Les folates sont des vitamines importantes dans le développement neurologique d’un enfant puisqu’elles sont impliquées dans deux pathologies : l’autisme et les anomalies de fermeture du tube neural (AFTN). Une carence en vitamine B9 et la présence de certains polymorphismes des gènes du métabolisme des monocarbones sont associées à un risque augmenté d’anomalies de fermeture du tube neural. A l’inverse, une supplémentation périconceptionnelle en vitamine B9 a permis de réduire l’incidence de ces malformations. Dans le cadre de l’autisme, la présence d’anticorps dirigés contre le récépteur aux folates FR aplha au niveau cérébral entraînant une carence en folate cérébral a été décrite avec une fréquence importante chez les enfants autistes. Un traitement par acide folinique permettrait une amélioration des symptômes en corrigeant la carence en folates grâce à un passage médié par le RFC (récépteur non bloqué par les anticorps). La première partie est une étude clinique randomisée versus placebo réalisée au CHU de Nancy dont le but est d’évaluer l’éfficacité d’un traitement par acide folinique pendant 12 semaines sur la réduction des troubles autistiques. 19 enfants ont été inclus dans l’étude.Une amélioration significative des symptômes autistiques est observée pour le score ADOS dans le groupe traité (p= 0,02), plus particulièrement pour les interactions sociales réciproques (p=0,019). La fréquence des Anticorps anti FR alpha au sein du groupe est de 58 %. Il n’y a pas de corrélation observée entre le taux d’anticorps et l’importance de la réponse au traitement. Aucun effet secondaire grave n’a été observé au cours de l’étude. La seconde partie est une étude par séquençage haut débit d’un large panel de gènes chez des patients présentant des anomalies de fermeture du tube neural (SureSelect Focused Exome Plus (Agilent®)). Le séquençage a été complété par une analyse de méthylation pan-génomique (Infinium HumanMethylation Beadchip (Illumina®)). 23 patients ont été inclus dans l’étude. Plusieurs variants rares ont été identifiés comme associés au risque de AFTN dont des variants de gènes du métabolisme des monocarbones : LRP2, rs137983840, p=0,005; MMAA, rs148142853, p= 0,005 ;TCN2, rs35838082, p=0,044, FPGS, rs41306702, p=0,0012, BHMT, rs763726268, p= 0,011 et de la voie Sonic Hedgehog (SHH) (GLI3, rs35364414, p=0,012). Une différence de méthylation significative a été mise en évidence au niveau du gène CFAP46 (hémiméthylation versus absence de méthylation chez les contrôles) chez un patient porteur des 4 variants à risque identifiés (LRP2, MMAA, BHMT et GLI3). Ces résultats renforcent l’implication des folates dans ces deux pathologies du neurodéveloppement que sont l’autisme et les anomalies de fermeture du tube neural. Une recherche des anticorps anti-FRalpha plus systématique chez les enfants autistes pourrait permettre de proposer un traitement par acide folinique ciblé. Dans le cadre des AFTN, notre étude a mis en évidence l’influence de gènes impliqués dans le métabolisme de la vitamine B12 et monocarbone sur le risque de AFTN. Un nouveau gène candidat (GLI3) est identifié ainsi qu’une signature de méthylation mettant en évidence l’influence de la voie SHH / Folates are essentials vitamins in children neurodevelopment with an implication in two pathologies : autism and neural tube defects (NTD). Folates deficiency and some polymorphisms of genes involved in one carbon metabolism (OCM) are associated with NTD. Contrary, periconceptional folate supplementation is associated with decreased NTD frequency.In autism, higher frequency of antibodies against Folate Receptor Alpha (FR alpha) is rapported and associated with folates cerebral deficiency. Folinic acid treatment could improve autistic symptoms by correcting cerebral folate deficiency (cerebral transport mediated by RFC, an other receptor which not blocked by antibodies anti-FR alpha). First part is a randomized controlled trial versus placebo realized in CHU of Nancy in order to evaluate efficiency of folinic acid treatment during 12 weeks on autistic symptoms. 