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Les transporteurs d’ammonium Mep/Amt/Rh de la levure Saccharomyces cerevisiae : fonctions et régulationsBoeckstaens, Mélanie 04 October 2007 (has links)
Les protéines de la famille Mep/Amt/Rh sont largement conservées dans l’évolution. Cette famille comprend les facteurs Rhésus dont les antigènes Rh humains sont les membres les plus notoires. Le rôle des protéines de type Mep/Amt/Rh en tant que transporteurs d’ammonium a largement été décrit chez les bactéries, les champignons et les plantes. Néanmoins, leur mécanisme de fonctionnement demeure élusif et la régulation de leur activité a été peu abordée chez les organismes eucaryotes. En utilisant comme modèles de la famille Mep/Amt/Rh les trois transporteurs d’ammonium de la levure Saccharomyces cerevisiae, nous avons tenté de comprendre les mécanismes de fonctionnement et de régulation de cette famille de protéines membranaires.
Nous montrons qu’un résidu aspartate, conservé dans la famille Mep/Amt/Rh et situé à proximité d’un vestibule cation-attractif, joue un rôle structural dans la reconnaissance de l’ammonium chez le transporteur Mep2. De plus, un résidu histidine très conservé dans le pore hydrophobe des protéines Mep/Amt/Rh est substitué par un aspartate chez un sous-groupe de transporteurs d’ammonium fongiques. Cette substitution permet de définir deux sous-familles fonctionnelles possédant des propriétés bien distinctes.
Nous montrons également que la kinase Npr1 intervient dans la modulation de l’activité intrinsèque des trois protéines Mep qui demeurent inactives mais stables à la membrane plasmique en absence de la kinase.
Hormis leur rôle dans le transport d’ammonium en tant que source d’azote, nous montrons que l’activité des protéines Mep est requise pour différentes réponses physiologiques. Une diminution d’entrée d’ammonium en absence des protéines Mep ou de leur régulateur positif Npr1 entraîne une dérépression des gènes soumis à la répression catabolique azotée ainsi qu’un défaut dans le repompage de l’ammonium catabolique excrété durant la croissance en présence d’autres sources azotées. Un rôle supplémentaire de senseur d’ammonium avait été attribué au transporteur Mep2 dans l’induction de la croissance filamenteuse en réponse à une limitation en ammonium. Nous montrons que l’état d’activité de la protéine Mep2 est étroitement lié à sa capacité à induire le développement filamenteux.
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Analys av felkällor vid mängdavtagning av ventilationssystem ur BIM-modeller / Analysis of error sources in quantity take off in ventilation systems from BIM modelsKakar, Adib, Turan, Ensari January 2014 (has links)
De senaste åren har det skett stora framsteg i byggbranschen från sedvanlig byggprojektering till avancerad BIM-projektering. Resultatet av denna studie visar att trots den hastiga utvecklingen så utförs det fortfarande mängdavtagningar ur 2D-ritningar. Detta på grund av problem som uppstår vid mängdavtagningar ur objektbaserade 3D-modeller. Mängdlistorna ur objektbaserade 3D-modeller stämmer inte alltid överens med mängdlistorna ur 2D-ritningar. Detta leder i sin tur till nödvändiga och tidskrävande manuella mängdavtagningskontroller ur pappersritningar. Detta för att säkerhetsställa den riktiga mängden. Ju större projekten blir, desto mer tid tar det att utföra de manuella mängdavtagningskontrollerna. Syftet har varit att lokalisera och analysera de olika felkällorna som uppkommer vid mängdavtagningar. Mängdavtagningsfunktionen i programmet RevitMEP (2014) och MagiCAD (2013.11) undersöktes. Resultatet jämfördes med manuella mängdavtagningar ur 2D-ritningar. Examensarbetet resulterade i en arbetsmodell som visar hur man på ett korrekt sätt utför mängdavtagningar ur 3D-modeller. Vinsten av detta blir att färre återkommande fel uppstår. Det är viktigt att ha ett välstrukturerat och tydligt arbetssätt vid användning av de olika BIM-verktygen. Vid användning av modellen blir det färre fel och minskad missförstånd uppstår vid projektering. Kontinuerliga mängdavtagningar bör genomföras för att så tidigt som möjligt möjliggöra upptäckten av fel. Att upptäcka felen i ett tidigt skede förhindrar att felet eskalerar. I studien påträffades även ett kritiskt programmeringsfel i programmet MagiCAD för Revit