Telomere maintenance is one of the mechanisms ensuring indefinite divisions of cancer and stem cells. Good understanding of telomere maintenance mechanisms (TMM) is important for studying cancers and designing therapies. However, molecular factors triggering selective activation of either the telomerase dependent (TEL) or the alternative lengthening of telomeres (ALT) pathway are poorly understood. In addition, more accurate and easy-to-use methodologies are required for TMM phenotyping. In this study, we have performed literature based reconstruction of signaling pathways for the ALT and TEL TMMs. Gene expression data were used for computational assessment of TMM pathway activities and compared with experimental assays for TEL and ALT. Explicit consideration of pathway topology makes bioinformatics analysis more informative compared to computational methods based on simple summary measures of gene expression. Application to healthy human tissues showed high ALT and TEL pathway activities in testis, and identified genes and pathways that may trigger TMM activation. Our approach offers a novel option for systematic investigation of TMM activation patterns across cancers and healthy tissues for dissecting pathway-based molecular markers with diagnostic impact.

A distração osteogênica tem sido extensamente empregada na correção da grave hipoplasia do terço médio da face de portadores de craniossinostose sindrômica. Contudo, poucos estudos têm apresentado os resultados da distração do terço médio da face através de avaliação cefalométrica. O objetivo do presente estudo foi o de avaliar os resultados obtidos com o avanço ósseo do terço médio da face após osteotomia tipo Le Fort III ou frontofacial em monobloco seguida da utilização de dispositivo rígido externo de distração (RED), em portadores de craniossinostose sindrômica, em termos de quantidade de alongamento ósseo, estabilidade esquelética e crescimento facial. Onze pacientes submetidos aos procedimentos de distração, de fevereiro de 2002 a janeiro de 2006, na unidade de cirurgia plástica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, foram avaliados retrospectivamente. Seis pacientes eram portadores da síndrome de Crouzon, quatro da síndrome de Apert, e um da síndrome de Saethre-Chotzen. Onze pacientes foram submetidos ao procedimento de alongamento ósseo do terço médio da face através do uso de dispositivo externo rígido (RED), após osteotomias tipo Le Fort III (N = 4) ou frontofacial monobloco (N = 7). Foram avaliadas retrospectivamente três telerradiografias de face em norma lateral de cada paciente (T1- préoperatório; T2 - pós-operatório recente, logo após a remoção do distrator; T3 - pós-operatório tardio, obtida com um intervalo mínimo de 12 meses após cirurgia). Três cefalogramas foram obtidos de cada paciente, através da direta sobreposição das três telerradiografias, tomado como referência reparos anatômicos do crânio e da porção anterior da fossa craniana. Desta forma, os três traçados cefalométricos foram obtidos no mesmo papel acetato, o qual foi digitalizado. Utilizando o programa de computação gráfica de domínio público Image J, várias mensurações foram realizadas com a intenção de determinar a extensão do avanço sofrido pelos segmentos ósseos na direção do vetor do movimento esquelético, assim como de seus componentes horizontal e vertical, tomando como referência pontos A e orbitário. Pacientes foram ainda divididos em dois grupos (G 1 - pacientes submetidos à osteotomia tipo Le Fort III; G 2 - pacientes submetidos à osteotomia frontofacial em monobloco), e os dados obtidos a partir mensurações de ambos os grupos foram comparados. Avanço significativo do terço médio da face foi obtido com os procedimentos. O componente horizontal do movimento esquelético predominou ao componente vertical. A taxa de reposicionamento posterior horizontal tardio (perda de resultado) foi mínima. Quando comparados os dois procedimentos, foi observada uma diferença significativa entre os grupos Le Fort III e monobloco. A quantidade de avanço obtido foi maior no grupo monobloco que no grupo Le Fort III. Em termos perda de resultado, o grupo Le Fort III foi mais estável que o grupo monobloco. Foi observada uma evidente alteração vertical no posicionamento dos pontos de referência no pós-operatório tardio, se comparado ao pós-operatório recente, evidenciando crescimento na vertical da face, ao contrário do que ocorre na direção horizontal, onde existiu um pequeno reposicionamento posterior e nenhuma evidência de crescimento. / Distraction osteogenesis has been applied extensively to correct the severe midface hipoplasia in syndromic craniosynostosis patients. However few studies have reported midface distraction outcomes through cephalometric evaluation. The purpose of the present study was to evaluate outcomes with midface distraction after Le Fort III and frontofacial monobloc osteotomy using a rigid external device (RED) in patients with syndromic craniosynostosis, in terms of quantity of bone lengthening, skeletal stability and facial growth. Eleven patients underwent to midface distraction from February of 2002 to January of 2006 at the plastic surgery unit of The \'Hospital das Clínicas\' of the Medical School of The University of São Paulo were retrospectively evaluated. Six patients had Crouzon, four had Apert, and one had Saethre-Chotzen syndrome. The patients were submit to bone lengthening procedure of the midface using a rigid external device (RED) after osteotomy type Le Fort III (n=4) and frontofacial monobloc osteotomy (n=7). Three teleradiography were retrospectively evaluated of each patient (T1 - before surgery; T2- after surgery, rigth after distractor removal; T3 - after surgery, obtained with a minimal interval of 12 months after surgery). The three lateral cephalograms were obtained from each patient by direct teleradiography superimposition taken as references the anatomic repairs in the cranium and anterior skull base. This way the three cephalometric tracings were obtained in the same acetate paper which was digitalized. Utilizing a public domain program Image J, various mensurations were accomplished with intension of determine the extent of advancement suffered by the bone segments in the direction of vector skeletal movement and its horizontal and vertical components as well, as taken as references point A and orbitale. Patients still were divided between two groups (G 1- patients submitted to an osteotomy type Le Fort III; G 2- patients submitted to monobloc frontofacial osteotomy), and the data obtained from mensurations from both groups were compared. Significant midface advancement was achieved with the procedures. The horizontal component of the movement was predominant if compared to vertical. The rate of horizontal relapse was minimal. When compared the two procedures was noted a significant difference between Le Fort III and monobloc groups. The advancement rate was greater in monobloc than Le Fort III group. In terms of relapse Le Fort III group was more stable than monobloc group. In vertical direction was noted an evident altered position of the reference points at late postoperative period if compared with recent postoperative period given evidence of facial vertical direction growth, contrary from what occurred in horizontal direction where existed a small relapse and no growth.