19 children have been included in the study. A significative improvement of autistic symptoms is observed by ADOS score in folinic acid group (p= 0.02) and particularly for mutual social interactions (p=0.012). FRalpha antibodies are present in 58 % of the group. We didn’t observed correlation between antibodies titers and folinic acid response. No serious adverse effects have been observed during the study. Second part is hight throughput next generation sequencing of DNA from patients with NTD using SureSelect Focused Exome Plus (Agilent®). Sequencing has been completed with DNA methylation analysis (Infinium HumanMethylation Beadchip (Illumina®)). 23 patients were included in the study. Six variants have been associated with NTD: from genes of B12 metabolism LRP2, rs137983840, p=0.005; MMAA, rs148142853, p= 0.005 and TCN2, rs35838082, p=0.044), folate cellular metabolism (FPGS, rs41306702, p=0.0012; choline metabolism, BHMT, rs763726268, p= 0.011) and Sonic Hedgehog pathway(SHH) (GLI3, rs35364414, p=0.012). A significative difference of methylation is identified in the vicinity of CFAP46 gene (hemimethylation versus no methylation in pseudo-controls) in one patient exhibited variants of BHMT, LRP2etMMAA. These results highlight implication of folates in these two pathologies of neurodevelopment, wich are autism and NTD. Anti-FRalpha should be routinely evaluated in case of autism in order to propose folinic acid treatment if they are positives. In the NTD study, we identified new variants from gene from one carbon metabolism probably implicated. A new candidate gene is identified (GLI3) and a methylation signature in association with B12 metabolism and OCM gene variants

Syfte: Syftet med detta projekt var att utvärdera kvaliteten på de digitala röntgenbilder som genereras med en On-Board imager® (OBI), monterad på en medicinsk linjäraccelerator på radioterapiavdelningen på Karolinska Universitetssjukhuset. Dessa kilovoltbilder används för att verifiera patientens position på behandlingsbordet, inför behandling, för att reducera risken att friskvävnad bestrålas i onödan. Detta utförs genom en online ortogonal 2D-2D matchningsteknik innan strålningen leveras. Material och metoder: OBI-system, utvecklad av Varian Medical System, erbjuder en protokoll med exponeringsparametrar för att hjälpa användaren att välja lämpliga inställningar för exempelvis lämplig rörström och spänning under bildtagningen de digitala kilovoltbilderna. Under detta projekt skapades flera testbilder tagna med ändrade exponeringsparametrarna i de befintliga protokollen. Dessa testbilders kontrast bedömdes sedan och jämfördes med bilder tagna med de förinställda parametrar från Varians protokoll. Resultat och slutsats: En utvärdering av de experimentella testbilderna, i jämförelse med bilder skapade med det befintliga protokollet, visade att en justering av exponeringsfaktorer inte leder till något signifikant förbättring av bildernas kontrast. / Purpose: The purpose of this project was to evaluate the quality of kilo Voltage- digital radiography images that are provided by an On-Board imager® (OBI) mounted on a medical linear accelerator at the Radiotherapy department of Karolinska University Hospital. The digital kV-images are used to verify patient position on the treatment table, in order to reduce healthy tissue irradiation, using an online orthogonal set of 2D-2D matching technique, before the treatment delivery. Material and methods: The OBI- system elaborated by Varian Medical System offers an exposure factor protocol in order to help users to choice proper exposure factors, as proper tube current and tube voltage, during acquisition of kV-images. In this project several test images were performed by changing the exposure factors. Further the test images quality regarding, quality index contrast, was assessed and compared with the image performed by the existent Varian protocol. Result and Conclusion: Evaluation of the tests images shows that changing of the exposure factors doesn’t result in any significant improvement of kV-images contrast as compared to images created with the existent protocols parameters.

