Дисертації: "Vit D"

1

Dolezal, Vit [Verfasser]. "Multifocus fluorescence correlation spectroscopy / Vit Dolezal." Lübeck : Zentrale Hochschulbibliothek Lübeck, 2016. http://d-nb.info/1121535380/34.

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2

Corr?a, Ludmila Campo Dall'orto. "? margem do corpo d ?gua: a rela??o entre a ba?a e a cidade de Vit?ria (ES)." Pontif?cia Universidade Cat?lica de Campinas, 2014. http://tede.bibliotecadigital.puc-campinas.edu.br:8080/jspui/handle/tede/124.

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Made available in DSpace on 2016-04-04T18:22:08Z (GMT). No. of bitstreams: 1 Ludmila Campo Dallorto Correa.pdf: 3039624 bytes, checksum: 0aa4abbaa853d5b8fade1a006fc4227e (MD5) Previous issue date: 2014-02-20
This work has the physical reference the city of Vit?ria and want to make a contribution of relationships that the city has with the water bodies. In the case of the city of Vit?ria, analysis and reflection to bring water bodies that surround it: Ba?a de Vit?ria, the Canal da Passagem and the channel between the islands. These are the most significant bodies of water which make the outline of the city. The paper also proposes a reflection about the role of local governments on the changes promoted in spaces located on the banks of water bodies for the qualification and integration of the city with the bay and channels.
O presente trabalho tem como referencia fisica a cidade de vit?ria e pretende trazer uma contribui??o das rela??es que a cidade estabelece com os corpos d agua. No caso da cidade de Vit?ria, trazemos para analise e reflex?o os corpos d ?gua que a cercam: a Ba?a de Vit?ria, o Canal da Passagem e o canal entre ilhas. Trata-se dos corpos d agua mais significativos que fazem o contorno da cidade. O trabalho tamb?m prop?e uma reflex?o a cerca da atua??o das administra??es locais quanto ?s modifica??es promovidas em espa?os localizados nas margens dos corpos d ?gua para a qualifica??o e para a integra??o da cidade com a ba?a e com os canais.

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3

POSA, FRANCESCA. "Vitamin d and nanostructured surfaces in osteoblastic differentiation of dental stem cells." Doctoral thesis, Università di Foggia, 2017. http://hdl.handle.net/11369/361973.

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1α, 25-diidrossivitamina D3 (1,25(OH)2D3), il metabolita attivo della Vitamina D (Vit D), aumenta l'assorbimento intestinale di calcio e fosfato, mantenendo un corretto bilanciamento nel rimodellamento osseo. La Vit D ha un effetto anabolizzante sul sistema scheletrico ed è fondamentale nel promuovere il differenziamento osteoblastico di cellule staminali mesenchimali umane (hMSCs) isolate da midollo osseo. Al fine di superare alcuni aspetti negativi associati all'utilizzo di MSCs da midollo osseo quali morbilità, dolore e bassa resa di cellule, sono state studiate fonti alternative di tali cellule. Le MSCs possono essere isolate anche dal dente nella sua forma immatura, il germoglio dentale: le Cellule Staminali da Gemma Dentale (Dental Bud Stem Cells - DBSCs) sono cellule staminali adulte che possono effettivamente differenziare in senso osteoblastico. Lo scopo del progetto è quello di studiare l'effetto della Vit D sulle DBSCs, che rappresentano un modello utile per comprendere l'attività anabolica delle cellule ossee a partire da precursori osteoblastici molto indifferenziati. Dal momento che l'adesione delle MSCs alla Matrice Extra Cellulare (ECM) è ancora poco caratterizzata, così come il ruolo delle proteine della ECM nella regolazione del differenziamento osteogenico, abbiamo innanzitutto studiato il nostro modello cellulare di DBSCs per l'espressione di Integrine e Caderine così come per l'interazione con proteine della ECM. Abbiamo osservato che le DBSCs mostrano un modello di adesione molecolare paragonabile a quello descritto per le MSCs. Abbiamo dimostrato una differenziazione delle DBSCs in senso osteogenico con acquisizione di un fenotipo osteoblastico, incrementata dal trattamento con la Vit D. Abbiamo osservato che le DBSCs, trattate con 1,25(OH)2D3, esprimevano livelli più elevati dei principali marcatori osteoblastici e formavano noduli di matrice mineralizzata in vitro. Questi risultati riflettono l'origine mesenchimale delle DBSCs e confermano le loro caratteristiche osteoblastiche. Inoltre, al fine di chiarire l'effetto del microambiente sul comportamento delle DBSCs, abbiamo analizzato anche la distribuzione dell’integrina αVβ3 e la formazione di Adesioni Focali (FAs) in cellule seminate su superfici con diversi rivestimenti in presenza di Vit D. Abbiamo quindi osservato che la Vit D sembra indurre l’espressione di tali adesioni focali nel nostro modello cellulare. Le nostre osservazioni suggeriscono che la Vit D sia in grado di agire direttamente su queste cellule, che possono essere considerate dei precursori degli osteoblasti, indirizzandole verso una formazione ossea più elevata.
1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active metabolite of Vitamin D (Vit D), increases intestinal absorption of calcium and phosphate, maintaining a correct balance of bone remodeling. Vit D has an anabolic effect on the skeletal system and is key in promoting osteoblastic differentiation of human Mesenchymal Stem Cells (hMSCs) from bone marrow. In order to overcome some negative aspects connected with the use of MSCs from bone marrow, i.e. morbidity, pain and low yield of cells, other sources of MSCs have been examined. MSCs can be also isolated from the immature form of the tooth, the dental bud: Dental Bud Stem Cells (DBSCs) are adult stem cells that can effectively undergo osteoblastic differentiation. The aim of the project is to study the effect of Vit D on DBSCs, which represent a useful model to understand the anabolic activity of the bone cells, starting from very undifferentiated osteoblast precursors. Since MSCs adhesion to Extra Cellular Matrix (ECM) is still poorly characterized, as well as ECM proteins role in regulating osteogenic differentiation, we studied our cell model of DBSCs for the expression of Integrins and Cadherins as well as for ECM protein interaction. We demonstrated a functional osteogenic differentiation of DBSCs towards an osteoblastic phenotype, being incremented by the Vit D treatment. We observed that DBSCs treated with 1,25(OH)2D3, expressed increased levels of the main osteoblastic markers and formed mineralized matrix nodules in vitro. These results reflected the mesenchymal origin of DBSCs and confirmed their osteoblast-like features. Moreover, in order to elucidate the effect of the microenvironment on DBSCs behavior, we also analyzed αVβ3 integrin distribution and Focal Adhesion formation in cells seeded on surfaces with different coatings in the presence of Vit D. We observed that Vit D seems to induce the expression of focal adhesions in our cell model. Our observations suggest that Vit D acts directly on these cells, that can be considered osteoblast precursors, directing them to an increased bone formation.

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4

Vit, Katharina Allegra [Verfasser], and Wulf [Akademischer Betreuer] Blankenfeldt. "Structural and Functional Studies on beta-alpha-beta-beta-beta-Module Resistance Proteins from Pseudomonas aeruginosa PAO1 and Structural Insights into Mycobacterial Ergothioneine Biosynthesis / Katharina Allegra Vit ; Betreuer: Wulf Blankenfeldt." Braunschweig : Technische Universität Braunschweig, 2015. http://d-nb.info/1175818577/34.

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5

Pierron, Géraldine. "Les enjeux psychiques de la relation d'aide entre l'aidant familial et son proche atteint de maladie d'Alzheimer ou de maladies apparentées, lorsque le patient vit à domicile." Thesis, Besançon, 2015. http://www.theses.fr/2015BESA1013/document.

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Si la littérature fait état des réticences des aidants familiaux, à demander de l'aide, leurs ressortspsychiques restent mal connus. Pourtant le sentiment de culpabilité a déjà été repéré, comme un obstacle à lademande d'aide de l'aidant, mais ce facteur a été peu exploré dans un axe de recherche. Cette rechercherepose sur l'hypothèse que le sentiment de culpabilité de l'aidant familial, représenterait le principal frein,susceptible d'empêcher sa demande d'aide et de soutien, face à la maladie d'Alzheimer ou à la maladieapparentée de son proche, lorsque le patient vit à domicile. Une sous-hypothèse vise à situer différemment lesentiment de culpabilité de l'aidant familial, selon sa position de conjoint, ou plus largement de descendant(enfant, belle-fille, gendre...), dans la relation d'aide. Pour tester cette hypothèse trente huit entretiens semidirectifsont été réalisés, et complétés par la passation des échelles d'attachement (RSQ), du caregiver(CRA), et de dépression (Beck).Cette recherche vise à expliciter les fondements, et les mécanismes du sentiment de culpabilité des aidantsfamiliaux, en l'articulant à la problématique de perte, qui est coeur de la maladie d'Alzheimer ou desmaladies apparentées. Elle apporte donc un éclairage nouveau sur le travail psychique de l'aidant familial,qui s'écarte de son seul abord sous l'angle du fardeau et de l'épuisement, pour l'envisager à la lumière dutravail du pré-deuil, qui apparaît comme la clé de voûte de la relation d'aide. Par conséquent, la recherchesuivra le cycle de la dépendance du patient, pour dégager à chacun de ses stades, les incidences de la pertedans l'espace psychique et intersubjectif chez l'aidant familial, selon la nature des liens d'attachementdéveloppés avec le patient, mais aussi avec le groupe familial. A partir de là, nous tenterons de relier leregistre principal d'élaboration de la perte, à un profil d'aidant singulier dans la relation d'aide, afin d'éclairerles liens entre ses manifestations de culpabilité, et sa demande d'aide
If the litterature states reservations of the family caregivers, to ask for help, their psychic springsremain badly known. Nevertheless the sense of guilt was already located, as an obstacle at the request ofhelp, of the caregiver, but this factor was little explored in a research theme. This research bases on thehypothesis that the sense of guilt of the family caregiver, would represent the main brake, susceptible toprevent his request of help and support, in front of the Alzheimer's disease or the related disease, when thepatient lives at home. A sub-hypothesis aims at placing differently the sense of guilt of the familiy caregiver,according to its spouse's position, or more widely of descendant (child, son-in-law, daughter-in-law) in therelation of help. To test this hypothesis, thirty eight semi-directive conversations were realized andcompleted by the signing of the scales of attachment (RSQ), the caregiver (CRA), and depression (Beck).This research aims at clarifying foudations, and mechanisms of the sense of guilt of the family caregivers, byarticulating it in the problem of loss, which is heart of Alzheimer's disease or the related diseases. It thusgives a new perspective on the psychic work of the family caregiver, which deviates from its only accessunder the angle of the burden and the exhaustion, to envisage it in the light of the work of the pre-mourning,which appears at the keystone of the relation of help. Consequently, the research will follow the cycle of thedependence of the patient, to release in each of its stages, the incidences of the loss in the psychic andintersubjective space at the family caregiver, according to the nature of the links of attachment developpedwith the patient, but also with the family group. From there, we shall try to connect the main register ofelaboration of the loss, in a profile of singular caregiver in the relation of help, to light the links between hisdemonstrations of guilt and his demand of help

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6

CHEVANCE, ANDRE. "Psychopathologie de la vie quotidienne du sujet age. Alzheimer le mal de lethe." Paris 7, 1999. http://www.theses.fr/1999PA070047.

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A partir d'un regard sur la psychopathologie de la vie quotidienne du sujet age, l'auteur nous propose une approche psychodynamique originale de la maladie d'alzheimer. Les outils methodologiques dont il a use lui ont permis d'aborder ces trois modes d'analyse bien distincts que sont: la clinique, la psychanalyse et la neuropsychologie. Ces trois approches lui ont permis de developper une hypothese psychogene de la maladie d'alzheimer, tout en prenant en compte les etiologies proposees par les biologistes, les neurologues et les geneticiens. L'exhumation du mythe de lethe permet par sa lecture d'ouvrir cette maladie a une vision psychodynamique. En revelant des intentions inconscientes ce mythe permet de donner du sens a cette maladie que l'on nomme "maladie du siecle".

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7

Coeytaux, Emmanuel. "Utilisation d' un peptide du VIH-1 pour la vectorisation d' ADN." Paris 7, 2003. http://www.theses.fr/2003PA077146.

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8

Dratwicki, Alexandre. "Un nouveau commerce de la virtuosité : métamorphoses de la symphonie concertante au sein des institutions musicales parisiennes (1780-1830) /." Paris : [A. Dratwicki], 2003. http://catalogue.bnf.fr/ark:/12148/cb39093293k.

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9

Drouin, Christian. "Vitamin D analogues via dynamic combinatorial chemistry." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=96890.