Ce travail a trois objectifs principaux. Tout d’abord, contribuer à l’étude du système rythmique des langues et des variétés dialectales à travers l’analyse du rythme de l’anglais parlé au pays de Galles et de la langue galloise en utilisant comme point de comparaison l’anglais dit standard. Puis, démontrer qu’il existe un allongement final bien plus marqué en gallois et en anglais gallois (bilingues & monolingues) qu’en anglais standard. Et enfin, prouver que les résultats obtenus lors de cette étude sont étroitement liés à l’influence majoritaire de la langue galloise sur celle des autres variétés d’anglais présentes dans ce pays. Dans cette optique, nous avons, dans un premier temps, élargi la base de données Eurom I et nous avons ensuite mené différents tests de perception et études statistiques. Il en ressort que la langue galloise est effectivement le substrat principal de l’anglais parlé au pays de Galles, que ce soit chez les gallois bilingues ou monolingues (personnes résidant au pays de Galles ne parlant qu’anglais). En effet, la longueur de l’allongement en syllabe finale inaccentuée va en décroissant du gallois à l’anglais standard. Cependant, étant donné l’impossibilité de catégoriser de façon précise le rythme du gallois et de l’anglais gallois en tenant compte de tous les paramètres métriques, il est plus difficile d’affirmer de façon catégorique que la langue galloise joue un rôle prépondérant sur ces derniers. / This thesis has three main objectives. First of all, to contribute to the study of the rhythmical system of languages and dialectal varieties through the analysis of rhythms in Welsh English and Welsh, using Standard English as a focal comparative element; then, to demonstrate that the final lengthening is much more notable in Welsh and in Welsh English (bilinguals and monolinguals) than in standard English; finally, to prove that this study’s results are tightly intertwined with the influence of the Welsh language, which is greater than that other English accents present in this country. For that purpose, we have first widened the Eurom 1 database and then carried out various perception tests and statistical analysis. The results show that the Welsh language is the substratum of the English spoken in Wales, as much for bilinguals as for monolinguals (residents of the country speaking only English). Indeed, the length of the final unstressed syllable decreases from Welsh to Standard English. However, as it is impossible to classify with precision the rhythm of Welsh and Welsh English taking into account all the metrics, it is more difficult to establish with certainty whether the Welsh language has a major influence on the latter.

