Rapid changes in relative helium abundance in solar wind are often attributed to the flux tube crossings - thus between solar wind streams coming from different parts of the solar corona. Recent studies however show, that the changes in relative helium abundance are not always correlated with changes in other parameters and therefore the relative helium abundance could be changed even during the propagation of solar wind inside a flux tube. The topic of this thesis is an analysis of rapid changes of solar wind parameters and their mutual connection. Using a multipoint (we use data from the SPEKTR-R, WIND and the THEMIS spacecraft) case study of interplanetary shocks, we show that a possible explanation of those changes could be a magnetosonic instability excited by the differential flow between helium and proton populations.

Cette thèse, de nature expérimentale, porte sur l'étude du couplage fluide / interface de croissance en solidification dirigée en lames minces. En solidification naturelle, les écoulements de nature convective ou solutale engendrent un transport de soluté devant le front et modifient la dynamique des microstructures. Ils sont modélisés ici en lames minces par un écoulement de Poiseuille induit par un thermosiphon. Au-delà des effets d'inclinaison de microstructures et d'asymétrie du développement des branchements, un nouveau phénomène est mis en évidence : des ondes progressives interfaciales modifiant fortement les microstructures. Trois types d'ondes sont observés. Leur diagramme d'existence est déterminé en fonction des vitesses de solidification et d'écoulement, et leurs caractéristiques principales en vitesse de phase, amplitude et asymétrie sont identifiées. Elles apparaissent quasi-insensibles à l'épaisseur de l'échantillon et à la longueur thermique. La cohérence de leur mécanisme de propagation est explicitée en tenant compte de la concentration et de la vitesse de l'interface, ainsi que de la forme des microstructures et de leur rejet de soluté. Ces ondes interfaciales créent des modulations de concentration, dont l'échelle caractéristique ne dépend pas de la nature des ondes ou du gradient thermique, mais seulement du rapport entre vitesse de l'écoulement et vitesse de solidification. La microségrégation et donc les propriétés résultantes des matériaux en sont alors directement influencées. / This thesis addresses the experimental study of the coupling between a flow and a growth interface in directional solidification in a thin sample. In natural solidification, the convective or solutal flows both generate a transport of solute along the front and modify the microstructure dynamics. They are modelled here in a thin sample by a Poiseuille flow induced by a thermosiphon. Beyond the effects of microstructure inclination and of asymmetry of sidebranch development, a new phenomenon is evidenced : the existence of the interfacial travelling waves that strongly affect microstructures. Three kinds of waves are observed. Their diagram of existence is determined as a function of both the pulling velocity and the flow velocity, and their main characteristics in phase velocity, amplitude and asymmetry are identified. They appear almost insensitive to the thickness of the sample and to the thermal length. The coherence of their propagation mechanism is made explicit when involving the concentration and the velocity of interface together with the form and the solute rejection of microstructures. These interfacial waves create concentration modulations whose characteristic scale does not depend on the wave type or the thermal gradient, but on the ratio of flow velocity to solidification velocity only. They then directly influence the microsegregation and thus, the resulting material properties.

The quality of convective precipitation and storm prediction is dependent on the level of knowledge of the convective environment. Convective environment characteristics describe various conditions in the atmosphere which are suitable for the convective storm formation and evolution. The characteristics CAPE, wind shear S01, S03 and S06 were selected for the discussion of their properties and predictive ability. This master thesis deals with the CAPE and S0X values analysis in the Czech Republic during the period May-August 2005-2011. Furthermore it analyzes the distribution of the combined characteristics CAPE × S0X and index NDSEV, especially in the critical interval of values which indicate a storm occurrence. It also deals with the estimation of relationship between NDSEV index and the heavy precipitation occurrence in the Czech Republic. The verification criterion CSI was applied to the evaluation of various threshold values for the NDSEV index.