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Calcitriol (1alpha,25-(OH)2 D3, 1,25D) is known for its calcium regulatory function, but also for being a powerful inhibitor of cell growth in a variety of normal and neoplastic cells. As such, it is a lead structure in the development of new cancer drugs. The goal of our project is to identify analogues of calcitriol which bind tightly to the vitamin D receptor (VDR) yet do not exhibit unwanted hypercalcemic effects. The development of novel analogues using conventional chemistry and dynamic chemistry was investigated. First, the numerous building blocks required for the exploration of the different libraries were created through the use of conventional techniques. We then developed different synthetic schemes based primarily on thiol alkylation and amide couplings, enabling rapid parallel synthesis of potential 1,25D analogues. Preliminary investigations allowed us to implement with our collaborators a set of biological assays to evaluate our compounds. Although some analogues appeared to bind to the VDR, it was found that none of the 8 analogues tested in the preliminary studies seemed to be vitamin D receptor (VDR) agonists. In a second part, our research focused on the study of dynamic combinatorial chemistry as a tool for the synthesis of 1,25D analogues. Our first dynamically-generated libraries were created via thioester exchange. It was found that the rate of thioester exchange was dependent on the nature of the thiols involved and the acyl portion of the thioesters. Aliphatic acid thioesters exchanged more slowly than aromatic acid thioesters. The use of branched (alpha-substituted) thiols also slowed the rate compared to primary ones. However, the use of large concentration of aliphatic or aromatic thiols could accelerate the thioester exchange. When thioesters were placed in presence of protein targets in a dynamic system, their inherent electrophilic nature rendered them prone to chemical decomposition (hydrolysis and acylation of protein nucleophilic residues) at basic pHs. Nonetheless, we created thioester libraries of up to 40 members from as few as 7 building blocks under near neutral conditions. We showed that these dynamic libraries ere influenced by the presence of proteins. We have not been able to confirm if thioester libraries were influenced exclusively by the VDR via its binding site. Some of our observations challenged the viability of the thioester exchange as a reversible process in the context of VD3 analogue synthesis. Finally, we created dithiol building blocks, amenable to disulfide exchange in dynamic libraries. Chemically stable, these disulfide entities easily generated libraries of at least 30 members from as few as 7 building blocks. Our preliminary disulfide libraries seemed uninfluenced by VDR's presence. These results still allowed us to understand better the characteristics and limitations of dynamic systems applied to the development of novel vitamin D analogues.
Calcitriol (1alpha,25-dihydroxyvitamine D3, 1,25D) est connu pour sa fonction dans la régulation du métabolisme du calcium, mais aussi comme étant un puissant inhibiteur de la prolifération cellulaire dans un éventail de cellules normales et néoplastiques. Comme tel, il représente le point de départ pour le développement de nouvelles molécules anticancéreuses. Le but de notre projet est d'identifier des analogues du calcitriol capables de se lier au récepteur de la vitamine D (RVD) sans causer d'hypercalcémie. Le développement de nouveaux analogues de la vitamine D3 a été exploré en utilisant la chimie conventionelle et la chimie dynamique. Dans un premier temps, de nombreux synthons nécessaires à la création des différentes librairies ont été fabriqués par des techniques de synthèse traditionnelles. Ensuite, des routes de synthèse basées sur l'alkylation de thiols et la formation d'amides ont été élaborées, permettant une synthèse en parallèle efficace d'analogues de la vitamine D. En collaboration avec nos partenaires, des études préliminaires ont permis d'établir la validité d'une série de tests pour évaluer l'activité biologique de nos analogues sur le récepteur de la vitamine D. Bien que plusieurs composés semblent se lier au récepteur, aucun des 8 analogues évalués de façon préliminaire n'ont révélé une activité agoniste du RVD. Dans un deuxième temps, nous avons axé notre recherche sur l'étude de la chimie combinatoire dynamique (CCD) comme outil pour la création et l'évaluation d'analogues de la vitamine D. La CCD est basée sur le fait qu'une protéine peut influencer la composition de bibliothèques dynamiques en favorisant la création de ses propres ligands, et ce, proportionnellement à leur constante d'affinité. Les premières bibliothèques dynamiques furent créées à partir d'échanges entre thioesters. Il a été évalué qualitativement que la vitesse de ce processus est dépendante de la nature des thiols impliqués ainsi que de la nature de la portion acyl des thioesters. L'échange des thioesters d'acides aliphatiques est plus lent que celui des thioesters d'acides aromatiques. Aussi, plus les thiols sont encombrés stériquement, plus le processus est lent. Toutefois, l'utilisation de grandes concentrations de thiols aromatiques et aliphatiques peut accélérer le processus d'échange. Lorsque des thioesters sont utilisés en présence de protéines à pH basique, leur caractère électrophilique les rend propices à la dégradation chimique par hydrolyse ou par acylation des fonctionnalités nucléophiles des protéines. Néanmoins, à pH neutre, des bibliothèques de thioesters possédant plus de 40 composantes furent facilement réalisées à partir de seulement 7 synthons. Il a pu être démontré que la composition de ces bibliothèques est influencée par la présence de protéines. Cependant, nous n'avons pas été en mesure de confirmer si le RVD a véritablement influencé la nature des bibliothèques de thioesters grâce à son site de liaison. Certaines de nos observations mettent en doute l'utilisation de la transthioestérification comme processus dynamique viable pour la création d'analogues de la vitamine D en présence de protéines.Finalement, des synthons dithiols furent créés et leur combinaison a permis la formation de bibliothèques dynamiques de plus de 30 composés, grâce à l'échange de disulfures. Les études préliminaires ont montré que les bibliothèques de disulfures ne semblent pas être influencées par la présence du RDV. Ces résultats ont permis de connaître les caractéristiques et les limites de ces systèmes dynamiques appliqués au développement de nouveaux analogues de la vitamine D.

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10

KARAM, SOFIA BAPTISTA. "CORPS EN COMBAT, SCÈNES D UNE VIE." PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO, 2018. http://www.maxwell.vrac.puc-rio.br/Busca_etds.php?strSecao=resultado&nrSeq=34268@1.

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PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO
COORDENAÇÃO DE APERFEIÇOAMENTO DO PESSOAL DE ENSINO SUPERIOR
CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO
PROGRAMA DE SUPORTE À PÓS-GRADUAÇÃO DE INSTS. DE ENSINO
PROGRAMA DE DOUTORADO SANDUÍCHE NO EXTERIOR
En partant d un contexte familial d une maladie neurodégénérative héréditaire rare et incurable qui atteint le cervelet, provoquant la perte progressive de la coordination motrice et des forces musculaires, sans que les capacités intellectuelles ne soient affectées, un corps se jette dans un parcours d étude et d écriture, où la recherche théorique et une vie s entrelacent. La thèse se compose de registres d écriture variés, entremêlant des scènes, des fabulations, des souvenirs, des délires, des essais, et d autres voix d intercesseurs divers qui traversent le texte en dialogue avec le corps-pensée en combat et en construction tout au long de la recherche et de l écriture.
A partir de um quadro familiar de uma doença neurodegenerativa hereditária rara e incurável que ataca o cerebelo, de corpos que perdem progressivamente sua coordenação motora e sua força muscular, sem ter sua capacidade intelectual afetada, um corpo se lança em um caminho de estudo e escrita, onde pesquisa teórica e uma vida se entrelaçam. A tese se desenrola com registros de escrita variados, misturando cenas, fabulações, memórias, delírios, ensaios, e vozes de intercessores diversos que atravessam o texto em diálogo com o corpo-pensamento em combate e em construção ao longo do processo de pesquisa e escrita.

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11

YASUDA, TAKEHIKO. "NONCOMMUTATIVE RESOLUTION VIA FROBENIUS MORPHISMS AND D-MODULES." 名古屋大学多元数理科学研究科, 2009. http://hdl.handle.net/2237/12256.

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12

Kimmel, Christine. "1,25-Dihydroxyvitamine D3 : aspects moléculaires de sa synthèse et de son action via son récepteur." Paris 5, 2002. http://www.theses.fr/2002PA05CD04.

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La 1,25-dihydroxyvitamine D3 [1,25-(OH)2D3] est le métabolite actif de la vitamine D3. Des travaux in vivo et in vitro ont montré que les concentrations circulantes de cette hormone sont principalement régulées à l'échelon de l'enzyme 25-hydroxyvitamine D 1a -hydroxylase (1-hydroxylase) rénale. Les différents facteurs régulant l'activité 1-hydroxylase sont connus, mais leur mode d'action, direct ou indirect, reste à élucider. Un premier objectif a été de cloner le gène de la 1-hydroxylase chez la souris et séquencer son promoteur. Nous avons identifié une boîte TATA et une boîte CAAT et montré l'activité promotrice d'un fragment de 1,7kb par transfections transitoires dans une lignée de cellules du tubule proximal, AOK-B50. Nous avons ainsi pu montrer qu'un stimulateur majeur de la 1-hydroxylase, l'hormone parathyroi͏̈dienne (PTH), augmente l'expression d'un gène rapporteur (luciférase) de façon dose dépendante. Cet effet est mimé par la forskoline, un activateur de l'adénalyte cyclase et donc de la voie de second messager AMPc. A l'inverse, la 1, 25-(OH) 2 D3, un facteur inhibiteur majeur, n'a pas révélé d'effet sur l'activité du promoteur in vitro. Des motifs putatifs CRE et API ont été identifiés dans la séquence du promoteur. Aucun site VDRE classique n'a été révélé. Nous avons séquencé le gène entier de la 1-hydroxylase de souris, qui comprend 9 exons pour une taille de 4,8kb. Un site de polyadénylation AUUAAA a été identifié, variant d'une base par rapport à la séquence consensus. Notre second objectif a consisté à étudier le mode d'action de la 1,25-(OH) 2 D3 via son récepteur nucléaire, le VDR. Nous avons utilisé la technique de retardement sur gel. A des concentrations en sels (150 mM KC1) se rapprochant des concentrations physiologiques intranucléaires, la présence de 1,25-(OH) 2 D3 est nécessaire à la formation des complexes VDR-RXR-VDRE qui stimulent la transcription de gènes cibles classiques de la vitamine D. Par contre aucun complexe spécifique n'est mis en évidence à 150 mM KC1 pour le VDRE répresseur du gène de la PTH humaine. Enfin, nous avons montré l'aptitude des hétérodimères VDR-RXR à induire une courbure de l'ADN d'amplitude similaire après liaison à différents VDRE stimulateurs ou répresseurs.

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13

Kang, Qinghua (George). "Characterization of Vertical Interconnects in 3-D Monolithic Microwave Integrated Circuits (3-D MMIC)." University of Cincinnati / OhioLINK, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1053630359.

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14

Gall, Olivia. "Trotsky et la vie politique dans le Mexique de Cardenas, 1937-1940." Lille 3 : ANRT, 1986. http://catalogue.bnf.fr/ark:/12148/cb37597764x.

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15

Billeau, Sébastien. "Synthèse de molécules dérivées du benzothiazole et de la tétrahydroacridine." Aix-Marseille 3, 2004. http://www.theses.fr/2004AIX30033.

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Au cours de ce travail, nous avons développé la synthèse d’une nouvelle famille de composés : les thiazolo-tétrahydroacridines. Une stratégie de synthèse a été élaborée puis optimisée et nous avons ainsi obtenu huit molécules originales. De nombreux composés benzothiazoliques préparés au cours de ce travail en tant qu’intermédiaires de synthèse, présentent, eux aussi, un intérêt certain. Ceci nous a permis de valoriser ces produits. Tous les composés synthétisés sont en cours d’évaluation dans différents domaines d’activité et notamment dans le domaine thérapeutique. Certains résultats au niveau de l’activité anti-VIH sont encourageants et montrent l’intérêt de pousser plus loin les travaux dans cette voie
During this work, we developed the synthesis of a new family of compounds: the thiazolo-tetrahydroacridines. A strategy of synthesis has been elaborated then optimized and we obtained eight original molecules. Although it is only intermediates of synthesis, many benzothiazolic compounds prepared during this work present a certain interest. It permitted us to increase the high specificity of our compounds. All synthesized compounds are tested in different fields of activity and notably in the therapeutic one. Some results as the anti-HIV activity are encouraging and show the interest to continue works in this way

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16

Mai, Nathalie. "Nouvelle synthèse asymétrique d'"alpha"-aminoacides via leurs cétènes." Montpellier 2, 1997. http://www.theses.fr/1997MON20148.

