Patients with Alzheimer's disease (AD) often have a family history of the disease, implicating genetics as a major risk factor. Three genes are currently known to cause familial early-onset AD (<65 years): the amyloid precursor protein (APP) and the presenilins (PSEN1 and PSEN2). For the much more common late-onset disease (>65 years), only the APOE gene has repeatedly been associated to AD, where the ε4 allele increases disease risk and decreases age at onset. As APOE ε4 only explains part of the total estimated disease risk, more genes are expected to contribute to AD. This thesis has focused on the study of genetic risk factors involved in AD. In the first study, we conducted a linkage analysis of six chromosomes previously implicated in AD in a collection of affected relative pairs from Sweden, the UK and the USA. An earlier described linkage peak on chromosome 10q21 could not be replicated in the current sample, while significant linkage was demonstrated to chromosome 19q13 where the APOE gene is located. The linkage to 19q13 was further analyzed in the second study, demonstrating no significant evidence of genes other than APOE contributing to this peak. In the third study, the prevalence of APP duplications, a recently reported cause of early-onset AD, was investigated. No APP duplications were identified in 141 Swedish and Finnish early-onset AD patients, implying that this is not a common disease mechanism in the Scandinavian population. In the fourth study, genes with altered mRNA levels in the brain of a transgenic AD mouse model (tgAPP-ArcSwe) were identified using microarray analysis. Differentially expressed genes were further analyzed in AD brain. Two genes from the Wnt signaling pathway, TCF7L2 and MYC, had significantly increased mRNA levels in both transgenic mice and in AD brains, implicating cell differentiation and possibly neurogenesis in AD.

This thesis deals with the phylogeny of the lichen genus Usnea (Parmeliaceae, Ascomycetes). The relationships and the morphological variation among Usnea species has been studied, as well as the relationship of Usnea to allied genera. Two species, U. florida and U. subfloridana, which earlier were regarded to form two separate species have been synonymized. In an analysis based on sequence data these two taxa formed a monophyletic group of intermixed specimens. Usnea florida and U. subfloridana have earlier been regarded to form a species pair, but the species pairs concept cannot be applied in this case. The morphological characters traditionally used for species recognition of a number of European Usnea species have been analyzed regarding their reliability. The evolution and distribution of the morphological characters was studied in relation to a phylogeny based on sequence data. Most characters proved to be homoplastic in relation to the phylogeny. Few characters were consistent in a clade, and the same character could be inconsistent in another clade. Therefore a combination of several characters is recommended for species recognition. The relationship of Neuropogon to Usnea was investigated based on sequence data. Neuropogon showed to be closely related to Usnea subg. Usnea. The subgenera Eumitria and Dolichousnea formed the sister group to the clade comprising subg. Usnea and Neuropogon. Usnea is paraphyletic in this investigation. Eumitria is treated as a genus and the subgenus Dolichousnea is elevated to generic rank. The position of Usnea, Neuropogon, Eumitria, and Dolichousnea in the family Parmeliaceae was investigated based on a phylogeny obtained by sequence data. Protousnea probably forms the sister group to the clade of Usnea, Neuropogon, Eumitria, and Dolichousnea. Several monophyletic groups in the family Parmeliaceae were identified.

Recognizing generic objects by single or multi view range images is a contemporary popular problem in 3D object recognition area with developing technology of scanning devices such as laser range scanners. This problem is vital to current and future vision systems performing shape based matching and classification of the objects in an arbitrary scene. Despite improvements on scanners, there are still imperfections on range scans such as holes or unconnected parts on images. This studyobjects at proposing and comparing algorithms that match a range image to complete 3D models in a target database.The study started with a baseline algorithm which usesstatistical representation of 3D shapesbased on 4D geometricfeatures, namely SURFLET-Pair relations.The feature describes the geometrical relationof a surface-point pair and reflects local and the global characteristics of the object. With the desire of generating solution to the problem,another algorithmthat interpretsSURFLET-Pairslike in the baseline algorithm, in which histograms of the features are used,isconsidered. Moreover, two other methods are proposed by applying 2D space filing curves on range images and applying 4D space filling curves on histograms of SURFLET-Pairs. Wavelet transforms are used for filtering purposes in these algorithms. These methods are tried to be compact, robust, independent on a global coordinate frame and descriptive enough to be distinguish queries&rsquo / categories.Baseline and proposed algorithms are implemented on a database in which range scans of real objects with imperfections are queries while generic 3D objects from various different categories are target dataset.