MEP vilket ger användaren felaktiga resultat. Problemet har påpekats till programutvecklaren CADCOM och korrigering av programmet kommer att ske. / The past years there have been vast progresses within the construction industry from traditional construction projection method to a more advanced BIM-projecting method. The results of this dissertation shows that in spite of these vast progresses it is still commonly conducted manual quantity calculations with 2D-drawings. The main reason to this is that when you compare the quantity results from object based 3D models to manual quantity calculation results with 2D-drawing, the results do not add up being equal to each other. Hence time consuming manual quantity calculations with paper drawings has to be conducted to verify the real material quantity. The larger the project, the more time is consumed to conduct manual calculation verification. The aim has been to identify and analyze the different sources of error arising from manual calculation verification. In assistance we used the quantity calculation functions in the software RevitMEP (2014) and MagiCAD (2013.11). To substantiate the results manual calculations were conducted. The results were compared to the manual calculations from 2D drawings, the profit of the method is that we get less reoccurring errors. The gain of this is resulting in fewer recurring of errors. It is important to have a well-structured and clear approach with the use of the various BIM tools. When using the model, there are fewer errors and reduced misunderstandings arise during project planning. Continuous calculation verifications should be implemented as early as possible to allow the discovery of errors. Detecting errors in the early stage will prevent the error from escalating. The study also found a critical programming error in the program MagiCAD for Revit which gives the user false results. The problem has been pointed out to the application developer CADCOM and correction of the program will occur.
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O espessamento primário no sistema caulinar e a continuidade entre esses tecidos nos órgãos vegetativos de Zingiberaceae e Costaceae: enfoque nos tecidos endoderme e periciclo / The primary thickening in stem system and the continuity between tissues in vegetative organs from Zingiberaceae e Costaceae: approach in tissues endodermis and pericycleSilva, Cristiane Gonçalves da 15 June 2009 (has links)
Essa dissertação foi subdivida em cinco capítulos que, apesar de relacionados entre, podem ser lidos e compreendidos de forma independente. O primeiro capítulo trata de um breve histórico sobre o espessamento primário em caules de monocotiledôneas. Seu principal objetivo é deixar evidente para o leitor a problemática referente tanto à nomenclatura dos tecidos relacionados ao espessamento primário em monocotiledôneas, quanto explicar as hipóteses que embasam essas nomenclaturas. O segundo capítulo teve como principal objetivo evidenciar que, apesar da discordância de muitos autores da atualidade, existe continuidade dos tecidos endoderme e periciclo entre os órgãos no corpo vegetativo de monocotiledôneas, apresentando indícios que apóiam esse pensamento. Já o terceiro capítulo, Caule, demonstra dados que corroboram o pensamento defendido nessa dissertação: endoderme e periciclo são os tecidos responsáveis pelo espessamento do corpo primário do caule de monocotiledôneas. O quarto capítulo, Folha, discute e demonstra a presença de endoderme (entorno da unidade vascular desse órgão) e periciclo (como parte dessa unidade vascular) em folhas de Zingiberaceae e Costaceae. O quinto e último capítulo aborda a importância dos já mencionados tecidos, quais sejam endoderme e periciclo, na formação da raiz primária. / Since ends of 19th century, arised a great diversity of terminologys to name meristematic region responsible for primary thickening in monocotyledons. Despite of this great number of denominations, a few hypothesis and ideas are utilized to base this great complex of terminologys. This historical chapter aims explain the origin from this terminologys and understand correlations between hypothesis basis. At the end of this explanation, you can understand why the defense of presence of endodermal and pericycle tissue as the two