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L'objectif de ce travail etait de developper un nouveau procede de deracemisation permettant d'obtenir des aminoacides optiquement actifs. Nous avons etudier la reaction d'addition stereoselective basocatalysee d'un alcool chiral en l'occurrence la (r)-pantolactone sur differents aminocetenes correctement proteges prepares in situ a partir des chlorures d'acide racemiques correspondants. Nous avons mis en evidence l'importance des conditions experimentales en soulignant plus particulierement le role essentiel de l'amine tertiaire et de la nature du substituant de l'aminoacide utilise sur la stereoselectivite de ce type de reaction. Afin de traduire ces resultats, nous proposons un mecanisme simplifie dont l'etape cle repose sur la formation intermediaire de deux zwitterions isomeres de structures e et z sur lesquels s'additionne la (r)-pantolactone. Les esters pantolactoniques n-proteges obtenus peuvent conduire facilement aux -aminoacides ou aux -aminoalcools optiquement actifs correspondants par simple hydrolyse acide ou par reduction par action du borohydrure de sodium. L'application de cette methode au cas des -aminoacides semble prometteuse puisque les premiers essais permettent d'obtenir des aminoesters avec des exces diastereoisomeriques atteignant 60%. Nous avons montre egalement que l'addition d'un aminoester chiral sur un aminocetene correctement protege conduisait aux dipeptides avec une bonne stereoselectivite. Enfin, dans le but de simplifier la methodologie nous avons ebauche la synthese d'inducteurs chiraux, analogues de la pantolactone, susceptibles d'etre ancres sur un polymere.

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Löfholm, Birgitta. "Examensarbete i industriell teknik vid Scania R&D." Thesis, Uppsala universitet, Institutionen för samhällsbyggnad och industriell teknik, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-413697.

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The study aims to study if it is possible to reduce lead time or resource needs by studying the PD process, Product Development Process linked to the improvement area Unclear requirements from managers on measuring the process. This is done by studying current control, the possibility of using other measuring points and how a measurement system could be established, including Scorecard within Scania R&D, Research and Development. The study is based on the questions What does the product development process look like? What could be measured in the product development process? and How could a measurement system with integrated Scorecard be implemented for better control of the product development process? Theories include the areas of processes, process control, process measurement and process management. Interviews, group interviews, document studies, literature studies and previous research were the basis for studying the problem and opportunities for improvement. All data collection was done remotely as Covid-19 had major impacts. The result of the study shows that R&D does not currently measure the PD process, but measurement is regulated in internal documents. Measurement of lead time, resources and costs was desired by interviewees to measure. Basing the measurement on the current KPI, Key Performance Indicators, and R&D strategic plan 2020 implies established support from the functions that produced the internal documents. The developed measurement system includes the measurement points lead time, cost and resource requirements as well as selected milestones. An introduction of the measurement system would, for Scania R&D, provide an opportunity to control the PD process linked to the measurement points. The measurement system has largely been based on internal documents to increase the relevance of the measurement system and the possibility of an introduction.
Studien syftar till att studera om det går att minska ledtid eller resursbehov genom att studera PD processen, Product Development Process, kopplat till förbättringsområdet Otydliga krav från chefer på mätning av processen. Det utförs genom att studera nuvarande styrning, möjligheten att använda andra mätpunkter samt hur ett mätsystem skulle kunna upprättas inkluderat Scorecard inom Scania R&D, Research and Development. Studien baserar sig på frågeställningarna Hur ser produktframtagningsprocessen ut? Vad skulle kunna mätas i produktframtagningsprocessen? samt Hur skulle ett mätsystem med integrerat Scorecard kunna implementeras för bättre styrning av produktframtagningsprocessen? Teorier berör områdena processer, processtyrning, processmätning och processledning. Intervjuer, gruppintervju, dokumentstudier, litteraturstudier och tidigare forskning låg till grund för att studera problemet och förbättringsmöjligheter. Samtlig datainsamling utfördes på distans då Covid-19 hade stora påverkningar. Studiens resultat visar att R&D i nuläget inte mäter PD processen men mätning finns reglerat i interna dokument. Mätning av ledtid, resurser och kostnader var önskat av intervjupersoner att mäta. Att basera mätningen på nuvarande KPI, Key Performance Indicators, och R&D strategisk plan 2020 innebär ett etablerat stöd hos de funktioner som tagit fram de interna dokumenten. Det framtagna mätsystemet inkluderar mätpunkterna ledtid, kostnad och resursbehov samt utvalda milstolpar. Ett införande av mätsystemet skulle för Scania R&D innebära en möjlighet till att styra PD processen kopplat till mätpunkterna. Mätsystemet har till stor del baserats på interna dokument för att öka mätsystemets relevans samt möjligheten till ett införande.

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Omoike, Gracious. "Har D-vitamintillskott effekt vid behandling av Systemisk Lupus Erythematosus? : En litteraturstudie." Thesis, Linnéuniversitetet, Institutionen för kemi och biomedicin (KOB), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-85942.

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Introduktion: Systemisk Lupus Erythematosus är en prototypisk autoimmun sjukdom som gör att immunförsvarets antikroppar angriper kroppens egna vävnader, vilket leder till kronisk inflammation i kroppens organsystem. Idag finns ingen verksam behandling för Systemisk Lupus Erythematosus. Syftet med denna studie var att undersöka hur Dvitamintillskott påverkar Systemisk Lupus Erythematosus. Metod: Artiklarna hittades i databasen ”Pubmed” med sökningen ”Systemic Lupus Erythematosus and vitamin D supplementation”. Bland sökresultaten fanns sex relevanta artiklar som hade undersökt effekten av D-vitamintillskott på SLE. Resultat: Mer än hälften av patienterna i samtliga studier nådde serum 25(OH) D-nivåer som ansågs vara tillräckliga. D-vitamintillskottet minskade Th1/Th17-cellerna men ökade också Treg-celler och Th2-celler. Tre studier visade sig ha en signifikant minskning i sjukdomsaktivitet och anti-dsDNA antikroppar. Komplement C3 minskade i studie 2. Diskussion: Fem av studierna tyder på att oral administrering av D-vitamin tillskott har gett positiv inverkan på SLE. Två av de granskade studierna rapporterades inge positiv klinisk effekt hos deltagarna. Slutsats: D-vitamintillskott dämpar immunsystemet genom att öka Treg-celler och Th-2-celler men även minska Th1/Th17-celler och B-celler samt produktionen av autoantikroppar och anti-dsDNA-antikroppar. Effekten av D-vitamintillskott på komplement C3 och C4 är oklar. Det krävs dock fler studier med fler deltagarantal för att dra en slutsats om Dvitamintillskott kan användas som behandling för SLE.
Background: Systemic Lupus Erythematosus is a prototypical autoimmune disease in which antibodies attack healthy tissues in the body, causing inflammation in several organs. Aim: The aim of this literature study was to investigate the effect of Vitamin Dsupplementation on SLE. Method: The articles were searched in the database called ”Pubmed” using the search terms ”Systemic Lupus Erythematosus and Vitamin D supplementation”. Six of the articles which examined the effects of D-vitamin supplementation on SLE were relevant for this study. Result: More than half of the patients in all six studies reached sufficient serum 25(OH)D. Vitamin D-supplement reduced Th1/Th17-cells but increased Tregs-cells and Th2-cells. 3 studies showed a decrease in disease-activity and anti-dsDNA. C3 decreased in study 2. Discussion: Five studies indicated that the oral administration of vitamin-D supplementation had a positive effect on SLE. Two of the examined studies did not observe any clinical effect of the vitamin-D supplement. Conclusion: Vitamin-D supplement suppresses the immunesystem by increasing Treg cells and Th-2 cells but also reducing Th1/Th17-cells and B-cells as well as the production of autoantibodies and anti-dsDNA antibodies. The effect of vitamin D-supplement is unclear. More studies with more participants are required to determine if vitamin-D supplement can be used as a treatment for SLE.

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Fernandes, Simone Crestoni. "Via da vitamina D em tumores de mama de cadelas." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/5/5155/tde-13022014-085013/.

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A vitamina D (VD) pode estar envolvida no controle da proliferação, diferenciação e apoptose em linhagens mamárias. Existem evidências de que mulheres com câncer de mama apresentam menor concentração sérica de 25(OH)D3 ou de 1,25(OH)2D3 em relação às mulheres sem câncer. Por outro lado, pouco se sabe se a concentração sérica de VD pode influenciar o desenvolvimento de câncer de mama em cadelas e se o hormônio pode ter efeito quimiopreventivo, inibindo o aparecimento de tumores ou mesmo efeito terapêutico, reduzindo a proliferação de células malignas. Logo, nossos objetivos foram comparar a concentração sérica de 25(OH)D3 em animais com e sem tumor mamário e analisar as ações de 1,25(OH)2D3 em glândulas mamárias normais e tumorais de cadelas, utilizando como modelo a cultura de tecidos. Inicialmente foram incluídas 39 cadelas portadoras de tumor de mama e 64 cães sem tumor (controle), sendo que 50 eram fêmeas e 14 eram machos. Observamos que os animais do grupo tumoral possuíam idade mais avançada (mediana de 108 meses) em relação ao grupo controle (mediana de 36 meses para os machos e 24 meses para as fêmeas). No grupo controle, a concentração sérica foi maior nos machos (32,5 ± 19,3 ng/mL) do que nas fêmeas (22,8 ± 9,6 ng/mL), mas não houve diferença em relação ao grupo tumor (26,62 ± 14,25 ng/mL). Em relação à dieta, a concentração sérica de 25(OH)D3 foi maior nas fêmeas do grupo controle que se alimentavam de ração em comparação às que se alimentavam de comida caseira e ração. Entretanto, não houve diferença em relação à exposição ao sol e características da pelagem em todos os animais. No grupo tumoral, houve correlação inversa da concentração sérica de 25(OH)D3 em relação à idade, mas não houve diferença quanto ao tipo histológico ou estadiamento da doença. Foram coletadas 70 amostras de tumor de mama e de tecido mamários normal de cadelas, as quais foram cultivadas em fatias. Dos tecidos tumorais, 50% eram positivos para receptor de estrógeno (acima de 10% de células marcadas) e 44% eram positivos para HER-2 (método HercepTest). Detectou-se expressão gênica e proteica do receptor da vitamina D (VDR) em tecido mamário normal e tumoral, sendo identificado três padrões na imunoistoquímica: I - células epiteliais e mioepiteliais (mais frequentemente encontrada em tecido normal), II - marcação predominante em células mioepiteliais (mais comum em tecido tumoral e III - marcação predominante em células epiteliais. As amostras foram tratadas com 1,25(OH)2D3 nas concentrações 0,228 nM, 2 nM e 100 nM (concentração fisiológica, farmacológica que não induz hipercalcemia e farmacológica que induz hipercalcemia, respectivamente). O conteúdo de VD tecidual avaliado por cromatografia líquida foi crescente de acordo com as concentrações de VD utilizadas, indicando penetração do hormônio nas fatias. Observou-se indução da expressão de CYP24A1, que variou de 27 a 158 vezes dependendo da concentração utilizada, indicando ativação genômica da via da VD e que o tecido permanece metabolicamente ativo em cultura. Entretanto, não houve diferença da expressão gênica de outros genes envolvidos com o metabolismo da VD (CYP27B1), genes envolvidos no controle da proliferação (CDKN1A e CDKN1B) e genes envolvidos com a imunidade (CD14). O tratamento com calcitriol nas diferentes concentrações não induziu a apoptose (expressão proteica de caspase-3 clivada) e não alterou a proliferação nos tecidos normais (expressão proteica de Ki-67), mas diminuiu a proliferação nos tecidos tumorais. Não foi observada correlação entre a indução da apoptose e redução da proliferação com os padrões de expressão proteica de VDR. Concluindo, não observamos diferença na concentração sérica de 25(OH)D3 entre cadelas com tumor de mama e animais controle. Detectamos que o calcitriol em concentração fisiológica ativa a via genômica de VD em mama normal e tumoral e reduz o índice de proliferação (expressão de Ki-67) nos tumores de mama
Vitamin D (VD) may be involved in the control of proliferation, differentiation and apoptosis of mammary cell lines exposed to high concentrations of the hormone. There is some evidence that women with breast cancer present lower serum level of 25(OH)D3 or 1,25(OH)2D3 compared to women without cancer. Moreover, little is known if serum concentration of VD can influence the development of mammary tumors in dogs and if the hormone may have chemopreventive effect by inhibiting the appearance of tumors or therapeutic effect, reducing the proliferation of malignant cells. Therefore, our goals were to compare the serum 25(OH)D3 level in animals with and without mammary tumor and to analyze 1,25(OH)2D3 effects in normal and tumoral canine mammary glands, using as a model the tissue culture. At first, 39 bitches with mammary tumor and 64 dogs without tumor (control), of which 50 were females and 14 were males were included. Animals in tumor group were older (median 108 months) compared to control group (median 36 months for males and 24 months for females). In control group, serum concentration was higher in males (32.5 ± 19.3 ng/mL) than in females (22.8 ± 9.6 ng/mL), but there was no difference when compared to tumor group (26.62 ± 14.25 ng/mL). Regarding diet, serum 25(OH)D3 level was higher in control bitches fed commercial pet food compared to those fed homemade and commercial pet food combined. However, there was no difference of serum 25(OH)D3 concentration, sun exposure and coat features. In tumor group, there was an inverse correlation between serum 25(OH)D3 and age, but there was no difference in 25(OH)D3 concentration among bitches with different histological type or clinical stage of the disease. Seventhy bitches diagnosed with mammary tumors had tumor and mammary samples collected, sliced and cultured. In tumor tissues, 50% were positive for estrogen receptor (over 10% of cells stained), and 44% were positive for HER-2 (HercepTest method). Vitamin D receptor (VDR) protein and genic expression was detected in normal and tumoral samples. Three patterns of VDR were detected by immunohistochemistry: I - localizated in epithelial and myoepithelial cells (more often in normal tissues), II - predominantly in myoepithelial cells (most common in tumor tissues) and III - predominantly in epithelial cells. Normal anmammary slices were treated with 1,25(OH)2D3 0.228 and 100nM concentrations (concentration physiological and pharmacological, respectively) and mammay tumor slices were treated with 1,25(OH)2D3 2 nM concentrations (drug concentration which does not induce hypercalcemia) and 100 nM, for 24 hours. VD tissue content measured by liquid chromatography was higher in samples exposed to high VD concentration, indicating penetration of the hormone in slices. VD treatment induced CYP24A1 expression, 27 to 158 fold depending on the concentration used, and indicating activation of the VD genomic pathway. This result also suggest that the tissue remains metabolically active in culture. However, no difference in gene expression of other target genes such as CYP27B1, genes involved in proliferation as CDKN1A and CDKN1B and genes involved in immunity, such as CD14. Calcitriol treatment at different concentrations did not induce apoptosis (protein expression of cleaved caspase-3) and did not alter proliferation in normal tissues (expression of protein Ki -67), but decreased proliferation in tumor tissues. No correlation was observed between the induction of apoptosis and reduction of proliferation with the protein expression patterns of VDR. In conclusion, no difference in serum 25(OH)D3 between bitches with mammary tumor and control animals was observed. In normal and tumoral mammary samples calcitriol physiologic concentration activated VD genomic pathway and in tumor samples calcitriol reduced the proliferation index (Ki-67)