Single particle electron cryomicroscopy (cryo-EM) is a method of structure determination that uses many randomly oriented images of the specimen to construct a three-dimensional density map. In this thesis, single particle cryo-EM has been used to determine the structure of intact adenosine triphosphate (ATP) synthase from bovine heart mitochondria, an approximately 550 kDa membrane protein complex. In respiring organisms, ATP synthase is responsible for synthesizing the majority of ATP, a molecule that serves as an energy source for many cellular reactions. In order to understand the mechanism of ATP synthase, knowledge of the arrangement of subunits in the intact complex is necessary. To obtain maps of intact ATP synthase showing internal density distributions by single particle cryo-EM, methodological improvements to image acquisition, map refinement, and data selection were developed. Further, a novel segmentation algorithm was developed to aid in interpretation of maps. The use of these tools allowed for construction and interpretation of two maps of ATP synthase, solubilized in different membrane mimetics, in which the arrangement of subunits could be identified. These maps revealed interactions within the complex important for its function. In addition, evidence was obtained for curvature of membrane mimetics around ATP synthase, suggesting a role for the complex in maintenance of mitochondrial membrane morphology.

Single particle electron cryomicroscopy (cryo-EM) is a method of structure determination that uses many randomly oriented images of the specimen to construct a three-dimensional density map. In this thesis, single particle cryo-EM has been used to determine the structure of intact adenosine triphosphate (ATP) synthase from bovine heart mitochondria, an approximately 550 kDa membrane protein complex. In respiring organisms, ATP synthase is responsible for synthesizing the majority of ATP, a molecule that serves as an energy source for many cellular reactions. In order to understand the mechanism of ATP synthase, knowledge of the arrangement of subunits in the intact complex is necessary. To obtain maps of intact ATP synthase showing internal density distributions by single particle cryo-EM, methodological improvements to image acquisition, map refinement, and data selection were developed. Further, a novel segmentation algorithm was developed to aid in interpretation of maps. The use of these tools allowed for construction and interpretation of two maps of ATP synthase, solubilized in different membrane mimetics, in which the arrangement of subunits could be identified. These maps revealed interactions within the complex important for its function. In addition, evidence was obtained for curvature of membrane mimetics around ATP synthase, suggesting a role for the complex in maintenance of mitochondrial membrane morphology.

Ce mémoire s'intéresse au problème du resquilleur dans la contribution privée à un bien collectif. Particulièrement, il mesure l'effet de réunions d'information sur les contributions ultérieures des participants qui sont invités de façon aléatoire parmi 1 487 membres d'une organisation qui construit un barrage au Kenya en mode coopératif. Ensuite, il s'intéresse aux effets des pairs : la contribution d'un membre incite les autres membres à contribuer différemment, selon que le contributeur soit dans un groupe de contributeurs ayant fortement contribué dans le passé ou pas. Cette expérience à assignation aléatoire en données panel est la première qui mesure les effets des pairs hors laboratoire et sur une longue période de 5 mois pour un projet indivisible. L'effet total des réunions et des pairs est difficile à estimer, entre autres parce que son effet persiste dans le temps après la période de l'expérience, mais les quelques schillings supplémentaires (quelques sous) par individu qu'il a été possible de mesurer dans le cadre rigoureux de l'expérience suffisent à justifier l'exercice, apportant un financement supplémentaire non négligeable à l'organisation. ______________________________________________________________________________