meristematic tissues responsible for this primary thickening in monocotyledonous rather than the currently most accepted name of \"PTM\", a single meristem advocated by many authors. Despite of many authors consider fact the continuity between the vascular tissues of stem and leaf and stem and root, few authors consider that the endodermis (between stem and leaf and between stem and root) and pericycle (between stem and leaf and stem and between root) of these organs may be continuous. It was shown, with verification of the continuity of the tissues mentioned above, the plant is a unit and can be found in the root and leaves the same tissues found in the stem, in this case, the main tissues examined in this chapter: endodermis and pericycle. This chapter aims to discuss, demonstrate, and finally prove the continuity of the tissues mentioned in Zingiberaceae, and also describe the morphology of these tissues in each of the aforementioned organs. The stems of monocots has been the subject of studies since the nineteenth century. But despite the large amount of work produced since then, there is still controversy regarding the primary tissue responsible for thickening of this organ. The families Zingiberaceae Costaceae and serve as a model for which more data were collected showing not only the presence of endodermis and pericycle in the stem, but also to show that these are the meristematic tissues responsible for primary thickening in this organ. It was observed in the underground stem, the presence of strips of Caspary in the region farthest from the apex. Already in the air stem, the endodermis was seen only parenchymatous, without any morphological alteration in its walls. The meristematic pericycle was found in the underground stem, but in the aerial stems it is pluriseriated and have cell walls thick. Many authors recognize that the leaf is a projection of stem. But despite this recognition of the origin of this organ, few authors admit that there is continuity between the tissue found in these two organs. This chapter aims to show that tissue found in the stem, which are endodermis and pericycle, are also present in the leaves of species of Zingiberaceae and Costaceae families. Although not possible to observe strips of Caspary involving the vascular unit found in the leaves, could be observed in leaf expansion an accumulation of phenolic substances in tissue, facilitating the visualization of the cells corresponding to the endodermis. The pericycle, forming pericycle fibers was also observed and described. The root is one of the most preserved organs of all vegetative organs of vascular plants. This is the only organ where the tissues endodermis and pericycle are found in any textbook and that are part of primary body of the root. But despite this recognition, the endodermis is not seen by the authors in general, as being important for the formation of the root cortex. This chapter shows the presence of endodermis with meristematic activity, and demonstrate its derivatives (DEMs) in the root cortex of species of families Zingiberacaea and Costaceae.
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O espessamento primário no sistema caulinar e a continuidade entre esses tecidos nos órgãos vegetativos de Zingiberaceae e Costaceae: enfoque nos tecidos endoderme e periciclo / The primary thickening in stem system and the continuity between tissues in vegetative organs from Zingiberaceae e Costaceae: approach in tissues endodermis and pericycleCristiane Gonçalves da Silva 15 June 2009 (has links)
Essa dissertação foi subdivida em cinco capítulos que, apesar de relacionados entre, podem ser lidos e compreendidos de forma independente. O primeiro capítulo trata de um breve histórico sobre o espessamento primário em caules de monocotiledôneas. Seu principal objetivo é deixar evidente para o leitor a problemática referente tanto à nomenclatura dos tecidos relacionados ao espessamento primário em monocotiledôneas, quanto explicar as hipóteses que embasam essas nomenclaturas. O segundo capítulo teve como principal objetivo evidenciar que, apesar da discordância de muitos autores da atualidade, existe continuidade dos tecidos endoderme e periciclo entre os órgãos no corpo vegetativo de monocotiledôneas, apresentando indícios que apóiam esse pensamento. Já o terceiro