A distração osteogênica tem sido extensamente empregada na correção da grave hipoplasia do terço médio da face de portadores de craniossinostose sindrômica. Contudo, poucos estudos têm apresentado os resultados da distração do terço médio da face através de avaliação cefalométrica. O objetivo do presente estudo foi o de avaliar os resultados obtidos com o avanço ósseo do terço médio da face após osteotomia tipo Le Fort III ou frontofacial em monobloco seguida da utilização de dispositivo rígido externo de distração (RED), em portadores de craniossinostose sindrômica, em termos de quantidade de alongamento ósseo, estabilidade esquelética e crescimento facial. Onze pacientes submetidos aos procedimentos de distração, de fevereiro de 2002 a janeiro de 2006, na unidade de cirurgia plástica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, foram avaliados retrospectivamente. Seis pacientes eram portadores da síndrome de Crouzon, quatro da síndrome de Apert, e um da síndrome de Saethre-Chotzen. Onze pacientes foram submetidos ao procedimento de alongamento ósseo do terço médio da face através do uso de dispositivo externo rígido (RED), após osteotomias tipo Le Fort III (N = 4) ou frontofacial monobloco (N = 7). Foram avaliadas retrospectivamente três telerradiografias de face em norma lateral de cada paciente (T1- préoperatório; T2 - pós-operatório recente, logo após a remoção do distrator; T3 - pós-operatório tardio, obtida com um intervalo mínimo de 12 meses após cirurgia). Três cefalogramas foram obtidos de cada paciente, através da direta sobreposição das três telerradiografias, tomado como referência reparos anatômicos do crânio e da porção anterior da fossa craniana. Desta forma, os três traçados cefalométricos foram obtidos no mesmo papel acetato, o qual foi digitalizado. Utilizando o programa de computação gráfica de domínio público Image J, várias mensurações foram realizadas com a intenção de determinar a extensão do avanço sofrido pelos segmentos ósseos na direção do vetor do movimento esquelético, assim como de seus componentes horizontal e vertical, tomando como referência pontos A e orbitário. Pacientes foram ainda divididos em dois grupos (G 1 - pacientes submetidos à osteotomia tipo Le Fort III; G 2 - pacientes submetidos à osteotomia frontofacial em monobloco), e os dados obtidos a partir mensurações de ambos os grupos foram comparados. Avanço significativo do terço médio da face foi obtido com os procedimentos. O componente horizontal do movimento esquelético predominou ao componente vertical. A taxa de reposicionamento posterior horizontal tardio (perda de resultado) foi mínima. Quando comparados os dois procedimentos, foi observada uma diferença significativa entre os grupos Le Fort III e monobloco. A quantidade de avanço obtido foi maior no grupo monobloco que no grupo Le Fort III. Em termos perda de resultado, o grupo Le Fort III foi mais estável que o grupo monobloco. Foi observada uma evidente alteração vertical no posicionamento dos pontos de referência no pós-operatório tardio, se comparado ao pós-operatório recente, evidenciando crescimento na vertical da face, ao contrário do que ocorre na direção horizontal, onde existiu um pequeno reposicionamento posterior e nenhuma evidência de crescimento. / Distraction osteogenesis has been applied extensively to correct the severe midface hipoplasia in syndromic craniosynostosis patients. However few studies have reported midface distraction outcomes through cephalometric evaluation. The purpose of the present study was to evaluate outcomes with midface distraction after Le Fort III and frontofacial monobloc osteotomy using a rigid external device (RED) in patients with syndromic craniosynostosis, in terms of quantity of bone lengthening, skeletal stability and facial growth. Eleven patients underwent to midface distraction from February of 2002 to January of 2006 at the plastic surgery unit of The \'Hospital das Clínicas\' of the Medical School of The University of São Paulo were retrospectively evaluated. Six patients had Crouzon, four had Apert, and one had Saethre-Chotzen syndrome. The patients were submit to bone lengthening procedure of the midface using a rigid external device (RED) after osteotomy type Le Fort III (n=4) and frontofacial monobloc osteotomy (n=7). Three teleradiography were retrospectively evaluated of each patient (T1 - before surgery; T2- after surgery, rigth after distractor removal; T3 - after surgery, obtained with a minimal interval of 12 months after surgery). The three lateral cephalograms were obtained from each patient by direct teleradiography superimposition taken as references the anatomic repairs in the cranium and anterior skull base. This way the three cephalometric tracings were obtained in the same acetate paper which was digitalized. Utilizing a public domain program Image J, various mensurations were accomplished with intension of determine the extent of advancement suffered by the bone segments in the direction of vector skeletal movement and its horizontal and vertical components as well, as taken as references point A and orbitale. Patients still were divided between two groups (G 1- patients submitted to an osteotomy type Le Fort III; G 2- patients submitted to monobloc frontofacial osteotomy), and the data obtained from mensurations from both groups were compared. Significant midface advancement was achieved with the procedures. The horizontal component of the movement was predominant if compared to vertical. The rate of horizontal relapse was minimal. When compared the two procedures was noted a significant difference between Le Fort III and monobloc groups. The advancement rate was greater in monobloc than Le Fort III group. In terms of relapse Le Fort III group was more stable than monobloc group. In vertical direction was noted an evident altered position of the reference points at late postoperative period if compared with recent postoperative period given evidence of facial vertical direction growth, contrary from what occurred in horizontal direction where existed a small relapse and no growth.