Title: Effect of core training on anterior shoulder instability on semiprofessional rugby players. The concept of the problem: With Rugby Union football being a contact-collision sport there is a high risk of injury incidence, especially for the upper extremities. The anterior shoulder dislocation carries the highest incidence and severity and may frequently lead to an anterior shoulder instability and is therefore a risk factor for decreasing sporting performance. Working with anterior shoulder instability on a complex basis, there are many possibilities to influence this problem and on of them is incorporating a "core-training" program into functional training patterns. In sports, the core provides a foundation upon which muscles of the extremties and their coordination rely. Objectives: To evaluate the incidence of anterior shoulder instability on semiprofessional rugby players and, subsequently, to attest the effectivity of the "core-training" exercise program on anterior shoulder instability of these athletes, on explosive power of the upper extremities and the performance of "medvěd"- an examination of the "Integrated Stabilizing System of the Spine" (HSSP) from Kolář. Methods: The theoretical part follows up the given issue as a research and theoretical overview of the current findings based...

DNA methylation is a major form of epigenetic modification and involves the addition of a methyl group covalently to the 5-position of the cytosine pyrimidine ring, mostly within the context of CpG dinucleotides in vertebrate somatic cells. Methylation of CpG dinucleotides at promoter regions is generally associated with transcriptional repression. In this context, the methyl-CpG binding proteins (MeCPs) that are capable of recognition of methylated CpG dinucleotides are proposed to play a central role in DNA methylation associated transcriptional repression. Methyl-CpG binding domain protein 4 (MBD4) is an MeCP that possesses a glycosylase domain at its C-terminal, which can excise and repair both G:T and G:U mutations derived from DNA deamination at CpG dinucleotides, in addition to its Nterminal MBD binding domain. MBD4 has been associated with a number of pathways including DNA repair, apoptosis, transcriptional repression, and possibly DNA demethylation processes. However, the precise contribution of MBD4 to these processes remains unclear. To explore the functional repertoire of MBD4 I decided to undertake multiple protein interaction studies to identify potential partner proteins. I performed yeast 2-hybrid screens with an 11.5 day mouse embryonic cDNA library and multiple mass spectrometry of immunoprecipitates of tagged versions of MBD4 that were over-expressed in human cell lines. I detected ~380 potential interacting candidates with these assays. A significant number of candidates were detected in both assay systems. Chosen candidates were further validated by reciprocal co-IP of expressed partners and by immunofluorescence (IF) microscopy to determine their potential co-localisation in mouse and human cell lines. Subsequently, I identified the intervening domain of MBD4 as a novel protein interaction region for tested candidates. My analysis suggests that MBD4 can have a role in regulation of post-replication methyl-error repair/methylation machinery through its direct interaction with DNMT1 (previously shown), UHRF1 (novel) and USP7 (novel), as well as possible cross-talk to histone modification and chromatin remodelling pathways, through partners such as PRMT5 and ACF1. Interestingly the transcription regulatory components KAP1 and CFP1 not only interact with but also dramatically influence the stability of exogenously expressed MBD4 in human cells. In general positive validation by IP and IF demonstrates the robustness of the initial screens, and implies that MBD4 may impact upon several transcriptional and epigenetic networks along with a number of nuclear pathways that include transcriptional repression, DNA repair and RNA processing. To test for transcriptional aberration in the absence of Mbd4 function I profiled two independent mouse cell lines that lack MBD4 activity using Illumina MouseWG-6 v2.0 Expression BeadChip arrays. A number of genes were identified that are significantly up- or down- regulated in both Mbd4-/- MEFs. This included mis-expression of insulin-like growth factor-binding proteins and two paternally imprinted genes Dio3 and H19. The cohort of genes that were mis-expressed in the Mbd4-/- MEFs overlap with genes that responsed to tamoxifen exposure in an ER-positive ZR-75-1 xenograft model. In response to this observation I identified a potential interaction between MBD4 and estrogen receptor α (ERα) by co-IP and IF co-localisation. This suggests that MBD4 might potentiate transcription of estrogen regulated genes via a direct interaction with ERα, supporting a possible link between replication repair remodelling and steroid/thyroid hormone receptor transcriptional regulation. Additionally I performed a pathway analysis by which several developmental genes including Sox9, Klf2 and Klf4, were prioritised as possible MBD4 targets. On this basis I propose a role for MBD4 in acquired diseases such as cancers and autoimmune diseases via transcriptional regulation. I also performed a comparison of MBD4 DNA binding activity with MBD4 homologues from the Medaka fish (Oryzias latipes) and the amphibian, Xenopus laevis. I could show that DNA binding specificity to a series of methylated and mismatched probes is conserved regardless of the poor sequence conservation of the MBD domain of MBD4 between the species. I conclude that MBD4 is integrated in multiple pathways in the nucleus that includes DNA repair, chromatin remodelling, transcriptional regulation and genome stability.