Chez les plantes à fleurs, la communication entre les grains de pollen et les cellules épidermiques du stigmate, aussi appelées papilles, est cruciale pour le succès de la reproduction. Lorsqu’il est accepté, le grain de pollen germe et émet un tube pollinique qui transporte les gamètes mâles jusqu’aux ovules. La rencontre et la fusion entre les gamètes mâles et femelles reposent par conséquent sur la bonne trajectoire des tubes polliniques lors de leur progression dans les différents tissus du partenaire femelle pour atteindre les ovules. Les tubes polliniques croissent dans la paroi cellulaire des papilles stigmatiques et génèrent une pression sur ces dernières. De telles forces sont connues pour modifier le réseau de microtubules corticaux (MTC) ainsi que le comportement de la cellule. La première partie de ma thèse a consisté à étudier le rôle des MTC du stigmate dans le contrôle de la croissance du tube pollinique. En combinant imagerie cellulaire et approches génétiques, nous avons mis en évidence que chez le mutant katanin1-5 (ktn1-5) d’Arabidopsis, les papilles ont un réseau de MTC très isotrope, associé à une forte tendance des tubes polliniques sauvages à faire des spires autour des papilles. Ce phénotype a pu être partiellement reproduit par traitement des papilles avec un agent dépolymérisant les MTC, l’oryzaline. Compte tenu que le réseau de MTC est fortement lié à l’organisation des fibres de cellulose, et donc potentiellement à la rigidité de la paroi, nous avons mesuré la rigidité des papilles du mutant ktn1-5 grâce au microscope à force atomique. L’ensemble de ces résultats suggère que la KATANIN, en régulant l’organisation des MTC et conférant des propriétés mécaniques particulières à la paroi cellulaire, joue un rôle primordial dans le guidage des tubes polliniques lors de leur croissance dans les papilles stigmatiques. De façon similaire à la croissance des tubes dans les papilles, les hyphes des pathogènes filamenteux pénètrent les tissus épidermiques de leur hôte. Lors d’une attaque par un pathogène, les cellules de l’épiderme de l’hôte réagissent rapidement pour mettre en place une réponse appropriée, décisive sur le résultat de l’interaction plante-pathogène. La seconde partie de ma thèse a eu pour objectif de comparer la réponse cellulaire des papilles stigmatiques suite à l’invasion par deux types d’organismes, le tube pollinique lors de la pollinisation et les hyphes de deux Oomycètes pathogènes, Phytophtora parasitica et Hyaloperonospora arabidopsidis durant leurs processus d’infection. Nos résultats démontrent que la papille stigmatique est capable d’adapter sa réponse en fonction de l’identité de l’envahisseur. / The epidermis is the first cellular barrier in direct contact with the environment in both animal and plant organisms. In plants, the result of the cell-to-cell communication that occurs between the pollen grain and the epidermal cells of the stigma, also called papillae, is crucial for successful reproduction. When accepted, the pollen grain germinates and emits a pollen tube that transports the male gametes towards the ovules. Effective fertilization in angiosperms depends on the proper trajectory that pollen tubes take while progressing within the pistil tissues to reach the ovules.Pollen tubes grow within the cell wall of the papilla cells, applying pressure to the wall. Such forces are known to alter the cortical microtubule (CMT) network and cell behaviour. The first part of my PhD thesis aimed at investigating the role of the microtubule cytoskeleton of stigmatic cells in pollen tube growth. By combining cell imaging and genetic approaches, we found that in the Arabidopsis katanin1-5 (ktn1-5) mutant, papillae have a highly isotropic CMT array, associated with a marked tendency of wild-type (WT) pollen tube to turn around the papillae. We could partially phenocopy this coiled growth of pollen tubes by treating WT papillae with the microtubule-depolymerizing drug oryzalin. As CMT pattern is linked to cellulose microfibrils organisation, and hence possibly to cell-wall stiffness, we assessed the stiffness of ktn1-5 and aged papillae using Atomic Force Microscopy. Altogether, our results suggest that both organisation of CMT and cell wall properties dependent on KATANIN have a major role in guiding early pollen tube growth in stigma papillae.Similarly to pollen tube growth within the stigmatic papilla, hypha of filamentous pathogens penetrates the epidermal tissue of the host. During pathogen attacks, epidermal cells promptly react to the invading organisms to adjust the most relevant response. Early response of the first cell layers including epidermal cells is decisive for the result of plant-pathogen interactions. The second part of my PhD work aimed at comparing the cellular response of stigmatic cells challenged by two types of invaders, the pollen tube during pollination and hyphae of two oomycete filamentous pathogens, Phytophtora parasitica and Hyaloperonospora arabidopsidis, during the infection process. We demonstrate that a stigmatic cell challenged by a pollen tube or an oomycete hypha adapts its response to the invader’s identity.