Les cellules souches de gliomes (CSG), une sous-population de cellules tumorales, seraient en partie responsables de l’échec des traitements des gliomes de par leur résistance et leur capacité régénérative. Le mécanisme alternatif (ALT) de maintenance des télomères, basé sur la recombinaison homologue et non pas sur la télomérase, est détecté dans environ 30% des gliomes humains suggérant que des stratégies thérapeutiques spécifiquement dirigées contre ALT pourraient avoir un intérêt thérapeutique. Dans ce travail, nous avons poursuivi la caractérisation du premier exemple de CSG humaines ayant un phénotype ALT, les cellules TG20. Nous avons montré que malgré leur très fort taux de recombinaison, les télomères de ces cellules continuaient à assurer leur fonction de protection des chromosomes. Nous avons vérifié que les cellules TG20 conservaient leur capacité à générer des tumeurs intracérébrales après des transplantations sériées chez les souris immunodéprimées tout en gardant un phénotype ALT. Ces résultats confirment à la fois les propriétés de cellules souches cancéreuses des cellules TG20 et la capacité de ALT à assurer la maintenance des télomères nécessaire à l’autorenouvellement et au fort taux de prolifération des CSG in vivo. La greffe intracérébrale de cellules TG20 chez des souris immunodéprimées représente donc un bon modèle d’étude préclinique des gliomes ALT. Nous avons ainsi montré qu’un traitement précoce par un ligand des G-quadruplexes télomériques, 360B, juste après la greffe de cellules TG20, était capable d’inhiber le développement tumoral suggérant l’intérêt de l’utilisation de ligands des G-quadruplexes pour cibler spécifiquement les CSG ALT. Une étude des profils d'expression transcriptomique des cellules TG20 et de plusieurs lignées de CSG humaines exprimant la télomérase, nous a conduit à nous intéresser aux rôles de deux lysine acétyl transférases homologues, PCAF (P300/CBP Associated Factor) et GCN5 (General Control Nonderepressible 5) dans la régulation de la recombinaison télomérique des cellules ALT. Nous avons montré que les inhibitions de ces deux protéines ont des effets opposés sur le mécanisme ALT. Nous proposons qu’une balance d’expression de PCAF et GCN5 régule la maintenance des télomères dans les cellules ALT via le contrôle du turnover de TRF1 ce qui pourrait constituer la base d’une nouvelle stratégie thérapeutique vis-à-vis des gliomes ayant un phénotype ALT. / Glioma stem cells (GSC), a subpopulation of tumor cells, are partly responsible for the failure of treatment of gliomas because of their resistance and regenerative capacity. The mechanism of alternative lengthening of telomere (ALT), based on homologous recombination, is detected in approximately 30 % of human gliomas. Therefore, therapeutic strategies directed specifically against ALT may have a therapeutic value. In this work, we further characterized the first model of human ALT GSC, the TG20 cells. We showed that despite their very high rate of recombination, the telomeres were still capable of fulfilling their protective function of chromosomes. We verified that the TG20 cells retained their ability to generate intracerebral tumors after serial transplantations in immunocompromised mice, while preserving an ALT phenotype. These results confirm the cancer stem properties of TG20 cells and the ability of ALT to ensure telomeres maintenance, which is required for the self-renewal and the high proliferation rate of GSC in vivo. Intracerebral grafts of TG20 cells in immunocompromised mice represent thus a good preclinical model for studying ALT gliomas. We have shown that treatment with a ligand of telomeric G-quadruplexes, the 360B, at an early stage of TG20 tumor engraftment, was able to inhibit tumor growth, showing the interest of the use of G-quadruplex ligands to specifically target ALT GSC. Transcriptomic profiling of TG20 cells and several other GSC telomerase-positive lines, incited us to study the roles of two homologous lysine acetyl transferases, PCAF (p300/CBP Associated Factor) and GCN5 (General Control Nonderepressible 5), in the regulation of telomeric recombination in ALT cells. We showed that the inhibition of these two proteins has opposite effects on the ALT mechanism. We propose that a balance of expression of PCAF and GCN5 regulates the telomere maintenance in ALT cells by controlling the turnover of TRF1. This model could serve for the development of new therapeutic strategies targeting ALT gliomas.

Thesis (DLitt (African Languages))--University of Stellenbosch, 2008. / ENGLISH ABSTRACT: This dissertation is an experimental investigation of vowel duration. It focuses on phonetic and phonological aspects of vowel duration in Civili, and African language spoken in Gabon and some of its neighboring countries. It attempts to bring new insights into the phenomenon of vowel lengthening, and to assess the implictions of these insights for standardizing the orthography of this language. ...