Recursive partitioning algorithms separate a feature space into a set of disjoint rectangles. Then, usually, a constant in every partition is fitted. While this is a simple and intuitive approach, it may still lack interpretability as to how a specific relationship between dependent and independent variables may look. Or it may be that a certain model is assumed or of interest and there is a number of candidate variables that may non-linearily give rise to different model parameter values. We present an approach that combines generalized linear models with recursive partitioning that offers enhanced interpretability of classical trees as well as providing an explorative way to assess a candidate variable's influence on a parametric model. This method conducts recursive partitioning of a the generalized linear model by (1) fitting the model to the data set, (2) testing for parameter instability over a set of partitioning variables, (3) splitting the data set with respect to the variable associated with the highest instability. The outcome is a tree where each terminal node is associated with a generalized linear model. We will show the methods versatility and suitability to gain additional insight into the relationship of dependent and independent variables by two examples, modelling voting behaviour and a failure model for debt amortization. / Series: Research Report Series / Department of Statistics and Mathematics

A unified toolbox for testing, monitoring, and dating structural changes is provided for likelihood-based regression models. In particular, least-squares methods for dating breakpoints are extended to maximum likelihood estimation. The usefulness of all techniques is illustrated by assessing the stability of de facto exchange rate regimes. The toolbox is used for investigating the Chinese exchange rate regime after China gave up on a fixed exchange rate to the US dollar in 2005 and tracking the evolution of the Indian exchange rate regime since 1993. / Series: Research Report Series / Department of Statistics and Mathematics

The solar wind interaction with an icy comet is studied through a model problem. A hybrid simulation is done of a box with evenly distributed water ions and protons, where initially the water ions are stationary, and protons move with the speed of the solar wind. The purpose of the thesis is to investigate the interaction between the two species through the convective electric field, and focus is on early acceleration of pick-up ions, and deflection of the solar wind. It is relevant to the cometary case, because it enables study of the physics of this interaction, without involving other mechanisms, such as bow shock, magnetic field pile-up and draping. The species are found to exchange kinetic energy similar to a damped oscillator, where the dampening is caused by kinetic energy being transferred to the magnetic field. At early times, i.e. times smaller than the gyration time for the water ions, the solar wind does not lose much speed when it is deflected. For comparable number densities, the solar wind can be deflected more than 90° at early times, and loses more speed, and water ions are picked up faster. The total kinetic energy of the system decreases when energy builds up in the magnetic field. The nature of the energy exchange is strongly dependent on the number density ratio between water ions and protons. A density instability with behaviour similar to a plasma beam instability forms as energy in the magnetic field increases, and limits the amount of time the simulation preserves total energy, for the particular hybrid solver used. There is a discussion on the structure of the density instability, and it is compared to cometary simulations.