capítulo, Caule, demonstra dados que corroboram o pensamento defendido nessa dissertação: endoderme e periciclo são os tecidos responsáveis pelo espessamento do corpo primário do caule de monocotiledôneas. O quarto capítulo, Folha, discute e demonstra a presença de endoderme (entorno da unidade vascular desse órgão) e periciclo (como parte dessa unidade vascular) em folhas de Zingiberaceae e Costaceae. O quinto e último capítulo aborda a importância dos já mencionados tecidos, quais sejam endoderme e periciclo, na formação da raiz primária. / Since ends of 19th century, arised a great diversity of terminologys to name meristematic region responsible for primary thickening in monocotyledons. Despite of this great number of denominations, a few hypothesis and ideas are utilized to base this great complex of terminologys. This historical chapter aims explain the origin from this terminologys and understand correlations between hypothesis basis. At the end of this explanation, you can understand why the defense of presence of endodermal and pericycle tissue as the two meristematic tissues responsible for this primary thickening in monocotyledonous rather than the currently most accepted name of \"PTM\", a single meristem advocated by many authors. Despite of many authors consider fact the continuity between the vascular tissues of stem and leaf and stem and root, few authors consider that the endodermis (between stem and leaf and between stem and root) and pericycle (between stem and leaf and stem and between root) of these organs may be continuous. It was shown, with verification of the continuity of the tissues mentioned above, the plant is a unit and can be found in the root and leaves the same tissues found in the stem, in this case, the main tissues examined in this chapter: endodermis and pericycle. This chapter aims to discuss, demonstrate, and finally prove the continuity of the tissues mentioned in Zingiberaceae, and also describe the morphology of these tissues in each of the aforementioned organs. The stems of monocots has been the subject of studies since the nineteenth century. But despite the large amount of work produced since then, there is still controversy regarding the primary tissue responsible for thickening of this organ. The families Zingiberaceae Costaceae and serve as a model for which more data were collected showing not only the presence of endodermis and pericycle in the stem, but also to show that these are the meristematic tissues responsible for primary thickening in this organ. It was observed in the underground stem, the presence of strips of Caspary in the region farthest from the apex. Already in the air stem, the endodermis was seen only parenchymatous, without any morphological alteration in its walls. The meristematic pericycle was found in the underground stem, but in the aerial stems it is pluriseriated and have cell walls thick. Many authors recognize that the leaf is a projection of stem. But despite this recognition of the origin of this organ, few authors admit that there is continuity between the tissue found in these two organs. This chapter aims to show that tissue found in the stem, which are endodermis and pericycle, are also present in the leaves of species of Zingiberaceae and Costaceae families. Although not possible to observe strips of Caspary involving the vascular unit found in the leaves, could be observed in leaf expansion an accumulation of phenolic substances in tissue, facilitating the visualization of the cells corresponding to the endodermis. The pericycle, forming pericycle fibers was also observed and described. The root is one of the most preserved organs of all vegetative organs of vascular plants. This is the only organ where the tissues endodermis and pericycle are found in any textbook and that are part of primary body of the root. But despite this recognition, the endodermis is not seen by the authors in general, as being important for the formation of the root cortex. This chapter shows the presence of endodermis with meristematic activity, and demonstrate its derivatives (DEMs) in the root cortex of species of families Zingiberacaea and Costaceae.
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MÄTNING AV ANDNINGSMUSKELSTYRKAFendi, Ranya January 2019 (has links)
No description available.