No description available.

<p>Of the various excitation mechanisms causing excessive tube vibrations in tube and shell heat exchangers, fluidelastic instability is the most dangerous, and therefore has received the most attention. The objective of this research is to advance the current understanding of the fluidelastic instability in tube arrays through a fundamental investigation of the phenomenon experimentally, numerically and analytically. The concept of using a single flexible tube in a rigid array to investigate fluidelastic instability has been critically reviewed. It was found that the fluidelastic instability threshold in tube arrays is significantly affected by array geometry, pitch ratio, mass ratio and tube row location in the array. The results showed that, in general, fluidelastic instability in tube arrays is caused by a combination of the damping and the stiffness mechanisms. It was concluded that while the use of a single flexible tube in a rigid array provided a useful model for fundamental research and physical insights, it must be cautioned that it is not generally adequate for determining the experimental stability limits of tube arrays. The outcomes of this critical review helped in the design of a new experiment which facilitated precise control of the system parameters, and provided more comprehensive measurements.</p> <p>Experimental investigation of the interaction between tube vibrations and fluid forces was conducted using surface pressure measurements at the tube surface. The results showed that, there is a finite time delay between tube vibration and the associated fluid forces acting on the tube. The resulting phase lag was found to increase as the mean gap velocity increased, and ultimately the fluid forces became in phase with the tube velocity during the onset of instability. Velocity measurements of the interstitial flow perturbations associated with tube vibrations were carried out along the flow path in the array. It was found that the flow perturbation amplitude is most pronounced at the flow separation point from the vibrating tube, and that the flow perturbation amplitude decays continuously to a negligible amplitude at about one and a half rows upstream. This suggests that the flow perturbations are caused by the flow separation from the tube and the associated vorticity shedding and convection. The phase lag measurements between tube vibrations and flow perturbations support this conclusion, and show that the flow perturbations propagate upstream and downstream at different rates. Computational Fluid Dynamics modeling of the tube array was developed to assist in understanding the experimental results. The CFD models were validated using experimental data from both the literature and from the present research. It was found that there are two propagation mechanisms for the flow perturbations associated with tube vibrations. The first mechanism is caused by the pressure pulsation due to tube vibrations. This mechanism is dominant at lower reduced velocities, and propagates at the speed of sound. The second mechanism is caused by the flow separation and the associated vorticity shedding, and this mechanism is dominant at higher reduced velocities. The transition between the two mechanisms occurs at a reduced velocity of about (U_r≈2). Mathematical models of the flow perturbation phase lag and amplitude decay were developed. The new models were coupled with the semi-analytical model after modifying its geometrical parameters according to the flow visualizations in the literature. The resulting stability maps show a significant improvement to the current prediction of the fluidelastic instability data in the literature. The outcomes of the present work can contribute to improve the future design guidelines for tube and shell heat exchangers to achieve extended service time with higher efficiency.</p> / Doctor of Philosophy (PhD)

This is a master thesis conducted at KTH Centre for Naval Architecture in collaboration with Wallenius Marine AB. Rolling motions is something that is undesired in all kinds of seafaring. In terms of propulsion resistance, comfort and route planning it would be desirable to reduce these motions. This thesis is an investigation on how different roll stabilising systems affect the performance of an 8000 unit PCTC vessel, special emphasis is put on investigating the performance of anti roll tanks. The ship in question has a recorded incidence of parametric rolling and the ability of the tanks to countervail this phenomenon is also investigated. The tank and fin stabilising systems are relatively equal when it comes to roll damping performance related to changes in the required forward propulsion power. The tanks however, have a higher