Illuminated metal nanoparticles (MNPs) feature collective electron oscillations (so-called localized surface plasmons or LSPs) which facilitate concentrating light-matter interactions to length scales below the diffraction limit. Part I of this book describes two applications of this confinement effect. Firstly, the use of single particles as optically active probes for scanning near-field optical microscopy is demonstrated. Secondly, fluorescence enhancement in the vicinity of a single MNP is described theoretically. This description focuses on how the particle diameter and the surrounding medium influence the enhancement. It turned out that in these two examples the optical signal levels can be improved by manipulating the spectral LSP resonance position of the particles. This finding triggered the search for a method allowing optical particle tuning. Part II of this thesis describes an approach which allows such a spectral LSP manipulation on the single-particle level. The method makes use of the optically induced reduction of metal salt complexes in solution, which leads to the deposition of thin layers of elemental metal onto single, intentionally addressed particles. The deposition process is monitored by optical LSP analysis, and thus the tuning of the optical particle properties is controlled in situ. With this technique, a manipulation of both the size and the shape of single nanoparticles was achieved. Initial experiences were gained by manipulating spherical and ellipsoidal gold particles, for which a red- and a blueshift of the LSP resonance was observed, respectively. The insights obtained from these experiments were then applied to tune the interparticle separation in nanoparticle pairs, i.e., to tune the resonance wavelength of these plasmonic nanoresonators. Subsequently, single resonators were used to reshape the fluorescence emission spectrum of organic molecules. Besides size and shape, also material parameters such as the surface roughness and the surface material composition influence the optical properties of MNPs. Both aspects are addressed using the example of rough platinum spheres and demonstrating the fabrication of bimetallic core-shell particles. As the material compositon of particles not only influences their optical, but for example also their catalytic or magnetic properties, photochemical metal deposition with in-situ optical LSP read-out builds a bridge to other fields of nanoscience. The presented method is a versatile tool for the fabrication and manipulation of nanostructures, and it is not limited to the field of plasmonics. / Metallische Nanopartikel (MNP) weisen unter Beleuchtung kollektive Schwingungen des Elektronengases auf (sogenannte lokalisierte Oberflächenplasmonen oder LOP). Die dadurch entstehende elektromagnetische Feldverteilung um die Partikel erlaubt die Konzentration von Licht-Materie-Wechselwirkungen auf einen Größenbereich unterhalb des Beugungslimits. In Teil I des vorliegenden Buches werden zwei Anwendungen dieses Konzentrationseffekts beschrieben. Zum einen wird die Verwendung eines einzelnen Partikels als Rastersonde für die optische Nahfeldmikroskopie gezeigt. Zum anderen wird die Fluoreszenzverstärkung in der unmittelbaren Umgebung eines Partikels untersucht. In letzterem Fall liegt der Fokus auf dem Einfluss der Partikelgröße und des Umgebungsmediums auf den Verstärkungsfaktor. Beide Untersuchungen zeigten, dass die Stärke der auftretenden optischen Signale von einer gezielten Steuerung der LOPResonanz profitieren kann. Diese Erkenntnis führte zur Entwicklung einer Methode, welche eine solche spektrale LOP-Steuerung erlaubt. Mit der in Teil II beschriebenen photochemischen Abscheidung von Metall auf einzelne Partikel wurde ein geeigneter Ansatz gefunden. Dabei wird die optisch induzierte Reduktion von Metallsalzkomplexen in einer Lösung ausgenutzt, um dünne Metallschichten auf gezielt ausgewählte Partikel aufzubringen. Der Abscheidungsprozess wird optisch über die Änderung der LOP-Resonanz des belichteten Partikels überwacht. Somit können dessen optische Eigenschaften gezielt in situ eingestellt werden. Mit der beschriebenen Technik können die Größe und die Form einzelner metallischer Partikel beeinflusst werden, was sich in einer Rot- bzw. Blauverschiebung der LOPResonanz äußert. Dieses Prinzip konnte zuerst an sphärischen und ellipsoidalen Goldpartikeln gezeigt werden. Die gewonnen Erkenntnisse wurden dann auf die gezielte Einstellung des Teilchenabstandes in Partikelpaaren übertragen, d. h., die Resonanzwellenlänge solcher plasmonischer Nanoresonatoren wurde gezielt manipuliert. Die Resonatoren konnten in einem zweiten Schritt zur Steuerung des Fluoreszenzspektrums organischer Moleküle eingesetzt werden. Neben Größe und Form spielen auch Materialparameter wie die Oberflächenrauigkeit und das Oberflächenmaterial eine wichtige Rolle für die optischen Eigenschaften der Partikel. Diese Parameter wurden am Beispiel von rauen Platinpartikeln sowie an bimetallischen Kern-Schale-Partikeln untersucht. Da das Oberflächenmaterial nicht nur die optischen, sondern z. B. auch katalytischen und magnetischen Eigenschaften der Partikel beeinflusst, verbindet die vorgestellte Methode die Plasmonik mit vielen anderen Bereichen der Nanotechnologie. Sie stellt eine vielseitige Technik zur Herstellung und Manipulation von Nanostrukturen dar, ohne dabei auf die Nanooptik limitiert zu sein.