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À procura da revolução brasileira: itinerários do Movimento pela Emancipação do Proletariado / Looking for a Brazilian Revolution - itineraries of Movement for the Emancipation of ProletariatCunha, Vinicius Moraes da 26 June 2019 (has links)
Este presente trabalho tem o objetivo de reconstruir a história do Movimento pela Emancipação do Proletariado (MEP), organização política que compôs o segundo momento da chamada Nova Esquerda, em meados dos anos 1970. Fazendo parte do tronco que tem em sua raiz a POLOP (Política Operária), o MEP compartilhava da visão que defendia o caráter socialista da revolução brasileira, uma vez que o Brasil possuía uma economia plenamente capitalista, embora atrasada e dependente dos centros metropolitanos da economia-mundo. Do ponto de vista teórico, o MEP seguia as formulações da Teoria da Dependência e as contribuições de autores como Caio Prado Júnior, Moniz Bandeira, Florestan Fernandes e Chico de Oliveira, dentre outros, para encontrar uma teoria da Revolução Brasileira. A partir dessas referências, a organização desenvolveu atuação clandestina contra a ditadura militar. Organizava-se com moldes no marxismo-leninismo e enxergava na classe operária o principal sujeito da revolução. Por fazer oposição ao regime, a organização foi vítima da máquina repressiva, sofrendo com prisões e tortura. O MEP desenvolveu atuação militante entre estudantes, professores, no meio operário e em bairros da periferia de grandes cidades e editou o jornal Companheiro. Além disso, atuou desde o início na fundação do Partido dos Trabalhadores. Em 1985, ao lado da Ala Vermelha do PCdoB e da Organização Comunista Democracia Proletária (OCDP), fundou o Movimento Comunista Revolucionário (MCR). / The present study aims to rebuild the story of Movimento pela Emancipação do Proletariado (Movement for the Emancipation of Proletariat - MEP), a political organization that integrated the second moment of the so called New Left, in the mid- 1970s. Stemming from POLOP (Política Operária), MEP shared a vision that advocated the socialist character of Brazilian Revolution, once the country had an enterely capitalist economy, albeit backward and depending on the metropolitan centers of the world economy. From a theoretical standpoint, MEP had followed the statements of Dependency Theory to develop a Brazilian Revolution theory based on the contributions of scholars like Caio Prado Júnior, Moniz Bandeira, Florestan Fernandes and Chico de Oliveira, among others. From these referencies, the organization have developed a clandestine practice against the Military Dictatorship. Grounded on Marxist-Leninist principles, MEP considered the working class as the revolution protagonist. As opponents of the regimen, the organization members were victims of the repressive apparatus, suffering persecution and torture. MEP developed a militant work between students, teachers, the labor movement and on the outskirts of big cities and edited the Companheiro newspaper. Furthermore, MEP participated in the Workers Party (PT) foundation. In 1985, along with PCdoB red wing and the Organização Comunista Democracia Proletária (OCDP), founded the Movimento Comunista Revolucionário (MCR).
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Description topologique des phénomènes d'hydratation et développement méthodologique de fonctionnelles doubles hybrides à séparation de portée / Topological description of hydration phenomena and development of range separated double-hybrid functionalsKalai, Cairedine 04 July 2018 (has links)
Cette thèse s’intéresse aux phénomènes d’hydratation de composés organiques à l’échelle moléculaire. Des méthodes basées sur une fonction d’onde multi-déterminantale sont capables de rendre compte des phénomènes de hydratation avec une précision approchant la réalité expérimentale. Or, ces méthodes sont limitées par la taille du système. L’utilisation de la DFT semble indispensable à une étude de complexes, même pour un nombre limité de molécules d’eau. Il s’avère que ces méthodes ne prennent pas en compte les interactions de nature dispersive. Des corrections empiriques ont été proposées récemment pour palier à ce problème. Cependant, ces corrections ne s’appliquent qu’à l’énergie et sur la géométrie des complexes hydratées, la fonction d’onde n’étant pas affectée par la correction. D’autres alternatives pour la prise en compte des effets de dispersion reposent sur l’emploi de méthodes hybrides fonction d’onde/DFT. Ceci peut s’effectuer en introduisant une séparation de portée dans le traitement des interactions électroniques. L’un des objectifs de cette thèse consiste à proposer une nouvelle méthode double hybride à séparation de portée permettant une bonne description des phénomènes d’hydratation. L’autre objectif de cette thèse consiste à utiliser des outils topologiques permettant la prédiction de composés organiques hydraté par l’étude du potentiel électrostatique moléculaire et la caractérisation de ces interactions non covalentes par la théorie AIM. / This thesis deals with hydration phenomena of organic compounds at the molecular scale. The Schrodinger equation considered within the Born-Oppenheimer approximation and within a non-relativistic context contains all the physics necessary to describe in particular the micro-solvation of organic compounds. Methods that are based on a multi-determinant wave function are able to account for micro-hydration phenomena with a precision approaching the experimental reality. These methods are limited by the size of the system. The use of DFT seems necessary for a study of complexes, even for a limited number of water molecules. It turns out that these methods do not take into account dispersive interactions. Empirical corrections have recently been proposed to address this problem. However, these corrections apply only to the energy and to the geometry of the hydrated complexes, the wave function not being affected by the correction. Other alternatives for taking into account dispersion effects using double-hybrid methods should thus be considered. This can be done by introducing a range separation on the electronic interactions. There are two main objectives in this thesis. The first one is to propose a new double-hybrid method with range separation allowing a satisfactorily description of the hydration phenomena at the molecular scale. The second objective consists in using topological tools allowing the prediction of hydrated organic compounds using the electrostatic molecular potential and the characterization of these non-covalent interactions by the "Atoms in molecules" theory.