potential for improvements, addition of features such as heeling systems and parametric roll prevention systems. The tank performance is also independent of the speed of the ship. The tanks are easier to retrofit and do not require the ship to be put in dry dock during installation. The conclusion of this thesis is that a combined anti roll and heeling system should be installed but that a further study has to be made on the performance of active rudder stabilisation. It is shown that passive tanks are efficient at preventing parametric rolling in some sea states. A proposal is made for a further study on a control system that could achieve the same performance for all sea states. / HTML clipboard Detta är ett examensarbete utfört på KTH Marina System i samarbete med Wallenius Marine AB. Rullningsrörelser är något som är oönskat i all form av sjöfart. Framsteg kan göras i både framdrivningsmotstånd, komfort och ruttplanering om dessa rörelser kunde minskas. Detta examensarbete består av en undersökning hur olika system för rulldämpning påverkar prestandan hos ett 8000 enheters PCTC-fartyg. Speciell vikt har lagts vid att undersöka prestandan hos antirulltankar. Det undersökta fartyget har en dokumenterad incident med parametrisk rullning och tankarnas förmåga att motverka detta fenomen undersöks. Tank- och fenstabilisatorer är i princip likvärdiga vad det gäller dämpningsprestanda relaterat till erforderliga ändringar i framdrivningseffekten. Tankarna har dock en större potential för förbättring och tillägg av ytterligare inslag som krängningshämmare och system för motverkan av parametrisk rullning. Tankarnas prestanda är också oberoende av fartygets fart. Tankarna är lättare att installera i efterhand och kräver inte att fartyget läggs i torrdocka under installationen. Slutsatsen av detta arbete är att en kombinerad antirull- och krängningshämmande tank bör installeras men att en vidare studie måste göras på prestandan hos aktiva roderstabiliseringssystem. Det visas att passiva tankar kan motverka parametrisk rullning i vissa sjötillstånd. Ett förslag om en vidare studie på reglersystem som skulle kunna ge samma prestanda vid alla sjötillstånd ges.

Geosynthetic tubes have the potential to replace the traditional flood protection device of sandbagging. These tubes are manufactured with many individual designs and configurations. A small number of studies have been conducted on the geosynthetic tubes as water barriers. Within these studies, none have discussed the dynamics of unanchored geosynthetic tubes. A two-dimensional equilibrium and vibration analysis of a freestanding geosynthetic tube is executed. Air and water are the two internal materials investigated. Three foundation variations are considered: rigid, Winkler, and Pasternak. Mathematica 4.2 was employed to solve the nonlinear equilibrium and dynamic equations, incorporating boundary conditions by use of a shooting method. General assumptions are made that involve the geotextile material and supporting surface. The geosynthetic material is assumed to act like an inextensible membrane and bending resistance is neglected. Friction between the tube and rigid supporting surface is neglected. Added features of viscous damping and added mass of the water were applied to the rigid foundation study of the vibrations about the freestanding equilibrium configuration. Results from the equilibrium and dynamic analysis include circumferential tension, contact length, equilibrium and vibration shapes, tube settlement, and natural frequencies. Natural frequencies for the first four mode shapes were computed. Future models may incorporate the frequencies or combinations of the frequencies found here and develop dynamic loading simulations. / Master of Science

No / Tapered concrete filled double skin steel tubular (CFDST) columns have been used in China for structures such as electricity transmission towers. In practice, the bearing capacity related to the connection details on the top of the column is not fully understood. In this paper, the experimental behaviour of tapered CFDST stub columns subjected to axial partial compression is reported, sixteen specimens with top endplate and ten specimens without top endplate were tested. The test parameters included: (1) tapered angle, (2) top endplate thickness, and (3) partial compression area ratio. Test results show that the tapered CFDST stub columns under axial partial compression behaved in a ductile manner. The axial partial compressive behaviour and the failure modes of the tapered CFDST stub columns were significantly influenced by the parameters investigated. Finally, a simple formula for predicting the cross-sectional capacity of the tapered CFDST sections under axial partial compression is proposed.

