médicinale (CHOM), de Chimie Structurale et des Mécanismes Réactionnels (CSTR), et de Chimie et Physique des Hauts Polymères (POLY). Il concerne la modification des propriétés du polypropylène (PP) isotactique par mise en œuvre réactive, et plus particulièrement le contrôle de sa cristallinité par l'action d'un composé bromé (N-bromosuccinimide) en présence d'un initiateur de radicaux libres à haute température (entre 180 et 260°C).
L'objectif principal de cette étude est de parvenir à identifier et à contrôler les modifications induites au sein des produits, ce qui implique une compréhension fine des mécanismes chimiques intervenant lors de la mise en œuvre réactive du PP. Ces connaissances permettraient en outre de substituer la N-bromosuccinimide (qui génère des sous-produits toxiques et polluants) par un autre additif en vue d'une meilleure valorisation du procédé et des produits.
La stratégie repose sur une double approche, basée d'une part sur une étude des divers paramètres qui influencent la réaction sur polymère, et d'autre part sur la synthèse d'un composé modèle du PP : le 2,4,6,8,10-pentaméthylundécane (PMU).
Par extrusion réactive du polymère, nous avons obtenu des PP à cristallinité contrôlée (PPCC ; de semi-cristallin à amorphe), dont certains présentent un caractère élastomère marqué. Des études effectuées principalement par analyse thermique et par résonance magnétique nucléaire ont permis de corréler ces propriétés macroscopiques à une microstructure à stéréoblocs isotactiques/atactiques (épimérisation des carbones tertiaires du PP), combinée à la présence de branchements longs (recombinaison de macroradicaux). Par ailleurs, nous avons mis en évidence les différents paramètres susceptibles d'influencer la réaction d'épimérisation du PP. Bien que les informations découlant de ces études nous aient permis de proposer les principaux mécanismes qui entrent en jeu lors de la réaction, seule une étude sur composé modèle peut néanmoins donner accès aux méthodes d'analyses nécessaires à la confirmation de ces mécanismes.
Nous avons par conséquent entrepris la synthèse d'un oligomère de propylène pour permettre cette étude sur composé modèle. La synthèse du PMU telle que rapportée dans la littérature s'est avérée plus difficile que prévu, principalement du fait d'un manque de reproductibilité au niveau de l'étape clé. Nous avons donc établi une voie de synthèse originale permettant l'obtention du PMU (mélange de stéréoisomères) avec un rendement global de 45% sur 7 étapes (à l'échelle de plusieurs grammes de produit). En outre, cette voie nous a donné accès au 6-hydroxyméthyl-2,4,8,10-tétraméthylundécane et au 6-p-toluènesulfonyloxyméthyl-2,4,8,10-tétraméthylundécane, pour lesquels des techniques chromatographiques ont permi une séparation des diastéréoisomères. La transposition de ces expériences à plus grande échelle permettra d'envisager l'obtention du (4R,6s,8S)-PMU, en vue de futures études mécanistiques relatives à l'épimérisation du PP de configuration initialement isotactique. / This work is part of a project supported by the Walloon Region, and it was performed in collaboration between the Chimie Organique et Médicinale (CHOM), Chimie Structurale et des Mécanismes Réactionnels (CSTR), and Chimie et Physique des Hauts Polymères (POLY) laboratories. Its object is the modification of the isotactic polypropylene (PP) properties by reactive processing, and more especially the control of PP crystallinity by means of a brominated additive (N-bromosuccinimide) in presence of a free radical initiator at high temperatures (between 180 and 260°C).
The main objective of this study is to identify and to control the modifications induced in the products, which implies a fine understanding of the chemical mechanisms occuring during the PP reactive processing. This knowledge would allow us, subsequently, to substitute another additive for the N-bromosuccinimide (which yields toxic and polluting by-products), in order to achieve a better applicability of both the process and the products.
The strategy relies on a double approach : on one side, on a study of the various parameters affecting the reaction on the polymer, and on the other side on the synthesis of a model compound of PP : 2,4,6,8,10-pentamethylundecane (PMU).
By means of reactive extrusion of the polymer, we obtained controlled crystallinity PP's (from semi-crystalline to amorphous), including some with an elastomeric behaviour. Studies carried out mainly by thermal analysis and nuclear magnetic resonance allowed us to correlate these macroscopic properties to an isotactic/atactic stereoblock microstructure (epimerization of the PP tertiary carbons), combined with the presence of long chain branchings (recombination of macroradicals). Moreover, we highlighted the various parameters that are able to influence the yield of the epimerization reaction. Even if the informations arising from these studies allowed us to propose the main mechanisms involved in the PP modification, only a mechanistic study carried out on a model compound would give us access to the characterization methods required for the confirmation of these mechanisms.
We undertook, subsequently, the synthesis of a propene oligomer. The PMU synthesis, as stated in the litterature, revealed itself more difficult than initially foreseen, mainly due to a lack of reproducibility concerning the key step. Therefore we established a new synthesis pathway for the PMU (as a mixture of stereoisomers) with a global yield of 45% over 7 steps (multigram scale). Moreover, this pathway gave us access to 6-hydroxymethyl-2,4,8,10-tetramethylundecane and 6-p-toluenesulfonyloxymethyl-2,4,8,10-tetramethylundecane, for which chromatographic techniques allowed a separation of the diastereoisomers. The transposition of these experiments on a larger scale would allow us to obtain the (4R,6s,8S)-PMU for future mechanistic studies relative to the epimerization reaction of initially isotactic PP.