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BIM SOM VERKTYGFör digitalisering inom installationssamordning : BIM AS A TOOLFor digitization in MEP coordinationHellman, Anna, Säfström, Hanna January 2023 (has links)
Samhället blir alltmer digitalt och digitaliseringen är viktig för samhällsutvecklingen. Av den anledningen är det inkluderat i FN:s Agenda 2030 och EU:s digitala kompass. Boverket har fått i uppdrag av regeringen att utveckla en digital miljö för Plan- och bygglagen (PBL). De flesta av de digitala tjänster som krävs för att utbyta information metodiskt är utvecklade ochfinns tillgängliga på Boverkets webbplats, men det är fortfarande de tryckta kopiorna som är juridiskt bindande.BIM har blivit allt vanligare i Sverige men då det inte finns några nationella krav på att använda BIM är det upp till varje aktör att implementera arbetssättet efter egen förmåga. I takt med att byggnader blir alltmer komplexa ökar även installationerna som behövs i en byggnad i både antal och komplexitet. Trots den ökade användningen av BIM har antalet problem med installationer varit oförändrade eller i vissa fall ökat under de senaste tio åren.Syftet med denna rapport är att undersöka om digitaliseringen genom BIM kan förenkla installationssamordningen i byggprojekt samt vilka utmaningar som kan uppstå vid implementeringen och användandet av BIM.Enkätstudier och observationer har genomförts på konsultbolaget KAMTech i Örebro, Sverige, för att undersöka installationssamordnarens arbete och deras användning av BIM.Litteraturstudier har gjorts för att undersöka tidigare forskning inom ämnet och för att se potentialen för digitalisering, i form av BIM, inom installationssamordning. De givna enkätsvaren visar att tydlig kommunikation, gemensam planering och ömsesidiga krav är viktiga för en lyckad installationssamordning. Respondenterna anser även att BIM ger klarhet och bättre översikt samt att tidiga kollisionskontroller ger positiv inverkan för projektets välgång. Däremot framgår det av enkätsvar och observationer att det är en utmaning att se till att alla arbetar i den senast uppdaterade modellen i projekten.Studien visar att dagens installationssamordnare huvudsakligen använder BIM för att genomföra kollisionskontroller. Installationssamordnarna tror att möjligheten att upprätta protokoll för samordnade kontroller som är kopplade till ritningar och beskrivningar genom hyperlänkar skulle underlätta deras arbete. Slutsatsen är att digitalisering genom BIM kan förenkla installationssamordningen i byggprojekt genom att samla all data på ett ställe och skapa tydlighet samt struktur. Användning av BIM kan också bidra till ökad effektivitet och produktivitet i projekt genom att ge en visuell överblick av hela projektet. Implementeringen av BIM kan dock vara utmanande på grund av bristen på lagstadgade krav och standarder i Sverige. / The digitalization in the society is increasing and it is crucial for societal development, and it is therefore included in the UN Agenda 2030 and the EU's Digital Compass. The Swedish National Board of Housing, Building and Planning has been commissioned by the Swedishgovernment to develop a digital environment for the Planning and Building Act (PBL). Most of the digital services are developed and available on the National Board's website, but hard copies are still required according to the law.Building Information Modeling (BIM) has become increasingly common in Sweden, but since there are no national requirements or standards for BIM, it is up to each company to implement the working method according to their own abilities. As buildings become more complex, the number and complexity of installations required within these structures hasincreased. Despite the growing adoption of BIM, the number of issues related to installations has remained stagnant or even increased during the past decade.The aim of this report is to investigate whether digitization through BIM can simplify the Mechanical, Electrical, and Plumbing (MEP) coordination in construction projects, as well as the challenges that may arise during the implementation and utilization of BIM.Survey studies