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Crevel-Thieffry, Isabelle. "Étude sur l'inhibiteur de la ribonucléase : son rôle éventuel dans la maladie d'Alzheimer, étude d'un peptide trypsique montant une activité inhibitrice vis-à-vis de la ribonucléase A." Lille 1, 1992. http://www.theses.fr/1992LIL10066.

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L'étude de 29 cerveaux provenant de patients décédés de la maladie d'Alzheimer, n'a pas fait apparaître de corrélation significative entre le degré de détérioration mentale des malades et l'activité de l'inhibiteur de la ribonucléase alcaline cérébrale, dans le cortex et le cervelet. Un anticorps dirigé contre l'inhibiteur placentaire humain de la ribonucléase n'a pu permettre de déceler l'inhibiteur cérébral dans ces mêmes cerveaux. L'inhibiteur placentaire humain de la ribonucléase, a été également étudié. A partir d'un extrait placentaire, précipité au sulfate d'ammonium, l'inhibiteur a été purifié en une seule étape de chromatographie d'affinité en modifiant un protocole. L'hydrolyse trypsique de cette protéine a permis d'isoler après CLHP en phase inverse un peptide présentant les mêmes caractéristiques enzymatiques que la protéine native. Pour cette étude un peptide synthétique a été utilisé. Un fragment du gène de cet inhibiteur a été isolé d'une banque d'ADNc à l'aide de la technique de la Pcr. Ce fragment de 500 pb a été séquencé, il possède la séquence codant pour le peptide de 15 acides aminés étudié cinétiquement. Cette région du gène de a été sous-clonée dans un système qui permettra de la faire s'exprimer sous forme d'une protéine de fusion

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Provencher, Véronique. "Exploration des divers impacts de l'apprentissage de tâches significatives liées à la vie quotidienne dans la démence de type Alzheimer (DTA) en début d'evolution." [S.l. : s.n.], 2006.

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Al, Kalanee T. "Étude du noyau d'9He via la réaction de transfert d(8He, p) à 15.4 MeV/nucléon." Phd thesis, Université de Caen, 2010. http://tel.archives-ouvertes.fr/tel-00557105.

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L'étude des noyaux légers riches en neutrons à la limite de la stabilité et au-delà suscite un intérêt marqué depuis quelques années car elle offre des tests approfondis de notre compréhension de la structure nucléaire. Expérimentalement, la disponibilité récente de faisceaux radioactifs avec des intensités suffisantes et le développement de nouveaux systèmes de détection de grande acceptance ont permis de sonder la structure de ces noyaux. Cette thèse porte sur l'étude de la structure de l'9He, système N = 7 non lié, via la réaction de transfert d'un neutron d(8He, p)9He avec l'aide d'un faisceau SPIRAL1. L'objectif principal de l'expérience était de clarifier la structure des états à basse énergie d'excitation de l'9He, en particulier l'inversion de parité possible de l'état fondamental. L'expérience a été une des premières à utiliser le nouvel ensemble de détection MUST2. Les statistiques relativement faibles dans la région du seuil d'émission de neutron et les divers fonds physiques, ne permettent pas de conclusion définitive concernant la nature de l'état de plus basse énergie. Des états à des énergies d'excitation plus élevées ont été identifiés. Une comparaison entre les distributions angulaires pour chacune des résonances avec des calculs DWBA et CRC a été effectuée. Les facteurs spectroscopiques ont été estimées pour chaque spin possible.

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Gracia, Gabriel Brandão de. "Um estudo dos modelos BF de D=1+1 até D=3+1 dimensões via Hamilton-Jacobi." Universidade Estadual Paulista (UNESP), 2017. http://hdl.handle.net/11449/152643.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Ao longo desta dissertação desenvolvemos o formalismo de Hamilton-Jacobi para teorias de campo para o caso de sistemas singulares e não-singulares. Em seguida, aplicamos tal formalismo nos modelos BF em D=1+1, D=2+1 e D=3+1 dimensões a fim de caracterizar os seus espaços de fase. Mostramos que a partir desse formalismo é possível obter as simetrias locais desses modelos assim como os seus respectivos geradores.
Throughout this dissertation we develop the Hamilton-Jacobi formalism for field theories in the case of singular and non-singular systems. Next, apply such formalism on the BF models in D=1+1, D=2+1 e D=3+1 dimensions in order to characterize their phase spaces. We show from this formalism, that is possible to find the local symmetries of those models as well as their respective generators.
CNPq: 132619/2015-6

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Santos, Renato da Costa [UNESP]. "Partículas de spin-1 em D-dimensões via tensor simétrico." Universidade Estadual Paulista (UNESP), 2012. http://hdl.handle.net/11449/91813.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Nesta disserta,ão obtemos modelos duais de rank superior para partículas de spin-0, spin-1 e spin-2 em D-dimensões utilizando a técnica da ação mestra. Como introdução obtemos um modelo simples para uma partícula de spin-0 utilizando um campo vetorial o qual servirá de paradigma para os capítulos posteriores. Verificamos o conteúdo físico obtido através de suas equações de movimento, propriedades analíticas do propagador e do algoritmo de Dirac-Bergman para sistemas vinculados. No caso de partículas de spin-1, fazemos um acoplamento mínimo na ação mestra tanto com o campo gravitacional quanto com o campo eletromagnético o que resulta, curiosamente, no aparecimento de termos não mínimos nas ações descendentes
In this master thesis we obtain dual models of the higher rank type for particles of spin-0, spin-1 and spin-2 in D-dimensions by using the master action technique. As an introduction we obtain a simple model for a spin-0 particle by using a vectorial field which serve as paradigm for the next chapters. We verify the particle content of the models through the analysis of the equations of motion, analytical properties of the propagator and we count the degrees of freedom by using the Dirac-Bergman algorithm for constrained systems. In the case of spin-1 particles, we do a minimal coupling in the master action first with the gravitational field and secondly with the electromagnetic field which result, curiously, in the appearance of non minimal couplings terms in the descendent actions

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Santos, Renato da Costa. "Partículas de spin-1 em D-dimensões via tensor simétrico /." Guaratinguetá : [s.n.], 2012. http://hdl.handle.net/11449/91813.

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Orientador: Denis Dalmazi
Banca: Marcelo Hott
Banca: Nathan Jacob Berkovits
Resumo: Nesta disserta,ão obtemos modelos duais de rank superior para partículas de spin-0, spin-1 e spin-2 em D-dimensões utilizando a técnica da ação mestra. Como introdução obtemos um modelo simples para uma partícula de spin-0 utilizando um campo vetorial o qual servirá de paradigma para os capítulos posteriores. Verificamos o conteúdo físico obtido através de suas equações de movimento, propriedades analíticas do propagador e do algoritmo de Dirac-Bergman para sistemas vinculados. No caso de partículas de spin-1, fazemos um acoplamento mínimo na ação mestra tanto com o campo gravitacional quanto com o campo eletromagnético o que resulta, curiosamente, no aparecimento de termos não mínimos nas ações descendentes
Abstract: In this master thesis we obtain dual models of the higher rank type for particles of spin-0, spin-1 and spin-2 in D-dimensions by using the master action technique. As an introduction we obtain a simple model for a spin-0 particle by using a vectorial field which serve as paradigm for the next chapters. We verify the particle content of the models through the analysis of the equations of motion, analytical properties of the propagator and we count the degrees of freedom by using the Dirac-Bergman algorithm for constrained systems. In the case of spin-1 particles, we do a minimal coupling in the master action first with the gravitational field and secondly with the electromagnetic field which result, curiously, in the appearance of non minimal couplings terms in the descendent actions
Mestre

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Lanelöv, Mattias. "Effekt och säkerhet av probiotika vid behandling av IBS-D." Thesis, Linnéuniversitetet, Institutionen för kemi och biomedicin (KOB), 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-102141.

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Bakgrund: Irritable bowel syndrome (IBS) karakteriseras av obehag i magtarmkanalen och förändrade avföringsvanor. Sjukdomen delas in i subtyperna IBS-C (förstoppning), IBS-D (diarré), IBS-M (blandad) och IBS-U (odiagnostiserad). Patofysiologin och etiologin är inte klarlagd, men bland annat störd tarmflora och inflammation har föreslagits. Prevalensen är 10-20 %. Denna litteraturstudie fokuserar på probiotika som behandling vid IBS-D, ett område med ökat intresse inom forskningen. Syfte och Metod: Syftet med litteraturstudien är att undersöka effekten och säkerheten av probiotika Clostridium butyricum, Saccharomyces boulardii, Bio-Kult® samt BIO-25 på IBS-D patienter. Sökning i den medicinska databasen PubMed januari 2021 genererade 5 dubbelblindade, randomiserade, placebokontrollerade studier. Resultat: Bio-Kult® och Clostridium butyricum resulterade i signifikant skillnad på symtom jämfört med placebo. Den förstnämnda hade inga biverkningar, medan den senare medförde åtta biverkningsfall. Saccharomyces boulardii förbättrade interleukin-8 (IL-8), tumor necrosis-α (TNF-α), IL-10 och IL-10/IL-12 kvoten, men inte symtomen jämfört med placebo. Nära hälften av deltagarna fick lättare biverkningar. BIO-25 medförde en förbättrad tarmflora vad gäller Lactococcus och Lactobacillus, men det gav inga symtomförbättringar jämfört med placebo. Inga biverkningar upptäcktes. Quality of Life (QOL) förbättrades i alla studier där variabeln mättes. Slutsats: Liksom tidigare studier av andra forskare genererade artiklarna i detta arbete ett tvetydigt utfall. En anledning till det varierande resultatet kan härledas till placeboeffekten. En del av resultaten är hoppingivande, speciellt när det gäller QOL. Samtidigt antyder undersökningarna att probiotikans effekt är beroende av tarmflorans sammansättning. Saccharomyces boulardii förbättrade IL-8, TNF-α, IL-10 och IL-10/IL-12 kvoten, medan BIO-25 förbättrade Lactococcus och Lactobacillus. Fyra av fem studier hade en bra biverkningsprofil. Slutsatsen blir att probiotika har viss effekt på IBS-D patienter och få biverkningar. Fler och större studier behövs för att få en klarare bild av probiotikans effekt och biverkningar på IBS-D patienter.
Background: Irritable bowel syndrome (IBS) is characterized by discomfort in gastrointestinal tract and change in the bowel motility. The subtypes of the disease are diveded into IBS-C (constipation), IBS-D (diarrhea), IBS-M (mixed) and IBS-U (undefined). The pathophysiology and etiology are incompletely understood but changed gut microbiota and inflammation has been proposed among other things as the underlying causes. The prevalence is 10-20 %. This study focused on probiotics as a treatment for IBS-D, which has been used during the last decade in the treatment of the disease. Purpose and method: This study aimed to assess the efficacy and safety of Clostridium butyricum, Saccharomyces boulardii, Bio-Kult® and BIO-25 on IBS-D patients. Searches in the medical database PubMed in January 2021 resulted in 5 double-blind, randomized, placebo-controlled trials. Results: Bio-Kult® and Clostridium butyricum resulted in significant differences compared with placebo. The prior had no adverse events, while the latter had eight adverse events. Saccharomyces boulardii improved interleukin-8 (IL-8), tumor necrosis-α (TNF-α), IL-10 och IL-10/IL-12 ratio, but not the symptoms compared with placebo. Nearly fifty percent of the patients had mild adverse events. BIO-25 resulted in improved Lactococcus and Lactobacillus but showed no improvements in symptoms compared with placebo. No adverse events were discovered. Quality of Life (QOL) improved in all studies the variable was measured. Conclusion: The outcome of this study was inconclusive and thus similar to previous studies. One of the reasons for the various outcomes can be derived from the placebo effect. In some of the results the use of probiotic treatment were positive, especially when it comes to the improvement of QOL. The studies suggested that the effect of probiotics is dependent on the composition of the gut microbiota. Saccharomyces boulardii improved IL-8, TNF-α, IL-10 och IL-10/IL-12 kvoten, while BIO-25 improved Lactococcus och Lactobacillus. Four out of five studies had a good outcome when it comes to adverse events. The conclusion of this thesis is that probiotics have some effect on IBS-D patients and few adverse events. Larger studies need to be done to evaluate the effect of probiotics and its adverse events.