Dans de nombreux comportements qui reposent sur le rappel et la production de séquences, des groupements temporels émergent spontanément, créés par des délais ou des allongements. Ce « chunking » a été observé tant chez les humains que chez certains animaux et plusieurs auteurs l’attribuent à un processus général de chunking perceptif qui est conforme à la capacité de la mémoire à court terme. Cependant, aucune étude n’a établi comment ce chunking perceptif s’applique à la parole. Nous présentons une recension de la littérature qui fait ressortir certains problèmes critiques qui ont nui à la recherche sur cette question. C’est en revoyant ces problèmes qu’on propose une démonstration spécifique du chunking perceptif de la parole et de l’effet de ce processus sur la mémoire immédiate (ou mémoire de travail). Ces deux thèmes de notre thèse sont présentés séparément dans deux articles. Article 1 : The perceptual chunking of speech: a demonstration using ERPs Afin d’observer le chunking de la parole en temps réel, nous avons utilisé un paradigme de potentiels évoqués (PÉ) propice à susciter la Closure Positive Shift (CPS), une composante associée, entre autres, au traitement de marques de groupes prosodiques. Nos stimuli consistaient en des énoncés et des séries de syllabes sans sens comprenant des groupes intonatifs et des marques de groupements temporels qui pouvaient concorder, ou non, avec les marques de groupes intonatifs. Les analyses démontrent que la CPS est suscitée spécifiquement par les allongements marquant la fin des groupes temporels, indépendamment des autres variables. Notons que ces marques d’allongement, qui apparaissent universellement dans la langue parlée, créent le même type de chunking que celui qui émerge lors de l’apprentissage de séquences par des humains et des animaux. Nos résultats appuient donc l’idée que l’auditeur chunk la parole en groupes temporels et que ce chunking perceptif opère de façon similaire avec des comportements verbaux et non verbaux. Par ailleurs, les observations de l’Article 1 remettent en question des études où on associe la CPS au traitement de syntagmes intonatifs sans considérer les effets de marques temporels. Article 2 : Perceptual chunking and its effect on memory in speech processing:ERP and behavioral evidence Nous avons aussi observé comment le chunking perceptif d’énoncés en groupes temporels de différentes tailles influence la mémoire immédiate d’éléments entendus. Afin d’observer ces effets, nous avons utilisé des mesures comportementales et des PÉ, dont la composante N400 qui permettait d’évaluer la qualité de la trace mnésique d’éléments cibles étendus dans des groupes temporels. La modulation de l’amplitude relative de la N400 montre que les cibles présentées dans des groupes de 3 syllabes ont bénéficié d’une meilleure mise en mémoire immédiate que celles présentées dans des groupes plus longs. D’autres mesures comportementales et une analyse de la composante P300 ont aussi permis d’isoler l’effet de la position du groupe temporel (dans l’énoncé) sur les processus de mise en mémoire. Les études ci-dessus sont les premières à démontrer le chunking perceptif de la parole en temps réel et ses effets sur la mémoire immédiate d’éléments entendus. Dans l’ensemble, nos résultats suggèrent qu’un processus général de chunking perceptif favorise la mise en mémoire d’information séquentielle et une interprétation de la parole « chunk par chunk ». / In numerous behaviors involving the learning and production of sequences, temporal groups emerge spontaneously, created by delays or a lengthening of elements. This chunking has been observed across behaviors of both humans and animals and is taken to reflect a general process of perceptual chunking that conforms to capacity limits of short-term memory. Yet, no research has determined how perceptual chunking applies to speech. We provide a literature review that bears out critical problems, which have hampered research on this question. Consideration of these problems motivates a principled demonstration that aims to show how perceptual chunking applies to speech and the effect of this process on immediate memory (or “working memory”). These two themes are presented in separate papers in the format of journal articles. Paper 1: The perceptual chunking of speech: a demonstration using ERPs To observe perceptual chunking on line, we use event-related potentials (ERPs) and refer to the neural component of Closure Positive Shift (CPS), which is known to capture listeners’ responses to marks of prosodic groups. The speech stimuli were utterances and sequences of nonsense syllables, which contained intonation phrases marked by pitch, and both phrase-internal and phrase-final temporal groups marked by lengthening. Analyses of CPSs show that, across conditions, listeners specifically perceive speech in terms of chunks marked by lengthening. These lengthening marks, which appear universally in languages, create the same type of chunking as that which emerges in sequence learning by humans and animals. This finding supports the view that listeners chunk speech in temporal groups and that this perceptual chunking operates similarly for speech and non-verbal behaviors. Moreover, the results question reports that relate CPS to intonation phrasing without considering the effects of temporal marks. Paper 2: Perceptual chunking and its effect on memory in speech processing: ERP and behavioral evidence We examined how the perceptual chunking of utterances in terms of temporal groups of differing size influences immediate memory of heard speech. To weigh these effects, we used behavioural measures and ERPs, especially the N400 component, which served to evaluate the quality of the memory trace for target lexemes heard in the temporal groups. Variations in the amplitude of the N400 showed a better memory trace for lexemes presented in groups of 3 syllables compared to those in groups of 4 syllables. Response times along with P300 components revealed effects of position of the chunk in the utterance. This is the first study to demonstrate the perceptual chunking of speech on-line and its effects on immediate memory of heard elements. Taken together the results suggest that a general perceptual chunking enhances a buffering of sequential information and a processing of speech on a chunk-by-chunk basis.