No / Rectangular concrete-filled steel tube (CFST) may be subjected to local bearing forces transmitted from brace members while being used as a chord of a truss, and thus development of finite element analysis (FEA) and simple design calculation method for rectangular CFSTs under local bearing forces are very important to ensure the safety and reliable design of such a truss with rectangular CFST chords in engineering practices. A three-dimensional FEA model was developed using ABAQUS software package to predict the performance of thin-walled rectangular CFST under local bearing forces. The preciseness of the predicted results was evaluated by comparison with experimental results reported in the available literature. The comparison and analysis show that the predicted failure pattern, load versus deformation curves and bearing capacity of rectangular CFST under local bearing forces obtained from FEA modelling were generally in good agreement with the experimental observations. After the validation, the FEA model was adopted for the mechanism analysis of typical rectangular CFSTs under local bearing forces. Finally, based on the parametric analysis, simple design equations were proposed to be used to calculate the bearing capacity of rectangular CFST under local bearing forces. / National Natural Science Foundation of China (51421064) and the Natural Science Foundation of Liaoning Province (2013020125). The financial support is gratefully acknowledged.

The majority of the vessels in the commercial fleet utilize oil lubricated stern tubes. Unfortunately, this brings about a risk of oil leaking from the stern tube into the marine environment if the stern tube seal would become worn or damaged by foreign materials. Previous studies concluded that, on average, 2.6 litres of oil per day leak out from the stern tube of ships. This essay has investigated the causes that could increase the leakage rate from the stern tube by reviewing literature, interviewing experts, and sending out surveys with questions regarding the subject. The answers that were received painted a clear picture that it is impossible to get a perfect seal on a stern tube. The causes that could influence the leakage rate were design related, such as vibrations, the rotational speed of the propeller shaft, radial and axial movements of the propeller shaft, as well as external causes such as the quality of water and foreign materials, for example, fishing lines and nets. The question whether water lubricated stern tubes were a viable alternative compared to oil lubricated stern tubes was also investigated. The result was that the bearing on a water lubricated stern tube did not have as long lifespan as an oil lubricated bearing. / Majoriteten av fartygen i handelsflottan använder oljesmorda propellerhylsor för att smörja propelleraxeln. Tyvärr medför det en risk att olja kan läcka ut från hylsan om tätningarna skulle bli utslitna eller skadas av främmande föremål. Tidigare forskning har visat att cirka 2,6 liter olja per dag läcker ut genomsnittligen från fartyg i handelsflottan. Denna uppsats har utrett vad som kan påverka läckagemängden från en propellerhylsa genom att utnyttja intervjuer och enkätsvar. Svaren som framkom var att det är mer eller mindre omöjligt att få en perfekt tätning på en propellerhylsa. Saker som kan påverka läckagemängden var designfenomen som vibrationer, axiella- och radiella rörelser och varvtal på propelleraxeln, samt yttre påverkan som vattenkvalité och främmande föremål som fiskelinor och nät. I uppsatsen jämförs även vattensmorda propellerhylsor med fokus på livstid, kostnad och underhåll, med en oljesmord propellerhylsa. En slutsats är att det vattensmorda lagret inte har samma livstid som det oljesmorda.