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Klanger, Cecilia. "D-vitaminstatus vid svår psykiatrisk sjukdom och samband med inflammationsparametrar." Thesis, Örebro universitet, Institutionen för medicinska vetenskaper, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-85660.

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Bakgrund Det är känt att vitamin D-receptorer finns i hjärnan och på immunceller och att D-vitamininteragerar med dessa. D-vitaminstatus vidpsykiatrisksjukdom, samt D-vitaminstatusi relation till immunförsvaretärdockrelativt outforskade områden.D-vitaminstatus speglas av 25-OHD-nivåer.SyfteSyftet med studien är att se huruvida det kan finnasen relation mellan 25-OHD och svår psykiatrisk sjukdom, samt att undersöka sambandetmellan 25-OHD och olika inflammationsparametrar. Metod Dettaär en explorativ fall-kontrollstudie. Till studien rekryterades80 studiedeltagare; 40 patienter med varierande gradav svår psykiatrisk sjukdom, samt 40friskamatchade kontroller. Serumnivåer av 25-OHD och olika inflammationsparametrar analyserades. Statistiska analyser genomfördesför att undersöka hur 25-OHD-nivåernakorreleradetill kontroll-respektive patientgrupp, antal diagnoser samt olika inflammationsparametrar. Resultat 25-OHD-nivåernavar något lägre hos de psykiatriska patienterna än hos kontrollerna. Sambandet var signifikant med Chi2-test (C2=8,12, p =0,044), men ej med Mann-Whitney U-test(U= 618,5, Z= -1,58, p = 0,11).Ett samband mellan antal diagnoser och sjunkande 25-OHD-nivåerkunde ejkonstateras. En korrelationmellan låga 25-OHD-nivåeroch ett högre antal vita blodkroppar fanns(Spearmans ρ= -0,28, p = 0,016). Inga övriga signifikanta samband med inflammationsparametrar kunde påvisas. Slutsats Studiepopulation var för liten för att påvisa tydligasamband mellan D-vitaminstatusoch psykiatrisksjukdom, men resultaten antyderatt en korrelation finns,och studien är i linje med tidigare forskning, varför fleroch störrestudier behöver göras. Ett samband mellan D-vitaminstatusoch vita blodkroppar kunde påvisas, men inte medövriga inflammationsparametrar, och fler studier kring D-vitamin och inflammationbehövs.

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Blériot, Yves. "Amidines cycliques dérivées du D-mannose : synthèse, structures et pouvoir inhibiteur vis-à-vis des glycosidases." Nantes, 1994. http://www.theses.fr/1994NANT2077.

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L'objectif de cette thèse est de synthétiser et d'évaluer de nouveaux inhibiteurs de glycosidases de type amidines cycliques, analogues d'état de transition, dans le but de les utiliser ultérieurement comme haptènes pour générer des anticorps catalytiques à activite glycosidasique. Dans le chapitre d'introduction, le mécanisme d'action des glycosidases est décrit. Une revue des principaux inhibiteurs de glycohydrolases isoles ou synthétisés jusqu'a present et un aperçu de leurs effets thérapeutiques sont présentés. Dans le deuxième chapitre, la synthèse des différentes amidines est décrite. Une nouvelle voie de synthèse originale pour aboutir aux amidines polyhydroxylées dérivées du d-mannose est présentée. Enfin la synthèse d'une amidine plus complexe, un pseudodimannoside lié en 1,6 par une liaison amidine, est détaillée. Dans le troisième chapitre, ces molécules sont étudiées du point de vue structural conjointement par modélisation moléculaire et RMN. Il est démontré une très grande analogie structurale avec l'ion oxocarbonium, état de transition supposé de la réaction d'hydrolyse de la liaison osidique catalysée par les glycosidases. Dans le dernier chapitre, le pouvoir inhibiteur de ces molécules, de type compétitif, est déterminé vis-à-vis de plusieurs exoglycosidases. Pour les amidines dérivées du mannose, une étude enzymologique approfondie est réalisée avec notamment l'étude du pouvoir inhibiteur en fonction du PH. Compte-tenu de l'excellent pouvoir inhibiteur de ces molécules, une utilisation ultérieure comme agent chimiothérapeutique peut être envisagée.

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Grange, Matthew. "Performance optimisation of through silicon via integrated 3-D die stacks." Thesis, Lancaster University, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.617806.

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This work describes a comprehensive modelling and analysis hierarchy which pursues the convergence point between system-level behaviour and low-level physical design of 3-D integrated circuits. The complete modelling, design and analysis methodology can be applied to wider technological design areas in deep submicron very large scale integrated systems such as massively parallel computational systems and high-speed digital signalling. The electrical parasitic signature of Through Silicon Vias (TSVs) are exhaustively defined with novel closed-form equations for various coupled and isolated 3-D interconnect configurations. The trade-offs in electrical performance for the 3- D interconnect for industry-standard on-chip CMOS signalling circuits including low-voltage, differential , current mode and shielding practices are then presented to define signalling conventions for 3-D circuits and arc compared to the planar 00- and off-chip interconnect. Thermal compact models of 3-D packages are discussed and used to develop a stand-alone thermal simulation tool to provide fast analysis of state-of-the-art IC packages. Moving from the physical-level, the communication infrastructure of 3-D ICs is rigorously investigated with particular attention to the packet-switching Network-on-Chip framework. The model for average distance is derived and rigorously analysed with cycle-accurate simulations to optimise the partitioning of multifunctional dies. The scalability and performance of 2-D and 3-D networks is then assessed where a custom cycle accurate simulator is developed for several traffic patterns, switch architectures and network configurations. Finally, to bring the physical and communication-level models into perspective, a set of hierarchical models are presented which are used to assess the computational efficiency of 2-D and 3-D silicon-based processors for early-chip planning. The development of comprehensive hierarchical models from the physical to the circuit to the system level in this work contributes significantly towards understanding the promises and limitations of future IC package design based on TSV integrated 3-D die stacking.

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Lindahl, Karlson Jenny. "Kan D-vitamin förbättra symtom vid autism hos barn? : En litteraturstudie." Thesis, Umeå universitet, Institutionen för integrativ medicinsk biologi (IMB), 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-170159.

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Laeng, Nathalie. "La maladie d'Alzheimer : variations mélodiques d'une vie psychique." Paris 5, 2001. http://www.theses.fr/2001PA05H022.

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Dans la maladie d'Alzheimer, les troubles mnésiques s'inscrivent dans le fonctionnement global de la psyché, conscient et inconscient. L'étude seule des fonctions instrumentales et cognitives ne suffit pas à mettre en lumière la spécificité démentielle. En effet, la perte des capacités intellectuelles ne justifie en rien l'hypothèse d'absence d'appareil psychique. La théorie psychanalytique offre les outils conceptuels permettant d'appréhender les fonctionnements psychiques qui aparaissent dans la démence. De plus, l'introduction de la musique au sein de la relation psychothérapique vise non seulement à déterminer les applications de la musicothérapie dans le champ de la démence mais encore à découvrir en quoi la musique nous éclaire sur le fonctionnement psychique du sujet dément. (. . . )
In Alzheimer's disease, memory troubles come up in the global functioning of the psyche, conscious and unconscious. Just studing the cognitive functions is not enough to bring out the demential specificity. In fact, the loss of intellectual capacities doesn't justify the hypothesis of an absent psychic system. The analytical theory gives the concepts the grasp of psychic functionings that can appear in dementia. Furthermore, the introduction of music in psychoterapic relationship aims not only at determining the applications of musictherapy in the field of dementia, but at discovering how music can help to understand the psychic functioning of a demented subjet. (. . . )

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Jönsson, Claudia. "Prestandaundersökning av den patientnära analysmetoden Biosynex® D-dimer via jämförelse med den laborativa analysmetoden STA-Liatest® D-Di PLUS." Thesis, Linnéuniversitetet, Institutionen för kemi och biomedicin (KOB), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-85649.

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The fibrinogen degradation product D-dimer is released in plasma during fibrinolysis. D-dimer analysis is mainly ordered for the exclusion of venous thromboembolism (VTE) in combination with a pre-test probability (PTP) score. D-dimer below 0,5 mg/L fibrinogen equivalent units (FEU) and a low PTP rules out VTE. D-dimer analysis contributes to the reduction of invasive and expensive imaging analyses, such as ultrasound and computed tomography. The Blekinge region primary care used a qualitative D-dimer point of care test (POCT) whose performance the clinical chemistry of Blekinge hospital had no insight into. The aim of the study was to investigate whether the qualitative D-dimer POCT was an adequate complement to the quantitative method used in the hospital laboratory. Fifty patients, whose blood samples arrived the laboratory in tubes with sodium citrate- and ethylenediaminetetraacetic acid (EDTA) additives, were chosen for the study. Citrate plasma was analyzed with the D-dimer laboratory method. Plasma and whole blood were analyzed with the D-dimer POCT. Quantitative results were converted to qualitative based on the cutoff value 0,5 mg/L FEU. POCT performance was computed and compared with the manufacturer’s specified values. A potential difference between the methods was evaluated with a Chi-squared test. A survey was performed where open care units answered questions regarding D-dimer POCT. The POCT performance was slightly lower than the manufacturer’s specifications. No statistically significant difference was seen between the methods. However, there were several sources of error with the latter. Some open care units mentioned weak lines in the reading area due to blood interference.
Vid fibrinolys av blodkoagel frisätts fibrinnedbrytningsprodukten D-dimer. D-dimeranalyser utförs främst för uteslutning av venös tromboembolism (VTE) i kombination med ett poängsystem för preanalytisk sannolikhet (PTP) för VTE. D-dimerhalter under 0,5 mg/L fibrinogenekvivalenta enheter (FEU) och en låg PTP utesluter med stor säkerhet VTE. Använd på rätt sätt bidrar D-dimeranalysen till att minimera onödiga invasiva och dyra undersökningar som ultraljud och datortomografi. I region Blekinge används en kvalitativ, patientnära analysmetod (PNA) för D-dimer vars prestanda Blekingesjukhusets laboratorium för klinisk kemi inte har någon insyn i. Studiens syfte var att undersöka om den kvalitativa PNA-metoden för D-dimer utgjorde ett lämpligt komplement till den kvantitativa metod som utfördes på klinisk kemi. Femtio patienter vars blodprov anlände laboratoriet i provrör med tillsats av natriumcitrat respektive etylendiamintetraättiksyra (EDTA) blev utvalda att delta i studien. D-dimer analyserades i citratplasma med laboratoriets analysmetod varefter plasma och tillhörande EDTA-blod analyserades med PNA-metoden. Kvantitativa resultat konverterades till kvalitativa efter beslutsvärdet 0,5 mg/L FEU. PNA-prestandan beräknades och jämfördes med tillverkarens angivna motsvarigheter. Med ett chi-squaretest undersöktes en eventuell signifikant skillnad mellan metodresultaten. En undersökning utfördes där regionens öppenvårdsenheter svarade på diverse frågor kring PNA-metoden. PNA-metodens beräknade prestanda var något lägre än tillverkarens. Ingen statistiskt signifikant skillnad förekom mellan laboratoriets metod och PNA-metoden, däremot fanns det flera potentiella felkällor hos den senare. Några öppenvårdsenheter vittnade om svåravlästa avläsningsområden på grund av blodinterferens.

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Jaquet-Langlais, Marie-Louise. "Jean Langlais (1907-1991), la vie et l'œuvre." Paris 4, 1992. http://www.theses.fr/1992PA040209.