Le travail présenté s'inscrit dans le champ de l'analyse des interactions verbales en contexte didactique. Il prend pour objet une situation d'apprentissage et d'interaction spécifique : la rédaction collective d'un texte narratif par des apprenants de français langue étrangère travaillant en dyade, avec un même ordinateur, en contexte d'enseignement-apprentissage formel.<br />Le principal ancrage théorique de ce travail se situe en pragmatique linguistique interactionniste mais il s'articule également aux recherches interactionnistes en acquisition d'une langue étrangère. <br />L'étude est empirique et principalement descriptive. Grâce à une approche qualitative et inductive, il s'agit de contribuer à une meilleure compréhension des modalités de collaboration entre pairs en langue cible. L'analyse met en relation ces modalités de collaboration avec la mobilisation par les sujets alloglottes de leur compétence interactionnelle, ainsi qu'avec leur capacité à gérer interactivement les problèmes linguistiques. En outre, il s'agit de s'interroger sur les effets potentiels de l'outil informatique sur les interactions décrites. A cette fin, deux types d'activités constitutives de la tâche sont examinées : les activités d'élaboration de contenu, au cours desquelles les apprenants négocient des contenus en lien avec l'univers fictionnel du texte à construire, et les activités métalinguistiques, au cours desquelles ils traitent les problèmes linguistiques rencontrés. <br />La catégorisation, la description et l'analyse des différentes modalités d'accomplissement de ces activités aboutissent à la mise en évidence d'indicateurs du degré de collaboration (conduites, indices énonciatifs et interactionnels, gestion des asymétries, profil interactionnel des sujets) et à une caractérisation des profils des dyades observées. L'analyse de la coordination entre actions verbales et actions non verbales montre que si le travail sur ordinateur semble favoriser l'engagement des sujets dans la tâche, il ne favorise pas nécessairement l'orientation des apprenants vers le processus interactionnel, et vers la négociation.

Thèse d'exercice : Médecine. Médecine générale : Paris 12 : 2004. / Titre provenant de l'écran-titre. Bibliogr.

BABAR is a particle physics experiment at the Stanford Linear Accelerator Center (SLAC). The purpose of BABAR is to study matter-antimatter asymmetry in the bottom quark system. At SLAC, electons and positrons collide, which annihilate and decay into a variety of daughters. An Upsilon(4S) meson is one of the possible daughters. An Upsilon(4S) decays into a B meson and an anti-B meson more than 96% of the time. A B meson has an anti-bottom quark and an anti-B meson has a bottom quark. The purpose of this thesis is to measure how many Upsilon(1S) originated from Upsilon(4S) in the entire BABAR data set. This thesis compares on-peak data and off-peak data. On-peak data was taken at center of mass energy 10.58GeV. One of the possible interactions is e+e− -> Upsilon(4S) since the mass of Upsilon(4S) is 10.58GeV/c^2. On-peak data, taken at center of mass energy 10.54GeV, is not enough to have any BB pairs because 10.54GeV is less than the mass of an Upsilon(4S). This thesis can be useful for BABAR physicist because it helps set an upper limit on how many BB pairs there are in the entire BABAR data set. In other words, it sets an upper limit on how much more than 96% does Upsilon(4S) decay to BB. Measurement of the decay of Upsilon(4S) -> Upsilon(1S) + X give evidence for non-BB decays of the Upsilon(4S). The final results of this study show that there were (110 +- 3) × 10^5 Upsilon(1S) on-peak, of which (10 +- 9) × 10^5 originated from an Upsilon(4S). Increasing the centre of mass energy from 10.54GeV to 10.58GeV increases the Upsilon(1S) production by (10 +- 8)%.