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The chemistry of Salvia divinorumMunro, Thomas Anthony Unknown Date (has links) (PDF)
Salvia divinorum is a hallucinogenic sage used to treat illness by the Mazatec Indians of Mexico. Salvinorin A (1a), a neoclerodane diterpenoid isolated from the plant, is a potent, selective agonist at the kappa opioid receptor (KOR), and is the first non-nitrogenous opioid. The plant is used recreationally as a hallucinogen, but is unpopular due to its dysphoric effects. 1a has been prohibited in Australia under an invalid systematic name. An early report of psychoactive alkaloids in S. divinorum proved to be irreproducible. Similarly, tests in mice suggesting the presence of psychoactive compounds other than 1a were confounded and therefore unreliable. In this work, an improved isolation method for 1a was developed, using filtration through activated carbon to decolourise the crude extract. Six new diterpenoids were isolated: salvinorins D–F (1d–1f) and divinatorins A–C (28a–28c). Five known terpenoids not previously reported from this species were also isolated. The structure–activity relationships of 1a were evaluated via selective modifications of each functional group. Useful synthetic methods are reviewed, including the first thorough review of furanolactone hydrogenations. Testing of the derivatives at the KOR suggests that the methyl ester and furan ring of 1a are required for activity, but that the lactone and ketone functionalities are not. Other compounds from S. divinorum did not bind to the KOR, suggesting that 1a is the plant’s active principle.
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Etudes structurales par RMN des profils Saccharidiques d'Héparanes sulfates et de leur régulation cellulaire : Mise en place d'un protocole de marquage, de purification et d'analyse de chaines entières / Structural studies of heparan sulfate profiles and their cellular regulation by nmr : set up of a labeling and purification protocol for full-length chains analysisPegeot, Mathieu 11 December 2014 (has links)
Les glycosaminoglycanes (GAG) forment une famille de polysaccharides linéaires retrouvés dans tous les tissus, au niveau des matrices extracellulaires et des surfaces cellulaires. Les héparanes sulfates (HS) sont des membres importants de cette famille et sont liés à une protéine dite cœur pour former ensemble le protéoglycane (PG). Selon le tissu et la nature de la protéine cœur, les HS, composés d'unités disaccharidiques de N-acétylglucosamine (GlcNAc) et d'acide glucuronique (GlcA) [-4GlcAβ1-4GlcNAcα1-] vont subir de nombreuses modifications. En effet, les HS sont modifiés par différentes sulfatations au niveau des deux oses et une épimérisation de l'acide glucuronique en acide iduronique (IdoA). Les différentes structures saccharidiques élaborées vont pouvoir être alors interagir avec une très grande quantité de protéines et jouer des rôles divers dans l'inflammation, la prolifération cellulaire, l'angiogenèse, la réponse immunitaire, l'attachement viral…L'étude de la structure des HS, du fait de la nature flexible et hétérogène de ces molécules, a été principalement focalisée sur des analyses fragmentaires du polysaccharide au niveau des séquences d'interaction avec les protéines. Lors de ces dépolymérisations, des informations sur le polysaccharide, notamment l'épimérisation, sont perdues.Dans ce travail, nous avons développé une approche basée sur la résonance magnétique nucléaire (RMN) bidimensionnelle 1H-13C pour l'étude de la composition saccharidique des HS réalisée directement à partir des HS isolés de cellules marquées au 13C. Pour cela, un protocole efficace de marquage et de purification des polysaccharides a été mis en place. En intégrant le volume des pics à différents déplacements chimiques par RMN, cette analyse non-destructive permet de déterminer à la fois le profil de sulfatation et d'épimérisation des HS. Cette analyse est appliquée efficacement à différents types cellulaires et est de grand intérêt pour mieux comprendre les changements dans les structures d'HS qui ont lieu lors de régulations physiologiques ou lors de développement pathologiques.Ces résultats ont permis d'ouvrir la voie à l'analyse des HS directement au niveau des cellules par RMN du solide. Les études dans ce contexte représentent un enjeu majeur pour la compréhension des différents rôles des HS et leur capacité à interagir avec une myriade de protéines in vivo. / Glycosaminoglycans (GAGs) belong to a linear polysaccharide family which are found within all tissues, at the extracellular matrix and cell surfaces levels. Heparan Sulfates (HS) are one of the major members of this family, they are bound to a core protein to form altogether the so-called proteoglycan (PG). Depending on the localization and on the core protein, the HS – composed of a N-acetylglucosamine (GlcNAc) and a glucuronic acid (GlcA) [-4GlcAβ1-4GlcNAcα1-] building block – undergo various modifications. Indeed, HS can be sulfated at different positions on both monosaccharide and the GlcA can be epimerized into an iduronic acid (IdoA). The fine structures of the polysaccharide will be able to interact with a large range of proteins and play a plethora of roles such as in inflammation processes, cell proliferation, angiogenesis, immune responses, viral attachment…The HS structural studies, due to the flexibility and heterogeneity of the polysaccharide, have so far been restricted to HS fragments able to bind proteins. The depolymerization techniques induce valuable information losses such as epimerization.In this work, we have successfully developed a nuclear magnetic resonance (NMR)-based approach to study HS features from 13C metabolically enriched cells. For this, an effective protocol to label and purify HS has been set up. By integrating peaks' volumes at well-resolved 1H-13C chemical shifts by NMR, the sulfation, epimerization and disaccharide profile can be determined from full-length HS. This method has been used to study HS from various cell types and is of important interest to better understand changes in HS structures that occur through physiologic and pathologic events.The results obtained open the way to analyze HS directly at the cell surface via solid state NMR techniques. In this context, these studies are a major challenge to decipher the different roles of HS and their ability to interact with so many partners in vivo.
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Progesterone metabolites learning, tolerance, antagonism & metabolism /Öfverman, Charlotte, January 2009 (has links)
Diss. (sammanfattning) Umeå : Umeå universitet, 2009. / Härtill 5 uppsatser. Även tryckt utgåva.
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