Im Jahre 1958, schlug Kenneth W. Robinson die Nutzung eines Korrektormagneten vor um den entdämpften radialen Betatronoszillationen im Cambridge electron accelerator entgegen zu wirken. Dieser Korrektormagnet sollte aus kurzen, alternierenden Dipolen mit einem starken Gradienten bestehen, sodass die Verluste durch Synchrotronstrahlung mit zunehmendem Trajektorienradius abnehmen. Diese Transversal-Gradienten-Wiggler werden auch "Robinson Wiggler" (RW) genannt. Die Metrology Light Source (MLS), welche Eigentum der Physikalisch-Technischen Bundesanstalt (PTB) ist und vom Helmholtz-Zentrum Berlin (HZB) entworfen und betrieben wird, ist ein Elektronen-Synchrotron, optimiert für die Produktion von Synchrotronstrahlung im Spektralbereich zwischen THz und EUV. Da die MLS eine gerampte Maschine ist, nimmt der gespeicherte Elektronenstrom mit der Zeit ab und die Strahllebensdauer ist von Bedeutung für die Nutzer der Synchrotronstrahlung. Es wird vorgeschlagen einen RW bei der MLS zu installieren um die Strahllebensdauer zu erhöhen. Mit RW wäre es möglich, Dämpfung aus der longitudinalen in die horizontale Ebene zu verschieben sodass sich die Energiebreite um einen Faktor 3 erhöht und die Emittanz sich um ungefähr einen Faktor 2 reduziert. Die Länge der Elektronenpakete wird dadurch stärker verlängert als die mittlere horizontale Paketbreite reduziert wird. So nimmt die Elektronendichte im Paket ab und die Verlustrate sinkt. Dies hat zu Folge dass sich die Lebensdauer verbessert und die Aktivierung von Komponenten reduziert wird. Mit erhöhter Energiebreite und verringerter Emittanz, wird der Beitrag der Dispersion zur horizontalen Quellgröße stärker. Durch geeignete Wahl der Magnetoptik kann die Brillianz am Quellpunkt erhöht werden bei gleichzeitiger Verbesserung der Lebensdauer. Simulationen zeigen dass die Lebensdauer an der MLS durch die Installation eines solchen RW um einen Faktor 2.3 ansteigt, was einem Zugewinn an integriertem Photonenfluss von 30 % entspricht. / In 1958, Kenneth W. Robinson proposed the usage of a magnetic correction device to reduce the antidamping of radial betatron oscillations in the Cambridge electron accelerator. The essence of this correction device are short, alternating dipoles with a strong gradient, such that the radiation loss decreases with increasing radius of trajectory. These transverse gradient wigglers are also called "Robinson Wigglers" (RW). The Metrology Light Source (MLS), owned by the Physikalisch-Technische Bundesanstalt (PTB) and designed and operated by Helmholtz-Zentrum Berlin (HZB), is an electron synchrotron, optimized for the production of synchrotron radiation in the THz to the EUV spectral region. Being a ramped machine, Top-Up operation is not possible. With a decaying beam current, the lifetime of the stored beam is of importance for the user community, for reasons of temporal stability and integrated photon flux. It is proposed to install a RW at the MLS in order to improve the beam lifetime. With a RW, it is possible to transfer damping from the longitundinal to the horizontal plane in a way, that the energy spread increases by a factor of 3 and the emittance reduces by a factor of 2. Doing so, the bunch length is increased by a larger fraction than the average bunch width is decreased. Thereby the electron density is reduced which results in a lower loss rate of electrons. This improves the beam lifetime and reduces induced radioactivity of accelerator components and shielding. With an increased energy spread and a reduced emittance, the contribution of the dispersion to source size becomes more important. By carefully choosing the magnet optics, the brilliance at the source point can be improved simultaneously to increasing the lifetime. Simulations indicate that a RW is able to increase the lifetime in the standard user operation mode at the MLS by a factor of 2.3, corresponding to an increase in photon flux for one standard user run of approximately 30 %.