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Vie et œuvre de l'organiste français Jean Langlais en Bretagne, pauvre et aveugle. Description de ses études (à l'institution des jeunes aveugles et au conservatoire de Paris) avec Marchal, Dupré, Dukas. Organiste de sainte-Clotilde en 1945. Carrière internationale de concertiste des 1945. 300 récitals en Amérique entre 1952 et 1981. Professeur à l'institut des jeunes aveugles. A la schola cantorm. Improvisateur, compositeur. 254 numéros d'opus, dont 40% de musique d'orgue, 30% de musique vocale sacrée. Reconnu principalement comme un compositeur pour orgue malgré diverses pages d'orchestre, musique de chambre, mélodies. Ses plus grands succès : "Missa salve Regina" (1954) pour cuivres, chœurs et orgues. (Prix "madame René Coty" en 1956), "te deum", "incantation pour un jour saint", orgue. Avec Messiaen, Duruflé et Alain, forme l'"école d'orgue française des années 30, qui rayonne dans le monde entier. Description de son système d'écriture, apparente au néo-classicisme tout en ayant une coloration personnelle
Life and works of the French organist Jean Langlais, born in 1907 in Brittany, poor and blind. Description of his studies (institution for the blind, Paris conservatoire) with Marchal, Dupré, Duras, named organist of sainte-Clotilde in 1945. International recitalist since 1945. 300 recitals in America between 1952 and 1981. Teacher at the institution for the blind, at the schola cantorum. Improviser, composer. 254 opus numbers, with 40% organ music, 30% sacred vocal. Known mainly as an organ composer even he composed much for orchestra, chamber music, melodies. His greatest successes include the "salve regina mass" (1954) for brass, choirs and organs, ("prix madame René Coty" in 1956) "te deum", "incantation for a holy day" for organ. Along with Messiaen, Duruflé and Alain, he forms the "French organ school of the thirties", which is known in the whole world. Description or his system of writing, related to "neo-classicism" but with a personal touch

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El, Abida Boutaïna. "Catabolisme du peptide ß-amyloïde : étude de sa "clearance" par des cellules neuronales et non neuronales en culture." Paris 12, 2005. https://athena.u-pec.fr/primo-explore/search?query=any,exact,990002316270204611&vid=upec.

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Les plaques séniles sont des dépôts fibrillaires extracellulaires associées à la maladie d'Alzheimer, dont le constituant principal est le peptide ß-amyloïde (Aß). Le taux circulant de l'Aß est fonction de l'équilibre entre les voies de sa biosynthèse à partir de son précurseur APP et celles de son catabolisme. Un défaut dans la dégradation de ce peptide, pourrait alors contribuer à son dépôt. Dans ce travail, nous démontrons que le peptide Aß est dégradé en présence de plusieurs lignées cellulaires selon un mécanisme identique qui implique deux activités enzymatiques : une activité thiol-metalloprotéase et une activité de type sérine protéase. Ces enzymes seraient impliquées dans le processus normal de dégradation du Aß. Lors du vieillissement cellulaire, les cellules subissent diverses modifications, leurs enzymes pourraient alors perdre, ou voir s'amoindrir, leur capacité à éliminer le peptide Aß, celui-ci pouvant alors s'accumuler et former des dépôts
Amyloid plaques are extracellular fibrillar lesions associated with Alzheimer's disease that are mainly composed of the amyloid peptide. The steady-state level of Aß depends on the balance between its biosynthesis from its APP precursor and its catabolism. The accumulation of the Aß peptide might be explained by the dysfunction of one process (or both). We demonstrate in this work that the Aß is degraded in contact with with neural or non-neural cells. We have identified the enzymatic activity responsible for the cleavage of the Aß peptide : it is a cell-surface thiol-metalloprotease activity followed by a secreted serine protease activity. These enzymes could be implicated in the normal process of Aß degradation. In the process of cellular aging, Cells undergo various modifications in which their enzymes might lose or diminish their capacity to eliminate the Aß peptide thus allowing it to accumulate and form deposits

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Honda, Kristl J. "Using color management to automate the color reproduction of 3-D images procured via a digital camera/3-D scanner /." Online version of thesis, 1995. http://hdl.handle.net/1850/12249.

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Rodríguez, Cadalso Mario Rolando [UNESP]. "Projeto via LMI de controladores gain scheduling com restrição de D-estabilidade." Universidade Estadual Paulista (UNESP), 2016. http://hdl.handle.net/11449/151098.

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Neste trabalho são propostas metodologias com base na teoria de estabilidade segundo Lyapunov para projetar controladores gain scheduling usando realimentação de estado ou derivativa e o conceito de D-estabilidade. As condições de projeto são dadas por desigualdades matriciais lineares (do inglês, Linear Matrix Inequalities - LMIs). A metodologia é aplicada em sistemas lineares sujeitos a parâmetros variantes no tempo (do inglês, Linear Parameter Varying - LPV). A utilização do Lema de Finsler eliminou a necessidade de inverter uma matriz literal para projetar o ganho de realimentação. Com o objetivo de satisfazer requisitos práticos, foi feito uso da restrição de D-estabilidade no projeto de um controlador para um sistema de suspensão ativa. A implementação prática mostra a eficiência da metodologia proposta.
In this work are proposed methologies based on Lyapunov stability theory for designing gain scheduling controller using state-derivative feedback or state feedback and considering D-stability constraint. The design conditions are given by Linear Matrix Inequalities. The methodology is applied on system with time-variant parameter. The use of Finsler’s Lemma eliminated the problem of inverting a symbolic matrix to calculate the feedback gain. The theory of D-stability allowed to get implementable controllers for an active suspension system. The practical implementation showed the efficiency of the proposed methodology.

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Rodríguez, Cadalso Mario Rolando. "Projeto via LMI de controladores gain scheduling com restrição de D-estabilidade /." Ilha Solteira, 2016. http://hdl.handle.net/11449/151098.

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Orientador: Edvaldo Assunção
Resumo: Neste trabalho são propostas metodologias com base na teoria de estabilidade segundo Lyapunov para projetar controladores gain scheduling usando realimentação de estado ou derivativa e o conceito de D-estabilidade. As condições de projeto são dadas por desigualdades matriciais lineares (do inglês, Linear Matrix Inequalities - LMIs). A metodologia é aplicada em sistemas lineares sujeitos a parâmetros variantes no tempo (do inglês, Linear Parameter Varying - LPV). A utilização do Lema de Finsler eliminou a necessidade de inverter uma matriz literal para projetar o ganho de realimentação. Com o objetivo de satisfazer requisitos práticos, foi feito uso da restrição de D-estabilidade no projeto de um controlador para um sistema de suspensão ativa. A implementação prática mostra a eficiência da metodologia proposta.
Abstract: In this work are proposed methologies based on Lyapunov stability theory for designing gain scheduling controller using state-derivative feedback or state feedback and considering D-stability constraint. The design conditions are given by Linear Matrix Inequalities. The methodology is applied on system with time-variant parameter. The use of Finsler’s Lemma eliminated the problem of inverting a symbolic matrix to calculate the feedback gain. The theory of D-stability allowed to get implementable controllers for an active suspension system. The practical implementation showed the efficiency of the proposed methodology.
Mestre

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38

Fuchs, Sébastien. "Synthèse stéréosélective de modèles d' α-méthylène-γ-butyrolactones : Etude de leur photoréactivité vis-à-vis de l'ADN". Université Louis Pasteur (Strasbourg) (1971-2008), 2004. http://www.theses.fr/2004STR13115.

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Анотація:

La dermatite actinique chronique, ou photosensibilité chronique, est une photodermatose observée chez des patients présentant souvent un long passé d'allergie aux lactones sesquiterpéniques. Ces substances naturelles chirales peuvent avoir des structures très différentes. Elles ont en commun la présence d'une lactone à cinq chaînons, majoritairement un motif a-méthylène-?-butyrolactone. Reconnues depuis longtemps pour leur allergénicité, leur aptitude à photoréagir avec les biomolécules a été peu étudiée. Notre objectif était donc de déterminer une éventuelle photoréactivité des lactones sesquiterpéniques. L'ADN semblant être atteint dans la photosensibilité chronique, nous avons utilisé des modèles capables de représenter l'ensemble des lactones sesquiterpéniques, d'une part, et un modèle représentant l'ADN, d'autre part. Ainsi, nous avons synthétisé les 4 stéréomères d'une méthylène hexahydrobenzufuranone. Deux des modèles énantiomères ont une jonction de cycle cis. Les deux autres modèles ont une jonction de cycle trans, et ont été préparés à partir d'un intermédiaire optiquement pur obtenu lors de la synthèse des modèles à jonction de cycle cis. Notre approche divergente permet d'obtenir les quatre modèles avec la même pureté optique élevée. Nous avons ensuite étudié la photoréactivité des quatre modèles avec la thymidine, servant de modèle de l'ADN. Chacun des modèles présente une photoréactivité importante dans les conditions utilisées, formant entre 5 et 6 photoadduits pour chaque modèle, sur 8 théoriquement possibles. Globalement, 21 photoadduits ont été isolés par HPLC et entièrement caractérisés par RMN bidimensionnelle
Chronic actinic dermatitis is a chronic photosensitivity often affecting patients suffering from allergic contact dermatitis to sesquiterpene lactones. The a-methylene-?-butyrolactone ring is the common moiety of these chiral natural products, which can have a wide structural diversity. Although it has been identified as the main function responsible for allergic dermatitis, its photoreactivity towards biomolecules has been poorly studied. Our goal was therefore to determine a potential photoreactivity of the sesquiterpene lactones. Because DNA seems to be involved in the chronic photosensitivity, we studied the photoreactivity of lactone models towards thymidine, which was used as a DNA model. Thus, four stereomers of a methylene hexahydrobenzofuranone were synthesized, two cis-enantiomers and two trans-enantiomers. The trans targets were obtained from enantiomeric intermediates of the cis targets. This divergent approach allowed the preparation of the four stereomers with an equally high optical purity. The photoreactivity of each model towards thymidine gives several photoadducts, attesting for the high photoreactivity of the a-methylene-?-butyrolactone ring. Between 5 to 6 photoadducts were formed for each model among the 8 theoretically possible. Overall, twenty-one photoproducts were isolated with preparative reversed-phase HPLC and identified by NMR bidimensional techniques

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39

Abadie, Nicole. "Le contenu du concept d"amenity" dans l'urbanisme anglais contemporain." Bordeaux 3, 1986. http://www.theses.fr/1986BOR30028.

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40

Paneru, Govind. "Nano-fabrication of cellular force sensors and surface coatings via dendritic solidification." Diss., Kansas State University, 2014. http://hdl.handle.net/2097/17195.

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Doctor of Philosophy
Department of Physics
Bret N. Flanders
Directed electrochemical nanowire assembly (DENA) is a method for fabricating nano-structured materials via electrochemical dendritic solidification. This thesis presents two new applications of nano-structured materials that are fabricated via the DENA methodology: cellular force sensors to probe adhesive sites on living cells and single-crystalline metallic dendrites as surface coating materials. Fast migrating cells like D. discoideum, leukocytes, and breast cancer cells migrate by attachment and detachment of discrete adhesive contacts, known as actin foci, to the substrate where the cell transmits traction forces. Despite their importance in migration, the physics by which actin foci bind and release substrates is poorly understood. This gap is largely due to the compositional complexity of actin foci in living cells and to a lack of technique for directly probing these sub-cellular structures. Recent theoretical work predicts these adhesive structures to depend on the density of adhesion receptors in the contact sites, the receptor-substrate potential, and cell-medium surface tension. This thesis describes the fabrication of sub-microscopic force sensors composed of poly(3,4-ethylene dioxythiophene) fibers that can interface directly with sub-cellular targets such as actin foci. The spring constants of these fibers are in the range of 0.07-430 nN m-1. These fibers were used to characterize the strength and lifetime of adhesion between the single adhesive contacts of D. discoideum cells and the fibers, finding an average force of 3.1 ± 2.7 nN and lifetime of 23.4 ± 18.5 s. This capability is significant because direct measurement of these properties will be necessary to measure the cell-medium surface tension and to characterize the receptor-substrate potential in the next (future) stage of this project. The fabrication of smart materials that are capable of the high dynamic range structural reconfiguration would lead to their use to confer hydrophobic, lipophobic, and anti-corrosive character to substrates in a regenerative manner. As a step towards this goal, we have extended the DENA method to enable repetitive growth and dissolution of metallic dendrites to substrates. The experimental parameters that control this process are the frequency and duty cycle of the alternating voltage signal that initiates the dendritic growth.

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41

Laplana, Lafaja Marina. "Variabilidad en genes de respuesta inmune : papel en la infección por VIH-1 y envejecimiento natural." Doctoral thesis, Universitat de Lleida, 2012. http://hdl.handle.net/10803/101203.