and observations have been conducted at the consulting company calledKAMTech in Örebro, Sweden, to investigate the MEP coordinator's work and their use of BIM. Literature studies have been conducted to investigate prior research within the field and to explore the potential for digitization in MEP coordination through the implementation of BIM.The survey results show that clear communication, shared planning, and requirements are essential for successful MEP coordination. According to the responders, the use of BIM in projects offers a sense of clarity and improved project overview. They also express that early clash detections have a positive impact of the project’s result. Survey results and observations also indicate that there are challenges to keep the model updated to the latest version in theprojects.Currently, BIM is primarily utilized by MEP coordinators to conduct clash detections. The MEP coordinators believe that having capability to establish protocols for coordinated checks, accompanied by hyperlinks to drawings and descriptions, would facilitate their work.The conclusion is that digitization through BIM can simplify the MEP coordination in construction projects by gathering all data in one place to organize and create clarity. The utilization of BIM can enhance efficiency and productivity in projects through its ability to provide a visual overview of the entire project. However, the implementation of BIM can be challenging due to the lack of legislated requirements and standards in Sweden.
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Auswirkungen der Stimulation des menschlichen Motorkortex mit randomisiertem Strom auf die kortikospinale Erregbarkeit / Effects of transcranial random noise stimulation of human motor cortex on corticospinal excitabilityTewes, Susanne 16 June 2010 (has links)
No description available.
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Etudes in silico et expérimentale de la DXR & synthèse de D- et L-GAP énantiomériquement purs / In silico and experimental studies of the DXR & enantiomerically pur D- and L-GAP synthesisKrebs, Fanny 21 December 2016 (has links)
La thèse porte sur l’étude des 2 premières enzymes de la voie du MEP: la DXS et DXR. La voie du MEP conduit à la biosynthèse des isoprénoïdes chez la plupart des bactéries, dont des pathogènes. Etant absente chez l’homme, les enzymes de cette voie cible idéale pour la recherche de nouveaux antimicrobiens. L’objectif principal était d’améliorer le développement de nouveaux antimicrobiens. Nous avons utilisé des outils computationnels : méthodes de docking et de mécanique moléculaire couplée à la méthode MM/PBSA. Nous avons identifié les résidus contribuant significativement à la fixation d’un ligand dans le site actif de la DXR. Ces résultats ont été utilisés lors de la conception de nouveaux candidats inhibiteurs de type bisubstrat, biligand et difluoro phosphonate, dont 2 ont pu être synthétisés. Nous avons également développé une méthode de synthèse donnant accès au L- et D-GAP énantiomeriquement purs, dans le but d’étudier l’énantiospécificité de la DXS face à son substrat D-GAP. / This thesis concerns the study of the 2 first enzymes of the MEP pathway: DXS and DXR. The MEP pathway permits the biosynthesis of isoprénoïdes in most bacteria, including pathogenic one. As it is not present in human, enzymes of MEP pathway are effective targets in the research of new antimicrobial drugs. The objective was to advance the development of new antimicrobiotic compounds. We used computational tools: molecular docking and molecular dynamics simulations coupled with an MM/PBSA approach. We were able to identify residues that contribute significantly to the ligand binding in the DXR active site. These results were used to guide the conception of new inhibitor models, such as bisubstrates, biligands and α,α-difluoro phosphonates, two of which were synthetized. We also developed a synthesis method to obtain L- and D-GAP as enantiomerically pure molecules. The goal was to study the enantiospecificity of DXS to its substrate, D-GAP.
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