Shoulder arthroplasty surgery has shown remarkable progress during the last few decades. A number of factors affect postoperative range of motion, pain and prosthetic durability. Among these factors, the length of the lever arm and joint stability is the ones that can be altered by the selected prosthetic component. It is uncertain how much of the normal anatomy needs to be re-established. Stemless prostheses with total reliance on metaphyseal fixation were introduced in France in 2004 (TESS, Zimmer Biomet). The goals were to avoid stem-related complications. Stemless implants have other potential benefits, including the ability to restore shoulder anatomy. Study I: This is a prospective cohort study of 49 patients with one of two versions of the TESS prosthesis (anatomical or reverse) with clinical and radiological follow-up ranging from 9–24 months. The TESS prosthesis showed short-term results that were comparable with other shoulder prosthetic systems. Study II: This is a prospective comparative non-randomised study of 37 patients (40 shoulders) who underwent TESS reverse shoulder arthroplasty (RSA) with a follow-up ranging from 15–66 months. We found a significant improvement in functional outcome and reduction of pain in both stemmed and stemless groups. Glenoid overhang influenced the occurrence of scapular notching (SN). Study III: This is a radiological study showing that CT had a good reliability and reproducibility in estimating LHO. Study IV: This is a prospective radiological study of 69 patients (70 shoulders) with primary osteoarthritis (OA) who had undergone stemless total anatomical shoulder arthroplasty (TSA). This study showed that stemless anatomical TSA could be useful in restoring shoulder anatomy. Study V: This is a prospective study of 44 patients with OA who had undergone stemless anatomical TSA with a clinical and radiological follow up ranging from 12 – 50 months. Our study showed that LHO reconstruction close to the anatomy of a healthy contralateral shoulder improved shoulder function. Stemless anatomical TSA help to restore LHO. Increasing LHO may have a negative effect on shoulder function at three months but had no effect at 12 months. The main conclusions of this thesis are: 1. TSA (anatomic and reverse) using stemless humeral components is reliable if bone quality is adequate. The complication rate is comparable with other shoulder prosthetic systems. 2. Glenoid overhang decreased complications in RSA. 3. LHO measurement on AP radiographs is less reliable and underestimates the distance when compared with CT. 4. Stemless TSA could be of help in reconstructing shoulder anatomy. 5. Shoulder reconstruction close to the anatomy of a healthy contralateral shoulder improves shoulder function. / Axelprotes kirurgi har visat avsevärd utveckling under de senaste decennierna. Ett antal faktorer påverkar postoperativt rörelseomfång, smärta och proteshållbarhet. Bland dessa faktorer utgör längden av hävarmen och ledstabilitet de faktorer som kan ändras genom val av proteskomponent. Det är osäkert om den normala anatomin måste återupprättas. Oskaftad protes med eliminering av humerusstamm och tillit till metafysär fixering introducerades i Frankrike år 2004 (TESS, Zimmer Biomet). Målen var att undvika stam relaterade komplikationer. Oskaftat implantat har andra potentiella fördelar, inklusive möjligheten att återställa axelnsanatomi. Syftet med denna avhandling var: (1) Att undersök radiologisk stabilitet av oskaftade axelproteser. (2) Att studera effekten av protes placering vid omvänd axelartroplastik både radiologiska och kliniskt utfall. (3) Att studera tillförlitlighet av mätningen av den laterala humeral offset (LHO), avståndet mellan processus coracoideus till laterala kanten av tuberkulum majus, med användning av CT eller röntgen. (4) Att studera oskaftad axelprotes förmåga att återställa axelnsanatomi. (5) Att studera den kliniska betydelsen av LHO återställning i för det funktionella resultatet efter axelartroplastik. Studie I: Detta är en prospektiv kohortstudie av 49 patienter med en av de två versionerna av TESS (anatomisk eller omvänd) med klinisk och radiologisk uppföljning från 9-24 månader. TESS protes visade lovande resultat på kort sikt med komplikationer som var jämförbar med andra axelprotessystem. Studie II: Detta är en prospektiv jämförande icke-randomiserad studie av 37 patienter (40 skuldror) som opererades med TESS omvänd axelartroplastik med en uppföljning från 15-66 månader. Vi fann en signifikant förbättring av funktion och minskning av smärta i både skaftad och oskaftad grupper. Glenoid overhang bedöms påverka risken för scapular notching (SN). Studie III: Detta är en radiologisk studie som visade att CT hade god tillförlitlighet och reproducerbarhet att mäta LHO. Studie IV: Detta är en prospektiv radiologisk studie av 69 patienter (70 skuldror) med primär artros som hade genomgått oskaftad total anatomisk axelprotes. Denna studie visade att oskaftad axelprotes kan vara till hjälp att återställa axelnsanatomi. Studie V: Detta är en prospektiv studie av 44 patienter med unilateral primär artros som hade genomgått oskaftad total axelprotes med en klinisk och radiologisk uppföljning från 12 - 50 månader. Vår studie visade att LHO rekonstruktion till den friska axeln förbättrar axelfunktion. Oskaftat implantat kan vara av hjälp till att återställa LHO. Ökad LHO kan ha en negativ effekt på axelnsfunktion vid tre månader, men denna effekt påvisade ej vid 12 månader. De viktigaste slutsatserna i denna avhandling är: 1. Oskaftad total axel artroplastik (anatomisk och omvänd) är tillförlitlig om benkvalitén är god med komplikationer som var jämförbar med andra axelprotessystem. 2. Glenoid overhang minskar komplikationer vid omvänd axelartroplastik. 3. LHO mätningen på röntgen är mindre tillförlitlig och underskattar avståndet jämfört med CT. 4. Oskaftad axelprotes skulle kunna vara till hjälp för att rekonstruera axelnsanatomi. 5. Axel rekonstruktion inom anatomi till att efterlikna anatomi på den friska kontralaterala axeln förbättrar axelfunktion.