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La modulació inadequada o el manteniment de forma crònica de la resposta immune poden provocar efectes adversos a sistemes i òrgans i donar lloc a la manifestació de patologies. En aquest context, els mecanismes de regulació de la resposta immune són un element clau per mantenir un estat òptim de salut i un envelliment saludable. La capacitat d'organitzar una resposta immune contra agents patògens o cèl·lules tumorals està en part determinada pel fons genètic de cada individu. Els estudis d'associació genètica han resultat d'utilitat per identificar variants de gens de resposta immune implicades en patologies que van des del càncer o les malalties cardiovasculars a infeccions com la tuberculosi o el VIH-‐1. En la present tesi s'ha estudiat la variabilitat de gens de resposta immune i el seu paper en dos models diferents: la infecció per VIH-‐1 i el procés d'envelliment natural. En el primer model s'ha estudiat la variabilitat del gen BST-‐2, factor de restricció en la infecció per VIH-‐1, i dels gens CYP27B1, GC i VDR, implicats en la síntesi, transport i acció genòmica de la vitamina D, hormona implicada en la modulació de la resposta immune. Així mateix, al segon model s'ha avaluat l'efecte de la variabilitat del gen VDR i dels gens RANTES i CCR5, implicats en la mediació de la resposta inflamatòria. En el model d'infecció per VIH-‐1 s'han identificat 2 variants del gen BST-‐2 associades amb progressió, una captura la variabilitat de la regió genòmica i l’altra amb potencial efecte funcional. En l'estudi de la relació de variants dels gens VDR, CYP27B1 i GC amb el ritme de progressió de la infecció s'han confirmat i ampliat el nombre de marcadors del gen VDR que mostren associació amb progressió. Les combinacions haplotípiques del gen VDR que s'associen amb progressió són aquelles que optimitzen la resposta a la vitamina D. Aquests resultats poden interpretar-‐se en funció del paper dual de la vitamina D en la modulació de la resposta immune. L'associació amb progressió de les variants identificades és més significativa en els pacients reclutats en el període pre-‐ TARGA (anterior a 1997). En el model d'envelliment natural, variants del gen VDR mostren associació amb envelliment saludable en homes. Les variants associades són aquelles que confereixen una capacitat de resposta intermèdia a la vitamina D. Això emfatitza el paper de la vitamina D en envelliment i posa de manifest la importància del fons genètic a l’hora d’establir els nivells òptims de vitamina D per a un envelliment saludable. En relació als polimorfismes dels gens CCR5 i RANTES no s'ha trobat associació significativa pel locus CCR5, encara que els resultats mostren una major prevalença de la variant no funcional, i per tant pitjor mediadora de la resposta inflamatòria, en individus longeus. Quant a les variants del gen RANTES, els resultats indiquen una associació específica de sexe que suggereix l'existència d'un determinant genètic de RANTES que predisposa a un fenotip proinflamatori en homes i a un fenotip antiinflamatori en dones
La modulación inadecuada o el mantenimiento de forma crónica de la respuesta inmune puede provocar efectos adversos en sistemas y órganos y dar lugar a la manifestación de patologías. Por ello, los mecanismos de regulación de la respuesta inmune son un elemento clave para el mantenimiento de un estado de salud óptimo y un envejecimiento saludable. La capacidad de organizar una respuesta inmune contra agentes patógenos o células tumorales está en parte determinada por la fondo genético de cada individuo. Los estudios de asociación genética han resultado de utilidad para identificar variantes de genes de respuesta inmune implicadas en patologías que van desde el cáncer o las enfermedades cardiovasculares a infecciones como la tuberculosis o el VIH-‐1. En la presente tesis se ha estudiado la variabilidad de genes de respuesta inmune y su papel en dos modelos distintos: la infección por VIH-‐1 y el proceso de envejecimiento natural. En el primer modelo se ha estudiado la variabilidad del gen BST-‐2, factor de restricción en la infección por VIH-‐1, y de los genes CYP27B1, GC y VDR, implicados en la síntesis, transporte y acción genómica de la vitamina D, hormona implicada en la modulación de la respuesta inmune. Asimismo, en el segundo modelo, se ha evaluado el efecto de la variabilidad del gen VDR y de los genes RANTES y CCR5, implicados en la mediación de la respuesta inflamatoria. En el modelo de infección por VIH-‐1, se han identificado 2 variantes del gen BST-‐ 2 asociadas con progresión, una que captura la variabilidad de la región genómica y otra con potencial efecto funcional. En el estudio de variantes de los genes VDR, CYP27B1 y GC con el ritmo de progresión de la infección se ha confirmado y ampliado el número de marcadores del gen VDR que muestran asociación con progresión. Las combinaciones haplotípicas del gen VDR que se asocian con progresión son aquellas que optimizan la respuesta a la vitamina D. Estos resultados pueden interpretarse en función del papel dual de la vitamina D en la modulación de la respuesta inmune. La asociación con progresión de las variantes identificadas incrementa su significación en los pacientes reclutados en el periodo pre-‐TARGA (anterior a 1997). En el modelo de envejecimiento natural, variantes del gen VDR muestran asociación con envejecimiento saludable en hombres. Las variantes asociadas son aquellas que confieren una capacidad de respuesta intermedia a la vitamina D. Ello revela el papel de la vitamina D en envejecimiento y enfatiza la importancia del fondo genético al establecer los niveles óptimos de vitamina D para un envejecimiento saludable. En relación a los polimorfismos de los genes CCR5 y RANTES no se ha encontrado asociación significativa para el locus CCR5, aunque los resultados muestran una mayor prevalencia de la variante no funcional, y por lo tanto peor mediadora de la respuesta inflamatoria, en individuos longevos. En cuanto a las variantes del gen RANTES, los resultados indican una asociación específica de sexo que sugiere la existencia de un determinante genético de RANTES que predispone a un fenotipo proinflamatorio en los varones y a un fenotipo anti-‐inflamatorio en las mujeres.
The improper balance or the maintenance of a chronic immune response can produce adverse effects on organs and systems and prone to diseases. Therefore, the regulatory mechanisms of the immune response are key factors to maintain an optimal health status and to follow a healthy aging. The capacity to produce an immune response against pathogens or tumour cells is partially determined by the genetic background of the individual. Genetic association studies have been useful to identify variants of immune response genes involved in diseases ranging from cancer or cardiovascular disease to infections such as tuberculosis or HIV-‐1. In this thesis we have studied the variability of immune response genes and their role in two models: the HIV-‐1 infection and the natural aging process. In the first model it has been studied the variability of BST-‐2 gene, which is an HIV restriction factor, and CYP27B1, GC and VDR genes, that are involved in the synthesis, transport and genomic action of vitamin D, hormone that modulates the immune response. In the second model, we have also evaluated the effect of VDR gene variability as well as RANTES and CCR5 gene variants, both involved in mediating the inflammatory response. In the model of the HIV-‐1 infection we have identified two variants of BST-‐2 gene associated with progression, one that captures the variability of the genomic region and the other with potential functional effect. In the study of VDR, CYP27B1 and GC gene variants related to progression rates we have confirmed and extended the number of VDR gene markers showing association with progression. The VDR gene haplotype combinations that are associated with progression are those that optimize the response to vitamin D. These results should be interpreted as a con to the dual role of vitamin D in the modulation of the immune response. The association with progression of the identified variants is significantly increased in patients enrolled in the pre-‐HAART (before 1997). In the model of aging, VDR gene variants were most associated with healthy aging in men. The associated variants are those that confer an intermediate responsiveness to vitamin D. This reveals the role of vitamin D in aging and emphasizes the role of genetic background in determining optimal levels of vitamin D for healthy aging. In relation to polymorphisms of CCR5 and RANTES genes we do not found significant association for the CCR5 locus, although the results show a higher prevalence of non-‐functional variant, and thus a poorer mediator of the inflammatory response, in long-‐lived individuals. In relation to RANTES gene variants, the results indicate a sex-‐specific association suggesting the existence of a genetic determinant of RANTES that predisposes to a proinflammatory phenotype in males and an anti-‐inflammatory phenotype in females.

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42

Enström, Sara, and Therese Lundell. "Energi och näringsintag hos studenter på handelshögskolan vid Umeå universitet : En tredagars kostregistrering." Thesis, Umeå universitet, Institutionen för kostvetenskap, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-102656.

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Bakgrund Intaget av mättat fett är högt hos Sveriges befolkning och intaget av fibrer, järn och D-vitamin har minskat på senare tid. Kostvanor och livsstil påverkar hälsan och risken att drabbas av folkhälsosjukdomarna; hjärtkärlsjukdom, diabetes, benskörhet, metabola syndromet och cancer. För att minska risken att drabbas av folkhälsosjukdomar är det även viktigt att minska stillasittande. Civilekonomstudenter är en grupp som traditionellt sett har ett stillasittande arbete. Det är därför viktigt att belysa hur närings- och energiintaget ser ut för denna grupp för att kunna motverka ohälsa i ett tidigt stadie. Syfte Syftet med studien var att undersöka om civilekonomstudenter vid Umeå universitet uppnår det genomsnittliga behovet (AR) och Nordiska näringsrekommendationer (NNR) gällande närings- och energiintag. Metod Metoden som användes var en tredagars kostregistrering. I studien deltog tio civilekonomstudenter. För att analysera rapporterat energi- och näringsintag användes Dietist XP och vid analys jämfördes de framtagna värdena mot NNR och för skillnader mellan kvinnor och män användes Mann- Whitney U test i SPSS med p≤0,05. Resultat Männen och kvinnorna hade ett lägre rapporterat energiintag i jämförelse med det beräknade energibehovet. Det totala fettintaget var inom NNR medan intaget av protein översteg NNR. Det rapporterade intaget av fibrer, frukt och grönsaker, enkel- och fleromättade fettsyror understeg NNR medan intaget av mättat fett var högre än NNR. AR för D-vitamin uppnåddes varken av männen eller kvinnorna, medan AR för folat uppnåddes av båda grupper. Järnbehovet uppnåddes av männen men inte av kvinnorna. Slutsats: Intaget av mikronäringsämnen var lågt i förhållande till NNR. D- vitaminintaget för samtliga deltagare var under AR. Kvinnorna i studien kan behöva öka intaget av järn då det finns ett ökat behov inom denna åldersgrupp.

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43

Magnifico, Giuseppe. "Quantum simulation of (1+1)D QED via a Zn lattice Gauge theory." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amslaurea.unibo.it/9532/.

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La simulazione di un sistema quantistico complesso rappresenta ancora oggi una sfida estremamente impegnativa a causa degli elevati costi computazionali. La dimensione dello spazio di Hilbert cresce solitamente in modo esponenziale all'aumentare della taglia, rendendo di fatto impossibile una implementazione esatta anche sui più potenti calcolatori. Nel tentativo di superare queste difficoltà, sono stati sviluppati metodi stocastici classici, i quali tuttavia non garantiscono precisione per sistemi fermionici fortemente interagenti o teorie di campo in regimi di densità finita. Di qui, la necessità di un nuovo metodo di simulazione, ovvero la simulazione quantistica. L'idea di base è molto semplice: utilizzare un sistema completamente controllabile, chiamato simulatore quantistico, per analizzarne un altro meno accessibile. Seguendo tale idea, in questo lavoro di tesi si è utilizzata una teoria di gauge discreta con simmetria Zn per una simulazione dell'elettrodinamica quantistica in (1+1)D, studiando alcuni fenomeni di attivo interesse di ricerca, come il diagramma di fase o la dinamica di string-breaking, che generalmente non sono accessibili mediante simulazioni classiche. Si propone un diagramma di fase del modello caratterizzato dalla presenza di una fase confinata, in cui emergono eccitazioni mesoniche ed antimesoniche, cioè stati legati particella-antiparticella, ed una fase deconfinata.

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Camara, Carlos Eduardo. "Construção de codigos esfericos via a D-cadeia e a geometria de grupos." [s.n.], 1995. http://repositorio.unicamp.br/jspui/handle/REPOSIP/260469.