Le but de cette thèse a été de redéfinir le diagnostic d’hyperlaxité de l’épaule. Ce travail s’appui sur plusieurs études cliniques, chirurgicales et d’analyse du mouvement. Pour mener ce travail, nous avons tout d’abord défini l’hyperlaxité telle qu’elle est actuellement décrite dans la littérature, ainsi que ses liens avec l’instabilité de l’épaule et son traitement. Ce premier chapitre décrit également les moyens techniques d’analyse du mouvement qui seront utilisés dans cette thèse. Ensuite, plusieurs études ont été proposées. L’étude 2 est une étude chirurgicale, qui a cherché à corréler la laxité capsulaire étudiée en per opératoire et l’hyperlaxité clinique. L’étude 3 a ensuite rechercher les moyens de rendre plus reproductible la mesure de la rotation externe dans le cadre de l’hyperlaxité. Les études 4 et 5 sont des études utilisant l’analyse du mouvement. La première a cherché à fiabiliser la mesure clinique des amplitudes articulaires de l’épaule en tentant d’analyser les facteurs d’erreur de mesure. La deuxième étude a ensuite eut pour but de définir le volume articulaire global du complexe articulaire de l’épaule et de préciser la relation de ce volume avec les différents degrés de liberté de l’épaule. Une dernière étude (Etude 6) a enfin permis de corréler le volume articulaire de l’épaule et les signes cliniques d’hyperlaxité. Enfin, le chapitre « conclusions générales et perspectives » rassemble les éléments de conclusion de ces différents travaux et a pour ambition de redéfinir le diagnostic d’hyperlaxité de l’épaule. Ce chapitre ouvre plusieurs perspectives. La première est de proposer des modifications de l’examen clinique de l’épaule et notamment pour le diagnostic d’hyperlaxité. La seconde est d’utiliser la description volumétrique de l’épaule dans d’autres situations physiologiques ou pathologiques. Enfin, nous rapportons les résultats préliminaires d’une étude anatomique visant à identifier la place respective de chaque articulation dans cette définition volumétrique des amplitudes articulaires de l’épaule. / The aim of this study was to give a new definition to shoulder hyperlaxity. This work was conduced with clinical, surgical andmotion capture experimentations. We first gave a definition of hyperlaxity, as described actually in the literature, and its link with shoulder instability and treatment. Chapter 1 described also motion capture technics used along this work. Then, several studies were proposed. Study n°2 was a surgical one, and tempted to correlate peroperative capsular laxity and hyperlaxity. Therafter, study n°3 looked for an optimized way to examine external rotation of the shoulder. Studies N° 4 and 5 used motion capture analysis to assess clinical shoulder examination patterns and global reachable shoulder space volume. This volume was finally correlated to shoulder sign of hyperlaxity in study n°6. The last chapter, « general conclusions and perspectives » gather together conclusions of each study and redefine hyperlaxity. Finally, we report our prospect, giving first results of an anatomical study exploring the volumetric definition of shoulder range of motion described previously

La maladie de Charcot-Marie-Tooth liée à l'X (CMTX), deuxième cause, en fréquence, de neuropathies héréditaire, est due à des mutations dans le gène Gjb1 codant pour la connexine 32. Afin de les utiliser comme modèle pré clinique, nous avons créé 5 lignées de souris transgéniques, ayant intégré un BAC humain portant une mutation observée dans plusieurs familles indépendantes. L'exploration de ces modèles a montré que la connexine 32 (Cx32) est impliquée dans le contrôle de la stabilité mitotique. Nous avons ensuite montré que cette instabilité implique l'activité des CaMKII et, peut être, de la kinase Pim1. Cette instabilité est corrigée par des inhibiteurs des CaMKII (KN62 et KN93). Nous avons retrouvé le même phénomène dans des cellules de malades CMTX. Nous avons également pu montrer que les animaux transgéniques montrent des anomalies du comportement locomoteur, corrigées par un traitement par des inhibiteurs de CaMKII. Finalement, nous proposons des pistes pour améliorer ces molécules, en synthétisant des analogues de KN93 / X-linked Charcot -Marie -Tooth (CMTX) disease, the second cause, in frequency, of hereditary neuropathies, is caused by mutations in the gene GJB1 encoding connexin 32. As a preclinical model, we created five lines of transgenic mice, which have integrated a human BAC contain mutation observed in several independent families. The exploration of models showed that the connexin 32 (Cx32) is involved in the control of mitotic stability. We then showed that this instability involves the activity of CaMKII and, perhaps, kinase Pim1. This instability is corrected by inhibitors of CaMKII (KN62 and KN93). We found the same phenomenon occuring in cells of CMTX patients. We also showed that transgenic animals show abnormal locomotor behavior corrected by treatment with inhibitors of CaMKII. Finally, we propose strategies to improve efficiency of these molecules by synthesizing analogues of KN93