Dans de nombreux comportements qui reposent sur le rappel et la production de séquences, des groupements temporels émergent spontanément, créés par des délais ou des allongements. Ce « chunking » a été observé tant chez les humains que chez certains animaux et plusieurs auteurs l’attribuent à un processus général de chunking perceptif qui est conforme à la capacité de la mémoire à court terme. Cependant, aucune étude n’a établi comment ce chunking perceptif s’applique à la parole. Nous présentons une recension de la littérature qui fait ressortir certains problèmes critiques qui ont nui à la recherche sur cette question. C’est en revoyant ces problèmes qu’on propose une démonstration spécifique du chunking perceptif de la parole et de l’effet de ce processus sur la mémoire immédiate (ou mémoire de travail). Ces deux thèmes de notre thèse sont présentés séparément dans deux articles. Article 1 : The perceptual chunking of speech: a demonstration using ERPs Afin d’observer le chunking de la parole en temps réel, nous avons utilisé un paradigme de potentiels évoqués (PÉ) propice à susciter la Closure Positive Shift (CPS), une composante associée, entre autres, au traitement de marques de groupes prosodiques. Nos stimuli consistaient en des énoncés et des séries de syllabes sans sens comprenant des groupes intonatifs et des marques de groupements temporels qui pouvaient concorder, ou non, avec les marques de groupes intonatifs. Les analyses démontrent que la CPS est suscitée spécifiquement par les allongements marquant la fin des groupes temporels, indépendamment des autres variables. Notons que ces marques d’allongement, qui apparaissent universellement dans la langue parlée, créent le même type de chunking que celui qui émerge lors de l’apprentissage de séquences par des humains et des animaux. Nos résultats appuient donc l’idée que l’auditeur chunk la parole en groupes temporels et que ce chunking perceptif opère de façon similaire avec des comportements verbaux et non verbaux. Par ailleurs, les observations de l’Article 1 remettent en question des études où on associe la CPS au traitement de syntagmes intonatifs sans considérer les effets de marques temporels. Article 2 : Perceptual chunking and its effect on memory in speech processing:ERP and behavioral evidence Nous avons aussi observé comment le chunking perceptif d’énoncés en groupes temporels de différentes tailles influence la mémoire immédiate d’éléments entendus. Afin d’observer ces effets, nous avons utilisé des mesures comportementales et des PÉ, dont la composante N400 qui permettait d’évaluer la qualité de la trace mnésique d’éléments cibles étendus dans des groupes temporels. La modulation de l’amplitude relative de la N400 montre que les cibles présentées dans des groupes de 3 syllabes ont bénéficié d’une meilleure mise en mémoire immédiate que celles présentées dans des groupes plus longs. D’autres mesures comportementales et une analyse de la composante P300 ont aussi permis d’isoler l’effet de la position du groupe temporel (dans l’énoncé) sur les processus de mise en mémoire. Les études ci-dessus sont les premières à démontrer le chunking perceptif de la parole en temps réel et ses effets sur la mémoire immédiate d’éléments entendus. Dans l’ensemble, nos résultats suggèrent qu’un processus général de chunking perceptif favorise la mise en mémoire d’information séquentielle et une interprétation de la parole « chunk par chunk ». / In numerous behaviors involving the learning and production of sequences, temporal groups emerge spontaneously, created by delays or a lengthening of elements. This chunking has been observed across behaviors of both humans and animals and is taken to reflect a general process of perceptual chunking that conforms to capacity limits of short-term memory. Yet, no research has determined how perceptual chunking applies to speech. We provide a literature review that bears out critical problems, which have hampered research on this question. Consideration of these problems motivates a principled demonstration that aims to show how perceptual chunking applies to speech and the effect of this process on immediate memory (or “working memory”). These two themes are presented in separate papers in the format of journal articles. Paper 1: The perceptual chunking of speech: a demonstration using ERPs To observe perceptual chunking on line, we use event-related potentials (ERPs) and refer to the neural component of Closure Positive Shift (CPS), which is known to capture listeners’ responses to marks of prosodic groups. The speech stimuli were utterances and sequences of nonsense syllables, which contained intonation phrases marked by pitch, and both phrase-internal and phrase-final temporal groups marked by lengthening. Analyses of CPSs show that, across conditions, listeners specifically perceive speech in terms of chunks marked by lengthening. These lengthening marks, which appear universally in languages, create the same type of chunking as that which emerges in sequence learning by humans and animals. This finding supports the view that listeners chunk speech in temporal groups and that this perceptual chunking operates similarly for speech and non-verbal behaviors. Moreover, the results question reports that relate CPS to intonation phrasing without considering the effects of temporal marks. Paper 2: Perceptual chunking and its effect on memory in speech processing: ERP and behavioral evidence We examined how the perceptual chunking of utterances in terms of temporal groups of differing size influences immediate memory of heard speech. To weigh these effects, we used behavioural measures and ERPs, especially the N400 component, which served to evaluate the quality of the memory trace for target lexemes heard in the temporal groups. Variations in the amplitude of the N400 showed a better memory trace for lexemes presented in groups of 3 syllables compared to those in groups of 4 syllables. Response times along with P300 components revealed effects of position of the chunk in the utterance. This is the first study to demonstrate the perceptual chunking of speech on-line and its effects on immediate memory of heard elements. Taken together the results suggest that a general perceptual chunking enhances a buffering of sequential information and a processing of speech on a chunk-by-chunk basis.