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Анотація:

Orientador: Reginaldo Palazzo Junior
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Eletrica
Made available in DSpace on 2018-07-20T14:45:52Z (GMT). No. of bitstreams: 1 Camara_CarlosEduardo_D.pdf: 7740040 bytes, checksum: b23f5a4a4eed9ff86a44c68076381518 (MD5) Previous issue date: 1995
Resumo: Os códigos esféricos ou códigos de Slepian são conjuntos de pontos de sinais dispostos sobre a superfícies de uma hiperesfera no espaço Euclidiano M-dimensional. A grande dificuldade para a sua construção está na busca por um valor (vetor) inicial ótmio cuja solução vem através de um problema de otimização. Neste trabalho apresentamos a proposta de um algoritmo de construção de conjuntos de sinais esféricos no espaço Euclidiano N-dimensional baseada na soma direta de grupos finitamente gerados e principalmente na geometria associada a cada um destes grupos. Uma vez que a geometria associada ao grupo fornece o elemento necessário para a determinação do valor (vetor) inicial, a solução do valor inicial vai métodos de pesquisa operacional, neste caso a programação linear é desnecessária. A justificativa para esta afirmação é que a distância Euclidiana mínima entre estes sinais estão definida pelos vértices do politopo formado pelo conjunto de sinais fornecido pela geometria. Esta características mostram a simplicidade do algoritmo proposto para a construção de códigos (constelações) esféricos. A construção sendo apresentada, é definida pelo casamento entre grupo abeliano ou não abeliano, e o conjunto de sinais determinado de foram natural o rotulamento para este conjunto de sinais ...Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da tese digital
Abstract: : Spherical (Slepian) Codes consist of sets of signal points on the surface of a sphere in Euclidean N-dimensional space. One difficulty in the construction of such codes is related to finding the optimal initial vector value through an optimization problem. We propose a construction method of spherical signal sets in Euclidean N-dimensional space based on the concept of finitely generated Abelian groups. As a consequence it is shown that there is no need to solve for the initial vector value since the minimum Euclidean distance among these signal the construction method can be. Furthermore the matching between groups and spherical signal sets comes naturally from the concept of group representation. Labeling and portioning of those spherical signal sets are a consequence of the group chain partition. Finally, we show how to extend the construction method by including the closed d-chain algorithm in it
Doutorado
Doutor em Engenharia Elétrica

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45

Sconza, Sarah <1976&gt. "Quadri clinici in situazioni di: acidosi metabolica, iper L-lattacidemia e iper D-lattacidemia sperimentalmente indotte nel vitello lattante." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2007. http://amsdottorato.unibo.it/546/1/sconza_sarah_tesi.pdf.

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46

Sconza, Sarah <1976&gt. "Quadri clinici in situazioni di: acidosi metabolica, iper L-lattacidemia e iper D-lattacidemia sperimentalmente indotte nel vitello lattante." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2007. http://amsdottorato.unibo.it/546/.

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47

Granados, Ramírez Carmen Giovana. "Diseño, síntesis y estructura de dominios helicoidales. Influencia de la introducción de aminoácidos D." Doctoral thesis, Universitat de Barcelona, 2008. http://hdl.handle.net/10803/2813.

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1) "Diseño, síntesis y caracterización de inhibidores de la fusión de VIH-1 análogos del péptido C34 de gp41 con D aminoácido"

En el proceso de fusión del virus del VIH-1 a la célula diana intervienen las proteínas de la cubierta viral gp120 y gp41. La gp120 al interaccionar con el receptor CD4 y co-receptores sufre un cambio conformacional que enseguida causa cambios en la estructura de gp41. Esta proteína sufre una reorganización que conduce al acercamiento entre la región N-terminal y la región C-terminal de gp41 aproximando las membranas celular y viral entre si. El péptido C34 tiene buenas propiedades como inhibidor de la fusión viral y forma complejos estables con el péptido N36 derivado de la región N-terminal de gp41. En este capítulo se discute el efecto de cambiar la quiralidad del péptido C34 total o parcialmente, para aumentar la estabilidad de este péptido frente a proteasas. Mientras los péptidos derivados de C34 con todo-D aminoácidos fueron incapaces de inhibir la fusión del VIH-1. Los péptidos heteroquirales, especialmente el péptido M3C34, son capaces de formar complejos estables con N36 e inhibir la fusión.

2) "Identificación de complejos heteroquirales entre péptidos todo-D y el fragmento N-terminal del dominio de B de la proteína A de Staphyloccus aureus"

La proteína A es un factor patogénico encontrado en la superficie del Staphylococcus aureus. Esta proteína es capaz de unirse al fragmento cristalizable de las inmunoglobulinas G. El dominio B, un trímero de hélices antiparalelas, es uno de los cinco dominios responsables de este reconocimiento. Péptidos derivados de la región N-terminal de este dominio no tienen una estructura estable en disolución. Sin embargo, la presencia de la de péptidos correspondientes a la región C-terminal del dominio forman complejos que aumentan el contenido helicoidal del sistema. En este capitulo se diseñó una quimioteca OBOC (del ingles "one bead one compound") de 4096 péptidos con aminoácidos D derivados de la secuencia de la hélice C-terminal el domino B, con el objetivo de identificar péptidos todo-D capaces de interactuar con el fragmento N-terminal del domino B y de formar complejos no covalentes heteroquirales.

3) "Síntesis, caracterización estructural y evaluación de la interacción con inmunoglobulina G de nuevos análogos del dominio B de la proteína A de Staphylococcus aureus"

Los fragmentos correspondientes a la hélice C-terminal y región N-terminal del domino B de la proteína A de Staphylococcus. aureus forman complejos que aumentan la helicidad del sistema. En nuestro grupo se identificaron dos péptidos derivados de la hélice C-terminal del dominio B que forman complejos con el fragmento N-terminal con mutaciones en los residuos Ser 44 y Leu 47. En esta parte se describe la caracterización estructural y evaluación de la actividad de los complejos no covalentes formados entre estos péptidos y el fragmento N-terminal del dominio B y los dominios enteros. Después de comprobar que el fragmento N-terminal interaccionaba con los análogos no naturales de la hélice C-terminal se sintetizaron los dos dominios análogos con las modificaciones encontradas en la región C-terminal (Ser44Phe Leu47Lys y Ser44Phe Leu47Val). El análisis de estructura por dicroísmo circular reveló que los análogos mostraban estructura helicoidal y eran térmicamente estables. Por resonancia de plasmon superficial se encontró que los análogos se unían a inmunoglobulina de conejo y al fragmento cristalizable de las inmunoglobulinas humano con una afinidad similar, aunque con cambios en las cinéticas de asociación y disociación. La información estructural de cada residuo se analizó por medio de resonancia magnética nuclear. Este estudio mostró que los dominios análogos conservan tres regiones helicoidales y de acuerdo a los experimentos de intercambio H/D se pliegan de forma similar al dominio natural.
This thesis is divided in three parts. The first part is about the design, synthesis and characterization of new peptide inhibitors of the HIV-1 fusion derived of the C-terminal region of gp41. In the second part was described the design and synthesis of a library of all-D peptide derived of the C-terminal region of B domain of protein A of Staphylococcus aureus to identify all-D peptides which could interact with the N-terminal fragment of B domain to get heteroquiral non covalent complexes. The third part is about the synthesis, structural characterization and activity evaluation of two new analogues en B domain of protein A of Staphylococcus aureus with mutations in Ser44 and Leu47.

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48

Musa, Matilda. "Lactobacillus plantarum i kombination med andra bakteriestammar vid diarré predominant IBS : Effekt att lindra symtomen buksmärta vid IBS-D?" Thesis, Linnéuniversitetet, Institutionen för kemi och biomedicin (KOB), 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-99215.

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Bakgrund: IBS (Irritable bowel syndrome) är en funktionell mag-tarmsjukdom med en oklar orsak och patofysiologi. IBS förekommer mest hos kvinnor och karakteriseras av buksmärta, uppblåsthet, diarré och/eller förstoppning samt ökad gasbildning. I nuläget finns inga läkemedel som botar sjukdomstillståndet, och den senaste tiden har intresset för probiotika som behandling av IBS ökat. Probiotika innehåller levande mikroorganismer som anses ha en gynnsam effekt på tarmflorans sammansättning, samt kan tros ha en symtomatisk effekt vid IBS. Syfte: Syftet med detta litteraturarbete är att ta reda på om kosttillskott som innehåller bakteriearten Lactobacillus plantarum har en positiv effekt för att lindra symtomen hos patienter som lider av en diarrépredominant IBS. Metod: Sex randomiserade, dubbelblinda och placebo-kontrollerade studier granskades. Studierna utvärderade effekten av den enskilda bakteriearten L. plantarum eller en kombination av probiotika som innehöll L. plantarum för symtomlindring hos IBS-patienter. Artikelsökning utfördes i databasen PubMed via Linnéuniversitetets bibliotek. Resultat: Tre av de fyra studierna som undersökte L. plantarum i kombination med andra bakteriestammar påvisade en statistiskt signifikant förbättring av symtomen buksmärta hos IBSpatienter. En av de två studierna som undersökte enbart L. plantarum visade en signifikant förbättring av symtomen buksmärta. Två av sex studier visade ingen signifikant förbättring av symtomlindring mellan probiotika- och placebo gruppen. Slutsats: Utifrån sammanställningen påvisades att effekten uppnåddes framförallt i gruppen med måttliga IBS besvär. Dock gav inte behandling med L. plantarum alltid en statistisk signifikant förbättring av symtomlindring hos diarré predominanta IBS-patienter. Vidare studier behövs på subtypen diarré predominant IBS för att stärka och fastställa L. plantarums effekt.

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Goncalves, Aurélie. "Optimiser le statut en vitamine D via la nutrition : des interactions alimentaires aux mécanismes d'absorption." Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM5018.

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Durant les dernières décennies, la vitamine D a été décrite comme un micronutriment d'intérêt, bénéfique pour la santé humaine, mais les mécanismes régissant son absorption intestinale ont été peu investigués. Il a longtemps été admis que son absorption était régie par un phénomène de diffusion passive. Nous avons tout d'abord montré qu'elle n'était pas uniquement passive mais impliquait des transporteurs membranaires du cholestérol tels que SR-BI, CD36 et NPC1-L1 et que des molécules pharmaceutiques utilisées pour inhiber l'absorption du cholestérol (Ezétimibe - Ezetrol®) pouvaient également diminuer celle de la vitamine D. Dans un second temps, nous avons montré que des composés présents au sein de notre alimentation comme les phytostérols pouvaient limiter l'absorption de la vitamine D. Au contraire, certains acides gras libres comme l'acide oléique pouvaient augmenter sa biodisponibilité. Ces données suggèrent que les autres composés lipidiques que nous consommons quotidiennement peuvent améliorer ou a contrario limiter l'absorption de la vitamine D. Pour finir, nous nous sommes intéressés aux mécanismes moléculaires en temps réel entre divers vecteurs lipidiques et les boucles extracellulaires de SR-BI et CD36 grâce à la technique de la résonnance plasmonique de surface. Nous avons montré que la nature et la composition des vecteurs lipidiques modulaient les interactions micelles-protéines. Ces travaux de thèse dégagent des perspectives prometteuses quant à l'avancement des connaissances et des mécanismes moléculaires régissant l'absorption intestinale de la vitamine D, et souligne le fait que nos choix alimentaires pourraient optimiser notre statut en vitamine D
Overs the last past decades, vitamin D has been described as a micronutrient of interest, beneficial to human health, but the mechanisms governing its intestinal absorption have been poorly investigated. Indeed, it has long been assumed that vitamin D was absorbed by a passive process. We first showed that vitamin D absorption was not only passive but involved membrane transporters including such as SR-BI, CD36 and NPC1-L1 and that pharmaceutical compounds used to inhibit cholesterol absorption (ei: Ezetimibe - Ezetrol ®) could also reduce vitamin D absorption. Then, we have shown that dietary molecules such as phytosterols could limit its absorption, while some free fatty acids such as oleic acid could increase its bioavailability. These data suggest that other dietary lipids daily consumed with vitamin D could improve or conversely limit its absorption. Finally, we investigated real-time interactions between various lipid ligands and scavenger receptors such as SR-BI and CD36 using the technique of surface plasmon resonance. This highlighted the fact that mixed-micelle lipid composition could modulate their interactions with these proteins.This thesis bring promising prospects in the advancement of knowledge and molecular mechanisms regulating vitamin D intestinal absorption, and enlightens the fact that our food choices could lead to an optimization of our vitamin D status

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ACI, Samia. "ETUDE PAR SIMULATION DE DYNAMIQUE MOLECULAIRE DE LA VARIABILITE CONFORMATIONNELLE DU DIMERE DE LA SEQUENCE SL1 DU GENOME DE VIH-1." Phd thesis, Université d'Orléans, 2004. http://tel.archives-ouvertes.fr/tel-00008151.

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Le génome du VIH-1, l'agent responsable du SIDA, est composé de deux molécules identiques d'ARN liées de façon non-covalente par une région de leur extrémité 5'. Il a été montré que la tige-boucle SL1, localisée dans cette région, était capable d'initier cette dimérisation. La dimérisation constitue une étape clé du cycle de réplication du virus et fait intervenir deux types de complexe de SL1 : un « kissing-complex » et un complexe en forme de double hélice contenant deux boucles internes. Plusieurs structures contradictoires ont été publiées pour ces deux complexes, et différents mécanismes de transition entre ces complexes ont été envisagés jusque là. Ce travail a permis d'étudier la stabilité des différentes structures publiées, et en particulier de faire ressortir de l'ensemble des structures de « kissing-complex » publiées une conformation plus probable. Parallèlement, l'étude du mécanisme de transition a mis en évidence une structure intermédiaire dans ce processus. Ce travail constitue un ensemble d'informations qui pourra par la suite être utilisé pour la conceptions d'inhibiteurs de la dimérisation.

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